Analysis of coronary vascular beta receptors in situ.
Observations were conducted in the isolated potassium-arrested dog heart to determine the direct vasodilator effects of adrenergic agonists and antagonists on the coronaryvascular beta receptors, independent of cardiac inotropic and chronotropic influences. Practocol (a selective beta-1-receptor antagonist) blocked coronary vasodilation activated by isoproternol (a combined beta-1-and beta-2-receptor agonist) only at the very high dose of 10-minus 3 M, whereas propranolol (a combined beta-1- and beta-2-receptor antagonist) blocked coronary vasodilation at 10-minus 7 to 10-minus 5 M. Salbutamol (a selective beta-2-receptor agonist) was one-eighth as potent as isoproterenol in producing coronary vasodilation. The potency ratio (1/8) is similiar to valuesreported for other beta receptors classified as type 2. It is concluded that the coronary vasodilator beta receptors are type 2, similiar to those found in peripheral bloodvessels.


Method for puncture trajectory planning in liver tumors thermal ablation based on NSGA-III.
Thermal ablation of liver tumors is a conventional mode for treating liver tumors. In order to reduce the damage to normal tissue endangered by thermal ablation, the physician needs to plan the puncture path before surgery. In this paper, a puncture trajectory planning method for thermal ablation of liver tumor based on NSGA-III is proposed. This method takes the clinical hard constraints and soft constraints into account. The feasible puncture region is solved by the hard constraints, and after that the pareto front points are obtained under the soft constraints. When accessing the feasible puncture region, an adaptive morphological closing operation method based on K-means algorithm is adopted to process the spherical angle binary image of obstacles that might be encountered in the puncture process. RANSAC is performed to fit the tangent plane of liver surface when calculating the angle between the puncture trajectory and liver surface. In order to evaluate the puncture path obtained by this method, 6 tumors are selected as experimental subjects, and Hausdorff distance and Overlap Rate of Pareto front points with manually recommend points are calculated respectively. The average value of Hausdorff distance is 24.91 mm, and the mean value of the overlap rate is 86.43%. The proposed method can provide high safety and clinical practice of the puncture route.


Complementation of a trpE deletion in Escherichia coli by Spirochaeta aurantia DNA encoding anthranilate synthetase component I activity.
A 2.7-kilobase Sau3A fragment of Spirochaeta aurantia DNA cloned in pBR322 complemented a trpE deletion in Escherichia coli. Deletion analysis and Tn5 mutagenesis of the resulting plasmid pBG100 defined a 2-kilobase-pair region that was required for both the complementation and the synthesis of 59,000- and 47,000-molecular-weight polypeptides (59K and 47K polypeptides) in maxicells. Both the 59K and the 47K polypeptides appear to be encoded by a single gene. A maxicell analysis of pBG100::Tn5 mutants suggests that the 47K polypeptide is not sufficient for the trpE complementation. In vitro and in vivo anthranilate synthetase (AS) assays indicate that the complementing activity encoded by pBG100 was functionally analogous to the AS component I of E. coli in that it utilized NH3 but not glutamine as the amino donor. pBG100 did not encode a glutamine amidotransferase activity, although the AS component I it encoded was capable of interacting with E. coli AS component II to catalyze the glutamine-requiring reaction. Expression appeared to depend on a promoter in the cloned S. aurantia DNA.


Computational and Experimental Confirmation of the Diradical Character of para-Quinonedimethide.
The ground-state structure of the parent para-quinonedimethide (p-QDM) molecule is generally represented in its closed shell form, i.e., as a cyclic, nonaromatic, through-conjugated/cross-conjugated hybrid comprising four C═C bonds. Nonetheless, p-QDM has been theorized to contain a contribution from its open-shell aromatic singlet diradical form. VBSCF calculations identify an open-shell contribution of 29% to the structure, while CASPT2(16,16)/def2-TZVP and ωB97XD/aug-cc-pVTZ calculations predict that dimerization proceeds along an open-shell singlet diradical pathway with a low (77 kJ/mol) barrier toward dimerization, which occurs by way of C-C bond formation between the exocyclic methylene carbons. A similar low (98 kJ/mol) barrier exists toward the reaction between a p-QDM molecule and the radical trap TEMPO. These predictions are verified experimentally through the isolation of bis-TEMPO-trapped p-QDM, its C-C coupled dimer, and by demonstrating that a mixture of p-QDM and TEMPO can initiate the radical polymerization of n-butyl acrylate at ambient temperature. In contrast to p-QDM, tetracyanoquinone (TCNQ) neither dimerizes nor reacts with TEMPO, despite having a similar diradical character to p-QDM. This lack of reactivity is consistent with both a higher kinetic barrier and a thermodynamically unfavorable process, which is ascribed to destabilizing steric clashes and polar effects.


Identification of rice purple acid phosphatases related to phosphate starvation signalling.
Purple acid phosphatases (PAPs) are a family of metallo-phosphoesterases involved in a variety of physiological functions, especially phosphate deficiency adaptations in plants. We identified 26 putative PAP genes by a genome-wide analysis of rice (Oryza sativa), 24 of which have isolated EST sequences in the dbEST database. Amino acid sequence analysis revealed that 25 of these genes possess sets of metal-ligating residues typical of known PAPs. Phylogenetic analysis classified the 26 rice and 29 Arabidopsis PAPs into three main groups and seven subgroups. We detected transcripts of 21 PAP genes in roots or leaves of rice seedlings. The expression levels of ten PAP genes were up-regulated by both phosphate deprivation and over-expression of the transcription factor OsPHR2. These PAP genes all contained one or two OsPHR2 binding elements in their promoter regions, implying that they are directly regulated by OsPHR2. Both acid phosphatase (AP) and surface secretory acid phosphatase (SAP) activity assays showed that the up-regulation of PAPs by Pi starvation, OsPHR2 over-expression, PHO2 knockout or OsSPX1 RNA interference led to an increase in AP and SAP activity in rice roots. This study reveals the potential for developing technologies for crop improvement in phosphorus use efficiency.


Overexpression and correlation of HIF-2α, VEGFA and EphA2 in residual hepatocellular carcinoma following high-intensity focused ultrasound treatment: Implications for tumor recurrence and progression.
Rapid growth of residual tumors can occur as a result of their recurrence and progression. The present study aimed to investigate the expression of hypoxia inducible factor-2 subunit α (HIF-2α), vascular endothelial growth factor A (VEGFA), erythropoietin-producing hepatocellular A2 (EphA2) and angiogenesis in residual hepatocellular carcinoma (HCC), following treatment with high-intensity focused ultrasound (HIFU) ablation, in order to investigate the association between protein expression and tumor recurrence and growth. Athymic BALB/c (nu/nu) mice were subcutaneously inoculated with the HCC cell line HepG2, in order to create xenograft tumors. Approximately 30 days post-inoculation, eight mice were treated with HIFU, whereas eight mice received no treatment and acted as the control group. Residual tumor tissues were obtained from the experimental groups after one month. Levels of HIF-2α, VEGFA, EphA2 and cluster of differentiation 31 (CD31) expression was measured by immunohistochemical staining. CD31-positive vascular endothelial cells were counted to calculate microvascular density (MVD), and western blot analysis was performed to determine levels of HIF-2α, VEGFA, and EphA2 protein. It was found that the expression levels of HIF-2α, VEGFA, EphA2, and MVD proteins in residual HCC tissues were significantly higher than in the control group tissues (P<0.05). Tumor MVD was strongly correlated with VEGFA (R=0.957, P<0.01) and EphA2 (R=0.993, P<0.01) protein expression levels. Furthermore, there was a significant positive correlation between HIF-2α and EphA2 expression (R=0.991, P<0.01). The correlation between VEGFA and EphA2 expression was also positive (R=0.985, P<0.01). These data suggest that overexpression of HIF-2α, VEGFA and EphA2 is related to angiogenesis in residual HCC following HIFU ablation, potentially via their association with key mediators of recurrence.


Resident Perspectives of an Interactive Case Review Following Independent Didactic Study as a Method of Teaching a Pediatric Imaging Curriculum.
The ABR has recently changed the format of the board examination, in which the oral examination was replaced by a computer based multiple-choice test. The purpose of this study was to determine resident's perceptions of a new conference resembling the new ABR format. Residents were requested to review a series of didactic pediatric imaging presentations prior to attending case conference. During conference, unknown cases reflecting the subject matter from the didactic presentations were presented along with multiple-choice questions. We then surveyed resident perspectives after each case conference. Between 14 and 18 residents were surveyed at the end of each subspecialty case review presentation. About 94% of resident respondents felt that the independent didactic study followed by an interactive case review session would better prepare them for the ABR certification exams, compared to didactic lectures alone. Furthermore, 95% of the respondents indicated that they preferred the independent didactic review followed by interactive case review versus didactic lecture alone. Most the respondents (85%) felt that combining independent didactic review with interactive unknown case sessions made the material more interesting and provided greater understanding of the material. There was no statistically significant difference in the distribution of answers across the subspecialty sessions (p > .05). Radiology residents favorably reviewed the combination of independent review of didactic material prior to interactive case review. Material presented in this fashion is felt to be more interesting and is thought to result in enhanced understanding of pediatric radiology material.


Explicitly correlated second order perturbation theory: introduction of a rational generator and numerical quadratures.
A rational generator, which fulfills the cusp conditions for singlet and triplet electron pairs, is proposed and applied to explicitly correlated second order Møller-Plesset perturbation theory calculations. It is shown that the generator in conjunction with frozen geminals improves the convergence of correlation energy without introducing any variational parameters in explicitly correlated functions. A new scheme for three-electron integrals based on numerical quadratures is also illustrated. The method is tested for the convergence of reaction enthalpies with various basis sets.


[Serum antibodies to the hepatitis A virus in persons following a history of the infection].
Enzyme immunoassay was used for titration of serum antibodies in subjects with a history of clinically pronounced or asymptomatic hepatitis A infection. Titers of hepatitis A virus antibodies (anti-HAV) essentially decreased during 3-4 years after the disease, then the rate of this decrease slowed down and antibody titers stabilized at low levels. After clinically pronounced hepatitis A anti-HAV levels were considerably higher than after the asymptomatic form of this infection.


