Monte Carlo calculation of monoenergetic and polyenergetic DgN coefficients for mean glandular dose estimates in mammography using a homogeneous breast model.
We computed normalized glandular dose (DgN) coefficients for mean glandular dose estimates in contemporary 2D mammography units, taking into account a homogeneous model for the breast which reflects recent literature reports. We developed a Monte Carlo code based on the simulation toolkit GEANT4 ver. 10.00. The breast was modelled as a cylinder with a semi-cylindrical section with a radius of 10 cm, enveloped in a 1.45 mm thick skin layer, as found out in recent reports in the analysis of breast computed tomography clinical scans. The compressed breast thickness was between 3 cm and 8 cm. The DgN coefficients were calculated for monoenergetic x-ray beams between 4.25 keV and 49.25 keV and were fitted with polynomial curves. Polyenergetic DgN coefficients were then computed for spectra obtained for various anode/filter combinations as adopted in routine clinical practice: Mo/Mo 30 µm (25-40 kV), Mo/Rh 25 µm (25-40 kV), Rh/Rh 25 µm (25-40 kV), W/Ag 50 µm (26-34 kV), W/Al 500 µm (26-38 kV), W/Al 700 µm (28-40 kV) and W/Rh 50 µm (24-35 kV). Monoenergetic DgN curve fit coefficients and polyenergetic DgNp coefficients were released for research and clinical work. Polyenergetic DgNp coefficients were 6% higher than those provided in the recent literature, on average. The differences range between -18% and 30%; up to 50% of the computed coefficients differed by less than 10%. The dataset of DgN coefficients are provided as tables for varying glandular fraction by mass and compressed breast thickness. Moreover, a computer code has been developed for generating user specific coefficients DgNp for user defined x-ray spectra up to 49 kV, calculated by spectral weighting from the dataset of monoenergetic DgN coefficients.


The concept of behavioral specificity: three concepts.
A brief review of specificity theories in relationship to illness is identified. Psychosomatic medicine has gradually moved from unitary-specificity relationships to multi-specificity ones. This movement has been determined by the increasing number of factors that are temporally and sequentially related to illness. The relationship of specific factors to disease is seen as derivative, generative or coincidental. Particular attention is addressed to the social life field in which illness develops, is responded to by the patient and treated by the physician. The emerging field of behavioral analysis allows for the identification of discrete factors which may be correlated with specific behaviors. Such relationships are amenable to behavioral interventions which are specific. Change is measurable. The patient takes an active part in the therapy by noting the relationship of environmental events to specific reactions. As these are recognized through encouragement, relaxation, desensitization and reinforcement, maladaptive responses are replaced by adaptive ones.


[Tobacco smoking among adolescents-self-reported psycho-somatic health].
Studies of self-reported psychosomatic health among non-smokers and current smokers were conducted among students aged 19-20 by means of a standardised questionnaire form concerning people actively and passively smoking. The analysis covered the number and type of cigarettes, time of exposure to tobacco smoke, as well as health effects in active and passive smokers. Tobacco smokers constituted 22% of the total number of the population examined, whereas passive smokers - 78%. Females constituted 56.3% of current smokers, and 78.7% of those passively exposed to tobacco smoke. The majority of respondents experienced health effects. Considering self-reported psycho-somatic health, 82.8% of respondents who were passive smokers mentioned irritation by tobacco smoke, the majority of them suffered headaches and burning sensation of the eyes. As many as 96.1% of non-smokers considered smoking as harmful for health. Health effects reported by current smokers concerned headaches, dyspnea, dry cough and general malaise (depression, low mood, anxiety). 70% of the respondents would like to discontinue cigarettes smoking.


Atlantoaxial rotatory fixation after ventriculoperitoneal shunting.
Ventriculoperitoneal (VP) shunting is a common neurosurgical procedure in the pediatric population. Atlantoaxial rotatory fixation (AARF) is not uncommon in this same group. We present the first reported case of AARF following a VP shunt procedure. A 10-year-old boy, with hydrocephalus and a left temporal arachnoid cyst since birth, underwent a revision of his VP and cystoperitoneal shunts. A second operation was performed 2 days later to optimize catheter placement. Postoperative neck pain was attributed to tunneling of the subcutaneous catheter. 2 months after surgery, the child had minimal neck discomfort but maintained his head in a "cock-robin" position. Plain radiographs and computed tomographic (CT) images confirmed AARF. The child was admitted and placed in halo traction. After 3 days of traction, analgesics, sedation, and muscle relaxants, anatomic re-alignment of the C1-C2 vertebral complex was confirmed on CT scan. Following 3 months of immobilization in a halo-vest apparatus, the halo was removed. At 8-year follow-up, the clinical examination is normal and repeat imaging studies remain normal. Due to surgical positioning, and postoperative signs attributed to normal postoperative pain, an AARF was not initially recognized. This case represents the first time that AARF has been reported following a VP shunt procedure.


Emergency aortocoronary bypass after failed angioplasty.
One thousand two hundred fourteen percutaneous transluminal coronary angioplasties were performed over a 38-month period. Sixty patients required immediate emergency coronary artery bypass grafting after angioplasty failure; 7 of these had evidence of acute myocardial infarction before angioplasty and were excluded from the study. Of the 53 patients remaining, 27 (51%) had electrocardiographic and enzyme evidence of postoperative myocardial infarction. Two patients died (4%), and 10 had postoperative complications (19%). No statistical significance was noted comparing age, sex, incidence of prior myocardial infarction or myocardial dysfunction, time for revascularization, or average number of grafts completed in those with single-vessel (n = 21) versus multiple-vessel (n = 32) coronary artery disease. Postoperatively, those with multiple-vessel disease required intraaortic balloon pump support (p = 0.06) and antiarrhythmic medications more frequently than single-vessel patients (p less than 0.01) and had a higher complication rate (p less than 0.05). Although not reaching statistical significance, the data also suggest a higher death and postoperative myocardial infarction rate in patients with multiple-vessel disease. Emergency coronary artery bypass grafting after failed percutaneous transluminal coronary angioplasty carries a higher morbidity and mortality than elective coronary artery bypass grafting, particularly for patients with multiple-vessel coronary artery disease.


Molecular Mechanisms Underlying the Association between Endometriosis and Ectopic Pregnancy.
Endometriosis is a common inflammatory disease characterized by the presence of endometrial cells outside the uterine cavity. It is estimated that it affects 10% of women of reproductive age. Its pathogenesis covers a wide range of abnormalities, including adhesion, proliferation, and cell signaling disturbances. It is associated with a significant deterioration in quality of life as a result of chronic pelvic pain and may also lead to infertility. One of the most serious complications of endometriosis is an ectopic pregnancy (EP). Currently, the exact mechanism explaining this phenomenon is unknown; therefore, there are no effective methods of prevention. It is assumed that the pathogenesis of EP is influenced by abnormalities in the contraction of the fallopian tube muscles, the mobility of the cilia, and in the fallopian microenvironment. Endometriosis can disrupt function on all three levels and thus contribute to the implantation of the embryo beyond the physiological site. This review takes into account aspects of the molecular mechanisms involved in the pathophysiology of endometriosis and EP, with particular emphasis on the similarities between them.


Association of serum uric acid and coronary artery disease in premenopausal women.
To date, no study in the published literature has investigated the role of various serum uric acid (SUA) concentrations in the development of angiographically-proven coronary artery disease (CAD) in premenopausal women. Therefore, the aim of this study was to investigate the role SUA levels may play in the prevalence, severity, and prognosis of CAD in premenopausal women. This cross-sectional retrospective study included 607 premenopausal women who had undergone coronary angiography. The CAD diagnosis was based upon stenosis affecting ≥ 50% of the luminal diameter. Association of the SUA levels with CAD prevalence, severity, and clinical outcomes were assessed by statistical analysis. In total, 369 (60.8%) of the patients were diagnosed with CAD. The CAD patients had significantly higher SUA levels than those without CAD (5.3 ± 1.9 vs. 4.8 ± 1.7 mg/dL, P = 0.001). The SUA levels were found to be significantly associated with CAD prevalence (P = 0.013). Patients with higher levels of SUA also showed increased rates of multivessel disease and composite end-points, such as major adverse cardiac events. Furthermore, multivariate analysis identified abnormally high levels of uric acid (hyperuricemia) as an independent risk factor for CAD (OR 1.51 (1.11-2.53), P<0.05). The SUA levels are significantly associated with the prevalence of CAD. The SUA levels may be a predictor for incidence of major cardiovascular events in premenopausal women.


Transfusion management in the trauma patient.
Transfusion of blood products is lifesaving in the trauma ICU. Intensivists must be familiar with contemporary literature to develop the optimal transfusion strategy for each patient. A balanced ratio of red-blood cells to plasma and platelets is associated with improved mortality and has therefore become the standard of care for resuscitation. There is a dose-dependent relationship between units of product transfused and infections. Liquid and freeze-dried plasma are alternatives to fresh frozen plasma that can be administered immediately and may improve coagulation parameters more rapidly, though higher quality research is needed. Trauma induced coagulopathy can occur despite a balanced transfusion, and administration of prothrombin complex concentrate and cryoprecipitate may have a role in preventing this. In addition to balanced ratios, viscoelastic guidance is being increasingly utilized to individualize component transfusion. Alternatively, whole blood can be used, which has become the standard in military practice and is gaining popularity at civilian centers. Hemorrhagic shock is the leading cause of death in trauma. Improved resuscitation strategy has been one of the most important contemporary advancements in trauma care and continues to be a key area of clinical research.


[Surgical treatment of aortic root disease].
We reviewed aortic root disease and operative procedures. Between January 1982 and December 2008, aortic root operation was performed for 58 patients with various aortic root disease. We chose Bentall type operations in extensive root destructive cases and urgent or reoperative cases. Overall in-hospital mortality was 8.6% (5/58). Four patients (7.5% of survivors) died during the period of followup. Actuarial survival at 15 years was 92%. Freedom from cardiovascular event at 10 and 15 years was 81% and 27%, respectively. Of 5 reoperations in 5 patients, only 1 was required due to complications of the initial Bentall type operation. The Bentall type operations resulted in a durable result. Although, in Marfan syndrome, freedom from cardiovascular event was lower than that in non-Marfan syndrome, actuarial survival rate was equal with non-Marfan syndrome. Close observation is necessary for detecting cardiovascular event, especially in Marfan syndrome.


