Atherosclerotic renovascular disease - epidemiology, treatment and current challenges.
The neutral results of recent large randomized controlled trials comparing renal revascularization with optimal medical therapy in patients with atherosclerotic renovascular disease (ARVD) have cast doubt on the role of revascularization in the management of unselected patients with this condition. However, these studies have strengthened the evidence base for the role of contemporary intensive medical vascular protection therapy and aggressive risk factor control in improving clinical outcomes in ARVD. Patients presenting with 'high-risk' clinical features such as uncontrolled hypertension, rapidly declining renal function or flash pulmonary oedema are underrepresented in these studies; hence these results may not be applicable to all patients with ARVD. In this 'high-risk' subgroup, conservative management may not be sufficient in preventing adverse events, and indeed, observational evidence suggests that this specific patient subgroup may gain benefit from timely renal revascularization. Current challenges include the development of novel diagnostic techniques to establish haemodynamic significance of a stenosis, patient risk stratification and prediction of post-revascularization outcomes to ultimately facilitate patient selection for revascularization. In this paper we describe the epidemiology of this condition and discuss treatment recommendations for this condition in light of the results of recent randomized controlled trials while highlighting important clinical unmet needs and challenges faced by clinicians managing this condition.


Physician experience with family presence during cardiopulmonary resuscitation in children.
Family presence during cardiopulmonary resuscitation in children is an emerging practice. Although many hospitals allow this practice, there is scant research on physician attitudes and opinions and on physician views about training for resident physicians. Survey method. University and community settings. We randomly selected 1,200 pediatric critical care and emergency medicine providers from professional association mailing lists. The providers were mailed up to two written surveys and two reminder cards. The survey consisted of 40 multiple-choice and short-answer questions about demographics, past experiences, and opinions on pediatric family presence. Of 1,200 surveys mailed, 521 were completed (43.4%) and 73 (6.1%) respondents returned the form declining to participate. More than 99% of respondents were physicians. Four hundred and thirty-three respondents (83%) reported participation in pediatric resuscitation with family members present, with a mean of 15 episodes ever and three episodes within the last year. Of those who had ever participated, more than half thought it was helpful for the family, and two thirds believed that parents wanted the option. Ninety-three percent would allow family presence in some situations. Seventy-four percent believed family presence would be stressful for a resident physician, but nearly 80% believed that residents working with children should be educated in this area. Family presence during cardiopulmonary resuscitation in children is not an uncommon experience for health care providers. Most respondents had resuscitated a child with family members present. The majority thought that presence was helpful to parents and that residents should be trained in this practice.


Detection of respiratory viruses by real-time polymerase chain reaction in outpatients with acute respiratory infection.
Viruses are the major contributors to the morbidity and mortality of upper and lower acute respiratory infections (ARIs) for all age groups. The aim of this study was to determine the frequencies for a large range of respiratory viruses using a sensitive molecular detection technique in specimens from outpatients of all ages with ARIs. Nasopharyngeal aspirates were obtained from 162 individuals between August 2007-August 2009. Twenty-three pathogenic respiratory agents, 18 respiratory viruses and five bacteria were investigated using multiplex real-time reverse transcriptase polymerase chain reaction (RT-PCR) and indirect immunofluorescence assay (IIF). Through IIF, 33 (20.4%) specimens with respiratory virus were recognised, with influenza virus representing over half of the positive samples. Through a multiplex real-time RT-PCR assay, 88 (54.3%) positive samples were detected; the most prevalent respiratory viral pathogens were influenza, human rhinovirus and respiratory syncytial virus (RSV). Six cases of viral co-detection were observed, mainly involving RSV. The use of multiplex real-time RT-PCR increased the viral detection by 33.9% and revealed a larger number of respiratory viruses implicated in ARI cases, including the most recently described respiratory viruses [human bocavirus, human metapneumovirus, influenza A (H1N1) pdm09 virus, human coronavirus (HCoV) NL63 and HCoV HKU1].


Vitamin E Decreases Cytotoxicity and Mitigates Inflammatory and Oxidative Stress Responses in a Ferret Organotypic Brain Slice Model of Neonatal Hypoxia-Ischemia.
The gyrencephalic ferret brain is an excellent model in which to study hypoxia-ischemia (HI), a significant contributor to neurological injury in neonates. Vitamin E, an essential fat-soluble antioxidant, reduces oxidative stress and inflammation in both animal models and human infants. The aim of this study was to assess the effects of vitamin E after oxygen-glucose deprivation (OGD) in an organotypic ferret brain slice model of neonatal HI. We hypothesized that vitamin E would decrease cytotoxicity, inflammation, and oxidative stress in OGD-exposed brain slices. Term-equivalent ferrets were sacrificed at postnatal (P) day 21-23 and 300 µM whole-hemisphere brain slices were obtained. During a 24-h rest period, slices were cultured in either nontreated control conditions or with erastin, a promotor of oxidative stress. Slices were then exposed to 2 h of OGD followed by vitamin E (25-100 IU/kg), erastin (10 µM), or ferrostatin (1 µM), an inhibitor of ferroptosis. Relative cytotoxicity was determined using a lactate dehydrogenase assay, cell death was quantified via nuclear propidium iodide staining, oxidative stress was quantified via cellular glutathione (GSH) levels, and target genes responsive to oxidative stress and inflammation were evaluated by qRT-PCR. OGD increased cytotoxicity, which was significantly reduced by treatment with vitamin E. Vitamin E also preserved GSH after OGD and decreased amplification of certain markers of oxidative stress (CHAC1, SLC7A11) and inflammation (TNF-alpha, IL-8). Vitamin E remained protective after pretreatment with erastin and was more protective than ferrostatin, presumably due to its added anti-inflammatory properties. Results from the ferret whole-hemisphere OGD model support the premise that vitamin E neuroprotection is mediated by restoring GSH and acutely decreasing inflammation and oxidative stress after neonatal HI.


Garden walking for depression: a research report.
This study was designed to determine the effect of garden walking and reflective journaling on adults who are 65 years old and older with depression. The Geriatric Depression Scale measured depression. Four themes emerged from the interview data collected from each participant.


[Application of high-flow humidified oxygen therapy in patients with tracheotomy and non-mechanical ventilation].
To observe the effect of tracheotomy high-flow oxygen therapy (THFO) on the clinical efficacy of non-mechanically ventilated patients undergoing a tracheotomy. Sixty adult patients with tracheotomy and non-mechanical ventilation who were diagnosed and treated from January 2019 to December 2020 in Fenyang Hospital of Shanxi Province were enrolled. According to the random number table, the patients were divided into Venturi oxygen therapy group and THFO group, 30 cases in each group. The THFO group was given oxygen therapy with THFO; the Venturi group (without mask) was given Venturi connected the MR850 base and the ventilator tube. Observe the changes of two groups at 7 AM within 5 days, including body temperature which was 1 centigrade higher than the baseline, white blood cell count (WBC) which was 2×109/L higher than baseline, oxygenation index (PaO2/FiO2) < 300 mmHg (1 mmHg = 0.133 kPa), the occurrence of lower respiratory tract infections (based on radiography), and changes in sputum indexing and sputum formation. Compared with the Venturi oxygen therapy group, the body temperature increased > 1 centigrade, WBC increased by 2×109/L, PaO2/FiO2 < 300 mmHg, and the proportion of lower respiratory tract infection in THFO group decreased significantly [body temperature increased > 1 centigrade: 10.0% (3/30) vs. 13.3% (4/30), WBC increased by 2×109/L: 10.0% (3/30) vs. 30.0% (9/30), PaO2/FiO2 < 300 mmHg: 3.3% (1/30) vs. 10.0% (3/30), the proportion of lower respiratory tract infection: 6.7% (2/30) vs. 13.3% (4/30), all P < 0.05]. The proportion of patients with sputum scab formation and sputum viscosity of I degree were significantly increased [sputum scab formation: 16.7% (5/30) vs. 6.7% (2/30), sputum viscosity of I degree: 30.0% (9/30) vs. 20.0% (6/30), both P < 0.05]. THFO during non-mechanical ventilation of adult patients with tracheotomy can maintain a higher oxygen partial pressure and ideally control the temperature and humidity of the inhaled gas, promote the discharge of sputum with degree I and II viscosity, thereby reducing the tracheotomy complications such as lower respiratory tract infections.


Psychometric properties of the Self-Perception Profile for Children in a biracial cohort of adolescent girls: the NHLBI Growth and Health Study.
The National Heart, Lung, and Blood Institute Growth and Health Study (NGHS) is an epidemiologic study of 1,213 Black and 1,166 White girls (ages 9-10) of risk factors for obesity. NGHS used Harter's Self-Perception Profile for Children (SPPC) to measure domain-specific competence and overall self-worth. This report reviews the psychometric properties of the SPPC in this biracial cohort at baseline and Year 3 visits (ages 11-12). Simple structure yielding unique components for each of the SPPC domains was obtained for White but not Black girls, whether analyzed overall or by parental education level. Internal consistency was higher for White girls in both years. The lack of simple structure was reflected in the higher correlations among the subscales for Black girls. The structure and internal consistency improved in Year 3 for Black girls, indicating that the physical appearance and athletic competence domains were not yet fully differentiated at baseline. Readers should be cautious, however, when interpreting the SPPC in young Black girls.


Amphiphilic ionic liquid induced fusion of phospholipid liposomes.
We have investigated the impact of increasing concentration of imidazolium-based ionic liquids ([CnMIM]+[Br]-) on the structural integrity of large unilamellar vesicles (LUVs) made of pure phosphatidylcholine (PC) and phosphatidylglycerol (PG) lipids. Calcein based dye leakage assays were used to monitor the permeability of LUVs in the presence of ionic liquids. As the ionic liquid concentration approaches the critical micelle value, vesicle fusion occurs resulting in unexpected quenching which is accompanied by rapid dye leakage due to the formation of transiently lived fusion-holes. Vesicle fusion is confirmed using dynamic light scattering based size measurements and fluorescence based lipid mixing assays. 1H-1H NOESY measurements using solid-state NMR spectroscopy were performed to obtain insights into the fusion mechanism. While POPC LUVs are more prone to membrane fusion, the overall extent of fusion is higher in POPG LUVs. Ionic liquid induced splaying of phospholipid chains is crucial for overcoming the hydration barrier between the merging bilayers.