Activity-dependent branching ratios in stocks, solar x-ray flux, and the Bak-Tang-Wiesenfeld sandpile model.
We define an activity-dependent branching ratio that allows comparison of different time series X(t). The branching ratio b(x) is defined as b(x)=E[xi(x)/x]. The random variable xi(x) is the value of the next signal given that the previous one is equal to x, so xi(x)=[X(t+1) | X(t)=x]. If b(x)>1, the process is on average supercritical when the signal is equal to x, while if b(x)<1, it is subcritical. For stock prices we find b(x)=1 within statistical uncertainty, for all x, consistent with an "efficient market hypothesis." For stock volumes, solar x-ray flux intensities, and the Bak-Tang-Wiesenfeld (BTW) sandpile model, b(x) is supercritical for small values of activity and subcritical for the largest ones, indicating a tendency to return to a typical value. For stock volumes this tendency has an approximate power-law behavior. For solar x-ray flux and the BTW model, there is a broad regime of activity where b(x) approximately equal 1, which we interpret as an indicator of critical behavior. This is true despite different underlying probability distributions for X(t) and for xi(x). For the BTW model the distribution of xi(x) is Gaussian, for x sufficiently larger than 1, and its variance grows linearly with x. Hence, the activity in the BTW model obeys a central limit theorem when sampling over past histories. The broad region of activity where b(x) is close to one disappears once bulk dissipation is introduced in the BTW model-supporting our hypothesis that it is an indicator of criticality.


Pan-enteric dysmotility, impaired quality of life and alexithymia in a large group of patients meeting ROME II criteria for irritable bowel syndrome.
Psychological factors, altered motility and sensation disorders of the intestine can be variably associated with irritable bowel syndrome (IBS). Such aspects have not been investigated simultaneously. The aim of this paper was to evaluate gastrointestinal motility and symptoms, psychological spectrum and quality of life in a large group of IBS patients in southern Italy. One hundred IBS patients (F:M=73:27, age 48+/-2 years, mean+/-SE) fulfilling ROME II criteria matched with 100 healthy subjects (F:M=70:30, 45+/-2 years). Dyspepsia, bowel habit, alexithymia, psycho-affective profile and quality of life were assessed using specific questionnaires. Basally and postprandially, changes in gallbladder volumes and antral areas after liquid meal and orocaecal transit time (OCTT) were measured respectively by ultrasonography and H(2)-breath test. Appetite, satiety, fullness, nausea, and epigastric pain/discomfort were monitored using visual-analogue scales. Compared with controls, IBS patients had increased dyspepsia (score 12.6+/-0.7 vs 5.1+/-0.2, P<0.0001), weekly bowel movements (12.3+/-0.4 vs 5.5+/-0.2, P<0.00001, comparable stool shape), alexithymia (score 59.1+/-1.1 vs 40.5+/-1.0, P=0.001), poor quality of life and psycho-affective profile. IBS patients had normal gallbladder emptying, but delayed gastric emptying (T50: 35.5+/-1.0 vs 26.1+/-0.6 min, P=0.00001) and OCTT (163.0+/-5.4 vs 96.6+/-1.8 min, P=0.00001). Fullness, nausea, and epigastric pain/discomfort were greater in IBS than in controls. ROME II IBS patients have a pan-enteric dysmotility with frequent dyspepsia, associated with psychological morbidity and greatly impaired quality of life. The presence of alexithymia, a stable trait, is a novel finding of potential interest to detect subgroups of IBS patients with different patterns recovered after therapy.


Biomechanical effects of exercise fatigue on the lower limbs of men during the forward lunge.
Background: During competition and training, exercises involving the lungs may occur throughout the sport, and fatigue is a major injury risk factor in sport, before and after fatigue studies of changes in the lungs are relatively sparse. This study is to investigate into how fatigue affects the lower limb's biomechanics during a forward lunge. Methods: 15 healthy young men participate in this study before and after to exposed to a fatigue protocol then we tested the forward lunge to obtain kinematic, kinetic changing during the task, and to estimate the corresponding muscles' strength changes in the hip, knee, and ankle joints. The measurement data before and after the fatigue protocol were compared with paired samples t-test. Results: In the sagittal and horizontal planes of the hip and knee joints, in both, the peak angles and joint range of motion (ROM) increased, whereas the moments in the sagittal plane of the knee joint smaller. The ankle joint's maximum angle smaller after fatigue. Peak vertical ground reaction force (vGRF) and peak contact both significantly smaller after completing the fatigue protocol and the quadriceps mean and maximum muscular strength significantly increased. Conclusion: After completing a fatigue protocol during lunge the hip, knee, and ankle joints become less stable in both sagittal and horizontal planes, hip and knee range of motion becomes greater. The quadriceps muscles are more susceptible to fatigue and reduced muscle force. Trainers should focus more on the thigh muscle groups.


Phorbol esters: useful tools to study megakaryocyte differentiation.
This review attempts 1) to enonciate recent observations made on the effects of phorbol esters on megakaryocyte cell lines, 2) to examine these effects taking into account megakaryocytopoiesis in vivo and 3) to demonstrate that phorbol esters stimulated megakaryocyte cell lines provide a good model to study the mechanisms governing megakaryocyte maturation.


Prevalence of hypertension in suspected hypertensive patients in Rajavithi Hospital using ambulatory blood pressure monitoring.
Hypertension (HTN) is one of the most important health problems in Thailand and worldwide. The accuracy of diagnosis of HTN is crucial to avoid adverse reactions from medications and reduce treatment costs. In 2011, The National Institute for Health and Clinical Excellence (NICE) recommended a diagnostic guidelines for hypertension using ambulatory blood pressure monitoring (ABPM) aiming to exclude patients with white coat hypertension (WCH). We investigated the prevalence of HTN in suspected hypertensive patients at Rajavithi Hospital according to the NICE guidelines and factors associated with WCH. To determine the prevalence of HTN in suspected hypertensive patients at Rajavithi Hospital according to the NICE guidelines (using ABPM) and risk factors associated with WCH. This cross-sectional study enrolled 31 subjects, age 18-80 years, with systolic blood pressure (SBP) ≥140 mmHg and/or diastolic blood pressure (DBP) ≥90 mmHg in the Outpatient Department at Rajavithi Hospital from March 2012 to December 2012. All participants had never had a diagnosis of HTN or been treated with anti hypertensive medications in the past four weeks. 24-hour ABPM was used to confirm the diagnosis of HTN based on daytime average blood pressure ≥135/85 mmHg. Subjects with an average daytime blood pressure below 135/85 mmHg were defined as having WCH. Among 31 subjects, 17 (54.8%) were confirmed to have HTN and 14 (45.2%) had WCH. Subjects with true HTN had a mean clinical blood pressure of 157.88±7.68/94.24±6.56 mmHg when measured at the initial presentation using a sphygmomanometer whereas subjects with WCH had a mean clinic blood pressure of 148.18±7.06/89.39±4.10 mmHg. Mean SBP and DBP were significantly lower among WCH subjects (p = 0.001 and p = 0.018 respectively). Age, sex, smoking, alcohol consumption, BMI, lipid profile, uric acid and hemoglobin levels were not associated with the diagnosis of WCH. The prevalence of hypertension in suspected hypertensive patients using ABPM was 54.8%. WCH should be suspected in patients with relatively lower clinic BP. We proposed that ABPM should be used to confirm the diagnosis of HTN according to the NICE guidelines as a standard practice among ambulatory patients suspected of having HTN.


Identification of sensitive serum microRNA biomarkers for radiation biodosimetry.
Exposure to ionizing radiation through environmental, occupational or a nuclear reactor accident such as the recent Fukushima Daiichi incident often results in major consequences to human health. The injury caused by radiation can manifest as acute radiation syndromes within weeks in organs with proliferating cells such as hematopoietic and gastrointestinal systems. Cancers, fibrosis and degenerative diseases are also reported in organs with differentiated cells, months or years later. Studies conducted on atom bomb survivors, nuclear reactor workers and animal models have shown a direct correlation of these effects with the absorbed dose. Physical dosimeters and the available radio-responsive biologics in body fluids, whose responses are rather indirect, have limitations to accurately evaluate the extent of post exposure damage. We have used an amplification-free, hybridization based quantitative assay utilizing the nCounter multiplex platform developed by nanoString Technologies to compare the levels of over 600 miRNAs in serum from mice irradiated at a range of 1 to 12 Gy at 24 and 48 hr time points. Development of a novel normalization strategy using multiple spike-in oligonucleotides allowed accurate measurement of radiation dose and time dependent changes in serum miRNAs. The response of several evolutionarily conserved miRNAs abundant in serum, were found to be robust and sensitive in the dose range relevant for medical triage and in patients who receive total body radiation as preparative regimen for bone marrow transplantation. Notably, miRNA-150, abundant in lymphocytes, exhibited a dose and time dependent decrease in serum, which we propose as a sensitive marker indicative of lymphocyte depletion and bone marrow damage. Our study has identified several markers useful for evaluation of an individual's response by minimally invasive methods, relevant to triage in case of a radiation accident and evaluation of toxicity and response during and after therapeutic radiation.


Obstetric venous thromboembolism prophylaxis, risk factors and outcomes.
Risk factors for obstetric venous thromboembolism (VTE), a leading cause of maternal mortality in the United States, are increasing on a population basis. This review provides the obstetrician with an update of current issues related to obstetric VTE risk, prophylaxis, outcomes, anaesthesia considerations and future research opportunities. Obstetric VTE affects approximately 1 per 1000 pregnancies and accounts consistently for 9-10% of maternal deaths in the United States. In industrialized countries, risk factors for VTE, including overweight/obesity, caesarean delivery and obstetrical complications such postpartum haemorrhage and infection continue to increase. VTE prophylaxis is central to reducing maternal mortality. However, recommendations for prophylaxis from leadership societies vary widely. In the UK, maternal mortality risk from VTE has decreased significantly in the setting of broader heparin prophylaxis. In the United States where mechanical VTE prophylaxis is used more commonly, mortality risk has remained constant. Obstetric VTE is a leading cause of maternal mortality in the United States. The incidence of risk factors for obstetric VTE continues to increase. Currently, recommendations for obstetric VTE prophylaxis vary substantially. Opportunities for research in this area exist to optimize prophylaxis and improve maternal outcomes.


A phase II study of flutamide in ovarian cancer.
A phase II study of flutamide was conducted in 24 patients with stage III and IV ovarian cancer who failed chemotherapy and who had measurable disease. Flutamide was administered at a dose of 100 mg three times daily continuously until evidence of progression. Partial response observed in 1 of the 23 evaluable patients (4.3%) lasted 3 months. Two patients had stable disease (8.7%) for 7 and 8 months. The remaining 20 patients had progression of disease within 3 months. Toxicity was mild.


25 tips for getting along with your co-workers.
Each member of the medical practice staff has the responsibility to develop positive relationships with his or her colleagues. Getting along is part of the job. Many employees do not realize this or they lack the tools to build strong co-worker relationships. This article offers 25 specific strategies that will help the staff of a medical practice build positive co-worker relationships and avoid disputes. It describes ways each member of the team can improve communication skills and foster an atmosphere of respect. This article also suggests specific language employees can use with one another and several communication don'ts that can foil positive co-worker relationships. The 25 tips offered in this article can be the subject ofa staff meeting, used for new employee training, and printed in the medical practice's employee handbook.