Distribution of Four Bioactive Flavonoids in Maize Tissues of Five Varieties and Correlation with Expression of the Biosynthetic Genes.
Flavonoids are characteristic in maize and have diverse biological functions. C-Glycosylflavones are neuroprotective against β-amyloid-induced tau hyperphosphorylation and neurotoxicity in SH-SY5Y cells, which is relevant to Alzheimer's disease prevention and treatment. The content of the flavonoids eriodictyol, luteolin, isoorientin, and maysin varied in pollens, silks, tassels, and seeds among five maize varieties. Eriodictyol content was high (51-322 ng/g dw) in pollens, while luteolin content was low (0.2-106 ng/g dw) in all four tissues. The isoorientin content was approximately 3- to 10-fold greater than eriodictyol in pollens and tassels, particularly in the hybrid M1 and sweet corn M5 varieties. Maysin content was high in most silks and tassels. The differential expression of five genes involved in the maysin biosynthesis correlated well with the profiles of the four flavonoids among tissues and varieties. The present study offers valuable data for maize breeding and the use of maize flavonoids as functional food components.


An instance of clinical radiation morbidity and cellular radiosensitivity, not associated with ataxia-telangiectasia.
A 14-year-old boy received standard induction chemotherapy for acute lymphoblastic leukaemia followed by standard dose cranial radiation prophylaxis (18 Gy). Severe chemosensitivity and acute radiation reactions occurred and he died at 8 months from late radiation damage. In vitro radiobiological studies of the boy's fibroblasts in culture demonstrated an enhanced radiosensitivity indistinguishable from ataxia-telangiectasia (A-T) cells. However, unlike A-T cells, DNA synthesis following irradiation was inhibited in a normal manner. This patient represents yet another example of extreme radiosensitivity, and the possibility of clinical prediction in the future is discussed.


A distinctive form of human chorionic gonadotropin beta-subunit-like material produced by cervical carcinoma cells.
The DoT and CaSki human cervical carcinoma cell lines ectopically produce material immunologically similar to the beta-subunit of human chorionic gonadotropin (hCG beta). Culture fluids were analyzed by gel filtration chromatography and radioimmunoassay (RIA) using (a) antiserum directed to conformation-specific (core-directed) determinants not involving the carboxyl-terminal peptide (CTP) in hCG beta purified from urinary hCG (i.e., standard hCG beta) or (b) antiserum directed to the CTP in standard hCG beta. CTP-directed RIA recognized a peak of hCG beta-like immunoreactive material that eluted in the same position as standard hCG beta. However, core-directed RIA recognized additional hCG beta-like material (i.e., ectopic beta-II), most of which eluted before standard hCG beta. CaSki cells were incubated with [3H]mannose, [3H]proline, and [3H] leucine, and the spent medium was immunoprecipitated and analyzed by gel electrophoresis. Several labeled peaks were detected in the lane from the anti-hCG beta X Sepharose immunoprecipitate, one of which corresponded in mobility to standard hCG beta, with two more intense components migrating at higher apparent molecular weights. Carboxypeptidase Y digestion released only 0.2 mol equivalents each of [3H]proline and [3H]leucine from the labeled CaSki material immunoprecipitated with anti-hCG beta X Sepharose, compared to 1 mol equivalent each in similar analysis of standard hCG beta. These findings were consistent with the absence of the 4-carboxy-terminal amino acids from 80% of the hCG beta-like immunoreactive material secreted by CaSki cells. The affinity purified ectopic beta-II failed to combine with standard hCG alpha under conditions in which combination of standard hCG beta with standard hCG alpha was essentially complete. Neither aggregation nor proteolytic degradation was the cause of failure of ectopic beta-II to combine with hCG alpha. We conclude that both the DoT and CaSki cervical carcinoma cell lines secrete a distinctive form of hCG beta-like material, ectopic beta-II. Lack of recognition by CTP-directed antisera and amino acid analysis suggest that ectopic beta-II may lack the CTP, despite its apparent larger size relative to standard hCG beta.


[3D reconstruction of anterior internal vertebral venous plexus of a human fetus: a feasibility study].
Anterior internal vertebral venous plexus have been studied extensively due to their clinical importance in diseases of the spine and obstruction of the inferior vena cava. The aim of this feasibility study was to reconstruct in 3D the lower thoracic area of the anterior epidural space of a 69 mm (crown-rump) human fetus from the Rouvière Collection, circa 1927. Forty slices (spaced by 40 microm) at the level of the tenth and eleventh thoracic vertebrae, and their lower adjacent intervertebral discs, were reconstructed in 3D using the commercial software SURFdriver. In a preliminary study, we had found that the structures of the epidural space are already formed at this stage of development, and that they are comparable to the adult stage (2002). Reconstruction of the microscopic slices in 3D allowed to better visualize spatially the structures of the venous plexus and their anatomical relationships. This technique could be used as a complement to the classically used histological studies.


Development of Lutzomyia intermedia and Lutzomyia longipalpis (Diptera: Psychodidae: Phlebotominae) larvae in different diets.
The objective of this research was to evaluate, in laboratory, the development of Lutzomyia intermedia and Lutzomyia longipalpis (Diptera: Psychodidae: Phlebotominae) larvae, vectors of leishmaniasis in Brazil, in the following diets: industrialized food for rabbits, dogs, hamsters and aquarium fishes, besides liver powder, cooked lettuce, wheat germ, beer yeast, oat, wheat bran and a diet denominated aged food. Except wheat bran for L. intermedia, all diets provided adequate development for both species, which showed that any of them can be used in laboratory insectaries for these insects. L. intermedia showed better development with most nutritious diets and both species presented better development with aged food. Fungi as an additional nutrient source for L. intermedia and L. longipalpis is suggested.


Gene expression studies of a human monocyte cell line identify dissimilarities between differently manufactured glatiramoids.
Glatiramer Acetate (GA) has provided safe and effective treatment for multiple sclerosis (MS) patients for two decades. It acts as an antigen, yet the precise mechanism of action remains to be fully elucidated, and no validated pharmacokinetic or pharmacodynamic biomarkers exist. In order to better characterize GA's biological impact, genome-wide expression studies were conducted with a human monocyte (THP-1) cell line. Consistent with previous literature, branded GA upregulated anti-inflammatory markers (e.g. IL10), and modulated multiple immune-related pathways. Despite some similarities, significant differences were observed between expression profiles induced by branded GA and Probioglat, a differently-manufactured glatiramoid purported to be a generic GA. Key results were verified using qRT-PCR. Genes (e.g. CCL5, adj. p < 4.1 × 10(-5)) critically involved in pro-inflammatory pathways (e.g. response to lipopolysaccharide, adj. p = 8.7 × 10(-4)) were significantly induced by Probioglat compared with branded GA. Key genes were also tested and confirmed at the protein level, and in primary human monocytes. These observations suggest differential biological impact by the two glatiramoids and warrant further investigation.


Ultrastructural aspects of nailfold capillaries in a case of eosinophilic fasciitis.
An ultrastructural study was made on the nailfold capillaries in an 18-year-old female with eosinophilic fasciitis. Scleroderma-like capillaroscopic lesions were visible at the sites where biopsy was performed. Light microscopy revealed ectasic capillaries at the apex of dermal papillae. Aspects of thickening and duplication of the epidermal basement membrane as well as an activation of endothelial cells were visualized at the ultrastructural level. These cells contained many virus-like tubulo-reticular inclusions, associated with cisternae of endoplasmic reticulum. Aspects of degeneration of nerve fibres and Schwann cells were also present. Large, homogeneously electron-dense deposits could be seen in the basement membrane at the dermo-epidermal junction. This study not only confirms previous observations on the microangiopathy in eosinophilic fasciitis, but also documents two new aspects: electron-dense deposits at the dermo-epidermal junction and tubulo-reticular inclusions within endothelial cells.


Successful osimertinib rechallenge after severe thrombocytopenia caused by osimertinib combined with sitagliptin: a case report.
Osimertinib is recommended as the first-line treatment of advanced non-small cell lung cancer (NSCLC) in adults. The most commonly reported adverse events for osimertinib are skin effects, diarrhea, nausea, decreased appetite, fatigue, paronychia, and stomatitis. Severe thrombocytopenia is rarely reported. We present a case of severe thrombocytopenia in a 70-year-old NSCLC patient caused by osimertinib combined with sitagliptin. After remission of thrombocytopenia, the patient was well tolerated with osimertinib re-administration in the absence of sitagliptin. We speculated that declined platelet count might be related to the interaction between osimertinib and sitagliptin by acting with a synergistic effect on platelets. Osimertinib rechallenge can be considered after discontinuing drugs that may contribute to platelet decline if possible, and making a careful assessment of complete blood count and risk of bleeding.


Embolic protection devices in saphenous vein graft interventions.
Saphenous vein grafts (SVGs) are widely used as aortocoronary conduits during coronary artery bypass surgery and are critical in the high early success of coronary bypass revascularization. Saphenous vein grafts tend to be more prone than native coronary arteries to accelerated atherosclerosis and intimal fibrosis and thus frequently lead to recurrent symptoms and require further revascularization. Percutaneous coronary interventions (PCI) have become the prime means of SVG mechanical revascularization but are plagued by higher complication rates than PCI on native coronaries, largely due to embolic debris mobilized from around the target lesion in the SVG. Several mechanical devices and techniques have been developed to capture this friable material during the PCI before it can embolize; these devices have shown great promise in reducing the morbidity and mortality of these interventions and should be employed routinely.


Variability of the response of human vaginal Lactobacillus crispatus to 17β-estradiol.
We previously showed that the physiological concentration of 17β-estradiol in the vaginal environment is sufficient to affect the membrane dynamics and adhesion phenotype of the Lactobacillus crispatus strain CIP104459. However, L. crispatus is a heterogeneous species. Here, we investigated the effect of 17β-estradiol on the recently isolated L. crispatus vaginal strain V4, related to a cluster distant from CIP104459 and at the limit of being a different subspecies. Grown in the same medium, the two strains expressed a highly similar pool of proteins. However, in contrast to CIP104459, L. crispatus V4 showed high aggregation potential and 17β-estradiol promoted this phenotype. This effect was associated with large changes in cell-surface polarity and Lewis acid/base properties. In addition, we observed no effect on the membrane dynamics, contrary to CIP104459. These results can be explained by differences in the properties and organization of the S layer between the two strains. However, as for CIP104459, 17β-estradiol increased biosurfactant production of L. crispatus V4 and their adhesion to vaginal cells. This suggests that 17β-estradiol agonists would be valuable tools to favor a stable re-implantation of L. crispatus in the vaginal mucosa.


