Continuous-wave Thulium Laser for Heating Cultured Cells to Investigate Cellular Thermal Effects.
An original method to heat cultured cells using a 1.94 µm continuous-wave thulium laser for biological assessment is introduced here. Thulium laser radiation is strongly absorbed by water, and the cells at the bottom of the culture dish are heated through thermal diffusion. A laser fiber with a diameter of 365 µm is set about 12 cm above the culture dish, without any optics, such that the laser beam diameter is almost equivalent to the inner diameter of the culture dish (30 mm). By keeping a consistent amount of culture medium in each experiment, it is possible to irradiate the cells with a highly reproducible temperature increase. To calibrate the temperature increase and its distribution in one cell culture dish for each power setting, the temperature was measured during 10 s of irradiation at different positions and at the cellular level. The temperature distribution was represented using a mathematical graphics software program, and its pattern across the culture dish was in Gaussian form. After laser irradiation, different biological experiments could be performed to assess temperature-dependent cell responses. In this manuscript, viability staining (i.e., distinguishing live, apoptotic, and dead cells) is introduced to help determine the threshold temperatures for cell apoptosis and death after different points in time. The advantages of this method are the preciseness of the temperature and the time of heating, as well as its high efficiency in heating cells in a whole cell culture dish. Furthermore, it allows for study with a wide variety of temperatures and time durations, which can be well-controlled by a computerized operating system.


Rhazes, a genius physician in diagnosis and treatment of kidney calculi in medical history.
Abu Bakr Mohammad Ibn Zakariya Razi, known in the west as Rhazes (865 to 925 AD), was born in the ancient city of Rayy, near Tehran, Iran. He was a renowned physician in medical history and not only followed Hippocrates and Galen, but also greatly extended the analytical approach of his predecessors. Based on the existing documents, he was known as the most distinguished character in the world of medicine up to the 17th century. A great number of innovations and pioneering works in the medical science have been recorded in the name of Rhazes. His fundamental works in urology as part of his research in the realm of medicine have remained unknown. Pathophysiology of the urinary tract, venereal diseases, and kidney and bladder calculi are among his main interests in this field. He also purposed and developed methods for diagnosis and treatment of kidney calculi for the first time in medical history. He also presented a very exact and precise description of neuropathic bladder followed by vertebral fracture. He advanced urine analysis and studied function and diseases of the kidneys. Rhazes recommendations for the prevention of calculi are quite scientific and practical and in accordance with current recommendations to avoid hypercalciuria and increased saturation of urine. Rhazes was not only one of the most important Persian physician-philosophers of his era, but for centuries, his writings became fundamental teaching texts in European medical schools. Some important aspects of his contributions to medicine are reviewed.


Oxidation of the GaAs semiconductor at the Al2O3/GaAs junction.
Atomic-scale understanding and processing of the oxidation of III-V compound-semiconductor surfaces are essential for developing materials for various devices (e.g., transistors, solar cells, and light emitting diodes). The oxidation-induced defect-rich phases at the interfaces of oxide/III-V junctions significantly affect the electrical performance of devices. In this study, a method to control the GaAs oxidation and interfacial defect density at the prototypical Al2O3/GaAs junction grown via atomic layer deposition (ALD) is demonstrated. Namely, pre-oxidation of GaAs(100) with an In-induced c(8 × 2) surface reconstruction, leading to a crystalline c(4 × 2)-O interface oxide before ALD of Al2O3, decreases band-gap defect density at the Al2O3/GaAs interface. Concomitantly, X-ray photoelectron spectroscopy (XPS) from these Al2O3/GaAs interfaces shows that the high oxidation state of Ga (Ga2O3 type) decreases, and the corresponding In2O3 type phase forms when employing the c(4 × 2)-O interface layer. Detailed synchrotron-radiation XPS of the counterpart c(4 × 2)-O oxide of InAs(100) has been utilized to elucidate the atomic structure of the useful c(4 × 2)-O interface layer and its oxidation process. The spectral analysis reveals that three different oxygen sites, five oxidation-induced group-III atomic sites with core-level shifts between -0.2 eV and +1.0 eV, and hardly any oxygen-induced changes at the As sites form during the oxidation. These results, discussed within the current atomic model of the c(4 × 2)-O interface, provide insight into the atomic structures of oxide/III-V interfaces and a way to control the semiconductor oxidation.


[Chronic intestinal angina and bypass revascularization: a case report].
Intestinal angina is a rare affection with a high morbidity-mortality rate if not diagnosed. It is characterized by abdominal pain and postprandial vomiting, weight loss and anorexia. Arteriography allows confirmation of the diagnosis. The following case is a typical example of its clinical presentation and surgical treatment. Different techniques of revascularisation in case of a stenosis of the main digestive arteries are discussed.


Vimentin antibody production in transplant patients and immunomodulatory effects of vimentin in-vitro.
We investigated the presence of antibodies to vimentin in 150 patients awaiting transplant, (50 kidney, 50 liver and 50 thoracic) and in 51 previously transplanted kidney patients whose grafts had failed. Patients with primary end stage thoracic or kidney disease did not have increased levels of vimentin antibodies, but those with primary liver failure and those with kidney graft failure did. Those with kidney graft failure were more likely to form vimentin antibodies if the patient was HLA-DQ2 positive (p=<0.001). Further to this, we observed antibody mediated rejection in five HLA-DQ2 positive re-transplant patients where no other antibodies were identified. We investigated the effects of vimentin protein on cytokine production in phytohaemagglutinin stimulated and unstimulated peripheral blood mononuclear cells. When exposed to vimentin at low levels there was increased production of IL-10. When cultures were stimulated, there was a decrease in IL-10, IL-2 and IFN-gamma production and a large increase in IL-4 production (p=0.028) compared to the controls. These results suggest that under normal conditions exposure to vimentin can lead to regulation of the immune response. However, if the immune system is active, exposure to vimentin can enhance Th-2 immunity.


Response Dynamics in an Olivocerebellar Spiking Neural Network With Non-linear Neuron Properties.
Sensorimotor signals are integrated and processed by the cerebellar circuit to predict accurate control of actions. In order to investigate how single neuron dynamics and geometrical modular connectivity affect cerebellar processing, we have built an olivocerebellar Spiking Neural Network (SNN) based on a novel simplification algorithm for single point models (Extended Generalized Leaky Integrate and Fire, EGLIF) capturing essential non-linear neuronal dynamics (e.g., pacemaking, bursting, adaptation, oscillation and resonance). EGLIF models specifically tuned for each neuron type were embedded into an olivocerebellar scaffold reproducing realistic spatial organization and physiological convergence and divergence ratios of connections. In order to emulate the circuit involved in an eye blink response to two associated stimuli, we modeled two adjacent olivocerebellar microcomplexes with a common mossy fiber input but different climbing fiber inputs (either on or off). EGLIF-SNN model simulations revealed the emergence of fundamental response properties in Purkinje cells (burst-pause) and deep nuclei cells (pause-burst) similar to those reported in vivo. The expression of these properties depended on the specific activation of climbing fibers in the microcomplexes and did not emerge with scaffold models using simplified point neurons. This result supports the importance of embedding SNNs with realistic neuronal dynamics and appropriate connectivity and anticipates the scale-up of EGLIF-SNN and the embedding of plasticity rules required to investigate cerebellar functioning at multiple scales.


Intensive insulin therapy in severely burned pediatric patients: a prospective randomized trial.
Hyperglycemia and insulin resistance have been shown to increase morbidity and mortality in severely burned patients, and glycemic control appears essential to improve clinical outcomes. However, to date no prospective randomized study exists that determines whether intensive insulin therapy is associated with improved post-burn morbidity and mortality. To determine whether intensive insulin therapy is associated with improved post-burn morbidity. A total of 239 severely burned pediatric patients with burns over greater than 30% of their total body surface area were randomized (block randomization 1:3) to intensive insulin treatment (n = 60) or control (n = 179). Demographics, clinical outcomes, sepsis, glucose metabolism, organ function, and inflammatory, acute-phase, and hypermetabolic responses were determined. Demographics were similar in both groups. Intensive insulin treatment significantly decreased the incidence of infections and sepsis compared with controls (P < 0.05). Furthermore, intensive insulin therapy improved organ function as indicated by improved serum markers, DENVER2 scores, and ultrasound (P < 0.05). Intensive insulin therapy alleviated post-burn insulin resistance and the vast catabolic response of the body (P < 0.05). Intensive insulin treatment dampened inflammatory and acute-phase responses by deceasing IL-6 and acute-phase proteins compared with controls (P < 0.05). Mortality was 4% in the intensive insulin therapy group and 11% in the control group (P = 0.14). In this prospective randomized clinical trial, we showed that intensive insulin therapy improves post-burn morbidity. Clinical trial registered with www.clinicaltrials.gov (NCT00673309).


Lysyl oxidase-like and lysyl oxidase are present in the dermis and epidermis of a skin equivalent and in human skin and are associated to elastic fibers.
Elastic fiber formation involves the secretion of tropoelastin which is converted to insoluble elastin by cross-linking, initiated by the oxidative deamination of lysine residues by lysyl oxidase. Five lysyl oxidase genes have been discovered. This study deals with the expression of two isoforms, LOX and LOX-like (LOXL), in human foreskin and in a human skin-equivalent (SE) model that allows the formation of elastic fibers. In this model, keratinocytes are added to a dermal equivalent made of fibroblasts grown on a chitosan-cross-linked collagen-GAG matrix. LOX and LOXL were detected by immunohistochemistry in the dermis and the epidermis of both normal skin and in a SE. This expression was confirmed by in situ hybridization on the SE. LOX and LOXL expression patterns were confirmed in human skin. The ultrastructural localization of LOXL was indicative of its association with elastin-positive materials within the SE and human skin, though interaction with collagen could not be discarded. LOX was found on collagen fibers and could be associated with elastin-positive materials in the SE and human skin. LOXL and LOX were detected in keratinocytes where LOX was mainly expressed by differentiating keratinocytes, in contrast to LOXL that can be found in both proliferating and differentiating fibroblasts. These data favor a role for LOXL in elastic fiber formation, together with LOX, and within the epidermis where both enzymes should play a role in post-translational modification of yet unknown substrates.