Association of the regulatory subunit of a type II cAMP-dependent protein kinase and its binding proteins with the fibrous sheath of rat sperm flagellum.
Demembranated rat sperm flagellar polypeptides capable of binding the regulatory subunit (RII) of a type II cAMP-dependent protein kinase, having apparent subunit molecular masses of 120, 80 and 57 kDa were identified by an RII overlay procedure [Horowitz, J. A., Wasco, W., Leiser, M. & Orr, G. A. (1988) J. Biol. Chem. 263, 2098-2104]. In this study it is shown that all three polypeptides capable of binding RII on a solid-phase blot are tightly associated with the fibrous sheath. Purified fibrous sheath preparations were capable of binding (a) [3H]cAMP and (b) purified catalytic subunits of cAMP-dependent protein kinase forming a functional holoenzyme. The 57-kDa protein was identified as RII by photoaffinity labeling with 8-azido[32P]cAMP. This peptide was phosphorylated by the catalytic subunit of cAMP-dependent protein kinase. RII alpha was also shown to form tight, specific complexes with the fibrous sheath demonstrating the presence of functional RII alpha-binding sites. Truncated RII beta fusion proteins were used to identify the N-terminal amino acids at positions 1-50 as a primary determinant for RII-binding protein interaction. Differential extraction of adult testis with buffers containing Triton X-100, urea and sodium dodecyl sulfate revealed the presence of 80-kDa (major) and 120-kDa (minor) RII-binding proteins in particulate extracts. The 80-kDa polypeptide is only expressed at late stages of spermatogenesis, i.e. during spermiogenesis, suggesting a developmental role for RII anchoring to the sperm flagellar fibrous sheath.


[Antiplatelet therapy and anticoagulation in patients with coronary heart disease].
Coronary heart disease (CHD) is a dynamic process with acute instable events and chronic periods leading to an increased mortality. Patients with CHD benefit from a differentiated antithrombotic therapy consisting of dual antiplatelet therapy in the acute phase and antiplatelet monotherapy or in combination with low dose anticoagulation (Xa-Inhibition) in the chronic phase. Current ESC-guidelines differentiate the acute coronary syndrome (ACS) and the chronic coronary syndrome (CCS). Depending on thrombotic burden, bleeding risk, comorbidities, such as atrial fibrillation, antiplatelet agents and oral anticoagulants in various combinations and dosages are used. In most scenarios in patients with ACS, the initial therapy will consist out of acetylsalicylic acid and a P2Y12-Inhibitor for 12 months followed by either a continuous monotherapy with acetylsalicylic acid (ASS), a prolonged dual antiplatelet therapy or a continuous dual antithrombotic therapy consisting of ASS and low dose rivaroxaban 2x daily. With atrial fibrillation as an underlying condition, an anticoagulant should be part of the therapy followed by anticoagulant monotherapy in the chronic phase of the disease (CCS). This article provides information about the different drugs and therapeutic algorithms based on the newest ESC-Guidelines and up to date studies.


Role of spatial contiguity in sensory preconditioning with humans.
The present study demonstrates the contribution of spatial contiguity in the formation of associations between two neutral stimuli. Using human participants, we used visual conditioned stimuli (CSs) in a sensory preconditioning design in which simultaneous CS2-CS1 pairings and CS4-CS3 pairings were interspersed during Phase 1, followed by sequential CS1-US+ (i.e., CS1-pleasant US) and CS3-US-- (i.e., CS3-unpleasant US) pairings during Phase 2. The conditioned response was a shift in the gaze of the participants to the location where the US+ (i.e., short video clip) appeared. Distances between CS2 and CS1 and between CS4 and CS3 were manipulated. Our results showed a greater response to CS2 when the Phase 1 stimuli were adjacent rather than separated by 100 pixels. Implications for the role of spatial contiguity in associative learning are discussed.


Prevalence of restless legs syndrome in Japanese patients with chronic liver disease.
Sleep disturbance is a major complication in patients with chronic liver disease, but causes are unclear. The aim of this study was to clarify the prevalence of restless legs syndrome (RLS) in Japanese chronic liver disease patients and investigate the influence on sleep and quality of life. The study included 149 consecutive outpatients with chronic liver disease at Nagasaki University Hospital between September 2008 and March 2010. The presence of RLS was evaluated by a written survey using the questionnaire for the epidemiological surveillance of the international RLS research group in 2003. In addition, 89 cases, including all RLS patients, were evaluated for sleep quality and health-related quality of life. Sleep quality was evaluated by using the Japanese version of the Pittsburgh Sleep Quality Index (PSQI), and health-related quality of life was evaluated by the Japanese SF-36 Health Survey. Twenty-five of the 149 patients (16.8%) fulfilled the diagnostic criteria for RLS. The median global PSQI score of the RLS group was significantly higher than the non-RLS group (9 vs 5, P < 0.01). The number of poor sleepers (global PSQI score, >5) in the RLS group was significantly higher than in the non-RLS group (P < 0.05). In SF-36, the mental component summary score of the RLS group was 43.8 ± 10.8, which was significantly lower than the non-RSL group (49.8 ± 10.5; P < 0.05). This is the first report that clarifies the prevalence of RLS in Japanese chronic liver disease patients. RLS worsens quality of sleep and life in chronic liver disease patients.


Tumour budding in cutaneous squamous cell carcinoma: A novel prognosis risk factor.
Most cutaneous squamous cell carcinomas (cSCC) have a good prognosis, there is a small group where metastasis and death occur and the evaluation of this risk is still cause for controversy. Tumour budding is a pattern of histological invasion that is an emerging risk factor in other solid tumours. To examine the association between tumour budding and other known high-risk predictors in cSCC. In addition, the impact of tumour budding on overall survival (OS) and disease-specific survival (DSS) was analysed. Retrospective study. It included patients with a diagnosis of non-genital cSCC by excisional biopsy at a university hospital, between 2010 and 2020. A pathologist re-analysed their histological slides and evaluated budding. Univariate and multivariate analyses were made to study the associations. 156 cSCC biopsies were found, and positive tumour budding was found in 13.5%. This correlated with worse DSS and OS. On univariate analysis, budding was correlated with the diameter, thickness of the tumour, histological grade, level of invasion, perineural and lymphovascular invasion, previous radiotherapy, recurrent tumours and lymph node metastasis (LNM). Multivariate analysis: tumour budding was associated with poorly differentiated tumours, prior radiotherapy and LNM. An association was found between tumour budding and most known risk factors in cSCC. We found findings that indicate that the presence of tumour budding is associated with a worse prognosis in terms of LNM, OS and DSS. This supports the results of previous work which has suggested that budding could be related to high-risk cSCC.


Symptomatic changes of oral mucosa during normal hormonal turnover in healthy young menstruating women.
Changes in hormonal levels, such as those that occur during puberty, pregnancy, menstruation and menopause, have varying effects on oral cavity. Many researchers have proposed a direct link between changing hormonal status and oral health among females. To study the various symptoms and clinical manifestations of oral cavity during normal course of menstrual cycle in healthy women. Our study comprised of forty healthy young women volunteers with normal menstrual cycle of 28 to 30 days. A proper menstrual history was recorded from the study subjects. The entire cycle was divided into four phases comprising of bleeding, proliferative, ovulation and secretory. All the study subjects had a menstrual cycle of 28 to 30 days. Thorough recording of oral discomforts during various phases of the cycle was done during the study period. 30% of study subjects complained of aphthous ulcers, 5% had herpes labialis, 25% of them complained of depression, 8% showed gingival bleeding. Complaints, like oral ulcerations, mood variations, recurrent herpetic lesions, gingival bleeding in females during normal menstrual period, are attributed to the role of female sex hormones. Lesions, like oral ulcers, recurrent herpetic lesions and increased gingival bleeding, seen in females during normal menstrual periods, could be related to hormonal turnover and therefore treated accordingly.


Impact of Left Atrial Appendage Closure Combined with Catheter Ablation on Endocrine and Mechanical Cardiac Function in Patients with Atrial Fibrillation.
The combined procedure of left atrial appendage closure (LAAC) and catheter ablation (CA) is a safe and feasible therapy to treat patients with atrial fibrillation (AF). However, the effect of the combined procedure on cardiac function remains unclear. This study aimed to investigate the changes in endocrine and mechanical function of the heart following the combined procedure. This retrospective study included 62 consecutive patients who underwent the combined procedure of AF ablation and WATCHMAN LAAC and 62 sex and age-matched patients who only received AF ablation. During follow-up, patients were examined for brain natriuretic peptide (BNP) levels to represent endocrine cardiac function. Mechanical cardiac function was assessed during echocardiographic examination by means of the LA ejection fraction, LA strain (Ƹ), and LA strain rate (SR). (1) The BNP levels decreased acutely after the procedure, rose at day 3 postoperation, but trended downwards at 3 months postoperation in both groups. No significant difference was observed between the two groups. (2) LA ejection fraction, LA Ƹ, and SR exhibited a continuous upward trend over a 3-month follow-up in both groups. There was no significant difference in LA ejection fractions, SRe (the parameter of LA conduit function), and SRa (the parameter of LA booster pump function) between the two groups. However, the Ƹ and SRs (the parameters of LA reservoir function) improved in patients treated with CA alone. The combined procedure of LAAC and CA significantly improved the endocrine and mechanical function of the heart. Compared to simple CA, based on CA with LAAC intervention, it does not significantly change LA endocrine function but may lead to a decline in the LA reservoir function.


Utility of galectin 3 expression in thyroid aspirates as a diagnostic marker in differentiating benign from malignant thyroid neoplasms.
Galectin-3 is a 31kD beta-galactoside binding lectin, which is known to be expressed in various neoplasms including thyroid tumors. This study was conducted to study the role of galectin-3 in differentiating benign from malignant thyroid nodules onfine needle aspirates (FNAC). Galectin-3 immuocytochemistry was performed in 70 cases with adequate smears. The cytology diagnosis of these cases was: papillary carcinoma (25), follicular neoplasm (16), adenomatous goiter (20), hyperplastic nodule (5), medullary carcinoma (5) and anaplastic carcinoma (1). Galectin-3 positivity was seen in 80% of papillary carcinomas, 37.5% offollicular neoplasms and in 60% of benign nodules. The single case of anaplastic carcinoma was positive but all the cases of medullary carcinoma were negativefor galectin-3. Three of thefollicular neoplasms that were diagnosed on histology as carcinoma were positive on cytology and one case offollicular adenoma was also positive. Our study shows that galectin-3 is strongly expressed in smears of papillary carcinoma. However, since it is also expressed in a variety of benign lesions, its role as a pre-surgical markerfor differentiating benignfrom malignant thyroid nodules is limited.


