Multivalent ion-induced re-entrant transition of carboxylated cellulose nanofibrils and its influence on nanomaterials' properties.
In this work, we identify and characterize a new intriguing capability of carboxylated cellulose nanofibrils that could be exploited to design smart nanomaterials with tuned response properties for specific applications. Cellulose nanofibrils undergo a multivalent counter-ion induced re-entrant behavior at a specific multivalent metal salt concentration. This effect is manifested as an abrupt increase in the strength of the hydrogel that returns upon a further increment of salt concentration. We systematically study this phenomenon using dynamic light scattering, small-angle X-ray scattering, and molecular dynamics simulations based on a reactive force field. We find that the transitions in the nanofibril microstructure are mainly because of the perturbing actions of multivalent metal ions that induce conformational changes of the nanocellulosic chains and thus new packing arrangements. These new aggregation states also cause changes in the thermal and mechanical properties as well as wettability of the resulting films, upon water evaporation. Our results provide guidelines for the fabrication of cellulose-based films with variable properties by the simple addition of multivalent ions.


[Mast cells and innervation of the wall of the hyperactive urinary bladder].
Anterior urinary bladder wall biopsy specimens were examined in 24 males and 4 females, aged 52 to 76 years, who had been suffering from the hyperactive urinary bladder for 1-10 years. Increases in the number and activity of interstitial mast cells and their degranulation and the symptoms of chronic immune inflammation were revealed. Neuromuscular spastic dysfunction of the detrusor is considered to result from the activation of mast cells.


The effect of antifreeze (ethylene glycol) on the survival and the life cycle of two species of necrophagous blowflies (Diptera: Calliphoridae).
Entomotoxicology involves the analysis of the presence and the effects of toxicological substances in necrophagous insects. Results obtained by entomotoxicological studies may assist in the investigation of both the causes and the time of death of humans and animals. Ethylene glycol (EG) is easy to purchase, sweet and extremely toxic. It may be consumed accidentally or purposefully, in an attempt to cause death for suicidal or homicidal intent. Several cases report fatalities of humans and animals. The present study is the first to examine the effects of EG on the survival, developmental rate and morphology of two blowfly species, (Diptera: Calliphoridae) typically found on corpses and carcasses: Lucilia sericata (Meigen) and L. cuprina (Wiedemann). Both species were reared on substrates (beef liver) spiked with three different concentrations of EG that could cause death in either a human or cat: 1/2LD50 (T1), LD50 (T2), 2LD50 (T3), in addition to a control treatment (C) with no EG. Results of this research show that: a) both species are unable to survive if reared on a food substrate spiked with the highest concentration of EG (T3), while lower and medium concentrations (T1, T2) affect, but not prevent, the survival and the completion of the life cycle of such species; b) adults of L. sericata eclose only in C and T1, while adults of L. cuprina in both C, T1, T2; however, c) the developmental time of both species reared in T1 and T2 is statistically slower than the control; d) the body length of the immatures of both of the species reared in T1 and T2 is statistically smaller than the control.


High performance liquid chromatography analysis of 1,25-dihydroxyvitamin D3 receptor in malignant cells. Correlation of effects on cell proliferation and receptor concentration.
Malignant cells were assayed for 1,25(OH)2D3 receptors and for the effects of 1,25(OH)2D3 on cell proliferation. The established lines studied were human promyelocytic leukemia (HL-60), T-cell lymphocytic leukemias (Molt-4, RPMI-8402, CEM), mouse leukemia (L1210), breast cancers (HT-39 and MCF-7) and a glioma (C-6) cultures. A TSK 3000 SW (0.75 X 60 cm) HPLC size exclusion column was used to characterize specific 1,25(OH)2D3 binding. We show for the first time that this column is capable of resolving the 3.2-3.5S 1,25(OH)2D3 mammalian receptor (Rs = 32 A) from the 5.5-6.0S form of the mammalian serum 25(OH)D3 transport receptor (Rs = 40 A). The molecular size of the 1,25(OH)2D3 receptors from these cancer cell lines was identical to that from rabbit intestine. HT-39, HL-60, MCF-7, Molt-4, C-6, RPMI-8402 and L1210 cells demonstrated specific 1,25(OH)2[3H]D3 binding (120, 90, 80, 45, 30 and 18 fmoles of sites/mg protein, respectively). Receptors were not detected in the CEM line. 1,25(OH)2D3 inhibited cell proliferation of HT-39, HL-60, MCF-7 and Molt-4 cells by 20% to 70%. In contrast, mouse leukemia (L1210) cells were stimulated to proliferate by this hormone. Proliferation of RPMI and CEM cells was not affected by 1,25(OH)2D3. We demonstrate that size-exclusion HPLC of 1,25(OH)2D3 binding proteins from mammalian intestine and cancer cells provided a rapid method for identification of specific 1,25(OH)2D3 receptors. Furthermore, in the cells studied, the presence and concentration of 1,25(OH)2D3 receptors qualitatively predicted the potency of this hormone to alter cell proliferation. We believe this assay will be useful for rapid analysis of human tumor receptor concentrations.


[Autonomic disorders in persons with asthenic syndrome and their correction with citrulline malate].
The paper presents the results of the investigation of psychoautonomic correlations in 15 patients with psychogenic asthenia. Spilberg's and Beck's tests as well as autonomic questionnaire were used for the psychologic testing. Sympathic-parasympathic correlations were investigated by means of cardiovascular tests, by evoked skin sympathetic potentials, variability of cardiac rhythm under conditions of different functional states. The patients had mild anxious-depressive and pronounced autonomic disorders with prevalence of cerebral sympathic-adrenal impacts, elevation of vagal influences in cardiovascular system, mediatory insufficiency of the sympathic sweating nerves and a decrease of the adaptive abilities of the regulatory systems. To correct the asthenic manifestations citrullin malate (stimol), a metabolic corrector produced by "Laboratories BIOCODEX" (France) was used. Stimol relieves psychoautonomic disorders by increasing both power capacities of the cells and synthesis of biologically active substances.


Revival of calcium-binding proteins for neuromorphology: secretagogin typifies distinct cell populations in the avian brain.
In the vertebrate nervous system, the Ca(2+)-binding proteins parvalbumin, calbindin and calretinin have been extensively used to elaborate the molecular diversity of neuronal subtypes. Secretagogin is a phylogenetically conserved Ca(2+)-binding protein, which marks neuronal populations largely distinct from other Ca(2+)-binding proteins in mammals. Whether secretagogin is expressed in nonmammalian vertebrates, particularly in birds, and, if so, with a brain cytoarchitectonic design different from that of mammals is unknown. Here, we show that secretagogin is already present in the hatchlings' brain with continued presence into adulthood. Secretagogin-immunoreactive neurons primarily accumulate in the olfactory bulb, septum, subpallial amygdala, hippocampus, hypothalamus, habenular nuclei and deep layers of the optic tectum of adult domestic chicks (Gallus domesticus). In the olfactory bulb, secretagogin labels periglomerular neurons as well as a cell continuum ascending dorsomedially, reaching the ventricular wall. Between the hippocampus and septal nuclei, the interconnecting thin septal tissue harbors secretagogin-immunoreactive neurons that contact the ventricular wall with their ramifying dendritic processes. Secretagogin is also present in the neuroendocrine hypothalamus, with particularly rich neuronal clusters seen in its suprachiasmatic and infundibular nuclei. Secretagogin expression identified a hitherto undescribed cell contingent along intratelencephalic cell-free laminae separating brain regions or marking the palliosubpallial boundary, as well as a dense neuronal population in the area corticoidea lateralis. In both the telencephalon and midbrain, secretagogin complemented the distribution of the canonical 'neuronal' Ca(2+)-binding proteins. Our findings identify novel neuronal subtypes, connectivity patterns in brain areas functionally relevant to olfaction, orientation, behavior as well as endocrine functions, which will help refine existing concepts on the neuronal diversity and organizational principles of the avian brain.


NT-proB natriuretic peptide, risk factors and asymptomatic left ventricular dysfunction: results of the SCReening Evaluation of the Evolution of New Heart Failure study (SCREEN-HF).
We assessed left ventricular dysfunction in a population at high risk for heart failure (HF), and explored associations between ventricular function, HF risk factors and NT-proB natriuretic peptide (NT-proBNP). 3550 subjects at high risk for incident HF (≥60 years plus ≥1 HF risk factor), but without pre-existing HF or left ventricular dysfunction, were recruited. Anthropomorphic data, medical history and blood for NT-proBNP were collected. Participants at highest risk (n = 664) (NT-proBNP highest quintile; >30.0 pmol/L) and a sample (n = 51) from the lowest NT-proBNP quintile underwent echocardiography. Participants in the highest NT-proBNP quintile, compared to the lowest, were older (74 years vs. 67 years; p < 0.001) and more likely to have coronary artery disease, stroke or renal impairment. In the top NT-proBNP quintile (n = 664), left ventricular systolic impairment was observed in 6.6% (95% CI: 4 to 8%) of participants and was associated with male gender, coronary artery disease, hypertension and NT-proBNP. At least moderate diastolic dysfunction was observed in 24% (95% CI 20 to 27%) of participants and was associated with diabetes and NT-proBNP. In this high risk population, NT-proBNP was associated with left ventricular systolic impairment (p < 0.001) and moderate to severe diastolic dysfunction (p < 0.001) after adjustment for age, gender, coronary artery disease, diabetes, hypertension and obesity. A high burden of ventricular dysfunction was observed in this high risk group. Combining NT-proBNP and HF risk factors may identify those with ventricular dysfunction. This would allow resources to be focused on those at greatest risk of progression to overt HF.


The spectrum of postinfectious encephalomyelitis.
The medical records of 52 consecutive patients diagnosed with postinfectious encephalitis/encephalomyelitis during the period from 1980 to 1998, including 29 males and 23 females, were reviewed. These patients were divided into three groups according to their clinical and neurodiagnostic characteristics: (1) group I: postinfectious encephalitis, 38 patients; (2) group II: acute disseminated encephalomyelitis (ADEM), 13 patients; (3) group III: multiphasic disseminated encephalomyelitis (MDEM), one patient. Fever, headache/vomiting, seizure and disturbance of consciousness were common clinical features in all patients, while pictures of pyramidal, extrapyramidal, brainstem, and spinal cord lesions were more often found in the group II and group III patients than in the group I patients. Magnetic resonance imaging (MRI) revealed abnormal lesions in six (60%) of ten group I patients, but all group II (n=7) and group III (n=1) patients who received MRI study showed abnormal signals in various regions of the brain including the cerebral hemisphere, basal ganglia, brainstem and cerebellum. Patients with ADEM and MDEM had a longer clinical course and more neurological sequelae than group I patients. This study demonstrates the breadth of the clinical spectrum of postinfectious encephalomyelitis. Thorough clinical observations and appropriate neurodiagnostic studies such as MRI are crucial for the diagnosis.