The analgesic effect of nefopam with fentanyl at the end of laparoscopic cholecystectomy.
Nefopam is a centrally acting analgesic that is used to control pain. The aim of this study was to find an appropriate dose of nefopam that demonstrates an analgesic effect when administered in continuous infusion with fentanyl at the end of laparoscopic cholecystectomy. Ninety patients scheduled for laparoscopic cholecystectomy were randomly assigned to receive analgesia with fentanyl alone (50 µg, Group 1, n = 30), or with fentanyl in combination with nefopam 20 mg (Group 2, n = 30) or in combination with nefopam 40 mg (Group 3, n = 30) at the end of surgery. Pain and side effects were evaluated at 10 minutes, 30 minutes, 1 hour, 2 hours, 6 hours, and 12 hours after arrival in the post-anesthesia care unit (PACU). Pain was statistically significantly lower in Groups 2 and 3 than in Group 1 at 10 minutes, 2 hours, and 6 hours after arrival in the PACU. Nausea was statistically significantly lower in Group 2 than in Groups 1 and 3 at 10 minutes after arrival in the PACU. Shivering was statistically significantly lower in Groups 2 and 3 than in Group 1 at 10 minutes after arrival in the PACU. Nefopam is a drug that can be safely used as an analgesic after surgery, and its side effects can be reduced when fentanyl 50 µg is injected with nefopam 20 mg.


Effects of smoked substance abuse on nonspecific airway hyperresponsiveness.
Previous data suggest that regular tobacco smoking may lead to nonspecific airway hyperresponsiveness (AHR) independent of airway obstruction, possibly because of effects on bronchial inflammation or mucosal permeability. Little is known concerning the effects on AHR of other widely smoked substances besides tobacco such as marijuana or cocaine. The smoke of both marijuana and cocaine contains respiratory irritants that elicit cough and produce abnormalities in airway dynamics and bronchial mucosal histopathology in habitual smokers. Therefore, regular smoking of one or both of these illicit substances could cause AHR or augment the AHR associated with tobacco smoking. The present study examined the influence of habitual smoking of marijuana, cocaine, and/or tobacco on nonspecific AHR in 542 (456 male) healthy participants (mean age, 34.8 +/- 6.8 SD yr) in an ongoing cohort study of the pulmonary effects of habitual smoking of illicit substances. Subjects with a history of intravenous drug abuse, significant occupational exposures, asthma, or recent upper respiratory tract infection were excluded. Inhalation challenge studies were performed using solutions of diluent and methacholine chloride (1.25 to 25 mg/ml) aerosolized by a DeVilbiss no. 646 nebulizer attached to a breath-activated dosimeter inhaled by three to five inspiratory capacity breaths. Positive responses to methacholine were defined by > or = 20% or > or = 10% declines in FEV1 from the postdiluent control value after inhalation of each concentration of methacholine. Participants were categorized by smoking status (nonsmoking and smoking of marijuana, cocaine, and/or tobacco alone and in combination); most analyses were performed in men and women separately.(ABSTRACT TRUNCATED AT 250 WORDS)


Eliminating a set of four penicillin binding proteins triggers the Rcs phosphorelay and Cpx stress responses in Escherichia coli.
Penicillin binding proteins (PBPs) are responsible for synthesizing and modifying the bacterial cell wall, and in Escherichia coli the loss of several nonessential low-molecular-weight PBPs gives rise to abnormalities in cell shape and division. To determine whether these proteins help connect the flagellar basal body to the peptidoglycan wall, we surveyed a set of PBP mutants and found that motility in an agar migration assay was compromised by the simultaneous absence of four enzymes: PBP4, PBP5, PBP7, and AmpH. A wild-type copy of any one of these restored migration, and complementation depended on the integrity of the PBP active-site serine. However, the migration defect was caused by the absence of flagella instead of improper flagellar assembly. Migration was restored if the flhDC genes were overexpressed or if the rcsB or cpxR genes were deleted. Thus, migration was inhibited because the Rcs and Cpx stress response systems were induced in the absence of these four specific PBPs. Furthermore, in this situation Rcs induction depended on the presence of CpxR. The results imply that small changes in peptidoglycan structure are sufficient to activate these stress responses, suggesting that a specific cell wall fragment may be the signal being sensed. The fact that four PBPs must be inactivated may explain why large perturbations to the envelope are required to induce stress responses.


[A case of failed laparoscopic and endoscopic cooperative surgery (LECS) for gastrointestinal stromal tumor of the stomach].
Recently, laparoscopic and endoscopic cooperative surgery (LECS) for submucosal gastric tumor has been developed to avoid an excessive surgical resection of gastric wall, which causes a deformity of the stomach and reduced oral intake. We report here a case of failed LECS for gastric submucosal tumor, and discuss the cause of failure. An 89-year-old woman underwent LECS for an intraluminal type submucosal tumor involving the upper and posterior gastric wall. Specifically, two sites of the gastric wall were fixed with subumbilical and left latero-abdominal wall approaches and two trocars with balloons were introduced into the stomach. Endoscopic submucosal resection was performed circumferentially around the tumor. Then, we tried to lift the tumor using an Endo-loop®. However, the amount of lifting was not sufficient for a safe surgical resection because the surgical field was extremely narrow. Therefore, we converted LECS to open surgery. In conclusion, it is important to consider clinical factors such as body size, tumor size and tumor location when planning LECS. Particularly, the intraabdominal suturing technique instead of using a linear stapler is desirable for a tumor involving the posterior wall.


Automatized determination of left ventricular systolic intervals and assessment of their significance in the epidemiology of ischaemic heart disease.
Knowledge of the functional state of the myocardium in patients with coronary heart disease is of essential importance for the prognosis and therapy of the disease. The PEP/LVET index is closely correlated with the ejection fraction and is a reliable criterion for separating patients with normal and disturbed function of the left ventricle, but it does not suffice for uncovering an initial haemodynamic alteration either at rest or during isometric exercise test. The good reproducibility of systolic intervals makes possible a long-term follow-up of patients, especially in cases in which direct examination methods have limited applicability. Computer processing of polygraph tracings makes possible to analyse data of large groups of patients. The accuracy of systolic intervals determination matches that of the classical reading by two independent observes. The use of computing techniques in the analysis of curves and in their statistical evaluation contributes to the standardization of the whole measuring procedure and makes possible a wide clinical use of non-invasive polygraphic methods.


Emergency department utilization by the elderly: analysis of the National Hospital Ambulatory Medical Care Survey.
To characterize the ED utilization patterns of the elderly population using nationally representative data. A secondary analysis was performed using the National Hospital Ambulatory Medical Care Survey (NHAMCS), a nationwide, stratified probability sample of ED encounters. Using these physician-reported data, the demographics, patient complaints, physician diagnoses, and dispositions were compared by age group, i.e., young-old (age 65-84 years) vs old-old (age > or = 85 years). The elderly (age > or = 65 years) represented 5,038 (19.6%) of 25,646 ED encounters for all adults (age > or = 18 years). The geriatric age groups (ages 65-74, 75-84, and > or = 85 years) accounted for 45.3%, 37.4%, and 17.2% of all the encounters by the elderly. The proportions of female patients and white patients were higher with increasing age. The proportion of elderly patients hospitalized was 4 times that of younger adults and reflected monotonic increase with increasing age among elders. Patient complaints and physician diagnoses were generally similar for the young-old (65-84 years) and the old-old (> or = 85 years). These findings are consistent with previous single-center studies of geriatric ED patients. This data source may be useful for investigation of clinical issues related to the care of elderly ED patients.


[Muscle cramps--differential diagnosis and therapy].
Calf cramps are sudden, involuntary, painful contractions of part of or the entire calf muscle that are visible, persist for seconds to minutes and then spontaneously resolve. They can occur with no identifiable cause, and are then referred to as common calf cramps. They may also be symptoms associated with diseases of the peripheral and central nervous system and muscle diseases. They also occur in association with metabolic disorders. In such cases the cramps are more extensive, intense and persist for longer. Cramp-fasciculation-myalgia syndrome additionally involves paresthesias and other signs of hyperexcitability of peripheral nerves. The recommended treatment for patients with frequent calf cramps causing significant impairment of well-being is oral administration of quinidine and/or botulinum toxin treatment of the calf muscles. During pregnancy both products are contraindicated, while probatory administration of magnesium is indicated.


Effect of intrahypothalamic injections of norepinephrine and serotonin on plasma arginine vasotocin and mesotocin in the White Leghorn cockerel.
1. Saline (10 microliters), norepinephrine (NE) and Serotonin (5-HT), 500 nmol each, were injected into the anterior third ventricle (A3V; n = 7) or the posterior third ventricle (P3V; n = 11) of ananesthetised, unrestrained White Leghorn cockerels. Plasma arginine vasotocin (AVT) and mesotocin (MT) were measured 20, 60 and 120 min after injection. 2. Injection of NE into both the A3V and P3V had no significant effect on either plasma AVT or plasma MT at any of the sampling times. 3. Administration of 5-HT into the A3V significantly increased plasma MT about two-fold 20 min following injection. At 120 min time, plasma MT returned to normal. 4. In P3V birds, 5-HT had no effect on plasma MT in the first 20 min, but a significant increase in plasma MT occurred 60 to 120 min after injection. The magnitude of the response was lower than in the A3V cockerels. 5. Plasma AVT was not affected by 5-HT administration into the A3V at any of the sampling times, but 5-HT administration into the P3V caused significant rises in plasma AVT at 120 min. 6. Serotonergic, but not noradrenergic, induction of neurohypophysial peptide secretion was demonstrated.


Nutrient deficiencies associated with nutrition-focused physical findings of the oral cavity.
Conducting nutrition-focused physical examinations and reporting the findings from the perspective of nutrition status strengthen the practitioner's assessments, interventions, and monitoring. The nutrition-focused physical examination of the oral cavity is particularly useful to identify nutrient deficiencies early and with accuracy as the tissues in the oral mucosa have a turnover rate of <1 week. As biomarkers may not always be reliable for identifying micronutrient deficiencies, these physical examinations are important for providing comprehensive nutrition care. The purpose of this article is to discuss the methods of conducting a nutrition-focused oral screening examination and compile and document the evidence regarding the effects of micronutrient deficiencies on the oral mucosa. The information is formatted into a table that can be used as a tool when conducting an oral screening by identifying possible deficiencies based on the observations and other relevant findings. The tool will also guide the practitioner in confirming the physical findings, suggesting interventions to treat the deficiency and how to monitor the outcomes.


