Structural basis of negative cooperativity in transthyretin.
A comparison of the AC and BD binding sites of transthyretin (TTR) was made in terms of the interatomic distances between the Ca atoms of equivalent amino acids, measured across the tetramer channel in each binding site. The comparison of the channel diameter for apo TTR from different sources revealed that in the unliganded transthyretin tetramers the distances between the A, D and H beta-strands are consistently larger, while the distances between the G beta-strands are smaller in one site than in the other. These differences might be described to have a 'wave' character. An analogous analysis performed for transthyretin complexes reveals that the shape of the plot is similar, although the amplitudes of the changes are smaller. The analysis leads us to a model of the changes in the binding sites caused by ligand binding. The sequence of events includes ligand binding in the first site, followed by a slight collapse of this site and concomitant opening of the second site, binding of the second molecule and collapse of the second site. The following opening of the first, already occupied site upon ligand binding in the second site is smaller because of the bridging interactions already formed by the first ligand. This explains the negative cooperativity (NC) effect observed for many ligands in transthyretin.


A case of residual inferior sinus venosus defect after ineffective surgical closure.
A 38-year-old woman presented with cyanosis and heart failure 34 years after patch closure of an atrial septal defect and partial anomalous pulmonary venous connection. CT and cardiac catheterisation showed a residual defect that caused right-to-left shunting. The patch almost blocked the inferior vena cava from the right atrium, resulting in uncommon drainage of the inferior vena cava into the left atrium. Other anomalies included the coronary-to-pulmonary artery fistula and duplicate inferior vena cava with dilated azygos venous system. A second surgery was performed, and we confirmed an inferior sinus venosus defect, which is rare and can be misdiagnosed. The ineffective patch closure had caused a haemodynamic status that rarely occurs. We describe the diagnostic process and emphasise the importance of correctly understanding the entity.


The effect of food on the absorption and pharmacokinetics of rivaroxaban.
Doses of 10 mg, 15 mg, and 20 mg of rivaroxaban are approved for the treatment and prevention of thromboembolic disorders in adult patients. In six Phase I studies, the pharmacokinetics, safety, and tolerability of 2.5 mg, 5 mg, 10 mg, 15 mg, and 20 mg rivaroxaban were investigated in healthy male subjects, and the influence of food on these parameters was investigated for the 10 mg, 15 mg, and 20 mg tablet doses. In addition, an oral suspension containing 1 mg/ml rivaroxaban, which is under investigation for future use in the pediatric population, was investigated at doses of 10 mg and 20 mg. Rivaroxaban was obtained from Bayer Pharma AG, Wuppertal, Germany. Six independent, single-dose, cross-over studies were performed in healthy male subjects (between 13 and 24 subjects were enrolled in each study) to determine the pharmacokinetics, safety, and tolerability of rivaroxaban under fasting and fed conditions. Study 1 was an absolute bioavailability study that compared 5 mg and 20 mg tablet doses with a 1 mg intravenous solution. Studies 2 and 3 were confirmatory food-effect studies that assessed 10 mg and 20 mg tablet doses, respectively, under fed and fasting conditions. Study 4 was a formulation study that evaluated oral suspensions of 10 mg (fasting) and 20 mg (fasting and fed) rivaroxaban vs. a 10 mg tablet (fasted). Study 5 was a dose-proportionality study that assessed 2.5 mg, 5 mg, and 10 mg tablets under fasting conditions. Study 6 was a dose-proportionality study that assessed tablet doses of 10 mg, 15 mg, and 20 mg under fed conditions. Pharmacokinetic parameters, including the area under the plasma concentration-time curve after a single dose, the maximum drug concentration in plasma after a single dose, dose-adjusted values of area under the plasma concentration-time curve and maximum drug concentration in plasma after a single dose, half-life associated with the terminal slope, and time to maximum concentration in plasma after a single dose were evaluated. Adverse events were classified according to their degree of severity and were summarized using Medical Dictionary for Regulatory Activities preferred terms. At all doses, rivaroxaban showed an acceptable safety profile and was well tolerated in healthy individuals. Independent of food and formulation, pharmacokinetic parameters of doses up to 10 mg rivaroxaban were dose proportional and had high oral bioavailability (≥ 80%). Under fasting conditions, pharmacokinetic parameters of 15 mg and 20 mg rivaroxaban increased with dose but were less than dose proportional. However, when taken with food, high bioavailability (≥ 80%) of these doses was achieved independent of formulation. Pharmacokinetic parameters of doses up to 10 mg rivaroxaban were dose proportional and had high oral bioavailability independent of food or whether administered as tablet or solution. High bioavailability (≥ 80%) of 15 mg and 20 mg rivaroxaban was achieved when taken with food; therefore, these doses need to be taken with food.


Estrogen-related receptor α decreases RHOA stability to induce orientated cell migration.
Several physiopathological processes require orientated cellular migration. This phenomenon highly depends on members of the RHO family of GTPases. Both excessive and deficient RHO activity impair directional migration. A tight control is thus exerted on these proteins through the regulation of their activation and of their stability. Here we show that the estrogen-related receptor α (ERRα) directly activates the expression of TNFAIP1, the product of which [BTB/POZ domain-containing adapter for Cullin3-mediated RhoA degradation 2 (BACURD2)] regulates RHOA protein turnover. Inactivation of the receptor leads to enhanced RHOA stability and activation. This results in cell disorientation, increased actin network, and inability to form a lamellipodium at the migration edge. As a consequence, directional migration, but not cell motility per se, is impaired in the absence of the receptor, under pathological as well as physiological conditions. Altogether, our results show that the control exerted by ERRα on RHOA stability is required for directional migration.


Nonfragile Finite-Time Synchronization for Coupled Neural Networks With Impulsive Approach.
This article addresses the problem of the average stochastic finite-time synchronization (ASFTS) for a set of coupled neural networks (NNs) with energy-bounded noises. Due to the channel capacity constraint, the impulsive approach is introduced so as to cut down the communication times among the leader NNs and the follower NNs. Then, a nonfragile controller is designed to improve the robustness of the controller with randomly occurred uncertainty. The sufficient conditions that guarantee the ASFTS of the coupled NNs and the leader NNs are achieved. The boundary of the synchronization error is also obtained by constructing the monotonic increasing functions. Finally, the controller gains are given based on the derived conditions, and their effectiveness is illustrated by a numerical example.


Factors Associated with Acute Kidney Injury among Children with Severe Malaria at Kiryandongo General Hospital, Uganda.
Malaria remains one of the leading health problems of the developing world, and acute kidney injury (AKI) is a well-recognized complication of severe malaria in adults; but the clinical importance of AKI in paediatric severe malaria is not well documented. Knowledge of the prevalence and factors associated with AKI among children with severe malaria is among the key strategies, which can help to reduce the burden of AKI among this vulnerable group. Methodology. A hospital-based prospective cross-sectional descriptive and analytic study of children with severe malaria was carried out at Kiryandongo General Hospital. The study involved 350 children with severe malaria attending the study site from August to October 2021. Questionnaires were administered to caretakers to obtain sociodemographic characteristics. Medical data were obtained through physical examination followed by laboratory tests. Blood samples were tested for creatinine and blood smear for malaria. Data were analyzed using binary logistic regression (bivariate and multivariate) to assess for the factors associated with AKI. A p value < 0.05 was considered statistically significant. The mean age of children with severe malaria was 7.0 ± 3.8 years, and 54.3% of them were male. Of the 350 children enrolled, 167 had AKI, giving an overall AKI prevalence of 47.7% (95% CI: 42.5-53.0). The factors that were significantly associated with AKI among children with severe malaria included caretaker with no formal education (aOR = 21.0, 95% CI: 1.68-261.18, p = 0.018), caretaker with primary education level (aOR = 4.5, 95% CI: 1.41-14.12, p = 0.011), age of child < 5 years (aOR = 1.8, 95% CI: 1.07-2.88, p = 0.025), history of receiving NSAIDs (aOR = 5.6, 95% CI: 2.34-13.22, p < 0.001), moderate anemia (aOR = 3.1, 95% CI: 1.39-6.94, p = 0.006), and severe anemia (aOR = 3.8, 95% CI: 1.66-8.55, p = 0.002). The prevalence of AKI was high among children with severe malaria in Kiryandongo General Hospital. Acute kidney injury among children with severe malaria was associated with low level of education of caretakers, age of children less than 5 years, history of receiving NSAIDs, and anemia. The management of severe malaria should include screening for AKI especially in children under five years of age, anemic, and those who have received NSAIDs.


Mechanism of multidrug resistance of human small cell lung cancer cell line H446/VP.
Small cell lung cancer (SCLC) is the most aggressive form of lung cancer. This study aimed to investigate the mechanism of human small cell lung cancer cell line resistance to etoposide (VP-16), H446/VP. The cell viability was measured by MTT assay. Immunocytochemistry, reverse transcription-polymerase chain reaction (RT-PCR) and Western blotting methods were used to detect the multidrug resistance gene (MDR1), bcl-2, bax and the topoisomerase II (Topo II) expressions in H446 and H446/VP cells after treated with or without VP-16. The 50% inhibition concentration (IC50) of VP-16 on H446 cells was 49 mg/L, and 836 mg/L was for H446/VP cells. The expressions of MDR1 and bcl-2 were up-regulated, while the amounts of bax and Topo II were reduced in H446/VP cells. After treated with 49 mg/L of VP-16, it showed that the drug could significantly inhibit bcl-2 and Topo II expressions, and increase bax expression in H446 cells compared with that of H446/VP cells. The H446/VP cell was stably resistant to VP-16. The decreased expression of Topo II was correlated with the H446/VP multidrug resistance. The elevated expressions of MDR1, and the altered apoptotic pathways also played an important role in VP-16 induced multidrug resistance of SCLC.


