Applications of electroencephalography to characterize brain activity: perspectives in stroke.
A wide array of neuroimaging technologies are now available that offer unprecedented opportunities to study the brain in health and disease. Each technology has associated strengths and weaknesses that need to be considered to maximize their utility, especially when used in combination. One imaging technology, electroencephalography (EEG), has been in use for more than 80 years, but as a result of recent technologic advancements EEG has received renewed interest as an inexpensive, noninvasive and versatile technique to evaluate neural activity in the brain. In part, this is due to new opportunities to combine EEG not only with other imaging modalities, but also with neurostimulation and robotics technologies. When used in combination, noninvasive brain stimulation and EEG can be used to study cause-and-effect relationships between interconnected brain regions providing new avenues to study brain function. Although many of these approaches are still in the developmental phase, there is substantial promise in their ability to deepen our understanding of brain function. The ability to capture the causal relationships between brain function and behavior in individuals with neurologic disorders or injury has important clinical implications for the development of novel biomarkers of recovery and response to therapeutic interventions. The goals of this paper are to provide an overview of the fundamental principles of EEG; discuss past, present, and future applications of EEG in the clinical management of stroke; and introduce the technique of combining EEG with a form of noninvasive brain stimulation, transcranial magnetic stimulation, as a powerful synergistic research paradigm to characterize brain function in both health and disease.Video Abstract available (see Supplemental Digital Content 1, http://links.lww.com/JNPT/A87) for more insights from the authors.


An immunohistochemical and ultrastructural study of the sinusoids of hepatocellular carcinoma.
The sinusoids of 30 human hepatocellular carcinomas of various types were examined by electron microscopy and histochemically for binding to the Ulex europaeus lectin (UEA1). A population of sinusoidal macrophages was identified with an antibody to lysozyme (muramidase). The UEA1 binding was negative in normal sinusoids but positive in the tumor vessels. Macrophages resembling Kupffer cells were found within the tumor vessels but in smaller numbers than in either normal or cirrhotic liver tissue. Fibrolamellar and sclerosing carcinomas contained the smallest numbers. Ultrastructurally, endothelial cells of tumor vessels were thicker than normal, with fewer fenestrations. They contained bundles of microfilaments and showed basement membrane formation. Subendothelial myoid cells were found. These findings indicate that the sinusoidal vessels of hepatocellular carcinomas show features of true capillaries and precapillary blood vessels. The degree of this difference from normal hepatic sinusoids may reflect the relative immaturity of the cancer cells.


The severity of respiratory syncytial virus bronchiolitis in young infants in the United Arab Emirates.
Respiratory syncytial virus (RSV) respiratory infections are very common during infancy and account for the majority of hospitalizations during the fall and winter seasons. Patients vary in the severity of their illnesses, with most hospitalized patients needing oxygen and intravenous fluids. The objective of this study was to assess in hospitalized patients the severity of the disease in relation to age. We compared children who were <90 days old with children who were >90 days old for the duration of oxygen therapy, maximum oxygen concentration used, duration of stay and duration of intravenous fluids. We conducted a retrospective case review of national children <2 years admitted to the pediatric ward at Sheikh Khalifa Medical City with RSV proven bronchiolitis/pneumonia over a 3-month period from 1 September to 30 November 2001. Morbidity for group 1 (birth-90 days) and group 2 (91 days-2 years) was compared by the Mann-Whitney U-test using duration of oxygen therapy, maximum oxygen concentration used, duration of stay and duration of intravenous fluids. Multiple regression for duration of oxygen therapy was tested using the following risk factors as predictors: age group (1 or 2), previous ventilation, bronchopulmonary dysplasia (BPD) and prematurity. A total of 89 patients were admitted during this period. The mean age (SD) of group 1 (n = 28) and group 2 (n = 61) was 46.35 (25.57) days and 275.67 (156.79) days, respectively. The only statistically significant difference using the Mann-Whitney U-test was detected for duration of oxygen between the groups (p = 0.002). Using multiple regression, only age group acted as a predictor for duration of oxygen therapy (p < 0.001). This implies that the youngest children, group 1, are at a risk for prolonged oxygen therapy. Four patients from group 1 were admitted to the intensive care unit, of which two received ventilatory support. RSV respiratory infections affect infants <3 months old in a more severe form than older infants. Even though overall duration of stay was similar for both groups, young infants who in fact did require oxygen had a more protracted and severe illness compared with the older infants. This was evidenced by their longer duration of oxygen and more frequent need to be managed in the intensive care unit.


Diplopia following blepharoplasty.
The complication of extraocular muscle palsy following blepharoplasty is rare. In a review of 920 blepharoplasties at Manhattan Eye, Ear and Throat Hospital, three well-documented cases of diplopia following blepharoplasty could be found. Only one of these cases resolved within two months postoperatively. The explanation offered for this phenomenon is a Volkmann type contracture of the extraocular muscles following edema and hemorrhage into the muscle sheath.


Ultrasound assessment of gastric emptying time after a standardised light breakfast in healthy children: A prospective observational study.
Current guidelines recommend 6 h of fasting for solids before anaesthesia. However, prolonged fasting may lead to discomfort, hunger, thirst, misbehaviour and lipolysis. To prevent this, a more liberal fasting regimen has been empirically implemented in our children's hospital, allowing a shorter fasting time of 4 h for a standardised light breakfast. The aim of this study was to determine the gastric emptying time after a standardised light breakfast in healthy children. A prospective observational noninterventional study. After fasting overnight, the children had a standardised light breakfast. Before and afterwards, ultrasound examinations of the gastric antrum were performed hourly to determine the gastric antral area (GAA), which is a surrogate parameter for gastric volume in children in the right lateral position (RLP). Demographic data and fasting times are presented as mean ± SD (range) and GAA as median (interquartile range). Twenty-two children aged 7.8 (2.5 to 13.6) years volunteered for this study. After fasting overnight [735 ± 120 (467 to 930) min], the initial GAA was 3.06 (2.35 to 4.03) cm in RLP. After the light breakfast, GAA in RLP initially increased and decreased subsequently. After 4 h, GAA in RLP was lower than the initial value (median of differences -0.54, 95% confidence interval -1.00 to -0.07, P < 0.05). Correlation between GAA in RLP and fasting time was significant (r = -0.62, P < 0.0001). Using a linear regression model, the calculated mean gastric emptying time after the standardised light breakfast was 211 min for GAA = 3.06 cm. The study showed a mean gastric emptying time of less than 4 h after a standardised light breakfast in children. These results encourage our current clinical practice and support the efforts towards a more liberal fasting regimen for light meals in paediatric anaesthesia. German Registry of Clinical Studies (DRKS-ID: DRKS 00013893).


Long-term therapy for the pain of osteoarthritis: a comparison of zomepirac sodium and aspirin.
In this long-term, double-blind, multicenter study, efficacy and safety of zomepirac sodium were compared with those of aspirin for treatment of the chronic pain associated with osteoarthritis in 607 patients, 405 of whom received zomepirac and 202 of whom received aspirin. Final evaluations during one year of treatment showed zomepirac significantly more effective than aspirin for reducing pain at rest (P = 0.02) and average pain (P = 0.04). Moreover, zomepirac was rated better than aspirin in physician global evaluations of overall response to therapy (P = 0.02) and patient evaluations of pain relief (P = 0.03). At the end of the one-year study, patients were permitted to extend double-blind treatment for an additional year. In final evaluations for patients who continued, zomepirac was significantly better than aspirin for relief of pain on motion (P = 0.05) and also in patient global evaluations of therapeutic response (P = 0.02). Side effect profiles during the first year of therapy were generally comparable for zomepirac and aspirin. However, complaints related to the special senses, especially tinnitus and hearing disturbances, were reported more frequently during aspirin therapy, and urogenital side effects were more common during zomepirac therapy. For both drug groups, the overall incidence of side effects was lower in the second year than in the first. This is the first published study to show a nonsteroidal antiinflammatory agent to be more effective than aspirin for the long-term treatment of pain associated with osteoarthritis.


Factors Associated With the Intention to Begin Physical Activity Among Inactive Middle-Aged and Older Adults.
Factors that affect physical activity (PA) behavior change are well established. Behavioral intention is a strong psychological predictor of behavior; however, there is less research on the factors that affect the intention to increase PA participation specifically, especially among adults in mid and later life who are inactive. Using data from the Canadian Community Health Survey, which was informed by the transtheoretical model (TTM), this study investigated the relationships between a range of demographic and biopsychosocial factors with the intention to become physically active among 1,159 inactive adults aged 40 years and older. Comparisons were made between participants reporting the intention to begin PA in the next 30 days (TTM Preparation; n = 610), 6 months (TTM Contemplation; n = 216), or not at all (TTM Precontemplation; n = 333). First, multinomial logistic regression identified age, sex, ethnicity, education, restriction of activities, self-perceived health, and community belonging as factors significantly associated with 30-day PA intention, while age and ethnicity were significantly associated with 6-month PA intention, compared with those reporting no intention. Second, binary logistic regression revealed that education was the only factor that differentially associated with intention timeframe as participants with lower levels of education were less likely to report PA intention in 30 days compared with 6 months. Findings demonstrate key demographic, biopsychosocial, and temporal factors that warrant consideration for tailored PA promotion programs that aim to effectively address the constraints and barriers that negatively influence PA intention among middle-aged and older adults.


Progressive multifocal exophytic pontine glioblastoma: a case report with literature review.
Multifocal pontine glioblastoma exhibiting an exophytic growth pattern in the cerebello-pontine angle (CPA) is rare. We present a case of a 5-year-old girl with consecutive neurological imaging and other clinical findings indicating progressive multifocal exophytic pontine glioblastoma. Three lesions were reported, of which two were initially presented, and one was developed 2 months later. One lesion demonstrated a progressing exophytic extension in the cistern of the left side of the CPA. The other two lesions were located and confined within the pons. Initial magnetic resonance imaging and positron emission tomography-computed tomography indicated low-grade glioma or inflammatory disease. However, 2 and 3 months later, subsequent magnetic resonance spectroscopy (MRS) displayed elevated choline and depressed N-acetyl aspartate peaks compared with the peaks on the initial MRS, indicating a high-grade glioma. Subtotal resection was performed for the CPA lesion. Histopathologic examination showed discrepant features of different parts of the CPA lesion. The patient received no further chemotherapy or radiotherapy and died 2 months after surgery. The multifocal and exophytic features of this case and the heterogeneous manifestations on neurological images were rare and confusing for both diagnosis and surgical decision-making. Our case report may contribute knowledge and helpful guidance for other medical doctors.