Epidemiology of multi-drug-resistant gram-negative bacteria: data from an university hospital over a 36-month period.
Multi-drug-resistant gram-negative rods (MRGN) are associated with increased morbidity and mortality. Little is known about the epidemiology of this group of pathogens in endemic situations. The aim of this study was to determine the epidemiology of MRGN in our facility during a 3-year period. Prospective surveillance of any patient colonized or infected with a MRGN during hospital stay from 2002 to 2004 was performed. Patients proven to harbour extended beta-lactamase (ESBL)-producing bacteria as well as cystic fibrosis (CF) patients were excluded. After culture of MRGN, patients were considered positive until three consecutive samples from all previously affected locations had been tested negative. Five hundred and three case-patients were enrolled accounting for 8081 isolation days and an incidence of 0.43 per 1000 patient days with an average length of stay of 37.5 days (average duration of isolation: 22.6 days). Sixty-six percent of case-patients were known to be positive at the time of admission. Fifty-one percent of MRGN were acquired within the hospital. The most frequently detected species was Pseudomonas aeruginosa. There were 108 case-patients with pan-resistant pathogens. Eight of 169 (4.7%) screened contact patients were found to be MRGN positive. In our hospital cross-transmission of MRGN seems to occur less frequently than cross-transmission of MRSA (9.0%) or ESBL (11.1%). To prevent nosocomial transmission it is recommended to isolate patients colonized or infected with MRGN in our hospital in single rooms. Because there are many immunocompromised patients in our facility we will continue our current infection control management until more data concerning MRGN are available.


Paget's disease of the lumbar spine: decompressive surgery following 17 years of bisphosphonate treatment.
We present a rare case of Paget's disease (PD) with involvement of the lumbar spine over a period of 19 years. We discuss the diagnostic process to rule out alternative diagnoses and medical and surgical treatment strategies. A 58-year-old man first diagnosed with PD in 1998 with solid involvement of the 4th lumbar vertebra has been undergoing periodic examinations over a period of 18 years. Since then, the patient has been treated conservatively with bisphosphonates. When conservative treatment options have been exhausted, surgery was indicated due to a progressively reduced ability to walk. Surgery with undercutting decompression via laminotomy was performed. PD was confirmed by biopsy. Bisphosphonate treatment was continued pre- and postoperatively. Follow-up examinations showed an improvement in clinical outcome measures. Conservative treatment remains the gold standard for PD with spinal involvement. This patient had been asymptomatic on bisphosphonate therapy for almost 17 years, but presented with new onset back pain. In such cases, fracture and rare conversion into sarcoma must be ruled out, and biopsy should be performed even in the absence of signs of malignancy. Currently, there are no clear treatment recommendations available in the literature regarding cases of PD with expansive growth and involvement of the spinal canal causing neurologic deficits. Furthermore, laminectomy has been shown to cause complications in up to 27% of cases with the risk of early postoperative death. In contrast, extended laminotomy and undercutting decompression should be considered.


Employment status and the risk of pregnancy complications: the Generation R Study.
This study explored the relationships of employment status, type of unemployment and number of weekly working hours, with a wide range of pregnancy outcomes. Information on employment characteristics and pregnancy outcomes was available for 6111 pregnant women enrolled in a population-based cohort study in the Netherlands. After adjustment for confounders, there were no statistically significant differences in risks of pregnancy complications between employed and unemployed women. Among unemployed women, women receiving disability benefit had an increased risk of preterm ruptured membranes (OR 3.16, 95% CI 1.49 to 6.70), elective caesarean section (OR 2.98, 95% CI 1.21 to 7.34) and preterm birth (OR 2.64, 95% CI 1.32 to 5.28) compared to housewives. Offspring of students and women receiving disability benefit had a significantly lower mean birth weight than offspring of housewives (difference: -93, 95% CI -174 to -12; and -97, 95% CI -190 to -5, respectively). In employed women, long working hours (>or=40 h/week) were associated with a decrease of 45 g in offspring's mean birth weight (adjusted analysis; 95% CI -89 to -1) compared with 1-24 h/weekly working hours. We found no indications that paid employment during pregnancy effects the health of the mother and child. However, among unemployed and employed women, women receiving disability benefit, students and women with long working hours during pregnancy were at risk for some adverse pregnancy outcomes. More research is needed to replicate these results and explain these findings. Meanwhile, prenatal care providers should be made aware of the risks associated with specific types of unemployment and long working hours.


Survey of contrast media use in southeastern U.S. hospitals.
This article reports the results of a survey of contrast media usage in hospitals in five southeastern states. Forty-three percent of hospitals surveyed reported using nonionic contrast media 100% of the time, while 71% used nonionic contrast more than 75% of the time. Hospitals with fewer than 399 beds showed an increase in universal nonionic contrast usage compared to hospitals with more than 400 beds. Survey results also showed that radiographers administer contrast media in 90% of hospitals. On average, radiographers administered contrast twice as often as radiologists. Hospitals favored selective protocols as the primary method to reduce nonionic contrast media usage. The low rate of reactions for nonionic contrast was the primary reason hospitals chose to use nonionic contrast.


Regulation of flowering time by Arabidopsis MSI1.
The transition to flowering is tightly controlled by endogenous programs and environmental signals. We found that MSI1 is a novel flowering-time gene in Arabidopsis. Both partially complemented msi1 mutants and MSI1 antisense plants were late flowering, whereas ectopic expression of MSI1 accelerated flowering. Physiological experiments revealed that MSI1 is similar to genes from the autonomous promotion of flowering pathway. Expression of most known flowering-time genes did not depend on MSI1, but the induction of SOC1 was delayed in partially complemented msi1 mutants. Delayed activation of SOC1 is often caused by increased expression of the floral repressor FLC. However, MSI1 function is independent of FLC. MSI1 is needed to establish epigenetic H3K4 di-methylation and H3K9 acetylation marks in SOC1 chromatin. The presence of these modifications correlates with the high levels of SOC1 expression that induce flowering in Arabidopsis. Together, the control of flowering time depends on epigenetic mechanisms for the correct expression of not only the floral repressor FLC, but also the floral activator SOC1.


[Accuracy of conservative treatment for infiltrating lobular breast cancer: a retrospective study of 217 infiltrating lobular carcinomas and 2155 infiltrating ductal carcinomas].
Prognosis factors used for the management of infiltrative lobular carcinoma (ILC) are not different from those for infiltrative cuctal carcinoma (IDC). The aim of our work was to evaluate indications for conservative treatment for patients with ILC and to compare the results to those of patients with IDC. MATERIAL AND METHODS. Between 1985 and 1999 we retrospectively compared cases of 217 ILC with cases of 2155 IDC treated in Centre Rene Gauducheau, Nantes. Clinical size of tumors was not different between ILC and IDC but pathological size>30 mm was more frequent for IDC. Good prognosis factors as pathological SBR classification I or II, positive hormone receptor, and the lack of axillary lymph node involvement, were more frequent for ILC. Clinical examination underestimated tumor size more frequently of ILC than IDC (p=0.02). Secondary mastectomy for involved margin was more frequent for ILC than IDC (p=0.001). For tumor with good prognosis factors, such as T<20mm, lack of lymph node involvement and SBR I or II with conservative treatment, 5 years local relapse were less frequent for ILC than IDC (p=0.025). Parameters to validate conservative or radical treatment are the same for ILC and IDC. Diagnosis of ILC should not influence decisions regarding surgical treatment.


Beyond the Swap Test: Optimal Estimation of Quantum State Overlap.
We study the estimation of the overlap between two unknown pure quantum states of a finite-dimensional system, given M and N copies of each type. This is a fundamental primitive in quantum information processing that is commonly accomplished from the outcomes of N swap tests, a joint measurement on one copy of each type whose outcome probability is a linear function of the squared overlap. We show that a more precise estimate can be obtained by allowing for general collective measurements on all copies. We derive the statistics of the optimal measurement and compute the optimal mean square error in the asymptotic pointwise and finite Bayesian estimation settings. Besides, we consider two strategies relying on the estimation of one or both states and show that, although they are suboptimal, they outperform the swap test. In particular, the swap test is extremely inefficient for small values of the overlap, which become exponentially more likely as the dimension increases. Finally, we show that the optimal measurement is less invasive than the swap test and study the robustness to depolarizing noise for qubit states.


Ophthalmic findings in patients with acquired immunodeficiency syndrome.
Ocular manifestations have been reported in up to 60% of individuals infected with human immunodeficiency virus (HIV) in the United States, and it is becoming increasing apparent that these ocular manifestations almost invariably reflect extent of progression of the disease. The prevalence of ocular abnormalities among acquired immunodeficiency syndrome (AIDS) patients in Taiwan has not been reported. In the present study, we examined and followed up the ophthalmic conditions of a total of 274 HIV-infected patients during the period from March 1993 to May 1999. The results show that cotton-wool spots was the most common ocular finding in this series of patients with AIDS, occurring in 22 (32.8%) of 67 AIDS patients. Cytomegalovirus (CMV) retinitis was the most commonly seen opportunistic ocular infection, occurring in 14 (20.8%) of 67 AIDS patients. These findings suggest that AIDS patients should be closely followed for signs of opportunistic ocular disease which may initially be asymptomatic. Close co-operation between the ophthalmologist and the internist is essential to ensure timely therapeutic intervention, which can decrease the risk of further complications including visual impairment and blindness.


Emerging Prognostic Biomarkers in Testicular Germ Cell Tumors: Looking Beyond Established Practice.
Testicular germ cell tumors are unique among solid cancers. Historically, this disease was deadly if progressed beyond the stage I. The implementation of cisplatin-based chemotherapy regimens has drastically changed the clinical outcome of metastatic testicular cancer. Several biomarkers were established to refine the prognosis by International Germ Cell Collaborative Group in 1997. Among these, the most significant were primary tumor site; metastatic sites, such as non-pulmonary visceral metastases; and the amplitude of serum tumor markers α-fetoprotein, β-chorionic gonadotropin, and lactate dehydrogenase. Since then, oncology has experienced discoveries of various molecular biomarkers to further refine the prognosis and treatment of malignancies. However, the ability to predict the prognosis and treatment response in germ cell tumors did not improve for many years. Clinical trials with novel targeting agents that were conducted in refractory germ cell tumor patients have proven to have negative outcomes. With the recent advances and developments, novel biomarkers emerge in the field of germ cell tumor oncology. This review article aims to summarize the current knowledge in the research of novel prognostic biomarkers in testicular germ cell tumors.