Transvenous embolization with a combination of detachable coils and Onyx for a complicated cavernous dural arteriovenous fistula.
Treatment of cavernous dural arteriovenous fistulas (DAVF) is usually made by a transarterial approach. However, in many complicated patients, treatments via transarterial approaches can not be achieved, and only an operation via a transvenous approach is feasible. We aimed to study the feasibility of transarterial embolization of cavernous dural arteriovenous fistulas with a combination detachable coils and Onyx to embolize a complicated cavernous DAVF via a transvenous approach. From August 2006 to August 2007, six cases of complicated cavernous DAVF were embolized with a combination of detachable coils and Onyx via a transvenous approach. Three cases were male and the other three were female. Their ages ranged from 36 to 69 years old. The fistula was in the right lateral cavernous sinus in one case, in the left lateral cavernous sinus in another, and in the bilateral cavernous sinus in 4 cases. One fistula was fed by the right internal carotid artery and its meningohypophyseal trunk; one was fed by the branches of the left internal carotid artery and left external carotid artery; four were fed by the branches of the bilateral internal carotid artery and/or the bilateral external carotid artery. One case was drained via one lateral inferior petrosal sinus; three were drained via bilateral inferior petrosal sinuses; one was drained via one lateral ophthalmic and facial veins; one was drained via the inferior petrosal sinus and the ophthalmic and facial veins. Four were embolized via the inferior petrosal sinus, and two were embolized via the ophthalmic and facial veins. Among six cases of complicated cavernous DAVF, four were fully embolized with Onyx by a single operation, and two cases were fully embolized with Onyx following two operations. Transient headache was found after operation in all patients, but was cured after several days by the symptomatic treatments. In one case, the first operation via the inferior petrosal sinus was a failure; the feeding branches of the external carotid artery were embolized, and transient facial palsy was appeared after operation. The fistula was fully embolized with Onyx via the inferior petrosal sinus after two months with no complications. One bilateral cavernous sinus DAVF was embolized with Onyx via the inferior petrosal sinus by two operations, and transient abducens nerve palsy occurred after embolization. Because Onyx may be injected via a transvenous approach and the microcatheter is easily withdrawn, cavernous sinus via transvenous catheterization and embolization is a safe and efficient way to treat complicated cavernous dural arteriovenous fistulas, especially those for which operations via transarterial approaches have failed, or spontaneous cavernous dural arteriovenous fistulas.


Public stigma towards informal caregiving in Germany: a descriptive study.
This study aims to investigate the public stigma towards informal caregivers of individuals aged 65 years and older in the German population. In an Online-Survey 1038 participants (18 years and older and living in Germany) were sampled using a quota-system based on the German micro census data. To assess public stigma towards informal caregiving for individuals aged 65 years and older, three aspects of stigma were assessed: 1) emotional reactions (adapted Emotional Reaction to Mental Illness Scale), 2) behavioral reactions (adapted Social Distance Scale), and 3) cognitive reactions (newly developed List of Cognitions regarding informal caregiving). Exploratory and confirmatory factor analyses were conducted for the development and adaptation of the three instruments, and their composite reliability is provided. Emotional reactions in terms of devaluing feelings and feelings of misery were low, while appreciative feelings were neither low nor high. Reported social distance was low. Agreement with cognitions towards informal care in terms of devaluing and accusative cognitions was on average low, but high regarding appreciative cognitions. The results show that there is stigma towards informal caregiving for older individuals (65 years and older) in terms of emotional reactions, cognitions and social distance, although the magnitude of this stigma seems to be small. Knowledge regarding the occurrence and magnitude of stigma, as well as the processes that underlie this, is needed to prevent stigmatization and its negative outcomes, or at the very least, to enable the development of support for the affected individuals.


RARγ activation sensitizes human myeloma cells to carfilzomib treatment through the OAS-RNase L innate immune pathway.
Proteasome inhibitors (PIs) such as bortezomib (Btz) and carfilzomib (Cfz) are highly efficacious for patients with multiple myeloma (MM). However, relapses are frequent, and acquired resistance to PI treatment emerges in most patients. Here, we performed a high-throughput screen of 1855 Food and Drug Administration (FDA)-approved drugs and identified all-trans retinoic acid (ATRA), which alone has no antimyeloma effect, as a potent drug that enhanced MM sensitivity to Cfz-induced cytotoxicity and resensitized Cfz-resistant MM cells to Cfz in vitro. ATRA activated retinoic acid receptor (RAR)γ and interferon-β response pathway, leading to upregulated expression of IRF1. IRF1 in turn initiated the transcription of OAS1, which synthesized 2-5A upon binding to double-stranded RNA (dsRNA) induced by Cfz and resulted in cellular RNA degradation by RNase L and cell death. Similar to ATRA, BMS961, a selective RARγ agonist, could also (re)sensitize MM cells to Cfz in vitro, and both ATRA and BMS961 significantly enhanced the therapeutic effects of Cfz in established MM in vivo. In support of these findings, analyses of large datasets of patients' gene profiling showed a strong and positive correlation between RARγ and OAS1 expression and patient's response to PI treatment. Thus, this study highlights the potential for RARγ agonists to sensitize and overcome MM resistance to Cfz treatment in patients.


Prognostic impact of vascular invasion in differentiated thyroid carcinoma: a systematic review and meta-analysis.
The role of vascular invasion (VI) as a prognostic marker in thyroid cancer is continuously debated among investigators. In this systematic review and meta-analysis, we aimed to investigate the association of VI with tumor recurrence and patient mortality in differentiated thyroid cancers (DTCs). We searched five electronic databases for cases of DTC matching our criteria. Data of tumor persistence, locoregional recurrence (LRR), distant recurrence (DR) and overall recurrence/persistence (RP) were extracted and pooled into odds ratios (OR) and corresponding 95% confidence intervals (CIs) using random effect model. Pooled hazard ratio (HR) for disease-specific survival (DSS) was calculated using random effect model weighted by inverse variance method. Publication bias was examined by using Egger's test and funnel plot. From 1650 studies, we included 26 studies comprising 11 961 DTCs for meta-analyses. In DTC patients, we found significant associations of VI with tumor persistence (OR = 2.75; 95% CI = 1.46-5.18), LRR (OR = 4.44; 95% CI = 2.94-6.71), DR (OR = 5.08; 95% CI = 2.95-8.75), overall RP (OR = 3.53; 95% CI = 2.09-5.96) and worse DSS (HR = 2.47; 95% CI = 1.45-4.21). Our results also demonstrated that the presence of extensive VI is associated with a significantly higher risk for DR in follicular thyroid carcinomas as compared with focal VI. Our study demonstrated a significant impact of VI on tumor recurrence and patient survival in DTC patients. The presence and extent of VI should be considered an adverse prognostic factor in DTCs.


Supernatant from stored red cells activates neutrophils.
Bioreactive substances including cytokines and lipids accumulate during storage of red blood cells (RBCs) but their clinical importance is uncertain. The goal of this study was to evaluate the effect of stored RBC supernatant on neutrophil activity in vitro. Packed RBCs (PRBCs) were collected and divided into two aliguots, one leukodepleted and the other nonleukodepleted. Plasma supernatant from PRBCs were collected on days 1, 8, 15, 29 and 35 and its effect on neutrophil expression of CD11b, CD16 and oxidative burst was measured by flow cytometry. Levels of tumour necrosis factor alpha (TNF alpha) and interleukin-8 (IL8) were also measured. The supernatant from PRBC units stored for greater than 15 days activated and primed neutrophils as evidenced by an increase CD11b and CD16 expression and oxidative burst. The greatest effect was seen in the oldest concentrates (35-day-old) (P < 0.008). Leukodepletion abrogated the effects of stored supernatant on CD11b and CD16 expression (P < 0.02) but did not reduce priming of the neutrophil oxidative burst (P > 0.1). Very low levels of IL8 and TNF alpha were detected in stored supernatants. Stored PRBC supernatant contains substances which directly enhance neutrophil expression of adhesion protein CD11b, CD16 and prime neutrophil oxidative burst. The exceedingly low level of IL8 and TNF alpha found in this study suggests that other factors may play a more important role in neutrophil priming and activation.


Prognosis of patients with new prostatitis/pelvic pain syndrome episodes.
Little is known about the natural history of nonbacterial prostatitis/male pelvic pain syndrome, the transition from acute to chronic pelvic pain and risk factors for chronicity. In this study we determined the course of symptoms after physician visits for new nonbacterial prostatitis/pelvic pain syndrome episodes, and determined predictors of symptom persistence 1 year later. A total of 286 male health maintenance organization enrollees (87% white, mean age 46.7 years, 83% completed the 12-month followup) with recent physician visits for new prostatitis/pelvic pain episodes completed baseline, and 3, 6 and 12-month followup telephone interviews, including the National Institutes of Health Chronic Prostatitis Symptom Index in a prospective longitudinal inception cohort study. On average symptoms improved substantially during months 1 to 3, modestly from months 3 to 6 and then remained unchanged. At each followup outcomes were better for men whose initial visit was for a first lifetime episode compared with a recurrent prostatitis/pelvic pain episode. Patients with more severe symptoms (Wald chi-square 11.27, p = 0.0008) and whose episode was recurrent (OR 2.2, 95% CI 1.16 to 4.06) at baseline were significantly more likely to report symptoms 1 year later. Most men who make physician visits for new nonbacterial prostatitis/pelvic pain episodes experience symptom improvement during the next 6 months. However, chronic, mild, persistent or recurrent symptoms are common. Patients with previous episodes and more severe symptoms are at higher risk for chronic pelvic pain.


Zoonotic implications of white-footed mice habitat selection and territoriality in fragmented landscapes.
White-footed mouse (Peromyscus leucopus) populations can thrive in fragmented suburban and urban parks and residential spaces and play a pivotal role in the spread and prevalence of tick-borne diseases. We collected spatial data on 58 individual mice living at the intersection of county park land and residential land in suburban Howard County, MD, U.S.A. We analyzed mouse density, home-range size and overlap, and a Bayesian mixed-effects model to identify the habitats where they were found relative to where they were caught, as well as a resource selection function for general habitat use. We found that as mouse density increased, home-range size decreased. The overlap indices and the resource selection function supported territoriality coupled with site-specific space use in these suburban mouse populations. While mice occurred in open areas, forest edge, and forest, they showed a strong preference for forested areas. Interestingly, mice captured only 30 to 40 m into the forest rarely used the nearby private yards or human structures and this has direct implications for the placement of rodent-targeted tick control treatments. Our study supports the need for zoonotic disease management frameworks that are based on site-specific land cover characteristics as well as specific management objectives.


