Efficacy of a single session in-series hemoperfusion and hemodialysis in the management of carprofen overdose in two dogs.
To describe the efficacy of in-series hemoperfusion and hemodialysis in 2 dogs with carprofen overdose. This report describes the treatment of 2 dogs following accidental carprofen overdoses who underwent a single in-series hemoperfusion and hemodialysis session. Serial serum carprofen concentrations were measured before, during, and after the session. The first patient's session lasted 5 hours, with the largest decrease in serum carprofen concentrations occurring during the first hour of treatment. The carprofen clearance during the following 4 hours of treatment decreased substantially compared to the first hour and was not different from the patient's intrinsic clearance of carprofen after the session was completed. Based on the findings from the first case, the second patient was treated with a 1 hour single hemoperfusion and hemodialysis session. Our results support the hypothesis that carprofen is not effectively removed by conventional hemodialysis and the efficacy of hemoperfusion is short lived due to rapid saturation of the charcoal filter. Once filter saturation occurs, the extracorporeal session is no longer efficacious. Using in-series hemoperfusion and hemodialysis is of benefit to correct the side effects seen with hemoperfusion alone, and hourly charcoal filter replacement may extend the efficacy of treatment in removing carprofen. This is the first published report of in-series hemoperfusion and hemodialysis being used to treat carprofen overdose in a dog. In these 2 cases, the intrinsic clearances of the patients were shown to be equivalent to that of standard hemodialysis alone, indicating that hemodialysis does not produce any advantage in carprofen clearance. In this limited report, we suggest that the efficacy of hemoperfusion in removing carprofen is short-lived, and extending the treatment beyond the first hour does not produce any therapeutic benefit. In order to extend the efficacy of hemoperfusion, hourly replacement of the charcoal filter should be considered.


[Redox-dependent ferric oxide nanoparticles loaded with doxorubicin and their influence on the functions of mitochondria].
The spectral, fluorescent and functional properties of ferric oxide and ferric hydroxide nanoparticles loaded with doxorubicin and stabilized with citric acid or lysine were studied in comparison with free doxorubicin. Their effect on the opening of calcium-induced mitochondrial pore and the possibility of the controlled release of doxorubicin under the influence of redox stimuli were investigated. The data show that the effect of nanoparticles on mitochondria depends on the type of a stabilizer. The spectral and fluorescence methods used allow us to estimate the presence or absence of free doxorubicin in solution of nanoparticles and the:concentration of bound doxorubicin. It is shown that the dithiotreitol and glutathione increase the amplitude of absorption and fluorescence of doxorubicin during incubation with nanoparticles. It is assumed that this effect may be associated with the reduction of the oxidized iron by thiols with subsequent release of doxorubicin.


Identification of two nuclear subclasses of the adenovirus type 5-encoded DNA-binding protein.
The synthesis, accumulation, and subcellular distribution of the adenovirus serotype 5 DNA-binding protein (DBP) has been examined during the infectious cycle in HeLa cells. With the onset of viral DNA replication and entry into the late phase, two nuclear subclasses of DBP are distinguishable by immunofluorescence microscopy and can be separately isolated by in situ cell fractionation. The first subclass, represented by diffuse-staining DBP, is released by the addition of 1% Nonidet P-40-150 mM NaCl. The second subclass of DBP, which is sequestered into intranuclear globular structures, requires a high ionic strength (2 M NaCl) for extraction and appears to be associated with centers of active viral DNA replication. This association is based on the observations that: DBP within the globules and viral DNA, as detected by in situ hybridization, form identical structures that colocalize within the nuclei of infected cells, the formation of DBP globular structures requires the onset and continuation of viral DNA replication, and once formed, the globular structures can be perturbed by modulating viral DNA synthesis.


Using distance education to promote the transfer of motivational interviewing skills among behavioral health professionals.
This study evaluated the effectiveness of distance education for training behavioral health professionals. Five live video workshops that covered key elements of Motivational Interviewing (MI) were delivered. The programs occurred a month apart, each 3 hours long. The programs used compressed video, transmitting the video signal through telephone lines. The audience was staff at substance abuse treatment organizations throughout the state of Arizona. Participants completed assessments regarding their training experiences, knowledge and self-efficacy in MI, and their satisfaction with the training, prior to, during, and subsequent to the workshops. Participation in the five workshops varied; the first workshop had the largest attendance of 351, the fourth the lowest of 92; 145 participants attended all five workshops. Participants expressed moderate levels of satisfaction with most aspects of the training, although some expressed frustration with interrupted audio or video signals during the programs. The handouts and videotaped examples of MI were identified as the more helpful aspects of the training. Participants reported statistically significant improvements in their self-perceived knowledge and skills. They demonstrated a statistically significant but clinically insignificant increase in knowledge. A small group of participants provided audiotapes of actual counseling sessions. These participants demonstrated minimal improvement in skills across the study that were not statistically significant. These results are discussed in terms of their implications for future research in the use of distance education as a technology transfer tool in the addiction treatment profession.


Development of a Contractile Cardiac Fiber From Pluripotent Stem Cell Derived Cardiomyocytes.
Stem cell therapy has the potential to regenerate cardiac function after myocardial infarction. In this study, we sought to examine if fibrin microthread technology could be leveraged to develop a contractile fiber from human pluripotent stem cell derived cardiomyocytes (hPS-CM). hPS-CM seeded onto fibrin microthreads were able to adhere to the microthread and began to contract seven days after initial seeding. A digital speckle tracking algorithm was applied to high speed video data (>60 fps) to determine contraction behaviour including beat frequency, average and maximum contractile strain, and the principal angle of contraction of hPS-CM contracting on the microthreads over 21 days. At day 7, cells seeded on tissue culture plastic beat at 0.83 ± 0.25 beats/sec with an average contractile strain of 4.23±0.23%, which was significantly different from a beat frequency of 1.11 ± 0.45 beats/sec and an average contractile strain of 3.08±0.19% at day 21 (n = 18, p < 0.05). hPS-CM seeded on microthreads beat at 0.84 ± 0.15 beats/sec with an average contractile strain of 3.56±0.22%, which significantly increased to 1.03 ± 0.19 beats/sec and 4.47±0.29%, respectively, at 21 days (n = 18, p < 0.05). At day 7, 27% of the cells had a principle angle of contraction within 20 degrees of the microthread, whereas at day 21, 65% of hPS-CM were contracting within 20 degrees of the microthread (n = 17). Utilizing high speed calcium transient data (>300 fps) of Fluo-4AM loaded hPS-CM seeded microthreads, conduction velocities significantly increased from 3.69 ± 1.76 cm/s at day 7 to 24.26 ± 8.42 cm/s at day 21 (n = 5-6, p < 0.05). hPS-CM seeded microthreads exhibited positive expression for connexin 43, a gap junction protein, between cells. These data suggest that the fibrin microthread is a suitable scaffold for hPS-CM attachment and contraction. In addition, extended culture allows cells to contract in the direction of the thread, suggesting alignment of the cells in the microthread direction.


How we do it? The surgical resection of a medial parietal arteriovenous malformation under multimodal imaging technology-guided hybrid operation.
This report described the surgical resection of a challenging medial parietal lobe arteriovenous malformation (AVM) using the hybrid operation theater with a multimodal imaging-guided technology. A 29-year-old male was admitted to treat a ruptured medial parietal AVM. The deep and diffusive compartment of the nidus was embolized before resection. Preoperatively and intraoperatively, mixed reality technology with multimodality imaging was utilized for surgical planning and navigation. The nidus was totally resected and confirmed by intraoperative angiography. The patient recovered without sequella. We hope this report provides new insights into applying multimodal imaging technology-guided hybrid operation for brain AVM.


[Pontine cavernous angioma (cavernoma) with initial ENT manifestations].
We report the case of a 22 years old female who consulted us for facial parestesias, hearing loss in right ear and sudden tinnitus. Her audiometry showed an unilateral discreet sensorineural hipoacusia and the cranial IRM, a mass of 20 mm diameter in right pontine region and bulbus informed as cavernous angioma with signs of recent bleeding. The patient was sent to Neurosurgery but she refused the intervention. The risk of hemorrhage in the cavernomas is estimated at 0.25% to 1.6% per year and represents the main reason to advise a surgical treatment.


Effectiveness of transitional care interventions for chronic illnesses: A systematic review of reviews.
This systematic review of reviews aims to critically evaluate and synthesize findings from recent systematic reviews to analyze the effectiveness of transitional care interventions in the management of adult patients with chronic illnesses. Transitional care interventions have been provided to patients with chronic illnesses for reducing fragmented care and hospital readmissions after discharge. However, the effectiveness of the interventions on outcomes other than hospital readmissions is still unclear. This study used the systematic review of systematic reviews methodology. From five electronic databases, systematic reviews published between January 2011 and December 2020 and those that met the inclusion and exclusion criteria were searched and screened to retrieve recent evidence. Eight systematic reviews that met the inclusion criteria and had high methodological quality were included. All included transitional care interventions aimed to reduce fragmented care and hospital admissions and improve health care outcomes in chronically ill patients. On summarizing and synthesizing the data, four common outcomes-hospital readmissions, quality of life, mortality, and health care cost savings-were retrieved. There was evidence regarding the effectiveness of transitional care on health care cost savings; however, other outcomes showed mixed results. Transitional care interventions are effective for patients with chronic illnesses. It is important to have standardized outcome measures; therefore, it is recommended to fund research and reimbursement of transitional care practices. The findings and implications of this review are important to nurse managers, health care practitioners, researchers, and policymakers.


Free energy of nascent-chain folding in the translocon.
During their synthesis, many water-soluble proteins and nearly all membrane proteins transit through a protein-conducting channel in the membrane, the Sec translocon, from where they are inserted into the lipid bilayer. Increasing evidence indicates that folding of the nascent protein begins already within the ribosomal exit tunnel in a sequence- and environment-dependent fashion. To examine the effects of the translocon on the nascent-chain folding, we have calculated the potential of mean force for α-helix formation of a 10-alanine oligopeptide as a function of its position within the translocon channel. We find that the predominant conformational states, α-helical and extended, reflect those found for the peptide in water. However, the translocon, via its surface properties and its variable diameter, shifts the equilibrium in favor of the α-helical state. Thus, we suggest that the translocon facilitates not only the insertion of membrane proteins into the bilayer but also their folding.