Transphyseal Fracture of the Distal Humerus.
Transphyseal fractures of the distal humerus often occur in children younger than 4 years as a result of birth trauma, nonaccidental trauma, or falls from a low height. It is important to identify and treat these injuries in a timely manner to ensure successful management. Most transphyseal fractures of the distal humerus are treated with closed reduction and percutaneous pinning with the aid of an elbow arthrogram. The most common complication following a fracture is cubitus varus caused by growth arrest, malunion, or osteonecrosis of the medial condyle. Normal carrying angles may be restored through corrective lateral closing wedge osteotomy.


Interaction between sodium-glucose co-transporter 2 and the sympathetic nervous system.
Sodium-glucose co-transporter 2 (SGLT2) inhibitors have taken centre stage in research and therapeutic efforts to modulate hard clinical outcomes in patients with heightened cardiovascular and renal risk profiles. Sympathetic nervous system (SNS) activation is a prominent feature across several cardiovascular and renal disease states. This review reflects on the remarkable clinical impact of SGLT2 inhibitors on cardiorenal outcomes, and navigates the evidence for a proposed clinically relevant interaction between SGLT2 and the SNS. SGLT2 inhibitors exert several pleiotropic effects beyond glucose-lowering. These include, but are not limited to, diuresis and natriuresis, blood pressure lowering, reduction in inflammation and oxidative stress, stimulation of erythropoiesis, and improvement in cardiac energetics. Treatment with SGLT2 inhibitors is associated with significant improvement in cardiorenal outcomes irrespective of diabetes status. In addition, evidence from preclinical studies points to a strong signal of a bidirectional temporal association between SGLT2 inhibition and reduction in SNS activation. Ongoing preclinical and clinical trials aimed at unravelling the proposed interaction between SGLT and SNS will enhance our understanding of their individual and/or collective contributions to cardiovascular disease progression and guide future targeted therapeutic interventions.


Five Regions of the Pea Genome Co-Control Partial Resistance to D. pinodes, Tolerance to Frost, and Some Architectural or Phenological Traits.
Evidence for reciprocal links between plant responses to biotic or abiotic stresses and architectural and developmental traits has been raised using approaches based on epidemiology, physiology, or genetics. Winter pea has been selected for years for many agronomic traits contributing to yield, taking into account architectural or phenological traits such as height or flowering date. It remains nevertheless particularly susceptible to biotic and abiotic stresses, among which Didymella pinodes and frost are leading examples. The purpose of this study was to identify and resize QTL localizations that control partial resistance to D. pinodes, tolerance to frost, and architectural or phenological traits on pea dense genetic maps, considering how QTL colocalizations may impact future winter pea breeding. QTL analysis revealed five metaQTLs distributed over three linkage groups contributing to both D. pinodes disease severity and frost tolerance. At these loci, the haplotypes of alleles increasing both partial resistance to D. pinodes and frost tolerance also delayed the flowering date, increased the number of branches, and/or decreased the stipule length. These results question both the underlying mechanisms of the joint control of biotic stress resistance, abiotic stress tolerance, and plant architecture and phenology and the methods of marker-assisted selection optimizing stress control and productivity in winter pea breeding.


New insights into the substrate-plasma polymer interface.
We describe a new method to characterize the underside (substrate interface) of plasma polymer (PP) thin films via their simple delamination from a sodium chloride single crystal substrate. By depositing the PP film onto an ionic bonded surface such as a sodium chloride crystal, the PP films investigated were easily delaminated from the substrate. Two plasma polymer films deposited from 1-bromopropane (BrPP) and allylamine (AAPP) were used to exemplify this new technique. The top- and underside (substrate-plasma polymer interface) of the films were examined by X-ray photoelectron spectroscopy (XPS) and synchrotron-based near edge X-ray adsorption fine structure (NEXAFS) spectroscopy. The results demonstrate that both films exhibit heterogeneous film structures with their chemical composition and levels of unsaturated species. The underside of both the BrPP and the AAPP films exhibited higher concentrations of oxygen, while their topsides contained higher levels of unsaturated species. These results provide useful insights into the BrPP and AAPP film formation and the chemistry. The delamination technique provides a simple method to analyze the early stages of film chemistry for plasma polymer thin films. Furthermore, this approach opens new opportunities for additional studies on the mechanisms and fundamentals of plasma polymer thin film formation with various monomers.


Technology-mediated interventions for enhancing medication adherence.
Despite effective therapies for many conditions, patients find it difficult to adhere to prescribed treatments. Technology-mediated interventions (TMIs) are increasingly being used with the hope of improving adherence. To assess the effects of TMI, intended to enhance patient adherence to prescribed medications, on both medication adherence and clinical outcomes. A secondary in-depth analysis was conducted of the subset of studies that utilized technology in at least one component of the intervention from an updated Cochrane review on all interventions for enhancing medication adherence. We included studies that clearly described an information and communication technology or medical device as the sole or major component of the adherence intervention. Thirty-eight studies were eligible for in-depth review. Only seven had a low risk of bias for study design features, primary adherence, and clinical outcomes. Eighteen studies used a TMI for education and/or counseling, 11 studies used a TMI for self-monitoring and/or feedback, and nine studies used electronic reminders. Studies used a variety of TMIs, with telephone the most common technology in use. Studies targeted a wide distribution of diseases and used a variety of adherence and clinical outcome measures. A minority targeted children and adolescents. Fourteen studies reported significant effects in both adherence and clinical outcome measures. This review provides evidence for the inconsistent effectiveness of TMI for medication adherence and clinical outcomes. These results must be interpreted with caution due to a lack of high-quality studies.


Comparison of three rapid influenza diagnostic tests with digital readout systems and one conventional rapid influenza diagnostic test.
Rapid influenza diagnostic tests (RIDTs) show variable sensitivities in clinical settings. We aimed to compare three digital RIDTs and one conventional RIDT. We assessed 218 nasopharyngeal swabs from patients between neonates and 90 years old in 2016. Three digital RIDTs were BUDDI, Sofia Influenza A+B Fluorescence Immunoassay, Veritor System Flu A+B assay. One conventional test was the SD Bioline Influenza Ag A/B/A(H1N1/2009). All test results were compared with those from the Anyplex Flu A/B Typing Real-time Detection real-time PCR. The four RIDTs were tested with diluted solutions from the National Institute for Biological Standards and Control (NIBSC) to compare lower detection limit. Cross-reactivity of four RIDTs within other respiratory viruses was identified. For influenza A, BUDDI, Sofia, Veritor, and Bioline showed 87.7%, 94.5%, 87.7%, and 72.6% sensitivity, and 100%, 97.7%, 96.5%, and 100% specificity. For influenza B, BUDDI, Sofia, Veritor, and Bioline showed 81.7%, 91.7%, 81.7%, and 78.3% sensitivity, and 100%, 95.3%, 100%, and 100% specificity, respectively. Each RIDT could detect diluted NIBSC solution, according to the level of dilution and specific influenza subtypes. Cross-reactivity of four RIDTs with other respiratory viruses was not noted. Sofia showed the highest sensitivity for influenza A and B detection. BUDDI and Veritor showed higher detection sensitivity than a conventional RIDT for influenza A detection, but similar results for influenza B detection. Further study is needed to compare the test performance of RIDTs according to specific, prevalent influenza subtypes.


Concise review: unraveling stem cell cocultures in regenerative medicine: which cell interactions steer cartilage regeneration and how?
Cartilage damage and osteoarthritis (OA) impose an important burden on society, leaving both young, active patients and older patients disabled and affecting quality of life. In particular, cartilage injury not only imparts acute loss of function but also predisposes to OA. The increase in knowledge of the consequences of these diseases and the exponential growth in research of regenerative medicine have given rise to different treatment types. Of these, cell-based treatments are increasingly applied because they have the potential to regenerate cartilage, treat symptoms, and ultimately prevent or delay OA. Although these approaches give promising results, they require a costly in vitro cell culture procedure. The answer may lie in single-stage procedures that, by using cell combinations, render in vitro expansion redundant. In the last two decades, cocultures of cartilage cells and a variety of (mesenchymal) stem cells have shown promising results as different studies report cartilage regeneration in vitro and in vivo. However, there is considerable debate regarding the mechanisms and cellular interactions that lead to chondrogenesis in these models. This review, which included 52 papers, provides a systematic overview of the data presented in the literature and tries to elucidate the mechanisms that lead to chondrogenesis in stem cell cocultures with cartilage cells. It could serve as a basis for research groups and clinicians aiming at designing and implementing combined cellular technologies for single-stage cartilage repair and treatment or prevention of OA.


Individualising the risks of statins in men and women in England and Wales: population-based cohort study.
To derive and validate risk algorithms so that the risks of four clinical outcomes associated with statin use can be estimated for individual patients. Prospective open cohort study using routinely collected data from 368 QResearch general practices in England and Wales to develop the scores. The scores were validated using two separate sets of practices-188 separate QResearch practices and 364 practices contributing to the THIN database. In the QResearch derivation cohort 225 922 new users of statins and 1 778 770 non-users of statins were studied. In the QResearch validation cohort 118 372 statin users and 877 812 non-users of statins were studied. In the THIN validation cohort, we studied 282 056 statin users and 1 923 840 non-users of statins were studied. Cox proportional hazards models in the derivation cohort to derive risk equations. Measures of calibration and discrimination in both validation cohorts. 5-Year risk of moderate/serious myopathic events; moderate/serious liver dysfunction; acute renal failure and cataract. The performance of three of the risk prediction algorithms in the THIN cohort was very good. For example, in women, the algorithm for moderate/serious myopathy explained 42.15% of the variation. The corresponding D statistics was 1.75. The acute renal failure algorithm explained 59.62% of the variation (D statistic=2.49). The cataract algorithm explained 59.14% of the variation (D statistic=2.46). The algorithms to predict moderate/severe liver dysfunction only explained 15.55% of the variation (D statistics=0.89). The performance of each algorithm was similar for both sexes when tested on the QResearch validation cohort. The algorithms to predict acute renal failure, moderate/serious myopathy and cataract could be used to identify patients at increased risk of these adverse effects enabling patients to be monitored more closely. Further research is needed to develop a better algorithm to predict liver dysfunction.