Pigs, pooches and pasteurisation: The changing face of brucellosis in Australia
Brucellosis, also known as undulant, Mediterranean or Malta fever, is a systemic infection that causes fever, sweats, arthralgias and myalgias. A globally important disease, brucellosis is re-emerging in Australia in association with feral pig hunting activities. This article aims to provide clinicians with an overview of brucellosis, covering epidemiology, clinical features, diagnosis, management and prevention. Brucellosis should be suspected in all patients with non-specific, flu-like illness who fall into one of the major risk groups (feral pig hunters, overseas travellers and migrants). Depression is common and often severe, relative to other symptoms. Early diagnosis and treatment are important for preventing complications, which include osteoarticular, genitourinary or, more rarely, neurological or cardiovascular diseases. Diagnosing acute infections is based on serology and blood cultures; imaging and biopsy may be required for diagnosis of focal infections. Dual therapy with doxycycline and gentamicin is the recommended treatment. Relapse occurs in up to 10% of patients. Prevention is achieved through the use of protective gear during hunting and avoidance of unpasteurised dairy products in countries where occur in animals.


A human herpesvirus 7 glycoprotein, U21, diverts major histocompatibility complex class I molecules to lysosomes.
All members of the herpesvirus family persist in their host throughout life. In doing so, herpesviruses exploit a surprising number of different strategies to evade the immune system. Human herpesvirus 7 (HHV-7) is a relatively recently discovered member of the herpesvirus family, and little is known about how it escapes immune detection. Here we show that HHV-7 infection results in premature degradation of major histocompatibility complex class I molecules. We identify and characterize a protein from HHV-7, U21, that binds to and diverts properly folded class I molecules to a lysosomal compartment. Thus, U21 is likely to function in the normal course of HHV-7 infection to downregulate surface class I molecules and prevent recognition of infected cells by cytotoxic T lymphocytes.


Indolent lymphoma: follicular lymphoma and the microenvironment-insights from the microscope.
Follicular lymphomas (FLs) are neoplasms of germinal center (GC) B cells, which retain many of the morphologic, immunophenotypic, genetic, and functional features of normal GC B cells. Both normal GCs and neoplastic follicles of FL also contain non-neoplastic cells (microenvironment) that influence and are influenced by the GC and FL B cells and are likely important for tumor cell survival. Many insights into the nature of the GC/FL microenvironment have come from morphologic and immunophenotypic analysis, both before and after the discoveries from gene expression profiling. This chapter reviews what we have learned from the microscope and highlights the pitfalls involved in trying to enumerate cells in the microenvironment for clinical prognostication.


Assessment of Bone Metabolism in Male Patients With Benign Paroxysmal Positional Vertigo.
Objective: Several studies have suggested a probable association between benign paroxysmal positional vertigo (BPPV) and both reduction of bone mineral density (BMD) and serum vitamin D levels, but none of these studies have explored their findings by examining bone turnover markers (BTM) in male idiopathic BPPV patients. This study aimed to evaluate the relationship between BMD and serum 25-hydroxyvitamin D (25(OH) D), with the occurrence of BPPV along with the characteristics of bone metabolism in male idiopathic BPPV patients. Methods: This retrospective study comprised 60 male idiopathic BPPV patients and 92 age-matched healthy controls referred to Ningbo No.2 Hospital during the period of February 2016 to February 2018. All subjects' serum levels of 25(OH) D, bone formation marker amino-terminal propeptide of type I procollagen (PINP), and bone resorption marker β-isomerized carboxy-terminal telopeptide of type I collagen (β-CTX) were measured. BMD was determined by dual energy X-ray absorption at the lumbar spine and hip. Results: Among male patients with BPPV, the prevalence of BMD reduction was 35.0%, which was similar to that of 27.2% in healthy controls. There were significant differences in the mean serum 25(OH) D level and prevalence of vitamin D deficiency between the two groups, with p-values of 0.049 and 0.009, respectively. The bone turnover markers of PINP and β-CTX in BPPV patients were lower than those in healthy controls. Logistic regression showed that vitamin D deficiency were associated with BPPV with an odds ratio of 3.8 (95% confidence interval = 1.25-11.73). Conclusion: Our study found that decreased serum vitamin D may be a risk factor for BPPV in male patients. The level of bone turnover among male patients with BPPV was lower than that among healthy controls.


Mixed method designs in implementation research.
This paper describes the application of mixed method designs in implementation research in 22 mental health services research studies published in peer-reviewed journals over the last 5 years. Our analyses revealed 7 different structural arrangements of qualitative and quantitative methods, 5 different functions of mixed methods, and 3 different ways of linking quantitative and qualitative data together. Complexity of design was associated with number of aims or objectives, study context, and phase of implementation examined. The findings provide suggestions for the use of mixed method designs in implementation research.


Electromyographic Patterns of Paratonia in Normal Subjects and in Patients with Mild Cognitive Impairment or Alzheimer's Disease.
Information on prevalence, pathophysiology, and clinical assessment of paratonia are scarce. In a previous study, we suggested that surface electromyography (EMG) can be used to assess paratonia. To assess clinical and EMG features of paratonia in both patients with cognitive impairment and healthy subjects. We examined 18 patients with Alzheimer's disease (AD), 21 patients with mild cognitive impairment (MCI), 30 healthy seniors (seniors), and 30 healthy juniors (juniors). Paratonia was assessed using the "Paratonia Scale". EMG bursts were recorded from biceps and triceps during manually applied passive movements of elbow joint. Continuous (sinusoidal) and discontinuous (linear) movements were applied at 2 different velocities (fast and slow). In comparison to juniors, seniors had higher clinical scores. In comparison to seniors, AD had higher oppositional scores, while MCI had higher facilitatory scores. EMG activity during passive movements correlated with paratonia clinical scores, was velocity-dependent and increased with movement repetition, most effectively for sinusoidal movements. Similar EMG activity was detected in not paratonic muscles. Paratonia increases with normal aging and cognitive decline progression. While facilitatory paratonia is due to involuntary contraction of the shortening muscle, oppositional paratonia is due, at least partially, to involuntary contraction of the lengthening muscle. Most characteristic feature of this muscle contraction is the progressive increase with movement repetition, that helps distinguish oppositional paratonia from spasticity and rigidity. A similar EMG activity is detected in not paratonic muscles, showing that, during tone assessment, the descending motor system is incompletely inactivated also in normotonic muscles.


[Laparoscopic adrenalectomy due to primary aldosteronism during pregnancy].
Primary aldosteronism (PA) during pregnancy is an extremely rare condition that may cause life threatening complications both for the mother and the fetus. A pregnant 31-year-old woman was referred to our hospital for the management of severe pregnancy hypertension at the beginning of her pregnancy. Her plasma aldosterone concentration (PAC) was markedly elevated (337 pg/ml), plasma rennin activity was suppressed (0.4 ng/ml/hr) and magnetic resonance imaging showed a 1.5 cm left adrenal tumor. PA due to an aldosterone producing-adenoma was diagnosed. Because of progressive uncontrollable hypertension and hypokalemia, a laproscopic adrenalectomy was performed at 24 weeks of gestation. The transabdominal approach was completed without any complication, resulting in normalization of PAC, easier management of blood pressure and improvement of hypokalemia. Because of severe pregnancy hypertension, cesarean operation was performed at 30 weeks of gestation and a girl weighing 1,235 g was delivered. The literature regarding PA during pregnancy was reviewed and the optimal timing of laparoscopic adrenalectomy during pregnancy and perioperative management were discussed.


[The chromosomal polymorphism and divergence of populations in Chironomus nuditarsis Str. (Diptera, Chironomidae)].
The karyotype structure and chromosomal polymorphisms were investigated in 6 natural and 2 laboratory populations of Chironomus nuditarsis from Europe and Asia. The pool of rearranged polytene chromosome banding sequences of this species was determined that includes 16 inversion banding sequences and sequences with giant DNA-knobs (ndtG1k, ndtG2k). Obvious differences were demonstrated in the level of chromosomal polymorphism between European and Asian (Siberian) populations: the former were highly polymorphic, while the latter were practically monomorphic. It was suggested to consider the Siberian populations as marginal one. Cytogenetic distances between populations of C. nuditarsis as well between C. nuditarsis and the related species C. plumosus were estimated. The data obtained show that chromosomal rearrangements play a very important role in cytogenetic divergence of populations.


Simvastatin improves fracture healing in mice.
Recently, several articles have been published dealing with the anabolic effects on bone by statins. Mundy and associates discovered that several statins were able to activate the promotor of bone morphogenetic protein (BMP) 2. Additionally, oral simvastatin and lovastatin increased the cancellous bone volume in rats, presumably an effect of the increase of BMP-2. Other studies have followed, with conflicting results; some have found a positive bone metabolic effect of statins and others have not. Studies published so far have focused on osteoporosis. In this study, femur fractures were produced in 81 mature male BALB/c mice and stabilized with marrow-nailing. Forty-one mice were given a diet prepared with simvastatin, so that each mouse received an approximate dose of 120 mg/kg of body weight per day. The remaining mice received the same diet with the exception of the simvastatin. Bilateral femurs were harvested at 8, 14, and 21 days postoperatively (po), the marrow-nail was extracted, and diameters were measured. Biomechanical tests were performed on 42 mice, by way of three-point bending. Histological specimens were prepared using standard techniques. For statistical analysis, ANOVA with Scheffés post hoc test was used. At 8 days, the fracture callus was too soft for meaningful biomechanical testing. At 14 days, the callus of the simvastatin-treated mice had a 53% larger transverse area than controls (p = 0.001), the force required to break the bone was 63% greater (p = 0.001), and the energy uptake was increased by 150% (p = 0.0008). Stiffness and modulus of elasticity were not significantly affected. At 21 days, the fractures were histologically healed and the mechanical differences had disappeared. The contralateral unbroken bone showed a slight increase in transverse area because of the simvastatin treatment, but there was no significant effect on the force required to break the bone or on energy uptake. These results point to a new possibility in the treatment of fractures.