[Gastroenterology in the new century in Venezuela. A first five years situational diagnosis].
Once the elaboration of CIE-10 Gastroenterology we used two indicators (Health and Management) as quantifiable measurements that reflect the critical success factors in the specialty. HEALTH INDICATORS: 13,21% of main medical complains in primary care concern to Gastroenterology. Four of them rank among the first 25 ("Diarrhea", "Abdominal pain", "Helmintiasis" and "Other Esophagus, Stomach and Bowel diseases"). At the specialty care, Acid-peptic disease ranked as the first main complain according with 56-73.3% of the gastroenterologist consulted (Public and Private care) followed by Gastrointestinal reflux, Irritable bowel, Constipation, Lithiasis, Diverticular disease, Hemorrhages, Jaundice, Cirrhosis, Amibiasis, Pancreatitis, Colon cancer, Polyps, Hepatitis and Colopathy. 11,4% of the total deaths among Venezuelans are by gastrointestinal causes and five of them count among the first 25, with wide regional variability. Trujillo reports major mortality by liver disease (3%) followed by Vargas, District Federal, Tachira (2.8%). Cirrhosis and Fibrosis are more frequent in Táchira (2.3%) Trujillo, Vargas (2,1%) Some regions report mainly infections and diarrheas. Major cancer mortality is in Táchira (6,73% of deaths in the State) followed by Merida and Trujillo. MANAGEMENT INDICATORS: Services Demand. 2,86 consult/habitant/year in internal medicine and 0.77 en specialties. Services Offer. 793 Gastroenterologists (3.4/10.000 habitants). 44.5% concentrated in D.Federal, followed by Táchira (3.9%) Carabobo, Zulia y Mérida. Human Resources Formation. 16 Post-graduated Programs graduate 70 gastroenterologists annually. The Gastroenterology Education Agreement 2006 unified the Venezuelan Gastroenterologist profile and the graduation requirements. The Venezuelan Gastroenterology Society, age 60, has extraordinary national and international projection through its scientific publication (GEN Magazine). This analysis of the present of Gastroenterology in Venezuela allows us the strategically planning of its future, in order to satisfy the population needs in the specialty in a rational and effective way.


If started early in life, metformin treatment increases life span and postpones tumors in female SHR mice.
Hyperglycemia and hyperinsulinemia accelerate both aging and cancer. Antidiabetic biguanides such as metformin decrease glucose, insulin and IGF-1 level. Metformin increases lifespan and prevents cancer in mice, although its effects vary, depending on mice strain and gender. Here we showed that chronic treatment of female outbred SHR mice with metformin started at the age of 3, 9 or 15 months decreased body temperature and postponed age-related switch-off of estrous function. Surprisingly, metformin did not affect levels of serum cholesterol, triglycerides, glucose and insulin. Treatment with metformin started at the age of 3 months increased mean life span by 14% and maximum life span by 1 month. The treatment started at the age of 9 months insignificantly increased mean life span by only 6%, whereas the treatment started at the age of 15 months failed to increase life span. The mean life span of tumor-free mice was increased by 21% in 'the youngest group', by 7% in 'middle-aged group' and in contrast was reduced by 13% in 'the oldest group'. When started at the age of 3 and 9 months, metformin delayed the first tumor detection by 22% and 25%, correspondingly. Thus, in female SHR mice, metformin increased life span and postponed tumors when started at the young and middle but not at the old age. In contrast, metformin improves reproductive function when started at any age.


Direct Dynamics Simulations of the CH2 + O2 Reaction on the Ground- and Excited-State Singlet Surfaces.
In a previous work [ Lakshmanan , S. ; J. Phys. Chem. A 2018 , 122 , 4808 - 4818 ], direct dynamics simulations at the M06/6-311++G(d,p) level of theory were reported for 3CH2 (X3B1) + 3O2 (X3∑g-) reaction on its ground-state singlet potential energy surface (PES) at 300 K. However, further analyses revealed the simulations are unstable for the 3CH2 (X3B1) + 3O2 (X3∑g-) reactants on the ground-state singlet surface and the trajectories reverted to an excited-state singlet surface for the 1CH2 (ã1A1) + 1O2 (b1∑g+) reactants. Thus, the dynamics reported previously are for this excited-state singlet PES. The PESs for the 3CH2 (X3B1) + 3O2 (X3∑g-) and 1CH2 (ã1A1) + 1O2 (b1∑g+) reactants are quite similar, and this provided a means to perform simulations for the 3CH2 (X3B1) + 3O2 (X3∑g-) reactants on the ground-state singlet PES at 300 K, which are reported here. The reaction dynamics are quite complex with seven different reaction pathways and nine different products. A consistent set of product yields have not been determined experimentally, but the simulation yields for the H atom, CO, and CO2 are somewhat lower, higher, and lower respectively, than the recommended values. The yields for the remaining six products agree with experimental values. Product decomposition was included in determining the product yields. The simulation 3CH2 + 3O2 rate constant at 300 K is only 3.4 times smaller than the recommended value, which may be accommodated if the 3CH2 + 3O2 → 1CH2O2 potential energy curve is only 0.75 kcal/mol more attractive at the variational transition state for 3CH2 + 3O2 → 1CH2O2 association. The simulation kinetics and dynamics for the 3CH2 + 3O2 and 1CH2 + 1O2 reactions are quite similar. Their rate constants are statistically the same, an expected result, since their transition states leading to products have energies lower than that of the reactants and the attractive potential energy curves for 3CH2 + 3O2 → 1CH2O2 and 1CH2 + 1O2 → 1CH2O2 are nearly identical. The product yields for the 3CH2 + 3O2 and 1CH2 + 1O2 reactions are also nearly identical, only differing for the CO2 yield. The reaction dynamics on both surfaces are predominantly direct, with negligible trapping in potential energy minima, which may be an important contributor to their nearly identical product yields.


IFNL3 rs12980275 Polymorphism Predicts Septic Shock-Related Death in Patients Undergoing Major Surgery: A Retrospective Study.
Interferon lambda 3 (IFNL3, previously called IL-28B) is a cytokine with effects against viral and bacterial pathogens. We aimed to analyze the IFNL3 rs12980275 SNP in patients who underwent major surgery, in order to establish its relationship with susceptibility to septic shock and septic shock-related death in these patients. We performed a case-control study on 376 patients to establish the association between IFNL3 rs12980275 SNP and the susceptibility to develop septic shock. Besides, we performed a longitudinal study among 172 septic shock patients using survival analysis with one censoring point of 28-days mortality. The IFNL3 rs12980275 polymorphism was genotyped by Agena Bioscience's MassARRAY platform. IFNL3 rs12980275 polymorphism was not associated with higher susceptibility to infection and septic shock development. Regarding survival analysis, the Kaplan-Meier analysis showed that patients with IFNL3 rs12980275 AA genotype had higher survival than patients with GG genotype (p = 0.003). The Cox regression analysis adjusted by the most relevant clinical and epidemiological characteristics showed that the GG genotype (recessive model) and the presence of the G allele (additive model) were associated with higher risk of death [adjusted hazard ratio (aHR) = 2.15, p = 0.034; aHR = 1.50, p = 0.030, respectively]. In conclusion, IFNL3 rs12980275 polymorphism was associated with septic shock-related death in patients who underwent major surgery. The A allele was linked to protection, and the G allele was associated with an increased risk of death. This is a first preliminary study that suggests for the first time a role of IFNL3 polymorphisms in the prognosis of septic shock.


Trans-subxiphoid robotic thymectomy.
Minimally invasive surgery has replaced median sternotomy for resectable anterior mediastinal masses and is performed by various approaches. We developed a new minimally invasive surgical procedure by combining the subxiphoid approach performed through a midline camera port with the use of a robotic surgery system (Intuitive Surgical, Sunnyvale, CA, USA). A 3-cm transverse incision was made 1 cm below the xiphoid process. Then, a port designed for single-port surgery was inserted. Through this port, CO2 gas was injected at 8 mmHg. The thymus was then detached from the back of the sternum. A 1-cm skin incision was made bilaterally in the sixth intercostal space, followed by insertion of a port for the robotic system. A camera port was inserted into the subxiphoid port, to which the camera scope was mounted, and thymectomy was performed. We have performed the operation in 3 patients. In our experience, this procedure provides a good operative view in the neck region and makes verification of the phrenic nerve easy. Furthermore, with the da Vinci surgical system, which enables surgical manipulation from a correct angle due to the multijoint robotic arms, trans-subxiphoid robotic thymectomy may be a promising new thymectomy procedure.


Correlates of Selected Indices of Physical Fitness And Duration of Incarceration among Inmates in Some Selected Nigeria Prisons.
Incarceration has been associated with reduced physical activity. However, physical inactivity is a major cause of morbidity and mortality. The aim of the present study was therefore, to evaluate the incidence and relationship between the measures of physical fitness and the duration of incarceration in of inmates in Kano-Nigeria prisons. A cross-sectional study was done to determine the relationship between the measures of physical fitness and the duration of incarceration of inmates in Kano prisons. Subjects' physical fitness level (cardio-respiratory fitness, body mass index and waist circumference) was assessed using standardized protocols. Simple percentage, Pearson moment correlation test and student's t-test were used to analyze variables of interest. One hundred and sixteen inmates; 108 (93.1%) males and 8 (6.9%) females participated in the study. The study revealed high (93.1%) prevalence of low cardio-respiratory fitness among inmates and significant correlation between the selected indices of physical fitness (cardio-respiratory fitness, body mass index and waist circumference) and duration of incarceration. The prevalence of low cardio-respiratory fitness was high among inmates and long period of inadequate physical activity may be implicated as causative factor of low physical fitness among inmates in Kano prison. Prison administration and staff should encourage healthy inmate behavior. Provision of adequate facilities to encourage physical activity and sports participation is highly needed.


Chronic treatment with a MEK inhibitor reverses enhanced excitatory field potentials in Syngap1+/- mice.
Synaptic Ras-GTPase-activating protein 1 (SYNGAP1) is an abundant brain-specific protein localized at the postsynaptic density of mammalian excitatory synapses. SYNGAP1 functions as a crucial regulator of downstream intracellular signaling triggered by N-methyl-d-aspartate receptor activation. One of the most important signaling pathways regulated by SYNGAP1 is the Ras-Raf-MEK-ERK pathway. SYNGAP1 deficiency is associated with hyperphosphorylation of MEK and ERK kinases and with altered synaptic function in Syngap1+/- mice. Loss-of-function mutations in the SYNGAP1 gene have been documented in many human cognitive and neurological disorders. However, there are currently no approaches that reverse the phenotypes of SYNGAP1 deficiency. Using electrophysiological recordings of field responses in hippocampal slices, we examined if disturbances of synaptic physiology in the hippocampus of 7-8-month old Syngap1+/- mice were sensitive to the effect of the MEK inhibitor PD-0325901 given orally for 6days. We found that in hippocampal slices from vehicle-treated Syngap1+/- mice, basal synaptic responses were higher and their long-term potentiation (LTP) was lower than in slices from wild-type littermates. Chronic administration of PD-0325901 normalized basal synaptic responses, but did not reverse LTP deficit. The differential sensitivity of basal synaptic transmission and LTP to MEK inhibition indicates that the effects of SYNGAP1 deficiency on these synaptic parameters are mediated by distinct pathways. Our findings also suggest that at least some physiological phenotypes of the germline Syngap1 mutation can be ameliorated by pharmacological treatment of adult animals.