The effect of context in rural mental health care: Understanding integrated services in a small town.
Unequal health care outcomes for those with mental illness mean that access to integrated models is critical to supporting good physical and mental health care. This is especially so in rural areas where geographic and structural issues constrain the provision of health services. Guided by a conceptual framework about rural and remote health, this study draws on interviews with health providers and other staff and examines the dynamics of integrated primary and community-based specialist care for people with severe and persistent mental illnesses living in rural Australia. Findings show that the facilitation of sustainable linkages between general practice and community mental health requires the skilful exercise of power, knowledge, and resources by partners in order to address the social and structural factors that influence local health situations. These findings suggest that incremental processes of integration that are responsive to patients' and stakeholders' needs and that build on success and increased trust may be more effective than those imposed from the 'top down' that pay insufficient attention to local contexts.


General practice based intervention to prevent repeat episodes of deliberate self harm: cluster randomised controlled trial.
To evaluate the impact of an intervention based in general practice on the incidence of repeat episodes of deliberate self harm. Cluster randomised controlled trial in which 98 general practices were assigned in equal numbers to an intervention or a control group. The intervention comprised a letter from the general practitioner inviting the patient to consult, and guidelines on assessment and management of deliberate self harm for the general practitioner to use in consultations. Control patients received usual general practitioner care. General practices within Avon, Wiltshire, and Somerset Health Authorities, whose patients lived within the catchment area of four general hospitals in Bristol and Bath. 1932 patients registered with the study practices who had attended accident and emergency departments at one of the four hospitals after an episode of deliberate self harm. Primary outcome was occurrence of a repeat episode of deliberate self harm in the 12 months after the index episode. Secondary outcomes were number of repeat episodes and time to first repeat. The incidence of repeat episodes of deliberate self harm was not significantly different for patients in the intervention group compared with the control group (odds ratio 1.2, 95% confidence interval 0.9 to 1.5). Similar findings were obtained for the number of repeat episodes and time to first repeat. Subgroup analyses indicated that there was no differential effect of the intervention according to patient's sex (P=0.51) or method used to cause deliberate self harm (P=0.64). The treatment seemed to be beneficial for people with a history of deliberate self harm, but it was associated with an adverse effect in people for whom the index episode was their first episode (interaction P=0.017). An invitation to consult, sent by the general practitioner of patients who have deliberately harmed themselves, and the use of management guidelines during any subsequent consultation did not reduce the incidence of repeat self harm. A subgroup analysis that indicated that patients who had previously harmed themselves benefited from the intervention was inconsistent with previous evidence and should be treated with caution. More research is needed on how to manage patients who deliberately harm themselves, to reduce the incidence of repeat episodes.


Topological Kondo insulators.
Kondo insulators are a particularly simple type of heavy electron material, where a filled band of heavy quasiparticles gives rise to a narrow band insulator. Starting with the Anderson lattice Hamiltonian, we develop a topological classification of emergent band structures for Kondo insulators and show that these materials may host three-dimensional topological insulating phases. We propose a general and practical prescription of calculating the Z(2) topological indices for various lattice structures. Experimental implications of the topological Kondo insulating behavior are discussed.


Heat transfer and lethality considerations in aseptic processing of liquid/particle mixtures: a review.
Consumer awareness and demand for nutritious yet inexpensive food products call for innovative processing techniques that have both safety and quality as primary objectives. These challenges appear to have been met by aseptic processing techniques, especially for liquid and high-acid foods. However, the extension of aseptic processing principles to low-acid foods containing discrete particles in viscous sauces has not been approved by regulatory agencies, particularly in North America. This apparent limitation is due primarily to the lack of adequate temperature monitoring devices to keep track of particles in dynamic motion, as well as to the residence time distribution of particles flowing in the continuous heat-hold-cool sections of the aseptic processing system. These problems have prompted active research to describe the phenomenal behavior of particulates through sound mathematical modeling and computer simulators. The accuracy of mathematical models depends heavily on how accurate input parametric values are. These parameters include the thermophysical properties of the carrier fluid and particles, as well as the aseptic processing system characteristics in relation to residence time distribution and the fluid-to-particle interfacial heat transfer coefficient. Apparently, several contradictory findings have been reported in the literature with respect to the effect of various processing parameters on the above-mentioned input parametric values. The need therefore arises for more collaborative studies involving the industry and academia. This review brings to perspective, the current status on the aseptic processing of particulate foods with respect to the critical processing parameters which affect the fluid-to-particle convective heat transfer coefficient associated with particulate laden products.


Preparation of chitosan from brine shrimp (Artemia urmiana) cyst shells and effects of different chemical processing sequences on the physicochemical and functional properties of the product.
Chitosan (CS) was prepared from Artemia urmiana cyst shells using the same chemical process as described for the other crustacean species, with minor adjustments in the treatment conditions. The influence of modifications of the CS production process on the physiochemical and functional properties of the CS obtained was examined. The study results indicate that Artemia urmiana cyst shells are a rich source of chitin as 29.3-34.5% of the shell's dry weight consisted of this material. Compared to crab CS (selected as an example of CS from a different crustacean source) Artemia CS exhibited a medium molecular weight (4.5-5.7 x10(5) Da), lower degree of deacetylation (67-74%) and lower viscosity (29-91 centiposes). The physicochemical characteristics (e.g., ash, nitrogen and molecular weight) and functional properties (e.g., water binding capacity and antibacterial activity) of the prepared Artemia CSs were enhanced, compared to control and commercial samples, by varying the processing step sequence.


Dialysis Catheter Placement in Patients With Exhausted Access.
Patients with end-stage renal disease undergo renal transplant, peritoneal dialysis, or intermittent hemodialysis for renal replacement therapy. For hemodialysis, native fistulas or grafts are preferred but hemodialysis catheters are often necessary. Per KDOQI, the right jugular vein is the preferred vessel of access for these catheters. However, in patients with long-standing end-stage renal disease vein thrombosis, stenosis and occlusion occurs. In these patients with end-stage vascular access, unconventional routes of placement of dialysis catheters are needed. These methods include placing them by means of sharp recanalization, via a translumbar route directly into the inferior vena cava, and via transhepatic and transrenal routes. These difficult, but potentially lifesaving methods of gaining vascular access are reviewed in this article.


[Imaging observation of live cells originating from osteoclasts of the blood system].
To study the application of the live cell imaging method to observe the whole process of osteoclast formation induced by monocyte macrophages in the blood system in order to clarify the origin of osteoclasts and their cytodynamics. Blood samples (8 ml) were collected from the abdominal aorta of male SD rats weighing 280 g. Mononuclear cells were obtained by density gradient centrifugation and induced by RANKL and M-CSF. The cells were cultured and divided into four groups: inverted phase contrast microscope (IPCM) group, TRAP group, SEM group and live cell imaging (LCI) group. Images of the IPCM group were captured by a digital microscopic imaging system and recorded daily. The TRAP group was identified by enzyme activity staining after a 21-day cultivation period. The SEM group was SEM-observed after a 21-day cultivation period. The LCI group was consecutively and dynamically observed for 35 days. After 2-week cultivation, IPCM observations showed the formation of numerous apocytes. These cells displayed round, fusiform, fan-shaped, elliptic or irregular gibbous profiles. TRAP staining showed that most apocytes and monocytes had positive(+)reaction. SEM observations showed many bone absorption lacunae, hollows and channels, in which many osteoclasts with absorption activity were observed. Live cell imaging observations found that multinuclear osteoclasts originating from peripheral blood were generated by fusion of monocytes and apocytes and intercross fusion of monocytes and apocytes,which occurred at the adherent stage of the cells. Cytodynamic observations showed that the cell form of osteoclasts was complex and changeable. RANKL and M-CSF can induce differentiation and formation from monocytes in rat peripheral blood into multinuclear osteoclasts with bone absorption activity. The osteoclasts were formed by various cell fusion processes at the adherent stage. The adherent property of osteoclasts is important for their survival and function. Osteoclasts have phagocytosis and their morphological structure is dynamically changeable, involving not only apocytes but monocytes. The osteoclast property of multinuclear giant cells formed by cell fusion may be a special biological behavior for their adaptation of functional needs and bone absorption efficiency. This experiment has further evidenced the theory of osteoclast origination in the blood system and provided new experimental clues for clarifying the cytodynamic and cytobiological properties of osteoclasts.


The impact of radiotherapy on the hypothalamo-pituitary axis: old vs new radiotherapy techniques.
Multimodality cancer therapy has led to remarkable improvements in survival of childhood and young adult cancer, with survival rates exceeding 85%. Such remission rates come with their own adverse sequelea or 'late effects'. Although the cause of these late effects is multi-factorial, radiation-related adverse effects are one of the most prevalent. Hypopituitarism is a recognised complication of irradiation of brain tumours distant to the hypothalamo-pituitary (HP) axis when the axis is included within the exposed field. Much of the data concerning the development of hypopituitarism, however, relate to early forms of photon-based radiotherapy. In this narrative review, we discuss advances in individual radiotherapy techniques currently used in treating brain tumours and their theoretical benefits based primarily on dosimetric studies. Increasingly precise radiation techniques, including advances in the delivery of photons (i.e. intensity-modulated radiotherapy) and proton beam therapy, are now available options. The premise behind these newer techniques is to reduce the dose and volume of normal tissue irradiated whilst maintaining an effective radiation dose to target tissue. When treating brain tumours distant to the HP axis the expectation, based upon dosimetric studies, is that newer forms of radiotherapy will less frequently involve the HP axis in the exposed field, and where incorporated within the field it will be exposed to a lower radiotherapy dosage. Intuitively the dosimetric studies should translate into significant reductions in the prevalence of HP dysfunction. These data are promising; however, to date there are minimal robust clinical data to determine if the theoretical benefits of these newer techniques on HP dysfunction is to be realised.