Picornavirus infections in children diagnosed by RT-PCR during longitudinal surveillance with weekly sampling: Association with symptomatic illness and effect of season.
RT-PCR is more sensitive for rhinovirus detection than cell culture, but healthy controls are frequently rhinovirus (or picornavirus) positive in cross-sectional studies. Fifteen healthy children were followed over at least three seasons of the year with weekly sampling of nasal/nasopharyngeal secretion for RT-PCR testing for picornavirus and daily recording of respiratory symptoms. One sample positive for picornavirus was diagnosed as an infection; consecutive positive weekly samples constituted a single infection. Picornavirus illness was diagnosed if RNA was detected 7 days prior through 21 days after onset. One hundred fifty-five (21%) of 740 weekly samples were picornavirus positive and associated with illness; 37(5%) positives were not associated with illness (P = 0.001). The 192 positive samples occurred in 121 infections, 74 with a single positive and 47 with "runs" of positives in two or more consecutive samples. Forty five (96%) of the 47 runs comprised 2 or 3 consecutive positives. Ninety six (52%) of 185 reported illnesses during 235 child-months were picornavirus positive (0.4/child-month); 25 infections were asymptomatic (0.11/child-month). The infection rate was highest in fall (0.66/child-month); the winter rate (0.44/child-month) was similar to that in spring (0.5) and summer (0.43). Picornavirus infections in healthy children were common (0.51/child-month), episodic, and usually associated with brief illness; one fifth of infections were asymptomatic. The infection rate was highest in fall; infections in winter occurred at the same rate as in spring and summer.


Thrombophilia and pulmonary endarterectomy.
In the present study, we compared groups of patients with and without thrombophilia, who underwent pulmonary endarterectomy (PEA), definitive treatment for chronic pulmonary hypertension resulting from thromboembolic disease. Between September 2004 and June 2007, we operated 54 patients with CTEPH. We divided our patients into three groups. Group I patients, had one or more signs of serious thrombophilia (15 patients), Group II patients, had no signs of thrombophilia (23 patients without thrombophilia and without Methylenetetrahydrofolate Reductase (MTHFR)), and Group III patients with MTHFR (16 patients with MTHFR only, without any serious thrombophilia). After the surgery, there was a statistically considerable improvement of hemodynamic parameters (mPA, CI, PVR) in all groups, without a statistical difference between the groups. Comparison of all these groups showed more complications in-group I (thrombophilia), in particular reperfusion oedema, pericardial effusion, and renal insufficiency. Within one month, there was a considerable improvement or normalisation of haemodynamic parameters, an increase in walking distance at the six-minute walking test, and NYHA classification with no significant difference between the three groups. Early hemodynamic results of patients with thrombophilia after PEA, were comparable to the results of patients without thrombophilia, when we looked at both clinical and hemodynamic improvements. We did not find any differences when we looked at the results between Group II and Group III (MTHF), when we considered the number and type of complications. Patients with thrombophilia in Group I had statistically higher morbidity, especially when it came to a higher number of reperfusion oedema, pericardial effusion, and renal insufficiency.


Solar UV-B radiation inhibits the growth of Antarctic terrestrial fungi.
We tested the effects of solar radiation, and UV-B in particular, on the growth of Antarctic terrestrial fungi. The growth responses to solar radiation of five fungi, Geomyces pannorum, Phoma herbarum, Pythium sp., Verticillium sp., and Mortierella parvispora, each isolated from Antarctic terrestrial habitats, were examined on an agar medium in the natural Antarctic environment. A 3-h exposure to solar radiation of >287 nm reduced the hyphal extension rates of all species relative to controls kept in the dark. Pythium sp. cultures exposed to solar radiation for 1.5 h on five consecutive days were most sensitive to radiation of >287 nm, but radiation of >313 nm also inhibited growth to a lesser extent. Radiation of >400 nm had no effect on hyphal growth relative to controls kept in the dark. Short-wave solar UV-B radiation of between 287 and 305 nm inhibited the growth of Pythium sp. hyphae on and below the surface of the agar medium after 24 h, but radiation of > or =345 nm only reduced the growth of surface hyphae. Similar detrimental effects of UV-B on surface and, to a lesser extent, submerged hyphae of all five fungi were shown in the laboratory by using artificial UV-B from fluorescent lamps. A comparison of growth responses to solar radiation and temperature showed that the species that were most resistant to UV radiation grew fastest at higher temperatures. These data suggest that solar UV-B reduces the growth of fungi on the soil surface in the Antarctic terrestrial environment.


First-trimester maternal serum alpha-fetoprotein is not a good predictor for adverse pregnancy outcomes: a retrospective study of 3325 cases.
It is well known that second-trimester maternal serum alpha-fetoprotein (MS-AFP) is a predictor for adverse pregnancy outcomes (APOs), such as preterm birth, stillbirth, preeclampsia and small for gestational age (SGA). However, it is unknown whether first-trimester MS-AFP is also predictive of APOs. We retrospectively reviewed the data on the first-trimester MS-AFP levels and pregnancy outcomes of 3325 singleton pregnant women. The cutoff value of 2.5 multiple of the median (MoM) was used to evaluate the risks of APOs regarding MS-AFP. The receiver operating characteristic (ROC) curves were used to evaluate the predictive efficiencies of MS-AFP to these disorders. A total of 181 pregnancies resulted in preterm birth, 32 in stillbirth, 81 in preeclampsia, and 362 in SGA. Compared to women with MS-AFP < 2.5MoM, those with MS-AFP ≥ 2.5MoM had increased risks (odds ratio, 95% confidence interval) of preterm birth (2.53, 1.65~3.88), preeclampsia (3.05, 1.71~5.43) and SGA (1.90, 1.34~2.69), and had an earlier distribution of gestational weeks at delivery (P = 0.004) and a lower distribution of neonatal birth weights (P = 0.000), but the actual between-group differences were minuscule. The areas under ROC curves were 0.572 (P = 0.001), 0.579 (P = 0.015) and 0.565 (P = 0.000) for preterm birth, preeclampsia and SGA, respectively. Subdivisions for the disorders did not obviously improve the performances of MS-AFP. Elevated first-trimester MS-AFP is associated with increased risk of preterm birth, preeclampsia and SGA. However, the predictive efficiencies were low and it is not a good predictor for these APOs.


Design and Development of a Behaviorally Active Recombinant Neurotrophic Factor.
Carbamoylated erythropoietin (CEPO) is a chemically engineered, nonhematopoietic derivative of erythropoietin (EPO) that retains its antidepressant and pro-cognitive effects, which are attributed to the increased expression of neurotrophic factors like brain derived neurotrophic factor (BDNF), in the central nervous system. However, the chemical modification process which produces CEPO from erythropoietin (EPO) requires pure EPO as raw material, is challenging to scale-up and can also cause batch-to-batch variability. To address these key limitations while retaining its behavioral effects, we designed, expressed and analyzed a triple, glutamine, substitution recombinant mimetic of CEPO, named QPO. We employ a combination of computational structural biology, molecular, cellular and behavioral assays to design, produce, purify and test QPO. QPO was shown to be a nonhematopoietic polypeptide with significant antidepressant-like and pro-cognitive behavioral effects in rodent assays while significantly upregulating BDNF expression in-vitro and in-vivo. The in-silico binding affinity analysis of QPO bound to the EPOR/EPOR homodimer receptor shows significantly decreased binding to Active Site 2, but not Active Site 1, of EPOR. The results of the behavioral and gene expression analysis imply that QPO is a successful CEPO mimetic protein and potentially acts via a similar neurotrophic mechanism, making it a drug development target for psychiatric disorders. The decreased binding to Active Site 2 could imply that this active site is not involved in neuroactive signaling and could allow the development of a functional innate repair receptor (IRR) model. Substituting the three glutamine substitution residues with arginine (RPO) resulted in the loss of behavioral activity, indicating the importance of glutamine residues at those positions.


Permanent small groups: group dynamics, learning, and change.
The concept of "communities of practice," a special facet of social constructivist learning theory, provides a new template against which we can examine the learning that goes on within permanent small groups of physicians. We interviewed participants and facilitators about the dynamics of these groups, their learning in conjunction with these groups, and the role the facilitator played to see the extent to which they captured the essence of communities of practice. Semistructured interviews were conducted with physicians known to be participants or facilitators of small groups that met regularly. A constant comparative method was used for data gathering and analysis leading to coded themes, categories, and subcategories. The coding schemas were tested, the analyses were reviewed, and data were recoded as necessary. To ensure accuracy, interviewees were provided with a preliminary copy of the manuscript to ensure that the interpretation of the data was appropriately handled. Interviews were conducted with 10 facilitators and 22 group members representing 24 different groups of physicians. The groups appeared to function as communities of practice in which the members were supportive of each other's learning and respectful of one another, reporting little conflict. Members preferred to agree to disagree rather than pursue a "right" answer or consensus. Most of the discussion focused on scientific information and the way in which their colleagues approached common problems. Practice refinement rather than new directions in patient care appeared to be the goal. The facilitators in these groups played a key role in providing administrative support for the group and often the energy needed to sustain them. Small groups that meet regularly provide a supportive network to share knowledge and validate clinical experience. There is some evidence that the groups have the potential to become communities of practice but do not actually achieve that level of sharing. Research needs to be done to determine how these groups could become more powerful as communities of practice and vehicles for more substantive learning and change.


Rowlinson's concept of an effective hard sphere diameter.
Attention is drawn to John Rowlinson's idea that the repulsive portion of the intermolecular interaction may be replaced by a temperature-dependent hard sphere diameter. It is this approximation that made the development of perturbation theory possible for realistic fluids whose intermolecular interactions have a steep, but finite, repulsion at short separations.


Foliar endophytic fungi as potential protectors from pathogens in myrmecophytic Acacia plants.
In defensive ant-plant interactions myrmecophytic plants express reduced chemical defense in their leaves to protect themselves from pathogens, and it seems that mutualistic partners are required to make up for this lack of defensive function. Previously, we reported that mutualistic ants confer plants of Acacia hindsii protection from pathogens, and that the protection is given by the ant-associated bacteria. Here, we examined whether foliar endophytic fungi may potentially act as a new partner, in addition to mutualistic ants and their bacteria inhabitants, involved in the protection from pathogens in myrmecophytic Acacia plants. Fungal endophytes were isolated from the asymptomatic leaves of A. hindsii plants for further molecular identification of 18S rRNA gene. Inhibitory effects of fungal endophytes were tested against Pseudomonas plant pathogens. Our findings support a potential role of fungal endophytes in pathogen the protection mechanisms against pathogens in myrmecophytic plants and provide the evidence of novel fungal endophytes capable of biosynthesizing bioactive metabolites.