Developmental expression of nerve growth factor in the eye of rats affected by inherited retinopathy: correlative aspects with retinal structural degeneration.
We have previously reported that exogenous administration of nerve growth factor (NGF) in C3H/HeJ mouse strain affected by retinitis pigmentosa (RP) delayed retinal degeneration, suggesting that NGF may be implicated in retinal development. Whether NGF is present in the developing eye was not investigated. To address this question we have used Royal College of Surgeons (RCS) rats, characterised by photoreceptor loss during postnatal life. The results of these studies showed that while the thickness of the outer nuclear layer (ONL) of RCS is comparable to controls, while the amount of NGF expressed in the eye of this mutant rat is significant lower, as compared to control eye. This observation suggests that the lower presence of NGF in the eye of RCS rats during early postnatal life might be one critical key factor implicated in RP. The results of these studies will be presented and discussed.


Positive regulation of botulinum neurotoxin gene expression by CodY in Clostridium botulinum ATCC 3502.
Botulinum neurotoxin, produced mainly by the spore-forming bacterium Clostridium botulinum, is the most poisonous biological substance known. Here, we show that CodY, a global regulator conserved in low-G+C Gram-positive bacteria, positively regulates the botulinum neurotoxin gene expression. Inactivation of codY resulted in decreased expression of botA, encoding the neurotoxin, as well as in reduced neurotoxin synthesis. Complementation of the codY mutation in trans rescued neurotoxin synthesis, and overexpression of codY in trans caused elevated neurotoxin production. Recombinant CodY was found to bind to a 30-bp region containing the botA transcription start site, suggesting regulation of the neurotoxin gene transcription through direct interaction. GTP enhanced the binding affinity of CodY to the botA promoter, suggesting that CodY-dependent neurotoxin regulation is associated with nutritional status.


Short- and Long-Term Self-Regulation and Sexual Risk-Taking Behaviors in Unmarried Heterosexual Young Adults.
The goal of this study was to explore associations between short- and long-term self-regulation and dimensions of oral and coital sexual risk-taking in emerging adulthood. A total of 287 unmarried heterosexual young adults ages 18 to 26 years (62% female; 87% European American; 81% enrolled in college) provided study data via Internet surveys. High levels of long-term self-regulation predicted later initiation of oral sex and coitus, fewer lifetime coital partners, increased likelihood of condom and other contraceptive use at last intercourse, and low composite levels of coital risk. High levels of short-term self-regulation predicted reduced likelihood of condom use and high overall coital risk. The discussion focuses on the interpretation of these effects and potential directions for future research.


Fine structure and origin of Kaposi's sarcoma.
Tumour cells in Kaposi's sarcoma with visceral involvement were studied by fine structural analysis. In the cytoplasm of these cells rod-shaped tubulated bodies resembling Weibel-Palade granules could be demonstrated. This finding and the occurrence of a basement membrane around the tumour cells characterize Kaposi cells as endothelial cells of blood vessels which may originate from undifferentiated vasoformative cells of the adventitia.


Syringic acid protects retinal ganglion cells against H2O2-induced apoptosis through the activation of PI3K/Akt signaling pathway.
Oxidative damage is believed to contribute to the pathogenesis of diabetic retinopathy. Syringic acid (SA), a naturally occurring O-methylated trihydroxybenzoic acid monomer extracted from Herba dendrobii, has been shown to possess antioxidant activity. However, the effects of SA on apoptosis of retinal ganglion cells (RGCs) induced oxidative damages have not yet been explored. The present study aimed to detect the effects of SA against hydrogen peroxide (H2O2)-induced cell damage in RGCs and to investigate the molecular mechanisms involved in this process. In the present study, we revealed that SA pretreatment obviously inhibited H2O2-induced RGC-5 cell injury. SA pretreatment also decreased H2O2-induced ROS production and MDA content in RGC-5 cells. In addition, SA pretreatment increased Bcl-2 expression and decreased the expression of Bax and cleaved caspase-3 in H2O2-induced RGC-5 cells. Moreover, SA pretreatment obviously increased PI3K and Akt phosphorylation in H2O2-induced RGC-5 cells. In conclusion, our results suggest that SA may protect RGC-5 cells against apoptosis induced by H2O2 through the activation of PI3K/Akt signaling pathway. Thus, SA may be beneficial in the treatment of diabetic retinopathy.


Intracavitary aspergilloma: transthoracic percutaneous injection of amphotericin gelatin solution.
For aspergillomas in patients with fibrocavitary lung disease, surgery is often not recommended. Injection or lavage of the cavities with solutions of potassium iodide or antifungal agents has had varying success and requires repeated sessions because of nonretention of the therapeutic agent within the cavity. In three patients with four aspergillomas, the authors used fluoroscopic or computed tomographic (CT) guidance to inject amphotericin in gelatin as a liquid that solidifies within the cavity at body temperature. The patients were followed up with serial chest radiography or CT. The mixture was successfully instilled in every case. Three of the four aspergillomas completely resolved within 3 months or less, with no evidence of recurrence at follow-up of 6-18 months. The remaining aspergilloma decreased in size, but the patient needed pneumonectomy because of recurrent hemoptysis within 6 months of amphotericin injection. Transthoracic instillation of a liquid mixture of amphotericin and gelatin that solidifies rapidly at body temperature may be useful as a one-step treatment for aspergillomas.


Interventional techniques in managing persistent pain after vertebral augmentation procedures: a retrospective evaluation.
Based on systematic reviews, it appears that at least 10% of patients may continue to suffer with residual or persistent pain after successful vertebral or sacral augmentation procedures. To report and evaluate the incidence and prevalence of different spinal injections in patients who received vertebroplasty, kyphoplasty, and sacroplasty procedures for both benign and malignant compression fractures. A retrospective case review. Retrospective review of all cases of vertebroplasty, sacroplasty, and kyphoplasty performed in a 12-month period in a single outpatient setting of interventional radiology was conducted. In a 12-month period starting from October 2005 to September 2006, 144 patients underwent cement augmentation procedures. Of the 144, 34 patients required a spinal injection procedure for residual or persistent pain within a 1-year period after the augmentation procedure. Twenty-four patients required epidural steroid injections, 6 patients required intercostal nerve blocks, 5 patients required trigger point injections, 5 patients required sacroiliac joint injections, and 1 patient required facet joint injections. Nine patients who required lumbar epidural steroid injections and all patients who required intercostal nerve blocks and had underwent a thoracic cement augmentation procedure. A small proportion of patients undergoing percutaneous cement augmentation for vertebral compression fractures or sacral insufficiency fractures potentially require spinal injections to treat residual pain after the procedure.


"I Felt Like I Was Being Abused All Over Again": How Survivors of Child Sexual Abuse Make Sense of the Perinatal Period Through Their Narratives.
Sequelae following child sexual abuse pervade the lives of adult survivors, significantly impacting on pregnancy and childbirth. Symptoms of this distress are recognized, but meanings for women are less understood. This research aimed to examine the meaning for women themselves of the impact of child sexual abuse on experiences of pregnancy, childbirth, and the postnatal period. Taking a critical feminist perspective, three open-ended interviews with three survivors enabled women's narratives of pregnancy and childbirth to be heard, explored the structure of these narratives, including how experiences were connected, and identified key themes and how selves and others were positioned. Women themselves contributed to the analysis of their own narratives. The different struggles of each woman occurred within three domains of experience: identity, embodiment, and parenting. They were underpinned by a fluctuation between empowerment and disempowerment. These findings, although based on detailed analysis of the experiences of only three women, dovetail with, integrate, and extend the existent literature, offering a framework for understanding the complexity of meaning making for women. Further research might develop this. The framework may facilitate clinicians' understandings of what it is like for some women having children who have experienced child sexual abuse.


p53 protein expression by hepatocarcinogens in the rat liver and its potential role in mitoinhibition of normal hepatocytes as a mechanism of hepatic tumour promotion.
The tumour suppressor gene p53 is expressed in response to DNA-damage; its protein product blocks cells in the G1-phase of the cell cycle. This gives cells additional time to repair their DNA-damage. However, it may trigger apoptosis if damage is too high. Loss of p53 function appears to be an important step in carcinogenesis because 50% of human tumours have lost functional p53. In order to study the role of p53 in experimental hepatocarcinogenesis, we determined the expression of p53 in rat liver in response to various hepatocarcinogenic and hepatotoxic compounds. Administration of hepatocarcinogenic compounds increased p53 protein levels in the liver as detected by immunoprecipitation followed by SDS-PAGE and Western blotting with ECL-detection. The hepatocarcinogens included N-hydroxy-2-acetylaminofluorene, aflatoxin B1, and diethylnitrosamine. Their structural analogues N-hydroxy-4-acetylaminobiphenyl and ethyl methane-sulphonate which are not hepatocarcinogenic, did not induce p53. Also, two hepatotoxic compounds (carbon tetrachloride, D-galactosamine) did not induce p53. Other compounds that induced p53 in the rat liver were 2-aminofluorene (administered by drinking water for two weeks) and tris-(2,3-dibromopropyl)phosphate. Benzo[a]pyrene did not induce p53. N-Hydroxy-2-acetylaminofluorene, aflatoxin B1, and diethylnitrosamine are potent hepatic tumour promoters. At the same time, they induce p53 protein expression and inhibit proliferation of normal hepatocytes. Because this is not observed with non-hepatocarcinogenic analogues, it suggests an involvement of p53 expression in hepatic tumour promotion. A possible mechanism is discussed.


Biomedical engineering at UCT - challenges and opportunities.
The biomedical engineering programme at the University of Cape Town has the potential to address some of South Africa's unique public health challenges and to contribute to growth of the local medical device industry, directly and indirectly, through research activities and postgraduate education. Full realisation of this potential requires engagement with the clinical practice environment and with industry.


Expression of cyclooxygenase-2 and 12-lipoxygenase in human breast cancer and their relationship with HER-2/neu and hormonal receptors: impact on prognosis and therapy.
A number of studies have shown over-expression of cox-2 in breast cancer. Also it has been recorded that human breast cancer expresses high level of cox-2 and 12-lipoxygenase which may be beneficial in future therapy plan for those patients. The present study aims to examine the level of transcripts of cox-2 and 12-lipoxygenase in Egyptian breast cancer patients and to compare between the expressions of both enzymes and TNM staging, hormone receptors status (including estrogen and progesterone) and HER2/neu expression. Total cellular RNA was extracted from 64 frozen tissue samples of breast carcinoma and their corresponding normal adjacent tissues. Cox-2 and 12-lipooxygenase expressions were detected using RT-PCR. Hormonal receptors as well as HER2/neu were detected immuno-histochemically for each patient. About 47 and 62.5% of carcinoma samples showed over-expression of cox-2 and 12-lipooxygenase respectively as compared to their corresponding normal tissues. The results revealed that cox-2 significantly associated with TNM staging (P = 0.0047) and hormonal receptors status (P = 0.0201). The relationship between cox-2 and HER2/neu expression was close to a significant value (P = 0.0747). 12-lipooxygenase showed only significant association with TNM staging (P = 0.0076). Neither hormonal receptors nor HER2/neu showed significant association with this enzyme. Elevated levels of cox-2 and 12-lipoxygenase expression were detected in human breast cancer. Also, the results revealed that cox-2 and 12-lipooxygenase mRNA expressions are associated with TNM staging in human breast cancer. Furthermore, there is an inverse association between cox-2 expression and hormonal receptor status. This observation may drive us to the possible role of those two enzymes in determining the plan of therapy of breast cancer patients.