Divergent selection for uterine capacity in rabbits. III. Responses in uterine capacity and its components estimated with a cryopreserved control population.
This work evaluated the response to 10 generations of divergent selection for uterine capacity (UC) in rabbits to determine whether this response was symmetric by contrasting both lines against a cryopreserved control population. Animals came from the 13th generation of an experiment of divergent selection for UC and from a cryopreserved control population. The two UC lines were divergently selected for 10 generations, and selection was relaxed from the 11th generation until the 13th generation. Uterine capacity was estimated as litter size (LS) in unilaterally ovariectomized (ULO) does. To create the control population, embryos from the base generation were vitrified and stored in liquid N2 for 10 generations. Data from 461 pregnancies produced by 134 ULO does were used: 62 does from the high UC line, 55 females from the low UC line, and 17 females from the control line. The following traits were analyzed: ovulation rate (OR); number of implanted embryos (IE); (UC), estimated as total number of rabbits born; number born alive (NBA); prenatal survival (PS), estimated as UC/OR; embryo survival (ES), estimated as IE/OR; and fetal survival (FS), estimated as UC/IE. Ovulation rate, IE, PS, ES, and FS were measured by laparoscopy only in the second parity. Uterine capacity and NBA were measured over four parities. Responses in UC and its components were estimated as differences between the selected lines and the control line using a Bayesian approach. Selection for UC led to differences of 1.01 kits between the high and low lines, but this response was asymmetric. No differences were found between the high and control lines (high - control = -0.08), whereas the low and control lines differed by 1.08 kits, with a probability of the difference being greater than zero of 0.98. Difference between the high and low lines and between the control and low lines was one-half of the difference reported for correlated response in LS in previous studies. No differences in OR were detected among lines. The control and low lines differed by 1.06 IE, with a probability of the difference being higher than zero of 0.84. Prenatal survival for the low line was less than that of the control line. In summary, selection for UC was asymmetric, which was mainly due to a correlated response in PS. Response in UC was one-half of the difference reported for correlated response in LS in previous studies.


Following in Soper's footsteps: northeast Brazil 63 years after eradication of Anopheles gambiae.
Sub-Saharan Africa has long suffered under the yoke of the Anopheles gambiae mosquito, but for northeast Brazil (figure 1) its arrival over 60 years ago was a new and horrifying experience. This African mosquito is an exceptionally effective malaria vector because it is well adapted to feeding upon people and to exploiting aquatic habitats associated with our daily activities. Anopheles gambiae sensu lato probably accounts for most of the world's malaria deaths and socioeconomic burden. Fortunately, the Brazilian experience had a happy ending. The prospect of A gambiae spreading across much of the Americas motivated a ruthlessly effective response that deserves a special and heroic place in the annals of public health. Building on the successes and infrastructure of the Yellow Fever Service for Aedes aegypti elimination, the Rockefeller Foundation and Brazilian government collaborated to form a new Malaria Service of the Northeast. This new entity rolled the invader back into oblivion with an aggressive eradication campaign, focusing primarily upon larviciding of all potential habitats. The driving force of this endeavour was an enigmatic man called Fred Soper whose sheer will and determination was a key element in this success, and a source of inspiration today (see Killeen GF, et al. Eradication of Anopheles gambiae from Brazil: lessons for malaria control in Africa? Lancet Infect Dis 2002; 2: 618-27). I recently took an opportunity to fulfil a long-held dream and follow in some of Soper's footsteps. Tired of gazing at yellowing maps like figure 1, I went to see the northeast of Brazil for myself.


Neuroglial cyst: a rare occurence in abdomen and pelvis.
We hereby report a case of a child who presented with abdominal distension and urinary retention. Radiological investigations and exploratory laparotomy revealed a cystic mass in the sacral region pushing the urinary bladder anteriorly and upwards. Histopathological examination revealed neuroglial elements. Neuroglial cysts are uncommon outside the central nervous system and this is the first report of its occurrence in abdomen and pelvis.


Antiidiotypic antibody mimicry of a bluetongue virus neutralizing antigen.
Syngeneic antiidiotypic (Anti-Id) mAb were produced to the Bluetongue virus (BTV) serotype 17 neutralizing mAb. Three anti-Id mAb had the characteristics of an internal image of the Id as demonstrated by 1) the internal image anti-Id mAb were capable of mimicking BTV by blocking the neutralizing activity of the idiotypic neutralizing mAb and 2) the anti-Id mAb bound specifically to the surface of BTV susceptible cells in indirect binding experiments as determined by immunocytochemistry and flow cytometric analysis. The potential application of these internal image anti-Id mAb in this arbovirus system is discussed.


Role of amniotic membrane graft for ocular chemical and thermal injuries.
To evaluate the results of amniotic membrane transplantation (AMT) for ocular surface reconstruction in chemical and thermal injuries. Retrospective review of case records of patients who had undergone AMT for chemical injuries (January 1998 to May 2001). Seventy two eyes of 69 patients were studied of which 24 were acute cases (median-2 days, range, 1-20 days) and 48 were chronic cases (median-12.4 months, range, 1.02-95.8 months). Mean age was 22.4 years (SD +/- 13.34 years) and average follow up duration was 7.8 months (SD +/- 7.1). Main clinical findings were symblephara (52.8%), corneal vascularization (51.3%), conjunctivalization (45.8%), Limbal ischemia (45.8%), Limbal stem cell deficiency (55.5%) and epithelial defect (48.6%). 18 cases were due to acid injuries (5 acute, 13 chronic), 52 were due to alkali (18 acute and 34 chronic) and 2 cases were due to thermal burns (1 each acute and chronic). Overall success rate was 87.5% in acute cases and 72.9% in chronic cases. Indication-wise success rates were 94.3% for epithelial defect healing, 88.2% for symptomatic relief, 59.7% for ocular surface reconstruction, and 55% for improving limbal stem cell function. Success was not achieved in any outcome measure in 1/24 (4.2%) in acute group and 6/48 (12.5%) in chronic group. AMT helps in ocular surface reconstruction, promotes rapid epithelial healing and partially restores limbal stem cell function. It can be considered as an effective modality for the ocular surface restoration in chemical and thermal injuries in selected cases. Success rates in acute and chronic cases are comparable.


Purkinje cell inclusions and 'atelencephaly' in 13q-chromosomal syndrome.
Severe microcephaly was present from birth in a child with a 13q-chromosomal syndrome [46,XY,del(13)(q22q31)]. He died at 20 months of age. Neuropathologic findings included atelencephaly and eosinophilic cytoplasmic inclusions in cerebellar Purkinje cells. Ultrastructurally, the inclusions consisted of stacks of parallel cisternae separated by electron-dense granular material. The relationship between these inclusions and the smaller cytoplasmic inclusions known as "lamellar bodies" is discussed, and the central nervous system malformations in this syndrome are reviewed.


Combined analysis of the salivary microbiome and host defence peptides predicts dental disease.
Understanding the triad of host response, microbiome and disease status is potentially informative for disease prediction, prevention, early intervention and treatment. Using longitudinal assessment of saliva and disease status, we demonstrated that partial least squares modelling of microbial, immunological and clinical measures, grouped children according to future dental disease status. Saliva was collected and dental health assessed in 33 children aged 4 years, and again 1-year later. The composition of the salivary microbiome was assessed and host defence peptides in saliva were quantified. Principal component analysis of the salivary microbiome indicated that children clustered by age and not disease status. Similarly, changes in salivary host defence peptides occurred with age and not in response to, or preceding dental caries. Partial least squares modelling of microbial, immunological and clinical baseline measures clustered children according to future dental disease status. These data demonstrate that isolated evaluation of the salivary microbiome or host response failed to predict dental disease. In contrast, combined assessment of both host response together with the microbiome revealed clusters of health and disease. This type of approach is potentially relevant to myriad diseases that are modified by host-microbiome interactions.


[Classification and therapy of the unstable shoulder].
Instability of the shoulder can be classified as uni- or multidirectional with or without general hyperlaxity. Instability of a shoulder without hyperlaxity is often caused by a single traumatic event for the unidirectional instability and by two or several different events for the rarer multidirectional instability. The diagnosis of unidirectional instability is made with a positive apprehension test. For multidirectional instabilities, the anterior and posterior apprehension tests are positive. The treatment consists of surgical repair of the labrum-capsule complex for both the uni- and the multidirectional instabilities without hyperlaxity. For shoulders with a concomitant hyperlaxity, uni- or multidirectional instability is often caused by only minor trauma. Hyperlaxity itself is not a disease but represents a risk factor of instability. The typical feature of hyperlaxity is the positive "sulcus sign". Unidirectional instability with hyperlaxity is characterised by a positive apprehension test combined with a positive sulcus sign. Multidirectionally unstable shoulders with hyperlaxity have a positive anterior and posterior apprehension test as well as a positive sulcus sign. The unidirectional instability with hyperlaxity is best treated surgically whereas conservative treatment is recommended for the multidirectional instability with hyperlaxity. The voluntary instability without loss of control of position of the shoulder is not a real instability and has an excellent prognosis without treatment.


Genotypic and phenotypic variations in methicillin-resistant Staphylococcus aureus isolates from outpatient, inpatient and nursing homes.
The epidemiological shift in MRSA distribution from healthcare-related facilities to the general population is distressing and requires continuous monitoring to manage and control the rate of incidences. The retrospective relationship between genetic and phenotypic variability of methicillin-resistant Staphylococcus aureus (MRSA) isolates was determined in respect to the specimen source, patient location, sex and age. A total of 521 MRSA isolates were classified based on SCCmec, mec, agr, pvl and spa genetic markers using three different multiplex PCRs. Based on the genetic variability, the isolates were divided into 97 profiles, of which 59% belonged to only two profiles (P17 and P33). P17 was the predominate profile, harbouring SCCmecIVa, ccr2, mecB, agr1, spa413 and pvl markers. P17 was more prevalent among the younger population (average 33.9 years) from outpatient (77%) locations and wound (88%) sources. The second largest profile was P33, harbouring SCCmecII, ccr2+ccr3, mecA, agr2, spa413 and no PVL. P33 was more prevalent in the older population (average 70.7 years) and more common in females (62%) than males (38%). With respect to antibiotic resistance, P33 exhibited a high rate of resistance to penicillins, cephalosporins, fluoroquinolones and macrolides, and P17 had a lower resistance to fluoroquinolones. This report contributes to the existing understanding of evolutionary epidemiology of antibiotic resistance in MRSA. The diversity of MRSA isolates and unique environmental preferences for each profile highlights the importance of epidemiological knowledge of MRSA distribution to determine the best treatment for patients in both community and hospital settings.


Broadband spatiotemporal axicon fields.
We study the properties of broadband optical fields produced by two classes of axicons: reflective axicons creating fields with a frequency-independent cone angle, and diffractive axicons that generate fields with frequency-independent transverse scale. We also consider two different types of illumination: spectrally completely coherent pulses and spectrally incoherent (stationary) light assuming that the spectra are the same in both situations. In the former case we evaluate the spatiotemporal shape of the output field, and in the latter case its spatiotemporal coherence properties. Physical reasons for the substantially different fields produced by the two types of axicons are identified. Our results are useful for optical applications in which joint spatial and temporal field localization is desired.