Experimental evaluation of aniline and methyl blue for intraocular surgery.
The purpose of this study was to investigate the biocompatibility of aniline and methyl blue in a well-established cell culture model and assess the staining properties of these dyes at the level of the internal limiting membrane (ILM) in human donor eyes. Dye-related toxicity was evaluated by a colorimetric test (MTT) measuring the inhibition of retinal pigment epithelium (ARPE-19 and primary human retinal pigment epithelium) cell proliferation. Cell viability was also quantified based on a two-color fluorescence assay (Life-Dead Assay). Aniline blue and methyl blue at a concentration of 0.2% was applied over the macula during vitrectomy in human donor eyes to evaluate the staining properties at the level of the ILM. Both dyes and dye concentrations of 0.1% and 0.2% showed no toxic effect on ARPE-19 and primary human retinal pigment epithelium cell proliferation for exposure times of 1 and 10 minutes, respectively. Cell viability was also not affected at all. Both dyes provided a good contrast at the level of the ILM and allowed for a controlled removal of the ILM during surgery. No penetration into deeper retinal layers was noted. Our results indicate that aniline blue and methyl blue might be applicable for intraocular surgery, providing a very good biocompatibility and required selective staining characteristics at the level of the ILM.


[Modeling of K+ATP channel activity in normotensive and hypertensive animals].
It was shown that vasodilatory effects of ATP-sensitive potassium channels opener--flocalin--depend from character of increase of initial vessel tone. Norepinephrine and angiotensin II partially inhibit effects of flocalin, thus they depressed of KATP channel activity. The inhibitory effect of angiotensin II increases under arterial hypertension conditions. It was shown that vasodilatory effects of flocalin significantly do not distinguish in experiments on normotensive and hypertensive rats under K(+)-depolarization conditions. While the vasodilatory effects acetylcholine on hypertensive rats are significantly diminished. These data suggests that flocalin could be a perspective substance for treatment of hypertension.


Compensating for losses in perceived personal control over health: a role for collective self-esteem in healthy aging.
Collective self-esteem (CSE) refers to an individual's self-evaluation of his or her social identity. We speculate that a positive social identity, or high CSE, facilitates accommodation to negative health-related circumstances in later life, especially when one feels unable to alter these circumstances directly. Accordingly, we hypothesized that CSE would be associated with fewer chronic conditions and greater perceived health for those with low perceived control. Hierarchical regression analyses of data from 1,267 respondents (60% women, aged 69-101) in the 1996 Aging in Manitoba survey confirmed the predicted CSE x Perceived Control interaction on both measures of health status. These findings persisted when respondents' self-rated loneliness was controlled. CSE may compensate to protect the health of older adults whose perceived personal control over health is low. Secondary control and alternative mechanisms for this protective effect are discussed.


Binding orientation and interaction of bile salt in its ternary complex with pancreatic lipase-colipase system.
The interfacial activity of pancreatic lipases (PL) depends on the presence of colipase and bile salt. The activity of PL is inhibited by micellar concentrations of bile salt which can be restored by the addition of colipase. Though the formation of 1:1:1 tertiary complex by lipase-colipase-bile salt micelle is well accepted, the residue-level interactions between lipase-colipase and bile salt are yet to be clearly understood. Molecular dynamic simulations of lipase-colipase complex, lipase and colipase were performed in the presence of a model bile salt, sodium taurocholate (NaTC), at its near-CMC and supra-micellar concentrations. From the interactions obtained from the molecular dynamic simulations, the ternary complex was modelled and compared with earlier reports. The analysis suggested that a micelle of NaTC consisting of nine monomers was formed at the concave groove between lipase and colipase chain and it mainly interacted with the fourth finger of colipase. This complex was mainly stabilized by van der Waals interactions. Interestingly, the C-terminal domain of lipase which holds the colipase did not show any significant role in formation or stabilization of NaTC micelle.


Potential role of statins on wound healing: review of the literature.
Wound healing is a dynamic and complex biological process, which requires coordinated events including haemostasis, inflammation, proliferation, revascularisation and remodelling. Impaired wound healing is a common problem that occurs in both community and hospital settings. Various experimental and clinical studies have evaluated different modalities for the treatment of topical wounds, such as sugar, antibiotics, honey and phytotherapies; also statins have diverse pleiotropic effects that have been suggested to be useful to improve wound healing. Data derived from both animal and human studies showed that statins especially atorvastatin, simvastatin and pravastatin can accelerate the wound-healing process. However, further high-quality and evidence-based studies are needed to address the best statin drug, appropriate dose, the best administration route, duration of treatment and to determine correlation between pleiotropic effects of statins and their probable clinical benefits.


On the role played by the chirality of ligands on the aggregation of heterometallic CuII -HgII complexes.
Copper(II) complexes constructed from enantiopure Schiff-base ligands derived from o-vanillin and methionine or from their racemic mixture have been employed as metalloligands towards mercury(II) ions. The nature of the heterometallic CuII -HgII complexes (coordination polymers or oligonucler species), resulted from the reactions of the copper(II) complexes with HgCl2 or HgI2 , is different. The enantiopure metalloligands lead to chiral coordination polymers, 1∞ [{Cu(R-/S-valmet)(H2 O)}2 HgCl2 ]·5H2 O·CH3 OH and 2∞ [{Cu2 (R-/S-valmet)2 (μ-H2 O)(H2 O)2 }HgI2 ]·4H2 O. The reaction of the racemic mixture of the metalloligands with HgX2 affords discrete complexes: [{Cu(R,S-valmet)(H2 O)2 }2 HgCl2 ]·2H2 O and [{Cu(R,S-valmet)(H2 O)(CH3 OH)}2 Hg2 I4 ].


Loudness growth in forward masking: relation to intensity discrimination.
The growth of loudness of a tone burst following an intense forward masker was measured as a function of the tone level. The level of the forward-masked tone was adjusted to balance the loudness of a standard tone presented without a forward masker, using a 2AFC, double-staircase, tracking procedure. The forward masker was a 90-dB SPL, 100-ms, 1000-Hz pure tone. The standard tone and the masked tone were both 25-ms, 1000-Hz pure tones. The forward masker and the masked tone were always presented in the first interval. With a 100-ms delay between them, there was little or no threshold elevation for the masked tone. However, the masker caused the masked tone to sound louder than it would if it had not been masked, a phenomenon termed "loudness enhancement" [Irwin and Zwislocki, Percept. Psychophys. 10, 189-192 (1971); Galambos et al., J. Acoust. Soc. Am. 52, 1127-1130 (1972)]. In addition, the present results show a nonmonotonic enhancement function that the forward masker introduced a 10-16-dB enhancement effect for tones of 40-65 dB SPL and no significant effect for the 30 and 90 dB SPL tones. The loudness variability in forward masking was estimated from the upper and lower sequences tracking the 21% and the 79% louder response levels on the psychometric function, respectively. The variability demonstrated a similar nonmonotonic function. In forward masking loudness grows more steeply at low-medium sensation levels, and merges with normal growth at high levels.(ABSTRACT TRUNCATED AT 250 WORDS)


Saphenous vein graft disease: review of pathophysiology, prevention, and treatment.
Saphenous vein graft (SVG) disease after coronary artery bypass grafting (CABG) occurs in three phases: thrombosis, intimal hyperplasia, and atherosclerosis. Within the first month, thrombosis plays a major role. From month 1 to month 12, intimal hyperplasia occurs. Beyond 12 months, atherosclerosis becomes the primary cause for late graft failure. Endothelial damage has been shown to be the major underlying pathophysiology of SVG disease. Many factors contribute to endothelial damage from the moment the vein is harvested to when the vein is grafted into an arterial environment. To address this disease process, various therapeutic modalities, from surgical methods to medical treatment, have been evaluated. Surgically, the technical method of harvesting the vein has been shown to affect SVG patency. From a pharmacologic perspective, only two guideline class I recommended medications, aspirin and statins, have been shown to improve short- and long-term SVG patency after CABG. Despite these surgical and medical advances, SVG disease remains a significant problem with 1-year patency rates of 89% dropping to 61% after 10 years. This review discusses the pathogenesis of SVG disease, predictors of SVG failure, and current surgical and pharmacologic therapies to address SVG disease, including possible future treatment.


Sociodemographic inequities in cervical cancer screening, treatment and care amongst women aged at least 25 years: evidence from surveys in Harare, Zimbabwe.
Cervical cancer is the most commonly diagnosed cancer among women in Zimbabwe; however; access to screening and treatment services remain challenged. The objective of this study was to investigate socio-demographic inequities in cervical cancer screening and utilization of treatment among women in Harare, Zimbabwe. Two cross sectional surveys were conducted in Harare with a total sample of 277 women aged at least 25 years. In the community survey, stratified random sampling was conducted to select 143 healthy women in Glen View, Cranborne, Highlands and Hopely communities of Harare to present high, medium, low density suburbs and rural areas respectively. In the patient survey, 134 histologically confirmed cervical cancer patients were also randomly selected at Harare hospital, Parirenyatwa Hospital and Island Hospice during their routine visits or while in hospital admission. All consenting participants were interviewed using a validated structured questionnaire programmed in Surveytogo software in an android tablet. Data was analyzed using STATA version 14 to yield descriptive statistics, bivariate and multivariate logistic regression outcomes for the study. Women who reported ever screening for cervical cancer were only 29%. Cervical cancer screening was less likely in women affiliated to major religions (p < 0.05) and those who never visited health facilities or doctors or visited once in previous 6 months (p < 0.05). Ninety-two (69%) of selected patients were on treatment. Women with cervical cancer affiliated to protestant churches were 68 times [95% CI: 1.22 to 381] more likely to utilize treatment and care services compared to those in other religions (p = 0.040). Province of residence, education, occupation, marital status, income (personal and household), wealth, medical aid status, having a regular doctor, frequency of visiting health facilities, sources of cervical cancer information and knowledge of treatability of cervical cancer were not associated with cervical cancer screening and treatment respectively. This study revealed few variations in the participation of women in cervical cancer screening and treatment explained only by religious affiliations and usage of health facilities. Strengthening of health education in communities including churches and universal healthcare coverage are recommended strategies to improve uptake of screening and treatment of cervical cancer.