Body mass and exercise variable relationships to lactate derived from gravity-independent devices.
Historically, exercise performance outcomes may be predicted with anthropometric variables such as body mass. To assess body mass and resistance exercise (REX) performance variable correlations to blood lactate values, subjects performed five different workouts on two devices that do not employ gravitational resistance. One device uses flywheels to impose a low-speed high-resistance exercise stimulus while the other, dubbed a Dual Performance Device (DPD), has a sled mounted on a very low friction track to enable high-speed low-resistance repetitions. Subjects (n = 18) performed 3 leg press workouts on the flywheel ergometer (FE), which entailed: 1) a 3-set 10-repetition protocol with concentric and eccentric actions; or 2) the same set-repetition paradigm with concentric-only actions; or 3) a 6-set 10-repetition protocol of concentric-only actions. DPD workouts, done by a separate (n = 22) group, involved 2 workouts each composed exclusively of tonic or phasic seated knee and hip extensor repetitions. Multivariate regression was employed, with post-exercise and delta (post/ pre) blood lactate values as criterion measures. While body mass and performance values from FE workouts were weakly correlated to the criterion measures, body mass and average power (AP) variables from DPD tonic workouts explained 99% of the post-exercise and delta[BLa-] variance and yielded two prediction equations: post-REX blood lactate' = 0.06 + 11.21(AP) + -11.53(body mass), delta blood lactate' = 0.03 + 11.83(AP) + -12.00(body mass). Results were most likely due to differences in central command requirements for each exercise device.


Meta-analysis of coronary artery bypass graft surgery combined with stem cell transplantation in the treatment of ischemic heart diseases.
The use of bone marrow cells (BMCs) to regenerate the myocardium and vessels is a new treatment for ischemic heart diseases (IHD) that has been receiving attention. In this study, a meta-analysis was used to analyze the efficacy of combining coronary artery bypass graft (CABG) surgery with BMC transplantation in the treatment of IHD. MEDLINE, EMBASE, Cochrane, CNKI, WAN-FANG, and WEI-PU databases were searched. The main inclusion criteria were as follows: (a) studies that analyzed patients diagnosed with chronic IHD. (b) Studies that had randomized-controlled trials. (c) Studies that included research comparing the efficacy of CABG and CABG combined with bone BMC transplantation in the treatment of IHD. (d) Studies with specific enumeration data at the end of the follow-up with a follow-up time of at least 3 months. Nine randomized trials were included. There were 158 patients in the group that received the treatment of CABG surgery as well as stem cell transplantation, referred to as the 'cell transplantation group.' A total of 147 patients were in the group that only received the treatment of CABG surgery, referred to as the 'CABG group'. Our data show that not only did stem cell transplantation significantly improve left ventricular ejection fraction (odds ratio=11.7, 95% confidence interval: 4.04-19.36; P=0.003) but it also significantly reduced the left ventricular end-diastolic volume and left ventricular end-systolic volume (P<0.001). BMC transplantation is associated with a significant improvement in left ventricular ejection fraction and the attenuation of left ventricular remodeling.


Production of stromal cell-derived factor-1 (SDF-1)and expression of CXCR4 in human bone marrow endothelial cells.
This study investigated the production of stromal cell-derived factor-1 (SDF-1) and the expression of CXCR4 in human bone marrow endothelial cells (BMECs). Human BMEC cell line BMEC-1 cells expressed SDF-1 mRNA, and conditioned medium induced chemoattraction of CD34+ cells. Migration was not inhibited by pretreating the input cells with pertussis toxin, indicating that the chemoattractive activity was not dependent on SDF-1. Three-day culture of BMEC-1 and primary human BMEC cells produced 1,710+/-204 and 1,050+/-153 pg/mL SDF-1alpha, respectively, which was much less than primary human BM stromal cells (29,536+/-532 pg/ mL). By immuno-histochemistry, CXCR4 was detected in the endothelial cells lining sinusoids, arterioles, and venules in the bone marrow. However, cultured BMECs and BMEC-1 cells did not express CXCR4 on their surfaces. These results indicate that BMECs produce and release small amounts of SDF-1 and express CXCR4 in vivo only.


[Blood ozonation in the treatment of patients with progressive pulmonary tuberculosis concurrent with diabetes mellitus].
Twenty nine patients with progressive pulmonary tuberculosis in the presence of diabetes mellitus were examined. Fifteen of them (a main group) had an additional course of intravenous dissolved ozone once 6-8 days (4 mg/ml per 400 ml of isotonic sodium chloride). By the end of month 2, 7 patients stopped massive bacterial expiration, which correlated with clinical improvement while a control group (n = 14) showed no clinical and laboratory changes. Following 3 months, 3 control patients stopped massive bacterial expiration. At month 6, 11 patients of the main group also did this, decay cavities became close in 8 patients while in the controls, these figures were 8 and 7, respectively. The use of systemic blood ozoning eliminated chemotherapy resistance and accelerated abacillation and healing in the decay cavities. The mechanism of action of dissolved ozone is discussed.


The effects of phlebotomy, hemodilution and autologous transfusion on systemic oxygenation and whole blood utilization in open heart surgery.
Blood utilization in 400 consecutive adult patients undergoing a wide variety of cardiovascular operations requiring cardiopulmonary bypass was documented following institution of: 1) complete oxygenator hemodilution; 2) intraoperative phlebotomy and autologous transfusion; 3) infusion of residual oxygenator red cells; and 4) use of reconstituted frozen cells in patients whose blood type was uncommon. These techniques have resulted in an average utilization of 4.8 units of blood per adult patient. Fourteen patients required no blood at all and a total of 259 patients required less than 5 units of blood during their entire hospital course. Physiologic effects of this blood program and hemodilution were evaluated in ten patients and the results indicate that marked reduction of red cell mass by hemodilution with hypothermia and low flow perfusion is not detrimental to satisfactory whole blood oxygenation during open heart surgery.


Current concepts in diagnosis and treatment of periodontitis.
This article describes some areas of periodontal research and current opinions regarding detection of disease progression, as well as risk indicators and risk factors associated with disease progression. Longitudinal probing of periodontal attachment level is considered the gold standard for detection of disease activity although there are problems with this concept. Digital subtraction radiography can assist in the detection of minor changes of alveolar bone height and density. Risk factors such as composition of subgingival plaque and gingival crevicular fluid, as well as the effect of smoking are discussed. Adjunctive treatment with both antibiotics and nonsteroidal anti-inflammatory drugs, systemic or local, seems to be helpful in some forms of disease. Immunization to prevent colonization of tooth surfaces and pockets by periodontal pathogens does not seem to be feasible in the near future.


Loss of LKB1 expression reduces the latency of ErbB2-mediated mammary gland tumorigenesis, promoting changes in metabolic pathways.
The tumor suppressor kinase LKB1 is mutated in a broad range of cancers however, the role of LKB1 mammary gland tumorigenesis is not fully understood. Evaluation of human breast cancer tissue microarrays, indicate that 31% of HER2 positive samples lacked LKB1 expression. To expand on these observations, we crossed STK11 (fl/fl) mice with mice genetically engineered to express activated Neu/HER2-MMTV-Cre (NIC) under the endogenous Erbb2 promoter, to generate STK11 (-/-/) NIC mice. In these mice, the loss of lkb1 expression reduced the latency of ErbB2-mediated tumorigenesis compared to the latency of tumorigenesis in NIC mice alone. Analysis of STK11(-/-/)NIC mammary tumors revealed hyperactivation of mammalian target of rapamycin (mTOR) through both mTORC1 and mTORC2 pathways as determined by the phosphorylation status of ribosomal protein S6 and AKT. Furthermore, STK11(-/-/)NIC mammary tumors had elevated ATP levels along with changes in metabolic enzymes and metabolites. The treatment of primary mammary tumor cells with specific mTOR inhibitors AZD8055 and Torin1, that target both mTOR complexes, attenuated mTOR activity and decreased expression of glycolytic enzymes. Our findings underscore the existence of a molecular interplay between LKB1-AMPK-mTORC1 and ErbB2-AKT-mTORC2 pathways with mTOR at its epicenter, suggestive that loss of LKB1 expression may serve as a marker for hyperactivated mTOR in HER2 positive breast cancer and warranting further investigation into therapeutics that target LKB1-AMPK-mTOR and glycolytic pathways.


Green-Light-Sensitive BODIPY Photoprotecting Groups for Amines.
We describe a series of easily accessible, visible-light-sensitive (λ > 500 nm) BODIPY (boron-dipyrromethene)-based photoprotecting groups (PPGs) for primary and secondary amines, based on a carbamate linker. The caged compounds are stable under aqueous conditions for 24 h and can be efficiently uncaged in vitro with visible light (λ = 530 nm). These properties allow efficient photodeprotection of amines, rendering these novel PPGs potentially suitable for various applications, including the delivery of caged drugs and their remote activation.


Long-term quality of life after en-bloc vertebrectomy: 25 patients followed up for 9 years.
Assess quality-of-life results in patients who have undergone extensive curative surgery for spinal tumor and compare them to the general population in France. Life expectancy is not the only criterion to assess the outcomes after massive tumor resections. Residual quality of life is also crucial. An indication for major surgery for spinal tumor should take the patient's long-term functional status into account, but the literature is limited on this question. Twenty-five living patients from a group of 120 operated were assessed, all of whom were operated on by the same surgeon between 1984 and 2007. The mean follow-up was 9 years (range, 3-25 years). The mean age at surgery was 49 years. The patients completed different functional and quality-of-life questionnaires: the Oswestry Disability Index version 2 (ODI), the PROLO, the Karnofsky Index of performance status (KI), the Eastern Cooperative Oncology Group performance status (ECOG), the Short Form-36 Health Survey (SF-36), and the EuroQol-5 Dimensions (EQ5D). In addition, each patient was clinically and radiographically evaluated. Subgroups were identified considering the number of levels resected and histology. Their results on the SF-36 were compared with the results from the general population in France. The mean PCS (physical component summary of the SF-36) was 52.4, the MCS (mental component summary, the psychological component of the SF-36) was 47.7, the ODI was 18.2, the PROLO was 7, the ECOG was 1, and the KI was 80%. The resections at three levels were associated with worse results in terms of quality of life, but overall, the results were similar to the French general population data for all categories of the SF-36. Appropriate indications for massive spinal resection give good oncological and functional results. Although the expected life expectancy justifies this aggressive surgery, postoperative quality of life shows that it can also be successful on a functional level. Level IV; retrospective clinical study.