Anxiety sensitivity, distress tolerance, and discomfort intolerance in relation to coping and conformity motives for alcohol use and alcohol use problems among young adult drinkers.
Anxiety sensitivity, distress tolerance, and discomfort intolerance have been identified as important factors related to alcohol use motives and alcohol-related problems. Yet, these variables are highly correlated and little work has delineated whether these psychological vulnerability factors are differentially related to alcohol use motives and problems. To fill this gap in the existing literature, the present study evaluated whether anxiety sensitivity, distress tolerance, and discomfort intolerance were differentially related to high-risk alcohol use motives (i.e., coping and conformity motives) and alcohol use problems among 224 young adult, current drinkers (52.3% women; M(age)=21.18, SD=7.08). Results indicated that distress tolerance, but not anxiety sensitivity or discomfort intolerance, was significantly related to coping motives for alcohol use. Additionally, anxiety sensitivity, but not distress tolerance or discomfort intolerance, was significantly related to conformity motives for drinking. For both sets of analyses, the observed significant effects were evident above and beyond the variance accounted for by alcohol consumption level, smoking rate, negative affectivity, and non-criterion alcohol use motives. Additionally, discomfort intolerance and anxiety sensitivity each predicted alcohol use problems; effects were not attributable to negative affectivity, cigarettes smoked per day, or shared variance with distress tolerance. Findings are discussed in relation to the role of emotional sensitivity and intolerance in terms of the motivational bases for alcohol use and alcohol use problems among young adult drinkers.


Rapid and sensitive routine detection of all members of the genus enterovirus in different clinical specimens by real-time PCR.
We developed a rapid and sensitive method for the routine detection of all members of the enterovirus genus in different clinical specimens by using real-time TaqMan quantitative PCR. Multiple primer and probe sets were selected in the highly conserved 5'-untranslated region of the enterovirus genome. Our assay detected all 60 different enterovirus species tested, whereas no reactivity was observed with the viruses from the other genera of the picornaviridae family, e.g., hepatovirus and parechovirus. Weak cross-reactivity was observed with 7 of the 90 different high-titer rhinovirus stocks but not with rhinovirus-positive clinical isolates. Analysis of a well-characterized reference panel containing different enteroviruses at various concentrations demonstrated that the enterovirus real-time TaqMan PCR is as sensitive as most of the currently used molecular detection assays. Evaluation of clinical isolates demonstrated that the assay is more sensitive than the "gold standard" method, i.e., viral culture. Moreover, the PCR assay can be used on different clinical specimens, such as plasma, serum, nose and throat swabs, cerebrospinal fluid, and bronchoalveolar lavage, without apparent inhibition. Our data demonstrate that the real-time TaqMan PCR is a rapid and sensitive assay for the detection of enterovirus infection. The assay has a robust character and is easily standardized, which makes it an excellent alternative for the conventional time-consuming viral culture.


Combination of alpha lipoic acid and gabapentin, its efficacy in the treatment of Burning Mouth Syndrome: a randomized, double-blind, placebo controlled trial.
Burning Mouth Syndrome (BMS) is a disease that manifests as burning in the tongue or in any area of the oral mucosa, in the absence of clinically verifiable injuries. To verify the efficacy of alpha lipoic acid (ALA) and gabapentin (GABA), used individually and jointly, to reduce the burning in patients with burning mouth and establish a drug therapy for the BMS. During April and May 2008, we conducted a randomized, double-blind, placebo-controlled trial in the Department of Clinical Stomatology, Faculty of Dentistry, Rosario, Argentina. The gathering of patients was between those ones with BMS who were treated in our service between March 2003 and March 2008 without complying with the applied treatments. The 120 patients were randomly divided into 4 groups and were provided, by lot and in a blinded fashion, with four different treatment cycles consisting of the following drugs: Group A (n = 20) 600 mg / day of alpha lipoic acid for two months, Group B (n = 20) 300 mg / day of gabapentin for two months, Group C (n = 20) a combination of both drugs for two months and Group D (n = 60) 100 mg / day of cellulose starch for two months (control group). all 120 patients completed the treatment. The best response was obtained with the combination of ALA + GABA, with a 70% of the cases with reduced burning in this group and a 13.2 times greater chance of presenting positive changes for these patients than those taking placebo. The combined use of drugs that act at different levels of the nociceptive system can be useful for the treatment of this syndrome.


Characteristics of [3H]nimodipine binding to sarcolemmal membranes from rat vas deferens and its regulation by guanine nucleotide.
The binding properties of a 1,4-dihydropyridine (DHP) calcium entry blocker, [3H]nimodipine, to a microsomal fraction from rat vas deferens was characterized. The specific binding was saturable, rapid and reversible. Scatchard analysis of the binding revealed a single binding site, and the dissociation constant and the maximum number of binding sites were 0.31 +/- 0.02 nM and 97.0 +/- 7.19 fmol/mg protein, respectively. Both the Kd value obtained from the kinetic study and the IC50 value from relaxation of the K+-depolarized organ were approximately 0.4 nM, indicating that the binding site is closely related to the functional Ca2+ channel. The specific [3H]nimodipine binding was displaced by DHP derivatives at low concentration and by verapamil at high concentration, but diltiazem had no effect on the binding. Calcium chelating agents decreased the [3H]nimodipine binding which was restored by adding Ca2+. 5'-Guanylylimidodiphosphate caused a rightward shift of the displacement curve for Bay K 8644 but not for nimodipine, suggesting the involvement of guanine nucleotide binding protein in the signal transduction between the DHP binding site and the Ca2+ channel.


Programmed cell death: will it become a factor in cancer prevention?
Among the factors triggering programmed cell death (PCD) are a number of known carcinogens, and several consequences of DNA abnormalities characteristic of cancer have been shown capable of eliciting the PCD response. So although elimination of a potentially malignant cell is likely to be a rare consequence of PCD it could turn out to be important for cancer development. A brief survey is given of the most well-known triggering factors, the molecular mechanisms of the pathways involved and the emerging experimental and clinical data relating capacity of PCD to cancer initiation and progression. It is suggested that future cancer prevention will have to consider also those factors which may abrogate normal PCD.


Charge Injection Mechanism at Heterointerfaces in CH3NH3PbI3 Perovskite Solar Cells Revealed by Simultaneous Time-Resolved Photoluminescence and Photocurrent Measurements.
Organic-inorganic hybrid perovskite solar cells are attracting much attention due to their excellent photovoltaic properties. In these multilayered structures, the device performance is determined by complicated carrier dynamics. Here, we studied photocarrier recombination and injection dynamics in CH3NH3PbI3 perovskite solar cells using time-resolved photoluminescence (PL) and photocurrent (PC) measurements. It is found that a peculiar slowdown in the PL decay time constants of the perovskite layer occurs for higher excitation powers, followed by a decrease of the external quantum efficiency for PC. This indicates that a carrier-injection bottleneck exists at the heterojunction interfaces, which limits the photovoltaic performance of the device in concentrator applications. We conclude that the carrier-injection rate is sensitive to the photogenerated carrier density, and the carrier-injection bottleneck strongly enhances recombination losses of photocarriers in the perovskite layer at high excitation conditions. The physical origin of the bottleneck is discussed based on the result of numerical simulations.


Turnover of plasma cholesterol in man.
Cholesterol-4-(14)C was injected intravenously into a series of normal men, untreated hyperlipidemic patients, and hyperlipidemic patients being treated with cholestyramine. The specific radioactivity of plasma total cholesterol was measured during the ensuing 10 wk. 16 studies were carried out in 10 subjects. Analysis of the turnover curves of plasma cholesterol revealed that in every study the turnover of plasma cholesterol conformed to a two-pool model. Each turnover curve was analyzed in terms of this model, as expressed by the equation: specific activity = C(A)e(-alphat) + C(B)e(-betat). The parameters which were calculated included the constants C(A), C(B), alpha, and beta; the size of the first pool (M(A)); the rate constants for the total rate of removal of cholesterol from each pool (k(AA) and k(BB)); and the production rate in pool A (PR(A)). In two normal men and five untreated patients the average size of pool A was 25g. The effect of cholestyramine was assessed by comparing the results obtained without therapy with those obtained during therapy in five subjects studied under both conditions. Cholestyramine therapy produced a large increase in PR(A) (from 0.98 to 1.98 g/day) and in the rate of removal of cholesterol from pool A. Cholestyramine did not significantly alter the size of pool A. It is not possible to calculate the size of the total body exchangeable pool of cholesterol from the turnover curve of plasma cholesterol. It is also not possible to calculate the metabolic turnover rate, i.e., the rate of cholesterol degradation and excretion, in the whole body. This parameter can, however, be estimated by assuming that cholesterol is removed from the body only by way of the tissue pools that comprise pool A. Under these conditions the metabolic turnover rate is equal to the production rate in pool A.


Client resistance to hepatitis C treatment initiation in opioid agonist treatment clinics in Sydney, Australia: A qualitative study.
Opioid agonist treatment (OAT) clinics play a key role in achieving elimination of hepatitis C virus (HCV) globally. Previous research has identified barriers to HCV treatment uptake in OAT clinics; however, most studies were conducted prior to the introduction of direct-acting antiviral treatments (DAA). It remains unclear whether progress has been made in responding to barriers and what challenges persist in this setting. Semi-structured in-depth interviews were conducted with staff (n = 20) and clients (n = 15) in two OAT clinics in Sydney, Australia. Interviews were transcribed verbatim and analysed using constant comparative methods. Despite progress in integrating hepatitis C care in the clinics, competing priorities, concerns about side-effects, distrust of staff, health problems and difficulties accessing testing and medication persisted as key reasons why clients had not initiated treatment. Most clients preferred to postpone treatment and focus on other priorities and some highlighted lack of medical evidence for urgent treatment. Pressure on services to achieve elimination targets within set time frames was a primary driver of repeated offers of treatment by staff and the framing of clients' preferences for postponing treatment, as a barrier. Current timelines for HCV elimination targets may have galvanised services into action but may have also created tensions at the coalface due to disparities between staff and clients' priorities. The involvement of peer workers and mechanisms to ensure continued follow up with clients about DAA treatments is required. Public health timelines for HCV elimination need to be informed by affected communities' priorities.