Non-surface activity and micellization of ionic amphiphilic diblock copolymers in water. Hydrophobic chain length dependence and salt effect on surface activity and the critical micelle concentration.
We reported previously (Macromolecules 2003, 36, 5321; Langmuir, 2004, 20, 7412) that amphiphilic diblock copolymers having polyelectrolytes as a hydrophilic segment show almost no surface activity but form micelles in water. In this study, to further investigate this curious and novel phenomenon in surface and interface science, we synthesized another water-soluble ionic amphiphilic diblock copolymer poly(hydrogenated isoprene)-b-sodium poly(styrenesulfonate) PIp-h2-b-PSSNa by living anionic polymerization. Several diblock copolymers with different hydrophobic chain lengths were synthesized and the adsorption behavior at the air/water interface was investigated using surface tension measurement and X-ray reflectivity. A dye-solubilization experiment was carried out to detect the micelle formation. We found that the polymers used in this study also formed micelles above a certain polymer concentration (cmc) without adsorption at the air-water interface under a no-salt condition. Hence, we further confirmed that this phenomenon is universal for amphiphilic ionic block copolymer although it is hard to believe from current surface and interface science. For polymers with long hydrophobic chains (more than three times in length to hydrophilic chain), and at a high salt concentration, a slight adsorption of polymer was observed at the air-water interface. Long hydrophobic chain polymers showed behavior "normal" for low molecular weight ionic surfactants with increasing salt concentration. Hence, the origin of this curious phenomenon might be the macroionic nature of the hydrophilic part. Dynamic light scattering analysis revealed that the hydrodynamic radius of the block copolymer micelle was not largely affected by the addition of salt. The hydrophobic chain length-cmc relationship was found to be unusual; some kind of transition point was found. Furthermore, very interestingly, the cmc of the block copolymer did not decrease with the increase in salt concentration, which is in clear contrast to the fact that cmc of usual ionic small surfactants decreases with increasing salt concentration (Corrin-Harkins law). These behaviors are thought to be the special, but universal, characteristics of ionic amphiphilic diblock copolymers, and the key factor is thought to be a balance between the repulsive force from the water surface by the image charge effect and the hydrophobic adsorption.


Primary localized bilateral conjunctival amyloidosis and epiphora.
Conjunctival amyloidosis is a rare entity, which can present with epiphora. The management options, including the surgical treatment of this disease, are illustrated with a case study. A combination of retrospective and prospective review of a patient's clinical findings, course and treatment outcome. A middle-aged patient with epiphora due to localized conjunctival amyloidosis is described. The clinical course of the epiphora during a 10-year period revealed a decrease on the initially symptomatic side and involvement of the opposite side despite bilateral progressive lacrimal drainage stenosis. The pathophysiology of this phenomenon is discussed. The progressive conjunctival deposits in this patient eventually required operative debulking through a conjunctival approach. Medial ectropion and punctal stenoses were also simultaneously corrected. The patient became symptom free one week after these operative interventions. Localized conjunctival amyloidosis is a chronic, slowly progressive disease, which is frequently bilateral. Associated ocular involvement does not seem to be a part of this disease, even with long-term follow-up. The treatment of associated epiphora requires an organized approach to the underlying cause(s). The epiphora may be managed by a staged correction of its pathogenic mechanisms.


Assessment of World Health Organization definition of dengue hemorrhagic fever in North India.
Classification of symptomatic dengue according to current World Health Organization (WHO) criteria is not straightforward. In this prospective study of dengue infection during an epidemic in India in 2004, we applied the WHO classification of dengue to assess its usefulness for our patients. The study included 145 clinically suspected cases of dengue infection of all ages. Dengue was confirmed by serological methods (IgM ELISA and HI test). WHO criteria were applied to classify dengue positive patients into Dengue Fever (DF), Dengue Hemorrhagic Fever (DHF) and Dengue Shock Syndrome (DSS). Clinical and laboratory parameters were compared between dengue patients with bleeding and those without bleeding. Out of the 50 serologically positive cases of dengue enrolled in the study, only 3 met the WHO criteria for DHF and 1 met the criteria for DSS; however, 21 (42%) cases had one or more bleeding manifestations. By using WHO criteria of DHF on Indian patients, all severe cases of dengue cannot be correctly classified. A new definition of DHF that considers geographic and age-related variations in laboratory and clinical parameters is urgently required.


Carbon monoxide-releasing molecules attenuate postresuscitation myocardial injury and protect cardiac mitochondrial function by reducing the production of mitochondrial reactive oxygen species in a rat model of cardiac arrest.
The objective of this study is to examine whether carbon monoxide-releasing molecules (CORMs) can decrease the generation of excessive reactive oxygen species (ROS) in cardiac mitochondria, thereby protecting against postresuscitation myocardial injury and cardiac mitochondrial dysfunction after resuscitation in a rat model of ventricular fibrillation (VF), and further investigated the underlying mechanism. Rats suffered 8 minutes of untreated VF and resuscitation and were randomized into the control group with vehicle infusion and the CORM group with CO-releasing molecule 2 (CORM2) treatment. Animals in the Sham group were instrumented without induced VF and resuscitation. Effects of CORM2 on cardiac function, myocardial oxidative stress, cardiac mitochondrial function, and mitochondrial ROS generation were assessed. Moreover, to further evaluate the direct effect of CORM2 on cardiac mitochondria isolated from resuscitated rats, we measured mitochondrial function and ROS generation when isolated cardiac mitochondria were directly incubated with different concentrations of (CORM2). Compared with the Sham group, the control and CORM groups demonstrated impaired cardiac function, increased myocardial injury, and aggravated mitochondrial damage. CORM2 improved cardiac performance and attenuated myocardial damage and oxidative stress in resuscitated rats. Additionally, animals with CORM2 treatment showed the decreased generation of cardiac mitochondrial ROS, alleviated mitochondrial injury, and preserved mitochondrial function and complex activities when compared with the control group. In isolated cardiac mitochondria incubated with CORM2, low concentrations of CORM2 (20 μmol/L) mildly uncoupled mitochondrial respiration, leading to reduced mitochondrial ROS production. In contrast, high concentrations of CORM2 (60 μmol/L) resulted in the reverse effect presumably due to its excessive uncoupling action. These findings suggest that CORM2 attenuates oxidative stress of the heart and improves cardiac function after resuscitation. The mechanism was probably that CO, the product of CORM2, reduces the production of cardiac mitochondrial ROS and thereby attenuates mitochondrial injury and dysfunction during the postresuscitation period, due to the transient uncoupling of mitochondrial respiration.


Real time non-invasive imaging of receptor-ligand interactions in vivo.
Non-invasive longitudinal detection and evaluation of gene expression in living animals can provide investigators with an understanding of the ontogeny of a gene's biological function(s). Currently, mouse model systems are used to optimize magnetic resonance imaging (MRI), positron emission tomography (PET), single-photon emission computed tomography (SPECT), and optical imaging modalities to detect gene expression and protein function. These molecular imaging strategies are being developed to assess tumor growth and the tumor microenvironment. In addition, pre-labeling of progenitor cells can provide invaluable information about the developmental lineage of stem cells both in organogenesis and tumorigenesis. The feasibility of this approach has been extensively tested by targeting of endogenous tumor cell receptors with labeled ligand (or ligand analog) reporters and targeting enzymes with labeled substrate (or substrate analog). We will primarily discuss MRI, PET, and SPECT imaging of cell surface receptors and the feasibility of non-invasive imaging of gene expression using the tumor microenvironment (e.g., hypoxia) as a conditional regulator of gene expression.


Perceptual processing in the ventral visual stream requires area TE but not rhinal cortex.
There is an on-going debate over whether area TE, or the anatomically adjacent rhinal cortex, is the final stage of visual object processing. Both regions have been implicated in visual perception, but their involvement in non-perceptual functions, such as short-term memory, hinders clear-cut interpretation. Here, using a two-interval forced choice task without a short-term memory demand, we find that after bilateral removal of area TE, monkeys trained to categorize images based on perceptual similarity (morphs between dogs and cats), are, on the initial viewing, badly impaired when given a new set of images. They improve markedly with a small amount of practice but nonetheless remain moderately impaired indefinitely. The monkeys with bilateral removal of rhinal cortex are, under all conditions, indistinguishable from unoperated controls. We conclude that the final stage of the integration of visual perceptual information into object percepts in the ventral visual stream occurs in area TE.


Ectoparasitic chigger mites on large oriental vole (Eothenomys miletus) across southwest, China.
An investigation of chigger mites on the large oriental vole, Eothenomys miletus (Rodentia: Cricetidae), was conducted between 2001 and 2013 at 39 localities across southwest China, and 2463 individuals of the vole hosts were captured and examined, which is a big host sample size. From the body surface of E. miletus, 49,850 individuals of chigger mites were collected, and they were identified as comprising 175 species, 13 genera, and 3 subfamilies in 2 families (Trombiculidae and Leeuwenhoekiidae). The 175 species of chigger mites from such a single rodent species (E. miletus) within a certain region (southwest China) extremely exceeded all the species of chigger mites previously recorded from multiple species of hosts in a wide region or a whole country in some other countries, and this suggests that E. miletus has a great potential to harbor abundant species of chigger mites on its body surface. Of 175 mite species, Leptotrombidium scutellare was the most dominant species, which has been proved as one of the main vectors of scrub typhus and the potential vector of haemorrhagic fever with renal syndrome (HFRS) in China. The patchiness index (m*/m) was used to measure the spatial patterns of the dominant chigger mite species, and all the three dominant mite species (L. scutellare, Leptotrombidium sinicum, and Helenicula simena) showed aggregated distributions among the different host individuals. The coefficient of association (V) was adopted to measure the interspecies interaction between the dominant mite species and a slightly positive association existed between L. scutellare and L. sinicum (V = 0.28, P < 0.01), which implies that these two mite species can co-exist on the same species of the host, E. miletus. The tendency curve of species abundance showed that the number of chigger mite species gradually decreased with the increase of mite individuals, and this revealed that most chigger mite species were rare with very few individuals, but few dominant species had abundant individuals. The species-sample relationship indicated that the number of chigger mite species increased with the increase of the host samples. The results suggest that a big host sample size over a wide realm of geographical regions is needed in the field investigation in order to obtain a true picture of species diversity and species composition.