Plasma and follicular fluid fatty acid profiles in dairy cows.
Composition of follicular fluid to which the preovulatory follicle is exposed may be one of the major factors determining subsequent fertility, as fatty acids are a precursor of hormones involved in dominance, ovulation and atresia mechanisms. The objective of this paper is to observe fatty acid profiles in various lipid classes according to estrogenic activity of follicles. For each of the 18 cows, we analysed plasma and follicular fluid fatty acid profiles of phospholipids, non-esterified fatty acid (NEFA), cholesteryl esters and triglycerides fractions. Follicles were classified as active (ratio oestrogen to progesterone E2/P4 > 1) and inactive (E2/P4 < 1). For seven cows, we get both types of follicles, six had only one active follicle and five cows had only one inactive follicle. The NEFA profile for palmitic acid, stearic acid, oleic acid, linoleic acid, C20:3n6, arachidonic acid and docosapentaenoic acid (DPA; p < 0.001) is different between inactive and active follicles and plasma. Compared with active follicular fluid and plasma, follicular fluid of inactive follicles showed lower stearic acid, higher oleic acid, arachidonic acid and DPA (p < 0.05) in phospholipids. No significant differences were observed in the cholesteryl ester fraction, which is composted mainly of linoleic acid. Triglyceride concentrations were too low to get reliable results. This study suggests that follicles have a specific fatty acid metabolism depending on oestrogen activity.


Pathways of Prion Spread during Early Chronic Wasting Disease in Deer.
Among prion infections, two scenarios of prion spread are generally observed: (i) early lymphoid tissue replication or (ii) direct neuroinvasion without substantial antecedent lymphoid amplification. In nature, cervids are infected with chronic wasting disease (CWD) prions by oral and nasal mucosal exposure, and studies of early CWD pathogenesis have implicated pharyngeal lymphoid tissue as the earliest sites of prion accumulation. However, knowledge of chronological events in prion spread during early infection remains incomplete. To investigate this knowledge gap in early CWD pathogenesis, we exposed white-tailed deer to CWD prions by mucosal routes and performed serial necropsies to assess PrPCWD tissue distribution by real-time quaking-induced conversion (RT-QuIC) and tyramide signal amplification immunohistochemistry (TSA-IHC). Although PrPCWD was not detected by either method in the initial days (1 and 3) postexposure, we observed PrPCWD seeding activity and follicular immunoreactivity in oropharyngeal lymphoid tissues at 1 and 2 months postexposure (MPE). At 3 MPE, PrPCWD replication had expanded to all systemic lymphoid tissues. By 4 MPE, the PrPCWD burden in all lymphoid tissues had increased and approached levels observed in terminal disease, yet there was no evidence of nervous system invasion. These results indicate the first site of CWD prion entry is in the oropharynx, and the initial phase of prion amplification occurs in the oropharyngeal lymphoid tissues followed by rapid dissemination to systemic lymphoid tissues. This lymphoid replication phase appears to precede neuroinvasion.IMPORTANCE Chronic wasting disease (CWD) is a universally fatal transmissible spongiform encephalopathy affecting cervids, and natural infection occurs through oral and nasal mucosal exposure to infectious prions. Terminal disease is characterized by PrPCWD accumulation in the brain and lymphoid tissues of affected animals. However, the initial sites of prion accumulation and pathways of prion spread during early CWD infection remain unknown. To investigate the chronological events of early prion pathogenesis, we exposed deer to CWD prions and monitored the tissue distribution of PrPCWD over the first 4 months of infection. We show CWD uptake occurs in the oropharynx with initial prion replication in the draining oropharyngeal lymphoid tissues, rapidly followed by dissemination to systemic lymphoid tissues without evidence of neuroinvasion. These data highlight the two phases of CWD infection: a robust prion amplification in systemic lymphoid tissues prior to neuroinvasion and establishment of a carrier state.


The effect of resin coating on the shear punch strength of restorative glass ionomer cements.
The aim of the current study was to examine the shear punch strength (SPS) of high-strength glass ionomer cements (HSGICs) in relation to coating applications and duration of coating. I-Ninety specimens each of Fuji IX GP Fast (FIX Fast), Ionofil Molar AC (IM), Riva Self Cure (R) and Ketac Molar (KM) were prepared and divided into uncoated and coated groups, sub-divided into three sub-groups and incubated for 24 h, 1 week or 8 weeks (distilled water, 37 °C) before SPS. II-Ninety specimens each of uncoated and coated Fuji IX GP Extra were similarly prepared, divided into six sub-groups and incubated for 2 h, 24 h, 1 week, 1 month, 2 months or 3 months (artificial saliva, 37 °C) before SPS. Another 90 specimens were coated for 2 h, 24 h, 1 week, 1 month or 2 months, after which the coating was removed. Specimens were re-incubated in artificial saliva until the end of the 3-month period and then subjected to SPS. None of the materials gained extra strength when coated. Uncoated KM, IM (at all times) and FIX Fast (at 24 h) were stronger. Fuji IX GP Extra achieved 11.5 MPa after 2 h, which increased to 56.7 MPa after 24 h. The highest strength after 3 months was achieved when the coating was retained for 2 h (71.7 MPa). A resin coating will not positively affect the SPS of HSGICs. There is no need to protect HSGICs from water to gain extra strength unless the coating is retained for 2 h.


Microparticle sorting with a virtual optical chip.
We proposed an automatic sorting method based on a virtual optical chip, which was formed by a complex-amplitude beam shaping system. The automatic sorting of different micro-particles was realized by the optical forces of the intensity and phase gradients of the reconstructed optical beam. The method was verified with theoretical analysis and experimental results. Compared with the traditional optical sorting methods, the proposed one does not need high-precision mechanical and/or microfluidic devices. The optical chip is flexible in structure and efficient in optical sorting and can be used in the fields of medical detection and material sensing.


Family profiles of maltreated children in Singapore: A latent class analysis.
Children who enter the child protection system often have complex family problems and have experienced early adverse experiences. Using latent class analysis, this study aimed to identify family classes of child protection cases in Singapore, to ascertain the prevalence of these family classes, and to test the association of family class membership to subsequent recurrence of harm. A sample of 440 cases who entered the Child Protective Service in Singapore was analyzed based on eight familial factors on the household and caregiver levels. A four-class solution was found to demonstrate the best fit: (a) the large household group was intergenerational and majority lived with extended family members, (b) the harsh parenting group showed high levels of parenting problems and the caregiver justifying his abuse/neglect, (c) the high criminality group had high levels of caregiver substance abuse and caregiver arrest and incarceration history, and (d) the low disadvantage group rated low on all the familial factors. A Cox Regression revealed that in comparison to the low disadvantage group, the harsh parenting group was twice as likely to have recurrence of harm. There were also differences across family classes with regard to age at entry into child protection, gender composition and abuse types. The findings and practice implications are discussed.


Biomaterial Cues Regulated Differentiation of Neural Stem Cells into GABAergic Neurons through Ca2+/c-Jun/TLX3 Signaling Promoted by Hydroxyapatite Nanorods.
Directed differentiation enables the production of a specific cell type by manipulating signals in development. However, there is a lack of effective means to accelerate the regeneration of neurons of particular subtypes for pathogenesis and clinical therapy. In this study, we find that hydroxyapatite (HAp) nanorods promote neural differentiation of neural stem cells due to their chemical compositions. Lysosome-mediated degradation of HAp nanorods elevates intracellular calcium concentrations and accelerates GABAergic neurogenesis. As a mechanism, the enhanced activity of a Ca2+ peak initiated by HAp nanorods leads to the activation of c-Jun and thus suppresses the expression of GABAergic/glutamatergic selection gene TLX3. We demonstrate the capability of HAp nanorods in promoting the differentiation into GABAergic neurons at both molecular and cellular function levels. Given that GABAergic neurons are responsible for various physiological and pathological processes, our findings open up enormous opportunities in efficient and precise stem cell therapy of neurodegenerative diseases.


[Traditional medicine and the present: the therapy of gout].
The authors describe the history of treatment of gout by using colchicine (colchicum; the active substance of Colchicum autumnale). The references to this plant and its effects (incl. several recipes for the preparation of remedies) in the gout treatment date back already from the antiquity, but the indisputable evidence of its use in the therapy of the disease in question comes only from the 6th century AD, by Alexander of Tralles. At present, colchicine became an officially preferred drug. Some other examples of medicines of plant origin (e.g. verbena), which were used already by ancient civilizations and are often chosen for therapy even today. The potential of medicinal drugs hasnt been completely exhausted yet.


Normal Neurochemistry in the Prefrontal and Cerebellar Brain of Adults with Attention-Deficit Hyperactivity Disorder.
Attention-deficit hyperactivity disorder (ADHD) is a common neurodevelopmental disorder. In an attempt to extend earlier neurochemical findings, we organized a magnetic resonance spectroscopy (MRS) study as part of a large, government-funded, prospective, randomized, multicenter clinical trial comparing the effectiveness of specific psychotherapy with counseling and stimulant treatment with placebo treatment (Comparison of Methylphenidate and Psychotherapy Study). We report the baseline neurochemical data for the anterior cingulate cortex (ACC) and the cerebellum in a case-control setting. For the trial, 1,480 adult patients were contacted for participation, 518 were assessed for eligibility, 433 were randomized, and 187 were potentially eligible for neuroimaging. The control group included 119 healthy volunteers. Single-voxel proton MRS was performed. In the patient group, 113 ACC and 104 cerebellar spectra fulfilled all quality criteria for inclusion in statistical calculations, as did 82 ACC and 78 cerebellar spectra in the control group. We did not find any significant neurometabolic differences between the ADHD and control group in the ACC (Wilks' lambda test: p = 0.97) or in the cerebellum (p = 0.62). Thus, we were unable to replicate earlier findings in this methodologically sophisticated study. We discuss our findings in the context of a comprehensive review of other MRS studies on ADHD and a somewhat skeptical neuropsychiatric research perspective. As in other neuropsychiatric disorders, the unclear nosological status of ADHD might be an explanation for false-negative findings.