Efficiency of risk-based vs . random sampling for the monitoring of tetracycline residues in slaughtered calves in Switzerland.
In all European Union countries, chemical residues are required to be routinely monitored in meat. Good farming and veterinary practice can prevent the contamination of meat with pharmaceutical substances, resulting in a low detection of drug residues through random sampling. An alternative approach is to target-monitor farms suspected of treating their animals with antimicrobials. The objective of this project was to assess, using a stochastic model, the efficiency of these two sampling strategies. The model integrated data on Swiss livestock as well as expert opinion and results from studies conducted in Switzerland. Risk-based sampling showed an increase in detection efficiency of up to 100% depending on the prevalence of contaminated herds. Sensitivity analysis of this model showed the importance of the accuracy of prior assumptions for conducting risk-based sampling. The resources gained by changing from random to risk-based sampling should be transferred to improving the quality of prior information.


Assessment of clients' satisfaction with health service deliveries at jimma university specialized hospital.
Client satisfaction is considered as one of the desired outcomes of health care and it is directly related with utilization of health services. Nonetheless, there is no adequate information on users' perception about the service provided in the hospital after the implementation of Business process re-engineering reform. Hence, the objective of this study was to assess the perceived levels of clients' satisfaction with health services rendered at Jimma University Specialized Hospital. A cross sectional study was conducted from March 1-8, 2010 on a sample of 422 service users of the hospital using systematic random sampling technique. Data was collected using structured questionnaire and analyzed by SPSS for windows version 16.0. Statistical tests were employed where necessary at 0.05 level of significance. The questionnaire was administered to a total of 422 clients , of which, 51.7 % were male, about 33.4% of the respondents were between the age group 25-34, 41.% of the clients were illiterates, 60% were from the rural areas and 57.8 % received the service free of charge. The findings of the study showed that the overall client satisfaction level with the health services rendered at the hospital was 77%. Satisfaction was reported to be highest (82.7%) with the way the doctors examined them and on the other hand dissatisfaction was reported to be highest (46.9%) by respondents with the time spent to see a doctor. Furthermore, satisfaction with the health care was found to have a significant association with the age of the respondents (p=0.034) and educational level of the respondents (p=0.003). This study showed higher clients' satisfaction level in the University Specialized Hospital when compared to previous studies in the same hospital as well as other similar studies in the country. Lack of drugs and supplies, poor information provision, long waiting time, poor cleanliness, lack of privacy and inadequate visiting hours, were found to be the major causes of dissatisfaction. Therefore, the Hospital management should understand these weak service areas and plan for a better service delivery.


[Assessment of the indicators of organizational activities of dental polyclinics in Moscow].
Presents the method of comprehensive probability assessment of a number of indexes calculated on the basis of the data derived from annual reports of 36 dental clinics of Moscow for 1994. Correlations between the indexes and their signal deviations from the mean values were assessed and their integration and ranging carried out. This confirmed the possibility of a more effective utilization of reported data in adopting the managerial solutions and improvement of the medical and technological process.


Microwave & magnetic proteomics of macrophages from patients with HIV-associated cognitive impairment.
HIV-infected monocytes can infiltrate the blood brain barrier as differentiated macrophages to the central nervous system, becoming the primary source of viral and cellular neurotoxins. The final outcome is HIV-associated cognitive impairment (HACI), which remain prevalent today, possibly due to the longer life-span of the patients treated with combined anti-retroviral therapy. Our main goal was to characterize the proteome of monocyte-derived macrophages (MDM) from HACI patients, and its association with their cognitive status, to find novel targets for therapy. MDM were isolated from the peripheral blood of 14 HIV-seropositive women characterized for neurocognitive function, including: four normal cognition (NC), five asymptomatic (A), and five with cognitive impaired (CI). Proteins from macrophage lysates were isobaric-labeled with the microwave and magnetic (M2) sample preparation method followed by liquid chromatography-tandem mass spectrometry-based protein identification and quantification. Differences in protein abundance across groups classified by HACI status were determined using analysis of variance. A total of 2,519 proteins were identified with 2 or more peptides and 28 proteins were quantified as differentially expressed. Statistical analysis revealed increased abundance of 17 proteins in patients with HACI (p<0.05), including several enzymes associated to the glucose metabolism. Western blot confirmed increased expression of 6-Phosphogluconate dehydrogenase and L-Plastin in A and CI patients over NC and HIV seronegatives. This is the first quantitative proteomics study exploring the changes in protein abundance of macrophages isolated from patients with HACI. Further studies are warranted to determine if these proteins may be target candidates for therapy development against HACI.


Mechanisms of pure alexia: spatially based impairment, letter identification deficit, or both?
We studied reading performance for words and for isolated letters in a pure alexic patient. She performed reasonably well when naming isolated letters but was slower in reading letters than a control subject when reaction times (RTs) were recorded. When the patient read isolated letters, RTs were slower for a subset of letters that cannot be recognized from their left part alone (e.g. "b", an ambiguous letter, could be read "b" "h" "l" or "k" whereas "a" has no predictable confounders). We observed a significant positive correlation between the RTs for reading a word and the mean RTs for reading each of its composing letters before its uniqueness point (i.e. the point, when reading from the left to the right, where a word cannot be a word other than the one it is). This result suggests that, in our patient, the letter identification deficit can account for the slow, letter-by-letter reading behaviour, insofar as each letter represents a perceptual problem. Our findings can be accounted for by a deficit in the parallel processing of the left and right parts of each letter, compounded with a bias to process first the left part of the letter, and may thus reconcile the hypotheses of spatially-based deficit (Rapp and Caramazza, 1991) and of a perceptual deficit occurring at the letter identification level (Behrmann and Shallice, 1995; Perri et al., 1996).


Clinical significance of tubular and podocyte biomarkers in acute kidney injury.
Acute kidney injury (AKI) is a common complication in critically ill patients. Urinary excretion of liver-type fatty acid-binding protein (L-FABP), which is expressed in the proximal tubules, reflects the presence of tubular injury. Urinary excretion of podocalyxin (PCX), a glycoprotein prominently expressed on podocytes, is associated with podocyte injury. Our aims were to evaluate the utility of urinary L-FABP for the early detection of AKI and to examine whether podocyte injury is present in AKI patients using the biomarker of urinary PCX. Patients admitted to the intensive care unit (ICU) were divided into the AKI group (n = 14) and non-AKI group (n = 11), according to the occurrence of AKI during hospitalization in the ICU. Changes in various biomarkers were evaluated. In the AKI group, elevation of urinary L-FABP level [maximum value of L-FABP, 199.0 (92.5-433.6) μg/g creatinine, median (25-75% interquartile range)], which reflects tubular injury (area under the curve 0.95, cut-off value 44.1 μg/g Cr), occurred between -30 and 0 h before the occurrence of AKI (i.e., the time at which serum creatinine peaked), and elevation of urinary PCX level [maximum value of PCX, 389.5 (267.0-501.0) μg/g creatinine; upper limit of reference value, 160 μg/g creatinine] occurred during the time of recovery from AKI when serum creatinine levels were decreasing between 34.0 and 72.0 h after the occurrence of AKI. Furthermore, a parameter with the primary large AUC for predicting the onset of AKI was urinary L-FABP. Our study suggests that L-FABP is a useful biomarker for early detection of AKI and that podocyte injury was induced during the recovery phase of AKI.


Control algorithms for dynamic attenuators.
The authors describe algorithms to control dynamic attenuators in CT and compare their performance using simulated scans. Dynamic attenuators are prepatient beam shaping filters that modulate the distribution of x-ray fluence incident on the patient on a view-by-view basis. These attenuators can reduce dose while improving key image quality metrics such as peak or mean variance. In each view, the attenuator presents several degrees of freedom which may be individually adjusted. The total number of degrees of freedom across all views is very large, making many optimization techniques impractical. The authors develop a theory for optimally controlling these attenuators. Special attention is paid to a theoretically perfect attenuator which controls the fluence for each ray individually, but the authors also investigate and compare three other, practical attenuator designs which have been previously proposed: the piecewise-linear attenuator, the translating attenuator, and the double wedge attenuator. The authors pose and solve the optimization problems of minimizing the mean and peak variance subject to a fixed dose limit. For a perfect attenuator and mean variance minimization, this problem can be solved in simple, closed form. For other attenuator designs, the problem can be decomposed into separate problems for each view to greatly reduce the computational complexity. Peak variance minimization can be approximately solved using iterated, weighted mean variance (WMV) minimization. Also, the authors develop heuristics for the perfect and piecewise-linear attenuators which do not require a priori knowledge of the patient anatomy. The authors compare these control algorithms on different types of dynamic attenuators using simulated raw data from forward projected DICOM files of a thorax and an abdomen. The translating and double wedge attenuators reduce dose by an average of 30% relative to current techniques (bowtie filter with tube current modulation) without increasing peak variance. The 15-element piecewise-linear dynamic attenuator reduces dose by an average of 42%, and the perfect attenuator reduces dose by an average of 50%. Improvements in peak variance are several times larger than improvements in mean variance. Heuristic control eliminates the need for a prescan. For the piecewise-linear attenuator, the cost of heuristic control is an increase in dose of 9%. The proposed iterated WMV minimization produces results that are within a few percent of the true solution. Dynamic attenuators show potential for significant dose reduction. A wide class of dynamic attenuators can be accurately controlled using the described methods.


Reducing burnout in mothers with an intellectually disabled child: an education programme.
This paper is a report of a study conducted to examine the effect of participating in an education program on burnout for mothers of children with an intellectual disability. Mothers with an intellectually disabled child are prone to suffer from excessive stress and burnout. There is limited evidence for the effectiveness of education interventions aimed at reducing burnout levels in this population. After baseline screening, mothers who agreed to participate (n = 90) were randomized to an intervention or control group. The intervention group participated in an interactive education programme for 1 hour, in addition to using an educational booklet designed and presented by the researchers. The booklet contained information about the characteristics of intellectually disabled children, the specific health care and education they require, non-profit organizations and foundations providing assistance, and ways in which mothers can cope with stress. The control group received the same intervention separately after completing the post-test. The study was carried out from 2004 to 2005. Intervention group members reported fewer episodes of emotional burnout compared to the control group, indicating that participation in a nursing education programme reduced the level of burnout experienced by mothers who have an intellectually disabled child. There were no effects of the education programme on perceptions of personal success, i.e. mother's feelings of competence and successful achievement in care of their intellectually disabled child. Nurse-administered education should be provided for mothers who have an intellectually disabled child in order to reduce the degree of emotional burnout that these mothers typically experience.