Recombination fraction and genetic linkage among key disease resistance genes (Co-42 /Phg-2 and Co-5/"P.ult") in common bean.
Anthracnose (Colletotrichum lindemuthianum), Angular leaf spot (Pseudocercospora griseola) and Pythium root rot are important pathogens affecting common bean production in the tropics. A promising strategy to manage these diseases consists of combining several resistance (R) genes into one cultivar. The aim of the study was to determine genetic linkage between gene pairs, Co-42 /Phg-2, on bean-chromosome Pv08 and Co-5/"P.ult" on-chromosome Pv07, to increase the efficiency of dual selection of resistance genes for major bean diseases, with molecular markers. The level of recombination was determined by tracking molecular markers for both BC3F6 and F2 generations. Recombination fraction r, among gene pairs, the likelihood of linkage, L(r), and logarithm of odds (LOD) scores were computed using the statistical relationship of likelihood which assumes a binomial distribution. The SCAR marker pair SAB3/PYAA19 for the gene pair Co-5/"P.ult" exhibited moderate linkage (r = 32 cM with a high LOD score of 9.2) for BC3F6 population, but relatively stronger linkage for the F2 population (r = 21 cM with a high LOD score of 18.7). However, the linkage among SCAR marker pair SH18/SN02, for the gene pair Co-42 /Phg-2 was incomplete for BC3F6 population (r = 47 cM with a low LOD score of 0.16) as well as F2 population (r = 44 cM with a low LOD score of 0.7). Generally, the weak or incomplete genetic linkage between marker pairs studied showed that all the four genes mentioned earlier have to be tagged with a corresponding linked marker during selection. The approaches used in this study will contribute to two loci linkage mapping techniques in segregating plant populations.


A national study of gender and racial differences in colorectal cancer screening among foreign-born older adults living in the US.
This study examined within group heterogeneity in colorectal cancer screening (CRCS) among foreign-born individuals. Data were from the 2010, 2013 and 2015 National Health Interview Survey data on older adults (N = 5529). In 2018, multivariable logistic regression analysis was conducted to determine whether gender and race/ethnicity were associated with CRCS after controlling for sociodemographic, health access, and acculturation related factors. Overall, Asians were significantly less likely to report CRCS compared with Whites (aOR 0.63, CI 0.52-0.76). Hispanic race/ethnicity was negatively associated with CRCS among men (aOR 0.68, CI 0.50-0.91), but not women compared to white men/women, respectively. Additionally, factors associated with CRCS include having fair/poor health, usual source of care, insurance, ≥ 10 years of US residency and citizenship. Screening disparities experienced by these immigrants may be addressed by improving healthcare access, especially for noncitizens and those with limited healthcare access.


[Parotid metastasis of renal adenocarcinoma: report of a case].
Renal adenocarcinomas are tumours which sometimes tend to remain clinically silent, and initially become evident through distant metastasis. This paper presents the case of a 54 year-old patient whose initial clinical evidence was parotid metastasis from kidney clear cells adenocarcinoma. The patient had a metastasis and renal tumour exeresis with application of supplementary chemotherapy and immunotherapy, presenting early pulmonary metastasis which remains currently unchangeable. Some comments apropos of distant metastasis, its prognosis and regression in renal tumours are made.


[Prevention of premature labor].
The prevention of premature birth remains a primary challenge to obstetricians because of its decisive effects with regard to mortality and morbidity. While causal treatment is still not available, the problems and necessity of calculating the related risks, and particularly the early identification of the symptoms of imminent premature delivery are discussed with pregnant women in Maternity Centers. At-the present time, the inhibition of labor using medication in different forms is the key approach to the symptomatic treatment of "genuine" dispositions to premature delivery. With a view to the related requirement for an optimal extension of the gestational period, the author also discusses premature birth as a function of different types of placental dysfunction and refers to the search for suitable treatment. The author presents selected results which indicate the role obstetrics can play in controlling the mortality and morbidity of premature babies who remain underweight to the same extent as in the past. This serves to stress the demand for the "prevention of very immature births" as a principal task facing the obstetrician.


Mussel-Inspired Multivalent Linear Polyglycerol Coatings Outperform Monovalent Polyethylene Glycol Coatings in Antifouling Surface Properties.
Biofouling constitutes a major challenge in the application of biosensors and biomedical implants, as well as for (food) packaging and marine equipment. In this work, an antifouling surface coating based on the combination of mussel-inspired dendritic polyglycerol (MI-dPG) and an amine-functionalized block copolymer of linear polyglycerol (lPG-b-OA11, OA = oligo-amine) was developed. The coating was compared to a MI-dPG surface which was postfunctionalized with commercially available amine-terminated polyethylene glycol (HO-PEG-NH2) of similar molecular weight. In the current work, these coatings were compared in their chemical stability, protein fouling characteristics, and cell fouling characteristics. The lPG-b-OA11-functionalized coating showed high chemical stability in both phosphate buffered saline (PBS) and sodium dodecyl sulfate (SDS) solutions and reduced the adhesion of fibrinogen from human plasma with 99% and the adhesion of human serum albumin with 96%, in comparison to the bare titanium dioxide substrate. Furthermore, the proliferation of human umbilical vein endothelial cells (HUVECs) was reduced with 85% when the lPG-b-OA11 system was compared to bare titanium dioxide. Additionally, a reduction of 94% was observed when the lPG-b-OA11 system was compared to tissue culture polystyrene.


Associations between local COVID-19 case rates, pandemic-related financial stress and parent and child functioning.
The COVID-19 global crisis led to unprecedented disruption of family routines and heightened family stress. This study examines the effects of local COVID-19 case rates and pandemic-related financial stress on family processes (e.g., caregiving behavior) and school-aged children's outcomes. The project was launched shortly after stay-at-home orders began in the U.S. Data were collected online using Amazon's Mechanical Turk (MTurk), which allowed for nationwide recruitment. Using four waves of data (N = 308), with initial data collected between 4/20/20 and 5/6/20 and 2-3 weeks between each wave, this study examined the influence of local rates of COVID-19 infection on pandemic-related financial stress and the association of these constructs on maternal psychological distress and negative parenting. We also examined the potential cascade linking COVID-19 case rates and pandemic-related financial stress with child behavior problems via maternal psychological distress and negative parenting behavior, while controlling for prior child behavior problems. In line with hypotheses, higher Wave 1 (W1) pandemic-related financial stress was significantly associated with higher Wave 2 (W2) maternal psychological distress, which was significantly associated with higher Wave 3 (W3) negative parenting, which, in turn, was significantly associated with higher Wave 4 (W4) child behavior problems. In addition, the indirect effect of W1 pandemic-related financial stress on W3 negative parenting through W2 maternal psychological distress was significant. Higher W1 local COVID-19 case rates were significantly related to higher W3 negative parenting. Results suggest local COVID-19 case rates and pandemic-related financial stressors are associated with poorer child and family functioning. Implications for policy and practice are discussed. (PsycInfo Database Record (c) 2022 APA, all rights reserved).


Beta-adrenergic stimulation contributes to incretin effect in conscious dogs.
Oral glucose administration increases insulin secretion to a greater extent than peripheral glucose infusion (incretin effect). It also augments protal vein blood flow, hepatic uptake of glucose, and fractional hepatic extraction of insulin. The mechanisms for these various effects are not known but could involve both neurogenic stimuli and gut hormones. The present studies examined the effect of a non-nutrient drink, 1 g/kg body wt oral mannitol, on these parameters during an intravenous glucose infusion in conscious dogs. The dogs had chronically implanted Doppler flow probes on the portal vein and hepatic artery and catheters in the portal vein, hepatic vein, and femoral artery. After a 30-min control period, an infusion of atropine, propranolol, phentolamine, or propranolol and phentolamine was begun. Thirty minutes later, glucose (13 mg.kg-1.min-1) was then infused into a peripheral vein for 120 min with continuation of the atropine and adrenergic blockade. Water or mannitol (10% solution) was administered orally 50 min after the initiation of the glucose infusion. Mannitol, but not water, significantly enhanced the insulin response to intravenous glucose, as indicated by higher insulin concentrations in the portal vein as well as more rapid reduction of the plasma glucose. This incretin effect was significantly attenuated by infusion of propranolol but not by atropine or phentolamine. Mannitol did not increase portal vein blood flow or have any effect on the hepatic uptake of glucose or the fractional hepatic extraction of insulin. Thus absorption of nutrient is not necessary for the incretin effect but is for the increased portal vein blood flow and increased fractional extraction of insulin.(ABSTRACT TRUNCATED AT 250 WORDS)


Travel-related leptospirosis: a series of 15 imported cases.
Leptospirosis belongs to the spectrum of travel-related infections. We retrospectively studied all the consecutive cases of travel-related leptospirosis seen in our department between January 2008 and September 2011. Patients were included with a clinical picture compatible with the disease within 21 days after return, the presence of a thermoresistant antigen or IgM antibodies, Elisa ≥ 1 /400, and a positive microagglutination test (MAT) ≥ 1/100. Fifteen leptospirosis cases were evaluated. Exposure occurred in Asia (47%), Africa (20%), the Caribbean (20%), and Indian Ocean (13%). Fourteen patients were infected during water-related activities. On admission the most frequent symptoms were fever (100%), headache (80%), and digestive disorders (67%). Relevant laboratory findings included impaired liver function tests (100%), lymphocytopenia (80%), thrombocytopenia (67%), and elevated C-reactive protein (CRP) (67%). Our cases were confirmed by MAT that found antibodies against nine different serovars. Seven patients were cured with amoxicillin, four with doxycycline, two with ceftriaxone, one with ceftriaxone, doxycycline, and spiramycin, whereas one recovered spontaneously (retrospective diagnosis). Eight patients were hospitalized. All patients recovered. Our cases involved nine different serovars. They were related to travel in Asia, Africa, and the Caribbean. Bathing or other fresh-water leisure activities (canoeing, kayaking, rafting) are the most likely at-risk exposure. Any traveler with fever and at-risk exposure should be investigated for leptospirosis.