Septin function in Candida albicans morphogenesis.
The septin proteins function in the formation of septa, mating projections, and spores in Saccharomyces cerevisiae, as well as in cell division and other processes in animal cells. Candida albicans septins were examined in this study for their roles in morphogenesis of this multimorphic, opportunistically pathogenic fungus, which can range from round budding yeast to elongated hyphae. C. albicans green fluorescent protein labeled septin proteins localized to a tight ring at the bud and pseudohyphae necks and as a more diffuse array in emerging germ tubes of hyphae. Deletion analysis demonstrated that the C. albicans homologs of the S. cerevisiae CDC3 and CDC12 septins are essential for viability. In contrast, the C. albicans cdc10Delta and cdc11Delta mutants were viable but displayed conditional defects in cytokinesis, localization of cell wall chitin, and bud morphology. The mutant phenotypes were not identical, however, indicating that these septins carry out distinct functions. The viable septin mutants could be stimulated to undergo hyphal morphogenesis but formed hyphae with abnormal curvature, and they differed from wild type in the selection of sites for subsequent rounds of hyphal formation. The cdc11Delta mutants were also defective for invasive growth when embedded in agar. These results further extend the known roles of the septins by demonstrating that they are essential for the proper morphogenesis of C. albicans during both budding and filamentous growth.


Evaluating the Effect of Different Intra-Orifice Barriers and Various Bleaching Agents on the Fracture Resistance of Teeth After the Walking Bleach Procedure: An In Vitro Study.
Objective This study aimed to evaluate the effect of three different commercially available intra-orifice barriers and bleaching agents on root canal-treated teeth. Materials and methods Forty-five freshly extracted single-rooted incisors, canine, and premolars were collected and stored in 10% formalin. Root canal procedures were performed on the extracted teeth and these were classified into three groups and three subgroups (n=5). Group 1: resin-modified glass ionomer cement (RMGIC); placed at the level of cemento-enamel junction (CEJ) and cured for 20 seconds. Group 2: BiodentinTM (Septodont Ltd., Saint Maur des Fausse´s, France); powder and liquid were mixed according to the manufacturer's instructions and placed at the level of CEJ, and waited for 15 minutes to set. Group 3: bulk-fill composite; placed at the level of CEJ. Group A was treated with 35% carbamide peroxide (Ultradent Opalescence 35% PF regular). Group B was bleached with 35% hydrogen peroxide (Pola Office). Group C, which was the control group, was treated with distilled water. The bleaching procedure was repeated once every seven days for a period of three weeks. After bleaching, every sample was sectioned 2 mm above the level of CEJ to remove the crown. Auniversal testing machine (UTM) was used for the evaluation of the fracture resistance of teeth. Data were analyzed for significance by using analysis of variance (ANOVA) and further pair-wise comparison was performed by pos-hoc analysis. The level of significance was set at p<0.05 Results There was a significant difference between the fracture resistance of the three materials when bleached using distilled water (p<0.05). The fracture resistance of Group 3 was significantly greater than that of Group 2 and Group 1 (p<0.05). The difference in the fracture resistance between Group 1 and Group 2 was nonsignificant (p>0.05). Conclusion Walking bleach performed via bleaching agents 35% carbamide peroxide and 35% hydrogen peroxide leads to a reduction in the fracture resistance of endodontically treated teeth; 35% hydrogen peroxide causes more fracture resistance reduction than carbamide peroxide of the same concentration. The presence of intra-orifice barriers leads to greater fracture resistance and reinforcement of endodontically treated teeth that undergo the walking bleach procedure. Bulk-fill composite can be used as an intra-orifice barrier with good fracture resistance.


Discovery of Novel 3-Quinoline Carboxamides as Potent, Selective, and Orally Bioavailable Inhibitors of Ataxia Telangiectasia Mutated (ATM) Kinase.
A novel series of 3-quinoline carboxamides has been discovered and optimized as selective inhibitors of the ataxia telangiectasia mutated (ATM) kinase. From a modestly potent HTS hit (4), we identified molecules such as 6-[6-(methoxymethyl)-3-pyridinyl]-4-{[(1R)-1-(tetrahydro-2H-pyran-4-yl)ethyl]amino}-3-quinolinecarboxamide (72) and 7-fluoro-6-[6-(methoxymethyl)pyridin-3-yl]-4-{[(1S)-1-(1-methyl-1H-pyrazol-3-yl)ethyl]amino}quinoline-3-carboxamide (74) as potent and highly selective ATM inhibitors with overall ADME properties suitable for oral administration. 72 and 74 constitute excellent oral tools to probe ATM inhibition in vivo. Efficacy in combination with the DSB-inducing agent irinotecan was observed in a disease relevant model.


[Prevalence and frequencies of human papilloma virus types in adenocarcinoma in situ of the uterine cervix].
Objective: To examine the prevalence and frequencies of human papillomavirus (HPV) genotypes in cervical adenocarcinoma in situ (AIS). Methods: The cases of cervical AIS with concurrent tests of cytology and HPV typing from January 2007 to February 2020 in the Obstetrics and Gynecology Hospital of Fudan University were collected and analyzed. Results: A total of 478 cases of cervical AIS were obtained. The average age of the patients was 39.4 years (range, 19-81 years). The largest age group was 30-39 years (44.8%), followed by 40-49 years (34.7%). Among the 478 patients, 355 underwent high-risk HPV (hrHPV) testing and had a hrHPV-positive rate of 93.8%. Of the 355 patients, 277 also underwent HPV typing and were mostly positive for either or both HPV16 and HPV18 (93.1%), with 55.6% positive for HPV18 and 48.7% positive for HPV16. Among the 478 cases, 266 cases (55.6%) were diagnosed with both AIS and squamous intraepithelial lesion (SIL), while 212 cases (44.4%) were diagnosed with only AIS. Patients infected with HPV16 in the AIS and SIL group significantly outnumbered those in the AIS alone group (P<0.05). Moreover, the rate of positive cytology was 55.9% (167/299 cases), while that of negative cytology was 44.1% (132/299). Among the 109 patients with negative cytology results and co-tested hrHPV, there were 101 HPV-positive cases (92.7%), of which 88 cases were subject to HPV typing and showed an HPV16/18 positive rate of 94.3% (83/88 cases). Conclusions: The combination of HPV typing and cytological screening can maximize the detection rate of cervical AIS, and should continue to be utilized, ideally on a larger scale, in the future.


Amino acid sequence of putative moult-inhibiting hormone from the crab Carcinus maenas.
Putative moult-inhibiting hormone (MIH) was isolated from sinus glands of the shore crab Carcinus maenas, and its primary structure determined by automated Edman degradation of endoproteinase derived peptide fragments. MIH is a 78 residue neuropeptide (deduced molecular mass 9181 Da) with three disulphide bridges and unblocked N- and C-termini. MIH shows some homology to the crustacean hyperglycemic hormone (CHH) neuropeptide family. However, consideration of the roles of various members of this group, together with sequence information recently reported, strongly suggests that these neuropeptides may be multifunctional.


Functionalized superparamagnetic nanoparticles with a polymer containing β-cyclodextrin for the extraction of sertraline hydrochloride in biological samples.
In this study, a novel magnetic nanoadsorbent was synthesized by grafting β-cyclodextrin onto the modified surface of Fe3 O4 nanoparticles for the sorption and extraction of sertraline hydrochloride from human biological fluids. The extracted sertraline hydrochloride was measured by high-performance liquid chromatography. The grafted nanosorbent was confirmed by Fourier transform infrared spectroscopy, transmission electron microscopy, thermogravimetric analysis, and elemental analysis. The kinetic sorption of sertraline hydrochloride by magnetic nanosorbent was 1 h. The best temperature for sorption of sertraline hydrochloride was at 25°C at an optimum pH of 5. The adsorbed sertraline hydrochloride can be desorbed by using methanol solution containing acetic acid (5%) and trifluoroacetic acid (1%).


Sex-specific effect of aging on submaximal leg exercise hemodynamics in middle-aged and older adults.
The purpose of the study was to examine predictors of the leg hemodynamic response to exercise in middle- and older-aged men and women. Femoral artery blood flow (FBF), mean arterial pressure (MAP), and femoral vascular conductance (FVC, calculated as the quotient of FBF and MAP) were measured at rest and during 5 min of single knee-extensor exercise at ~10 W workload in healthy men (n = 31) and women (n = 32) (age 40-72 years). Age, menopausal status, maximal quadriceps strength, blood lipids, vitamin D levels, maximal oxygen uptake (VO(2max)), physical activity, blood pressure, estimated quadriceps muscle mass, and body mass index (BMI) were also assessed. The effect of age on FBF and FVC was negative and significant in men (r = -0.44 and -0.42 and p = 0.01 and 0.02, respectively) but was abolished by normalization to estimated quadriceps muscle (p = 0.18 and 0.73, respectively). There was no effect of age on leg hemodynamic responses to exercise in women (alone or normalized to quadriceps muscle), but menopausal status was a significant predictor of FVC and normalized FVC (p = 0.04 and 0.02, respectively). The multivariate model for exercising FVC in men (in order of strongest to weakest predictors) included quadriceps strength, BMI, resting FVC, age, and high-density lipoprotein cholesterol. The multivariate model for exercising FVC in women included quadriceps mass, systolic blood pressure, vitamin D, age, VO(2max), waist circumference, and physical activity score. These findings suggest that factors besides chronological age mediate exercising leg hemodynamics in middle-aged to older adults and that these factors are sex-specific.


Texture analysis of pulmonary parenchymateous changes related to pulmonary thromboembolism in dogs - a novel approach using quantitative methods.
Diagnosis of pulmonary thromboembolism (PTE) in dogs relies on computed tomography pulmonary angiography (CTPA), but detailed interpretation of CTPA images is demanding for the radiologist and only large vessels may be evaluated. New approaches for better detection of smaller thrombi include dual energy computed tomography (DECT) as well as computer assisted diagnosis (CAD) techniques. The purpose of this study was to investigate the performance of quantitative texture analysis for detecting dogs with PTE using grey-level co-occurrence matrices (GLCM) and multivariate statistical classification analyses. CT images from healthy (n = 6) and diseased (n = 29) dogs with and without PTE confirmed on CTPA were segmented so that only tissue with CT numbers between -1024 and -250 Houndsfield Units (HU) was preserved. GLCM analysis and subsequent multivariate classification analyses were performed on texture parameters extracted from these images. Leave-one-dog-out cross validation and receiver operator characteristic (ROC) showed that the models generated from the texture analysis were able to predict healthy dogs with optimal levels of performance. Partial Least Square Discriminant Analysis (PLS-DA) obtained a sensitivity of 94% and a specificity of 96%, while Support Vector Machines (SVM) yielded a sensitivity of 99% and a specificity of 100%. The models, however, performed worse in classifying the type of disease in the diseased dog group: In diseased dogs with PTE sensitivities were 30% (PLS-DA) and 38% (SVM), and specificities were 80% (PLS-DA) and 89% (SVM). In diseased dogs without PTE the sensitivities of the models were 59% (PLS-DA) and 79% (SVM) and specificities were 79% (PLS-DA) and 82% (SVM). The results indicate that texture analysis of CTPA images using GLCM is an effective tool for distinguishing healthy from abnormal lung. Furthermore the texture of pulmonary parenchyma in dogs with PTE is altered, when compared to the texture of pulmonary parenchyma of healthy dogs. The models' poorer performance in classifying dogs within the diseased group, may be related to the low number of dogs compared to texture variables, a lack of balanced number of dogs within each group or a real lack of difference in the texture features among the diseased dogs.