Sesquiterpene lactone dermatitis in the young: is atopy a risk factor?
Screening for Compositae contact allergy has documented fairly high prevalence in adults, and recent studies indicate that the allergy may be more common in children than previously believed. However, detailed information on sensitization in this age group is sparse. The objective of this study was to present another 2 cases in children and review the literature. Screening with sesquiterpene lactone (SL) mix has shown prevalence of 0.5% and 1.8% in 2 studies, while screening with 2 different Compositae mixes detected 4.2% and 2.6% positives among children and adolescents. All individual case reports describe sensitization in atopic children, and the largest screening study showed a prevalence of Compositae mix sensitization that was significantly higher in children with atopic dermatitis compared with non-atopics. Compositae sensitization should be considered in children with a family or personal history of atopy, summer-related, or -exacerbated dermatitis of any kind, and a history of plant exposure. Screening with SL mix is recommended but should be supplemented with plant extracts based on exposure history. Compositae weeds, especially dandelions, seem to be important sensitizers in children.


Radioiodinated p-iodoclonidine: a high-affinity probe for the alpha 2-adrenergic receptor.
The chemical synthesis of 2-[(2,6-dichloro-4-iodophenyl)imino]imidazolidine (PIC) and its radioiodinated analogue [125I]PIC is described. PIC was synthesized from 2,6-dichloroaniline in five synthetic steps. This agent displayed a high affinity for the alpha 2-adrenergic receptor (IC50 = 1.5 nM) in competitive binding assays conducted with purified human platelet plasma membrane fractions. For the synthesis of radioiodinated PIC the triazene intermediate 11 was synthesized from 2,6-dichloro-4-nitroaniline in five synthetic steps. Acid-catalyzed decomposition of 11 with no-carrier-added Na125I afforded high specific activity [125I]PIC. In view of its high affinity for the alpha 2-adrenergic receptor, [125I]PIC is a potentially useful probe for studies in adrenergic pharmacology.


Insertion and Deletion Mismatches Distant from the Target Position Improve Gene Correction with a Tailed Duplex.
A 5'-tailed duplex (TD) DNA corrects a base-substitution mutation. In this study, the effects of insertion and deletion (indel) mismatches distant from the target position on the gene correction were examined. Three target plasmid DNAs with and without indel mismatches ∼330 bases distant from the correction target position were prepared, and introduced into HeLa cells together with the TD. The indel mismatches improved the gene correction efficiency and specificity without sequence conversions at the indel mismatch site. These results suggested that the gene correction efficiency and specificity are increased when an appropriate second mismatch is introduced into the TD fragment.


Coexpression and spatial association of nicotinic acetylcholine receptor subunits alpha7 and alpha10 in rat sympathetic neurons.
Fast excitatory synaptic transmission in sympathetic ganglia is mediated by nicotinic acetylcholine receptors (nAChRs). Although it is known that the nAChR alpha7-subunit occurs in sympathetic ganglia, the expression of the recently cloned subunit alpha10 (Elgoyhen et al., 2001; Lustig et al., 2001; Sgard et al., 2002) has not been analyzed. Until now, functional receptors containing alpha10-subunits have been found only in combination with alpha9-subunits (Elgoyhen et al., 2001; Lustig et al., 2001; Sgard et al., 2002). The alpha9-subunit exhibits a restricted expression pattern, whereas the alpha10-subunit is expressed more widely. This broad distribution resembles more closely that known for subunit alpha7 than for subunit alpha9. On this background, we investigated the distribution of nAChR subunits alpha7, alpha9, and alpha10 in rat sympathetic ganglia and studied a possible interaction between subunit alpha7 and potential partners by double-labeling immunofluorescence and fluorescence resonance energy transfer (FRET) (Kam et al., 1995; Jares-Erijman and Jovin, 2003).


Mortality Rate and Years of Life Lost Due to Prostate Cancer in Yazd Province, Iran: A 10-year study.
Prostate cancer is a leading cause of cancer-related deaths. The number of deaths and years of life lost (YLL) due to a disease can be used to monitor health status, assess healthcare needs and determine the prioritisation and allocation of health resources within a population; in addition, the latter calculation can serve as a baseline indicator of premature mortality. This study aimed to measure prostate cancer-related mortality and YLL in Yazd Province, Iran. This study included all prostate cancer-related deaths in Yazd Province reported between March 2001 and March 2010. Mortality data were obtained from a provincial death registration system which integrates data from different sources. YLL was calculated based on an individual's age at death and their life expectancy according to age group. During the study period, prostate cancer was the fourth most common fatal cancer among men, resulting in 324 deaths or 10.0% of all cancer-related deaths. The crude mortality rate per 100,000 individuals increased from 4.7 in 2001 to 8.8 in 2010. Premature deaths caused 1,358.7 YLL and the YLL caused by prostate cancer deaths more than doubled from 94.7 in 2001 to 196.5 in 2010. Due to changes in population structure, it is likely that the burden of prostate cancer will continue to increase in Yazd Province. As such, it is necessary that the national health system implements screening programmes and improves public awareness of prostate cancer-associated risk factors.


Short term efficacy of capacitive-resistive diathermy therapy in patients with low back pain: a prospective randomized controlled trial.
To compare the effectiveness of Doctor Tecar TherapyTM with that of laser therapy in the management of low back pain (LBP), a total of 60 patients with LBP were enrolled. The participants were randomly divided into two groups: a Tecar group (experimental group, 30 subjects), and a laser group (control group, 30 subjects). All the subjects received 10 sessions of therapy: one each day from Monday to Friday and the same again the following week. All the subjects were evaluated for pain (VAS) and disability (Roland and Morris score and Oswestry score) at baseline (T0), and 2 weeks (T1), 1 month (T2) and 2 months (T3) after the end of treatment. The pain and disability presented a trend to improvement over time in both groups. This improvement was statistically significant at all follow-ups (FUs) in the Tecar group but only at T1 for the Laser group (p less than 0.01). Comparing the two methods, there emerged a significant difference in favour of the Tecar group at T2 and T3 (p less than 0.01). The results show that Tecar therapy determined significant improvement already by the end of the treatment. Moreover, at the first and second month FUs, the Tecar therapy showed statistically better results than laser therapy.


[Exoenzymes of dermatophytes isolated from acute and chronic tinea].
The presence of five enzymes (deoxyribonuclease, elastase, lipase, caseinase and hemolysin) in 76 strains of dermatophytes 47 of Trichophyton rubrum, 10 of T. mentagrophytes, five of T. tonsurans, 10 of Microsporum canis and four of Epidermophyton floccosum) isolated from 30 cases of acute dermatophytosis and from 46 chronic ones was determined by a qualitative plate assay; in the same way, the presence of these five enzymes with the acute and chronic dermatophytosis was correlated. It was observed that three of the enzymes were produced by the strains with a meaningful frequency; deoxyribonuclease was produced by 84.2% of the strains; elastase by 82.9%; and lipase by 65.8%. In T. rubrum the DNase was produced in 100% of strains. DNase and elastase were related to fungi which caused acute or chronic dermatophytosis in 93.3/78.2% and 96.6/74% respectively. On the other hand, lipase was present in 76% of strains, the ones that caused the chronic infections.


The importance of analytical quality specifications for biomarker assays currently used in acute cardiac care.
It is very important that cardiac biomarkers on which clinically relevant decisions will rest are measured with highly reliable assays. Adequate studies are needed before new methods can be implemented in the laboratory routine, and only well-documented assays should be considered for clinical use. Therefore, it is critical that, as new biomarkers are proposed, quality specifications are developed. Only after appropriate analytical quality specifications are addressed, the issues pertaining to methodological differences that result in non-harmonized concentration values, and clinical interpretation of biomarker concentrations will be reconciled. Today, the technology to address many analytic problems is at hand, but commitment on the part of manufacturers and their customers in the laboratory and clinical communities is essential. The design control loop is not closed until the finished in vitro diagnostic system is adequately validated to meet the customer needs, including analytical quality specifications. It is essential to determine the attributes and performance characteristics of relevant competitive systems and their degree of acceptance by clinical laboratories in order to demonstrate that user needs are definitely met. The responsibility of defining and implementing these issues must be a shared responsibility among laboratorians, clinicians, industry, and regulatory agencies on an international front. To date, two sets of quality specifications have been published, one for cardiac troponin assays and one for B-type natriuretic peptide assays. Both address analytical factors, such as calibrator characterization, antibody specificity, assay sensitivity and imprecision, and interferents, as well as preanalytical factors, such as sample type and stability. It would be ideal if regulatory agencies, such as FDA in the United States, accept these criteria for premarket approval clearance applications.


[Appropriate dosage of unfraction heparin and low molecular weight heparin in hemodialysis patients].
To investigate the appropriate dose of unfraction heparin and low molecular weight heparin (LMWH) in hemodialysis patients. Thirty-eight hemodialysis patients were enrolled and randomly allocated into four groups.The initial bolus dose for the Low-dose (LH, n = 10) and high-dose heparin (HH, n = 10) groups were 35 U/kg and 55 U/kg, respectively.The repeated maintenance dose for both groups were 10 U/kg.h and 16 U/kg.h, respectively. Fragmin were administered as single bolus (60 U/kg or 80 U/kg) at 30 minutes before hemodialysis in Low-dose LMWH(LLMWH, n = 10) and High-dose LMWH (HLMW, n = 8) group, respectively. Furthermore, the dialysis circuits in LUFH and LLMWUFH groups were primed with with 4 mg/dl heparinized saline before hemodialysis. Glass bead active clotting time (gbACT), clot rate (CR) and platelet function (PF) were examined using Sonoclot analysator at 0 h, 2 h and the end of hemodialysis at the arterial circuit and 2 h at the venous circuit. (1) LH and LUFH: the increase of gbACT and decrease of CR at the arterial circuit and the venous circuit at 2 h of hemodialysis were significant compared with baseline. While they recovered at the end of hemodialysis. No difference between the two groups at different time points was found, either. (2) LLMWH: No change were found in gbACT during hemodialysis. CR at the arterial circuit and the venous circuit were significantly decreased at 2 h and recovered at the end of hemodialysis. (3) LLMWUFH: gbACT at the arterial circuit was significantly increased only at 2 h of hemodialysis. CR at the arterial circuit and the venous circuit at 2 h of hemodialysis were significantly decreased and recovered when hemodialysis finished. (4) HH and HLMWH: gbACT were significantly increased and CR were rapidly decreased at both the arterial circuit and venous circuit at 2 h of hemodialysis. Low-dose heparin was effective and safe as anticoagulant in hemodialysis. Low-dose low-molecular-weight heparin was efficient in anticoagulation to some extent. However, High-dose low-molecular-weight heparin, high-dose heparin and flushing with heparinized saline may increase the risk of hemorrhage.