Under the influence of the active deodorant ingredient 4-hydroxy-3-methoxybenzyl alcohol, the skin bacterium Corynebacterium jeikeium moderately responds with differential gene expression.
A 70mer oligonucleotide microarray was constructed to analyze genome-wide expression profiles of Corynebacterium jeikeium, a skin bacterium that is predominantly present in the human axilla and involved in axillary odor formation. Oligonucleotides representing 100% of the predicted coding regions of the C. jeikeium K411 genome were designed and spotted in quadruplicate onto epoxy-coated glass slides. The quality of the printed microarray was demonstrated by co-hybridization with fluorescently labeled cDNA probes obtained from exponentially growing C. jeikeium cultures. Accordingly, genes detected with different intensities resulting in log(2) transformed ratios greater than 0.8 or smaller than -0.8 can be regarded as differentially expressed with a confidence level greater than 99%. In an application example, we measured global changes of gene expression during growth of C. jeikeium in the presence of different concentrations of the deodorant component 4-hydroxy-3-methoxybenzyl alcohol that is active in preventing body odor formation. Global expression profiling revealed that low concentrations of 4-hydroxy-3-methoxybenzyl alcohol (0.5 and 2.5mg/ml) had almost no detectable effect on the transcriptome of C. jeikeium. A slightly higher concentration of 4-hydroxy-3-methoxybenzyl alcohol (5mg/ml) resulted in differential expression of 95 genes, 86 of which showed an enhanced expression when compared to a control culture. Besides many genes encoding proteins that apparently participate in transcription and translation, the drug resistance determinant cmx and the predicted virulence factors sapA and sapD showed significantly enhanced expression levels. Differential expression of relevant genes was validated by real-time reverse transcription PCR assays.


Nanoscale quantitative surface roughness measurement of articular cartilage using second-order statistical-based biospeckle.
Quantitative measurement of nanoscale surface roughness of articular cartilage tissue is significant to assess the surface topography for early treatment of osteoarthritis, the most common joint disease worldwide. Since it was not established by clinical diagnostic tools, the current studies have been suggesting the use of alternative diagnostic tools using pre-clinical methods. This study aims to measure the nanoscale surface roughness of articular cartilage tissue utilizing biospeckle which is used as a non-destructive and non-contact optical imaging technique. An experimental setup was implemented to capture biospeckle images from twelve cross-section areas of articular cartilage tissue gathered from bovine knee joints at 632 nm wavelength laser radiation. Then, to analyze the biospeckle image, a second-order statistical-based method was proposed through the combination of 308 highly correlated statistical features extracted from implemented gray-level co-occurrence matrices by employing principal component analysis. The result indicated that the measurement of the nanoscale surface roughness based on the first principal component only is able to provide accurate and precise quantitative measurement of early signs of articular cartilage degeneration up to 2500 nm.


SARS-CoV-2 Detection using Real Time PCR by a Commercial Diagnostic Kit.
There is a new public health problem around the world with the emergence and spread of 2019 novel corona virus (2019-nCoV). The disease "coronavirus disease 2019" (COVID-19) was caused by SARS-CoV-2. As virus isolates are unavailable so the public laboratories are now facing a challenge for detecting the virus because there is growing evidence of the outbreak which is more widespread than initially thought. We aimed here to discuss about the current diagnostic methodology for detecting the SARS-CoV-2 in health laboratories. Here we use the Novel Corona virus (2019-nCoV) Nucleic Acid Diagnostic Kit (PCR-Fluorescence Probing) which is a real time reverse transcription polymerase chain reaction (rRT-PCR) test. A total of 230 samples in the department of microbiology, Mymensingh Medical College from 1st, April 2020 were selected for this study. Among them 20(8.69%) were positive for SARS CoV-2 and remaining were negative. Among the positive samples 55% could amplify both the ORF 1ab and N genes. The single gene ORF 1ab or N was positive in 15% and 30% cases respectively. The Ct values (<38) of ORF 1ab gene indicated by FAM dye was 92.8% and N gene curve indicated by ROX dye was 100%. The presence of IC gene curve with Ct values (<38) indicated by CY5 dye among the positives were 70% and 100% in negatives. The Ct values (38-40) of IC (CY5) among the positives were 15%. The present study demonstrates the enormous response capacity of the study kit for detecting SARS-CoV-2 within the laboratories in Bangladesh.


Location of the ostia of the renal arteries in the aorta.
A total of 30 adult abdominal aorta specimens dissected from cadavers was used in our study. The location of the ostium of the superior mesenteric a. relative to the ostium of the celiac trunk was identified on the aortic wall. Following this, the locations of the ostia of the renal aa. on the internal wall of the abdominal aorta were examined relative to the ostia of the arteries mentioned earlier. The ostium of the superior mesenteric a. was usually localized on the inferior-right side of the ostium of the celiac trunk. The mean value of the distance between the ostia was 17.9 mm. The ostium of the right renal a. was more cranial than the ostium of the left renal a. (53.3%). However, the ostia of both right and left renal aa. were at the same level in three cases (10%). Locations of the ostia of the renal aa. were usually on the lateral and anterolateral regions of the aortic wall. This study was carried out in order to contribute to selective angiography and surgical interventions for the removal and transplantation of organs, particularly of the kidney. Our results are compared with previous similar studies in man.


Impaired stem cell collection by consecutive courses of high-dose mobilizing chemotherapy using cyclophosphamide, etoposide, and G-CSF.
Tandem cycles of myeloablative chemotherapy can increase dose intensity and total dose of chemotherapy, but sufficient numbers of progenitor cells must be collected to ensure hematologic recovery after each treatment. This study was undertaken to determine if two courses of mobilizing chemotherapy given 4 weeks apart using cyclophosphamide 4000 mg/m2 and etoposide 400 mg/m2, combined with G-CSF 5-10 mg/kg on days 3-16 could each provide sufficient numbers of peripheral blood progenitor cells to support tandem cycles of myeloablative chemotherapy in 20 patients with stage IV breast cancer. Leukapheresis of blood with WBC > 1000/mm3 was performed daily for up to five collections (days 12-16), and mononuclear cells, CFU-GM, and CD34+ cells were compared between the first and second collections. The second course of mobilizing treatment resulted in similar numbers of mononuclear cells collected but far fewer CFU-GM and CD34+ progenitor cells. This prevented using the second collection of progenitor cells as the sole source for the second transplant. The data suggest that a second course of cyclophosphamide, etoposide, and G-CSF given 4 weeks after the first leads to progenitor cell depletion, and efforts to increase the yield of blood-derived progenitors should focus on the initial mobilizing procedure.


Stromal pH and Photosynthesis Are Affected by Electroneutral K and H Exchange through Chloroplast Envelope Ion Channels.
Potassium movement across the limiting membrane of the chloroplast inner envelope is known to be linked to counterex-change of protons. For this reason, K(+) efflux is known to facilitate stromal acidification and the resultant photosynthetic inhibition. However, the specific nature of the chloroplast envelope proteins that facilitate K(+) fluxes, and the biophysical mechanism which links these cation currents to H(+) counterflux, is not characterized. It was the objective of this work to elucidate the nature of the system regulating K(+) flux linked to H(+) counterflux across the chloroplast envelope. In the absence of external K(+), exposure of spinach (Spinacia oleracea) chloroplasts to the K(+) ionophore valinomycin was found to increase the rate of K(+) efflux and H(+) influx. These data were interpreted as suggesting that H(+) counterexchange must be indirectly linked to movement of K(+) across the envelope. Studies using the K(+) channel blocker tetraethylammonium indicated that K(+) likely moves, in a uniport fashion, into or out of the stroma through a monovalent cation channel in the envelope. Blockage of K(+) efflux from the stroma by exposure to tetraethylammonium was found to restrict H(+) influx, further substantiating an indirect linkage of these cation currents. Further studies comparing the effect of exogenous H(+) ionophores and K(+)/H(+) exchangers suggested that K(+) uniport through this ion channel likely is the main endogenous pathway for K(+) currents across the envelope. These experiments were also consistent with the presence of a proton channel in the envelope. Movement of H(+) through this channel was speculated to be regulated and rate limited by an electroneutral requirement for K(+) countercurrents through the separate K(+) uniport pathway. K(+) and H(+) fluxes across the chloroplast envelope were envisioned to be interrelated via this mechanism. The significant effect of cation currents across the envelope, as mediated by these channels, on photosynthetic capacity of the isolated chloroplast was also demonstrated.


Osteoclastic resorption of biphasic calcium phosphate ceramic in vitro.
Neonatal rabbit bone cells were cultured for 1 and 4 days on biphasic calcium phosphate ceramic specimens to study the osteoclastic resorption of the ceramic. Scanning electron microscopic studies after removal of stromal cells with pronase E and EDTA revealed many osteoclast-associated lacunae on the ceramic surface. The degraded crystals inside the lacunae appeared to have been dissolved by acids. Cellular degradation of the ceramic was clearly due to the extracellular process characteristic of osteoclastic resorption.


Extracellular Vesicles Derived from Human Umbilical Cord Mesenchymal Stromal Cells Protect Cardiac Cells Against Hypoxia/Reoxygenation Injury by Inhibiting Endoplasmic Reticulum Stress via Activation of the PI3K/Akt Pathway.
Endoplasmic reticulum (ER) stress is implicated in the pathogenesis of many diseases, including myocardial ischemia/reperfusion injury. We hypothesized that human umbilical cord mesenchymal stromal cells derived extracellular vesicles (HuMSC-EVs) could protect cardiac cells against hyperactive ER stress induced by hypoxia/reoxygenation (H/R) injury. The H/R model was generated using the H9c2 cultured cardiac cell line. HuMSC-EVs were extracted using a commercially available exosome isolation reagent. Levels of apoptosis-related signaling molecules and the degree of ER stress were assessed by western blot. The role of the PI3K/Akt pathway was investigated using signaling inhibitors. Lactate dehydrogenase leakage and 3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium Bromide (MTT) analysis were used for evaluating the therapeutic effects of HuMSC-EVs in vitro. The results showed that ER stress and the rate of apoptosis were increased in the context of H/R injury. Treatment with HuMSC-EVs inhibited ER stress and increased survival in H9c2 cells exposed to H/R. Mechanistically, the PI3K/Akt pathway was activated by treatment with HuMSC-EVs after H/R. Inhibition of the PI3K/Akt pathway by a specific inhibitor, LY294002, partially reduced the protective effect of HuMSC-EVs. Our findings suggest that HuMSC-EVs could alleviate ER stress-induced apoptosis during H/R via activation of the PI3K/Akt pathway.


Comparison of clinical and electrophysiological findings in patients with suspected radiculopathies.
Cervical and lumbar roots may be irritated or compressed due to the pathological conditions such as disc herniations, degenerative foraminal stenosis, trauma and tumors. Electrophysiologic tests are frequently used in conjunction with imaging modalities for evaluation of low back and neck pain radiating to extremities, primarily for the purpose of establishing the presence or absence of a radiculopathy. In this study, we aimed to evalulate the relationship between clinic and electroneuromyographic (ENMG) findings in patients with suspected radiculopathies. Forty one patients with radicular complaints in the upper extremities and 51 patients with radicular complaints in the lower extremities were included in this study. McNemar test and Kappa coefficients between the two methods were applied to each group of patients, in order to test the significance of the difference between the two diagnostic procedures' ability on finding out the pathology. The McNemar test identified a significant difference between the two diagnostic approaches both for cervical and lumbar radiculopathies (p<0.001). The Kappa coefficients between the two methods were determined as 0.08 and 0.07, respectively. This means, efficacy of anamnesis and neurological examination for the prediction of electrodiagnostic tests was found to be limited. Normal neurological examination results in a patient with suspected radiculopathy can not eliminate abnormal electrodiagnostic test results; likewise, abnormal findings in the neurological examination would not mean finding pathologies in the electrodiagnostic tests. For more accurate approach to a patient, neurological examination and electrodiagnostic tests must be used and interpreted together.