Physicochemical and histological changes in the arterial wall of nonhuman primates during progression and regression of atherosclerosis.
To identify the temporal changes occurring during progression and regression of atherosclerosis in nonhuman primates, we have studied the physicochemical and histological characteristics of arterial wall lesions during a 30-mo progression period of diet-induced hypercholesterolemia and during a 12-mo period of regression. Three groups of cynomolgous monkeys (Macaca fascicularis) were studied. Control groups were fed a basal chow diet for 18, 24, and 30 mo and were compared with progression groups that were fed a high-cholesterol-containing diet for up to 30 mo. Regression groups were fed a high-cholesterol diet for 18 mo to induce atherosclerosis and then fed monkey chow for up to 12 mo. The progression group monkeys were killed at 6, 12, 18, 24, and 30 mo, and the regression animals were killed at 24 and 30 mo (i.e., after 6 and 12 mo of being fed a noncholesterol-containing chow diet). Histology and morphometry, physical microscopy for cholesterol monohydrate crystals, foam cell and droplet melting points and chemical composition studies were completed on a large number of individual arterial lesions. Control animals had very little cholesterol ester, rare foam cells, and no extracellular cholesterol ester droplets or cholesterol crystals. During progression, the arteries first increased cholesterol ester content to produce high melting (approximately 45 degrees C) foam cell-rich lesions essentially devoid of cholesterol crystals. With time, the number of cholesterol crystals increased so that by 30 mo large numbers were present. Foam cells decreased with time but their melting temperature remained high while that of extracellular droplets fell to approximately 38 degrees C. Between 18 and 30 mo necrosis appeared and worsened. After 6-mo regression, unexpected changes occurred in the lesions. Compared with 24-mo progression, the chemical composition showed a relative increase in free cholesterol, a decrease in cholesterol ester and microscopy revealed large numbers of cholesterol crystals. Concomitantly, foam cells decreased and the melting temperature of both intra- and extracellular cholesterol ester markedly decreased. After 12-mo regression cholesterol decreased, cholesterol crystals and necrosis diminished and collagen appeared increased. Thus, during progression there is initially an increase in the number of foam cells containing very high-melting intracellular cholesterol ester droplets. By 30 mo, cholesterol crystals and necrosis dominate and high-melting foam cells appear only at lesion margins, suggesting that the initial process continues at the lesion edge. The lower melting point of extracellular esters indicates a lipid composition different from intracellular droplets. Thus, the changes observed in these animals generally reflect those predicted for progression of human atherosclerosis. During the initial 6 mo of regression, necrosis remains, the number of foam cell decreases, and cholesterol ester content decreases; however the relative proportion of free cholesterol content increases, and large numbers of cholesterol content are formed. Thus, large and rapid decreases in serum cholesterol concentration to produce regression in fact may result in the precipitation of cholesterol monohydrate and an apparent worsening of the lesions. More prolonged regression (12-mo) tends to return the lipid composition of the artery wall towards normal, partially reduces cholesterol crystals, and results in an improved but scarred intima.


2D-LCoLBP: A Learning Two-Dimensional Co-Occurrence Local Binary Pattern for Image Recognition.
The rotation, scale and translation invariance of extracted features have a high significance in image recognition. Local binary pattern (LBP) and LBP-based descriptors have been widely used in image recognition due to feature discrimination and computational efficiency. However, most of the existing LBP-based descriptors have been designed to achieve rotation invariance while fail to achieve scale invariance. Moreover, it is usually difficult to achieve a good trade-off between the feature discrimination and the feature dimension. In this work, a learning 2D co-occurrence LBP termed 2D-LCoLBP is proposed to address these issues. Firstly, a weighted joint histogram is constructed in different neighborhoods and scales of an image to represent the multi-neighborhood and multi-scale LBP (2D-MLBP) and achieve the rotation invariance. A feature learning strategy is then designed to learn the compact and robust descriptor (2D-LCoLBP) from LBP pattern pairs across different scales in the extracted 2D-MLBP to characterize the most stable local structures and achieve the scale invariance, as well as decrease the feature dimension and improve the noise robustness. Finally, a linear SVM classifier is employed for recognition. We applied the proposed 2D-LCoLBP on four image recognition tasks-texture, object, face and food recognition with ten image databases. Experimental results show that 2D-LCoLBP has obviously low feature dimension but outperforms the state-of-the-art LBP-based descriptors in terms of recognition accuracy under noise-free, Gaussian noise and JPEG compression conditions.


Polyphenolic characterisation and antiprotozoal effect of extracts obtained by maceration, ultrasound, microwave and ultrasound/microwave of Porophyllum ruderale (Jacq.) Cass.
Porophyllum ruderale (Jacq.) Cass. (Asteraceae) has antiprotozoal properties and contains extractable phenolic compounds by the maceration method (M). However, new extraction proposals such as ultrasound (U), microwaves (MW), and ultrasound/microwaves (U/MW) have emerged to optimise yields, but it is unknown if these methods modify effectiveness. Therefore, the study consisted of extracting the aerial part of P. ruderale with ethanol using the M, U, MW and U/MW methods to study its composition by RP-HPLC-ESI-MS, its total polyphenol content and its effect against Entamoeba histolytica. The study showed that U, MW and U/MW did not modify the extraction yield compared to M, but they did change the composition and the total polyphenol content. All extracts contain phloretin, caffeic acid 4-O-glucoside, todolactol A, quercetin 3-O-glucoside, quercetin 3-O-rhamnoside, luteolin and 3,7-dimethylquercetin, and affected the growth of E. histolytica. However, M and U extracts were the most effective at 5 mg/mL.


NMR study on the major mite allergen Der f 2: its refined tertiary structure, epitopes for monoclonal antibodies and characteristics shared by ML protein group members.
Group 2 major mite allergens Der f 2 and Der p 2 are classified into the recently identified group of MD-2-related lipid-recognition (ML) proteins, but the ligands and biological functions of these allergens are unknown. We have obtained a high-quality NMR structure for Der f 2, and found that it is more similar to the crystal structure of NPC2, a distant homologue, than to that of Der p 2, in terms of the separation and angle between the two major beta-sheets. This made us propose that ML proteins undergo clamshell-like motions that change the sizes of ligand-binding spaces inside their immunoglobulin-fold beta-sandwich to accommodate lipid molecules. This type of motion in lipopolysaccaride recognition of MD-2 is suggested to be likely as well by structural models. We also report the applicability of NMR differential exchange broadening experiments for complexes of intact monoclonal antibodies and antigens; using this technique, we have detected the conformational epitopes for monoclonal antibodies 15E11 and 13A4 as two separate surface patches.


Myocardial paramagnetic contrast agents for MR imaging.
Several different paramagnetic contrast agents have been investigated for use in myocardial MR imaging. Gd-DTPA, the most extensively studied agent, has been shown to improve the conspicuity of acute myocardial infarcts on MR images in experimental animals and humans. However, this agent is limited as a marker of perfusion because of its rapid elimination by renal excretion and equilibration within the extracellular fluid space. Future investigation of Gd-DTPA as a myocardial perfusion agent may involve rapid-scanning techniques to define time-dependent accumulation of the contrast agent in normal and ischemic myocardium during the first pass after IV injection. Nondiffusable paramagnetic agents and agents with prolonged retention in myocardium are being studied actively, but further tests of toxicity and metabolism are needed before clinical trials. Additional macromolecular-bound metal chelates will be tested in the future. It is hoped that these agents will allow detection of the jeopardized region of myocardium in the setting of acute ischemia, before the onset of myocardial edema.


Distribution of Scedosporium species in soil from areas with high human population density and tourist popularity in six geographic regions in Thailand.
Scedosporium is a genus comprising at least 10 species of airborne fungi (saprobes) that survive and grow on decaying organic matter. These fungi are found in high density in human-affected areas such as sewage-contaminated water, and five species, namely Scedosporium apiospermum, S. boydii, S. aurantiacum, S. dehoogii, and S. minutisporum, cause human infections. Thailand is a popular travel destination in the world, with many attractions present in densely populated areas; thus, large numbers of people may be exposed to pathogens present in these areas. We conducted a comprehensive survey of Scedosporium species in 350 soil samples obtained from 35 sites of high human population density and tourist popularity distributed over 23 provinces and six geographic regions of Thailand. Soil suspensions of each sample were inoculated on three plates of Scedo-Select III medium to isolate Scedosporium species. In total, 191 Scedosporium colonies were isolated from four provinces. The species were then identified using PCR and sequencing of the beta-tubulin (BT2) gene. Of the 191 isolates, 188 were S. apiospermum, one was S. dehoogii, and species of two could not be exactly identified. Genetic diversity analysis revealed high haplotype diversity of S. apiospermum. Soil is a major ecological niche for Scedosporium and may contain S. apiospermum populations with high genetic diversity. This study of Scedosporium distribution might encourage health care providers to consider Scedosporium infection in their patients.


A voice of experience: Positive and negative experiences of mental health from a service user's/lived experience perspective.
WHAT IS KNOWN ON THE SUBJECT?: People with mental health problems are often left behind, forgotten and excludedLittle is known or written from a service user perspective about experiences of psychiatry, mental health nursing, Mental Health Tribunals and alternative approaches (such as counselling, peer support, psychological and recovery approaches, cognitive behavioural therapy-CBT and creative/art/music/drama/horticultural/dance therapies). WHAT THE PAPER ADDS TO EXISTING KNOWLEDGE?: This paper aims to remedy this gap in knowledgeIt focuses on positive and negative experiences of psychiatry, Mental Health Tribunals and alternative treatments from a service user's perspective. WHAT ARE THE IMPLICATIONS FOR PRACTICE?: The paper makes several recommendations. In brief, (1) psychiatrists need to listen more attentively rather than being focused on signs of psychosis; (2) de-escalation techniques (for example, talking calmly with the patient) should be used by nurses before physical restraint; (3) psychiatry should be less biomedical. Nurses and social care professionals deserve better training, time for and practice in alternative and more therapeutic forms of care; (4) carers need to be more involved; (5) there need to be better, more democratic, more open processes of law; (6) voluntary work and supported employment schemes should be run by health and social services for people who want to work and want to have a vocational life. This paper aims to describe the lived experience of mental illness, coercive treatment by psychiatry and mental health nursing, and the problematic case and bias of Mental Health Tribunals. It then looks at more positive experiences of alternative approaches and makes recommendations for improving mental health services and people's experiences of them.