Elevated mortality among the second-generation (children of migrants) in Europe: what is going wrong? A review.
The 'second-generation' (i.e. the children of migrants) represent one of the fastest growing subpopulations of the child and young adult populations in Europe today. The research so far appears to indicate that their mortality risk is elevated relative to people with non-migrant backgrounds. Peer-reviewed publications. Second-generation status is a clear marker of elevated mortality risk in Europe in early life (including stillbirth, perinatal, neonatal and infant mortality) and adulthood, particularly if the parent(s) were born outside of Europe. Socioeconomic inequality plays an important, albeit rarely defining, role in these elevated risks. It remains unclear what causes-of-death are driving these elevated mortality risks. The exact influence of (non-socioeconomic) explanatory factors (e.g. health care, racism & discrimination, and factors related to integration) on the elevated mortality risks of the second-generation also remains unclear. The second-generation will continue to grow and diversify in Europe; we must intervene to address these inequalities now. Place more emphasis on the complexity of migration background, specific causes-of-death, and understanding the roles of explanatory factors beyond socioeconomic background.


The design and evaluation of a hearing aid with trainable amplification parameters.
A prototype hearing aid with trainable amplification parameters (compression threshold, gain below the compression threshold, compression ratio, and noise suppression strength) was evaluated to answer the following research questions: (1) In everyday listening situations, do aid users prefer amplification parameters that were a result of training the aid in such situations to a set of untrained parameters that were prescribed and customized in a clinic? (2) Does the provision of trained noise suppression significantly increase the preference for the trained settings? (3) Is the preference for the trained settings correlated with a measure of training? Three take-home trials were conducted. I. The training trial: Eighteen subjects with symmetric, sensorineural hearing loss were recruited. The aid was fitted with untrained settings based on the NAL-NL1 prescription, and the subjects then attempted to train the aid's amplification settings to their preference in everyday situations for a period of between 1 and 4 weeks. II. The first double-blind comparison trial: Thirteen of the training-trial subjects agreed to participate. These subjects blindly compared their trained settings to untrained settings and voted for their preferred settings in everyday situations for a period of 1 week. Noise suppression was enabled for the trained settings (with trained noise suppression strength), but not for the untrained settings. III. The second double-blind comparison trial: A repeat of the first comparison trial, but with noise suppression disabled for both the trained and untrained settings. Subjects who had high trained noise suppression strength values for the first comparison trial were recruited (eight subjects agreed to participate). This trial more clearly evaluated the effect of training the compression characteristics, and differences between the results of the comparison trials showed the effect of the trained noise suppression. For the first comparison trial, nine subjects voted for the trained settings significantly more often than the untrained settings in real life environments. Three subjects had nonsignificant results, and one subject had a significant preference for the untrained settings. The results of the first and second comparison trials were not significantly different for seven of the eight subjects who participated in both trials. Thus, for these subjects (and the group data) the provision of trained noise suppression did not have a significant effect on the preference for the trained settings. Data logged during the trials showed that the percentage of votes for the trained settings for the first comparison trial was most strongly correlated with the number of hours of aid use during the training trial, although this was not significant when all subjects were included. In everyday listening situations, aid users can train this prototype aid to provide amplification parameters that, in such situations, they prefer significantly more often than untrained parameters prescribed and adjusted in a clinic. The preference for the trained settings was not significantly affected by the training of the noise suppression strength, and was moderately but not significantly correlated with the hours of aid use during the training period. Therefore, the customization of compression parameters that is currently performed in the clinic can at least partly be performed in real life listening situations by clients who have been fitted with this trainable aid.


Kinetics of exocytosis is faster in cones than in rods.
Cone-driven responses of second-order retinal neurons are considerably faster than rod-driven responses. We examined whether differences in the kinetics of synaptic transmitter release from rods and cones may contribute to differences in postsynaptic response kinetics. Exocytosis from rods and cones was triggered by membrane depolarization and monitored in two ways: (1) by measuring EPSCs evoked in second-order neurons by depolarizing steps applied to presynaptic rods or cones during simultaneous paired whole-cell recordings or (2) by direct measurements of exocytotic increases in membrane capacitance. The kinetics of release was assessed by varying the length of the depolarizing test step. Both measures of release revealed two kinetic components to the increase in exocytosis as a function of the duration of a step depolarization. In addition to slow sustained components in both cell types, the initial fast component of exocytosis had a time constant of <5 ms in cones, >10-fold faster than that of rods. Rod/cone differences in the kinetics of release were substantiated by a linear correlation between depolarization-evoked capacitance increases and EPSC charge transfer. Experiments on isolated rods indicate that the slower kinetics of exocytosis from rods was not a result of rod-rod coupling. The initial rapid release of vesicles from cones can shape the postsynaptic response and may contribute to the faster responses of cone-driven cells observed at light offset.


Enhancing motor skill learning with transcranial direct current stimulation - a concise review with applications to stroke.
In the past few years, there has been a rapid increase in the application of non-invasive brain stimulation to study brain-behavior relations in an effort to potentially increase the effectiveness of neuro-rehabilitation. Transcranial direct current stimulation (tDCS), an emerging technique of non-invasive brain stimulation, has shown to produce beneficial neural effects in consequence with improvements in motor behavior. tDCS has gained popularity as it is economical, simple to use, portable, and increases corticospinal excitability without producing any serious side effects. As tDCS has been increasingly investigated as an effective tool for various disorders, numerous improvements, and developments have been proposed with respect to this technique. tDCS has been widely used to identify the functional relevance of particular brain regions in motor skill learning and also to facilitate activity in specific cortical areas involved in motor learning, in turn improving motor function. Understanding the interaction between tDCS and motor learning can lead to important implications for developing various rehabilitation approaches. This paper provides a concise overview of tDCS as a neuromodulatory technique and its interaction with motor learning. The paper further briefly goes through the application of this priming technique in the stroke population.


The WTO's balancing act.
The 146 member nations of the World Trade Organization recently came to an agreement that will allow poor nations to avoid patent restrictions and import generic versions of urgently needed medicines, but this accord has been met with criticism from international aid organizations. What effects will this agreement have on reducing the burden of disease in the developing world, and also on the pharmaceutical industry?


Randomized trial of trimethoprim-sulfamethoxazole versus pyrimethamine-sulfadiazine for therapy of toxoplasmic encephalitis in patients with AIDS. Italian Collaborative Study Group.
The aim of the present pilot study was to compare the efficacy and safety of trimethoprim (TMP) and sulfamethoxazole (SMX) with those of the standard therapy pyrimethamine (P)-sulfadiazine (S) for the treatment of toxoplasmic encephalitis in patients with AIDS. This was a pilot, multicenter, randomized, and prospective study. Patients were randomly assigned to receive TMP (10 mg/kg of body weight/day) and SMX (50 mg/kg/day) or P (50 mg daily) and S (60 mg/kg/day) as acute therapy (for 4 weeks) and then as maintenance therapy for 3 months at half of the original dosage. Seventy-seven patients were enrolled and randomized to the study: 40 patients were treated with TMP-SMX and 37 were treated with P-S. There was no statistically significant difference in clinical efficacy during acute therapy. In contrast, patients randomized to TMP-SMX appeared more likely to achieve a complete radiologic response after acute therapy. Adverse reactions were significantly more frequent in patients treated with P-S, and skin rash was the most common adverse event noted in these patients. In conclusion, the results of the study suggest that TMP-SMX appears to be a valuable alternative to P-S, in particular in patients with opportunistic bacterial infections.


Opportunistic pathogenic fungi isolated from feces of feral pigeons in Mafikeng, North West Province of South Africa.
Pigeon feces are increasingly being implicated in the spread of bacterial pathogens such as Escherichia coli, Campylobacter, Salmonella, Listeria, and Chlamydia. Fungi are rarely investigated except for Cryptococcus that has emerged as an important pathogen in old people and immunosuppressed patients. This study investigated fungi in pigeon feces collected from Mafikeng, the North West Province of South Africa. Freshly dropped feces were collected and enriched in phosphate-buffered saline overnight at 48°C and then subcultured on Sabouraud's dextrose agar and incubated at 48°C for 2 weeks observing any fungal growth from day 2. The growths were picked up, DNA extracted, and polymerase chain reaction was done using the internal transcribed spacer primers. Fungi isolated included: Aspergillus (Aspergillus tubingensis), Cryptococcus (Cryptococcus albidus and Cryptococcus randhawai), Fusarium spp., and Rhodotorula (Rhodotorula mucilaginosa and Rhodotorula kratochvilovae). Most of these isolates are known opportunistic pathogens and have been isolated in clinical conditions elsewhere. Other isolates such as Graphium dubautiae, Myrmecridium schulzeri, Naganishia albida, Paecilomyces lilacinus, and Zygopleurage zygospora were not found to be of any human health significance. We, therefore, concluded that the presence of these opportunistic pathogens is a significant human health risk, especially in the face of the HIV/AIDS pandemic that results in immunosuppression.