Effect of TLR4 on the growth of SiHa human cervical cancer cells via the MyD88-TRAF6-TAK1 and NF-κB-cyclin D1-STAT3 signaling pathways.
The present study aimed to investigate the effect of Toll-like receptor 4 (TLR4) on SiHa human cervical cancer cells and its potential molecular biological mechanisms. The expression of TLR4 following treatment with lipopolysaccharide (LPS) in in SiHa cervical cancer cells was detected by quantitative polymerase chain reaction (qPCR). LPS-induced cell proliferation and apoptosis were detected by MTT assay as well as staining with propidium iodide (PI) and Annexin V/PI double staining. qPCR was performed to analyze the expression levels of tumor necrosis factor receptor-associated factor 6 (TRAF6) and transforming growth factor-activated kinase 1 (TAK1) genes. Western blot analysis was performed to analyze the expression of myeloid differentiation 88 (MyD88), nuclear factor-κB (NF-κB), cyclin D1 and signal transducer and activator of transcription 3 (STAT3) proteins. In the present study, it was revealed that TLR4 expression in SiHa cervical cancer cells may be upregulated by LPS. Additionally, LPS was able to increase the proliferation of SiHa cells. However, LPS treatment did not have an effect on apoptosis of the cells. In addition, the MyD88-TRAF6-TAK1 and NF-κB-cyclin D1-STAT3 signaling pathways were induced in SiHa cells by LPS. These results suggested the effect of LPS and TLR4 on proliferation of SiHa human cervical cancer cells via the MyD88-TRAF6-TAK1 and NF-κB-cyclin D1-STAT3 signaling pathways.


Updating motor unit number estimation (MUNE).
Motor unit number estimation (MUNE) is a unique electrophysiologic technique that can provide a numeric estimate of the number of axons innervating a muscle or group of muscles. The first technique was first described in 1971, and since then different techniques have been developed to address specific methodologic issues. The field was reviewed in this journal in 2001, and this update covers new information and uses of MUNE over the past five years. These include models of muscles that allow evaluation of MUNE techniques and comparisons between techniques. There have been further investigations of specific technical aspects of MUNE. Modifications to MUNE techniques have been offered that permit more rapid acquisition of data. MUNE has been used in clinical situations to elucidate the pathophysiology features of axonal loss in a number of disorders. There is now more experience with MUNE as endpoint measures in clinical trials.


Hydrotropic Action of Cationic Hydrotrope p-Toluidinium Chloride on the Solubility of Sparingly Soluble Gliclazide Drug Molecule: A Computational Study.
We perform classical molecular dynamics simulations of sparingly soluble drug gliclazide (GLC) and hydrotrope p-toluidinium chloride (PTOL) in water with a regime of PTOL concentrations. Our results demonstrate that PTOL starts to self-aggregate above its minimum hydrotrope concentration (MHC). Further, these PTOL aggregates create a mixed micellar-like framework in which the hydrophobic small tail part of most of the PTOL molecules direct toward the inside, whereas in order to make favorable contact with water molecules its hydrophilic ammonium group points outward. But, in order to make hydrogen bonds with GLC molecules, the polar groups of a few of the hydrotropes direct inward also. This provides an environment for the incorporation of the drug molecules into the mixed environment (hydrophobic as well as hydrophilic core) of PTOL clusters. The average number of hydrogen bond calculations indicates that PTOL aggregate does not have much effect on the average number of water-PTOL hydrogen bonds, but it has an influence on the average number of water-GLC, GLC-GLC, and GLC-PTOL hydrogen bonds. Both electrostatic and van der Waals energy components of drug and hydrotrope interactions play vital roles in the solubilization process. Furthermore, the estimation of Flory-Huggins interaction parameters also suggests favorable interactions between hydrotrope PTOL and GLC drug molecules.


Myeloid Sarcoma: Presentation, Diagnosis, and Treatment.
Myeloid sarcoma is an extramedullary tumor of immature granulocytic cells. It is a rare condition, most often associated with acute myeloid leukemia (AML), although in some rare cases it may present in nonleukemic patients. It should therefore be considered as a differential diagnosis of any atypical cellular infiltrate. It may occur at any site, leading to very varied clinical presentations. Diagnosis is challenging and relies on a high index of suspicion as well as radiology, histology, immunophenotyping, and molecular analyses, which also are essential for risk stratification and treatment planning. Systemic chemotherapy using AML-like regimens should be commenced early, even in nonleukemic disease. Surgery and/or radiotherapy may be indicated for symptomatic lesions or tumors causing local organ dysfunction or obstruction. Allogeneic hematopoietic stem cell transplantation has demonstrated promising results, particularly in patients who achieved complete remission with AML-induction protocols, and recent advances in genetic profiling may enable the development of novel targeted therapies. Prospective multicenter controlled trials are required to further refine management decisions and investigate the role of novel targeted therapies.


Distribution of vespid species in Europe.
Knowledge of the different stinging vespids found in various parts of Europe and their venom cross-reactivity is important in order to improve the venoms available for diagnostic and therapeutic purposes. In recent years the amino acid sequences of different vespid venom allergens have been determined. Comparison of these sequences has led to an improved taxonomical classification of vespids compared with that based on morphological differences. However, the distribution of vespids in Europe is still based on a very good but somewhat old study carried out in the 1970s. Most recent epidemiological studies focus on the type of reaction produced rather than the insect responsible. The genera Vespula, Dolichovespula and Vespa are found all over Europe, but the genus Polistes, although present in central Europe, is not found in the UK and only represents a specific clinical problem in areas around the Mediterranean sea. Although there are significant differences in the distribution of stings, the genus Vespula predominates over Polistes and Vespa throughout Europe, except in Mediterranean areas. The different species of Polistes in Europe show a great similarity in the sequences of their venom allergens, but the similarity to their American counterparts is less marked. Vespula allergens show up to 95% sequence identity and almost complete cross-reactivity. There is also great cross-reactivity among the genera Vespula, Vespa and Dolichovespula. This identity of amino acid sequences confirms the latest morphological taxonomy of Hymenoptera and opens the way for the use of recombinant hybrids of different species in venom immunotherapy.


System-structured management of acutely ill surgical patients.
The management of surgical patients requiring intensive care is complicated by abnormalities in multiple body systems. An effective method of organizing data collection and treatment is essential. The widely applied "problem-oriented" approach is not entirely satisfactory in the context of surgical intensive care. An alternative method is presented in which management is structured by body systems. The function of each system is analyzed and a plan for each is defined. Data display is arranged by systems rather than problems and is compatible with modern computer technology. A surgical patient under treatment for pancreatitis is presented to illustrate this approach. Experience with 220 patients on a residency teaching service supports the impression that system-structured management is an effective method of managing the course of an acutely ill patient and should be widely applicable to such patients in any general surgical environment.


Comparative efficacy of a specially engineered sonic powered toothbrush with unique sensing and control technologies to two commercially available power toothbrushes on established plaque and gingivitis.
To evaluate the efficacy on plaque and established gingivitis of a new specially engineered sonic powered toothbrush with unique sensing and control technologies as compared to two commercially available power toothbrushes. This examiner-blind, three-treatment, parallel clinical study assessed plaque reduction via the comparison of pre- to postbrushing after a single use, and following four weeks' use measured by the Rustogi Modification of the Modified Navy Plaque Index. This study also assessed gingivitis using the Löe and Silness Gingival Index after four weeks' use. Qualifying adult male and female subjects from the northern New Jersey area reported to the study site after refraining from all oral hygiene procedures for 24 hours, and from eating, drinking, or smoking for four hours. Following an examination for gingivitis and plaque (pre-brushing), they were randomized into three balanced groups, each group using one of the three study toothbrushes in the order specified by a predetermined randomization plan. Subjects were instructed to brush their teeth for two minutes under supervision with their assigned toothbrush according to the manufacturers' instructions and a commercially available toothpaste (Colgate Cavity Protection), after which they were once again evaluated for plaque (post-brushing). Subjects were then dismissed from the study site with the toothpaste and their assigned toothbrush to use at home twice daily for the next four weeks. They again reported to the study site at which time they were evaluated for plaque and gingivitis. One-hundred eighty-four subjects complied with the protocol and completed the clinical study. Relative to the two commercially available toothbrushes, the new specially engineered sonic powered toothbrush with unique sensing and control technologies provided statistically significantly (p < 0.05) greater reductions in whole mouth plaque index scores (21.9 and 25.8%, respectively), gingival margin plaque index scores (14.5% and 18.9%, respectively), interproximal plaque index scores (160.0% and 136.4%, respectively), facial plaque index scores (17.9% for both), lingual plaque index scores (29.2% for both), and interproximal lingual plaque index scores (200.0% and 350.0%, respectively) after a single tooth brushing. Relative to the two commercially available toothbrushes, the new sonic powered toothbrush also provided statistically significantly (p < 0.05) greater reductions in whole mouth plaque index scores (47.4% and 40.0%, respectively), gingival margin plaque index scores (46.2% and 40.7%, respectively), interproximal plaque index scores (650% and 1400%, respectively), facial plaque index scores (47.6% and 40.9%, respectively), lingual plaque index scores (47.1% and 31.6%, respectively), and interproximal lingual plaque index scores (350.0% and 500.0%, respectively) after four weeks. There was no statistically significant (p > 0.05) difference between the two commercially available toothbrushes for any plaque index score comparison. Relative to one of the commercially available toothbrushes, the new sonic powered toothbrush provided statistically significant reductions (p < 0.05) in gingival index scores (25.0%) and gingivitis severity scores (33.3%) after four weeks of product use. There were no statistically significant (p > 0.05) differences in gingivitis or gingivitis severity index scores between the new sonic powered toothbrush and the other commercially available toothbrush. A new specially engineered sonic powered toothbrush with unique sensing and control technologies provides significantly greater levels of efficacy on the removal of dental plaque after a single tooth brushing and after four weeks' use when compared to two commercially available power toothbrushes. The new sonic powered toothbrush also provides significantly greater levels of efficacy on the reduction of gingivitis and gingival bleeding when compared to one of the commercially available power toothbrushes.