The experience of family carers of children with incurable cancer: a qualitative study from the occupied Palestinian territory.
Treatments for childhood cancers have raised the survival rate, however different forms of malignancy continue to cause untimely deaths, and cancer remains a leading cause of death among children. Global research on paediatric cancer is limited for several reasons. Most research has focused on specific methodologies, including questionnaires with heterogeneous samples. In addition, many studies have covered a broad range of cancer diagnoses, and a wide range of children's ages and periods between diagnosis and treatment. These methods are unable to capture the essence of experiences and cultural differences. This study aimed to explore the experience of family carers of children with incurable cancer in occupied Palestinian territory. The study was conducted in the Paediatric Cancer Department of Beit Jala Hospital, which is the first public cancer department for children in the West Bank. The family carers of children aged 1-18 years with any type of incurable cancer in this hospital were considered eligible for participation, and the individual most involved in the care of the child was selected. To recruit participants, head nurses of medical and surgical paediatric floors provided assistance in approaching the carers of eligible children. The main objectives of the study were then discussed with the family carers. Semi-structured interviews were conducted with participants, and an interpretative phenomenological analysis approach was used to analyse the collected information. Ethical approval was obtained from the Beit Jala Hospital ethical review board and written informed consent was obtained from all participants. 14 interviews were conducted. Participants were nine mothers, four grandmothers, and one father. Family carers discussed their caring experiences, including their experiences in administering special treatments, their suffering due to treating irritable children, and the information given to them about their children's illness. Family carers reported that they changed the focus of their care from an initial emphasis on normalising their children's lives to relieving their physical and psychological discomfort. This change of focus accompanied changes in carers' understanding of their child's disease over time. As carers became more realistic regarding the future of their children, they attempted to make their lives as comfortable as possible. Finally, carers discussed the support system around them; they found several resources to support them in the care of their children, including the experiences of other parents of children with similar diseases, the hospital environment, and their religious beliefs. Nevertheless, they stated that they needed more support during this difficult time of their lives. There is a need to support parents of children with incurable cancer in the occupied Palestinian territory. Suggestions to improve the quality of care provided for these parents include the education and recruitment of health care professionals, including social workers and psychologists, to provide emotional and spiritual support. None.


Comparison of corticosteroid nasal sprays in relation to concomitant use and cost of other prescription medications to treat allergic rhinitis symptoms: retrospective cohort analysis of pharmacy claims data.
Intranasal corticosteroids are considered to be highly effective in patients with perennial or seasonal allergic rhinitis. Multiple intranasal corticosteroid products are available; however, an intranasal corticosteroid that treats nasal and ocular seasonal allergic rhinitis symptoms may be more cost effective by reducing the need for concomitant drugs. The purpose of this study was to compare the utilization and costs of concomitant allergic rhinitis drugs among commonly used branded intranasal corticosteroid drugs. Pharmacy claims data between 1 April 2006 and 31 January 2008 were obtained from the Wolters Kluwer SourceLx dataset. Patients with at least one pharmacy claim for a branded intranasal corticosteroid agent (fluticasone furoate, budesonide, mometasone or triamcinolone) during the index period of 1 April 2007 through 31 July 2007 were included. Study outcomes assessed were time to concomitant use of prescription allergic rhinitis drugs (other than intranasal corticosteroids) and costs of those medications and intranasal corticosteroid drugs during a 60-day post-index period. A total of 793 349 patients were included in the study. At index, a majority of the patients were using mometasone (62.9%), followed by triamcinolone (21.1%), budesonide (15.1%) and fluticasone furoate (1.0%). After controlling for other covariates, patients receiving fluticasone furoate had on average a 21% lower risk of concomitant prescription allergic rhinitis drug use (adjusted hazard ratio [HR] 0.79; 95% CI 0.75, 0.83) compared with the other three branded intranasal corticosteroid agents. Compared with fluticasone furoate, all other branded intranasal corticosteroid agents incurred statistically significant higher costs of concomitant allergic rhinitis drugs (6.3%, p = 0.002), resulting in increased costs to health plans of $US5-$US6 per patient over a 60-day period. Mean intranasal corticosteroid costs per patient during the 60-day follow-up period were lowest for budesonide ($US70.15), followed by fluticasone furoate ($US70.86), triamcinolone ($US73.23) and mometasone ($US75.48). In this cohort of intranasal corticosteroid users, fluticasone furoate was shown to reduce the need for concomitant prescription allergic rhinitis medications compared with other leading branded intranasal corticosteroid therapies, resulting in lower costs per patient and potentially leading to significant savings for health plans.


[Forced medical care for convicts with drug addiction].
An analysis of the dynamics of unlawful activity of alcohol and drug addicts is carried out. All forms of treatment of drug addictions, either voluntary or forced, are considered as relevant to the prevention of repeated unlawful activity of convicts with drug addiction. Principles and basic criteria for the assignment of forced treatment of alcoholism and drug addiction to convicts are presented.


Wanting without enjoying: The social value of sharing experiences.
Social connection can be a rich source of happiness. Humans routinely go out of their way to seek out social connection and avoid social isolation. What are the proximal forces that motivate people to share experiences with others? Here we used a novel experience-sharing and decision-making paradigm to understand the value of shared experiences. In seven experiments across Studies 1 and 2, participants demonstrated a strong motivation to engage in shared experiences. At the same time, participants did not report a commensurate increase in hedonic value or emotional amplification, suggesting that the motivation to share experiences need not derive from their immediate hedonic value. In Study 3, participants reported their explicit beliefs about the reasons people engage in shared experiences: Participants reported being motivated by the desire to forge a social connection. Together, these findings suggest that the desire to share an experience may be distinct from the subjective experience of achieving that state. People may be so driven to connect with each other that social experiences remain valuable even in the most minimalistic contexts.


High-Fat Diet and Female Fertility across Lifespan: A Comparative Lesson from Mammal Models.
Female reproduction focuses mainly on achieving fully grown follicles and competent oocytes to be successfully fertilized, as well as on nourishing the developing offspring once pregnancy occurs. Current evidence demonstrates that obesity and/or high-fat diet regimes can perturbate these processes, leading to female infertility and transgenerational disorders. Since the mechanisms and reproductive processes involved are not yet fully clarified, the present review is designed as a systematic and comparative survey of the available literature. The available data demonstrate the adverse influences of obesity on diverse reproductive processes, such as folliculogenesis, oogenesis, and embryo development/implant. The negative reproductive impact may be attributed to a direct action on reproductive somatic and germinal compartments and/or to an indirect influence mediated by the endocrine, metabolic, and immune axis control systems. Overall, the present review highlights the fragmentation of the current information limiting the comprehension of the reproductive impact of a high-fat diet. Based on the incidence and prevalence of obesity in the Western countries, this topic becomes a research challenge to increase self-awareness of dietary reproductive risk to propose solid and rigorous preventive dietary regimes, as well as to develop targeted pharmacological interventions.


A flavonol glycoside, isolated from roots of Panax notoginseng, reduces amyloid-beta-induced neurotoxicity in cultured neurons: signaling transduction and drug development for Alzheimer's disease.
A Radix Notoginseng flavonol glycoside (RNFG), quercetin 3-O-beta-D-xylopyranosyl-beta-D-galactopyranoside, was isolated from roots of Panax notoginseng. Among different biological properties tested, RNFG possessed a strong activity in preventing amyloid-beta (Abeta)-induced cell death. In an in vitro assay, RNFG inhibited the aggregation of Abeta in a dose-dependent manner. Moreover, application of RNFG in cultured cortical neurons, or PC12 cells, reduced the Abeta-induced cell death in time- and dose-dependent manners, with the suppression of Abeta-induced DNA fragmentation and caspase-3 activation. In cultured neurons, the pre-treatment of RNFG abolished the increase of Ca(2+) mobilization triggered by Abeta. The neuroprotective properties of RNFG required a specific sugar attachment within the main chemical backbone because the flavonol backbone by itself did not show any protective effect. In memory impairment experiments using the passive avoidance task, the administration of RNFG reduced brain damage in scopolamine-treated rats. These results therefore reveal a novel function of Radix Notoginseng and its flavonol glycoside that could be very useful in developing food supplements for the prevention, or potential treatment, of Alzheimer's disease.


Distribution and ecology of small mammals in Albania.
In order to gain an insight into the population dynamics and habitat preferences of rodents in Albania, small mammals were collected during 2006-2009 in various districts of the country. Of the 15 species of small mammals captured (12 in Rodentia and 3 in Insectivora order), the yellow-necked mouse (Apodemus flavicollis) was the most frequently collected, representing 50% of the 325 small mammals captured, followed by the wood mouse (Apodemus sylvaticus) (20.62%). Apodemus flavicollis is the primary reservoir for Dobrava-Belgrade virus which causes to humans hemorrhagic fever with renal syndrome; the places with A. flavicollis abundance were those with records of the human disease. Knowledge of the reservoir ecology in a country facilitates risk assessments for rodent-borne diseases.


Therapeutic human papilloma virus vaccination in patients at risk for cervical dysplasia.
Shared decision making between patients and their healthcare providers is recommended for use of the human papillomavirus (HPV) vaccine Gardasil 9 (9v-HPV) in women ages 27-45 years. We studied HPV vaccination as a treatment modality for patients undergoing colposcopy older than age 26 years who tested positive for high-risk subtypes of HPV (HR-HPV). A retrospective study (n=155) was performed for patients that were evaluated for cervical dysplasia who tested positive for HR-HPV and received the 9v-HPV vaccine prior to repeat cervical cancer screening with co-testing. Demographic information, risk factors for cervical dysplasia, and treatment outcomes were assessed for response to vaccination as treatment. Repeat co-testing was negative for HR-HPV in 76 patients (49%) and was positive in 79 patients (51%). A greater percentage of Hispanic patients cleared the virus and Black patients had a greater percentage of persistent HR-HPV on repeat co-testing (p=0.047). When comparing those who cleared the virus and those who had persistent HRHPV, there were no differences observed for associated risk factors for dysplasia, HPV subtype, cytology or colposcopy results, vaccine dosing interval, or total number of vaccine doses received. While the HPV vaccine is effective for prevention of infection by highrisk strains of HPV, it remains unclear whether 9v-HPV vaccine should be recommended as a treatment option in exposed patients beyond age 26. We recommend healthcare providers discuss usefulness of 9v-HPV vaccine with their unvaccinated patients 27 years and older at risk for cervical dysplasia.


Hydrogen Peroxide Generation of Copper/Ascorbate Formulations on Cotton: Effect on Antibacterial and Fibroblast Activity for Wound Healing Application.
Greige cotton (unbleached cotton) is an intact plant fiber that retains much of the outer cotton fiber layers. These layers contain pectin, peroxidases, and trace metals that are associated with hydrogen peroxide (H₂O₂) generation during cotton fiber development. When greige cotton is subjected to a nonwoven hydroentanglement process, components of the outer cotton fiber layers are retained. When hydrated, this fabric can generate H₂O₂ (5⁻50 micromolar). This range has been characterized as inducing accelerated wound healing associated with enhanced cell signaling and the proliferation of cells vital to wound restoration. On the other hand, H₂O₂ levels above 50 micromolar have been associated with bacteriostatic activity. Here, we report the preparation and hydrogen peroxide activity of copper/ascorbate formulations, both as adsorbed and in situ synthesized analogs on cotton. The cooper/ascorbate-cotton formulations were designed with the goal of modulating hydrogen peroxide levels within functional ranges beneficial to wound healing. The cotton/copper formulation analogs were prepared on nonwoven unbleached cotton and characterized with cotton impregnation titers of 3⁻14 mg copper per gram of cotton. The copper/ascorbate cotton analog formulations were characterized spectroscopically, and the copper titer was quantified with ICP analysis and probed for peroxide production through assessment with Amplex Red. All analogs demonstrated antibacterial activity. Notably, the treatment of unbleached cotton with low levels of ascorbate (~2 mg/g cotton) resulted in a 99 percent reduction in Klebsiella pneumoniae and Staphylococcus aureus. In situ synthesized copper/ascorbate nanoparticles retained activity and did not leach out upon prolonged suspension in an aqueous environment. An assessment of H₂O₂ effects on fibroblast proliferation are discussed in light of the copper/cotton analogs and wound healing.