Acute Kidney Injury in Pregnancy-specific Disorders.
The incidence of acute kidney injury in pregnancy (P-AKI) has declined significantly over the last three decades in developing countries. However, it is still associated with significant fetomaternal mortality and morbidity. The diagnosis of P-AKI is based on the serum creatinine increase. The usual formulas for estimating glomerular filtration rate (GFR) are not validated in this population. The incidence of P-AKI with respect to total AKI cases has decreased in the last three decades from 25% in 1980s to 9% in 2000s at our centre. During the first trimester of gestation, AKI develops most often due to septic abortion or hyperemesis gravidarum. Septic abortion related AKI with respect to total AKI decreased from 9% to 5% in our study. Prevention of unwanted pregnancy and avoidance of septic abortion are keys to eliminate abortion associated AKI in early pregnancy. However, we have not seen AKI on account of hyperemesis gravidarum over a period of 33 years at our center. In the third trimester, the differential diagnosis of AKI in association with pregnancy specific conditions namely preeclampsia/HELLP syndrome, acute fatty liver of pregnancy and thrombotic microangiopathies of pregnancy (P-TMA) is more challenging, because these 3 conditions share several clinical features of thrombotic microangiopathy which makes the diagnosis very difficult on clinical grounds. It is imperative to distinguish these conditions to make appropriate therapeutic decisions. Typically, AFLP and HELLP syndrome improve after delivery of the fetus, whereas plasma exchange is the first-line treatment for pregnancy associated thrombotic microangioathies (P-TMA). We observed that preclampsia/eclampsia is the most common cause of AKI in late third trimester and postpartum periods followed by puerperal sepsis and postpartum hemorrhage. Pregnancy-associated thrombotic microangiopathies (aHUS/TTP) and AFLP are rare causes of AKI during pregnancy in developing countries.


Length and curvature of the dog diaphragm.
Transdiaphragmatic pressure is a result of both tension in the muscles of the diaphragm and curvature of the muscles. As lung volume increases, the pressure-generating capability of the diaphragm decreases. Whether decrease in curvature contributes to the loss in transdiaphragmatic pressure and, if so, under what conditions it contributes are unknown. Here we report data on muscle length and curvature in the supine dog. Radiopaque markers were attached along muscle bundles in the midcostal region of the diaphragm in six beagle dogs of approximately 8 kg, and marker locations were obtained from biplanar images at functional residual capacity (FRC), during spontaneous inspiratory efforts against a closed airway at lung volumes from FRC to total lung capacity, and during bilateral maximal phrenic nerve stimulation at the same lung volumes. Muscle length and curvature were obtained from these data. During spontaneous inspiratory efforts, muscle shortened by 15-40% of length at FRC, but curvature remained unchanged. During phrenic nerve stimulation, muscle shortened by 30 to nearly 50%, and, for shortening exceeding 52%, curvature appeared to decrease sharply. We conclude that diaphragm curvature is nearly constant during spontaneous breathing maneuvers in normal animals. However, we speculate that it is possible, if lung compliance were increased and the chest wall and the diameter of the diaphragm ring of insertion were enlarged, as in the case of chronic obstructive pulmonary disease, that decrease in diaphragm curvature could contribute to loss of diaphragm function.


Advances in targeted and immunobased therapies for colorectal cancer in the genomic era.
Targeted therapies require information on specific defective signaling pathways or mutations. Advances in genomic technologies and cell biology have led to identification of new therapeutic targets associated with signal-transduction pathways. Survival times of patients with colorectal cancer (CRC) can be extended with combinations of conventional cytotoxic agents and targeted therapies. Targeting EGFR- and VEGFR-signaling systems has been the major focus for treatment of metastatic CRC. However, there are still limitations in their clinical application, and new and better drug combinations are needed. This review provides information on EGFR and VEGF inhibitors, new therapeutic agents in the pipeline targeting EGFR and VEGFR pathways, and those targeting other signal-transduction pathways, such as MET, IGF1R, MEK, PI3K, Wnt, Notch, Hedgehog, and death-receptor signaling pathways for treatment of metastatic CRC. Additionally, multitargeted approaches in combination therapies targeting negative-feedback loops, compensatory networks, and cross talk between pathways are highlighted. Then, immunobased strategies to enhance antitumor immunity using specific monoclonal antibodies, such as the immune-checkpoint inhibitors anti-CTLA4 and anti-PD1, as well as the challenges that need to be overcome for increased efficacy of targeted therapies, including drug resistance, predictive markers of response, tumor subtypes, and cancer stem cells, are covered. The review concludes with a brief insight into the applications of next-generation sequencing, expression profiling for tumor subtyping, and the exciting progress made in in silico predictive analysis in the development of a prescription strategy for cancer therapy.


Reduction of angiotensin II in the cerebrospinal fluid of patients with multiple sclerosis.
We previously demonstrated that angiotensin II acts as a crucial neuroprotective factor after neural injury through angiotensin II type-2 (AT2) receptor signaling. Although the pathway is known to play an important role in the development of experimental autoimmune encephalomyelitis, cerebrospinal fluid (CSF) angiotensin II levels in patients with multiple sclerosis (MS) have never been studied. To clarify the significance of angiotensin II in MS, we assayed angiotensin II concentrations using an established enzyme-linked immunoabsorbent assay in CSF samples from patients with MS (n = 21), patients with inflammatory neuropathies (IN) (n = 23) and control individuals who did not have either of the neurological diseases or any other disease that might affect the angiotensin II levels in the CSF (control) (n = 24). Angiotensin II levels in the CSF were 3.79 +/- 1.54 pg/ml in the MS group, 5.13 +/- 2.27 pg/ml in the IN group and 6.71 +/- 2.65 pg/ml in the control group. The angiotensin II levels in the CSF of the MS group were significantly lower than in the control group (p = 0.00057). Angiotensin II concentration in the CSF tended to have a negative correlation with the Kurtzke's Expanded Disability Status Scale scores during MS relapse (p = 0.0847). These findings suggest that reduced levels of intrathecal angiotensin II may be related to the abnormal neural damage and repair processes in MS.


Exome sequencing and diffusion tensor imaging in developmental disabilities.
We had previously shown that arcuate fasciculus is poorly developed in patients with intellectual and developmental disabilities (IDD) using diffusion tensor imaging (DTI). In the present study, we used exome sequencing to identify the candidate variants in IDD patients with and without DTI abnormalities. Eighteen children with IDD (age: 67 ± 36 mo, 9 females) were included in the present study. The DTI was used to determine the integrity of arcuate fasciculus. The next-generation sequencing was performed on the Solid 4 platform. A novel, analytical strategy was developed to identify a set of candidate genes of interest. We then searched for novel, nonsynonymous variants in the patients within this subset of genes and in known IDD genes. Seven novel, nonsynonymous (all of them were heterozygous, missense) variants belonged to ultraconserved genes that are known to cause abnormal brain morphology in mutant mice. Similarly, three novel, nonsynonymous (all of them were heterozygous, missense) variants belonged to known IDD genes. Two patients with underdeveloped arcuate fasciculus had novel, nonsynonymous variants in genes (MID1 and EN2) regulating axon guidance pathway. Exome sequencing identified several new genetic causes of IDD.


The aspect ratio effect on plasmonic properties and biosensing of bonding mode in gold elliptical nanoring arrays.
We investigate both numerically and experimentally the optical properties and biosensing of gold elliptical nanoring (ENR) arrays with various aspect ratios. The gold ENR exhibits a strong localized surface plasmon bonding mode in near-infrared region, whose peak wavelength is red-shifted as increasing the aspect ratio under longitudinal and transverse polarizations. Furthermore, the disk- and hole-like optical properties for longitudinal and transverse modes are observed, which cause different behaviors in field intensity enhancement. For biomolecule sensing, we find that both modes show increased surface sensitivities when enlarging the aspect ratio of gold ENR.


The cytosolic thiouridylase CTU2 of Arabidopsis thaliana is essential for posttranscriptional thiolation of tRNAs and influences root development.
A large number of post-transcriptional modifications of transfer RNAs (tRNAs) have been described in prokaryotes and eukaryotes. They are known to influence their stability, turnover, and chemical/physical properties. A specific subset of tRNAs contains a thiolated uridine residue at the wobble position to improve the codon-anticodon interaction and translational accuracy. The proteins involved in tRNA thiolation are reminiscent of prokaryotic sulfur transfer reactions and of the ubiquitylation process in eukaryotes. In plants, some of the proteins involved in this process have been identified and show a high degree of homology to their non-plant equivalents. For other proteins, the identification of the plant homologs is much less clear, due to the low conservation in protein sequence. This manuscript describes the identification of CTU2, the second CYTOPLASMIC THIOURIDYLASE protein of Arabidopsis thaliana. CTU2 is essential for tRNA thiolation and interacts with ROL5, the previously identified CTU1 homolog of Arabidopsis. CTU2 is ubiquitously expressed, yet its activity seems to be particularly important in root tissue. A ctu2 knock-out mutant shows an alteration in root development. The analysis of CTU2 adds a new component to the so far characterized protein network involved in tRNA thiolation in Arabidopsis. CTU2 is essential for tRNA thiolation as a ctu2 mutant fails to perform this tRNA modification. The identified Arabidopsis CTU2 is the first CTU2-type protein from plants to be experimentally verified, which is important considering the limited conservation of these proteins between plant and non-plant species. Based on the Arabidopsis protein sequence, CTU2-type proteins of other plant species can now be readily identified.


Identifying tumor cell growth inhibitors by combinatorial chemistry and zebrafish assays.
Cyclin-dependent kinases (CDKs) play important roles in regulating cell cycle progression, and altered cell cycles resulting from over-expression or abnormal activation of CDKs observed in many human cancers. As a result, CDKs have become extensive studied targets for developing chemical inhibitors for cancer therapies; however, protein kinases share a highly conserved ATP binding pocket at which most chemical inhibitors bind, therefore, a major challenge in developing kinase inhibitors is achieving target selectivity. To identify cell growth inhibitors with potential applications in cancer therapy, we used an integrated approach that combines one-pot chemical synthesis in a combinatorial manner to generate diversified small molecules with new chemical scaffolds coupled with growth inhibition assay using developing zebrafish embryos. We report the successful identification of a novel lead compound that displays selective inhibitory effects on CDK2 activity, cancer cell proliferation, and tumor progression in vivo. Our approaches should have general applications in developing cell proliferation inhibitors using an efficient combinatorial chemical genetic method and integrated biological assays. The novel cell growth inhibitor we identified should have potential as a cancer therapeutic agent.