Singular localization of sodium channel β4 subunit in unmyelinated fibres and its role in the striatum.
Voltage-gated Na(+) channel β-subunits are multifunctional molecules that modulate Na(+) channel activity and regulate cell adhesion, migration and neurite outgrowth. β-subunits including β4 are known to be highly concentrated in the nodes of Ranvier and axon initial segments in myelinated axons. Here we show diffuse β4 localization in striatal projection fibres using transgenic mice that express fluorescent protein in those fibres. These axons are unmyelinated, forming large, inhibitory fibre bundles. Furthermore, we report β4 dimer expression in the mouse brain, with high levels of β4 dimers in the striatal projection fascicles, suggesting a specific role of β4 in those fibres. Scn4b-deficient mice show a resurgent Na(+) current reduction, decreased repetitive firing frequency in medium spiny neurons and increased failure rates of inhibitory postsynaptic currents evoked with repetitive stimulation, indicating an in vivo channel regulatory role of β4 in the striatum.


A preliminary study on the diagnostic value of PSADR, DPC and TSRP in the distinction of prostatitis and prostate cancer.
The purpose of this study was to investigate the ability of differential diagnosis of prostate specific antigen decline rate (PSADR) per week, degree of prostatic collapse (DPC) and tissue signal rate of prostate (TSRP) between prostatitis and prostate cancer. The clinical data of 92 patients [prostate specific antigen (PSA) > 10 ng/mL] who underwent prostate biopsy in the Department of Urology, the Second Affiliated Hospital of Xi 'an Jiaotong University from May 2017 to April 2020 were reviewed retrospectively. They were divided into two groups, prostatitis group (n = 42) and prostate cancer (PCa) group (n = 50), according to pathological results. Parameters, like patient characteristics, PSADR, DPC, TSRP and infectious indicators, were compared and analyzed by t test or non-parametric test to identify if there were significant differences. The thresholds of parameters were determined by the receiver operating characteristic curve (ROC), and the data were analyzed to investigate the diagnostic value in distinguishing of prostatitis and prostate cancer. There were statistical differences in age, PSADR, DPC, TSRP, neutrophil percentage in serum, white blood cell (WBC) in urine and prostate volume between prostatitis group and PCa group (P < 0.001, < 0.001, = 0.001, 0.001, 0.024, 0.014, < 0.001 respectively). There was no statistical difference in serum WBC count, serum neutrophil count, monocyte percentage and urine bacterial count between two groups (P = 0.089, 0.087, 0.248, 0.119, respectively). Determined by ROC curve, when the thresholds of PSADR per week as 3.175 ng/mL/week, DPC as 1.113, TSRP as 2.708 were cutoffs of distinguishing prostatitis and prostate cancer. When combining these three indexes to diagnose, the accuracy rate of diagnosis of prostatitis was 78.85%, the accuracy rate of diagnosis of prostate cancer was 97.50%. Univariate analysis suggested that PSADR, DPC and TSRP played an important role in differentiating prostate cancer from prostatitis (P < 0.05), multivariate analysis suggested PSADR > 3.175 might be good indicators when distinguishing prostate disease with prostatitis (OR = 14.305, 95%CI = 3.779 ~ 54.147), while DPC > 1.113 and TSRP > 2.708 might be associated with a higher risk of prostate cancer (OR = 0.151, 95%CI = 0.039 ~ 0.588; OR = 0.012, 95%CI = 0.005 ~ 0.524, respectively). The combination of PSADR per week, DPC, and TSRP might be helpful to distinguish prostate cancer and prostatitis, and can reduce unnecessary invasive and histological procedure.


Marine Develops Chronic Right Knee Granuloma After Initial Injury at The Basic School.
With skin lesions that have failed previous treatments, consideration for an atypical mycobacteria, specifically Mycobacterium marinum, infection should be suspected. Importance of the history cannot be stressed as this is a clue that the patient may have been inoculated and infected in the field environment. A marine with chronic right knee plaque for 3 yr that first appeared after a field exercise at The Basic School but worsened despite treatment with clindamycin, TMP-SMX, and incision and drainage in 2012. Examination revealed a 4 × 4 cm pink, pearly, scaly plaque with scabbing. Deroofing caused puncta to bleed and suppurate. Empiric therapy with doxycycline topical fluocinonide were initiated. Histopathological findings showed dermal fibrosis, granulomatous inflammation, and overlying epidermal inflammation and hyperplasia. Sections also revealed scattered admixed non-necrotizing granulomata. Initial stains, tissue and wound cultures were negative. Acid-fast bacilli broth and smear culture with growth after 4 wk, growing M. marinum. Doxycycline was continued for 2 more months. Mycobacterium marinum is a nontuberculous mycobacterium responsible for skin infections. Sources of infections usually are non-chlorinated water. Infections are rare, an estimated annual incidence of 0.27 cases per 100,000 patients, within the USA and do not cause significant morbidity in immunocompetent patients. Initial M. marinum infections can be mistaken as methicillin resistant Staph aureus infections in the active duty population. If the infection recurs or does not resolve with methicillin resistant Staph aureus-targeted antibiotics, consider cultures specific to acid-fast bacilli and keep in the differential until long term culture results are obtained.


Spontaneous formation and growth of a new polytype on SiC(0001).
Using in situ electron microscopy, we have measured the structure of SiC(0001)-4H during annealing in vacuum. Above 1000 degrees C, an additional SiC bilayer forms on the surface that changes the polytype from hexagonal (4H) to cubic (3C). The interaction with surface steps prevents the cubic layer from growing thicker: the new phase does not wet the steps of the underlying 4H substrate. Instead, the cubic layer expands laterally, accelerating step bunching in the surrounding hexagonal regions. During SiC homoepitaxy, this lack of step edge wetting leads to the growth of 3C twins separated by deep grooves.


Abnormal dynamic scintigraphy in hydrocephalus: a proposed mechanism.
Dynamic brain scintigraphy was performed on seven patients with documented hydrocephalus of various aetiologies. The patients had a characteristic abnormality consisting of lateral displacement of the proximal middle cerebral activity associated with a paracentral lucent zone. No focal areas of increased activity were identified on the static brain images. A proposed mechanism for these findings is discussed.


[The occurrence of gastrointestinal cestode and nematode infections in stray dogs in Afyonkarahisar and Eskisehir provinces].
This study was carried out to determine the prevalence of cestode and nematode infections in stray dogs in Afyonkarahisar and Eskisehir provinces. A total of 287 dogs (n=150 from Afyonkarahisar and n=137 from Eskisehir) of different ages and sexes living in animal shelters were used in this study. After the coprological examination, dogs were found to be infected with various gastrointestinal cestode and nematode species. It was found that rates of infection were 46% (69 out of 150) in Afyonkarahisar and 33.6% (46 out of 137) in Eskisehir provinces. Species responsible for the infection were the same in both provinces. In the Afyonkarahisar province 59.4% hookworms, 47.8% Toxascaris leonina, 36.2% Toxocara canis, 2.9% Dipylidium caninum and 2.9% Taenia spp. were detected. In the Eskisehir province 60.9% Toxascaris leonina , 47.8% Toxocara canis, 23.9% Taenia spp., 6.5% hookworms and 4.3% Dipylidium caninum were detected. It was concluded that in Afyonkarahisar and Eskisehir provinces, stray dogs might be infected with helminths which put humans in danger and necessary measures are needed.


Influence of Side Chain Sizes on Dielectric and Electrorheological Responses of Poly(ionic liquid)s.
Poly(ionic liquid)s (PILs) show potential as new anhydrous polyelectrolyte-based smart electrorheological (ER) materials. Understanding the structure-property relationship on a molecular level is very important for guiding the design of PIL-based ER materials. In this paper, a family of (p-vinylbenzyl)trialkylammonium hexafluorophosphate-based PIL particles containing different length of substituent alkyl chains attached to immobile ammonium charged site is synthesized for especially understanding the size effect of side chains on ER property. To exclude the particle shape effect, the PIL particles are controlled to be monodisperse sphere-like morphology with a similar size. The ER property of PIL particles when dispersed in insulating oil is investigated and compared by temperature-modulated rheological test under external electric fields. The dielectric spectroscopy is finally performed to study the mechanism behind the size effect of side chains on the ER property of PIL particles. We demonstrate that the size of side chains on the charged site has a significant impact on the ER effect of PIL particles and the PIL particles with shorter side chains have stronger ER property but degraded temperature dependence, and this is related to the fact that the variation of side chain size alters the transport dynamic of mobile counterions and ion motion-induced interfacial polarization.


Impacts of alcohol duty reductions on cardiovascular mortality among elderly Chinese: a 10-year time series analysis.
In March 2007, the Hong Kong Government halved its heavy excise taxes on beer and wine, and 1 year later, it eliminated all duties on these beverages. This study examines the impact of such duty reductions on cardiovascular disease (CVD)-related mortality among the elderly in Hong Kong. Box-Jenkins autoregressive integrated moving average intervention time series analyses were applied to monthly morality data from 2001 to 2010 to quantify the impacts of duty reduction and exemption on CVD death rates among those aged 65 years or older. The alcohol duty reduction in March 2007 was associated with an estimated 13% increase (95% CI 2% to 24%) in CVD death rates among elderly men, after controlling for the other intervention, outlier, trends and seasonal variations. This was equivalent to an extra 11 CVD deaths per 100 000 elderly men each month. Much of the observed impacts on CVD death rates were found to have contributed only by that on ischaemic heart disease mortality (18% increase in rate for men (95% CI 4% to 34%); 15% increase for women (95% CI 0.4% to 31%)), not by mortality due to stroke or hypertension. The alcohol duty exemption on March 2008 was not found to have impacted the CVD death rates. The increase in CVD death rates among the Chinese elderly after alcohol duty reduction suggest that the purported beneficial effect of moderate alcohol use may not apply to certain Chinese populations, adding fuel to the ongoing debate on the risks and benefits of moderate alcohol consumption on mortality.


TRPV1 antagonist attenuates postoperative hypersensitivity by central and peripheral mechanisms.
Acute postoperative pain is one of the frequent reasons for pain treatment. However, the exact mechanisms of its development are still not completely clear. Transient receptor potential vanilloid 1 (TRPV1) receptors are involved in nociceptive signaling in various hypersensitive states. Here we have investigated the contribution of TRPV1 receptors expressed on cutaneous peripheral nociceptive fibers and in the spinal cord on the development and maintenance of hypersensitivity to thermal and mechanical stimuli following surgical incision. A rat plantar incision model was used to test paw withdrawal responses to thermal and mechanical stimuli. The effect of the TRPV1 receptor antagonist SB366791 was investigated 1) by intrathecal injection 15 min before incision and 2) intradermal injection before (30 min) and immediately after the surgery. Vehicle-injected rats and naïve animals treated identically were used as controls. Plantar incision induced mechanical allodynia and hyperalgesia and thermal hyperalgesia. A single intrathecal administration of SB366791 significantly reduced postincisional thermal hyperalgesia and also attenuated mechanical allodynia, while mechanical hyperalgesia remained unaffected. Local intradermal SB366791 treatment reduced thermal hyperalgesia and mechanical allodynia without affecting mechanical hyperalgesia. Our experiments suggest that both peripheral and spinal cord TRPV1 receptors are involved in increased cutaneous sensitivity following surgical incision. The analgesic effect of the TRPV1 receptor antagonist was especially evident in the reduction of thermal hyperalgesia. The activation of TRPV1 receptors represents an important mechanism in the development of postoperative hypersensitivity.