Change in follicle-stimulating hormone and estradiol across the menopausal transition: effect of age at the final menstrual period.
To determine whether patterns of change in serum estradiol (E2) and FSH across the menopausal transition were associated with age at the final menstrual period (FMP). The Study of Women's Health Across the Nation (SWAN) is a seven-site, multiethnic, longitudinal study of the menopausal transition being conducted in 3302 menstruating women who were aged 42-52 yr at the 1996 study baseline. Annually collected serum was assayed for E2 and FSH levels. Patterns of hormone change were evaluated in the 1215 women with a documented natural FMP by follow-up visit 9 (2006) using semiparametric stochastic and piecewise linear mixed modeling. The FSH pattern across the menopausal transition began with an increase 6.10 yr before the FMP, an acceleration 2.05 yr before the FMP, deceleration beginning 0.20 yr before the FMP, and attainment of stable levels 2.00 yr after the FMP, independent of age at the FMP, race/ethnicity, or smoking status. Obesity attenuated the FSH rise and delayed the initial increase to 5.45 yr before the FMP. The mean E2 concentration did not change until 2.03 yr before the FMP when it began decreasing, achieving maximal rate of change at the FMP, then decelerating to achieve stability 2.17 yr after the FMP. Obesity, smoking behavior, and being Chinese or Japanese were associated with some variation in E2 levels but not the pattern of E2 change. Time spans and overall patterns of change in serum FSH and E2 across the menopausal transition were not related to age at FMP or smoking, whereas time spans but not overall patterns were related to obesity and race/ethnicity.


Better sensitivity to linear and nonlinear trends with position than with color.
Useful data visualizations have the potential to leverage the visual system's natural abilities to process and summarize simple and complex information. Here, we tested whether the design recommendations made for pairwise comparisons generalize to the detection of trends. We created two different types of graphs: line graphs and stripplots. These graphs were created from identical datasets that simulated temperature changes across time. These datasets varied in the type of trend (linear and exponential). Human observers performed a trend detection task for which they judged whether the trend in temperature over time was increasing or decreasing. Participants were more sensitive to trend direction with line graphs compared to stripplots. Participants also demonstrated a systematic bias to respond that the trend was increasing for line graphs. However, this bias decreased with increasing sensitivity. Despite the better sensitivity to line graphs, more than half of the participants found the stripplots more appealing and liked them more than the line graphs. In conclusion, our results indicate that, for trend detection, depicting data with position (line graphs) leads to better performance compared to depicting graphs with color (stripplots). Yet, graphs with color (stripplots) were preferred over the line graphs, suggesting that there may be a tradeoff between the aesthetic design of the graphs and the precision in communicating the information.


Visual field defects in Alzheimer's disease patients may reflect differential pathology in the primary visual cortex.
The aim of this study was to test the hypothesis that differences in density of senile plaques (SP) and neurofibrillary tangles (NFT) in the cuneal and lingual gyri of area V1 of the visual cortex could explain the predominantly inferior visual field defects seen in patients with Alzheimer's disease (AD). The density of SP and NFT was measured in the cuneal and lingual gyri of 18 AD patients. In 7/18 (39%) patients, the density of SP and/or NFT was significantly greater in the cuneal compared with the lingual gyri. In 3/18 (17%) patients, densities were greater in the lingual than the cuneal gyri and in 8/18 (44%) patients there were no significant differences among gyri. The data suggest that pathological differences between cuneal and lingual gyri could contribute to the reported visual field defects in some AD patients.


Childhood Adversities and Substance Misuse Among the Incarcerated: Implications for Treatment and Practice in Correctional Settings.
Incarcerated populations have high rates of childhood adversities and substance use problems. Moreover, childhood adversities are well-documented predictors of substance misuse. To investigate the impact of childhood sexual and physical abuse, caregiver abuse of drugs or alcohol, and time spent in foster care on several substance misuse outcomes. Data comes from a sample of 16,043 incarcerated men and women in the United States Survey of Inmates in State and Federal Facilities. Bivariate analyses revealed differences by sex in childhood adversities and socioeconomic characteristics. Logistic regression analyses assessed the data for a link between childhood adversities and substance misuse after adjusting for other variables. Analyses were stratified by sex to show differences in predictors of substance misuse between men and women. Childhood adversities increased the risk of many substance misuse outcomes. The prevalence of physical abuse, sexual abuse, foster care, and caretaker abuse of drugs or alcohol were greatest for inmates who reported injecting and sharing drugs. Growing up with a caregiver that used drugs or alcohol was a consistent predictor of increased risk of substance misuse for men and women. However, childhood sexual abuse increased risk for only women. Inmates who experience physical abuse, sexual abuse, foster care involvement and caretakers who use drugs and alcohol are at an increased risk of substance misuse, injecting drug use and syringe sharing. Implications suggest correctional HIV prevention and substance misuse programs must address unresolved trauma and important gender differences.


Phenotypic variation in nurse traits and community feedbacks define an alpine community.
Much is known about facilitation, but virtually nothing about the underlying genetic and evolutionary consequences of this important interaction. We assessed the potential of phenotypic differences in facilitative effects of a foundation species to determine the composition of an Alpine community in Arizona. Two phenotypes of Geum rossii occur along a gradient of disturbance, with 'tight' competitive cushions in stable conditions and 'loose' facilitative cushions in disturbed conditions. A common-garden study suggested that field-based traits may have a genetic basis. Field experiments showed that the reproductive fitness of G. rossii cushions decreased with increasing facilitation. Finally, using a dual-lattice model we showed that including the cost and benefit of facilitation may contribute to the co-occurrence of genotypes with contrasting facilitative effects. Our results indicate that changes in community composition due to phenotypic differences in facilitative effects of a foundation species may in turn affect selective pressures on the foundation species.


Physiological and Metabolic Responses of Freshwater and Brackish-Water Strains of Microcystis aeruginosa Acclimated to a Salinity Gradient: Insight into Salt Tolerance.
Proliferation of microcystin (MC)-producing Microcystis aeruginosa in brackish waters has been described in several locations and represents a new concern for public and environmental health. While the impact of a sudden salinity increase on M. aeruginosa physiology has been studied, less is known about the mechanisms involved in salt tolerance after acclimation. This study aims to compare the physiological responses of two strains of M. aeruginosa (PCC 7820 and PCC 7806), which were isolated from contrasted environments, to increasing salinities. After acclimation, growth and MC production rates were determined and metabolomic analyses were conducted. For both strains, salinity decreased the biovolume, growth, and MC production rates and induced the accumulation of polyunsaturated lipids identified as monogalactosyldiacylglycerol. The distinct salt tolerances (7.5 and 16.9) obtained between the freshwater (PCC 7820) and the brackish-water (PCC 7806) strains suggested different strategies to cope with the osmotic pressure, as revealed by targeted and untargeted metabolomic analyses. An accumulation of trehalose as the main compatible solute was obtained in the freshwater strain, while sucrose was mainly accumulated in the brackish one. Moreover, distinct levels of glycine betaine and proline accumulation were noted. Altogether, metabolomic analysis illustrated a strain-specific response to salt tolerance, involving compatible solute production.IMPORTANCE Blooms of Microcystis aeruginosa and the production of microcystins are major issues in eutrophic freshwater bodies. Recently, an increasing number of proliferations of M. aeruginosa in brackish water has been documented. The occurrence of both M. aeruginosa and microcystins in coastal areas represents a new threat for human and environmental health. In order to better describe the mechanisms involved in Microcystis sp. proliferation in brackish water, this study used two M. aeruginosa strains isolated from fresh and brackish waters. High salinity reduced the growth rate and microcystin production rate of M. aeruginosa In order to cope with higher salinities, the strains accumulated different cyanobacterial compatible solutes, as well as unsaturated lipids, explaining their distinct salt tolerance.


The Anoikis Effector Bit1 Inhibits EMT through Attenuation of TLE1-Mediated Repression of E-Cadherin in Lung Cancer Cells.
The mitochondrial Bcl-2 inhibitor of transcription 1 (Bit1) protein is part of an anoikis-regulating pathway that is selectively dependent on integrins. We previously demonstrated that the caspase-independent apoptotic effector Bit1 exerts tumor suppressive function in lung cancer in part by inhibiting anoikis resistance and anchorage-independent growth in vitro and tumorigenicity in vivo. Herein we show a novel function of Bit1 as an inhibitor cell migration and epithelial-mesenchymal transition (EMT) in the human lung adenocarcinoma A549 cell line. Suppression of endogenous Bit1 expression via siRNA and shRNA strategies promoted mesenchymal phenotypes, including enhanced fibroblastoid morphology and cell migratory potential with concomitant downregulation of the epithelial marker E-cadherin expression. Conversely, ectopic Bit1 expression in A549 cells promoted epithelial transition characterized by cuboidal-like epithelial cell phenotype, reduced cell motility, and upregulated E-cadherin expression. Specific downregulation of E-cadherin in Bit1-transfected cells was sufficient to block Bit1-mediated inhibition of cell motility while forced expression of E-cadherin alone attenuated the enhanced migration of Bit1 knockdown cells, indicating that E-cadherin is a downstream target of Bit1 in regulating cell motility. Furthermore, quantitative real-time PCR and reporter analyses revealed that Bit1 upregulates E-cadherin expression at the transcriptional level through the transcriptional regulator Amino-terminal Enhancer of Split (AES) protein. Importantly, the Bit1/AES pathway induction of E-cadherin expression involves inhibition of the TLE1-mediated repression of E-cadherin, by decreasing TLE1 corepressor occupancy at the E-cadherin promoter as revealed by chromatin immunoprecipitation assays. Consistent with its EMT inhibitory function, exogenous Bit1 expression significantly suppressed the formation of lung metastases of A549 cells in an in vivo experimental metastasis model. Taken together, our studies indicate Bit1 is an inhibitor of EMT and metastasis in lung cancer and hence can serve as a molecular target in curbing lung cancer aggressiveness.


An analytical approximation of depth-dose distributions for therapeutic proton beams.
A simple analytical approximation for the proximal part of the depth-dose distribution of a spread-out-Bragg-peak (SOBP) proton beam is derived. The basic assumption made is that the range-energy relationship follows a power law. The analytical formula depends only on the ratio of the distance from the proximal edge of the SOBP and the width of the SOBP. A comparison with measurements and with exact numerical calculations reveals a maximum deviation of 5% and a typical deviation of less than 2% of the target dose. The model comprises an analytical expression for the weighting of individual Bragg peaks as a function of the range, which is necessary to obtain an SOBP of the desired width and depth. Finally, an analytical expression for the total energy released in normal tissue is found by integrating the depth-dose distribution.