Breath analysis in pulmonary arterial hypertension.
Pulmonary arterial hypertension (PAH) is a progressive and devastating condition characterized by vascular cell proliferation and is associated with several metabolic derangements. We hypothesized that metabolic derangements in PAH can be detected by measuring metabolic by-products in exhaled breath. We collected breath and blood samples from patients with PAH at the time of right-sided heart catheterization (n=31) and from healthy control subjects (n=34). Breath was analyzed by selected ion flow tube-mass spectrometry in predetermined training and validation cohorts. Patients with PAH were 51.5±14 years old, and 27 were women (85%). Control subjects were 38±13 years old, and 22 were women (65%). Discriminant analysis in the training set identified three ion peaks (H3O+29+, NO+56+, and O2+98+) and the variable age that correctly classified 88.9% of the individuals. In an independent validation cohort, 82.8% of the individuals were classified correctly. The concentrations of the volatile organic compounds 2-propanol, acetaldehyde, ammonia, ethanol, pentane, 1-decene, 1-octene, and 2-nonene were different in patients with PAH compared with control subjects. Exhaled ammonia was higher in patients with PAH (median [interquartile range]: 94.7 parts per billion (ppb) [70-129 ppb] vs 60.9 ppb [46-77 ppb], P<.001) and was associated with right atrial pressure (ρ=0.57, P<.001), mean pulmonary artery pressure (ρ=0.43, P=.015), cardiac index by thermodilution (ρ=-0.39, P=.03), pulmonary vascular resistance (ρ=0.40, P=.04), mixed venous oxygen (ρ=-0.59, P<.001), and right ventricular dilation (ρ=0.42, P=.03). Breathprint is different between patients with PAH and healthy control subjects. Several specific compounds, including ammonia, were elevated in the breath of patients with PAH. Exhaled ammonia levels correlated with severity of disease.


Evaluating re-identification risks with respect to the HIPAA privacy rule.
Many healthcare organizations follow data protection policies that specify which patient identifiers must be suppressed to share "de-identified" records. Such policies, however, are often applied without knowledge of the risk of "re-identification". The goals of this work are: (1) to estimate re-identification risk for data sharing policies of the Health Insurance Portability and Accountability Act (HIPAA) Privacy Rule; and (2) to evaluate the risk of a specific re-identification attack using voter registration lists. We define several risk metrics: (1) expected number of re-identifications; (2) estimated proportion of a population in a group of size g or less, and (3) monetary cost per re-identification. For each US state, we estimate the risk posed to hypothetical datasets, protected by the HIPAA Safe Harbor and Limited Dataset policies by an attacker with full knowledge of patient identifiers and with limited knowledge in the form of voter registries. The percentage of a state's population estimated to be vulnerable to unique re-identification (ie, g=1) when protected via Safe Harbor and Limited Datasets ranges from 0.01% to 0.25% and 10% to 60%, respectively. In the voter attack, this number drops for many states, and for some states is 0%, due to the variable availability of voter registries in the real world. We also find that re-identification cost ranges from $0 to $17,000, further confirming risk variability. This work illustrates that blanket protection policies, such as Safe Harbor, leave different organizations vulnerable to re-identification at different rates. It provides justification for locally performed re-identification risk estimates prior to sharing data.


Failure to diagnose cardiac treatment rejection with Tc99m-PYP images.
The possibility of diagnosing transplant rejection using Tc-99m-PYP imaging was examined in 12 cardiac transplant recipients. Two patients were studied on two occasions. The presence or absence of active rejection was established by endomyocardial biopsy. The intensity and pattern of myocardial uptake of the tracer did not differ significantly in the two patients studied at the time of rejection compared to the remainder. It is concluded that a single Tc-99m-PYP study cannot be used to diagnose cardiac transplant rejection.


Enhanced G2 chromatid radiosensitivity, an early stage in the neoplastic transformation of human epidermal keratinocytes in culture.
A deficiency in DNA repair, manifest as enhanced chromatid radiosensitivity during the G2 phase of the cell cycle, together with a proliferative stimulus such as that provided by active oncogenes may be necessary and sufficient for the malignant neoplastic transformation of human keratinocytes in culture. Normal epidermal keratinocytes established as continuous cell lines by transfection with pSV3-neo or infection with adeno 12-SV40 hybrid virus developed enhanced G2 chromatid radiosensitivity after 18 passages in culture. In contrast to cells from primary or secondary culture, these cells could be transformed to malignant neoplastic cells by infection with Kirsten murine sarcoma virus containing the Ki-ras oncogene or in one line by the chemical carcinogen, N-methyl-N'-nitro-N-nitrosoguanidine; both of these agents produced a marked proliferative response. Cytological heterogeneity and karyotypic instability characterized the cells during their progression to neoplasia. These results are interpreted in terms of a mechanism for neoplastic transformation.


[The dependence of the dynamics of the extinction of a temporary connection on the recognizability of a reinforcing stimulus].
Dynamics was studied of the extinction of temporary connection, elaborated by means of motivationally significant word, in patients with chronic alcoholism. Two series of studies were conducted. In the first one the reinforcing stimulus was not recognized by the subject and was perceived as a dull light flash on the screen. In the second one the word was easily read, i.e. it was recognized. It was found that conditioned changes of P300 wave at the elaboration of temporary connection depend on the recognition of the reinforcing stimulus. Temporary connections, elaborated by non-recognized motivationally significant stimulus are considerably stronger that the connections, elaborated by means of recognized reinforcement.


Non-Pharmacological Management of Painful Peripheral Neuropathies: A Systematic Review.
Peripheral neuropathic pain (PNP) is defined as the neuropathic pain that arises either acutely or in the chronic phase of a lesion or disease affecting the peripheral nervous system. PNP is associated with a remarkable disease burden, and there is an increasing demand for new therapies to be used in isolation or combination with currently available treatments. The aim of this systematic review was to evaluate the current evidence, derived from randomized controlled trials (RCTs) that assess non-pharmacological interventions for the treatment of PNP. After a systematic Medline search, we identified 18 papers eligible to be included. The currently best available evidence (level II of evidence) exist for painful diabetic peripheral neuropathy. In particular, spinal cord stimulation as adjuvant to conventional medical treatment can be effectively used for the management of patients with refractory pain. Similarly, adjuvant repetitive transcranial magnetic stimulation of the motor cortex is effective in reducing the overall pain intensity, whereas adjuvant static magnetic field therapy can lead to a significant decrease in exercise-induced pain. Weaker evidence (level III of evidence) exists for the use of acupuncture as a monotherapy and neurofeedback, either as an add-on or a monotherapy approach, for treatment of painful chemotherapy-induced peripheral neuropathy CONCLUSIONS: Future RCTs should be conducted to shed more light in the use of non-pharmacological approaches in patients with PNP.


Comparison of Sperm Telomere Length between Two Sperm Selection Procedures: Density Gradient Centrifugation and Zeta Potential.
Telomeres are particular sequences of DNA located at the end of the eukaryotic chromosomes that are essential for genome integrity. Telomere length in spermatozoa differs among males, as well as spermatozoa. Also, decreased telomere length in spermatozoa of infertile men is associated with the reduction of fertility potential and embryo quality. Density gradient centrifugation (DGC) and swim-up are useful techniques for separation of spermatozoa with longer telomeres. Also, the selection of sperm based on surface negative electric charge or "Zeta potential", can separate high percentage of spermatozoa with intact chromatin compared to DGC alone, and also the combination of DGC-Zeta can improve clinical outcomes of infertile men candidate for intracytoplasmic sperm injection (ICSI). Therefore, we compared sperm telomere length and DNA fragmentation between two sperm preparation procedures, namely DGC and zeta potential. In this experimental study, we assessed sperm telomere length and DNA fragmentation by quantitative real-time polymerase chain reaction (PCR) and TUNEL assay methods, respectively. The spermatozoa were obtained from infertile men with normozoospermia between September 2017 and December 2017 and prepared either by DGC or zeta potential methods. Sperm telomere length was expressed as relative and absolute units. Compared with washed semen samples or control, no significant (P>0.05) difference was observed in the mean relative or absolute sperm telomere length when the two methods DGC or zeta potential were compared. However, the mean percentage of DNA fragmentation was significantly (P<0.05) lower in spermatozoa prepared by DGC or zeta potential methods than spermatozoa obtained from control samples. This is the first study that compared the effect of DGC and zeta potential as the sperm preparation methods on sperm telomere length. It seems that both methods can select sperm population with high DNA integrity and the same sperm telomeres length.


Stroke prophylaxis in atrial fibrillation: who gets it and who does not? Report from the Stockholm Cohort-study on Atrial Fibrillation (SCAF-study).
Underuse of warfarin for stroke prophylaxis in atrial fibrillation (AF) is extensive and represents a major problem in clinical practice. To identify factors associated with warfarin treatment in eligible AF patients. The study population consisted of all Swedish resident AF patients at the Stockholm South General Hospital during 2002 (n=2796). Medical records were examined and complemented by data from the Swedish National Hospital Discharge Register. Sixty-eight percent of the patients (1898/2796) had indications, and no apparent contraindications for warfarin treatment. Of these 54% (1029/1898) got warfarin. Factors favouring warfarin treatment after adjustment for other factors were history of ischaemic stroke, an implanted pacemaker, treatment in a cardiology rather than internal medicine ward and valvular defect. Factors associated with a reduced likelihood of warfarin treatment were paroxysmal type of AF and age >80 years. Important risk factors for stroke in AF like heart failure, hypertension, and diabetes did not increase the chances of warfarin treatment. Risk stratification using known risk factors of stroke seems to affect warfarin treatment only to a minor degree in clinical practice. Undertreatment was particularly common in patients with paroxysmal AF and in patients aged >80 years and calls for improved clinical routines in accordance with international guidelines.


[Hypertension in the elderly].
Hypertension (HT) is a common problem in elderly persons (age >65 years), reaching a prevalence as high as 60 to 80%. Isolated systolic HT mostly occurs in older patients. Treatment of HT in all patients, independent of age, consists of lifestyle modifications and antihypertensive therapy. Randomized trials have provided clear evidence of benefit from treating HT in elderly patients, including those over the age of 80 years. Drug therapy should be started in elderly hypertensive patients if lifestyle changes are insufficient and in the absence of a hypertensive emergency or urgency, blood pressure reduction should always be gradual. A long-acting dihydropyridine or a thiazide diuretic is generally preferred because of increased blood pressure-lowering efficacy in this population. Goal blood pressure recommendation for most hypertensive elderly is to attain a systolic pressure below 140 mmHg.