Pregnancy and Tumor Outcomes in Women with Prolactinoma.
Context Management of prolactinomas during pregnancy has always been a challenge. There is a concern about the risk of tumor growth, as well as the effects of the treatment on the developing fetus. Another issue that has been less studied is the outcome of women with prolactinoma after pregnancy and lactation. Objectives To evaluate remission of hyperprolactinaemia after pregnancy and lactation in women with prolactinoma. To describe the safety of dopamine agonists for the fetus and pregnancy outcomes. Methods A retrospective study of 32 pregnancies in women with prolactinoma was conducted in a single-centre. Other causes of hyperprolactinemia were excluded. Prolactin level was recorded at the time of diagnosis, during treatment, and during follow-up. Results The pregnancies resulted in one spontaneous abortion (3.1%) and 31 live births (96.9%). No stillbirths, multiple or ectopic pregnancies or trophoblastic disease were recorded. There was only one malformation (club foot) recorded (3.1%) and normalisation of prolactin after pregnancy without medical treatment occurred in 12% of patients. Conclusions Fetal exposure to bromocriptine or cabergoline during pregnancy is not associated with an increased risk of adverse neonatal or pregnancy disclosures. There is considerable diversity among endocrinologists in the management of prolactinomas during pregnancy and after birth, which indicates that there is a need for better consensus and for carefully drawn-up guidelines to follow.


Differences in Inflammation Patterns Induced by African and Asian Burkholderia pseudomallei Isolates in Mice.
AbstractBurkholderia pseudomallei is the causative agent of melioidosis, an emerging tropical disease of high mortality. Sub-Saharan Africa represents potential melioidosis "hotspots"; however, to date, only a few cases have been reported. Here in, we compared the inflammatory patterns induced by a B. pseudomallei strain recently isolated from a fatal Gabonese case with the Thai reference strain B. pseudomallei-1026b and Burkholderia thailandensis-E264. Ex vivo, no differences were observed in terms of cellular responsiveness between strains. However, when compared with the B. pseudomallei-1026b strain, the Gabonese isolate was significantly less virulent in terms of bacterial dissemination, inflammatory response, and organ damage in mice. Genomic comparison between strains showed differences in regions containing a fimbriae/adhesion virulence protein. In addition to a lack of microbiology facilities, differences in virulence of Burkholderia strains might contribute to the diverse global clinical occurrence of melioidosis.


Survival of Patients with Cystic Fibrosis Depending on Mutation Type and Nutritional Status.
The purpose of the study was to evaluate the influence of nutrition and of the severity of mutation type on survival rate in cystic fibrosis (CF) patients. Data were longitudinally collected from 60 hospitalized adult CF patients, aged 18-50. The variables consisted of body mass index (BMI) ratio, Cole's BMI cut-off points, severity of mutation type, and survival rate of CF patients. We found that the mean BMI was strongly associated with the severity of mutation type and was significantly lower in patients with severe mutations of grade I and II. The mutation type significantly affected the patients' survival rate; survival was greater in patients with mild and undefined mutation types. The BMI and Cole's cut-off points also had a significant influence on survival rate. CF patients, who suffered from malnutrition and emaciation, had a shorter survival rate than those with proper nutritional status. In conclusion, the study findings confirmed a significant effect of nutritional status and of mutation type on survival rate of CF patients.


Inhibition of Naja naja venom hyaluronidase by plant-derived bioactive components and polysaccharides.
The inhibitory effect of several bioactive compounds on the activity of hyaluronidase enzyme purified from Naja naja venom was investigated in vitro. Compounds were found to inhibit the hyaluronidase activity dose dependently. Among glycosaminoglycans, heparin, heparan sulfate, and dermatan sulfate showed maximum inhibition compared to chondroitin sulfates. Different molecular forms of chitosan inhibit the enzyme, and inhibition appears to depend on the chain length. In addition, plant-derived bioactive compounds also inhibited the activity of hyaluronidase dose dependently. Among those tested, aristolochic acid, indomethacin, quercetin, curcumin, tannic acid, and flavone exhibited inhibition, with aristolochic acid and quercetin completely inhibiting the enzyme activity. It is concluded that the inhibitors of hyaluronidase could be used as potent first aid agents in snakebite therapy. Furthermore, these inhibitors not only reduce the local tissue damage but also retard the easy diffusion of systemic toxins and hence increase survival time.


The Effectiveness of Enhanced Primary Healthcare (EnPHC) interventions on Type 2 diabetes management in Malaysia: Difference-in-differences (DID) analysis.
To evaluate the effectiveness of the Enhanced Primary Healthcare (EnPHC) interventions on process of care and intermediate clinical outcomes among type 2 diabetes patients. This was a quasi-experimental controlled study conducted in 20 intervention and 20 control public primary care clinics in Malaysia from November 2016 to June 2019. Type 2 diabetes patients aged 30 years and above were selected via systematic random sampling. Outcomes include process of care and intermediate clinical outcomes. Difference-in-differences analyses was conducted. We reviewed 12,017 medical records of patients with type 2 diabetes. Seven process of care measures improved: HbA1c tests (odds ratio (OR) 3.31, 95% CI 2.13, 5.13); lipid test (OR 4.59, 95% CI 2.64, 7.97), LDL (OR 4.33, 95% CI 2.16, 8.70), and urine albumin (OR 1.99, 95% CI 1.12, 3.55) tests; BMI measured (OR 15.80, 95% CI 4.78, 52.24); cardiovascular risk assessment (OR 174.65, 95% CI 16.84, 1810.80); and exercise counselling (OR 1.18, 95% CI 1.04, 1.33). We found no statistically significant changes in intermediate clinical outcomes (i.e. HbA1c, LDL, HDL and BP control). EnPHC interventions was successful in enhancing the quality of care, in terms of process of care, by changing healthcare providers behaviour.


Targeting the epithelial-mesenchymal transition (EMT) pathway with combination of Wnt inhibitor and chalcone complexes in lung cancer cells.
Non-small cell lung cancer (NSCLC) is the most common type of the lung cancer. Despite development in treatment options in NSCLC, the overall survival ratios is still poor due to epithelial and mesenchymal transition (EMT) feature and associated metastasis event. Thereby there is a need to develop strategy to increase antitumor response against the NSCLC cells by targeting EMT pathway with combination drugs. Niclosamide and chalcone complexes are both affect cancer cell signaling pathways and therefore inhibit the EMT pathway. In this study, it was aimed to increase antitumor response and suppress EMT pathway in NSCLC cells by combining niclosamide and chalcone complexes. SRB cell viability assay was performed to investigate the anticancer activity of drugs. The drugs were tested on both NSCLC cells (A549 and H1299) and normal lung bronchial cells (BEAS-2B). Then the two drugs were combined and their effects on cancer cells were evaluated. Fluorescence imaging and enzyme-linked immunosorbent assay were performed on treated cells to observe the cell death manner. Wound healing assay, real-time quantitative polymerase chain reaction, and western blot analysis were performed to measure EMT pathway activity. Our results showed that niclosamide and chalcone complexes combination kill cancer cells more than normal lung bronchial cells. Compared to single drug administration, the combination of both drugs killed NSCLC cells more effectively by increasing apoptotic activity. In addition, the combination of niclosamide and chalcone complexes decreased multidrug resistance and EMT activity by lowering their gene expressions and protein levels. These results showed that niclosamide and chalcone complexes combination could be a new drug combination for the treatment of NSCLC.


VEGF, HIF-1α expression and MVD as an angiogenic network in familial breast cancer.
Angiogenesis, which plays an important role in tumor growth and progression of breast cancer, is regulated by a balance between pro- and anti-angiogenic factors. Expression of vascular endothelial growth factor (VEGF) is up-regulated during hypoxia by hypoxia-inducible factor-1α (HIF-1α). It is known that there is an interaction between HIF-1α and BRCA1 carrier cancers, but little has been reported about angiogenesis in BRCA1-2 carrier and BRCAX breast cancers. In this study, we investigated the expression of VEGF and HIF-1α and microvessel density (MVD) in 26 BRCA1-2 carriers and 58 BRCAX compared to 77 sporadic breast cancers, by immunohistochemistry. VEGF expression in BRCA1-2 carriers was higher than in BRCAX cancer tissues (p = 0.0001). Furthermore, VEGF expression was higher in both BRCA1-2 carriers and BRCAX than the sporadic group (p<0.0001). VEGF immunoreactivity was correlated with poor tumor grade (p = 0.0074), hormone receptors negativity (p = 0.0206, p = 0.0002 respectively), and MIB-1-labeling index (p = 0.0044) in familial cancers (BRCA1-2 and BRCAX). The percentage of nuclear HIF-1α expression was higher in the BRCA1-2 carriers than in BRCAX cancers (p<0.05), and in all familial than in sporadic tumor tissues (p = 0.0045). A higher MVD was observed in BRCA1-2 carrier than in BRCAX and sporadic cancer tissues (p = 0.002, p = 0.0001 respectively), and in all familial tumors than in sporadic tumors (p = 0.01). MVD was positively related to HIF-1α expression in BRCA1-2 carriers (r = 0.521, p = 0.006), and, in particular, we observed a highly significant correlation in the familial group (r = 0.421, p<0.0001). Our findings suggest that angiogenesis plays a crucial role in BRCA1-2 carrier breast cancers. Prospective studies in larger BRCA1-2 carrier series are needed to improve the best therapeutic strategies for this subgroup of breast cancer patients.


Autonomic regulation of cardiovascular function in neonates.
The degree of participation of the vascular bed supplied by the superior mesenteric artery in autonomic regulation of cardiovascular function during postnatal maturation was evaluated in piglets, ranging in age from birth to two months. Animals were anaesthetized with 0.25-0.5% halothane in a 50% mixture of N2O and O2, paralysed with decamethonium bromide and artificially ventilated to maintain normal arterial blood gases and pH. Mesenteric arterial flow was recorded continuously with an electromagnetic flow transducer; simultaneously aortic pressure, heart rate, and femoral, renal and carotid flows were monitored. Resistance was calculated as the ratio of mean aortic pressure to mean flow. The central neural regulation of the cardiovascular system was altered: (1) by electrical stimulation of medullary vasoactive sites, (2) by changing the input from visceral or somatic afferents and (3) by subjecting the animals to stress, such as haemorrhage or hypoxia. Postnatal development of adrenergic mechanisms was studied with the aid of adrenergic agonist both in vivo and in vitro (helical strips cut from superior mesenteric artery were placed in an organ bath for isometric tension recordings). Recordings of spontaneous efferent splanchnic discharge permitted a more direct examination of autonomic regulation of the mesenteric vascular bed. The results indicate that the vascular bed supplied by the superior mesenteric artery and innervated by the efferent splanchnic nerve is actively involved in the cardiovascular responses to alterations in the cardiovascular regulatory system. Furthermore, this vascular bed may have an inappropriate response to both feeding and stress such that pathological changes in the gastrointestinal tract may result.