Association of aflatoxin with gallbladder cancer in a case-control study nested within a Chinese cohort.
We evaluated whether aflatoxin B1 (AFB1 ) exposure was associated with later risk of developing gallbladder cancer (GBC). We measured AFB1 -lysine albumin adducts in baseline samples from the Shanghai Cohort Study of 18 244 men aged 45 to 64 years (recruited 1986-1989). We included 84 GBC cases with sufficient serum and 168 controls matched on age at sample collection, date of blood draw and residence. We calculated adjusted odds ratios (ORs) and 95% confidence intervals (95% CIs) for detectable vs non-detectable AFB1 -lysine albumin adducts and gallbladder cancer. AFB1 -lysine albumin adducts were detected in 50.0% of GBC cases, and risk of GBC was twice as high in those with detectable vs undetectable levels (OR = 2.0, 95% CI = 1.0-3.9). ORs ranged from 1.8 (95% CI = 0.75-4.3) for 0.5 to <1.75 pg/mg vs undetectable adduct levels to 2.2 (95% CI = 0.91-5.6) for >3.36 pg/mg vs undetectable, suggesting a dose-response (Ptrend = .05). When restricted to cases diagnosed before the median time to diagnosis after blood draw (18.4 years), results were similar (OR = 2.2, 95% CI = 0.80-5.8) to those for the entire follow-up duration. The OR was 9.4 (95% CI = 1.7-51.1) for individuals with detectable AFB1 -lysine albumin adducts and self-reported gallstones compared to individuals with neither. Participants with detectable AFB1 -lysine albumin adducts at baseline had increased risk of developing GBC, replicating the previously observed association between AFB1 exposure and providing the first evidence of temporality.


Body condition score of Nellore beef cows: a heritable measure to improve the selection of reproductive and maternal traits.
Despite the economic importance of beef cattle production in Brazil, female reproductive performance, which is strongly associated with production efficiency, is not included in the selection index of most breeding programmes due to low heritability and difficulty in measure. The body condition score (BCS) could be used as an indicator of these traits. However, so far little is known about the feasibility of using BCS as a selection tool for reproductive performance in beef cattle. In this study, we investigated the sources of variation in the BCS of Nellore beef cows, quantified its association with reproductive and maternal traits and estimated its heritability. BCS was analysed using a logistic model that included the following effects: contemporary group at weaning, cow weight and hip height, calving order, reconception together with the weight and scores of conformation and early finishing assigned to calves at weaning. In the genetic analysis, variance components of BCS were estimated through Bayesian inference by fitting an animal model that also included the aforementioned effects. The results showed that BCS was significantly associated with all of the reproductive and maternal variables analysed. The estimated posterior mean of heritability of BCS was 0.24 (highest posterior density interval at 95%: 0.093 to 0.385), indicating an involvement of additive gene action in its determination. The present findings show that BCS can be used as a selection criterion for Nellore females.


Barriers and facilitators: Clinicians' opinions and experiences of telehealth before and after their use of a telehealth platform for child language assessment.
Despite emerging evidence of validity and reliability, speech and language therapists' (SLT) uptake of telehealth has been limited and barriers remain to the effective and confident use of this service model. The COVID-19 pandemic has caused significant disruption to essential health services, including speech and language therapy assessment and intervention, meaning that telehealth must now be considered as part of the suite of service delivery options for all clinicians. To explore the perceived barriers and facilitators of telehealth among community paediatric SLTs before and after their use of a telehealth platform with an embedded standardised assessment tool. Mixed-methods questionnaires were developed for this study and completed by SLTs before and after the 3-month trial of the telehealth platform. A total of 38 SLTs completed the pre-trial questionnaire and training in the use of telehealth platform (Coviu), including instruction in using a standardised, norm referenced language test as an integrated tool within the Coviu platform. A total of 27 SLTs went on to use the telehealth platform, and 25 of these completed the post-trial questionnaire on which subsequent qualitative and quantitative analysis was completed. Prior to using the platform, perceived barriers included technology issues, limited clinician experience and concerns around parent acceptance of the service. Potential facilitators included access to appropriate platforms, tools and resources as well as increased clinician confidence with telehealth. Following the trial, barriers to telehealth use continued to include technology barriers, particularly internet stability, and client issues, including suitability for telehealth services. Facilitators for future telehealth use included access to appropriate platforms for telehealth, stable and appropriate internet connectivity, and more extensive telehealth resources for both assessment and intervention for this mode of service delivery. This study provides insights into the perceptions of the barriers and facilitating factors for telehealth use among community-based SLTs. This information will be useful in developing strategies to promote uptake and effective and confident use of telehealth as a mode of service delivery beyond the pandemic. What is already known on the subject Research about telehealth has shown that it is a reliable and valid way of delivering speech pathology services, yet many clinicians have been wary of its use and uptake of telehealth prior to COVID-19 had been limited. We wanted to know what SLTs thought about using telehealth before and after participating in a 3-month trial of a telehealth platform with an embedded formal language assessment. What this study adds to existing knowledge This study indicates that technology issues including internet stability are a barrier to effective telehealth services, but that appropriate telehealth platforms, resources and experience are facilitators of uptake and successful use of telehealth. What are the potential or actual clinical implications of this work? This information will be useful in developing strategies to promote uptake and effective and confident use of telehealth as a mode of service delivery for children during and beyond the pandemic, including those isolated by geographical or transport barriers.


Flow-dependent vascular heat transfer during microwave thermal ablation.
Microwave tumor ablation is an attractive option for thermal ablation because of its inherent benefits over radiofrequency ablation (RFA) in the treatment of solid tumors such as hepatocellular carcinoma (HCC). Microwave energy heats tissue to higher temperatures and at a faster rate than RFA, creating larger, more homogenous ablation zones. In this study, we investigate microwave heating near large vasculature using coupled fluid-flow and thermal analysis. Low-flow conditions are predicted to be more likely to cause cytotoxic heating and, therefore, vessel thrombosis and endothelial damage of downstream tissues. Such conditions may be more prevalent in patient with severe cirrhosis or compromised blood flow. High-flow conditions create the more familiar heat-sink effect that can protect perivascular tissues from the intended thermal damage. These results may help guide placement and use of microwave ablation technologies in future studies.


Impact of switching from lopinavir/ritonavir to atazanavir/ritonavir on body fat redistribution in virologically suppressed HIV-infected adults.
Changes in body fat distribution in virologically suppressed HIV-infected patients switching from lopinavir/ritonavir (LPV/r) to atazanavir/ritonavir (ATV/r) were assessed. A prospective comparative study was conducted of 37 patients receiving LPV/r regimens switching to ATV/r with 46 patients continuing with LPV/r. Body composition was assessed with whole-body dual-energy x-ray absorptiometry (DXA). Abdominal CT scans were also performed in a subset of patients. Groups were comparable in baseline demographic, clinical, and anthropometric characteristics. After 12 months, peripheral fat did not change significantly, but an increase in trunk fat was observed only in the ATV/r group (0.87 kg, p = 0.021). The percentage of patients with an increase ≥20% in total fat was 37.8% and 15.2% in the ATV/r and LPV/r groups, respectively (p = 0.018). In the ATV/r group, the increase in trunk fat (9.4%) was significantly higher than in peripheral fat (3.7%) (p = 0.007), leading to a significant increase in fat mass ratio (3.76%, p = 0.028), whereas no significant differences were found among LPV/r patients. CT scans showed that abdominal fat increase corresponded to both visceral (28%, p = 0.008) and subcutaneous fat (42%, p = 0.008). These data suggest that switching from LPV/r to ATV/r is associated with increased trunk fat, both subcutaneous and visceral.


Aberrant expression of CXCR4 significantly contributes to metastasis and predicts poor clinical outcome in breast cancer.
Triple negative breast cancer is known for its visceral metastasis. We have found that CXCR4 is overexpressed in triple negative breast cancer and is associated with visceral metastasis. We further investigated whether CXCR4 is a prognostic factor affecting survival following visceral metastasis in breast cancer patients. Our results indicate that increased CXCR4 expression among breast cancer patients with visceral metastasis was positively correlated with poor overall survival (P<0.001). Silencing of CXCR4 was associated with a decrease in the tumorigenic properties of MDA-MB-231 breast cancer cells, caused reversion of EMT and suppression of MMP-9, increased apoptosis, and caused a reduced incidence of tumor lung metastasis in mice. These results are indicative of CXCR4 having a predictive role in patients with visceral metastasis and indicate that shRNA knock down of CXCR4 might be a novel therapeutic strategy to prevent breast cancer metastasis when CXCR4 is overexpressed.


Quality assurance of progenitor cell content of apheresis products: a comparison of clonogenic assays and CD34+ enumeration. The Canadian Apheresis Group and Canadian Bone Marrow.
The most common methods used for evaluation of the haematopoietic stem cell content of peripheral blood apheresis products are the colony forming cell assay and the enumeration of CD34+ cells by flow cytometry. The Canadian Apheresis Group and the Canadian Bone Marrow Transplant Group established a multicentre study to compare the reproducibility of colony forming cell assays and CD34+ enumeration by flow cytometry in six transplant centres routinely performing haematopoietic stem cell apheresis. Over a 5-month period in 1996, 31 fresh apheresis samples were shipped by overnight courier for testing at six centres to perform CD34+ enumeration by flow cytometry and clonogenic assays. The mean coefficient of variation and range for the following assays were: cell count 36% (2.6-148%), CFU-GM 82% (46-123%), CD34+ absolute/kg 60% (14-174%) and CD34+ per cent 42% (12-84%). The wide variation in cell count in this pilot study highlights the difficulties related to provision of samples for quality assessment programmes. Results showed poor interinstitutional reproducibility even among selected samples with similar cell counts for both CFC and CD34+ assays demonstrating the need for development and implementation of an interinstitutional quality assurance programme for haematopoietic stem cell assessment. Provision of a reliable source of testing material will be a necessary next step.


Satisfaction and attitude of bipolar patients regarding electroconvulsive therapy: modified or unmodified.
Objective: Ministry of Health of Turkey issued a legislation to use only modified electroconvulsive therapy (ECT) in 2005, and this study aimed to assess satisfaction and attitude of bipolar patients regarding modified and unmodified electroconvulsive therapy.Methods: A total of 100 patients (50 treated with modified electroconvulsive therapy (M-ECT) and 50 treated with unmodified ECT (UM-ECT) with a diagnosis of Bipolar Disorder (depressive or manic episode) were invited to participate in this study. Patients with euthymic mood were included. Satisfaction and attitude towards ECT were evaluated with a structured attitude questionnaire, and M-ECT and UM-ECT patients, and their subgroups (depressive vs. manic) were compared.Results: No significant differences were found between M-ECT and UM-ECT groups regarding age, sex, marital status and occupation. The majority of all patients (78%) were satisfied from treatment with ECT and with the outcome (88%), without significant differences between modified and unmodified groups. Forgetfulness (70%) and headaches (57%) occurred in all groups, with the only significant difference in forgetfulness being reported by more manic patients treated with UM-ECT. Depressive and manic patients treated with UM-ECT reported concerns of brain damage and physical harm significantly more frequently. While 86% of patients treated with M-ECT consented to a future treatment, this was significantly less in patients treated with UM-ECT (50%).Conclusions: Bipolar patients report a high degree of satisfaction treated either with modified or unmodified ECT but there was a significant difference in perception of adverse effects and willingness for receiving ECT in future.