Effect of preterm birth on morphosyntactic development.
Background: Preterm children are at risk of deficits in language, including grammatical skills. The main purpose of this survey was to investigate whether Persian-speaking children born preterm differ in their morphosyntax ability compared to full-term children. Methods: Morphosyntactic performance was assessed in 86 Persian-speaking children (43 healthy preterm and 43 full-term children) aged 4 and 5 years using the Persian Developing Sentence Scoring (PDSS). Participants were matched for age, gender, and gestational age. Results: The healthy preterm children who participated in this study were significantly outperformed by the full-term children in the morphosyntactic evaluation (p<0.05). Furthermore, their grammatical skills, based on PDSS, were not as developed as 4 to 5-year-old full-term children. Gender, in general, and gestational age had no effect on the PDSS scores of preterm children (p>0.05). Conclusion: Preterm children, regardless of gestational age, are at risk of morphosyntax impairments, which may not be recovered during the normal development. Therefore, grammatical evaluation and treatment seem to be necessary for these children.


Vested interests in addiction research and policy. Why do we not see the corporate interests of the alcohol industry as clearly as we see those of the tobacco industry?
To compare the current status of global alcohol corporations with tobacco in terms of their role in global governance and to document the process by which this difference has been achieved and the consequences for alcohol control policy. Participant observation in the global political arena, review of industry materials (submissions, publications, conference presentations, websites) and review of published literature formed the basis for the current analysis. Recent events in the global political arena have highlighted the difference in perception of the alcohol and tobacco industries which has allowed alcohol corporations to participate in the global governance arena in a way in which tobacco has not been able. The transnational producers of alcohol have waged a sophisticated and successful campaign during the past three decades, including sponsorship of intergovernmental events, funding of educational initiatives, research, publications and sponsoring sporting and cultural events. A key aspect has been the framing of arguments to undermine perceptions of the extent of alcohol-related harms to health by promoting ideas of a balance of benefits and harms. An emphasis on the heaviest drinkers has been used to promote the erroneous idea that 'moderate' drinkers experience no harm and a goal of alcohol policy should be to ensure they are unaffected by interventions. This leads to highly targeted interventions towards the heaviest drinkers rather than effective regulation of the alcohol market. A sophisticated campaign by global alcohol corporations has promoted them as good corporate citizens and framed arguments with a focus on drinkers rather than the supply of alcohol. This has contributed to acceptance in the global governance arena dealing with policy development and implementation to an extent which is very different from tobacco. This approach, which obscures the contribution supply and marketing make to alcohol-related harm, has also contributed to failure by governments to adopt effective supply-side policies.


Summary of the 4th Nordic Symposium on Digital Pathology.
The Nordic symposium on digital pathology (NDP) was created to promote knowledge exchange across stakeholders in health care, industry, and academia. In 2016, the 4th NDP installment took place in Linköping, Sweden, promoting development and collaboration in digital pathology for the benefit of routine care advances. This article summarizes the symposium, gathering 170 attendees from 13 countries. This summary also contains results from a survey on integrated diagnostics aspects, in particular radiology-pathology collaboration.


Tick-borne infections in wolves from an expanding population in Eastern Europe.
In Central and Eastern Europe, wolf populations have been increasing over the last two decades, recolonizing areas from which the species had been previously exterminated. As wolves are still recovering after years of persecution by humans, recognizing pathogens infecting this species, including tick-borne infections, is crucial for its conservation. On the other hand the high mobility of wolves and their frequent contacts with humans, dogs, and other domestic species make them a potentially important zoonotic reservoir. In this paper, we used molecular methods to determine the prevalence of tick-borne pathogens in the following genera: Anaplasma, Babesia, Bartonella, Borrelia, and Rickettsia in 50 free-ranging wolves from Poland. We detected Babesia canis in the blood of nine individuals (prevalence 9/50=18 %). The obtained sequence showed the highest similarity to B. canis isolated from dogs and ticks, and all infected individuals originated from regions endemic to the ornate tick, Dermacentor reticulatus. Anaplasma phagocytophilum was found in tissue from one individual (1/50=2 %), and the sequence was assigned to the zoonotic ecotype I.


A possible role for cyclosporins in cancer chemotherapy.
It has been established for some time that cyclosporin A (CsA) can exert cytotoxic effects in T-cell neoplasms. More recently, antiproliferative effects in a variety of non-T-cell tumour cell lines have been demonstrated. Inhibition of polyamine synthesis is a possible mechanism and combination of CsA with other polyamine inhibitors may be particularly effective. The non-immunosuppressive analogue, B3-243, is at least as effective as CsA as an antiproliferative in human lung cancer cell lines. CsA potentiates the effect of a number of cytotoxic drugs (eg adriamycin, vincristine, VP16) both in vitro and in vivo. Differential potentiation in vitro is often seen in cells with acquired drug resistance compared with their parent lines. A number of non-immunosuppressive analogues of CsA also act as 'resistance modifiers' and hence the structure/activity requirements for immunosuppression and resistance modification appear to differ.


Distribution of mouse adenovirus type 1 in intraperitoneally and intranasally infected adult outbred mice.
In situ nucleic acid hybridization and immunohistochemistry were used to determine the histological localization of mouse adenovirus type 1 (MAV-1) during acute infection of adult mice infected either intraperitoneally or intranasally with 1,000 PFU of wild-type virus. Organ samples were collected from days 1 to 17 postinfection for the intraperitoneally infected mice and from days 1 to 13 for the intranasally infected mice. Endothelial cells of the brain and spinal cord showed extensive evidence of MAV-1 infection. Endothelial cells in lungs, kidneys, and other organs were also positive for MAV-1, indicating a widespread involvement of the systemic circulation. The presence of viral nucleic acid and/or antigen was also demonstrated in lymphoid tissue. The spleens, Peyer's patches, and peripheral lymph nodes showed positive staining at various times postinfection in mice infected by either route. Virus-infected cells in the spleen exhibited a stellate shape and were localized to the red pulp and germinal centers, suggesting that they are cells of the mononuclear phagocytic system.


Effect of fragile X on physical and intellectual traits estimated by pedigree analysis.
A maximum likelihood scoring technique for analysis of pedigree data, which allows for estimation of random effects (variance components) concurrently with other "fixed" effects in a quantitative trait, was applied to establish the effect of the fragile X condition in the variation of intellectual and physical traits. In 52 fragile X families, intellectual status was represented by measures of vocabulary knowledge (PPVT) and of nonverbal visuospatial skills (BDT), and physical status by a combined physical (anthropometric) score, and jaw length. The fixed effects included fragile X and sex and their interaction on the mean and covariances between relatives for the intellectual and physical scores. The random effects included environmental (common and individual) and genetic (additive and dominance) components. Different genetic models were tested by the likelihood ratio criterion, and the maximum likelihood parameters for each of the three scores were based on the most appropriate models. The effect of fragile X on the mean values was found to be significant for all the traits, and much more conspicuous in male than in female individuals, the effects in the PPVT and the anthropometric score being intercorrelated. The effect of fragile X on growth of a single physical trait relative to height was demonstrated using jaw length as an example. We have also demonstrated an effect of fragile X on genetic (additive) variance, as well as on the mean of the BDT score, and the effect of age on the nongenetic variance of PPVT, and jaw length.


Immunosuppressant quantification in intravenous microdialysate - towards novel quasi-continuous therapeutic drug monitoring in transplanted patients.
Therapeutic drug monitoring (TDM) plays a crucial role in personalized medicine. It helps clinicians to tailor drug dosage for optimized therapy through understanding the underlying complex pharmacokinetics and pharmacodynamics. Conventional, non-continuous TDM fails to provide real-time information, which is particularly important for the initial phase of immunosuppressant therapy, e.g., with cyclosporine (CsA) and mycophenolic acid (MPA). We analyzed the time course over 8 h of total and free of immunosuppressive drug (CsA and MPA) concentrations measured by liquid chromatography-tandem mass spectrometry (LC-MS/MS) in 16 kidney transplant patients. Besides repeated blood sampling, intravenous microdialysis was used for continuous sampling. Free drug concentrations were determined from ultracentrifuged EDTA-plasma (UC) and compared with the drug concentrations in the respective microdialysate (µD). µDs were additionally analyzed for free CsA using a novel immunosensor chip integrated into a fluorescence detection platform. The potential of microdialysis coupled with an optical immunosensor for the TDM of immunosuppressants was assessed. Using LC-MS/MS, the free concentrations of CsA (fCsA) and MPA (fMPA) were detectable and the time courses of total and free CsA comparable. fCsA and fMPA and area-under-the-curves (AUCs) in µDs correlated well with those determined in UCs (r≥0.79 and r≥0.88, respectively). Moreover, fCsA in µDs measured with the immunosensor correlated clearly with those determined by LC-MS/MS (r=0.82). The new microdialysis-supported immunosensor allows real-time analysis of immunosuppressants and tailor-made dosing according to the AUC concept. It readily lends itself to future applications as minimally invasive and continuous near-patient TDM.


Comparison of oculoplethysmography/carotid phonoangiography with duplex scan/spectral analysis in the detection of carotid artery stenosis.
The accuracy of the duplex scan with spectral analysis (DS/SA) in predicting the presence of arteriographic carotid stenosis was compared to that of oculoplethysmography/carotid phonoangiography (OPG/CPA) in 234 vessels from 117 patients who had had both non-invasive studies in addition to independently interpreted arteriograms. The DS/SA with 212/234 (91%) overall correct responses was superior to the OPG/CPA which properly classified 181/234 (77%) of the vessels (p less than .01). Of major clinical impact was the superiority of the DS/SA (p less than .001) in identifying the 72 vessels with 50-99% stenosis. The OPG/CPA had a discouraging 39/72 (54%) false-negative rate in this group whereas the DS/SA missed only 9/72 (12%) of these arteries. Of those 39 incorrect responses for the OPG/CPA, 26/39 (67%) were in patients with a 50% or greater stenosis on the contralateral side. This is a recognized area of weakness for that test. Based on the results of this study, we have abandoned the use of the OPG/CPA in the evaluation of patients with suspected carotid stenosis and rely solely on the duplex scan with spectral analysis.