Bioactive Compounds from Germinated Brown Rice Protect Cardiomyocytes Against Simulated Ischemic/Reperfusion Injury by Ameliorating Mitochondrial Dysfunction.
Ischemic/reperfusion (I/R) injury is the principal mechanism during Ischemic Heart Disease (IHD). The key modulator of I/R injury is dysregulation of mitochondria function. Germinated Brown Rice (GBR) has been recommended as a bio-functional food and has clarified the potential properties in several effects. However, the effect of GBR mediated cardioprotective properties, focusing on mitochondrial function's role, remains unexplored. Thus, this study aims to investigate the cardioprotective effects of GBR pretreatment against simulated I/R injury. H9c2 cardiomyocytes were incubated with GBR at a five ƞg/mL concentration for 24 hours and simulated I/R (sI/R) for 40 minutes. Cell viability and cell apoptosis were assessed by 7-AAD staining and Annexin V/PI staining, respectively. The mitochondrial membrane potential was determined by JC-1 staining and mitochondrial respiration represented by oxygen consumption rate (OCR) using Seahorse Flux analyzer. The results revealed that the administration of GBR before sI/R significantly decreased the percentage of cell death and total cell apoptosis in H9c2 during stimulation of ischemic/reperfusion. Besides, pretreatment of cardiomyocytes with GBR remarkably stabilized mitochondrial membrane potential and improved impaired mitochondrial respiration in simulated-H9c2 injury. The present research is the first study to report the effective cardioprotection of GBR. Pretreatment of GBR potentially protects H9c2 cardiomyocytes against sI/R injury through mitochondrial function. The underlying therapeutic activities are possibly associated with its bio-functional compounds. However, the underlying mechanism on the cardioprotective effects of GBR needs further studies.


Accuracy of tumor motion compensation algorithm from a robotic respiratory tracking system: a simulation study.
The Synchrony Respiratory Tracking System (RTS) is a treatment option of the CyberKnife robotic treatment device to irradiate extra-cranial tumors that move due to respiration. Advantages of RTS are that patients can breath normally and that there is no loss of linac duty cycle such as with gated therapy. Tracking is based on a measured correspondence model (linear or polynomial) between internal tumor motion and external (chest/abdominal) marker motion. The radiation beam follows the tumor movement via the continuously measured external marker motion. To establish the correspondence model at the start of treatment, the 3D internal tumor position is determined at 15 discrete time points by automatic detection of implanted gold fiducials in two orthogonal x-ray images; simultaneously, the positions of the external markers are measured. During the treatment, the relationship between internal and external marker positions is continuously accounted for and is regularly checked and updated. Here we use computer simulations based on continuously and simultaneously recorded internal and external marker positions to investigate the effectiveness of tumor tracking by the RTS. The Cyberknife does not allow continuous acquisition of x-ray images to follow the moving internal markers (typical imaging frequency is once per minute). Therefore, for the simulations, we have used data for eight lung cancer patients treated with respiratory gating. All of these patients had simultaneous and continuous recordings of both internal tumor motion and external abdominal motion. The available continuous relationship between internal and external markers for these patients allowed investigation of the consequences of the lower acquisition frequency of the RTS. With the use of the RTS, simulated treatment errors due to breathing motion were reduced largely and consistently over treatment time for all studied patients. A considerable part of the maximum reduction in treatment error could already be reached with a simple linear model. In case of hysteresis, a polynomial model added some extra reduction. More frequent updating of the correspondence model resulted in slightly smaller errors only for the few recordings with a time trend that was fast, relative to the current x-ray update frequency. In general, the simulations suggest that the applied combined use of internal and external markers allow the robot to accurately follow tumor motion even in the case of irregularities in breathing patterns.


Endothelin induces tyrosine phosphorylation and GRB2 association of Shc in astrocytes.
While the mitogen-activated protein kinase (MAPK) pathway coupled to receptor tyrosine kinases has been largely clarified, little is known about MAPK activation mediated by heterotrimeric G protein-coupled receptors. In a previous study, it has been shown that endothelin-1 (ET-1) signaling through heterotrimeric G protein-coupled receptors stimulates MAPK activity in primary cultures of astrocytes (Cazaubon, S., Parker, P. J., Strosberg, A.D., and Couraud, P.O. (1993) Biochem. J. 293, 381-386). To clarify the molecular mechanism responsible for this response, involvement of the adapter proteins, Shc and Grb2, has now been investigated. It is shown here that in these cells, ET-1 stimulates tyrosine phosphorylation of Shc, resulting in its stable association with Grb2 but not with Grb3-3, a Grb2 isoform with partially deleted SH2 domain. These results demonstrate that tyrosine-phosphorylated Shc specifically interacts with the SH2 domain of Grb2. This response was rapid and transient, showing a maximum at 10 min and declining at 60 min. Interestingly, direct activation of G proteins by fluoroaluminate mimics the ET-1 effect. In addition, a shift to a higher apparent molecular mass of Raf-1 kinase, likely reflecting its hyperphosphorylation, was also detected in ET-1-treated cells. These data strongly suggest that ET-1-induced MAPK activation is a G protein-coupled pathway that involves Shc, Grb2, and probably Raf-1. In conclusion, the Shc-Grb2 complex may be involved in the activation of the MAPK pathway, not only by several receptor tyrosine kinases but also by heterotrimeric G protein-coupled receptors, such as ET-1 receptors.


The impact and determinants of the energy paradigm on economic growth in European Union.
Contemporary economies are strongly reliant on energy and analyzing the determining factors that trigger the changes in energy paradigm and their impact upon economic growth is a topical research subject. Our contention is that energy paradigm plays a major role in achieving the sustainable development of contemporary economies. In order to prove this the panel data methodology of research was employed, namely four panel unit root tests (LLC, IPS, F-ADF and F-PP) aiming to reveal the connections and relevance among 17 variables denoting energy influence on economic development. Moreover, it was introduced a specific indicator to express energy consumption per capita. Our findings extend the classical approach of the changes in energy paradigm and their impact upon economic growth and offer a comprehensive analysis which surpasses the practices and policy decisions in the field.


Three Sides of a Coin in the Life of People Living with HIV (PLWH).
Human Immunodeficiency Virus (HIV)/Acquired Immune Deficiency Syndrome (AIDS) is a global epidemic, a major challenge as a health care problem of modern times. As the survival of life increases from the time of an HIV-positive diagnosis, growing concern for the quality of the life has been extended. To assess and correlate the coping, social support and quality of life. A descriptive cross-sectional study was conducted at antiretroviral therapy (ART) clinic of AIIMS, New Delhi. The sample comprised people living with HIV/AIDS (PLWHA) who were seropositive for last six months. The tools used to assess the coping, social support and quality of life were BREF COPE, MOS social support survey and WHO QOL-HIV BREF, respectively. Permission was taken from the authors of the tools. The ethical permission was taken from the center. The coping, social support and quality of life were assessed and their association was observed. Data were analyzed using SPSS 17. The most commonly used coping styles were acceptance and religion. The social support used by most of PLWHA was tangible support and affectionate support, while the least used support was positive social interaction. The lowest quality of life is seen in social relations, followed by physical quality of life. There was positive association seen between coping and quality of life as well as social support and quality of life. There was positive association between coping, social support and quality of life.


Overlapping and disease specific trait, response, and reflection impulsivity in adolescents with first-episode schizophrenia spectrum disorders or attention-deficit/hyperactivity disorder.
Schizophrenia and attention-deficit/hyperactivity disorder (ADHD) are developmental disorders with shared clinical characteristics such as cognitive impairments and impulsivity. Impulsivity is a core feature of ADHD and an important factor in aggression, violence, and substance use in schizophrenia. Based on the hypothesis that schizophrenia and ADHD represent a continuum of neurodevelopmental impairments, the aim was to identify overlapping and disease specific forms of impulsivity. Adolescents between 12 and 17 years of age were assessed with the Schedule for Affective Disorders and Schizophrenia for School-aged Children - Present and Lifetime Version. Subjects with early-onset, first-episode schizophrenia spectrum disorders (EOS) (N = 29) or ADHD (N = 29) and healthy controls (N = 45) were compared on two performance measures (Information Sampling Task, Stop Signal Task) and a subjective personality trait measure of impulsivity (Barratt Impulsiveness Scale, Version 11 (BIS-11)). Significantly increased reflection impulsivity was observed in ADHD but not in the EOS group. No significant response inhibition deficits (stop signal reaction time) were found in the two clinical groups. The ADHD and the EOS group showed significantly increased motor, attentional, and non-planning subtraits of impulsivity. Impaired pre-decisional information gathering appeared to be specific for ADHD while the information gathering was not significantly reduced in subjects with EOS. Neither the ADHD nor EOS group showed impaired response inhibition but shared increased personality subtraits of attentional, non-planning, and motor impulsivity although the latter was significantly more pronounced in ADHD. These increased subtraits of impulsivity may reflect diagnostic non-specific neurodevelopmental impairments in ADHD and EOS in adolescence.


Rule extraction with fuzzy neural network.
This paper deals with the learning of understandable decision rules with connectionist systems. Our approach consists of extracting fuzzy control rules with a new fuzzy neural network. Whereas many other works on this area propose to use combinations of nonlinear neurons to approximate fuzzy operations, we use a fuzzy neuron that computes max-min operations. Thus, this neuron can be interpreted as a possibility estimator, just as sigma-pi neurons can support a probabilistic interpretation. Within this context, possibilistic inferences can be drawn through the multi-layered network, using a distributed representation of the information. A new learning procedure has been developed in order that each part of the network can be learnt sequentially, while other parts are frozen. Each step of the procedure is based on the same kind of learning scheme: the backpropagation of a well-chosen cost function with appropriate derivatives of max-min function. An appealing result of the learning phase is the ability of the network to automatically reduce the number of the condition-parts of the rules, if needed. The network has been successfully tested on the learning of a control rule base for an inverted pendulum.