Emerging role of chemoprotective agents in the dynamic shaping of plasma membrane organization.
In the context of an organism, epithelial cells by nature are designed to be the defining barrier between self and the outside world. This is especially true for the epithelial cells that form the lining of the digestive tract, which absorb nutrients and serve as a barrier against harmful substances. These cells are constantly bathed by a complex mixture of endogenous (bile acids, mucus, microbial metabolites) and exogenous (food, nutrients, drugs) bioactive compounds. From a cell biology perspective, this type of exposure would directly impact the plasma membrane, which consists of a myriad of complex lipids and proteins. The plasma membrane not only functions as a barrier but also as the medium in which cellular signaling complexes form and function. This property is mediated by the organization of the plasma membrane, which is exquisitely temporally (nanoseconds to minutes) and spatially (nanometers to micrometers) regulated. Since numerous bioactive compounds found in the intestinal lumen can directly interact with lipid membranes, we hypothesize that the dynamic reshaping of plasma membrane organization underlies the chemoprotective effect of select membrane targeted dietary bioactives (MTDBs). This article is part of a Special Issue entitled: Membrane Lipid Therapy: Drugs Targeting Biomembranes edited by Pablo V. Escribá.


Immobilization of cellulase on TiO2 nanoparticles by physical and covalent methods: a comparative study.
Immobilization of cellulase from Aspergillus niger on TiO2 nanoparticles was studied by two different approaches--physical adsorption and covalent coupling. A. niger was selected, as it is generally non-pathogenic, is found in nature in the broad range of habitats and produces cellulase extracellulary. For covalent method, TiO2 nanoparticles were modified with aminopropyltriethoxysilane (APTS). The adsorbed and covalently immobilized enzymes showed 76% and 93% activity, respectively, as compared to the free enzyme. The catalytic efficiency V(max)/K(m) increased from 0.4 to 4.0 after covalent attachment, whereas in adsorption method, it increased slightly from 0.4 to 1.2. The covalently-immobilized and adsorbed cellulase lost only 25% and 50% of their activity, respectively after 60 min of incubation at 75 degrees C. The reusability and operational stability data also showed that covalent coupling increased the stability of the enzyme. The presence of enzyme on TiO2 nanoparticles was confirmed by Fourier-transform infrared spectroscopy. The high-resolution transmission electron microscopy (HR-TEM) and atomic force microscopy (AFM) studies indicated aggregation of enzyme when adsorbed on TiO2 surface and a monolayer of enzyme in covalent attachment. In conclusion, covalently attached cellulase retained good activity and thermal stability, as compared to physically adsorbed enzyme. The lower amount of enzyme activity and thermal stability in case of physically adsorbed immobilized enzyme was due to aggregation of the enzyme after adsorption on TiO2 nanoparticles, as revealed by HR-TEM and AFM. Thus, TiO2 nanoparticles could be suitable candidates for immobilization of cellulase for industrial applications like paper, textile, detergent and food industries.


Effects of cryopreservation of immune responses. XI. Heightened secretion of tumor necrosis factor-alpha by frozen human peripheral blood mononuclear cells.
In view of the wide usage of frozen PBMCs as stem cell support following high-dose chemo- and/or radiotherapy, and the pleiotropic activities of tumor necrosis factor-alpha (TNF-alpha), the influences of freezing and radiation on LPS-induced TNF-alpha production by human peripheral blood mononuclear cells (PBMCs) were studied. Frozen PBMCs secreted significantly larger quantities of TNF-alpha than fresh cells. Blocking of endogenous IL-10 by neutralization with anti-IL-10 monoclonal antibody resulted in further augmented and prolonged secretion of TNF-alpha by both the fresh and frozen cells. In contrast, addition of exogenous IL-10 to LPS-stimulated cultures inhibited TNF-alpha secretion. In vitro irradiation had an inconsistent effect on TNF-alpha production by the fresh PBMCs. Taken together, these results suggest that the endogenously hypersecreted TNF-alpha is indirectly responsible for the previously reported elevated IL-1-, IL-6-, and IL-10-secreting capabilities of frozen PBMCs. They also indicate that the TNF-alpha induced IL-10 and then down-regulates the monocytes from further TNF-alpha secretion. Considering the vital role played by TNF-alpha in antimicrobial and antitumor activities, in the immune system, and in the pathogenesis of many acute and chronic diseases, the abilities of frozen cells to produce large quantities of TNF-alpha in response to infectious agents could have profound impact on patients receiving such frozen PBMCs as stem cell support following myeloablative therapies.


Effects of Long-Term Alpha-mangostin Supplementation on Hyperglycemia and Insulin Resistance in Type 2 Diabetic Rats Induced by High Fat Diet and Low Dose Streptozotocin.
The present study investigated the effects of long-term supplementation of alpha-mangostin (MG; a xanthone isolated from mangosteen fruit) on hyperglycemia, and insulin resistance in type 2 diabetic rats. Type 2 diabetes (DM2) was induced in male Sprague-Dawley rats by feeding high fat diet for three weeks followed by an IP injection of low dose streptozotocin. The rats were divided into four groups: control and diabetes without or with alpha-MG supplementation (CON, DM2, CON-MG and DM2-MG group, respectively). Alpha-MG was administered by gavage feeding in the amount of 200 mg/kg BW/day for 8 or 40 weeks. Fasting blood glucose, plasma HbA1c, cholesterol, and triglyceride were determined in all groups of rats. Serum insulin, calculated HOMA-IR and Oral glucose tolerance test were also carried out. The results showed that both 8 and 40 weeks DM2 groups had a significant increase in fasting blood glucose, HbA1c, plasma cholesterol and triglyceride compared with their aged-match control groups. Furthermore, the serum insulin and HOMA-IR were significantly elevated in 8 weeks DM2 whereas these two parameters were significantly decreased in 40 weeks DM2 group compared with their aged-match CON groups (p < 0.001). The OGTT showed impaired glucose tolerance in DM2 groups. Interestingly, alpha-MG supplemented DM2-MG group had significantly decreased levels of fasting blood glucose, HbA1c, plasma cholesterol, triglyceride when compared with the untreated DM2 groups. Supplementation of alpha-MG for 40 weeks in DM2-MG group showed significantly increase serum insulin levels compared with that of DM2 group (p < 0.001). Moreover alpha-MG supplemented DM-MG group demonstrated a better glucose tolerance pattern which was different from that of DM2 group at both 8 weeks and 40 weeks experimental periods. Long-term alpha-mangostin supplementation has anti-hyperglycemic, anti-hyperlipidemic effects and increase insulin sensitivity by improving beta-cell functions in type 2 diabetes mellitus.


Spontaneous subcutaneous emphysema and pneumomediastinum during second stage of labour.
A 27-year-old healthy primigravida presented with spontaneous labour at 40 weeks gestation and proceeded to an unassisted vaginal delivery of a 3.2 kg infant. She immediately developed swelling in the neck and facial area associated with pleuritic chest pain. There was palpable crepitus throughout her anterior chest wall and neck. CT confirmed pneumomediastinum. She was managed with oxygen and analgesia in the intensive care unit and subsequently discharged with resolution of her symptoms. Postpartum pneumomediastinum with subcutaneous emphysema is treated conservatively after cardiac and embolic causes have been excluded; however, there is no consensus on the management of subsequent pregnancies.


Proteoglycans in the microvasculature. I. Histochemical localization in microvessels of the rabbit eye.
The ultrastructural organization of ruthenium red (RR) stainable material within small blood vessels located in the limbus of the rabbit eye was studied. Proteoglycans were identified in this material by digesting tissues with Streptomyces hyaluronidase, testicular hyaluronidase, chondroitinase ABC, or heparinase before ruthenium red staining. Neuraminidase digestion enabled separate identification of sialoglycoprotein. The luminal surface of endothelial cells demonstrates an RR-stained glycocalyx containing both sialoglycoprotein and proteoglycans, which are removed by testicular hyaluronidase and crude heparinase. The basal coat of endothelial cells and small granules (10-20 nm in diameter) located within the basal lamina stain with RR and are removed only by crude heparinase. The surface coat of smooth muscle cells and small granules (10-20 nm) within their basal laminas are also digested by crude heparinase. Large proteoglycan granules (20-50 nm), which are completely removed by testicular hyaluronidase and partially digested by Streptomyces hyaluronidase, are deposited between the connective tissue fibers of the media and adventitia. Other large granules that are attached to collagen fibers contain enzyme-resistant anionic materials. The surface coat of adventitial fibroblasts is removed only by crude heparinase. Thin filaments (3-5 nm in diameter) interconnect the cell coat material, basal lamina granules, and large connective tissue granules, to form a network of proteoglycans that traverses the intima, media, and adventitia. The highly ordered arrangement of proteoglycans in the microvascular wall suggests that these macromolecules play several roles in microvascular function.


Accumulation of Polychlorinated Biphenyls in Mussels: A Proteomic Study.
Polychlorinated biphenyls (PCBs) are environmental pollutants of industrial origin that can contaminate food, mainly food of animal origin. Although production of PCBs has been banned in many countries since the 1980s, they are still present in the environment and are considered dangerous pollutants for human health. In fact, they can bioaccumulate in living organisms such as marine organisms because of their chemical and physical properties. New analytical approaches are useful to monitor the presence of such contaminants in seafood products and in the environment. In this work, we evaluate changes in protein expression of Mytilus galloprovincialis (Lam.) experimentally exposed to a PCB mixture and identify chemically specific protein expression signatures by using a proteomic approach. In particular, we identify 21 proteins whose levels of expression are sensibly modified after 3 weeks of exposure. The present work shows that a proteomic approach can be a useful tool to study alterations of protein expression in mussels exposed to PCBs and represents a first step toward the development of screening protocols to be used for biomonitoring surveys of fishery products.


The "five minute" consultation: effect of time constraint on verbal communication.
In a study in which patients were allocated non-systematically to surgeries booked at 5, 7.5, and 10 minute intervals 623 consultations were taperecorded. In surgeries booked at longer intervals doctors used the extra time to take a fuller history from their patients. In surgeries booked at 10 minute intervals doctors spent more time explaining the patient's problem, explaining the proposed management, and in discussing prevention and health education, these increases not being evident in surgeries booked at 7.5 minute intervals.