Mutations affecting gluconate catabolism in Escherichia coli. Genetic mapping of the locus for the thermosensitive gluconokinase.
An Escherichia coli strain unable to use gluconate was isolated by spontaneous curing of lambda cI857 s7 xis6 b515 b519, lambda cI857 s7 delta(A-att) dargI valS lysogens. Two lesions, linked to asd and pyrB markers, respectively, were necessary to produce this phenotype. The asd-linked mutation gnt-17, of regulatory type, seems to affect the expression of the major system of gluconate utilization (min 75) as well as that of 6-phosphogluconate dehydratase (gene edd, min 41), the first enzyme of the Entner-Doudoroff pathway. A closely linked suppressor of gnt-17 causes constitutivity of these activities; this suppressor resembles gntR, which is also in the asd region. Hence, it is possible that gnt-17 is a super-repressing allele of gntR, rather than a positive controlling element. Lesion gnt-17 alone does not prevent the utilization of gluconate; for this, the mutation gnt-18 at 96.9 min is also necessary. This mutation abolishes the thermosensitive gluconokinase activity and thus eliminates the subsidiary ability to catabolize gluconate. Accordingly, gnt-18 seems to be allelic with gntV, the locus postulated as being in the pyrB region specifying the thermosensitive gluconokinase.


Haemodynamic effects of secretory agents on the isolated elasmobranch rectal gland.
Perfusion flow rate in the isolated elasmobranch rectal gland, perfused at in vivo pressures, was measured in Scyliorhinus canicula L. and Squalus acanthias L. Flow through the secretory parenchyma of the gland was reduced in the presence of concentrations of catecholamines in the physiological range, an effect mediated via alpha-adrenergic receptors within the gland vasculature. Flow through the non-secretory vascular shunts of the rectal gland was unaffected. The vasoconstriction induced by noradrenaline was blocked by the addition of cyclic AMP + theophylline or adenosine at concentrations known to stimulate secretion by the gland. In Squalus, a similar effect was seen with the secretagogue vasoactive intestinal peptide, but this agent had no effect in the glands of Scyliorhinus. Experiments indicate that the blockage of the noradrenaline effect by the secretory agents does not involve any stimulation of vasodilatory beta-adrenergic receptors and, furthermore, that the vasomotor effects of these agents appear to be entirely independent of their actions on the secretory cells. Evidence is presented indicating that the vasomotor action of adenosine may be mediated via receptors specific for the ribose moiety of the nucleoside (Ra receptors) activating adenylate cyclase, and that this may, in turn, explain the observed effects of the addition of exogenous cyclic AMP. The significance of the observed vascular effects in the overall control of secretion rate by the gland in vivo is discussed.


EEG-based Emotion Recognition Using Sub-Band Time-Delay Correlations.
Emotion recognition is a challenging task with many potential applications in psychology, psychiatry, and human-computer interaction (HCI). The use of time-delay information in the controlled time-delay stability (cTDS) algorithm can help to capture the temporal dynamics of EEG signals, including sub-band information and bi-directional coupling that can aid in emotion recognition and identification of specific connectivity patterns between brain rhythms. Incorporating EEG frequency bands can be used to design better emotion recognition systems. This paper evaluates the cTDS algorithm for binary classification tasks of arousal and valence using EEG sub-band signals. This method achieved a high accuracy of 91.1% for arousal and 91.7% for valence based on one electrode recording site at Fp1. The cTDS algorithm is a promising approach to analyzing brain network interactions. It can be particularly applicable to arousal and valence classification tasks, especially within a complex, multimodal feature space associated with understanding psychiatric disorders and HCI applications.


Effect of a sudden infant death syndrome risk reduction education program on risk factor compliance and information sources in primarily black urban communities.
In the US, a higher incidence of sudden infant death syndrome (SIDS) and a slower decline in the incidence of SIDS has been found among blacks when compared with white infants. The continued racial disparity in SIDS is thought to be attributable to lack of compliance with SIDS risk reduction recommendations. To better understand the disparities in SIDS risk reduction behaviors, we sought to study compliance and information sources related to SIDS among primarily black communities in a city with a high SIDS incidence rate before and after a targeted educational campaign. Pre- and post-SIDS Risk Reduction Education Program telephone surveys were performed in targeted Chicago communities with at least 86% blacks. Data collection for Survey 1 was from September 22 to November 4, 1999. Data collection for Survey 2 was from November 17, 2001, to January 12, 2002, 24 months after the aggressive implementation of a comprehensive, ethnically sensitive risk reduction program. Survey 1 analyzed data from 480 mothers with an infant <12 months of age (327 black, 66 white, and 87 Hispanic) and Survey 2 had 472 mothers (305 black, 77 white, and 90 Hispanic). The incidence of nighttime prone sleeping at Survey 1 was 25% among black respondents, 17% in whites, and 12% in Hispanics and decreased (but not significantly) among all groups by Survey 2. Overall, in Survey 2 compared with Survey 1, fewer mothers reported putting their infants on an adult bed, sofa, or cot both during the day and at night, with the biggest change seen in black mothers for daytime naps. Despite the same educational initiative, blacks increased the use of pillows, stuffed toys, and soft bedding in the sleep environment as compared with whites. More mothers in Survey 2 than in Survey 1 said that they noticed their infants sleeping on their back during the newborn hospitalization. Significantly more black and white mothers in Survey 2 compared with Survey 1 reported that a doctor or nurse had told them what the best position was for putting their infants to sleep, and all 3 groups said that the health care providers indicated that placing the infant on its back was the best sleep position. In examining the relationship between information sources and SIDS risk behaviors, among all groups observation of sleep position in hospital had no effect on behavior after newborn discharge; however, specific instruction by a nurse or doctor in the hospital about how to properly place the infant for sleep influenced behavior after the mother left the hospital. The Surveys indicate the greatest impact of the SIDS risk factor educational initiative targeted at black communities was changing behaviors regarding safe sleep locations by reducing the incidence of infants placed for nighttime and daytime sleep in adult beds, sofas, or cots. Although these data indicate considerable progress as a result of the targeted educational initiative, our findings suggest that cultural explanations for specific infant care practices must be more clearly understood to close the gap between SIDS risk factor compliance and apparent knowledge about SIDS risk factors.


RhoA and rho kinase regulate the epithelial Na+/H+ exchanger NHE3. Role of myosin light chain phosphorylation.
The activity of the Na(+)/H(+) exchanger NHE3 isoform, which is found primarily in epithelial cells, is sensitive to the state of actin polymerization. Actin assembly, in turn, is controlled by members of the small GTPase Rho family, namely Rac1, Cdc42, and RhoA. We therefore investigated the possible role of these GTPases in modulating NHE3 activity. Cells stably expressing NHE3 were transiently transfected with inhibitory forms of Rac1, Cdc42, or RhoA and transport activity was assessed using microfluorimetry. NHE3 activity was not adversely affected by either dominant-negative Rac1 or Cdc42. By contrast, the inhibitory form of RhoA greatly depressed NHE3 activity, without noticeably altering its subcellular distribution. NHE3 activity was equally reduced by inhibiting p160 Rho-associated kinase I (ROK), a downstream effector of RhoA, with the selective antagonist Y-27632 and a dominant-negative form of ROK. Furthermore, inhibition of ROK reduced the phosphorylation of myosin light chain. A comparable net dephosphorylation was achieved by the myosin light chain kinase inhibitor ML9, which similarly inhibited NHE3. These data suggest that optimal NHE3 activity requires a functional RhoA-ROK signaling pathway which acts, at least partly, by controlling the phosphorylation of myosin light chain and, ultimately, the organization of the actin cytoskeleton.


Effect of antisense RNA targeting polo-like kinase 1 on cell cycle and proliferation in A549 cells.
Expression of polo-like kinase 1 (Plk1) is elevated in lung cancer and has been proposed as having prognostic value and related to resistance to chemotherapy and radiation. In addition, Plk1 has several functions in mitotic progression. In this study, the authors investigated the effect of Plk1 depletion on cell cycle progression and proliferation in A549 cells, a lung cancer cell line. A recombinant plasmid containing antisense RNA targeting Plk1 (pcDNA3-Plk1) was transfected into A549 cells. Reverse transcription-polymerase chain reaction and Western blot were used to examine Plk1 gene expression. Cell proliferation was evaluated by direct cell counting and bromodeoxyuridine (BrdU) labelling. Cell cycle and apoptosis were examined by flow cytometry. Expression of alpha-tubulin was detected by immunofluorescence, and the inhibition rate (IR) by chemotherapeutic agents was determined by 3-(4,5-dimethylthiazol-2-yl) 2,5-diphenyl-tetrazolium bromide assay. After transfection into A549 cells, pcDNA3-Plk1 reduced Plk1 mRNA by 46.75% for 24 hours and by 61.84% for 48 hours. Plk1 protein was significantly decreased simultaneously (P < 0.05). Abnormal morphological changes of cells and growth inhibition were observed in pcDNA3-Plk1 transfected groups. The BrdU labelling index was 25.59% 48 hours after transfection, which was significantly lower than that of the control groups (P < 0.05). Forty-eight hours after transfection, there showed absence of microtubule polymerization and spindle abnormalities in staining for alpha-tubulin. A549 cells showed a strong G2/M arrest and apoptosis 72 hours post transfection. IR of vinorelbine in pcDNA3-Plk1 transfected groups was significantly higher than that of the other groups (P < 0.05, respectively). Plk1 depletion interferes with spindle formation, induces cell cycle arrest and apoptosis, and consequently inhibits cell proliferation in A549 cells. Moreover, it sensitizes lung cancer cells to chemotherapy.


Up-regulation of ECT2 is associated with poor prognosis in gastric cancer patients.
The aim of this study was to investigate the expression of ECT2 in gastric cancer and its clinical significance. We investigated the differentially expressed genes between gastric cancer tissues and normal gastric mucosa by cDNA microarray, and then we found ECT2 was up-regulated in gastric cancer. What is more, we verified ECT2 expression level by quantitative real-time reverse transcription-polymerase chain reaction (qRT-PCR) and measured its protein level by immunohistochemistry (IHC). qRT-PCR analysis indicated ECT2 was significantly up-regulated in gastric cancer and Immunohistochemistry confirmed the percentage of ECT2-positive specimens was significantly higher in gastric carcinoma than in non-tumor tissues. Up-regulation of ECT2 is associated with the degree of histological differentiation (P = 0.007), invasion depth (P = 0.047), lymph node metastasis (P = 0.016), distant metastasis (P = 0.021) and TNM stage (P = 0.016), patients with up-regulated ECT2 had a lower overall survival rate (P = 0.000). Cox regression analysis revealed that up-regulation of ECT2 is an independent prognostic factor in gastric cancer patients (P = 0.012). Up-regulation of ECT2 might contribute to the progression of gastric carcinogenesis and may be a useful prognostic indicator in gastric cancer.