Terrorist homicide bombings: a primer for preparation.
Contemporary planning for disaster response to terrorist events usually assumes the use of chemical, radiological, or biological weapons. Historically, most victims of terrorist attacks are injured by the use of conventional explosives rather than weapons of mass destruction. Such attacks will likely produce victims who have suffered burn injuries along with conventional trauma. Alternately, the large number of patients sustaining conventional soft-tissue or crush injuries will benefit from burn center expertise. This study summarizes the current state of knowledge related to the management of terrorism mass casualty incidents caused by the use of conventional explosives. A review of pertinent medical, technical, and popular literature relating to terrorism and explosives, along with instruction received at Hadassah Hospital, Jerusalem, Israel on the management of mass casualty terrorism events was undertaken, and the pertinent medical and scientific literature relating to bomb delivery methods, blast mechanics, blast pathophysiology, and medical response to a terrorist bombing is presented here. Although terrorist use of chemical, radiological, or biological weapons is possible, historical analysis consistently demonstrates that the most likely terrorist weapon causing a mass casualty event is a standard explosive device detonated in a crowded area. The medical basis for management of such casualties is herein described.


Ultrastructure of the bullfrog (Lithobates catesbeianus-Shaw, 1802) oviduct in different seasons.
The bullfrog (Lithobates catesbeianus) is an exotic animal that adapted perfectly to the climatic conditions of Brazil after introduction in the country. These climatic conditions favor the reproduction and fattening of bullfrogs. However, the development of the bullfrog is significantly reduced in colder regions because low temperatures affect the secretion of gonadotropins and change the sensitivity of the germinal epithelium to gonadotropic hormones. Thus, the temperature and photoperiod are abiotic factors that influence the life cycle of this species, especially with regard to reproduction. Samples from different regions of the oviducts (the infundibulum, magnum, and isthmus) of 9 bullfrogs were collected in the different seasons of the year. The samples were fixed and processed for analysis with scanning and transmission electron microscopy. A comparison of the morphology of the oviducts collected during different seasonal periods suggests that the frogs have greater reproductive potential in the spring due to the development of the structures related to the oviduct, presence of developed cilia, and electron-dense granules. However, seasonal changes were noted in the animal throughout the year in preparation for reproduction during the spring and summer.


Diamond based integrated detection system for dosimetric and microdosimetric characterization of radiotherapy ion beams.
Ion beam therapy allows for a substantial sparing of normal tissues and higher biological efficacy. Synthetic single crystal diamond is a very good material to produce high-spatial-resolution and highly radiation hard detectors for both dosimetry and microdosimetry in ion beam therapy. The aim of this work is the design, fabrication and test of an integrated waterproof detector based on synthetic single crystal diamond able to simultaneously perform dosimetric and microdosimetric characterization of clinical ion beams. The active elements of the integrated diamond device, that is, dosimeter and microdosimeter, were both realized in a Schottky diode configuration featured by different area, thickness, and shape by means of photolithography technologies for the selective growth of intrinsic and boron-doped CVD diamond. The cross-section of the sensitive volume of the dosimetric element is 4 mm2 and 1 μm-thick, while the microdosimetric one has an active cross-sectional area of 100 × 100 μm2 and a thickness of about 6.2 μm. The dosimetric and microdosimetric performance of the developed device was assessed at different depths in a water phantom at the MedAustron ion beam therapy facility using a monoenergetic uniformly scanned carbon ion beam of 284.7 MeV/u and proton beam of 148.7 MeV. The particle flux in the region of the microdosimeter was 6·107 cm2 /s for both irradiation fields. At each depth, dose and dose distributions in lineal energy were measured simultaneously and the dose mean lineal energy values were then calculated. Monte Carlo simulations were also carried out by using the GATE-Geant4 code to evaluate the relative dose, dose averaged linear energy transfer (LETd ), and microdosimetric spectra at various depths in water for the radiation fields used, by considering the contribution from the secondary particles generated in the ion interaction processes as well. Dosimetric and microdosimetric quantities were measured by the developed prototype with relatively low noise (∼2 keV/μm). A good agreement between the measured and simulated dose profiles was found, with discrepancies in the peak to plateau ratio of about 3% and 4% for proton and carbon ion beams respectively, showing a negligible LET dependence of the dosimetric element of the device. The microdosimetric spectra were validated with Monte Carlo simulations and a good agreement between the spectra shapes and positions was found. Dose mean lineal energy values were found to be in close agreement with those reported in the literature for clinical ion beams, showing a sharp increase along the Bragg curve, being also consistent with the calculated LETd for all depths within the experimental error of 10%. The experimental indicate that the proposed device can allow enhanced dosimetry in particle therapy centers, where the absorbed dose measurement is implemented by the microdosimetric characterization of the radiation field, thus providing complementary results. In addition, the proposed device allows for the reduction of the experimental uncertainties associated with detector positioning and could facilitate the partial overcoming of some drawbacks related to the low sensitivity of diamond microdosimeters to low LET radiation.


Reliability of lower leg muscle elasticity using shear wave elastography in non-weight-bearing and weight-bearing.
Muscle elasticity can be quantified with shear wave elastography (SWE) and has been used as an estimate of muscle force but reliability has not been established for lower leg muscles. The purpose of this study was to examine the intra-rater and inter-rater reliability of elasticity measures in non-weight-bearing (NWB) and weight-bearing (WB) for the tibialis anterior (TA), tibialis posterior (TP), peroneal longus (PL), and peroneal brevis (PB) muscles using SWE. A total of 109 recreationally active healthy adults participated. The study employed a single-cohort, same-day repeated-measures test-retest design. Elasticity, measured in kilopascals as the Young's modulus, was converted to the shear modulus. All four muscles were measured in NWB and at 90% WB. Intra-rater reliability estimates were good to excellent for NWB (ICC = 0.930-0.988) and WB (ICC = 0.877-0.978) measures. Inter-rater reliability estimates were moderate to good (ICC = 0.500-0.795) for NWB measures and poor to good (ICC = 0.346-0.910) for WB measures. Despite the studies poor to good inter-rater variability, the intra-rater reproducibility represents the potential benefit of SWE in NWB and WB. Establishing the reliability of SWE with clinical and biomechanical approaches may aid in improved understanding of the mechanical properties of muscle.


Improvement in RBC flux, acidosis and oxygenation in tumour microregions by Fluosol-DA 20%.
Using laser Doppler flowmetry, we investigated the effects of Fluosol-DA 20% on RBC flux in FSaII tumours and on RBC flux in normal skin of C3H mice. The RBC flux in tumours was significantly increased; however, the RBC flux in normal skin fluctuated only slightly after the treatment with Fluosol-DA 20%. Since an increase in RBC flux by Fluosol-DA 20% may facilitate the removal of acidic metabolites from the tumours, the effects of Fluosol-DA 20% on intratumour pH was also measured. We also measured intratumour pO2 after various dosages of Fluosol-DA 20% with carbogen inhalation. We concluded that the administration of Fluosol-DA 20% selectively increased the RBC flux in tumours compared to that in normal skin. Moreover, carbogen inhalation combined with increasing dosages up to 36 ml/kg of Fluosol-DA 20% effectively enhanced tumour oxygenation in FSaII tumours.


Some events of thyrotropin-releasing hormone metabolism are regulated in lactating and cycling rats.
Levels of thyrotropin-releasing hormone (TRH), TRH mRNA and pyroglutamyl peptidase II were analyzed in the hypothalamus-adenohypophyseal axis during lactation and estrous cycle. Mediobasal hypothalamic levels of TRH dropped 41% (p less than 0.01) from pregnancy levels (taken as 100%) on the first day of lactation, recovering until day 15 to the values observed at pregnancy. A sharp decrease was also observed during weaning (36%, p less than 0.01 compared to last day of lactation). TRH levels in the neurohypophysis increased during lactation and dropped at weaning. Highest TRH mRNA levels in the paraventricular nucleus were found at the end of pregnancy and beginning of lactation; they decreased 37% (p less than 0.05) at day 5 of lactation and stayed constant thereafter. Pyroglutamyl peptidase II adenohypophyseal activity was not modified during lactation but changed during estrous cycle. Relative to estrous values, activity diminished 58% (p less than 0.05) at 10.00 h (57% at 14.00 h) during diestrus 2 and 27% at 10.00 h (37% at 14.00 h) during proestrus. Hypothalamic TRH mRNA levels fluctuated in an opposite manner to adenohypophyseal pyroglutamyl peptidase II during the estrous cycle with a peak at diestrus 2: 183% of the estrous value (p less than 0.05). These data point to a regulation of TRH metabolism in conditions where prolactin (PRL) secretion fluctuates. They also suggest a sharp release of TRH between the end of pregnancy and the first day of lactation and that translational efficiency or post-translational processing of TRH precursor in the paraventricular neurons (projecting to the median eminence) increases during lactation and drops at weaning, concomitantly with PRL secretion.


New form of administering chlorhexidine for treatment of denture-induced stomatitis.
The purpose of this study was to evaluate the release of chlorhexidine as an antifungal drug from doped self-cured poly (methyl methacrylate) (PMMA) acrylic resin and the effect of the drug released on the growth of Candida albicans. Release of chlorhexidine was evaluated using liquid chromatography, and the effect of the drug on the growth of C. albicans was investigated microbiologically using a "well" technique on Saboraud culture medium inoculated with a resistant strain of C. albicans. Chlorhexidine leached steadily out of the acrylic resin into distilled water at mouth temperature, and the sustained drug release continued throughout the 28-day test period. The drug released also demonstrated antifungal activity against the resistant strain of C. albicans. The findings of this study support the use of chlorhexidine-impregnated self-cured PMMA chair-side resin as a new dosage form for the treatment of denture-induced stomatitis.


Insulin-Sensitizing Effects of Omega-3 Fatty Acids: Lost in Translation?
Omega-3 polyunsaturated fatty acids (n-3 PUFA) of marine origin, eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA), have been long studied for their therapeutic potential in the context of type 2 diabetes, insulin resistance, and glucose homeostasis. Glaring discordance between observations in animal and human studies precludes, to date, any practical application of n-3 PUFA as nutritional therapeutics against insulin resistance in humans. Our objective in this review is to summarize current knowledge and provide an up-to-date commentary on the therapeutic value of EPA and DHA supplementation for improving insulin sensitivity in humans. We also sought to discuss potential mechanisms of n-3 PUFA action in target tissues, in specific skeletal muscle, based on our recent work, as well as in liver and adipose tissue. We conducted a literature search to include all preclinical and clinical studies performed within the last two years and to comment on representative studies published earlier. Recent studies support a growing consensus that there are beneficial effects of n-3 PUFA on insulin sensitivity in rodents. Observational studies in humans are encouraging, however, the vast majority of human intervention studies fail to demonstrate the benefit of n-3 PUFA in type 2 diabetes or insulin-resistant non-diabetic people. Nevertheless, there are still several unanswered questions regarding the potential impact of n-3 PUFA on metabolic function in humans.