[Computer diagnosis of gastric dysplasia and program design].
Two step processes were taken in computer diagnosis of gastric dysplasia. 1. 5 measurement values of dysplastic glandular tube obtained by using image analysis system were taken as the basis for judging the degree of dysplasia. Three glandular tubes of dysplasia were measured in each case. 2. Computer pathology diagnostic program using BASIC language ran in IBM computer. 5 parameters were input into computer for three stage-diagnosis. The first stage: 5 parameters were counted basing on three models to obtain three values which reflected the objective feature of the same glandular tube from different aspects. The second stage: diagnosis of a dysplastic glandular tube was obtained depending on the three values judged synthetically. Variate 'N' was introduced for controlling the first and second stage diagnosis of the three glandular tubes. The third stage diagnosis started as soon as N = 3. The third stage: diagnostic values of three glandular tubes were balanced and analysed depending on diagnostic criteria to reach the final diagnosis.


Cytotoxic activities of chemical constituents from Mesua daphnifolia.
Detail chemical investigations on the stem bark of Mesua daphnifolia gave three triterpenoids and four xanthones. They are friedelin (1), friedelan-1,3-dione (2), lup-20(29)- en-3ss-ol (3), cudraxanthone G (4), ananixanthone (5), 1,3,5-trihydroxy-4-methoxyxanthone (6) and euxanthone (7). These chemical constituents were tested in vitro for their cytotoxic activities against four cell lines, MDA-MB-231 (human estrogen receptor negative breast cancer), HeLa (cervical carcinoma), CEM-SS (T-lymphoblastic leukemia) and CaOV3 (human ovarian cancer). Compound 4 showed a broad spectrum of activity against the MDA-MB-231, HeLa and CEM-SS cell lines with IC5 0 values of 1.3, 4.0 and 6.7 microg/ml respectively. Meanwhile, the other compounds 1, 2, 3, 5, 6 and 7 gave only selective activities against the cell lines.


The COOH-terminal nuclear localization sequence of interferon gamma regulates STAT1 alpha nuclear translocation at an intracellular site.
We have recently shown that the nuclear localization of IFN gamma is mediated by a polybasic nuclear localization sequence (NLS) in its C terminus. This NLS is required for the full expression of biological activity of IFN gamma, both extracellularly and intracellularly. We now show that this NLS plays an integral intracellular role in the nuclear translocation of the transcription factor STAT1 alpha activated by IFN gamma. Treatment of IFN gamma with antibodies to the C-terminal region (95-133) containing the NLS blocked the induction of STAT1 alpha nuclear translocation. The antibodies had no effect on nuclear translocation of STAT1 alpha in IFN gamma treated cells. A deletion mutant of human IFN gamma, IFN gamma (1-123), which is devoid of the C-terminal NLS region was found to be biologically inactive, but was still able to bind to the IFN gamma receptor complex on cells with a K(d) similar to that of the wild-type protein. Deletion of the NLS specifically abolished the ability of IFN gamma(1-123) to initiate the nuclear translocation of STAT1 alpha, which is required for the biological activities of IFN gamma following binding to the IFN gamma receptor complex. Thus, the NLS region appears to contribute minimally to extracellular high-affinity receptor-ligand binding, yet exerts a strong functional role in STAT1 alpha nuclear localization. A high-affinity site for the interaction of the C-terminal NLS domain of IFN gamma with a K(d) approx. 3 x 10(-8) M(-1) has been described by previous studies on the intracellular cytoplasmic domain of the IFN gamma receptor alpha-chain. To examine the role of the NLS at the intracellular level, we microinjected neutralizing antibodies raised against the C-terminal NLS domain of IFN gamma into the cytoplasm of cells before treatment of cells with IFN gamma. These intracellular antibodies specifically blocked the nuclear translocation of STAT1 alpha following the subsequent treatment of these cells extracellularly with IFN gamma. These data show that the NLS domain of IFN gamma interacts at an intracellular site to regulate STAT1 alpha nuclear import. A C-terminal peptide of murine IFN gamma, IFN gamma(95-133), that contains the NLS motif, induced nuclear translocation of STAT1 alpha when taken up intracellularly by a murine macrophage cell line. Deletion of the NLS motif specifically abrogated the ability of this intracellular peptide to cause STAT1 alpha nuclear translocation. In cells activated with IFN gamma, IFN gamma was found to as part of a complex that contained STAT1 alpha and the importin-alpha analog Npi-1, which mediates STAT1 alpha nuclear import. The tyrosine phosphorylation of STAT1 alpha, the formation of the complex IFN gamma/Npi-1/STAT1 alpha complex and the subsequent nuclear translocation of STAT1 alpha were all found to be dependent on the presence of the IFN gamma NLS. Thus, the NLS of IFN gamma functions intracellularly to directly regulate the activation and ultimate nuclear translocation STAT1 alpha.


P-chlorophenoxyisobutyric acid impairs auxin response for gravity-regulated peg formation in cucumber (Cucumis sativus) seedlings.
Cucumber (Cucumis sativus L.) seedlings form a specialized protuberance, the peg, on the transition zone between the hypocotyl and the root. When cucumber seeds germinate in a horizontal position, the seedlings develop a peg on the lower side of the transition zone. To verify the role of auxin action in peg formation, we examined the effect of the anti-auxin, p-chlorophenoxyisobutyric acid (PCIB), on peg formation and mRNA accumulation of auxin-regulated genes. Application of PCIB to cucumber seedlings inhibited peg formation. The application of indole-3-acetic acid (IAA) competed with PCIB and induced peg formation. Furthermore, application of PCIB decreased auxin-inducible CsIAA1 mRNA and increased auxin-repressible CsGRP1 mRNA in the lower side of the transition zone. The differential accumulation of CsIAA1 and CsGRP1 mRNAs in the transition zone of cucumber seedlings grown in a horizontal position was smaller in the PCIB-treated seedlings. These results demonstrate that endogenous auxin redistributes and induces the differential expression of auxin-regulated genes, and ultimately results in the suppression or induction of peg formation in the gravistimulated transition zone of cucumber seedlings.


Bladder cancer mortality of workers exposed to aromatic amines: a 58-year follow-up.
We previously investigated bladder cancer risk in a cohort of dyestuff workers who were heavily exposed to aromatic amines from 1922 through 1972. We updated the follow-up by 14 years (through 2003) for 590 exposed workers to include more than 30 years of follow-up since last exposure to aromatic amines. Expected numbers of deaths from bladder cancer and other causes were computed by use of national mortality rates from 1951 to 1980 and regional mortality rates subsequently. There were 394 deaths, compared with 262.7 expected (standardized mortality ratio = 1.50, 95% confidence interval = 1.36 to 1.66). Overall, 56 deaths from bladder cancer were observed, compared with 3.4 expected (standardized mortality ratio = 16.5, 95% confidence interval = 12.4 to 21.4). The standardized mortality ratio for bladder cancer increased with younger age at first exposure and increasing duration of exposure. Although the standardized mortality ratio for bladder cancer steadily decreased with time since exposure stopped, the absolute risk remained approximately constant at 3.5 deaths per 1000 man-years up to 29 years after exposure stopped. Excess risk was apparent 30 years or more after last exposure.


The psychological and social aspects of orthognathic treatment.
Cooperative management of dentofacial abnormalities by orthodontists and oral and maxillofacial surgeons has experienced tremendous growth in recent years. Frequently these patients have suffered considerable emotional trauma from ridicule of their deformity. This history of emotional abuse may influence the patient's attitude and expectations regarding corrective treatment and even lead to dissatisfaction in spite of technical success. Review of the literature and interviews with patients previously treated for dentofacial abnormalities revealed a very high rate of satisfaction. This high degree of satisfaction is in contrast to several studies involving patients undergoing cosmetic plastic surgery. However, in spite of over-all satisfaction, retrospective interviews identified a number of concerns which deserve additional attention. These concerns would be best approached with a preoperative interview to delineate the patient's motivation and expectations. Such an interview, including a cursory psychological evaluation, could provide increased insight and communication among orthodontist, surgeon, and patient. The results would help identify and prevent some of the pitfalls leading to patient dissatisfaction after treatment.


The reaction of protein amino groups with methyl 5-iodopyridine-2-carboximidate. A possible general method of preparing isomorphous heavy-atom derivatives of proteins.
1. The synthesis of methyl 5-iodopyridine-2-carboximidate and its reaction with amino groups of model compounds and performic acid-oxidized insulin are described. The reagent was designed to introduce heavy atoms into specific sites in proteins. 2. Specific reaction with the amino groups of oxidized insulin can be achieved under reasonably mild conditions giving rise to the corresponding N-monosubstituted amidines. 3. The extent of reaction of this reagent with protein amino groups can be readily determined by difference spectroscopy. Modification of lysine residues inhibits tryptic cleavage at such residues, and this can be of assistance in establishing the site of modification in the primary structure. 4. Evidence is presented to show that methyl 5-iodopyridine-2-carboximidate can react specifically, at pH5.0, with the aromatic amino group of 3-amino-l-tyrosine; the final product of this reaction is a 2-arylbenzoxazole. 5. The use of this reagent as a general method for preparing heavy-atom isomorphous derivatives of proteins is discussed.


Palladium-catalyzed coupling of sp(2)-hybridized tellurides.
Vinylic tellurides are of importance due to their useful behavior as synthons and intermediates. Recently, the use of these compounds in place of vinylic halides or triflates in the palladium-catalyzed cross-coupling reaction has emerged as a powerful tool in the preparation of conjugated enyne and enediyne. In this way, vinylic tellurides can behave as aryl or vinyl carbocation equivalents. This review focuses on methods that involve the use of vinylic tellurides in palladium-catalyzed cross coupling reaction.