Interactions with M-band titin and calpain 3 link myospryn (CMYA5) to tibial and limb-girdle muscular dystrophies.
Mutations in the C terminus of titin, situated at the M-band of the striated muscle sarcomere, cause tibial muscular dystrophy (TMD) and limb-girdle muscular dystrophy (LGMD) type 2J. Mutations in the protease calpain 3 (CAPN3), in turn, lead to LGMD2A, and secondary CAPN3 deficiency in LGMD2J suggests that the pathomechanisms of the diseases are linked. Yeast two-hybrid screens carried out to elucidate the molecular pathways of TMD/LGMD2J and LGMD2A resulted in the identification of myospryn (CMYA5, cardiomyopathy-associated 5) as a binding partner for both M-band titin and CAPN3. Additional yeast two-hybrid and coimmunoprecipitation studies confirmed both interactions. The interaction of myospryn and M-band titin was supported by localization of endogenous and transfected myospryn at the M-band level. Coexpression studies showed that myospryn is a proteolytic substrate for CAPN3 and suggested that myospryn may protect CAPN3 from autolysis. Myospryn is a muscle-specific protein of the tripartite motif superfamily, reported to function in vesicular trafficking and protein kinase A signaling and implicated in the pathogenesis of Duchenne muscular dystrophy. The novel interactions indicate a role for myospryn in the sarcomeric M-band and may be relevant for the molecular pathomechanisms of TMD/LGMD2J and LGMD2A.


Experimental gingivitis in a Down's syndrome child and sibling.
Biopsies were taken from a child with Down's syndrome and her sibling under experimental gingivitis conditions and analyzed with monoclonal antibodies. At first, plaque caused a shift from a predominance of T cells to a predominance of B cells. Later, a gradual increase of T cells and a looser arrangement of B cells were observed.


Present state of medication therapy in fibromyalgia syndrome.
For the treatment of primary fibromyalgia syndrome (FMS) the low dose application of tri- and tetracyclic antidepressive drugs was often studied. Up to now from all those drugs the effects of amitriptyline (AMI) are best documented. Because of its sedative properties it doesn't only influence pain but also improves the often disturbed sleep. Its use in patients with FMS is limited by the occurrence of side effects and the lack of response in a substantial number of patients. Serotonin reuptake inhibitors alone seem to be of little value. Nevertheless there is evidence that they may improve pain in combination with other antidepressive agents. Regarding pain moclobemide a reversible inhibitor of monoamine oxidase seems to be inferior to AMI. In controlled studies corticosteroids and non-steroidal anti-inflammatory drugs (NSAIDs) also failed to improve FMS. The combination of NSAIDs with benzodiazepines gave inconsistent results. Although often used, we have only small information about the effectiveness of opioids. No beneficial effect could be attributed to the muscle relaxant chlormezanone. In conclusion, although only about 1/3 of the patients respond, AMI remains the drug of first choice in the conventional medication treatment of FMS.


Conceptual encoding following severe closed head injury.
This investigation examined whether survivors of severe closed head injury encode semantic properties of to-be-remembered words and the relationship of such processing to frontal lobe functioning. Fourteen patients enrolled in rehabilitation and 12 controls were administered the Release from Proactive Inhibition paradigm involving trials of recalling words from the same category followed by a shift to a new category or continued presentation of identical material. Similar to the controls, patients demonstrated a facilitation in recall when the category shifted. An association between the amount of release and frontal lobe functioning (as evaluated by neuropsychological tests and magnetic resonance imaging) was not compelling and depended upon the particular measure of release that was utilized. Pending replication in a larger, more representative sample, we suggest that conceptual encoding is relatively preserved in long-term survivors. The failure to find a robust relationship between frontal lobe pathology and semantic encoding is discussed in light of other investigations suggesting an association.


[Prevalence of vesicular lithiasis in hospitalized patients in Curitiba: ultrasonographic evaluation].
The prevalence of gallstones was determined in Curitiba. A total of 384 patients older than 20 years of age was randomly selected from four general hospitals and subjected to ultrasonographic examination of the gallbladder. Of the 384 patients, 327 had normal gallbladder (85.2%) and 57 (14.8%) had gallstones (48 patients) or had been previously subjected to cholecystectomy due to gallstones (9 patients). Six out of the 48 patients with gallstones referred biliary colic (12.5%). Gallstone prevalence increased with age and number of pregnancies.


Isolation of a novel amylase and lipase-producing Pseudomonas luteola strain: study of amylase production conditions.
An amylase and lipase producing bacterium (strain C2) was enriched and isolated from soil regularly contaminated with olive washing wastewater in Sfax, Tunisia. Cell was aerobic, mesophilic, Gram-negative, motile, non-sporulating bacterium, capable of growing optimally at pH 7 and 30°C and tolerated maximally 10% (W/V) NaCl. The predominant fatty acids were found to be C(18:1)ω7c (32.8%), C(16:1)ω7c (27.3%) and C16:0 (23.1%). Phylogenetic analysis of the 16S rRNA gene revealed that this strain belonging to the genus Pseudomonas. Strain C2 was found to be closely related to Pseudomonas luteola with more than 99% of similarity. Amylase optimization extraction was carried out using Box Behnken Design (BBD). Its maximal activity was found when the pH and temperature ranged from 5.5 to 6.5 and from 33 to 37°C, respectively. Under these conditions, amylase activity was found to be about 9.48 U/ml.


Ion-Gel-Gated Graphene Optical Modulator with Hysteretic Behavior.
We propose a graphene-based optical modulator and comprehensively investigate its photonic characteristics by electrically controlling the device with an ion-gel top-gate dielectric. The density of the electrically driven charge carriers in the ion-gel gate dielectric plays a key role in tuning the optical output power of the device. The charge density at the ion-gel-graphene interface is tuned electrically, and the chemical potential of graphene is then changed to control its light absorption strength. The optical behavior of the ion-gel gate dielectric exhibits a large hysteresis which originates from the inherent nature of the ionic gel and the graphene-ion-gel interface and a slow polarization response time of ions. The photonic device is applicable to both TE- and TM-polarized light waves, covering two entire optical communication bands, the O-band (1.26-1.36 μm) and the C-band (1.52-1.565 μm). The experimental results are in good agreement with theoretically simulated predictions. The temporal behavior of the ion-gel-graphene-integrated optical modulator reveals a long-term modulation state because of the relatively low mobility of the ions in the ion-gel solution and formation of the electric double layer in the graphene-ion-gel interface. Fast dynamic recovery is observed by applying an opposite voltage gate pulse. This study paves the way to the understanding of the operational principles and future applications of ion-gel-gated graphene optical devices in photonics.


A Multi-scale Fusion and Transformer Based Registration Guided Speckle Noise Reduction for OCT images.
Optical coherence tomography (OCT) images are inevitably affected by speckle noise because OCT is based on low-coherence interference. Multi-frame averaging is one of the effective methods to reduce speckle noise. Before averaging, the misalignment between images must be calibrated. In this paper, in order to reduce misalignment between images caused during the acquisition, a novel multi-scale fusion and Transformer based (MsFTMorph) method is proposed for deformable retinal OCT image registration. The proposed method captures global connectivity and locality with convolutional vision transformer and also incorporates a multi-resolution fusion strategy for learning the global affine transformation. Comparative experiments with other state-of-the-art registration methods demonstrate that the proposed method achieves higher registration accuracy. Guided by the registration, subsequent multi-frame averaging shows better results in speckle noise reduction. The noise is suppressed while the edges can be preserved. In addition, our proposed method has strong cross-domain generalization, which can be directly applied to images acquired by different scanners with different modes.


The diagnosis and classification of scleroderma (systemic sclerosis).
Difficulty in the diagnosis of the disease scleroderma may occur at the early stage prior to the development of obvious skin sclerosis. A presumptive diagnosis may be made if Raynaud's phenomenon is accompanied by a positive 'neck test', 'scleroderma' capillary changes in the nailfolds or antinuclear antibodies. Definitive diagnosis may have to be delayed for several years from the onset of Raynaud's phenomenon until definite characteristic skin changes are seen. Ten cases in which an earlier diagnosis of scleroderma was not substantiated are listed. The earlier incorrect diagnosis would have been avoided by use of the methods described in this paper. Various terms have been used to denote subdivisions of scleroderma. These include acrosclerosis, diffuse scleroderma and CREST. We have used the terms Type 1, Type 2 and Type 3 based on the early extent of the skin sclerosis where Type 1 (limited extent) indicates sclerodactyly only, Type 2 (moderate extent) indicates sclerosis proximal to the metacarpophalangeal joints but excluding the trunk and Type 3 (extensive) indicates diffuse skin sclerosis including the trunk. The clinical value of this simple classification is reviewed and contrasted to other classifications which appear to be poorly defined and of limited use.


Effects of improvement in aerobic power on resting insulin and glucose concentrations in children.
In this study we determined the influence of improving aerobic power (VO(2max)) on basal plasma levels of insulin and glucose of 11- to 14-year-old children, while accounting for body fat, gender, pubertal status, and leisure-time physical activity (LTPA) levels. Blood samples were obtained from 349 children after an overnight fast and analyzed for plasma insulin and glucose. Height, mass, body mass index (BMI), and sum of skinfolds (Sigma triceps + subscapular sites) were measured. LTPA levels and pubertal status were estimated from questionnaires, and VO(2max) was predicted from a cycle ergometry test. Regardless of gender, insulin levels were significantly correlated (P = 0.0001) to BMI, skinfolds, pubertal stage, and predicted VO(2max), but were not related to LTPA levels. Fasting glucose levels were not correlated to measures of adiposity or exercise (LTPA score, VO(2max)) for females; however, BMI and skinfolds were correlated for males (P < 0.006). The children then took part in an 8-week aerobic exercise program. The 60 children whose VO(2max) improved (>/=3 ml x kg(-1) x min(-1)) had a greater reduction in circulating insulin than the 204 children whose VO(2max) did not increase -16 (41) vs -1 (63) pmol x l(-1); P = 0.028. The greatest change occurred in those children with the highest initial resting insulin levels. Plasma glucose levels were slightly reduced only in those children with the highest insulin levels whose VO(2max) improved (P < 0.0506). The results of this study indicate that in children, adiposity has the most significant influence on fasting insulin levels; however, increasing VO(2max) via exercise can lower insulin levels in those children with initially high levels of the hormone. In addition, LTPA does not appear to be associated with fasting insulin status, unless it is sufficient to increase VO(2max).