[Expression of erythropoietin receptor mRNA in mouse brain hemispheres].
Now there is a growing evidence that erythropoietin receptors (Epo-R) are present also in some nonhematopoietic tissues such as endothelial cells and fetal cells of neural origin, although the physiological role of Epo-R at these sites is unclear. There are some speculations that Epo-R may be expressed on cells only in the developing CNS. The objective of this study was to determine whether Epo-R mRNA may be expressed in the brain hemispheres of Balb/c mice of different age groups: 1) newborn mice, 2) young 2 months old mice, 3) old 1.8 year old mice. We also studied the in vivo effect of recombinant erythropoietin on the expression of Epo-R mRNA in the brain hemispheres of (CBA x C57BL)F1 mice by RT-PCR. We have detected the existence of Epo-R mRNA expression in brain hemispheres of all the groups, but in old mice this expression was significantly higher. We have discovered a decrease in Epo-R mRNA expression in brain hemispheres of (CBA x C57BL)F1 mice 24 h after in vivo administration of recombinant erythropoietin. The Epo-R mRNA expression in the left brain hemispheres of (CBA x C57BL)F1 was considerably higher than in the right one.


[A case of HTLV-I associated myelopathy (HAM) complicated by mononeuritis multiplex].
A 42-year-old woman with progressive myelopathy and mononeuritis multiplex is reported. The neurological examination on admission revealed hyperreflexia of the four extremities with pathological reflexes and moderate muscle weakness of the lower extremities with spasticity. Sensory disturbance was distributed on the areas of the bilateral lateral cutaneous femoral, the superficial peroneal and sural nerves. The antibody to HTLV-I in the serum and cerebrospinal fluid was more than 8192X and 512X, respectively. No sensory potential was recorded in the sensory conduction study of bilateral lateral femoral cutaneous nerves. Corticosteroid therapy caused a marked improvement of the sensory and urinary disturbances and had a slight effect on the spastic gait. Our nerve conduction study found small sensory potentials with normal conduction velocities in the bilateral lateral femoral cutaneous nerves. These results suggested the presence of an axonal degeneration in the peripheral nerves in this case. There have been no reports in the literature regarding a case of HAM with mononeuritis multiplex.


Effects of nonsteroidal anti-inflammatory drugs on experimental allergic conjunctivitis in Guinea pigs.
The effects of nonsteroidal anti-inflammatory drugs (NSAIDs) on experimental allergic conjunctivitis, induced by ocular challenge with antigen in actively sensitized guinea pigs, were investigated. NSAIDs reduced the increase in prostaglandin D2 (PGD2) and E2 (PGE2) in the ocular lavage fluid. The inhibition of NSAIDs to these increases was approximately 90%-95%. NSAIDs also lowered itch-scratch response (ISR) to approximately one-third to one-half of the vehicle-treated group. However, these drugs scarcely affected plasma exudation in the conjunctiva. Ketotifen, an H1 histamine receptor antagonist, inhibited both pathophysiological changes (inhibition: 70%-80%). However, this drug was less efficacious than NSAIDs in reducing PGD2 and PGE2 levels. Moreover, topical administration of histamine induced ISR and plasma exudation; in contrast, PGD2 induced ISR exclusively. These results suggest that a part of antigen-induced ISR may be attributable to PGs. However, PGs may not play a key role in plasma exudation; other mediators such as histamine may be involved.


Application of ionic liquid to enhance the nose-to-brain delivery of etodolac.
The purpose of this study was to enhance the delivery of Etodolac (ETD) to the brain through intranasal administration using an ionic liquid (IL) consisting of ETD and proline ethyl ester. The IL of ETD was prepared by mixing ETD with proline ethyl ester as a counterion in a molar ratio of 1:2.The formation of the IL was confirmed by differential scanning calorimetry (DSC), infrared spectroscopy (IR) and proton nuclear magnetic resonance (1H-NMR).The solubility of ETD in simulated nasal fluids was improved by approximately 200-fold due to the formation of IL. The intranasal administration of ETD-containing IL, which is viscous, increased the nose-to-brain delivery by approximately 7-fold 30 min after an administration of the ETD solution alone. The enhancement of ETD delivery to the brain from the nose was attributed to the enhanced retention of ETD in the nasal mucosal surface due to the viscosity of IL. The induction of prostaglandin E2 in the brain inflammation that was induced by lipopolysaccharides was significantly suppressed by up to 40% in the IL-treated group compared with the drug-untreated group. Therefore, ETD-containing IL were suggested to be useful in designing intranasal formulations for the nasal delivery of ETDs to the brain.


Cox-2 levels in canine mammary tumors, including inflammatory mammary carcinoma: clinicopathological features and prognostic significance.
Cyclo-oxygenase (Cox-2) plays an important role in mammary carcinogenesis, nevertheless, its role in canine mammary tumors, and particularly in inflammatory mammary carcinoma (IMC), is unknown. Tumor Cox-2 levels were analyzed by enzyme immunoassay, in post-surgical tumor homogenates of 129 mammary tumors (62 dysplasias and benign tumors, 57 malignant non-IMC and 10 IMC) from 57 female dogs. The highest Cox-2 values were detected in the IMC group. In non-IMC malignant tumors, high values of Cox-2 were related to skin ulceration (p < 0.001) and tumor size (p < 0.001). The follow-up study revealed that high Cox-2 levels were related with recurrence (p = 0.002), metastases (p < 0.001), disease-free survival (p < 0.001) and overall survival (p < 0.001). This study demonstrates an association between intra-tumor Cox-2 levels and poor prognosis. The high levels found in IMC cases could indicate a special role of Cox-2 in the inflammatory phenotype and open the possibility of additional new therapeutic approaches in this special type of mammary cancer in humans and dogs.


Oxidation-Responsive Aliphatic Polycarbonates from N-Substituted Eight-Membered Cyclic Carbonate: Synthesis and Degradation Study.
Oxidation-responsive aliphatic polycarbonates represent a promising branch of functional biodegradable polymers. This paper reports the synthesis and ring-opening polymerization (ROP) of an eight-membered cyclic carbonate possessing phenylboronic pinacol ester (C3) and the H2 O2 -triggered degradation of its polymer (PC3). C3 is prepared from the inexpensive and readily available diethanolamine with a moderate yield and undergoes the well-controlled anionic ROP with a living character under catalysis of 1,8-diazabicyclo[5.4.0]undec-7-ene. It can also be copolymerized with l-lactide, trimethylene carbonate, and 5-ter-butyloxycarbonylamino trimethylene carbonate, affording the copolymers with a varied distribution of the repeating units. To clearly demonstrate the oxidative degradation mechanism of PC3, this paper first investigates the H2 O2 -induced decomposition of small-molecule model compounds by proton nuclear magnetic resonance (1 H NMR). It is found that the adduct products formed by the in-situ-generated secondary amines and p-quinone methide (QM) are thermodynamically unstable and can decompose slowly back to QM and the amines. On this basis, this paper further studies the H2 O2 -accelerated degradation of PC3 nanoparticles that are prepared by the o/w emulsion method. A sequential process of oxidation of the phenylboronic ester, 1,6-elimination of the in-situ-generated phenol, releasing CO2 and intramolecular cyclization or isomerization is proposed as the degradation mechanism of PC3.


Interstitial Telomeric-like Repeats (ITR) in Seed Plants as Assessed by Molecular Cytogenetic Techniques: A Review.
The discovery of telomeric repeats in interstitial regions of plant chromosomes (ITRs) through molecular cytogenetic techniques was achieved several decades ago. However, the information is scattered and has not been critically evaluated from an evolutionary perspective. Based on the analysis of currently available data, it is shown that ITRs are widespread in major evolutionary lineages sampled. However, their presence has been detected in only 45.6% of the analysed families, 26.7% of the sampled genera, and in 23.8% of the studied species. The number of ITR sites greatly varies among congeneric species and higher taxonomic units, and range from one to 72 signals. ITR signals mostly occurs as homozygous loci in most species, however, odd numbers of ITR sites reflecting a hemizygous state have been reported in both gymnosperm and angiosperm groups. Overall, the presence of ITRs appears to be poor predictors of phylogenetic and taxonomic relatedness at most hierarchical levels. The presence of ITRs and the number of sites are not significantly associated to the number of chromosomes. The longitudinal distribution of ITR sites along the chromosome arms indicates that more than half of the ITR presences are between proximal and terminal locations (49.5%), followed by proximal (29.0%) and centromeric (21.5%) arm regions. Intraspecific variation concerning ITR site number, chromosomal locations, and the differential presence on homologous chromosome pairs has been reported in unrelated groups, even at the population level. This hypervariability and dynamism may have likely been overlooked in many lineages due to the very low sample sizes often used in cytogenetic studies.


Early Outcomes of a High-Resolution Anoscopy-Based Anal Cancer Screening Program Among People With HIV Enrolled in an Integrated Health Care System.
Few studies have examined outcomes of high-resolution anoscopy (HRA)-based screening for people with HIV infection (PWH), a population at increased risk for anal cancer. Large integrated health care system. Cohort study of 13,552 people with HIV infection, comparing incidences of anal cancer and advanced anal cancer (higher stage, recurrence, death, or surgical salvage) before and after HRA became available (2008). Calendar time was divided as 1998-2007, 2008-2010, and 2011-2012. Rate ratios (RRs) were obtained from Poisson regression models with adjustment for baseline demographic and health variables. Cohort cases during 2008-2012 were included in a nested case-control study, evaluating association of screening with anal cancer (33 cases, 330 controls) and advanced anal cancer (19 cases, 190 controls). Odds ratios (ORs) for receipt of screening were obtained from conditional logistic regression models with adjustment for baseline demographic and health history variables. Compared with 1998-2007 (pre-HRA), 2008-2010 adjusted RRs were 1.32 [95% confidence intervals (CI): 0.77 to 2.27; P = 0.31] for anal cancer and 2.11 (95% CI: 0.99 to 4.48; P = 0.053) for advanced anal cancer; and 2011-2012 adjusted RRs were 0.35 (95% CI: 0.12 to 0.99; P = 0.048) for anal cancer and 0.23 (95% CI: 0.03 to 1.77; P = 0.16) for advanced anal cancer. Individual history of screening did not reach statistical significance for anal cancer (OR 1.7; 0.6-4.6) or advanced anal cancer (OR 0.44; 0.1-3.8). Despite the possible effect of secular trends, we found 2008-2012 incidence trends for anal cancer and advanced anal cancer that seem consistent with expected findings of a beneficial screening program.