[Extrahepatic obstructive jaundice caused by Fasciola hepatica].
A 58 year old female patient with diabetes manifested 30 years ago is reported. She had digestive disorders since 20 years ago, and a diagnosis of cholecystopathy had been established. Furtherly, she had jaundice, acholia and pruritus; this picture remitted spontaneously. During the next year she had again jaundice, epigastric pain and vomitings; this picture also remitted with home rest. Fifteen days prior to her admittance she had again jaundice, epigastralgia extending to the back, vomitings and pruritus, as well as a diabetic uncontrol. She was admitted though bile ducts were not roentgenographically explored as a result of iodine allergy. A Fasciola hepatica was intraoperatively found.


Topical Tranexamic Acid for the Treatment of Acute Epistaxis: A Systematic Review and Meta-analysis.
To compare topical tranexamic acid (TXA) with control groups for the treatment of acute epistaxis assessing bleeding cessation, discharge within 2 hours, rebleeding rates, complication rates, and patient satisfaction. PubMed, CINAHL, LILACS, Scopus, the Cochrane Database of Systematic Reviews, and the Cochrane Central Register of Controlled Trials were searched from inception to November 2018. All randomized controlled trials comparing topical TXA with control groups for the treatment of acute epistaxis in humans were included. There were no age, language, or date restrictions. Data were double extracted into a predefined worksheet, and quality analysis was performed using the Cochrane Risk of Bias tool. Three studies (n = 408 patients) were identified. Topical TXA was not associated with a statistically significant difference in cessation of bleeding within 30 minutes. However, more patients were discharged within 2 hours of arrival, there were fewer episodes of rebleeding within both the first 24 hours and at 1 week, and there was higher patient satisfaction in the TXA group. There was no difference identified in complication rates. Relevance to Patient Care and Clinical Practice: This review compares topical TXA with control groups for epistaxis and discusses the risks and benefits of adding this therapy to usual care. Topical TXA appears to be a reasonable option for the treatment of acute epistaxis, with reduced rebleeding rates, shorter discharge times, and minimal risk of complications. Topical TXA may be considered as part of the treatment of acute epistaxis.


Yttrium-90 Radioembolization in Patients with Hepatocellular Carcinoma Who have Previously Received Sorafenib.
Yttrium-90 radioembolization (RE) is a locoregional therapy option for hepatocellular carcinoma (HCC). Sorafenib is a multikinase inhibitor used in HCC that can potentially affect the efficacy of RE by altering tumor vascularity or suppressing post-irradiation angiogenesis. The safety and efficacy of sorafenib followed by RE has not been previously reported. Patients with HCC who received RE after sorafenib were included in this retrospective review. Overall survival, toxicity, and maximal radiographic response and necrosis criteria were examined. Ten patients (15 RE administrations) fit the inclusion criteria. All were Barcelona Clinic Liver Cancer (BCLC) stage C. Median follow-up was 16.5 weeks. Median overall survival and radiographic progression-free survival were 30 and 28 weeks, respectively. Significant differences in overall survival were seen based on Child-Pugh class (p = 0.002) and radiographic response (p = 0.009). Three patients had partial response, six had stable disease, and one had progressive disease. Grade 1 or 2 acute fatigue, anorexia, and abdominal pain were common. Three patients had Grade 3 ascites in the setting of disease progression. Two patients had Grade 3 biochemical toxicity. One patient was sufficiently downstaged following RE and sorafenib to receive a partial hepatectomy. Yttrium-90 RE in patients with HCC who have received sorafenib demonstrate acceptable toxicity and rates of radiographic response. However, the overall survival is lower than that reported in the literature on RE alone or sorafenib alone. This may be due in part to more patients in this study having advanced disease compared to these other study populations. Larger prospective studies are needed to determine whether the combination of RE and sorafenib is superior to either therapy alone.


Atmospheric halocarbons, hydrocarbons, and sulfur hexafluoride: global distributions, sources, and sinks.
The global distribution of fluorocarbon-12 and fluorocarbon-11 is used to establish a relatively fast interhemispheric exchange rate of 1 to 1.2 years. Atmospheric residence times of 65 to 70 years for fluorocarbon-12 and 40 to 45 years for fluorocarbon-l1 best fit the observational data. These residence times rule out the possibility of any significant missing sinks that may prevent these fluorocarbons from entering the stratosphere. Atmospheric measurements of methyl chloroform support an 8-to 10-year residence time and suggest global average hydroxyl radical (HO) concentrations of 3 x 10(5) to 4 x 10(5) molecules per cubic centimeter. These are a factor of 5 lower than predicted by models. Additionally, methyl chloroform global distribution supports Southern Hemispheric HO levels that are a factor of 1.5 or more larger than the Northern Hemispheric values. The long residence time and the rapid growth of methyl chloroform cause it to be a potentially significant depleter of stratospheric ozone. The oceanic sink for atmospheric carbon tetrachloride is about half as important as the stratospheric sink. A major source of methyl chloride (3 x 10(12)grams per year), sufficient to account for nearly all the atmospheric methyl chloride, has been identified in the ocean.


Discreteness-induced transitions in multibody reaction systems.
A decrease in system size can induce qualitatively different behavior compared to the macroscopic behavior of the corresponding large-size system. The mechanisms of this transition, which is known as the small-size transition, can be attributed to either a relative increase in the noise intensity or to the discreteness of the state space due to the small system size. The former mechanism has been intensively investigated using several toy and realistic models. However, the latter has rarely been analyzed and is sometimes confused with the former, because a toy model that extracts the essence of the discreteness-induced transition mechanism is lacking. In this work, we propose a one- and three-body reaction system as a minimal model of the discreteness-induced transition and derive the conditions under which this transition occurs in more complex systems. This work enriches our understanding of the influence of small system size on system behavior.


Obesity and Overweight in American Indian and Alaska Native Children, 2006-2015.
To estimate obesity and overweight prevalence in American Indian and Alaska Native (AI/AN) children across genders, ages, and geographic regions in the Indian Health Service active clinical population. We obtained data from the Indian Health Service National Data Warehouse. At least 184 000 AI/AN children aged 2 to 19 years had body mass index data for each year studied, 2006 to 2015. We calculated body mass index percentiles with the 2000 Centers for Disease Control and Prevention growth charts. In 2015, the prevalence of overweight and obesity in AI/AN children aged 2 to 19 years was 18.5% and 29.7%, respectively. Boys had higher obesity prevalence than girls (31.5% vs 27.9%). Children aged 12 to 19 years had a higher prevalence of overweight and obesity than younger children. The AI/AN children in our study had a higher prevalence of obesity than US children overall in the National Health and Nutrition Examination Survey. Results for 2006 through 2014 were similar. The prevalence of overweight and obesity among AI/AN children in this population may have stabilized, while remaining higher than prevalence for US children overall.


Development of squamous cell carcinoma on an inflammatory linear verrucous epidermal nevus in the genital area.
Inflammatory linear verrucous epidermal nevus is a rare cutaneous disorder characterized by pruritic, erythematous, and verrucous papules and plaques along the lines of Blaschko. Histopathologically, there is a benign verrucous proliferation of keratinocytes together with alternating parakeratosis and orthokeratosis as well as inflammatory changes. We report a patient who developed squamous cell carcinoma (SCC) on an inflammatory linear verrucous epidermal nevus and we discuss the importance of regular follow-up of patients with epidermal nevi.


[Changes in individual profiles of cerebral hemispheric asymmetry during somatosensory stimulation due to wearing of G-suits by healthy adults and children].
Presented are results of the investigations of individual profiles of the brain interhemispheric asymmetry (IPIHA) in healthy grown-ups and children prior to, during, and immediately after somatosensory stimulation. The somatosensory stimulation was performed by one-time wearing of space g-loading suit PENGUIN and its modification ADELIE. IPIHA was studied by the main functional asymmetries including motor hand asymmetry, sensory asymmetry of the visual hemispheres, body mass center asymmetry (BMA) using a computerized stabilimeter indirectly measuring the muscle tone of contralateral extensor. Results demonstrate differences in IPIHA of grown-ups and children, persons with right- and left-hand motor asymmetry. It was shown that peculiar features of standing posture acquisition with and without visual control are original IPIHA and age dependent. Initial stability was higher in grown-ups than children and right-handed grown-ups and left-handed children. IPIHA and stability of the vertical posture can be modified even during single somatosensory stimulation. Unequal effects of the somatosensory stimulation on IPIHA in right- and left-handed subjects of varying age dictate the necessity to allow for these differences when assessing effects of the somatosensory stimulation in grown-ups and developing criteria of effective therapy of patients with CNS pathology, specifically, infantile cerebral paralysis.


Longitudinal assessment of occupational determinants of chlorpyrifos exposure in adolescent pesticide workers in Egypt.
Chlorpyrifos (CPF) is an organophosphourus insecticide applied to cotton fields by adolescents employed by the Egyptian Ministry of Agriculture. Urinary 3,5,6-trichloro-2-pyridinol (TCPy) is a biomarker of CPF exposure that has substantial variability among these applicators. In order to identify predictors of CPF exposure, we conducted a longitudinal study of 43 adolescent pesticide applicators in Egypt from April 2010 to January 2011 in Egypt. Urinary TCPy was quantified at 25 time-points, prior to, during, and following application. We used log-linear regression and a best subset selection approach to identify the exposure determinants that were most predictive of cumulative TCPy and participants' highest TCPy values (peak exposure). Applicators had cumulative urinary TCPy levels ranging from 167 to 49,8208μg/g creatinine. Total hours applying CPF (semi-partial r2=0.32), and total hours in the field applying other pesticides (semi-partial r2=0.08) were the strongest predictors of cumulative TCPy. Applicators had peak urinary TCPy levels ranging from 4 to 5715μg/g creatinine. The amount of time applying pesticides prior to blood draw was the strongest predictor of peak TCPy (semi-partial r2=0.30). We also observed evidence that wearing clean clothes to work was associated with lower longitudinal TCPy. Our results suggest there is an opportunity for targeted interventions, particularly related to hygiene or implementation of personal protective equipment usage to reduce CPF exposure among adolescent pesticide workers.