Mollicellins: mutagenic and antibacterial mycotoxins.
Eight mollicellins (depsidones) were assayed for mutagenicity and antibacterial activity in Salmonella/microsome tests involving histidine reversion and forward mutation to 8-azaguanine resistance. Two of them, mollicellins C and E, which contain a 3-methylbutenoic acid moiety, were mutagenic and bactericidal for Salmonella typhimurium in the absence of microsomes. Mollicellins D and F, each containing a chlorine atom, were bactericidal but not mutagenic. The mutagenic activity was completely abolished and the antibiotic activity was greatly reduced by coincubation with rat liver microsomes.


Differentiation of Salmonella strains from the SARA, SARB and SARC reference collections by using three genes PCR-RFLP and the 2100 Agilent Bioanalyzer.
Rapid molecular typing methods are important tools in surveillance and outbreak investigations of human Salmonella infections. Here we described the development of a three-genes PCR-RFLP typing method for the differentiation of Salmonella species, subspecies and serovars using the Agilent 2100 Bioanalyzer. The fliC, gnd, and mutS genes were PCR-amplified in 160 Salmonella strains representing the two Salmonella species, six subspecies, and 41 different serovars of S. enterica subspecies enterica. PCR products were individually cut with two different restriction enzymes and the resulting 930 restriction patterns were collected using the Agilent 2100 Bioanalyzer followed by cluster analysis. Both species of Salmonella were differentiated by conventional PCR. All of S. bongori tested were gnd PCR negative due to a mismatch at the 3'-end in one the PCR primers. Salmonella subspecies were differentiated into third-teen homogeneous groups representing each of the six subspecies by cluster analysis of restriction patterns generated from the mutS gene cut with AciI. S. enterica subspecies enterica serovars were further differentiated by the combination of the three target genes and five out the six sets of restriction patterns with a discriminatory power of 0.9725 by cluster analysis. The combined RFLP results of five sets of restriction patterns allowed us to assign each of the 160 strains to one of 128 restriction types. During inoculation studies we were able to identify S. Saintpaul and Typhimurium from 24 h pre-enrichment samples using the described method. The use of fliC, gnd, and mutS PCR-RFLP with the Agilent 2100 Bioanalyzer can provide an accessible and automated alternative method for differentiation of Salmonella pathogens.


Caragana sinica (Buc'hoz) Rehd. (jin ji er) polysaccharide regulates the immune function and intestinal microbiota of cyclophosphamide (CTX) induced immunosuppressed mice.
Caragana sinica (Buc'hoz) Rehd. is a plant widely grown in Yunnan, China, for both medicinal and edible purposes. The "National Compilation of Chinese Herbal Medicine" describes its nature as "slightly temperate and sweet". Caragana sinica is usually medicated with whole herbs, the main function is to replenish the kidneys and stop bleeding. Caragana sinica was used in folk medicine in Chuxiong, Yunnan, to treat deficiency colds, fatigue, fever, cough, hypertension, and other diseases. This article investigates the structural characteristics of Caragana sinica polysaccharide (CSP) and explores its immune-regulatory activity and molecular biological mechanisms in cyclophosphamide-induced immunosuppressed mice, as well as its effects on intestinal bacteria. With the water-extraction and alcohol-precipitation method, Caragana sinica polysaccharide were extracted, obtaining CSP by purification. A variety of methods and techniques have been used to analyze the chemical properties and structural characteristics of CSP. Immunosuppressive mice model was established through intraperitoneal injection of cyclophosphamide (CTX) to study the immune-regulatory effects and mechanisms of CSP. The data indicated that CSP is a neutral heteropolysaccharide mainly composed of arabinose and galactose. This article uses immunosuppressive mice induced by cyclophosphamide (CTX) as the model. The results showed that CSP can promote the immune function of CTX treated immunosuppressed mice and regulate the diversity and composition of intestinal microbiota. CSP can increase macrophage phagocytosis, NK cell killing activity, and lymphocyte proliferation activity. It can also repair the index and morphological damage of the thymus and spleen. And by binding to the TLR4 receptor, MyD88 was activated and interacted with TRAF6 to promote the transfer of NF-κB into the nucleus. Thereby promoting cytokine release and increasing the production of IL-1β, IL-6, IL-10, TNF-α, IgA, and IgG in the serum. CSP also effectively alleviated the liver damage caused by CTX through antioxidant activity. Furthermore, CSP can dramatically affect the intestinal microbiota and the body's immunity by boosting the relative presence of Bacteroides and Verrucamicrobiota. Research results indicated that CSP can regulate the immune function of mice, providing a basis for developing CSP as a potential immune modulator and functional food.


Characterization of Periodic Acid-Schiff-Positive Granular Deposits in the Hippocampus of SJL/J Mice.
Periodic acid-Schiff (PAS)-positive granular deposits in the hippocampus have been reported previously in certain inbred mouse strains such as C57BL/6 and the senescent-accelerated mouse prone-8. Here, we report for the first time that similar PAS-positive granules age dependently occur in SJL/J mice, a mouse strain, for instance, used for central nervous system disease research. Moreover, similar granules stained intensely positive with a polyclonal antibody directed against p75 neurotrophin receptor (p75(NTR)). Granular deposits were absent in young mice and developed with aging in CA1 and CA2 regions of the hippocampus. Interestingly, granules significantly diminished in SJL/J mice previously treated with cuprizone, a copper chelator, which is a useful model for toxic demyelination. The presented data support the idea that granules might be the result of an imbalance of redox-active metals and/or a dysregulation of complementary mechanisms that regulate their homeostasis in astrocyte-neuron coupling, respectively. It remains to be determined whether the unsuspected immunoreactivity for p75(NTR) represents a false-positive reaction or whether p75(NTR) is crucially involved in the pathogenesis of age-related hippocampal granular deposits in mice.


Protein expression and localization of ABC transporters in pancreatic adenocarcinoma: Prognostic role of ABCC8.
ATP-binding cassette (ABC) transporters translocate various substances across cellular membranes. Their deregulation may cause cancer drug resistance or perturbations in the supply of building blocks for cancer cells and modify patients' prognosis. This study investigated protein expression and cellular localization of the previously suggested putative prognostic biomarkers - ABCB2/TAP1, ABCC7/CFTR, ABCC8/SUR1, and ABCD4 in patients with pancreatic ductal adenocarcinoma (PDAC). Protein expression and localization were assessed by immunohistochemistry in formalin-fixed paraffin-embedded primary tumor tissue blocks of 61 PDAC patients and associated with clinical data and the survival of patients. No CFTR protein expression was observed in PDAC, while TAP1 and ABCC8 were expressed predominantly in the cytoplasm of tumor cells. Most samples (81 %) had detectable both membranous and cytoplasmic ABCD4 staining and 42 % had ABCD4 expressed in the apical orientation. Negative membranous ABCD4 staining was significantly more frequent in advanced stage III or IV tumors (p = 0.022). Small or medium counts of individual ABCC8-positive cells in the stroma surrounding tumor tubules were also more often found in stage III or IV (p = 0.044). Patients with moderate or strong ABCC8 cytoplasmic staining intensity in tumor cells had a 3.5-fold higher risk of disease progression than those with weak staining (p = 0.002). The study shows for the first time that the cytoplasmic ABCC8 protein expression has prognostic value in PDAC.


Predictors of occupational status six months after hospitalization in persons with a recent onset of psychosis.
Participation in work or school activity is an important aspect of social functioning in individuals with a recent onset of psychosis. We measured the predictors of occupational status 6 months following hospitalization in a sample of 71 adults with recent onset affective or non-affective psychosis. At baseline, participants were evaluated with cognitive measures including the Wisconsin Card Sorting Test, symptom rating scales, the Modified Vocational Index to assess occupational status, and other clinical and demographic measures. At follow-up, occupational status was re-assessed and categorized as whether or not the patient had any current work or school activity. Results of a backwards stepwise logistic regression examining occupational status at follow-up yielded a significant model with the following independent predictors: a higher baseline level of cognitive functioning as measured by performance on the Wisconsin Card Sorting Test lower level of baseline depression as measured by the Calgary Depression Scale; and better socioeconomic status as measured by level of maternal education. Cognitive functioning, but not psychosis severity, is a significant independent predictor of occupational status early in the course of psychotic illness.


Multiple environmental contexts and communication in pygmy marmosets (Cebuella pygmaea).
There are multiple components to the concept of Umwelt experienced by an organism that may constrain the type and structure of communication signals as well as the usefulness of these signals. To illustrate the impact of these multiple environmental components, the authors used signals of the pygmy marmoset (Cebuella pygmaea), a small primate from the western Amazon. The authors summarize studies to show how the physical effects of the habitat; effects of other species, both predators and nonpredators; anthropogenic effects on the communication environment; within-group and between-groups influences other pygmy marmosets exert; and ontogeny influence the structure and usage of vocal signals. Communication within a species can be understood only in consideration of each of these contexts.


Does the Cardiologist Have a Key Role in Long-Term Management of Hypertension?
Hypertension is a widespread chronic condition which is usually treated with hypertensive drugs. However, 50% of hypertensive patients do not achieve control of their blood pressure below the standard target of 140/90 mmHg when treated with a single antihypertensive drug. Generally, hypertension specialists have a key role in managing hypertensive patients. A retrospective case note review based on observations made in a cardiological outpatient clinic in Germany was carried out to assess whether the recommendation given by hypertension specialists were followed. The aim was to lower the blood pressure to < 130/85 mmHg over a period of six months by administering the new antihypertensive drug Zaneril® (lercanidipine/enalapril). Twenty-four hour blood pressure profiles were monitored a fortnight and six months later. Of the 130 patients, whose average blood pressure was 163/87 mmHg before receiving hypertensive treatment, only 44 (34%) were still on Zaneril® therapy six months later. Eighty-four patients (65%) did not turn up for follow-up examinations. The blood pressure of patients who were under Zaneril® therapy for the whole six months was better adjusted than that of patients who changed their treatment in the meantime (133/78 mmHg vs. 139/80 mmHg). Specialists have only little influence on the long-term therapy of hypertensive patients.