Presentation of renal tumor antigens by human dendritic cells activates tumor-infiltrating lymphocytes against autologous tumor: implications for live kidney cancer vaccines.
The clinical impact of dendritic cells (DCs) in the treatment of human cancer depends on their unique role as the most potent antigen-presenting cells that are capable of priming an antitumor T-cell response. Here, we demonstrate that functional DCs can be generated from peripheral blood of patients with metastatic renal cell carcinoma (RCC) by culture of monocytes/macrophages (CD14+) in autologous serum containing medium (RPMI) in the presence of granulocyte macrophage colony-stimulating factor and interleukin (IL) 4. For testing the capability of RCC-antigen uptake and processing, we loaded these DCs with autologous tumor lysate (TuLy) using liposomes, after which cytometric analysis of the DCs revealed a markedly increased expression of HLA class I antigen and a persistent high expression of class II. The immunogenicity of DC-TuLy was further tested in cultures of renal tumor infiltrating lymphocytes (TILs) cultured in low-dose IL-2 (20 Biologic Response Modifier Program units/ml). A synergistic effect of DC-TuLy and IL-2 in stimulating a T cell-dependent immune response was demonstrated by: (a) the increase of growth expansion of TILs (9.4-14.3-fold; day 21); (b) the up-regulation of the CD3+ CD56- TcR+ (both CD4+ and CD8+) cell population; (c) the augmentation of T cell-restricted autologous tumor lysis; and (d) the enhancement of IFN-gamma, tumor necrosis factor-alpha, granulocyte macrophage colony-stimulating factor, and IL-6 mRNA expression by TILs. Taken together, these data implicate that DC-TuLy can activate immunosuppressed TIL via an induction of enhanced antitumor CTL responses associated with production of Thl cells. This indicates a potential role of DC-TuLy vaccines for induction of active immunity in patients with advanced RCC.


Characterization of Sweetmeat Waste and Its Suitability for Sorption of As(III) in Aqueous Media.
Presence of arsenic in effluents from mining, mineral processing, and metal plating industries pose a serious health hazard to human beings. In this research, suitability of cheap sweetmeat waste (SMW), which is sweet industry byproduct, was investigated for the treatment of As(III). The physicochemical properties of the sorbent were characterized. The SEM images revealed highly heterogeneous sorbent surface. XRD analysis showed the presence of different polysaccharides mainly containing hydroxyl functional group. FTIR analysis was also performed to confirm the functional groups present in the sorbent. Batch experiments were conducted for kinetic analysis, effect of initial As(III) concentration, sorbent dose, electrolytes, pH, and temperature in order to understand sorption behavior. Presence of electrolyte, solution pH, and temperature were found to affect the performance of the sorbent. The sorption followed pseudo-second order reaction and Langmuir isotherm model best. The studies revealed SMW to be an efficient media for removal of As(III) from aqueous environment.


Unnecessity of Routine Dissection of Right Central Lymph Nodes in cN0 Papillary Thyroid Carcinoma Located at the Left Thyroid Lobe.
The lymph node posterior to the right recurrent laryngeal nerve (LN-prRLN) is an important part of the central lymph nodes (LNs). We aimed to explore the rate and predictors of LN-prRLN metastasis in cN0 papillary thyroid carcinoma (PTC) located at the left thyroid lobe. Patients with surgically treated primary left lobe PTC were retrospectively enrolled. The metastatic distribution of LN-prRLN and postoperative complications were assessed. The association between LN-prRLN metastasis and clinicopathological variables was evaluated by univariate and multivariate analyses. A total of 857 patients were included for the analysis. Central LN metastasis was noted in 310 (35.3%) cases. The most (27.6%) and least (1.7%) commonly involved LNs were the left paratracheal LN and the LN-prRLN. In the univariate analysis, the tumor size, multifocality, the extent of extrathyroidal extension (none vs. macroscopic vs. macroscopic maximal), and perineural invasion were associated with positive LN-prRLN. In the multivariate analysis, tumor size of >40.0 mm and macroscopic maximal invasion were found as the only two independent predictors. Transient and permanent hypoparathyroidism were noted in 90 (10.2%) and 13 (1.5%) patients, respectively. Voice change was noted in 40 (4.6%) patients, and 20 patients recovered. In cN0 PTC located at the left lobe, LN-prRLN metastasis was very uncommon. We found that LN-prRLN dissection is not required routinely, but should be performed if the tumor size is >40.0 mm and macroscopic maximal extrathyroidal extension is present.


Hypoalbuminemia and Elevated CRP are Risk Factors for Deep Infections and Urinary Tract Infections After Lumbar Spine Surgery in a Large Retrospective Patient Population.
Retrospective cross-sectional study. To determine if pre-operative albumin and CRP can predict post-operative infections after lumbar surgery. Patients who underwent an anterior lumbar interbody fusion (ALIF), posterior lumbar interbody fusion (PLIF), or lumbar discectomy were identified using a patient record database (PearlDiver) and were included in this retrospective study. Patients were stratified by Charlson Comorbidity Index (CCI) scores and pre-operative albumin and CRP status. Post-operative complications included deep infections and urinary tract infections within 3 months of the surgery and revisions within 1 year of the surgery. 74,280 patients were included in this study. 21,903 had pre-operative albumin or CRP lab values. 7,191 (33%), 12,183 (56%), and 2,529 (12%) patients underwent an ALIF, PLIF, and a lumbar discectomy, respectively. 16,191 did not have any complication (74%). The most common complication was UTI (16%). Among all patients, hypoalbuminemia was a significant risk factor for deep infection and UTI after ALIF, deep infection, UTI, and surgical revision after PLIF, and deep infection after lumbar discectomy. Elevated CRP was a significant risk factor for deep infection after ALIF, UTI after PLIF, and deep infection after lumbar discectomy in patients with a CCI ≤ 3. Pre-operative hypoalbuminemia and elevated CRP were significant risk factors for deep infection, UTI, and/or revision, after ALIF, PLIT, and/or lumbar discectomy. Future studies with a larger population of patients with low albumin and high CRP values are needed to further elaborate on the current findings.


Differential expression of histone deacetylases HDAC1, 2 and 3 in human breast cancer--overexpression of HDAC2 and HDAC3 is associated with clinicopathological indicators of disease progression.
In breast cancer, the role of epigenetic alterations including modifications of the acetylation status of histones in carcinogenesis has been an important research focus during the last years. An increased deacetylation of histones leads to increased cell proliferation, cell migration, angiogenesis and invasion. Class 1 histone deacetylases (HDAC) seem to be most important during carcinogenesis. The immunhistochemical expression of HDAC1, 2 and 3 was analyzed on tissue microarrays (TMAs) from 238 patients with primary breast cancer. We analyzed the nuclear staining intensity (negative, weak, moderate, strong) as well as the percentage of positive tumor cells and calculated the immunoreactivity score (0-12). Expression was correlated with clinicopathological parameters and patient survival. In this cohort, we found a differential positive expression of HDAC1, HDAC2 and HDAC3. HDAC2 and HDAC3 expression was significantly higher in less differentiated tumors: HDAC2 (n=207), p<0.001 and HDAC3 (n=220), p<0.001 and correlated with negative hormone receptor status: HDAC2 (n=206), p=0.02 and HDAC3 (n=219), p=0.04. Additionally, a high HDAC2 expression was significantly associated with an overexpression of HER2 (n=203, p=0.005) and the presence of nodal metastasis (n=200, p=0.04).HDAC1 was highly expressed in hormone receptor positive tumors (n=203; p<0.001). As a conclusion, our results show that the class-1 HDAC isoenzymes 1, 2 and 3 are differentially expressed in breast cancer. HDAC2 and HDAC3 are strongly expressed in subgroups of tumor with features of a more aggressive tumor type.


Membranous Extracellular Matrix-Based Scaffolds for Skin Wound Healing.
Membranous extracellular matrix (ECM)-based scaffolds are one of the most promising biomaterials for skin wound healing, some of which, such as acellular dermal matrix, small intestinal submucosa, and amniotic membrane, have been clinically applied to treat chronic wounds with acceptable outcomes. Nevertheless, the wide clinical applications are always hindered by the poor mechanical properties, the uncontrollable degradation, and other factors after implantation. To highlight the feasible strategies to overcome the limitations, in this review, we first outline the current clinical use of traditional membranous ECM scaffolds for skin wound healing and briefly introduce the possible repair mechanisms; then, we discuss their potential limitations and further summarize recent advances in the scaffold modification and fabrication technologies that have been applied to engineer new ECM-based membranes. With the development of scaffold modification approaches, nanotechnology and material manufacturing techniques, various types of advanced ECM-based membranes have been reported in the literature. Importantly, they possess much better properties for skin wound healing, and would become promising candidates for future clinical translation.


Novel thyrotropin (TSH)-TSH antibody complex in a healthy woman and her neonates.
A novel high-molecular-weight (MW) form of immunoreactive TSH [35,000 Da on Sephacryl S-200HR gel chromatography (S-200 chromatography)] was documented in a 32-year-old healthy woman who delivered two neonates with transient hyperthyrotropinemia. Her TSH levels ranged from 21.2 to 53.9 mU/L on different days or from 11.0 to 48.1 mU/L by the different immunoradiometric assay methods. The IgG fractions showed specific 125I-labeled hTSH binding and inhibited in vitro cAMP increase induced by hTSH but not that induced by bTSH. On protein G Superose HR affinity chromatography (protein G chromatography) equilibrated with 10 mmol/L sodium/potassium phosphate buffer (PB) followed by elution with 0.1mol/L glycine buffer, 95-99% of her TSH immunoreactivity eluted in the latter (bound) fraction while almost all was in the former (unbound) fraction in the control serum containing authentic hTSH. However, after dialysis of this bound fraction overnight with PB adding 0.5 mol/L NaCl (PB/NaCl), which exhibited greater ionic strength than PB, almost all TSH immunoreactivity changed from the bound fraction into the unbound fraction on the protein G chromatography equilibrated with PB/NaCl. These data indicate that the novel immunoreactive TSH was due to hTSH and hTSH-specific antibody complex, and dissociation of the complex may be incomplete on direct S-200. The immunoreactive TSH showed high MW form (35,000 Da). The dissociation may be almost complete during dialysis with greater ionic strength; the native TSH then appeared to be of formal size.