National Structural Survey of Veterans Affairs Home-Based Primary Care Programs.
To describe the current structural and practice characteristics of the Department of Veterans Affairs (VA) Home-Based Primary Care (HBPC) program. We designed a national survey and surveyed HBPC program directors on-line using REDCap. We received 236 surveys from 394 identified HBPC sites (60% response rate). HBPC site characteristics were quantified using closed-ended formats. HBPC program directors were most often registered nurses, and HBPC programs primarily served veterans with complex chronic illnesses that were at high risk of hospitalization and nursing home care. Primary care was delivered using interdisciplinary teams, with nurses, social workers, and registered dietitians as team members in more than 90% of the sites. Most often, nurse practitioners were the principal primary care providers (PCPs), typically working with nurse case managers. Nearly 60% of the sites reported dual PCPs involving VA and community-based physicians. Nearly all sites provided access to a core set of comprehensive services and programs (e.g., case management, supportive home health care). At the same time, there were variations according to site (e.g., size, location (urban, rural), use of non-VA hospitals, primary care models used). HBPC sites reflected the rationale and mission of HBPC by focusing on complex chronic illness of home-based veterans and providing comprehensive primary care using interdisciplinary teams. Our next series of studies will examine how HBPC site structural characteristics and care models are related to the processes and outcomes of care to determine whether there are best practice standards that define an optimal HBPC structure and care model or whether multiple approaches to HBPC better serve the needs of veterans.


Anomalous surface states modify the size-dependent mechanical properties and fracture of silica nanowires.
Molecular dynamics simulations of amorphous silica nanowires under tension were analyzed for size and surface stress effects on mechanical properties and for structural modifications via bond angle distributions. Their fracture behavior was also investigated beyond the elastic limit. The Young's moduli of silica nanowires were predicted to be about 75-100 GPa, depending on the nanowire size. The ultimate strength was calculated to be ∼10 GPa, depending on the diameter, which is in excellent agreement with the experiments. The dependence of the Young's modulus on nanowire diameter is explained in terms of surface compressive stress effects. The fracture behavior of nanowires was also found to be influenced by surface compressive stresses. Bond angle distribution analysis of various nanowires reveals significant compressive surface states, as evidenced by the appearance of a secondary peak in the Si-O-Si bond angle distribution at ∼97°, which is absent in bulk silica. The strain rate was found to have a negligible effect on the Young's modulus of the silica nanowires, but it has a critical role in determining their fracture mode.


Cutting efficiency of Reciproc and waveOne reciprocating instruments.
The aim of the present study was to evaluate the cutting efficiency of 2 new reciprocating instruments, Reciproc and WaveOne. Twenty-four new Reciproc R25 and 24 new WaveOne Primary files were activated by using a torque-controlled motor (Silver Reciproc) and divided into 4 groups (n = 12): group 1, Reciproc activated by Reciproc ALL program; group 2, Reciproc activated by WaveOne ALL program; group 3, WaveOne activated by Reciproc ALL program; and group 4, WaveOne activated by WaveOne ALL program. The device used for the cutting test consisted of a main frame to which a mobile plastic support for the handpiece is connected and a stainless steel block containing a Plexiglas block (inPlexiglass, Rome, Italy) against which the cutting efficiency of the instruments was tested. The length of the block cut in 1 minute was measured in a computerized program with a precision of 0.1 mm. Means and standard deviations of each group were calculated, and data were statistically analyzed with 1-way analysis of variance and Bonferroni test (P < .05). Reciproc R25 displayed greater cutting efficiency than WaveOne Primary for both the movements used (P < .05); in particular, Reciproc instruments used with their proper reciprocating motion presented a statistically significant higher cutting efficiency than WaveOne instruments used with their proper reciprocating motion (P < .05). There was no statistically significant difference between the 2 movements for both instruments (P > .05). Reciproc instruments demonstrated statistically higher cutting efficiency than WaveOne instruments.


Histological and immunohistochemical detection of different Helicobacter species in the gastric mucosa of cats.
Detailed histopathological evaluation of the gastric mucosa of Helicobacter-infected cats is complicated by the difficulty of recognizing Helicobacter organisms on hematoxylin and eosin (HE)-stained sections and the ability of multiple Helicobacter species to infect cats. In this study, the presence and localization of different species of Helicobacter in the stomachs of cats was investigated using silver staining and immunohistochemistry. Five groups containing 5 cats each were established (group 1: urease negative and Helicobacter free; groups 2, 3, 4, and 5: urease positive and infected with Helicobacter heilmannii, unclassified Helicobacter spp., Helicobacter felis, and Helicobacter pylori, respectively). Gastric samples were evaluated by HE and silver staining and by immunohistochemistry with 3 different anti-Helicobacter primary antibodies. Helicobacter were detected by Steiner stain in all infected cats at the mucosal surface, in the lumen of gastric glands, and in the cytoplasm of parietal cells. In silver-stained sections, H. pylori was easily differentiated from H. felis, H. heilmannii, and unclassified Helicobacter spp., which were larger and more tightly coiled. No organisms were seen in uninfected cats. Helicobacter antigen paralleled the distribution of organisms observed in Steiner-stained sections for 2 of the 3 primary antibodies tested. The antisera were not able to discriminate between the different Helicobacter species examined. A small amount of Helicobacter antigen was present in the lamina propria of 3 H. pylori-, 3 H. felis-, and 1 H. heilmannii-infected cat. Minimal mononuclear inflammation was present in uninfected cats and in those infected with unclassified Helicobacter spp. and H. heilmannii cats. In H. felis-infected cats, lymphoid follicular hyperplasia with mild pangastric mononuclear inflammation and eosinophilic infiltrates were present. The H. pylori-infected cats had severe lymphoid follicular hyperplasia and mild to moderate mononuclear inflammation accompanied by the presence of neutrophils and eosinophils. These findings indicate that Steiner staining and immunohistochemistry are useful for detecting Helicobacter infections, particularly when different Helicobacter species can be present. Monoclonal antibodies specific for the different Helicobacter species could be important diagnostic aids. There appear to be differences in the severity of gastritis in cats infected with different Helicobacter species.


Maternal mental health predicts risk of developmental problems at 3 years of age: follow up of a community based trial.
Undetected and untreated developmental problems can have a significant economic and social impact on society. Intervention to ameliorate potential developmental problems requires early identification of children at risk of future learning and behaviour difficulties. The objective of this study was to estimate the prevalence of risk for developmental problems among preschool children born to medically low risk women and identify factors that influence outcomes. Mothers who had participated in a prenatal trial were followed up three years post partum to answer a telephone questionnaire. Questions were related to child health and development, child care, medical care, mother's lifestyle, well-being, and parenting style. The main outcome measure was risk for developmental problems using the Parents' Evaluation of Developmental Status (PEDS). Of 791 children, 11% were screened by the PEDS to be at high risk for developmental problems at age three. Of these, 43% had previously been referred for assessment. Children most likely to have been referred were those born preterm. Risk factors for delay included: male gender, history of ear infections, a low income environment, and a mother with poor emotional health and a history of abuse. A child with these risk factors was predicted to have a 53% chance of screening at high risk for developmental problems. This predicted probability was reduced to 19% if the child had a mother with good emotional health and no history of abuse. Over 10% of children were identified as high risk for developmental problems by the screening, and more than half of those had not received a specialist referral. Risk factors for problems included prenatal and perinatal maternal and child factors. Assessment of maternal health and effective screening of child development may increase detection of children at high risk who would benefit from early intervention. Current Controlled Trials ISRCTN64070727.


Left ventricular function before and following aortic valve replacement.
Twenty-four patients with aortic valve disease were studied before and 19+/-12 months following valve replacement with a well functioning prosthesis. Biplane left ventricular angiography and pressures were utilized to determine end-diastolic volume/m2 (EDV), end-systolic volume/m2 (ESV), ejection fraction (EF), left ventricular mass/m2 (LVM) and stroke work (SW). There were nine patients with aortic stenosis (AS), ten patients with combined stenosis and regurgitation (AS-AR), and five patients with aortic regurgitation (AR). Following surgery, patients with regurgitation preoperatively showed marked regression in EDV and ESV. All groups demonstrated regression in LVM. Fifteen patients with a normal EF preoperatively (65+/-11%) had no change after surgery; the nine patients with a low EF before surgery (38+/-8%) had a normal EF after surgery (60+/-16%). We conclude that left ventricular dilatation, hypertrophy, and reduced left ventricular pump function are largely reversible after successful aortic valve replacement.


Attending to physical health in mental health services in Australia: a qualitative study of service users' experiences and expectations.
Evidence is unequivocal: the premature death of people with severe mental health problems is attributable primarily to cardiovascular disease, and healthcare provided is often suboptimal. With the overarching aim of improving outcomes, policies and guidelines oblige mental health services and psychiatrists to monitor cardio-metabolic health of patients and intervene as appropriate. Practice is highly variable; however, with ongoing debate about resourcing and responsibilities dominated by clinicians who have identified disinterest among patients as influencing practice. Seeking to balance discussion, we posed the question 'what do patients experience and expect of mental health services in relation to their physical health?' To answer it, we interviewed a convenience sample of 40 service users recruited from a mental health service in Australia, early in 2015. Data were analysed using the framework approach. With few regarding themselves as healthy, participants were commonly concerned about side effects of medication, weight and fitness but rarely mentioned tobacco smoking. Participants' accounts reinforce extensive research demonstrating variability in attention to physical health in mental health services. Reports by some participants of comprehensive care are encouraging, but widespread uncertainty about reasons for various assessments and denial of requests for management of medication side effects, including weight gain, gives cause for concern. Although participants in this study wanted to improve their health and health-related quality of life, they acknowledged that their motivation and ability to do so fluctuated with mental health. They expected clinicians to work proactively, especially when symptoms compromised capacity for self-care, and mental health services to provide or enable access to health-promoting interventions. Attention should be given, as a matter of priority, to creating conditions (culture and infrastructure) needed to support sustained attention to physical health within services and, importantly, to full engagement of service users in management of their physical health.