Regulation of tomato fruit ascorbate content is more highly dependent on fruit irradiance than leaf irradiance.
The mechanisms involving light control of vitamin C content in fruits are not yet fully understood. The present study aimed to evaluate the impact of fruit and leaf shading on ascorbate (AsA) accumulation in tomato fruit and to determine how fruit sugar content (as an AsA precursor) affected AsA content. Cherry tomato plants were grown in a glasshouse. The control treatment (normally irradiated fruits and irradiated leaves) was compared with the whole-plant shading treatment and with leaf or fruit shading treatments in fruits harvested at breaker stage. In a second experiment, the correlation between sugars and AsA was studied during ripening. Fruit shading was the most effective treatment in reducing fruit AsA content. Under normal conditions, AsA and sugar content were correlated and increased with the ripening stage. Reducing fruit irradiance strongly decreased the reduced AsA content (-74 %), without affecting sugars, so that sugar and reduced AsA were no longer correlated. Leaf shading delayed fruit ripening: it increased the accumulation of oxidized AsA in green fruits (+98 %), whereas it decreased the reduced AsA content in orange fruits (-19 %), suggesting that fruit AsA metabolism also depends on leaf irradiance. Under fruit shading only, the absence of a correlation between sugars and reduced AsA content indicated that fruit AsA content was not limited by leaf photosynthesis or sugar substrate, but strongly depended on fruit irradiance. Leaf shading most probably affected fruit AsA content by delaying fruit ripening, and suggested a complex regulation of AsA metabolism which depends on both fruit and leaf irradiance and fruit ripening stage.


Impact of the COVID-19 pandemic on audiology services in South Africa: A preliminary study.
Hygiene-, work practices, travel, personal interactions and access to healthcare services changed for the majority of the world during the pandemic. This study aimed to discover the knowledge, impact and attitudes towards COVID-19 on the professional practices of public and private sector audiologists in South Africa. The study included 76 audiologists registered with the Health Professions Council of South Africa (HPCSA) and employed in the public, educational, tertiary or private practice and private sector in South Africa. A cross-sectional self-administered electronic survey study design was implemented. Audiologists had appropriate knowledge regarding COVID-19. During hard lockdown, 69% of respondents saw less than 40% of their usual patient load, only 31% saw 60% - 100% of their usual patient load. During lower lockdown levels, majority of respondents (73.7%) saw 60% - 100% of their patient load while 26.3% still saw less than 40% of their usual patient load. Only hearing aid reprogramming, hearing aid trouble shooting, cochlear implant pre-counselling and adult hearing screening could be offered via tele-audiology. The main challenges faced were fear of infection, infection control measures in the workplace, accessibility and limited services provided during the various lockdown levels. The pandemic and lockdown levels had a definite impact on audiological service provision and many adaptations regarding service delivery and infection control in the workplace were required. The relevance of this work for health services is the identification of the challenges experienced by audiologists during the pandemic and the opportunities to prepare for the future.


[Application of quantitative fluorescence PCR for the prenatal diagnosis of common fetal chromosomal aneuploidies].
OBJECTIVE To assess the value of quantitative fluorescence PCR (QF-PCR) for the prenatal diagnosis of common fetal chromosomal aneuploidies. METHODS A total of 2436 amniotic fluid samples were collected at 18 to 22 gestational weeks. Multiplex QF-PCR was performed with fluorescence-labeled primers specific for 32 polymorphic short tandem repeat (STR) sites on chromosomes 21, 18, 13, X and Y. The PCR products were assayed by capillary electrophoresis. All samples were also assayed by karyotyping. RESULTS Seventy-six (3.12%) samples were diagnosed as chromosomal aneuploidies by QF-PCR, among which 51 were trisomy 21, 12 were trisomy 18, 2 were trisomy 13, and 1 was triploidy. The results were all consistent with those of karyotyping. Ten samples were suspected as sex chromosomal aneuploidies, among which 9 were confirmed, except for 1 case with X structural abnormality. In addition, karyotyping has diagnosed 24 (0.99%) cases of structural abnormalities, only one of which was suspected by QF-PCR with partial abnormal STR results. Two (0.08%) samples were found to be mosaic by karyotyping, one of which was suggested by QF-PCR with cut-off ratios of STR markers. CONCLUSION QF-PCR is reliable for the diagnosis of numerical abnormalities of chromosomes 21, 18, 13, X and Y. The method can serve as an effective technique for rapid prenatal screening of common chromosome aneuploidies in fetus.


[Combined surgical treatment of patients with multifocal atherosclerosis].
Multifocal manifestation of atherosclerosis (ATS) is common for this pathology and demands special diagnostic and therapeutic approaches. The need of active screening of basic clinical forms of multifocal ATS--carotid, peripheral arterial disease (PAD), aortic abdominal aneurysms(AAA) and coronary (IHD) is mandatory along with precise indications of therapeutical strategy and operative tactics in cases when surgical treatment is needed. The aim of this study is the evaluation of our results in operative treatment of combined forms of ATS and proper indication for simultaneous or two staged surgical approach. Our experience dictates simultaneous operative strategy only in cases of: 1. Carotid stenosis > 70% even asympthomatic, or > 50% sympthomatic stenosis (group A) combined with coronary artery disease in III-IV stage and 2-3 main vessel disease and unstable angina. 2. AAA > 7 cm. (group B) associated with IHD. 3. PAD with critical limb ischemia associated with unstable IHD. The absence of this specific indications allows not so aggressive surgical approach--two staged procedures (coronary artery bypass surgery first and several months later arterial reconstructive surgery of carotid or abdominal aortic lesions.


Recent progress on the effects of microRNAs and natural products on tumor epithelial-mesenchymal transition.
Epithelial-mesenchymal transition (EMT) is a biological process of phenotypic transition of epithelial cells that can promote physiological development as well as tissue healing and repair. In recent years, cancer researchers have noted that EMT is closely related to the occurrence and development of tumors. When tumor cells undergo EMT, they can develop enhanced migration and local tissue invasion abilities, which can lead to metastatic growth. Nevertheless, two researches in NATURE deny its necessity in specific tumors and that is discussed in this review. The degree of EMT and the detection of EMT-associated marker molecules can also be used to judge the risk of metastasis and to evaluate patients' prognosis. MicroRNAs (miRNAs) are noncoding small RNAs, which can inhibit gene expression and protein translation through specific binding with the 3' untranslated region of mRNA. In this review, we summarize the miRNAs that are reported to influence EMT through transcription factors such as ZEB, SNAIL, and TWIST, as well as some natural products that regulate EMT in tumors. Moreover, mutual inhibition occurs between some transcription factors and miRNAs, and these effects appear to occur in a complex regulatory network. Thus, understanding the role of miRNAs in EMT and tumor growth may lead to new treatments for malignancies. Natural products can also be combined with conventional chemotherapy to enhance curative effects.


Recent advances and controversies in adult cardiopulmonary resuscitation.
Since its introduction more than four and half decades ago, the science of cardiopulmonary resuscitation has been enriched with a significant amount of scientific evidence. This in turn has led to the birth of new evidence based guidelines for resuscitation published by the European Resuscitation Council and the American Heart Association in late 2005. This article aims to review the recent advances and controversies in the science of resuscitation.


In vitro adrenaline and collagen-induced mobilization of platelet calcium and its inhibition by naftopidil, doxazosin and nifedipine.
The aim of the study was to obtain further information regarding the modes of action of doxazosin, naftopidil and nifedipine on platelet function. We conducted an in vitro study of drug influences on adrenaline and collagen-induced mobilization of platelet calcium. In the presence of fibrinogen (300 micrograms ml-1) both collagen (5 micrograms ml-1) and adrenaline (16 microM) stimulated the aggregation of washed platelets. Collagen induced a transient rise (+4.97 +/- 0.63 microM) in platelet Ca2+ concentration, [Ca2+]i, as measured using the photoprotein aequorin, which coincided with the onset of aggregation. Adrenaline induced a smaller rise (+3.6 +/- 0.96 microM) which, however, occurred after the onset of aggregation. Naftopidil, an alpha 1-adrenoreceptor antagonist produced a concentration-dependent inhibition of collagen-induced Ca2+ mobilization, maximum inhibition (22.9 +/- 4%, P < 0.05) occurring with 40 microM naftopidil. The inhibition of Ca2+ mobilization was not reflected by a concentration-dependent inhibition of platelet aggregation, although 40 microM naftopidil produced statistically significant inhibition (23.3 +/- 11.7%, P < 0.05). The adrenaline-induced rise in [Ca2+]i was inhibited dose dependently by naftopidil (e.g. 40 microM naftopidil, 100 +/- 0%, P < 0.05), as was aggregation (40 microM naftopidil, 100 +/- 0%, P < 0.05). Doxazosin, another alpha 1-adrenoreceptor blocker, inhibited Ca2+ mobilization induced by collagen to similar extents as for naftopidil (30 microM doxazosin, 17.4 +/- 2.5%, P < 0.05), but did not inhibit platelet aggregation. It also inhibited the adrenaline-induced rise in [Ca2+]i in a concentration-dependent manner (30 microM doxazosin, 37.6 +/- 13.7%, P < 0.05), significant inhibitions of platelet aggregation also being produced (30 microM, 49.6 +/- 17.2%, P < 0.05). As expected, the calcium channel blocker nifedipine produced concentration-dependent inhibitions of both collagen-induced Ca2+ mobilization (e.g. 28 microM nifedipine, 47.8 +/- 2.7%, P < 0.05) and aggregation (28 microM, 55.1 +/- 9.2%, P < 0.05). These data indicate that the alpha 1-adrenoreceptor blockers, naftopidil and doxazosin, inhibit Ca2+ mobilization, this mechanism being possibly the means whereby these drugs inhibit platelet aggregation.