Gene and haplotype frequencies of HLA antigens in 269 patients with Crohn's disease.
Evidence of strong genetic markers in Crohn's disease (CD) is still absent. Many investigations have focused on HLA antigens, with conflicting results. To obtain more detailed information on the relation of HLA to the disease, we used the HLA data from 269 CD patients to compute the maximum-likelihood estimates of HLA gene and haplotype frequencies. These results provide further evidence that HLA B44 and Cw5 do indeed play a role in the development of CD. Furthermore, it is conceivable from our results that HLA Cw7 may protect against being affected with this disease.


Comparison of Fixation Techniques for Acetabular Fractures Involving the Anterior Column with Disruption of the Quadrilateral Plate: A Biomechanical Study.
In elderly patients who have sustained an acetabular fracture involving disruption of the quadrilateral plate (QLP), postoperative loading of the joint beyond the level of partial weight-bearing can result in medial redisplacement of the QLP. The purpose of this biomechanical study was to compare the performances of 4 different fixation constructs intended to prevent medial redisplacement of the QLP. Anterior column posterior hemitransverse (ACPHT) fractures with disruption of the QLP were created on synthetic hemipelves (fourth-generation Sawbones models) and subsequently stabilized with (1) a 12-hole plate bridging the QLP (Group 1), (2) the plate with added periarticular screws along the QLP (Group 2), (3) the plate combined with an infrapectineal buttress plate (Group 3), or (4) the plate with the added periarticular screws as well as the buttress plate (Group 4). The point of load application on the acetabulum was defined to be the same as the point of application of maximum vertical hip contact force during normal walking. Loads were applied to simulate either partial weight-bearing (20 cycles, from 35 to 350 N) or inadvertent supraphysiologic loads (linearly increasing loads until the onset of failure, defined as fragment displacement of >3 mm). A universal testing machine was synchronized with a digital image correlation system to optically track redisplacement at the QLP. The level of significance was set at p < 0.05. During experimental simulation of partial weight-bearing, maximum fracture step openings never exceeded 2 mm. During simulation of inadvertent supraphysiologic load, the median load to failure was higher (p < 0.05) in Group 2 (962 N; range, 798 to 1,000 N) and Group 4 (985 N; range, 887 to 1,000 N) compared with Group 1 (445 N; range, 377 to 583 N) and Group 3 (671 N; range, 447 to 720 N). All 4 fixation constructs performed in an acceptable manner on testing with simulated partial weight-bearing. Only additional periarticular screws along the QLP increased the fixation strength. Redisplacement of the QLP resulting in an incongruency of the hip joint has been associated with poor long-term outcomes. Within the constraints of this study, periarticular long screws were superior to infrapectineal buttress plates in preventing medial redisplacement of the QLP.


Outcomes of Third-Attempt Breast Reconstruction following Infection-Associated Failure of Secondary Implant-Based Reconstruction.
Implant-based reconstruction (IBR) is the most common method of breast reconstruction in the United States. Despite ongoing advancements, periprosthetic infection is a serious problem that often results in device explantation. The objective of this study was to evaluate the outcomes of third-attempt reconstruction in patients in whom secondary implant-based reconstruction failed because of infection. The authors performed a retrospective review of patients who underwent mastectomy followed by IBR from 2000 to 2019. The outcomes of patients in whom secondary IBR failed because of infection and who ultimately underwent third-attempt breast reconstruction were analyzed. Of 6093 patients who underwent primary IBR, 13 patients had third-attempt breast reconstruction following infection-related explantation [median age, 52 years (interquartile range, 51 to 56 years); median body mass index, 23 kg/m 2 (interquartile range, 22 to 31 kg/m 2 ); median follow-up, 46 months (interquartile range, 16 to 62 months)]. Nine patients (70%) underwent IBR, two (15%) underwent IBR combined with pedicled latissimus dorsi flap, and two (15%) underwent abdominally based free tissue transfer. Third-attempt breast reconstruction was immediate in 46% of patients and delayed in 54%. The success rate was 78% in the IBR group, with a 23% complication rate. The success rate for autologous breast reconstruction was 100%, with one patient developing venous congestion necessitating return to the operating room. Third-attempt breast reconstruction following infection-associated failed secondary IBR is a safe and feasible option. Although the risk of failure is higher than that for primary implant-based reconstruction, a third attempt after secondary IBR infection had a surprisingly high 78% success rate. Risk, III.


Glucagon-like peptide-1 modulates neurally evoked mucosal chloride secretion in guinea pig small intestine in vitro.
Glucagon-like peptide-1 (GLP-1) acts at the G protein-coupled receptor, GLP-1R, to stimulate secretion of insulin and to inhibit secretion of glucagon and gastric acid. Involvement in mucosal secretory physiology has received negligible attention. We aimed to study involvement of GLP-1 in mucosal chloride secretion in the small intestine. Ussing chamber methods, in concert with transmural electrical field stimulation (EFS), were used to study actions on neurogenic chloride secretion. ELISA was used to study GLP-1R effects on neural release of acetylcholine (ACh). Intramural localization of GLP-1R was assessed with immunohistochemistry. Application of GLP-1 to serosal or mucosal sides of flat-sheet preparations in Ussing chambers did not change baseline short-circuit current (I(sc)), which served as a marker for chloride secretion. Transmural EFS evoked neurally mediated biphasic increases in I(sc) that had an initial spike-like rising phase followed by a sustained plateau-like phase. Blockade of the EFS-evoked responses by tetrodotoxin indicated that the responses were neurally mediated. Application of GLP-1 reduced the EFS-evoked biphasic responses in a concentration-dependent manner. The GLP-1 receptor antagonist exendin-(9-39) suppressed this action of GLP-1. The GLP-1 inhibitory action on EFS-evoked responses persisted in the presence of nicotinic or vasoactive intestinal peptide receptor antagonists but not in the presence of a muscarinic receptor antagonist. GLP-1 significantly reduced EFS-evoked ACh release. In the submucosal plexus, GLP-1R immunoreactivity (IR) was expressed by choline acetyltransferase-IR neurons, neuropeptide Y-IR neurons, somatostatin-IR neurons, and vasoactive intestinal peptide-IR neurons. Our results suggest that GLP-1R is expressed in guinea pig submucosal neurons and that its activation leads to a decrease in neurally evoked chloride secretion by suppressing release of ACh at neuroepithelial junctions in the enteric neural networks that control secretomotor functions.


Darapladib, a Lipoprotein-Associated Phospholipase A2 Inhibitor, Reduces Rho Kinase Activity in Atherosclerosis.
Increased lipoprotein-associated phospholipase A2 (Lp-PLA2) activity and Rho kinase activity may be associated with atherosclerosis. The principal aim of this study was to examine whether darapladib (a selective Lp-PLA2 inhibitor) could reduce the elevated Lp-PLA2 and Rho kinase activity in atherosclerosis. Studies were performed in male Sprague-Dawley rats. The atherosclerosis rats were prepared by feeding them with a high-cholesterol diet for 10 weeks. Low-dose darapladib (25 mg·kg⁻¹·d⁻¹) and high-dose darapladib (50 mg·kg⁻¹·d⁻¹) interventions were then administered over the course of 2 weeks. The serum levels of triglycerides, total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), high-sensitivity C-reactive protein (hs-CRP), and Lp-PLA2, significantly increased in atherosclerosis model groups, as did Rho kinase activity and cardiomyocyte apoptosis (p<0.05 vs. sham group), whereas nitric oxide (NO) production was reduced. Levels of TC, LDL-C, CRP, Lp-PLA2, and Rho kinase activity were respectively reduced in darapladib groups, whereas NO production was enhanced. When compared to the low-dose darapladib group, the reduction of the levels of TC, LDL-C, CRP, and Lp-PLA2 was more prominent in the high-dose darapladib group (p<0.05), and the increase of NO production was more prominent (p<0.05). Cardiomyocyte apoptosis of the high-dose darapladib group was also significantly reduced compared to the low-dose darapladib group (p<0.05). However, there was no significant difference in Rho kinase activity between the low-dose darapladib group and the high-dose darapladib group (p>0.05). Darapladib, a Lp-PLA2 inhibitor, leads to cardiovascular protection that might be mediated by its inhibition of both Rho kinase and Lp-PLA2 in atherosclerosis.


[A case report of ureteropelvic junction obstruction and multiple renal stones associated with nutcracker syndrome].
A 20 year-old man presented to emergency room with severe left-sided flank pain. Urinalysis showed hematuria and he was referred to the urology department. KUB, DIP and retrograde pyelography (RP) revealed multiple renal stones, left hydronephrosis (grade 2) and ureteropelvic junction obstruction (UPJO). Abdominal CT revealed shortened nutcracker distance and renal angiography showed left renal vein hypertension. From these findings, diagnosis of nutcracker syndrome was made. Transposition of the left renal vein, dismembered pyeloplasty and left pyelolithotomy were performed simultaneously. 2 months after the procedure, his symptom and hematuria disappeared. 3 months after the procedure, DIP revealed improvement of hydronephrosis (grade 1) and CT showed elongation of nutcracker distance. In 12 months follow-up, there was no recurrence of symptom and hydonephrosis. To the best our knowledge, there has been no report of UPJO associated with nutcracker syndrome and the simultaneous treatment for the both diseases.