Regional tumor oxygenation and measurement of dynamic changes.
We recently described a novel approach to measuring regional tumor oxygen tension using (19)F pulse burst saturation recovery (PBSR) nuclear magnetic resonance (NMR) echo planar imaging (EPI) relaxometry of hexafluorobenzene. We now compare oxygen tension measurements in a group of size-matched R3327-AT1 Dunning prostate rat tumors made using this new method with those using a traditional polarographic method: the Eppendorf histograph. Similar oxygen tension distributions were found using the two methods, and both techniques showed that tumors with volume greater than 3.5 cm(3) were significantly (P < 0.0001) less well oxygenated than smaller tumors (volume less than 2 cm(3)). Using the (19)F EPI approach, we also examined the response to respiratory challenge. Increasing the concentration of inspired oxygen from 33% to 100% O(2) produced a significant increase (P < 0.0001) in tumor oxygenation for a group of small tumors. In contrast, no change was observed in the mean pO(2) for a group of large tumors. Consideration of individual tumor regions irrespective of tumor size showed a strong correlation between the maximum pO(2) observed when breathing 100% O(2) compared with mean baseline pO(2). These results further demonstrate the usefulness of (19)F EPI to assess changes in regional tumor oxygenation.


Immune System Stimulation Reduces the Efficiency of Whole-Body Protein Deposition and Alters Muscle Fiber Characteristics in Growing Pigs.
The effects of immune system stimulation (ISS), induced by repeated injection of Escherichia coli lipopolysaccharide, on the whole-body protein synthesis versus degradation rates, the efficiency of protein deposition (PD), and muscle fiber characteristics in pigs were evaluated. Twelve growing gilts were assigned to two levels of amino acid intake that was predicted based on the potential of each group's health status for PD and feed intake. Isotope tracer, nitrogen balance, and immunohistochemical staining techniques were used to determine protein turnover, PD, and muscle fiber characteristics, respectively. Protein synthesis, degradation, and PD were lower in immune-challenged pigs than in control pigs (p < 0.05). Strong tendencies for a higher protein synthesis-to-PD ratio (p = 0.055) and a lower protein synthesis-to-degradation ratio (p = 0.065) were observed in immune-challenged pigs. A decrease in muscle cross-sectional area of fibers and a shift from myosin heavy chain (MHC)-II towards MHC-I fibers (p < 0.05) were observed in immune-challenged pigs. These results indicated that ISS reduces PD not only by suppressing the whole-body protein synthesis and degradation rates, but also by decreasing the efficiency of PD in growing pigs. In addition, ISS induces atrophy in skeletal muscles and favors a slow-twitch oxidative fiber type composition.


Phagocytosis-induced chemotaxis receptor cycling in neutrophils is mediated by thiol oxidation.
We previously demonstrated that neutrophil (PMN) phagocytosis of opsonized zymosan (OPZ) caused oxygen-dependent inhibition of chemotactic peptide receptor (CPR) binding using the ligand 3H-formyl-methionyl-leucyl-phenylalanine (3H-FMLP). In the current studies we sought to determine the mechanism of CPR inhibition by OPZ. We found that 3 mM cysteine and 5 mM dithiothreitol (DTT) did not decrease PMN phagocytosis, but abolished CPR inhibition by OPZ. Furthermore, incubation of PMN with DTT after OPZ partially restored the suppressed CPR. PMN CPR saturation studies with 3H-FMLP on PMN incubated with or without DTT after phagocytosis indicated that DTT restored receptor numbers to 92% +/- 6% of prephagocytosis values and also improved CPR affinity for 3H-FMLP. In additional studies we found that the cell penetrating thiol reagents mercuric chloride (HgCl2), N-ethylmaleimide (NEM), and diamide, but not the nonpenetrating agents p-chloromercuriphenylsulfonic acid and p-chloromercuribenzoate, caused rapid, dose-dependent, DTT-inhibitable suppression of up to 85% CPR binding. CPR inhibition by HgCl2 and NEM was irreversible. PMN CPR saturation studies showed that NEM decreased total receptor numbers, not CPR affinity. The effect of NEM was not inhibited by receptor occupancy at 4 degree C or at 37 degree C. These studies indicate that: (1) intact thiol groups are a requirement for CPR ligand-binding; (2) the thiol groups are presumptively located on the interior side of, or within hydrophobic portions of, the plasma membrane and are not part of the 3H-FMLP binding site; (3) thiol oxidation-reduction induces reversible alteration in CPR binding; (4) phagocytosis-induced modulation of the CPR is due, in part, to thiol oxidation. These studies suggest that postphagocytic, thiol-mediated reduction in CPR binding may play a physiologic role in the inhibition of PMN chemotaxis at inflammatory sites. The state of CPR-associated thiols may be an important determinant of CPR binding under physiologic conditions other than phagocytosis.


[Anatomy of the pelvic lymph nodes in the green marmoset].
The iliac lymphatic caudal nodes disposed along the external iliac artery as three chains (lateral, median or prevenous, and medial) were studied in 89 corpses of green monkeys. In two chains (lateral and retrovascular) the cranial iliac lymphatic nodes are adjacent to the common iliac artery. The number of nodes in each chain varies from one to five. One node of the group of caudal iliac nodes-femoral-is present almost in all preparations. The lymphatic system of the pelvis of the monkeys studied is arranged according to a common bilateral plan characteristic of all mammals.


Combination therapy in the management of atrophic acne scars.
Atrophic acne scars are difficult to treat. The demand for less invasive but highly effective treatment for scars is growing. To assess the efficacy of combination therapy using subcision, microneedling and 15% trichloroacetic acid (TCA) peel in the management of atrophic scars. Fifty patients with atrophic acne scars were graded using Goodman and Baron Qualitative grading. After subcision, dermaroller and 15% TCA peel were performed alternatively at 2-weeks interval for a total of 6 sessions of each. Grading of acne scar photographs was done pretreatment and 1 month after last procedure. Patients own evaluation of improvement was assessed. Out of 16 patients with Grade 4 scars, 10 (62.5%) patients improved to Grade 2 and 6 (37.5%) patients improved to Grade 3 scars. Out of 22 patients with Grade 3 scars, 5 (22.7%) patients were left with no scars, 2 (9.1%) patients improved to Grade 1and 15 (68.2%) patients improved to Grade 2. All 11 (100%) patients with Grade 2 scars were left with no scars. There was high level of patient satisfaction. This combination has shown good results in treating not only Grade 2 but also severe Grade 4 and 3 scars.


In vitro analysis of the homing properties of human lymphocytes: developmental regulation of functional receptors for high endothelial venules.
Circulating lymphocytes leave the blood by binding to specialized high endothelial cells lining postcapillary venules in lymphoid organs or sites of chronic inflammations, migrating through the vessel wall into the surrounding tissue. The capacity of lymphocytes to recognize and bind to high endothelial venules (HEVs) is thus central to the overall process of lymphocyte traffic and recirculation. We show that viable human lymphocytes bind selectively to HEVs in frozen sections of normal human lymph nodes, thus defining a simple in vitro model for the study of human lymphocyte homing properties. Optimal conditions for the quantitative analysis of lymphocyte-HEV interaction are described. Furthermore, by using this assay, we demonstrate that the ability of human lymphocyte populations to bind to HEVs parallels their presumed migratory status in vivo. Thus, thymocytes and bone marrow cells, which are sessile in vivo, bind poorly to HEVs in comparison with mature circulating lymphocytes in peripheral blood or in peripheral lymphoid tissues. These results indicate that HEV-binding ability is a regulated property of mature lymphocytes and, as demonstrated previously in animal models, probably plays a fundamental role in controlling lymphocyte traffic in humans. The in vitro model of lymphocyte-HEV interaction thus provides a unique means to assay the migratory properties of normal and neoplastic human lymphocyte subsets, to analyze the role of lymphocyte traffic mechanisms in normal and pathologic inflammatory reactions, and to define some of the molecular mechanisms responsible for the control of lymphocyte migration and positioning in humans.


Alterations in Phenotypes and Responses of T Cells Within 6 Months of Recovery from COVID-19: A Cohort Study.
The COVID-19 pandemic, caused by the SARS-CoV-2 infection, is a global health crisis. While many patients have clinically recovered, little is known about long-term alterations in T cell responses of COVID-19 convalescents. In this study, T cell responses in peripheral blood mononuclear cells of a long-time COVID-19 clinically recovered (20-26 weeks) cohort (LCR) were measured via flow cytometry and ELISpot. The T cell responses of LCR were comparatively analyzed against an age and sex matched short-time clinically recovered (4-9 weeks) cohort (SCR) and a healthy donor cohort (HD). All volunteers were recruited from Wuhan Jinyintan Hospital, China. Phenotypic analysis showed that activation marker PD-1 expressing on CD4+ T cells of LCR was still significantly lower than that of HD. Functional analysis indicated that frequencies of Tc2, Th2 and Th17 in LCR were comparable to those of HD, but Tc17 was higher than that of HD. In LCR, compared to the HD, there were fewer IFN-γ producing T cells but more IL-2 secreting T cells. In addition, the circulating Tfh cells in LCR were still slightly lower compared to HD, though the subsets composition had recovered. Remarkably, SARS-CoV-2 specific T cell responses in LCR were comparable to that of SCR. Collectively, T cell responses experienced long-term alterations in phenotype and functional potential of LCR cohort. However, after clinical recovery, SARS-CoV-2 specific T cell responses could be sustained at least for six months, which may be helpful in resisting re-infection.


RET and GDNF mutations are rare in fetuses with renal agenesis or other severe kidney development defects.
The RET/GDNF signalling pathway plays a crucial role during development of the kidneys and the enteric nervous system. In humans, RET activating mutations cause multiple endocrine neoplasia, whereas inactivating mutations are responsible for Hirschsprung disease. RET mutations have also been reported in fetuses with renal agenesis, based on analysis of a small series of samples. To characterise better the involvement of RET and GDNF in kidney development defects, a series of 105 fetuses with bilateral defects, including renal agenesis, severe hypodysplasia or multicystic dysplastic kidney, was studied. RET and GDNF coding sequences, evolutionary conserved non-coding regions (ECRs) in promoters, 3'UTRs, and RET intron 1 were analysed. Copy number variations at these loci were also investigated. The study identified: (1) a low frequency (<7%) of potential mutations in the RET coding sequence, with inheritance from the healthy father for four of them; (2) no GDNF mutation; (3) similar allele frequencies in patients and controls for most single nucleotide polymorphism variants, except for RET intron 1 variant rs2506012 that was significantly more frequent in affected fetuses than in controls (6% vs 2%, p=0.01); (4) distribution of the few rare RET variants unidentified in controls into the various 5'-ECRs; (5) absence of copy number variations. These results suggest that genomic alteration of RET or GDNF is not a major mechanism leading to renal agenesis and other severe kidney development defects. Analysis of a larger series of patients will be necessary to validate the association of the RET intron 1 variant rs2506012 with renal development defects.