Successes and challenges in translational research: the development of targeted therapy for gastrointestinal stromal tumours.
Gastrointestinal stromal tumors (GISTs) are mesenchymal neoplasms that most commonly affect the stomach or small intestine, but that can occur anywhere within the gastrointestinal tract. The annual incidence of GISTs is estimated to be 10 to 20 cases per million. Traditionally, the only effective treatment was surgical resection, and recurrences were common even with complete removal of tumor. Systemic therapy with standard cytotoxic chemotherapeutic agents was completely ineffective. A series of exciting laboratory developments led to the discovery that the small molecule tyrosine kinase inhibitor STI571 (imatinib mesylate) has significant clinical activity in GISTs, representing one of the first therapeutic uses of a targeted agent directed against a solid tumor. In this article we will describe the key steps that led to the initial clinical trials of imatinib in GISTs, and we will also discuss the process of incorporating this novel therapy into mainstream oncologic practice.


Cell adhesion and sorting in embryoid bodies derived from N- or E-cadherin deficient murine embryonic stem cells.
The primitive endoderm epithelial structure in mouse blastocysts forms following cell differentiation and subsequent sorting, and this two-step process can be reproduced in vitro using an embryoid body model. We found that in the chimeric embryoid bodies consisting of paired wildtype and E-cadherin null ES cells, the wildtype sorted to the center and were enveloped by the less adhesive E-cadherin null cells, in accord with Steinberg's hypothesis. However, wildtype and N-cadherin null ES cells intermixed and did not segregate, a situation that may be explained by Albert Harris' modified principle, which incorporates the unique properties of living cells. Furthermore, in chimeric embryoid bodies composed of N-cadherin and E-cadherin null ES cells, the two weakly interacting cell types segregated but did not envelop one another. Lastly, the most consistent and striking observation was that differentiated cells sorted to the surface and formed an enveloping layer, regardless of the relative cell adhesive affinity of any cell combination, supporting the hypothesis that the ability of the differentiated cells to establish apical polarity is the determining factor in surface sorting and positioning.


Cryopreservation of platelets using trehalose: the role of membrane phase behavior during freezing.
In blood banks, platelets are stored at 20-24 °C, which limits the maximum time they can be stored. Platelets are chilling sensitive, and they activate when stored at temperatures below 20 °C. Cryopreservation could serve as an alternative method for long term storage of platelet concentrates. Recovery rates using dimethyl sulfoxide (DMSO) as cryoprotective agent, however, are low, and removal of DMSO is required before transfusion. In this study, we have explored the use of trehalose for cryopreservation of human platelets while using different cooling rates. Recovery of membrane intact cells and the percentage of nonactivated platelets were used as a measure for survival. In all cases, survival was optimal at intermediate cooling rates of 20 °C min(-1). Cryopreservation using DMSO resulted in high percentages of activated platelets; namely 54% of the recovered 94%. When using trehalose, 98% of the platelets had intact membranes after freezing and thawing, whereas 76% were not activated. Using Fourier transform infrared spectroscopy, subzero membrane phase behavior of platelets has been studied in the presence of trehalose and DMSO. Furthermore, membrane hydraulic permeability parameters were derived from these data to predict the cell volume response during cooling. Both trehalose and DMSO decrease the activation energy for subzero water transport across cellular membranes. Platelets display a distinct lyotropic membrane phase transition during freezing, irrespective of the presence of cryoprotective agents. We suggest that concomitant uptake of trehalose during freezing could explain the increased survival of platelets cryopreserved with trehalose.


Object Categorization Processing Differs According to Category Level: Comparing Visual Information Between the Basic and Superordinate Levels.
Object category levels comprise a crucial concept in the field of object recognition. Specifically, categorization performance differs according to the category level of the target object. This study involved experiments with two types of stimulus sequences (i.e., forward condition: presenting the target name before the line-drawing stimulus; and reverse condition: presenting the target name after the line-drawing stimulus) for both basic- and superordinate-level categorizations. Adult participants were assigned to each level and asked to judge whether briefly presented stimuli included the same object and target name. Here, we investigated how the category level altered the categorization process. We conducted path analyses using a multivariate multiple regression model, and set our variables to investigate whether the predictors affected the categorization process between two types of stimulus sequence. Dependent variables included the measures of performance (i.e., reaction time, accuracy) for each categorization task. The predictors included dimensions and shapes of the line-drawings, such as primary and local shape information, shape complexity, subject estimation, and other shape variables related to object recognition. Results showed that the categorization process differed according to shape properties between conditions only for basic-level categorizations. For the forward condition, the bottom-up processing of primary visual information depended on matches with stored representations for the basic-level category. For the reverse condition at the basic-level category, decisions depended on subjective ratings in terms of object-representation accessibility. Finally, superordinate-level decisions depended on higher levels of visual information in terms of complexity, regardless of the condition. Thus, the given category level altered the processing of visual information for object recognition in relation to shape properties. This indicates that decision processing for object recognition is flexible depending on the criteria of the processed objects (e.g., category levels).


An investigation on the shear bond strength of one dentin adhesive at two different dentin depths.
The aim of this investigation was to study the effect of dentin depth and patient's age on the shear bond strength of one dentin adhesive (ART Bond), using an Instron Universal testing machine at a cross-head speed of 0.5 mm/min. Forty human molar teeth were used and were divided into two main groups, twenty each representing two age groups of patients, i.e., between 20 to 30 years and between 30-40 years of age. Every group was further subdivided into two subgroups of different dentin depths, i.e., superficial and deep. Results were recorded in Kg/Cm2 and converted into MPa units, then tabulated and statistically analyzed. A Duncan's range statistic test at P < or = 0.05 showed statistically significant differences between the bond strength values for both age groups at different dentin depths, with the superficial dentin showing higher bond values, and there were also statistically significant differences between the bond strength values of the two age groups at the same dentin depth, with the older age group showing higher bond values.


Identifying tumor cell-released extracellular vesicles as biomarkers for breast cancer diagnosis by a three-dimensional hydrogel-based electrochemical immunosensor.
Tumor cell-released LC3+ extracellular vesicles (LC3+ EVs) participate in immunosuppression during autophagy and contribute to the occurrence and development of breast cancer. In view of the strong association between the LC3+ EVs and breast cancer, developing an effective strategy for the quantitative detection of LC3+ EVs levels with high sensitivity to identify LC3+ EVs as new biomarkers for accurate diagnosis of breast cancer is crucial, but yet not been reported. Herein, an ultrasensitive electrochemical immunosensor is presented for the quantitative determination of LC3+ EVs using a three-dimensional graphene oxide hydrogel-methylene blue composite as a redox probe, showing a low detection limit and a wide linear range. With this immunosensor, the expression levels of LC3+ EVs in various practical sample groups including different cancer cell lines, the peripheral blood of tumor-bearing mice before and after immunotherapy, and the peripheral blood from breast cancer patients with different subtypes and stages were clearly distinguished. This study demonstrated that LC3+ EVs were superior as biomarkers for the accurate diagnosis of breast cancer compared to traditional biomarkers, particularly for cancer subtype discrimination. This work would provide a new noninvasive detection tool for the early diagnosis and prognosis assessment of breast cancer in clinics.


Haemophilus influenzae type B meningitis: a contagious disease of children.
The families of 126 consecutive patients with Haemophilus influenzae type B meningitis were surveyed for secondary invasive H influenzae disease among household contacts. A total of 120 of the families were contacted. In six cases no contact was possible and the medical record was reviewed. Some 555 household contacts were found; 31% (171) were under 5 years of age. A secondary case was defined as a household contact with H influenzae type B isolated from blood or cerebrospinal fluid more than 24 hours, but less than 30 days, after admission to hospital of the index case. Four secondary cases were identified, all in children aged under 5 years. The secondary attack rate in children under 5 years or less in the month after exposure to an index case was thus 2.3%, 800 times the endemic attack rate for H influenzae meningitis. This is a conservative estimate since five additional contact cases were documented, but not included in the secondary attack rate. Young contacts of a child with H influenzae meningitis are thus at significant risk of life-threatening secondary disease.


Multimodality imaging of acute locoregional and systemic complications in the setting of assisted reproduction.
Over the past 40 years since the first in vitro fertilization was performed, both the role of assisted reproductive technology (ART) in establishing viable pregnancy as well as the available treatment options have expanded enormously. Annually in the USA, nearly 2% of pregnancies now employ some form of ART assistance, with in vitro fertilization (IVF) being the most commonly utilized methodology. Both maternal and fetal risks are elevated in ART pregnancies, the latter including adverse outcome due to both increased gestational number as well as advanced maternal age. Maternal risks may be divided into locoregional and systemic complications. Adverse pelvic complications include those relating to gamete harvesting and transfer, ovarian hyperstimulation, the sequela of ectopic and heterotopic pregnancies, as well as ovarian torsion, all of which are elevated in the ART cohort. Ovarian hyperstimulation syndrome is the most commonly encountered complication, with both systemic and pelvic features relating to increased vascular permeability, hemoconcentration, and ascites. While life-threatening cases are relatively rare, moderate and severe manifestations may occur in up to 10% of ART cycles and, as such, are a not infrequent cause for ER visitation. Familiarity with the clinical and imaging manifestations of ART complications as well as their prognostic implications will facilitate a timely diagnosis and assist the interpreting radiologist in best expediting appropriate clinical care. In this article, we will briefly discuss the current methodology of ART then present an imaging-based multimodality review of the potentially encountered adverse maternal sequela, highlighting key diagnostic features and differential considerations as well as potential prognostic implications.


Secondary loss of miR-3607 reduced cortical progenitor amplification during rodent evolution.
The evolutionary expansion and folding of the mammalian cerebral cortex resulted from amplification of progenitor cells during embryonic development. This process was reversed in the rodent lineage after splitting from primates, leading to smaller and smooth brains. Genetic mechanisms underlying this secondary loss in rodent evolution remain unknown. We show that microRNA miR-3607 is expressed embryonically in the large cortex of primates and ferret, distant from the primate-rodent lineage, but not in mouse. Experimental expression of miR-3607 in embryonic mouse cortex led to increased Wnt/β-catenin signaling, amplification of radial glia cells (RGCs), and expansion of the ventricular zone (VZ), via blocking the β-catenin inhibitor APC (adenomatous polyposis coli). Accordingly, loss of endogenous miR-3607 in ferret reduced RGC proliferation, while overexpression in human cerebral organoids promoted VZ expansion. Our results identify a gene selected for secondary loss during mammalian evolution to limit RGC amplification and, potentially, cortex size in rodents.