Oral somatosensory factors in dietary self-selection after food deprivation and supplementation.
In order to study the role of oral somatosensory input in the ability of rats to adjust protein selection to changing metabolic conditions, trigeminally deafferented animals were subjected to nutritional stresses while being allowed to balance protein and carbohydrate intake from two separate dietary fractions. Partially trigeminally deafferented rats that had recovered a normal protein ratio (protein/total intake) underwent total food deprivation (Experiment 1) or intragastric (IG) supplementation of protein or carbohydrate suspensions (Experiment 2). In response to deprivation, control rats increased protein intake above ad-lib levels, but not carbohydrate intake. In response to IG supplementation, they decreased protein intake disproportionately more than carbohydrate intake when the fluid consisted of protein and vice versa when the fluid consisted of carbohydrate. The recovered deafferented rats showed no selective increase in protein intake after deprivation and no differential compensation to nutrient supplementation. This suggests that recovery of the protein ratio after partial trigeminal deafferentation is incomplete and that the compensatory mechanisms used cannot fully replace the function of trigeminal somatosensory input. The possible role of other orosensory and of postingestional factors for recovery is discussed.


Progesterone receptor modulators for endometriosis.
Endometriosis is defined as the presence of endometrial tissue (glands and stroma) outside the uterine cavity. This condition is oestrogen-dependent and thus is seen primarily during the reproductive years. Owing to their antiproliferative effects in the endometrium, progesterone receptor modulators (PRMs) have been advocated for treatment of endometriosis. To assess the effectiveness and safety of PRMs primarily in terms of pain relief as compared with other treatments or placebo or no treatment in women of reproductive age with endometriosis. We searched the following electronic databases, trial registers, and websites: the Cochrane Gynaecology and Fertility Group (CGFG) Specialised Register of Controlled Trials, the Central Register of Studies Online (CRSO), MEDLINE, Embase, PsycINFO, clinicaltrials.gov, and the World Health Organization (WHO) platform, from inception to 28 November 2016. We handsearched reference lists of articles retrieved by the search. We included randomised controlled trials (RCTs) published in all languages that examined effects of PRMs for treatment of symptomatic endometriosis. We used standard methodological procedures as expected by the Cochrane Collaboration. Primary outcomes included measures of pain and side effects. We included 10 randomised controlled trials (RCTs) with 960 women. Two RCTs compared mifepristone versus placebo or versus a different dose of mifepristone, one RCT compared asoprisnil versus placebo, one compared ulipristal versus leuprolide acetate, and four compared gestrinone versus danazol, gonadotropin-releasing hormone (GnRH) analogues, or a different dose of gestrinone. The quality of evidence ranged from high to very low. The main limitations were serious risk of bias (associated with poor reporting of methods and high or unclear rates of attrition in most studies), very serious imprecision (associated with low event rates and wide confidence intervals), and indirectness (outcome assessed in a select subgroup of participants). Mifepristone versus placebo One study made this comparison and reported rates of painful symptoms among women who reported symptoms at baseline.At three months, the mifepristone group had lower rates of dysmenorrhoea (odds ratio (OR) 0.08, 95% confidence interval (CI) 0.04 to 0.17; one RCT, n =352; moderate-quality evidence), suggesting that if 40% of women taking placebo experience dysmenorrhoea, then between 3% and 10% of women taking mifepristone will do so. The mifepristone group also had lower rates of dyspareunia (OR 0.23, 95% CI 0.11 to 0.51; one RCT, n = 223; low-quality evidence). However, the mifepristone group had higher rates of side effects: Nearly 90% had amenorrhoea and 24% had hot flushes, although the placebo group reported only one event of each (1%) (high-quality evidence). Evidence was insufficient to show differences in rates of nausea, vomiting, or fatigue, if present. Mifepristone dose comparisons Two studies compared doses of mifepristone and found insufficient evidence to show differences between different doses in terms of effectiveness or safety, if present. However, subgroup analysis of comparisons between mifepristone and placebo suggest that the 2.5 mg dose may be less effective than 5 mg or 10 mg for treating dysmenorrhoea or dyspareunia. Gestrinone comparisons Ons study compared gestrinone with danazol, and another study compared gestrinone with leuprolin.Evidence was insufficient to show differences, if present, between gestrinone and danazol in rate of pain relief (those reporting no or mild pelvic pain) (OR 0.71, 95% CI 0.33 to 1.56; two RCTs, n = 230; very low-quality evidence), dysmenorrhoea (OR 0.72, 95% CI 0.39 to 1.33; two RCTs, n = 214; very low-quality evidence), or dyspareunia (OR 0.83, 95% CI 0.37 to 1.86; two RCTs, n = 222; very low-quality evidence). The gestrinone group had a higher rate of hirsutism (OR 2.63, 95% CI 1.60 to 4.32; two RCTs, n = 302; very low-quality evidence) and a lower rate of decreased breast size (OR 0.62, 95% CI 0.38 to 0.98; two RCTs, n = 302; low-quality evidence). Evidence was insufficient to show differences between groups, if present, in rate of hot flushes (OR 0.79, 95% CI 0.50 to 1.26; two RCTs, n = 302; very low-quality evidence) or acne (OR 1.45, 95% CI 0.90 to 2.33; two RCTs, n = 302; low-quality evidence).When researchers compared gestrinone versus leuprolin through measurements on the 1 to 3 verbal rating scale (lower score denotes benefit), the mean dysmenorrhoea score was higher in the gestrinone group (MD 0.35 points, 95% CI 0.12 to 0.58; one RCT, n = 55; low-quality evidence), but the mean dyspareunia score was lower in this group (MD 0.33 points, 95% CI 0.62 to 0.04; low-quality evidence). The gestrinone group had lower rates of amenorrhoea (OR 0.04, 95% CI 0.01 to 0.38; one RCT, n = 49; low-quality evidence) and hot flushes (OR 0.20, 95% CI 0.06 to 0.63; one study, n = 55; low quality evidence) but higher rates of spotting or bleeding (OR 22.92, 95% CI 2.64 to 198.66; one RCT, n = 49; low-quality evidence).Evidence was insufficient to show differences in effectiveness or safety between different doses of gestrinone, if present. Asoprisnil versus placebo One study (n = 130) made this comparison but did not report data suitable for analysis. Ulipristal versus leuprolide acetate One study (n = 38) made this comparison but did not report data suitable for analysis. Among women with endometriosis, moderate-quality evidence shows that mifepristone relieves dysmenorrhoea, and low-quality evidence suggests that this agent relieves dyspareunia, although amenorrhoea and hot flushes are common side effects. Data on dosage were inconclusive, although they suggest that the 2.5 mg dose of mifepristone may be less effective than higher doses. We found insufficient evidence to permit firm conclusions about the safety and effectiveness of other progesterone receptor modulators.


Pleuropulmonary infections caused by Mycobacterium bovis: a re-emerging disease.
Between 1980 and 2003, 13 patients (0.95% of all cases of tuberculosis) at a 600-bed university hospital in Madrid, Spain, were diagnosed with Mycobacterium bovis infection. All 13 cases occurred between 1994 and 1999; the mean age of the patients was 50 years (range 23-83 years), and 77% were males. Four (30%) patients were also positive for human immunodeficiency virus (HIV). The most frequent localisation of the disease was the lung (ten patients; 77%). Seven patients, including four HIV-positive patients who died, had multidrug-resistant M. bovis infection. No other patient died, including two HIV-negative patients with multidrug-resistant disease.


Association between within-visit blood pressure variability, stroke, coronary heart disease, and cardiovascular mortality.
Long-term variability in systolic blood pressure (SBP) is associated with a higher risk of cardiovascular events. Little is known about any association between within-visit SBP variability, stroke, coronary heart disease (CHD), and cardiovascular (CV) death. Participants included adults ≥ 18 years who participated in the US National Health and Nutrition Examination Surveys from 1999 to 2012 linked to the national death index in 2012. Stroke was self-reported. SBP was obtained up to four times by a physician, using a manual sphygmomanometer according to standard procedures. Within-visit SBP variability was defined as the standard deviation of the BP measurements, stratified into quartiles. We evaluated the relationship between within-visit SBP variability and the odds of stroke or CHD using multivariable logistic regression, and with CV mortality, using multivariable Cox regression. Of the 27,987 adults, 16.4% were aged ≥ 65 years, 51.3% were female, 71.2% were white, and 10.7% were black. Factors associated with higher mean SBP variability included older age, hypertension, chronic kidney disease, peripheral artery disease, and smoking (all p < 0.05). The prevalence of stroke significantly increased across SBP variability quartiles, from 2.1% for quartile 1 to 3.7% for quartile 4 (p < 0.001). High SBP variability was associated with higher odds of stroke [odds ratio (OR) 1.8, 95% confidence interval (CI) 1.4-2.2], coronary heart disease (OR 2.0, 95% CI 1.6-2.4), and increased risk of CV mortality [hazard ratio (HR) 2.7, 95% CI 2.3-3.1]. The relationships were not observed after adjusting for covariables. Within-visit variability in SBP is associated with increased risks of stroke, coronary heart disease, and cardiovascular mortality, but the relationship is confounded by age and covariates.


The effect of social class on psychiatric psychological evaluations in patients with pulmonary tuberculosis.
The present study is a methodological examination in which the social and psychic background factors of 100 tuberculous patients, aged 20 to 45 years, were explored using psychiatric interview and psychological tests (MMPI, Rorschach, and Wartegg). The purpose of the study was to analyse the effect of social background factors on the psychiatric and psychological examination. With the help of correlation coefficients and three-factor factor analysis, the variable indicating the social class of the subject could be proved to correlate significantly to the projective test variables (Rorschach, Wartegg). No such correlation between the social group variable and those obtained in the psychiatric interview or the MMPI test could be demonstrated. On the basis of the projective tests, subjects in the lower social classes were considered more disturbed. It can be supposed that the background factors characteristic of lower social classes would contribute to the unfamiliar test situation, causing reactions disturbing the test performance. This suggests that the mentioned tests should be used with caution in the evaluation of personality disturbances.