Reduction of ischemic damage by application of insulin-like growth factor-1 in rat brain after transient ischemia.
In order to investigate a possible effect of insulin-like growth factor-1 (IGF-1) on ischemic brain injury, IGF-1 was applied topically on the brain surface of reperfused rat brain after 60 min of transient middle cerebral artery occlusion. In contrast to the cases treated with vehicle, the infarct volume was greatly reduced at 24 h of reperfusion by the treatment with IGF-1. Immunohistochemical analysis in the middle cerebral artery territory showed that Caspase-3 staining was markedly reduced in the cases with IGF-1 treatment, but 72-kDa heat shock protein staining remained almost unchanged. The present results suggest that treatment with IGF-1 exerts a significant effect on ameliorating brain injury after transient focal brain ischemia. Moreover, this effect is greatly associated with the reduction of Caspase-3 staining, but is only minimally associated with a decreasd stress response at the cellular level.


Comparison of racemic albuterol and levalbuterol for treatment of acute asthma.
To determine whether levalbuterol resulted in fewer hospital admissions than racemic albuterol when used for treatment of acute asthma. Study design A randomized, double-blind, controlled trial was conducted in the emergency department (ED) and inpatient asthma care unit of an urban tertiary children's hospital. Children age 1 to 18 years (n=482) provided a total of 547 enrollments. Patients received a nebulized solution of either 2.5 mg racemic albuterol or 1.25 mg levalbuterol every 20 minutes (maximum six doses). Patients admitted to the asthma care unit were treated in a standardized fashion by using the same blinded drug assigned in the ED. Hospitalization rate was the primary outcome. Hospitalization rate was significantly lower in the levalbuterol group (36%) than in the racemic albuterol group (45 %, P=.02). The adjusted relative risk of admission in the racemic group compared with the levalbuterol group was 1.25 (95% confidence interval, 1.01-1.57). Hospital length of stay was not significantly shorter in the levalbuterol group (levalbuterol, 44.9 hours; racemic albuterol, 50.3 hours; P=.63). No significant adverse events occurred in either group. Substituting levalbuterol for racemic albuterol in the ED management of acute asthma significantly reduced the number of hospitalizations.


Fast, economic and simultaneous identification of clinically relevant Gram-negative species with multiplex real-time PCR.
A newly designed multiplex real-time PCR (rt-PCR) was validated to detect four clinically relevant Gram-negative bacteria (Escherichia coli, Acinetobacter baumannii, Klebsiella pneumoniae and Pseudomonas aeruginosa). Serial dilutions of genomic DNA were used to determine the limit of detection. Colony PCR was performed with isolates of the four selected species and other species as negative controls. Isolates were characterized genotypically and phenotypically to evaluate the assay. Specific signals of all target genes were detected with diluted templates comprising ten genomic equivalents. Using colony rt-PCR, all isolates of the target species were identified correctly. All negative control isolates were negative. The genes gad, basC, khe and ecfX can reliably identify these four species via multiplex colony rt-PCR.


Insulin growth factor 1 receptor/PI3K/AKT survival pathway in outer segment membranes of rod photoreceptors.
The authors previously reported that physiological light induces the tyrosine phosphorylation of insulin receptors (IRs), which leads to the activation of the phosphoinositide 3-kinase (PI3K) and Akt (serine/threonine protein kinase B) survival pathway in rod photoreceptor cells. Tissue-specific deletion of IRs from photoreceptors resulted in stress-induced photoreceptor degeneration. Insulin growth factor 1 receptor (IGF-1R) is highly related in sequence and structure to the IR and shares 70% sequence identity overall and 84% identity within the tyrosine kinase domain. The role of IGF-1R in photoreceptor function is unknown. In this study the authors examined IGF-1R signaling in rod outer segment (ROS) membranes. IGF-1R localization was examined in the plasma and disc membranes of ROS. Activation of the IGF-1R/PI3K/Akt pathway was analyzed using specific antibodies against phospho-tyrosine, IGF-1R, and phospho-Akt. PI3K activity was determined in the anti-phospho-tyrosine and anti-IGF-1R immunoprecipitates. Glutathione-S-transferase fusion proteins containing two Src homology 2 (SH2) domains of the p85 subunit of PI3K and their mutants were used to study the molecular interaction between IGF-1R and p85. In vivo IGF-1R signaling was studied in rats exposed to physiological light or to constant light. IGF-1R is predominately localized to plasma membranes of ROS. These studies indicate that light stress results in an increase in tyrosine phosphorylation of IGF-1R and an increase in PI3K enzyme activity in anti-phosphotyrosine and anti-IGF-1R immunoprecipitates of ROS and retinal homogenates. The authors observed that light stress induces tyrosine phosphorylation of IGF-1R in ROS membranes, which leads to the binding of p85 through N-SH2 and C-SH2 domains. Finally, the authors observed a significant activation of Akt in light-stressed retinas, indicating activation of the Akt survival pathway downstream of IGF-1R activation. Light stress induced the activation of PI3K through activation and binding of IGF-1R, which leads to activation of the Akt survival pathway in photoreceptors.


Two types of dopamine receptors in behavioral regulation.
Evidence has been presented indicating the existence of distinct dopamine receptors in the brain. The experimental proof that two types of dopamine receptors--the excitation-mediating (DAe) receptors and the inhibition-mediating (DAi) receptors--exist in the snail brain is put forward. The functioning of DAi and DAe receptors in locomotor activity and stereotyped behavior is discussed along with implications of dopaminergic involvement in a gratification system.


Comparison of BCG vaccination at birth and at third month of life.
Tuberculosis is an important health problem in developing countries and the BCG vaccine plays an important part in preventing the disease. There are different reports about the preventive value of BCG. Some of them claim that it is satisfactory while others suggest that it provides little protection. There are also varying ideas about the optimum time to vaccinate babies, some studies suggesting that late vaccination confers a high degree of protection. This prospective controlled study has been undertaken to evaluate the value of BCG vaccine given to babies during their first three days of life versus its value when given in their third month of life. Evaluation was measured by the results of tests with purified protein derivative (PPD), by vaccine scars, that by the complications of the vaccine. It was found that BCG given at the end of the third month provides a higher rate of response and fewer complications than when given during the first three days of life.


Industrial emergency planning modeling: a first step toward a robustness analysis tool.
The purpose of this paper is to present a model-based approach to the analysis of the robustness of industrial emergency plans, established by the European Union SEVESO II Directive. Robustness is defined in terms of the capacity of the mechanism to respond to deteriorated conditions. Analysis of emergency plans has been so far based mainly upon lessons learned from past major accidents or exercises, which do not allow for an integral analysis of the response mechanism. The proposed methodology is based upon a systemic, hierarchical and generic model of an internal or external industrial emergency plan, using the FIS modeling approach. The process generally found within an industrial emergency plan is identified through the model. Potential failures are estimated through an a priori analysis of the plan model and an a posteriori analysis of lessons learned from exercises and past accidents. Assessment of the plan's functions is carried out via assessment checklists, structured via the systemic model for each of the plan's process. This approach can hence be used as a toolbox both for the assessment of existing plans and the development of industrial emergency plans.


Cations in a molecular funnel: vibrational spectroscopy of isolated cyclodextrin complexes with alkali metals.
The benchmark inclusion complexes formed by α-cyclodextrin (αCD) with alkali-metal cations are investigated under isolated conditions in the gas phase. The relative αCD-M(+) (M=Li(+), Na(+), K(+), Cs(+)) binding affinities and the structure of the complexes are determined from a combination of mass spectrometry, infrared action spectroscopy and quantum chemical computations. Solvent-free laser desorption measurements reveal a trend of decreasing stability of the isolated complexes with increasing size of the cation guest. The experimental infrared spectra are qualitatively similar for the complexes with the four cations investigated, and are consistent with the binding of the cation within the primary face of the cyclodextrin, as predicted by the quantum computations (B3LYP/6-31+G*). The inclusion of the quantum-chemical cation disrupts the C(6) symmetry of the free cyclodextrin to provide the optimum coordination of the cations with the -CH(2)OH groups in C(1), C(2) or C(3) symmetry arrangements that are determined by the size of the cation.


Efficacy of Modified Dose-dense Paclitaxel in Recurrent Cervical Cancer.
To examine survival outcomes of women with recurrent cervical cancer who received salvage chemotherapy with modified dose-dense paclitaxel (MDDP) monotherapy (paclitaxel 80 mg/m, administered on day 1, 8, and 15 without day 22). A retrospective study was conducted to evaluate cause-specific survival after the first recurrence (SAR) of women with recurrent cervical cancer diagnosed between 2006 and 2014. Pooled analyses were performed to examine SAR in women who received MDDP monotherapy (n=17) for any treatment line, compared with those who received salvage chemotherapy with paclitaxel-doublet (n=18) and nonpaclitaxel regimens (n=52). In the whole cohort, median SAR was 13.7 months including 63 (72.4%) events. MDDP monotherapy regimen was most commonly used in the second-line setting (35.3%) followed by the third/fourth lines (both, 23.5%). Among the women who received MDDP regimen, there were 6 (35.3%) women who received ≥6 cycles; there was 1 (5.9%) women who discontinued the regimen due to adverse effects (grade 3 transaminitis); regimen postponement was seen in 2 (1.4%) of 140 total cycles; and the response rate after the sixth cycle of this regimen was 29.4% (1 complete and 4 partial responses). On univariate analysis, MDDP usage had the highest 2-year SAR rate (MDDP 54.1%, paclitaxel-doublet 43.6%, and nonpaclitaxel regimens 28.1%; Ptrend=0.044). On multivariate analysis, MDDP monotherapy remained an independent prognostic factor for improved SAR compared with the nonpaclitaxel regimen (adjusted-hazard ratio, 0.50; 95% confidence interval, 0.26-0.95; P=0.036). Our results suggested that MDDP monotherapy is a tolerable and relatively effective regimen for recurrent cervical cancer.


Trophic and size structure of West Indian bird communities.
Much discussion has occurred in recent years on whether observed patterns of structure in island bird communities are the result of competitive interactions among species or independent rates of colonization and extinction. Here two patterns of structure are presented for birds on 12 West Indian islands. Each of four major foraging guilds shows a distinct species-area pattern on the islands and saturation of species within habitats on larger islands. Frugivores have the steepest species-area curve and highest species numbers at saturation while nectarivores are lowest in both values. Coexisting guild members in saturated habitats are generally of different sizes, with weight differences by a factor of 2 common. On smaller islands, small guild members are absent and size differences among coexisting guild members may increase. In many cases, birds have apparently shifted size to conform to the structural patterns. The consistency of the patterns and variation within component species is highly compatible to explanations invoking competition and complements previously described population and community characteristics of West Indian birds.