Total brain tissue sialic acid levels due to glutathione effect in experimental epilepsy.
Epilepsy can be described as a group of neurological disorders, characterized by recurrent episodes of convulsive seizures, loss of consciousness, sensory disturbances, abnormal behavior, or all of these. Altered glutathione metabolism in association with increased oxidative stress has been implicated in the pathogenesis of many diseases such as seizures. It is therefore reasonable to propose that sialic acid levels can be affected by this pathological state or, alternately, by seizures. The present study showed that the sialic acid levels were significantly different between the experimental groups as well as in the subgroup analysis. The results suggest that glutathione may have a neuroprotective effect by decreasing sialic acid levels in mice brain.


Epidemiological Aspects of Age and Genotypical Occurrence of HPV Infection Among Females of Canton Sarajevo Over a 10-year Period.
Human papillomaviruses (HPV) are one of the most prevalent causes of cervical, anal, and oral cancer, and it is believed that nearly all sexually active males and females have been infected with HPV at some point in their lives. The purpose of this study is to highlight epidemiological characteristics of the age and genotypical incidence of HPV infection among females in Canton Sarajevo during a 10-year period. This cross-sectional study was conducted in the period between January 2012 and December 2021 at the medical institutions "Zavod za Ginekologiju, Perinatologiju i Neplodnost "Mehmedbašić" among females who were admitted for a routine gynaecological exam in Canton Sarajevo in Bosnia and Herzegovina. In total, 1517 patients who reported typical sexarche at 18.35±1.92, having one 721 (47.5%) sexual partner, regular use of contraceptive methods 820 (54.5%) with male condom 513 (62.6%) being the dominant choice of contraception and having gynacological hereditary oncological positive history 141 (9.3%), were included in the study from which 653 (43.05%) patients had positive HPV test and 864 (56.95%) had negative HPV results. HPV positive patients, 386 (59.1%) were infected either with one type of virus only, while 267 (40.9%) patients were infected with multiple virus strains where we have identified 166 virus strain combinations. Analysis showed that the patients infected by only one virus strain were one of next specific HPV viruses: 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66 and 68. HPV-16 was the predominately strain 16 (22.5%) identified among all the patients. Mean age of HPV positive patients was 33.38±7.85, ranging from 18 to 61 years. This study highlights the significance of the most frequent HPV high-risk strains (HPV-16, -18, -31.-33,-45,-52, and -58) among the Bosnia and Herzegovina population as one of the most common cancer-causing strains worldwide.


Deficiency of miR-29a/b1 leads to premature aging and dopaminergic neuroprotection in mice.
Parkinson's disease (PD) is a neurodegenerative disorder characterized by progressive degeneration of midbrain dopaminergic neurons. The miR-29s family, including miR-29a and miR-29b1 as well as miR-29b2 and miR-29c, are implicated in aging, metabolism, neuronal survival, and neurological disorders. In this study, the roles of miR-29a/b1 in aging and PD were investigated. miR-29a/b1 knockout mice (named as 29a KO hereafter) and their wild-type (WT) controls were used to analyze aging-related phenotypes. After challenged with the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), dopaminergic injuries, glial activation, and mouse behaviors were evaluated. Primary glial cells were further cultured to explore the underlying mechanisms. Additionally, the levels of miR-29s in the cerebrospinal fluid (CSF) of PD patients (n = 18) and healthy subjects (n = 17) were quantified. 29a KO mice showed dramatic weight loss, kyphosis, and along with increased and deepened wrinkles in skins, when compared with WT mice. Moreover, both abdominal and brown adipose tissues reduced in 29a KO mice, compared to their WT counterpart. However, in MPTP-induced PD mouse model, the deficiency of miR-29a/b1 led to less severe damages of dopaminergic system and mitigated glial activation in the nigrostriatal pathway, and subsequently alleviated the motor impairments in 3-month-old mice. Eight-month-old mutant mice maintained such a resistance to MPTP intoxication. Mechanistically, the deficiency of miR-29a/b-1 promoted the expression of neurotrophic factors in 1-Methyl-4-phenylpyridinium (MPP+)-treated primary mixed glia and primary astrocytes. In lipopolysaccharide (LPS)-treated primary microglia, knockout of miR-29a/b-1 inhibited the expression of inflammatory factors, and promoted the expression of anti-inflammatory factors and neurotrophic factors. Knockout of miR-29a/b1 increased the activity of AMP-activated protein kinase (AMPK) and repressed NF-κB/p65 signaling in glial cells. Moreover, we found miR-29a level was increased in the CSF of patients with PD. Our results suggest that 29a KO mice display the peripheral premature senility. The combined effects of less activated glial cells might contribute to the mitigated inflammatory responses and elicit resistance to MPTP intoxication in miR-29a/b1 KO mice.


Polymorphism in the MHC2TA gene is associated with features of the metabolic syndrome and cardiovascular mortality.
Recently, a -168A-->G polymorphism in the MHC class II transactivator gene (MHC2TA) was shown to be associated with increased susceptibility to myocardial infarction (MI). To confirm the association between the MHC2TA -168A-->G polymorphism and MI and to study its putative role for microalbuminuria, the metabolic syndrome (MetS) and cardiovascular mortality. Using an allelic discrimination method we genotyped 11,064 individuals from three study populations: 1) 4,432 individuals from the Botnia type 2 diabetes (T2D) study, 2) 1,222 patients with MI and 2,345 control subjects participating in the Malmö Diet and Cancer study and comprising an MI case-control sample, and 3) 3,065 T2D patients from the Local Swedish Diabetes registry. No association between the -168A-->G polymorphism in MHC2TA and MI was observed. However, in the Botnia cohort the AG/GG genotypes were associated with cardiovascular mortality after MI (1.78 [1.09-2.92], p = 0.02). In addition, the AG/GG genotypes were more common in subjects with MetS (40.1% vs. 36.9%, p = 0.03) and in non-diabetic subjects with microalbuminuria (45.4% vs. 36.5%, p = 0.003) compared to control subjects. A polymorphism in MHC2TA was associated with cardiovascular mortality and predictors of cardiovascular mortality, microalbuminuria and MetS.


The Pharmacological Mydriatic Pupil-to-Limbal Diameter Ratio as an Intuitive Predictor for the Risk of Intraoperative Floppy Iris Syndrome.
To predict development of intraoperative floppy iris syndrome (IFIS) using the preoperative pharmacologically dilated pupil-to-limbal diameter (PL) ratio. The subjects were male patients treated by phacoemulsification who were or were not taking α1-adrenoceptor antagonists (ARAs). The PL ratio was calculated from the horizontal dilated pupil diameter and the horizontal corneal white-to-white distance measured by two observers in surgical videos. IFIS severity was graded using the criteria of Chang et al. We predicted the intuitive PL ratio to describe how precisely the experimenter can estimate the PL ratio without any tools. There were 36 eyes in the α1-ARA group and 48 eyes in the control group. The pupil diameter and PL ratio were both significantly smaller in the α1-ARA group compared to the control group (p < 0.001). All of pupil diameter, PL ratio, and intuitive PL ratio were negatively correlated with IFIS severity. The cutoff value for prediction of IFIS from the ROC curve was 7.20 mm for the pupil diameter, 58.7% for the PL ratio, and 62.5% for the intuitive PL ratio. The AUC for the ROC curve using the PL ratio (0.913) and intuitive PL ratio (0.892) did not perform substantially worse than that for the ROC curve based on the pupil diameter (0.875). The PL ratio is a simple and useful parameter for compensated prediction of IFIS development. Patients in whom this ratio is <60% are particularly likely to develop IFIS, and measures against onset of IFIS should be considered. This study is registered with UMIN000033012.


Deep lingual arterial chemoembolization of tongue carcinoma with microcapsuled anticancer drug.
Microcapsule chemoembolism is a promising treatment of tumors. We describe a deep lingual arterial embolization of tongue carcinoma with microcapsuled carboplatinum. Lingual artery cast specimens from cadavers were microscopically examined, and 78 patients with tongue cancer were recruited and treated with the deep lingual arterial embolization therapy. Microcapsule embolism occurred approximately at the fifth or sixth level of the deep lingual artery branches. The five-year survival rate was 88.5% (69 out of 78), and the ten-year survival rate 52.6% (41 out of 78). The deep lingual arterial embolization of tongue carcinoma with microcapsuled carboplatinum is an effective therapy to treat carcinoma in mid-margin or mid-body of the tongue.


Development of a Triplet-Triplet Absorption Ruler: DNA- and Chromatin-Mediated Drug Molecule Release from a Nanosurface.
Triplet-triplet (T-T) absorption spectroscopy has been used successfully as a molecular ruler to understand the actual release process of sanguinarine as a drug molecule from a gold nanoparticle surface in the presence of cell components, that is, DNA and chromatin. The obtained results have been verified by fluorescence and surface-enhanced Raman spectroscopy (SERS), and a plausible explanation has been put forward to describe the underestimation and overestimation of the percentage (%) of the release of drug molecules measured by fluorescence- and SERS-based techniques, respectively, over the highlighted T-T absorption spectroscopy. Because of the intrinsic nature of absorption, the reported T-T absorption spectroscopic assay overpowers fluorescence- and SERS-based assays, which are limited by the long-range interaction and nonlinear dependence of the concentration of analytes, respectively.


Radiation-induced changes in gene expression and distribution of atrial natriuretic peptide (ANP) in different anatomical regions of the rat heart.
To examine the effects of whole-heart irradiation on gene expression and distribution of atrial natriuretic peptide (ANP) in atrial appendages and left ventricles of the rat heart. Female Sprague-Dawley rats were irradiated with a single dose of 0, 15 or 20 Gy locally to the heart. At intervals up to 16 months post-irradiation, the localization of ANP was examined using immunohistochemical techniques. Absolute mRNA concentrations were determined using the competitive PCR assay. Histological and immunohistochemical studies demonstrated that whole-heart irradiation caused a reduction of atrial ANP, which is due to a substantial loss of ANP-producing atrial myocytes and accumulation of collagen (replacement fibrosis). On the other hand, ANP became detectable in the subendocardium of the irradiated left ventricles. Positive staining of ANP was mainly found in the proximity of injured areas consisting of degeneration of myocytes and fibrosis. At the transcriptional level, reduction of atrial ANP expression at 1 month post-irradiation was followed by recovery at 3 months. Thereafter, ANP mRNA concentrations followed the mRNA pattern of controls and even appeared to increase at 16 months. In the left ventricle, dose-dependent and progressive elevation of ANP gene expression could be observed during the observation period and reached a 20-fold increase as compared with sham-irradiated age-matched controls. The distribution of ANP after local irradiation of the rat heart depends on the severity of the pathological/structural changes (i.e. myocyte degeneration and fibrosis). In radiation-induced heart disease, elevated ANP expression in the left ventricle is most probably involved in the observed chronic elevation of plasma ANP levels.