Thermal Responses in Football and Cross-Country Athletes During Their Respective Practices in a Hot Environment.
OBJECTIVE: To determine if football (FB) players and cross-country (CC) runners had different thermal responses to their respective training sessions. DESIGN AND SETTING: On days 4 and 8 of preseason training, we assessed core (T(c)) and skin (T(sk)) temperatures. SUBJECTS: Fifteen collegiate athletes volunteered: 10 FB players (age = 21.2 +/- 1.14 years, height = 193.5 +/- 4.8 cm, mass = 116.6 +/- 16.3 kg, and V(2max) = 44.7 +/- 9.4 mLkg(-1)min(-1)) and 5 CC runners (age = 22.8 +/- 2.77 years, height = 176.3 +/- 8.9 cm, mass = 71.16 +/- 8.9 kg, and V(2max) = 71.3 +/- 6.18 mLkg(-1)min(-1)). MEASUREMENTS: We measured T(c) using ingestible sensors before, during, and immediately after exercise. The T(sk) was measured at the calf, forearm, back, chest, and forehead sites. Level of dehydration was assessed by urine specific gravity. RESULTS: Mean wet-bulb temperature was 74 degrees F (23.33 degrees C). Resting T(c) in shorts and T-shirts was higher in the FB group. The T(c) midway through practices and runs was higher in the CC and FB subjects when active, compared with the FB subjects when inactive. Postexercise T(c) was higher in the CC group than the FB group with pads, and postconditioning T(c) was higher in the FB subjects with pads versus no pads. Forehead, chest, back, and mean weighted T(sk) were higher in the FB group. The T(c) and urine specific gravity were not correlated. CONCLUSIONS: The T(c) fluctuated in the FB subjects during practice depending on exercise intensity, whereas T(c) increased steadily in the CC subjects during continuous running. Thus, CC athletes may have to decrease intensity to maintain thermoregulation. Our FB players seemed to dissipate heat adequately during rest periods.


Osteoblast viability on hydroxyapatite with well-adjusted submicron and micron surface roughness as monitored by the proliferation reagent WST-1.
The impact of the cell surface roughness on titanium alloys used for biomedical implants has been extensively studied, whereas the dependency of human osteoblast viability on hydroxyapatite (HA) submicron and micron surface roughness has hitherto not yet been investigated in detail. Therefore, we investigate in this study the effect of HA substrates with different well-adjusted surface roughness on human osteoblast proliferation using the standard colorimetric reagent WST-1. By grinding, we obtained HA surfaces with six levels of well-defined surface roughness ranging from Sa = 3.36 µm down to 0.13 µm, resulting in hydrophilic contact angles from 11° to 27°. Energy dispersive X-ray spectroscopy, X-ray diffraction, and X-ray fluorescence measurements confirmed that neither grinding paper residues nor changes of the crystal structure were introduced to the HA substrates by the grinding process. By applying this simple surface treatment, we were able to isolate other effects from surface chemistry, crystal structure, and relative density. The changes of the osteoblast proliferation (WST-1 assay) on these different roughened HA surfaces after 7 days were found to be insignificant (p > 0.05), evaluated by one-way analysis of variance and Tuckey's Multiple Comparison Method. The results of this study show that all roughened HA surfaces, regardless of the microtopography, are biocompatible and allow osteoblast attachment, proliferation, and collagen type I production. The comparison with surface roughness used for standard Ti-based implants yielded that for HA no finishing process is necessary to ensure a sound human osteoblast cell proliferation in vitro.


Achieving Ultrasensitive Point-of-Care Assay for Mercury Ions with a Triple-Mode Strategy Based on the Mercury-Triggered Dual-Enzyme Mimetic Activities of Au/WO3 Hierarchical Hollow Nanoflowers.
The exploration of new strategies for portable detection of mercury ions with high sensitivity and selectivity is of great value for biochemical and environmental analyses. Herein, a straightforward, convenient, label-free, and portable sensing platform based on a Au nanoparticle (NP)-decorated WO3 hollow nanoflower was constructed for the sensitive and selective detection of Hg(II) with a pressure, temperature, and colorimetric triple-signal readout. The resulting Au/WO3 hollow nanoflowers (Au/WO3 HNFs) could efficaciously impede the aggregation of Au NPs, thus significantly improving their catalytic activity and stability. The sensing mechanism of this new strategy using pressure as a signal readout was based on the mercury-triggered catalase mimetic activity of Au/WO3 HNFs. In the presence of the model analyte Hg(II), H2O2 in the detection system was decomposed to O2 fleetly, resulting in a detectable pressure signal. Accordingly, the quantification of Hg(II) was facilely realized based on the pressure changes, and the detection limit could reach as low as 0.224 nM. In addition, colorimetric and photothermal detection of Hg(II) using the Au/WO3 HNFs based on their mercury-stimulated peroxidase mimetic activity was also investigated, and the detection limits were calculated to be 78 nM and 0.22 μM for colorimetric and photothermal methods, respectively. Hence, this nanosensor can even achieve multimode determination of Hg(II) with the concept of point-of-care testing (POCT). Furthermore, the proposed multimode sensing platform also displayed satisfactory sensing performance for the Hg(II) assay in actual water samples. This promising strategy may provide novel insights on the fabrication of a multimode POCT platform for sensitive, selective, and accurate detection of heavy metal ions.


Structural determinants for plant annexin-membrane interactions.
The interactions of two plant annexins, annexin 24(Ca32) from Capsicum annuum and annexin Gh1 from Gossypium hirsutum, with phospholipid membranes have been characterized using liposome-based assays and adsorption to monolayers. These two plant annexins show a preference for phosphatidylserine-containing membranes and display a membrane binding behavior with a half-maximum calcium concentration in the sub-millimolar range. Surprisingly, the two plant annexins also display calcium-independent membrane binding at levels of 10-20% at neutral pH. This binding is regulated by three conserved surface-exposed residues on the convex side of the proteins that play a pivotal role in membrane binding. Due to quantitative differences in the membrane binding behavior of N-terminally His-tagged and wild-type annexin 24(Ca32), we conclude that the N-terminal domain of plant annexins plays an important role, reminiscent of the findings in their mammalian counterparts. Experiments elucidating plant annexin-mediated membrane aggregation and fusion, as well as the effect of these proteins on membrane surface hydrophobicity, agree with findings from the membrane binding experiments. Results from electron microscopy reveal elongated rodlike assemblies of plant annexins in the membrane-bound state. It is possible that these structures consist of protein molecules directly interacting with the membrane surface and molecules that are membrane-associated but not in direct contact with the phospholipids. The rodlike structures would also agree with the complex data from intrinsic protein fluorescence. The tubular lipid extensions suggest a role in the membrane cytoskeleton scaffolding or exocytotic processes. Overall, this study demonstrates the importance of subtle changes in an otherwise conserved annexin fold where these two plant annexins possess distinct modalities compared to mammalian and other nonplant annexins.


Structure of a complete four-domain chitinase from Moritella marina, a marine psychrophilic bacterium.
X-ray crystallography reveals chitinase from the psychrophilic bacterium Moritella marina to be an elongated molecule which in addition to the catalytic β/α-barrel domain contains two Ig-like domains and a chitin-binding domain, all linked in a chain. A ligand-binding study using NAG oligomers showed the enzyme to be active in the crystal lattice and resulted in complexes of the protein with oxazolinium ion (the reaction intermediate) and with NAG2, a reaction product. The characteristic motif DXDXE, containing three acidic amino-acid residues, which is a signature of type 18 chitinases, is conserved in the enzyme. Further analysis of the unliganded enzyme with the two protein-ligand complexes and a comparison with other known chitinases elucidated the roles of other conserved residues near the active site. Several features have been identified that are probably important for the reaction mechanism, substrate binding and the efficiency of the enzyme at low temperatures. The chitin-binding domain and the tryptophan patch on the catalytic domain provide general affinity for chitin, in addition to the affinity of the binding site; the two Ig-like domains give the protein a long reach over the chitin surface, and the flexible region between the chitin-binding domain and the adjacent Ig-like domain suggests an ability of the enzyme to probe the surface of the substrate, while the open shallow substrate-binding groove allows easy access to the active site.


A novel recombinant marker virus assay for comparing the relative fitness of hiv-1 reverse transcriptase variants.
A novel recombinant marker virus assay (RMVA) has been developed to perform growth competition assays for assessing fitness of HIV-1. This assay allowed the generation of replication-competent viruses by homologous recombination of polymerase chain reaction (PCR)-derived reverse transcriptase (RT) coding sequences in RT-deleted proviral clones of HIV-1 in which the nef gene was replaced by the Salmonella typhimurium histidinol dehydrogenase (hisD) or human heat-stable placental alkaline phosphatase (PLAP) gene (pHIVDeltaRTBalIDeltanefhisD and pHIVDeltaRTBalIDeltanefPLAP, respectively). The proportion of a given RT species in a mixed culture was determined by quantifying the linked hisD or PLAP marker gene using real-time PCR. The RMVA was tested by comparing the relative fitness of wild-type and lamivudine-resistant recombinant viruses. The RMVA reproducibly detected differences in the fitness of these two viruses in growth competition assays. With appropriate modification of the recombination vectors, the RMVA should be useful for analyzing the fitness of viruses resistant to protease, integrase, or fusion inhibitors and should be applicable in clinical research.


Role of anticyclic citrullinated peptide in the diagnosis of early rheumatoid factor-negative suspected rheumatoid arthritis: is it worthwhile to order the test?
Anticyclic citrullinated peptide (anti-CCP) is a relatively new serologic marker, which has been proposed for use in the diagnosis of rheumatoid arthritis (RA) and is said to be a highly specific. The aim of the study was to evaluate the role of anti-CCP in a South Indian population of patients with suspected RA in the early stages when rheumatoid factor is negative and clinical presentation is atypical. Patients with early inflammatory arthritis who were rheumatoid factor-negative were investigated for anti-CCP. The patients were reviewed by a rheumatologist and, based on American College of Rheumatology criteria, were diagnosed with RA or another disease after a follow-up period of 3 to 6 months. The rheumatologist was blinded to the results of the anti-CCP. The sensitivity and specificity of anti-CCP was estimated in comparison to follow up and final clinical diagnosis. The anti-CCP was estimated by the enzyme-linked immunosorbent assay method using a commercially available kit (Euroimmune). One hundred forty-three patients with a mean age of 47.1 years and a male to female ratio of 0.22:1 were recruited for the study. Thirty cases were positive for anti-CCP and 41 cases were finally diagnosed RA. Twenty-six of the 30 anti-CCP-positive patients were diagnosed with RA. Thus, the sensitivity of anti-CCP in our institution for the diagnosis of RA in the early stage in a group of rheumatoid factor-negative patients with atypical presentation was 63.4% with 36.6% false-negatives and the specificity was 96.1% with 3.9% false-positive cases. The positive predictive value of anti-CCP was 86.7% and the negative predictive value was 86.7%. Kappa statistic of agreement, chi McNemar test, indicated anti-CCP to be an efficient test in this study population. Anti-CCP is a useful and highly specific but not absolutely specific or sensitive test to detect RA and supplements rheumatoid factor in the presence of a strong clinical suspicion.