Sweet rescue or surrender of the failing heart?
Natriuretic peptides (NPs) are hormones involved in maintaining heart health that undergo proteolytic cleavage to become activated. Previous work has shown that O-GalNAc glycans affect their processing and activation. Here, Goetze, Schjoldager, and colleagues now provide comprehensive characterization of O-glycosylation of NPs, revealing that all members of the NP family can be modified by O-GalNAc glycans. Intriguingly, the study discovers glycans in the receptor-binding region of the A-type natriuretic peptide (ANP), demonstrating that they affect both stability and activity of ANP. These results may inform future therapeutic approaches for heart failure using peptide glycoforms.


A hospital and community in partnership: "case management coordinated care model in a community setting.".
Eighteen months ago, a small Ontario community hospital teamed up with Home Care to develop and implement a system of care delivery that would provide quality care within existing financial obligations and constraints. This article describes why the model, "Case Management Coordinated Care Model in a Community Setting," was chosen, how it works and how it is evaluated. Readers are encouraged to examine the successful implementation of this new collaborative concept of care, given today's limited funds and mandate to improve the use of community and hospital resources.


[Analysis of the spectra of mutational damage of the 21-hydroxylase gene in patients with adreno-genital syndrome].
The spectrum of mutations in the steroid 21-hydroxylase gene (CYP21B) and the frequency of 11 mutations among 66 patients with different forms of congenital adrenal hyperplasia (CAH) were analyzed by means of PCR amplification. Each of the CAH forms was characterized by specific spectrum of diagnostically important mutations. The salt-losing (SL) form of the disease was most frequently associated with gene deletion (39%) and the 668-13C-G mutation in the second intron (23.5%), whereas the majority of simple virilizing (SV) CAH cases were associated with the 1172N mutation in exon 4 (22%), gene deletion (16.5%), and the 668-13C-G mutation (16.5%). Mutations in the steroid 21-hydroxylase gene were detected in 70% of the chromosomes from the patients with the SL and SV forms of CAH, and only in 1.3% of the chromosomes from the patients with the nonclassic (NC) form. A total of 78 mutant chromosomes from the NC CAH patients were examined, and only one case of a gene deletion in the heterozygous state was revealed. In the individuals examined, the V281L and P30L mutations described in the NC CAH patients from other populations were not detected. This result can be explained either by the fact that NC CAH cases in Russia are associated with other major mutations, or by difficult clinical diagnosis questionable CAH cases.


Signs and symptoms of temporomandibular dysfunction in fibromyalgic patients.
The objective of this study was to determine the frequency of signs and symptoms of temporomandibular disorder (TMD) in fibromyalgic patients. Sixty subjects of both sexes (mean age, 49.2 ± 13.8 years) with fibromyalgia (FM) diagnosis were included in this study. All patients were examined by a calibrated investigator to identify the presence of TMD using the Research Diagnostic Criteria for TMD. The most common signs (A) and symptoms (B) reported by FM patients were (A) pain in the masticatory muscles (masseter, 80%; posterior digastric, 76.7%), pain in the temporomandibular joint (83.3%), and 33.3% and 28.3%, respectively, presented joint sounds when opening and closing the mouth; (B) headache (97%) and facial pain (81.7%). In regard to the classic triad for the diagnosis of the TMD, it was found that 35% of the FM patients presented, at the same time, pain, joint sounds, and alteration of the mandibular movements. It was verified that myofascial pain without limitation of mouth opening was the most prevalent diagnosis (47%) for the RDC subgroup I. For the subgroup II, the disk displacement with reduction was the most prevalent diagnosis (21.6%). For the subgroup III, 36.7% of the subjects presented osteoarthritis. Thus, there is a high prevalence of signs and symptoms of TMD in FM patients, indicating the need for an integrated diagnosis and treatment of these patients, which suggest that the FM could be a medium- or long-term risk factor for the development of TMD.


Clinical signs and mortality of non-released stranded California sea lions housed in display facilities: the suspected role of prior exposure to algal toxins.
Stranded California sea lions considered unable to survive in the wild are often placed in public display facilities. Exposure to the biotoxin domoic acid (DA) is a common cause of stranding, and chronic effects are observed long after initial exposure. Medical records for 171 sea lions placed in US institutions between 2000 and 2016 were reviewed, including results from clinical examinations, histopathology, behavioural testing and advanced imaging. There was a statistically significant increase in neurological disease detected in neonates (24%) compared with other age classes (11%). Sixty per cent of all neurological cases died during the study period. In the 11 neurological neonate cases, six died (55%) and five are still alive with three of five developing epilepsy during placement. Of the six neurological neonate cases that died, one was attributed to DA toxicosis, one to seizures and four to acute unexplained neurological disease. This survey suggests delayed neurological disease can develop in sea lions after stranding as neonates. These data coupled with stranding records and epidemiological data on DA-producing algal blooms suggest further research into effects of neonatal exposure to DA on risk of neurological disease in later life is warranted. California sea lions offer a natural model of DA exposure to study such effects.


Analysis of selenium accumulation, speciation and tolerance of potential selenium hyperaccumulator Symphyotrichum ericoides.
Symphyotrichum ericoides was shown earlier to contain hyperaccumulator levels of selenium (Se) in the field (>1000 mg kg(-1) dry weight (DW)), but only when growing next to other Se hyperaccumulators. It was also twofold larger next to hyperaccumulators and suffered less herbivory. This raised two questions: whether S. ericoides is capable of hyperaccumulation without neighbor assistance, and whether its Se-derived benefit is merely ecological or also physiological. Here, in a comparative greenhouse study, Se accumulation and tolerance of S. ericoides were analyzed in parallel with hyperaccumulator Astragalus bisulcatus, Se accumulator Brassica juncea and related Asteraceae Machaeranthera tanacetifolia. Symphyotrichum ericoides and M. tanacetifolia accumulated Se up to 3000 and 1500 mg Se kg(-1) DW, respectively. They were completely tolerant to these Se levels and even grew 1.5- to 2.5-fold larger with Se. Symphyotrichum ericoides showed very high leaf Se/sulfur (S) and shoot/root Se concentration ratios, similar to A. bisulcatus and higher than M. tanacetifolia and B. juncea. Se X-ray absorption near-edge structure spectroscopy showed that S. ericoides accumulated Se predominantly (86%) as C-Se-C compounds indistinguishable from methyl-selenocysteine, which may explain its Se tolerance. Machaeranthera tanacetifolia accumulated 55% of its Se as C-Se-C compounds; the remainder was inorganic Se. Thus, in this greenhouse study S. ericoides displayed all of the characteristics of a hyperaccumulator. The larger size of S. ericoides when growing next to hyperaccumulators may be explained by a physiological benefit, in addition to the ecological benefit demonstrated earlier.


Clinical inertia in the pharmacological management of hypertension: A systematic review and meta-analysis.
Clinical Inertia is defined as "failure of health care providers to initiate or intensify therapy according to current guidelines". This phenomenon is gaining increasing attention as a major cause of clinicians' failure to adequately manage hypertension, thus leading to an increased incidence of cardiovascular events. We performed a systematic review and meta-analysis of randomized controlled trials to determine whether interventions aimed at reducing clinical inertia in the pharmacological treatment of hypertension improve blood pressure (BP) control. MEDLINE, Embase, and Cochrane Database of Systematic Reviews were searched from the start of their database until October 3, 2017 for the MESH terms "Hypertension" or "Blood Pressure", their subheadings, and the keywords "Therapeutic Inertia" or "Clinical Inertia". Studies were included if they addressed pharmacologic hypertension management, clinical inertia, were randomized controlled trials, reported an outcome describing prescriber behavior, and were available in English. Data for the included studies was extracted by two independent observers. Quality of studies was analyzed using the Cochrane Risk of Bias Assessment. Data was pooled for statistical analysis using both fixed- and random-effects models. The primary study outcome was the percentage of patients achieving blood pressure control as defined by the Joint National Committee guidelines or study authors. Of 474 citations identified, ten met inclusion criteria comprising a total of 26,871 patients, and eight were selected for meta-analysis. Interventions included Physician Education, Physician Reminders, Patient Education, Patient Reminders, Ambulatory BP Monitoring, Digital Medication Offerings, Physician Peer Visits, and Pharmacist-led Counselling. Pooled event rates revealed more patients with controlled BP in the intervention group versus control (55%, 95% CI 46-63% versus 45%, 95% CI 37-53%) and interventions significantly improved the odds of BP control (OR = 1.19, 95% CI = 1.12-1.27, P < .001). Heterogeneity in the quantitative analysis was moderate. Addressing clinical inertia through physician reminders, ambulatory BP monitoring, and educational interventions for primary care providers was associated with an improvement in blood pressure control. Our findings encourage further research to investigate strategies at reducing clinical inertia in the management of hypertension.


Absence of sensorineural hearing loss in treated infants and children with congenital toxoplasmosis.
Educationally significant hearing loss has been reported in 10% to 15% of children with congenital toxoplasmosis. As part of a pilot study to assess feasibility and safety of prolonged therapy for congenital toxoplasmosis, 30 congenitally infected infants and children were evaluated for auditory function. Serial testing, beginning within 2 months of birth, was performed. Availability of auditory brainstem response (ABR) testing made evaluation at an earlier age than previously possible. Six (20%) of the 30 infants had mild to moderate conductive type hearing loss associated with otitis media. No infant or child had sensorineural hearing loss. The better outcome we observed compared to previous reports of a 15% to 26% incidence of sensorineural hearing loss and 10% to 15% incidence of educationally significant, bilateral hearing impairment may be related to early initiation and/or prolonged institution of antimicrobial therapy. Continued followup to exclude progressive hearing impairment and study of larger numbers of children are needed to verify these preliminary findings.


[Restoring the tracheal lumen in the scar closure of its upper part by lysing of the cartilaginous frame].
Reestablishment of the tracheal lumen in its scarring is described. External approach is used to dissect scars in the trachea. The laryngotracheal prosthesis (water-filled cylindric latex balloon fixed to the tracheotomy tube) is placed in the lumen until epithelized (at least for 4 months). The plates 10 mm in size are cut off the rib auto-cartilage, formed as a ring and fixed on the teflon coils which are inserted in the tissues of the anterior abdominal wall for a month. Thus, the plates acquire a stable semi-ring form. Without removal of the laryngotracheal prosthesis, the semi-rings are implanted into the tissues around the upper tracheal part. The laryngotracheal prosthesis is removed 1 month after this. The trachea was reconstructed in 3 patients by this procedure. All of them resumed normal natural breathing.