[Antitumor effects of sulindac in ovarian cell cultures].
The purpose of our study was to assess susceptibility of cells of various ovarian cell lines on different nonsteroidal anti-inflammatory drugs (NSAIDs). Cytotoxic effect of NSAIDs was tested using MTT colorimetric assay. Amongst 6 NSAIDs tested: sulindac, sulindac sulfide, sulindac sulfone, acetylsalicylic acid, nimesulide, and rofecoxib, viability of ovarian carcinoma cells was compromised most strongly by sulindac and sulindac sulfide and concerned all the cell lines tested: SKOV-3, MDAH 2774, OVCA-1, and OVP-10. Sulindac sulfone and rofecoxib also displayed some cytotoxic effect during prolonged 72-hour incubation. Other NSAIDs tested: nimesulide and acetylsalicylic acid were devoid of cytotoxic effect on ovarian cancer cells. Our results are encourage enough to conduct clinical trials that could allow to draw conclusions regarding potential application of sulindac in the adjuvant treatment of a standard chemotherapy of ovarian cancer.


Mycology - an update part 2: dermatomycoses: clinical picture and diagnostics.
Most fungal infections of the skin are caused by dermatophytes, both in Germany and globally. Tinea pedis is the most frequent fungal infection in Western industrial countries. Tinea pedis frequently leads to tinea unguium, while in the elderly, both may then spread causing tinea corporis. A variety of body sites may be affected, including tinea glutealis, tinea faciei and tinea capitis. The latter rarely occurs in adults, but is the most frequent fungal infection in childhood. Following antifungal treatment of tinea unguium and also tinea capitis a dermatophytid or hyperergic reaction to dermatophyte antigens may occur. Yeast infections affect the mucous membranes both of the gastro-intestinal system and the genital tract as candidiasis mostly due to Candida albicans. Cutaneous candidiasis affects predominantely the intertriginous regions such as groins and the inframammary area, but also the intertriginous space of fingers and toes. In contrast, pityriasis versicolor is a superficial epidermal fungal infection primarily on the the trunk. Mold infections are rare in dermatology; they play a role nearly exclusively in nondermatophyte-mold (NDM) onychomycosis. The diagnosis of dermatomycoses comprises the microscopic detection of fungi using the potassium hydroxide preparation or alternatively the fluorescence optical Blankophor preparation together with culture. The histological fungal detection with PAS staining possesses a high sensitivity, and it should play a more important role in particular for diagnosis of onychomycosis. Molecular biological methods, based on the amplification of fungal DNA with use of specific primers for the distinct causative agents are on the rise. With PCR, such as dermatophyte-PCR-ELISA, fungi can be detected directly in clinical material in a highly specific and sensitive manner without prior culture. Today, molecular methods, such as Matrix Assisted Laser Desorption/Ionization Time-Of-Flight Mass Spectrometry (MALDI TOF MS) as culture confirmation assay, complete the conventional mycological diagnostics.


Transient lens spectroscopy of ultrafast internal conversion processes in citranaxanthin.
The ultrafast internal conversion (IC) dynamics of the apocarotenoid citranaxanthin have been studied for the first time by means of two-color transient lens (TL) pump-probe spectroscopy. After excitation into the high-energy edge of the S2 band by a pump pulse at 400 nm, the subsequent intramolecular processes were probed at 800 nm. Experiments were performed in a variety of solvents at room temperature. Upper limits for the S2 lifetime tau2 on the order of 100-200 fs are estimated. The S1 lifetime tau1 varies only slightly between solvents (10-12 ps), and the only clear decrease is observed for methanol (8.5 ps). The findings are consistent with earlier results from transient absorption studies of other apocarotenoids and carotenoid ketones and transient lens experiments of C40 carbonyl carotenoids. Possible reasons for the observed weak solvent dependence of tau1 for citranaxanthin are discussed.


A new concept for multidimensional selection of ligand conformations (MultiSelect) and multidimensional scoring (MultiScore) of protein-ligand binding affinities.
In this work, eight different scoring functions have been combined with the aim of improving the prediction of protein-ligand binding conformations and affinities. The obtained scores were analyzed using multivariate statistical methods to generate expressions, with the ability (1) to select the best candidate between different docked conformations of an inhibitor (MultiSelect) and (2) to quantify the protein-ligand binding affinity (MultiScore). By use of the docking program GOLD, 40 different inhibitors were docked into the active site of three matrix metalloproteinases (MMP's), yielding a total of 120 enzyme-inhibitor complexes. For each complex, a single conformation of the inhibitor was selected using principal component analysis (PCA) for the scores obtained by the eight functions SCORE, LUDI, GRID, PMF_Score, D_Score, G_Score, ChemScore, and F_Score. Binding affinities were estimated based on partial least-squares projections onto latent structures (PLS) on the eight scores of each selected inhibitor conformation. By use of this procedure, R(2) = 0.78 and Q(2) = 0.78 were obtained when comparing experimental and calculated binding affinities. MultiSelect was evaluated by applying the same method for selecting docked conformations for 18 different protein-ligand complexes of known three-dimensional structure. In all cases, the selected ligand conformations were found to be very similar to the experimentally determined ligand conformations. A more general evaluation of MultiScore was performed using a set of 120 different protein-ligand complexes for which both the three-dimensional structures and the binding affinities were known. This approach allowed an evaluation of MultiScore independently of MultiSelect. The generality of the method was verified by obtaining R(2) = 0.68 and Q(2) = 0.67, when comparing calculated and experimental binding affinities for the 120 X-ray structures. In all cases, LUDI, SCORE, GRID, and F_Score were included as important functions, whereas the fifth function was PMF_Score and ChemScore for the MMP and X-ray models, respectively.


MicroRNA-155: A Master Regulator of Inflammation.
MicroRNAs (miRNAs) are naturally occurring, highly conserved families of transcripts (∼22 nucleotides in length) that are processed from larger hairpin precursors. miRNAs primarily regulate gene expression by promoting messenger RNA (mRNA) degradation or repressing mRNA translation. miRNAs have been shown to be important regulators of a variety of cellular processes involving development, differentiation, and signaling. Moreover, various human diseases, including cancer and immune dysfunction, are associated with aberrant expression of miRNAs. This review will focus on how the multifunctional miRNA, miR-155, regulates inflammatory diseases, including cancer and pulmonary disorders, and also how miR-155 expression and biogenesis are regulated. We will also provide examples of miR-155-regulated networks in coordination with other noncoding RNAs, including long noncoding RNAs as well as coding mRNAs acting as competing endogenous RNAs.


Identification of potent HDAC 2 inhibitors using E-pharmacophore modelling, structure-based virtual screening and molecular dynamic simulation.
Histone deacetylase 2 (HDAC 2) of class I HDACs plays a major role in embryonic and neural developments. However, HDAC 2 overexpression triggers cell proliferation by diverse mechanisms in cancer. Over the decades, many pan and class-specific inhibitors of HDAC were discovered. Limitations such as toxicity and differential cell localization of each isoform led researchers to hypothesize that isoform selective inhibitors may be relevant to bring about desired effects. In this study, we have employed the PHASE module to develop an e-pharmacophore model and virtually screened four focused libraries of around 300,000 compounds to identify isoform selective HDAC 2 inhibitors. The compounds with phase fitness score greater than or equal to 2.4 were subjected to structure-based virtual screening with HDAC 2. Ten molecules with docking score greater than -12 kcal/mol were chosen for selectivity study, QikProp module (ADME prediction) and dG/bind energy identification. Compound 1A with the best dock score of -13.3 kcal/mol and compound 1I with highest free binding energy, -70.93 kcal/mol, were selected for molecular dynamic simulation studies (40 ns simulation). The results indicated that compound 1I may be a potent and selective HDAC 2 inhibitor. Further, in vitro and in vivo studies are necessary to validate the potency of selected lead molecule and its derivatives.


[A new flavonoid with an aryl moiety from Selaginella uncinata].
The present study is to investigate the chemical constituents of the whole plants of Selaginella uncinata. A new flavonoid was isolated from the 75% ethanol extract of Selaginella uncinata by column chromatographies over macroporous resin, silica gel, Sephadex LH-20 and prep-HPLC. The structure was elucidated as 8-[4-(carboxyl)phenoxy]-5,4'-dihydroxy-7-methoxyflavanone (1) and named unciflacone G.


Effects of different periods of paradoxical sleep deprivation and sleep recovery on lipid and glucose metabolism and appetite hormones in rats.
Sleep has a fundamental role in the regulation of energy balance, and it is an essential and natural process whose precise impacts on health and disease have not yet been fully elucidated. The aim of this study was to assess the consequences of different periods of paradoxical sleep deprivation (PSD) and recovery from PSD on lipid profile, oral glucose tolerance test (OGTT) results, and changes in insulin, corticosterone, ghrelin, and leptin concentrations. Three-month-old male Wistar rats weighing 250-350 g were submitted to 24, 96, or 192 h of PSD or 192 h of PSD with 480 h of recovery. The PSD was induced by the multiple platforms method. Subsequently, the animals were submitted to an OGTT. One day later, the animals were killed and the levels of triglycerides, total cholesterol, lipoproteins (low-density lipoprotein, very-low-density lipoprotein, and high-density lipoprotein), insulin, ghrelin, leptin, and corticosterone in plasma were quantified. There was a progressive decrease in body weight with increasing duration of PSD. The PSD induced basal hypoglycemia over all time periods evaluated. Evaluation of areas under the curve revealed progressive hypoglycemia only after 96 and 192 h of PSD. There was an increase in corticosterone levels after 192 h of PSD. We conclude that PSD induces alterations in metabolism that are reversed after a recovery period of 20 days.


Atypical presentation of necrotising autoimmune myopathy.
Necrotising autoimmune myopathy (NAM) is characterised by a common phenotype of profound symmetrical proximal muscle weakness, elevated creatine kinase levels, irritable myopathy on electromyography and histological findings of myocyte necrosis and regeneration without remarkable inflammation. NAM is associated with autoimmune antibodies including anti-3-hydroxy-3-methylglutaryl-coenzyme receptor, which is strongly associated with statin use. We report a case of statin-associated NAM with an atypical presentation of severe oropharyngeal dysphagia and no remarkable proximal muscle weakness at initial presentation but with rapid progression to severe quadriparesis in weeks. This case expands the spectrum of presentation patterns of this rare disease and highlights the need for a high index of suspicion in patients with a remote history of statin use.


Increased incidence of neuroleptic-induced perioral movements in the rat by hyperglycemia.
It has been suggested that Tardive dyskinesia (TD) is associated with abnormal glucose metabolism. To investigate further the issue the effects of alloxan-induced hyperglycemia on the incidence and severity of haloperidol-induced perioral movements were studied in the rat. Hyperglycemic rats showed significantly higher incidence and severity of rating of abnormal perioral movements than did control rats. Severity ratings of perioral movements were significantly correlated with blood glucose levels in the hyperglycemic rats. These findings suggest that hyperglycemia may increase the severity of neuroleptic-induced perioral movements, and support the possibility that glucose intolerance may increase the risk of TD.