Metastatic transitional cell carcinoma of the urinary bladder presenting as a mandibular gingival swelling.
Oral cavity metastases mostly originate from the breasts, lungs, or kidneys. Transitional cell carcinoma (TCC), the most frequent malignant tumor of the urinary bladder, rarely metastasizes to the jaws. To the best of our knowledge, only 8 cases of bladder carcinoma have been reported in the English literature to metastasize to the jawbones. A new case of mandibular metastasis of urinary bladder TCC with extension to the gingiva is presented in a 64-year-old white man. The patient was referred for a periodontal infection of the upper right first molar. The clinical examination also showed a gingival swelling located in the lower left premolar region with a hypoasthesia of the left side of the lower lip. The gingival mass was biopsied, and the microscopy showed a mandibular metastatic TCC of the urinary bladder extending to the gingiva. Periodontists should be aware that, although gingival metastases are rare, when they occur they may mimic other local benign pathological conditions.


[One century of "sleeping sickness" in West Africa].
This paper summarizes the geography of sleeping sickness disease (or Human African Trypanosomiasis, HAT) over the last 100 years in West Africa, with the objective of identifying today's priority areas for the sleeping sickness surveillance. The history and geography of the disease are based on a bibliographic review of old reports and recent publications on recent results obtained from medical surveys conducted in West Africa up to 2007. This allowed us to situate the historical geography of HAT from the beginning of the 20th century to nowadays. For instance, active HAT foci seem to have moved from the North (savannah area) to the South (forest area) in the last century. Taking into account the limited nature of the information available, endemic HAT presently appears to be limited to areas where annual rainfall is higher than 1,200 mm, although the reasons for this remain unknown. During this period of time there has also been a shift towards the south of the isohyets and of the northern distribution limit of tsetse. Currently the most severely affected countries are Guinea and Ivory Coast, whereas the northern countries seem less affected, but many parts of West Africa still lack information on HAT and remain to be investigated. These observations, put back in the current context of demographic growth and climatic global change, responsible for landscape evolution, political instability and population movements, raise the question of HAT becoming.


Congenital Pulmonary Airway Malformation in an Adult Male Presenting With Hemoptysis.
Congenital pulmonary airway malformations (CPAMs) are rarely encountered in the adult population. Although they are typically diagnosed in the prenatal period, some may not cause symptoms and go unnoticed until adulthood. Patients with CPAM are at risk of developing pneumonia, hemorrhage, pneumothorax, and malignancy. There is a paucity of evidence regarding the management and prognostication of adults with CPAM. Patients often need to undergo surgical resection to prevent further episodes of infection, bleeding, or malignant transformation. Here, we present the case of an adult male with a CPAM who presented with frank hemoptysis. Computed tomography scan and bronchoscopy localized the lesion to the lingula. The patient underwent elective surgical resection of the lesion by video-assisted thoracoscopy and did not suffer any adverse outcomes. Surgical resection is generally recommended and appears to be a safe and effective approach to treating patients with symptomatic CPAMs. Inhaled tranexamic acid and bronchial artery embolization are valuable interventions in our armamentarium for managing hemoptysis but should not replace a definite surgical intervention due to the risk of recurrence.


Engineering hydrophobically modified chitosan for enhancing the dispersion of respirable microparticles of levofloxacin.
The potential of amphiphilic chitosan formed by grafting octanoyl chains on the chitosan backbone for pulmonary delivery of levofloxacin has been studied. The success of polymer synthesis was confirmed using FT-IR and NMR, whilst antimicrobial activity was assessed against Pseudomonas aeruginosa. Highly dispersible dry powders for delivery as aerosols were prepared with different amounts of chitosan and octanoyl chitosan to study the effect of hydrophobic modification and varying concentration of polymer on aerosolization of drug. Powders were prepared by spray-drying from an aqueous solution containing levofloxacin and chitosan/amphiphilic octanoyl chitosan. l-leucine was also used to assess its effect on aerosolization. Following spray-drying, the resultant powders were characterized using scanning electron microscopy, laser diffraction, dynamic light scattering, HPLC, differential scanning calorimetry, thermogravimetric analysis and X-ray powder diffraction. The in vitro aerosolization profile was determined using a Next Generation Impactor, whilst in vitro antimicrobial assessment was performed using MIC assay. Microparticles of chitosan have the property of mucoadhesion leading to potential increased residence time in the pulmonary mucus, making it important to test the toxicity of these formulations. In-vitro cytotoxicity evaluation using MTT assay was performed on A549 cell line to determine the toxicity of formulations and hence feasibility of use. The MTT assay confirmed that the polymers and the formulations were non-cytotoxic. Hydrophobically modifying chitosan showed significantly lower MIC (4-fold) than the commercial chitosan against P. aeruginosa. The powders generated were of suitable aerodynamic size for inhalation having a mass median aerodynamic diameter less than 4.5μm for formulations containing octanoyl chitosan. These highly dispersible powders have minimal moisture adsorption and hence an emitted dose of more than 90% and a fine particle fraction (FPF) of 52%. Powders with non-modified chitosan showed lower dispersibility, with an emitted dose of 72% and FPF of 20%, as a result of high moisture adsorption onto the chitosan matrix leading to cohesiveness and subsequently decreased dispersibility.


Intermingled skin grafting: a valid transplantation method at low cost.
The almost forgotten method of intermingled skin grafting of allogeneic material with small autogeneic islets, once developed in the People's Republic of China, proves the feasibility of permanent healing of even extensive burn wounds, at low cost, and therefore an effective treatment possibility in poorer countries, as well as under conditions of a burn disaster. Intermingled skin grafting obtains a better elasticity of the reconditioned skin as elastic fibres of the allodermis survive, and this results in fewer contractures. From the cosmetic point of view the transplantation of autologous keratinocytes results in a better aesthetic homogeneous texture.


Pigmented purpuric eruptions: immunopathologic studies supportive of a common immunophenotype.
Traditionally, the pigmented purpuric eruptions (PPE) have been subdivided into four histologic categories, based upon variations in histologic pattern and clinical morphologies. In recent years, it has become apparent that the lesions behave similarly, and this family of eruptions has become grouped under the term PPE. The pathogenesis of these eruptions is largely unknown. In this study, we examined 13 examples of the histologic and clinical subtypes of the PPE with a panel of hematolymphoid immunophenotypic markers, in hopes of better understanding the pathogenesis of these curious eruptions. All lesions examined showed a predominantly T cell infiltrate composed of a mixture of OPD4 (CD4) positive and OPD4 negative cells. B cells were rare. Macrophages did not comprise a significant component of the infiltrate. The staining pattern was relatively constant, independent of the histologic pattern (i.e., Schamberg's vs. Gougerot-Blum, etc) of the PPE. Our results suggest that PPE are a group of related eruptions which may have a common pathogenesis. It seems likely that the vascular damage and erythrocyte extravasation are secondary to a localized cell-mediated immunologic event.


The association between clinical oral health status and oral impacts experienced by older individuals in Sri Lanka.
The aim of this study was to determine the association between clinical oral status and oral impacts experienced by older individuals in Sri Lanka. A total of 585 individuals who were above 60 years and were residents of an urban area was selected using a multistage cluster sampling combined with probability proportionate to size technique. However the present analysis is limited to 235 individuals who were subjected to a clinical oral examination. An interviewer administered Sinhala translation of the Oral Health Impact Profile-14 (OHIP-14) scale was used to assess the oral impacts experienced by the sample. An oral examination was carried out following the interview. Of the 235 subjects clinically examined 64 (27%) were edentulous. The associations between clinical parameters and oral impacts were assessed in the 171 dentate subjects. There were positive, weak but significant correlations between the number of missing teeth, the number of teeth with third degree mobility and the OHIP score. Also those who wore dentures and had halitosis had significantly higher OHIP scores than those who did not wear dentures and did not have halitosis. Logistic regression analysis revealed that 'wearing denture' and 'having halitosis' were significant predictors of the OHIP score. In conclusion, there was a weak association between clinical parameters and oral impacts experienced by these older individuals.


Factors affecting usefulness of triticale grain for bioethanol production.
Triticale grain could be a useful material for bioethanol production. The aim of this study was to examine how grain cultivar, nitrogen fertilisation level, location and year affect the starch content in triticale grain and which method of starch determination, polarimetric, enzymatic or near-infrared transmission (NIT), gives the best prediction of real bioethanol productivity from triticale grain. It was found that the starch content in triticale grain was correlated positively with test weight and 1000-kernel weight but negatively with falling number and protein content. All factors, i.e. cultivar, nitrogen fertilisation level, location and year, as well as the intrinsic interaction between these factors, had a significant effect on the starch level in triticale grain. The NIT procedure of starch determination gave the best results in predicting the real yield of ethanol obtained on the basis of classic fermentation (95% match), while the enzymatic and polarimetric methods corresponded with the real results at levels of 89-90 and 78-82% respectively. Grain growth conditions related to location and nitrogen fertilisation level had the most noticeable effect on grain starch content, while grain yield per hectare had the most significant effect on ethanol productivity.


Pressure induced magnetic phase separation in La0.75Ca0.25MnO3 manganite.
The pressure dependence of the Curie temperature T(C)(P) in La(0.75)Ca(0.25)MnO(3) was determined by neutron diffraction up to 8 GPa, and compared with the metallization temperature T(IM)(P) (Postorino et al 2003 Phys. Rev. Lett. 91 175501). The behavior of the two temperatures appears similar over the whole pressure range, suggesting a key role of magnetic double-exchange also in the pressure regime where the superexchange interaction is dominant. The coexistence of antiferromagnetic and ferromagnetic peaks at high pressure and low temperature indicates a phase separated regime which is well reproduced with a dynamical mean-field calculation for a simplified model. A new P-T phase diagram has been proposed on the basis of the whole set of experimental data.