Screening for inhibitors of the hepatitis C virus internal ribosome entry site RNA.
The highly conserved internal ribosome entry site (IRES) of hepatitis C virus (HCV) regulates translation of the viral RNA genome and is essential for the expression of HCV proteins in infected host cells. The structured subdomain IIa of the IRES element is the target site of recently discovered benzimidazole inhibitors that selectively block viral translation through capture of an extended conformation of an RNA internal loop. Here, we describe the development of a FRET-based screening assay for similarly acting HCV translation inhibitors. The assay relies on monitoring fluorescence changes that indicate rearrangement of the RNA target conformation upon ligand binding. Screening of a small pilot set of potential RNA binders identified a benzoxazole scaffold as a ligand that bound selectively to IIa IRES target and was confirmed as an inhibitor of in vitro viral translation. The screening approach outlined here provides an efficient method to discover HCV translation inhibitors that may provide leads for the development of novel antiviral therapies directed at the highly conserved IRES RNA.


Comparison of bispectral index and patient state index as measures of sedation depth during surgeries using remimazolam tosilate.
The Bispectral Index (BIS) and the Patient State Index (PSI) are commonly used measures to assess intraoperative sedation depth. However, model differences lead to different results, which in turn interferes with clinicians' judgment on the depth of anesthesia. Remimazolam tosilate (RT) for injection is a new benzodiazepine used in sedation. In its clinical application, there are few effective indicators for sedation depth monitoring. To close this gap, this study aims to compare BIS and PSI in measuring the sensitivity and specificity of intraoperative RT and to explore the safety of RT for intraspinal anesthesia in elderly patients. This study included 40 patients undergoing elective electro-prostatectomy with intraspinal anesthesia, who were monitored by BIS and PSI simultaneously during operation. Remimazolam tosylate 0.1 mg/kg was intravenously administered after the intraspinal anesthesia when patients were in a completely painless status. Then BIS, PSI, the Modified Observer's Assessment of Alertness and Sedation (MOAA/S) scores and vital signs were observed and recorded per minute for 10 min. Pearson's correlation analysis and linear regression model were used to compare BIS and PSI sedation scores, and to test their associations with the MOAA/S score, respectively. ROC curves were drawn to compare the sensitivity and specificity of BIS and PSI. Changes of vital signs were presented as mean ± standard deviation. Perioperative liver and kidney function indicators were analyzed using a paired t-test to evaluate the safety of RT for intraspinal anesthesia in the elderly patients. According to Pearson's correlation analysis, a significant (P < 0.01) correlation between BIS and PSI was found when used to monitor intraoperative sedation of RT (r = 0.796). Significant associations between BIS and MOAA/S (r = 0.568, P < 0.01), and between PSI and MOAA/S (r = 0.390, P < 0.01) were also found. The areas under the ROC curves of BIS and PSI were 0.801 ± 0.022 and 0.734 ± 0.026, respectively, suggesting that both measures may predict patients' state of consciousness and BIS was more accurate than PSI. Vital signs remained stable throughout the study. No abnormal changes of clinical significance were found based on laboratory test results of liver and kidney function. BIS and PSI are strongly associated for monitoring the sedation of RT intraoperatively. Both methods can accurately reflect sedation depth. According to correlation analyses with MOAA/S scale and ROC curves, BIS is more accurate than PSI during such intraoperative monitoring. In addition, RT can be safely used in elderly patients under intraspinal anesthesia for supportive sedation, with stable vital signs and sound kidney and liver safety profiles. http://www.chictr.org.cn (ChiCTR2100051912).


Recent progress in revealing the biological and medical significance of the non-neuronal cholinergic system.
This special issue of International Immunopharmacology is the proceedings of the Fourth International Symposium on Non-neuronal Acetylcholine that was held on August 28-30, 2014 at the Justus Liebig University of Giessen in Germany. It contains original contributions of meeting participants covering the significant progress in understanding of the biological and medical significance of the non-neuronal cholinergic system extending from exciting insights into molecular mechanisms regulating this system via miRNAs over the discovery of novel cholinergic cellular signaling circuitries to clinical implications in cancer, wound healing, immunity and inflammation, cardiovascular, respiratory and other diseases.


Effects of independently altering body weight and mass on the energetic cost of a human running model.
The mechanisms underlying the metabolic cost of running, and legged locomotion in general, remain to be well understood. Prior experimental studies show that the metabolic cost of human running correlates well with the vertical force generated to support body weight, the mechanical work done, and changes in the effective leg stiffness. Further, previous work shows that the metabolic cost of running decreases with decreasing body weight, increases with increasing body weight and mass, and does not significantly change with changing body mass alone. In the present study, we seek to uncover the basic mechanism underlying this existing experimental data. We find that an actuated spring-mass mechanism representing the effective mechanics of human running provides a mechanistic explanation for the previously reported changes in the metabolic cost of human running if the dimensionless relative leg stiffness (effective stiffness normalized by body weight and leg length) is regulated to be constant. The model presented in this paper provides a mechanical explanation for the changes in metabolic cost due to changing body weight and mass which have been previously measured experimentally and highlights the importance of active leg stiffness regulation during human running.


Visibility aids for pedestrians and cyclists: a systematic review of randomised controlled trials.
This study aims to quantify the effect of visibility aids on the occurrence of pedestrian and cyclist-motor vehicle collisions and injuries, and drivers' responses in detection and recognition. Trial reports were systematically reviewed according to predefined eligibility criteria, including randomised controlled trials or controlled before-and-after trials comparing visibility aids and no visibility aids, and of different visibility aids on pedestrian and cyclist safety, and drivers' responses in detection and recognition. This included trials in which the order of interventions was randomised, or balanced using a Latin square design. Two reviewers independently assessed validity of trials and abstracted data. The main outcome measures were pedestrian and cyclist-motor vehicle collisions and injuries, and drivers'/observers' responses in the detection and recognition time, distance and frequency. No trials which assessed the effect of visibility aids on pedestrian and cyclist-motor vehicle collisions and injuries were identified. Twelve trials examined the effectiveness of daytime visibility aids and 25 trials on night time visibility aids, including 882 participants. Drivers' and observers' detection and recognition improved with visibility aids. For daytime, fluorescent materials in yellow, red and orange colours enhanced detection and recognition. "Biomotion" markings enhanced recognition. Substantial heterogeneity between the trials limits the possibility for meta-analysis. Visibility aids have the potential to improve detection and recognition and would merit further development to gain public acceptance. However, the impact of visibility aids on pedestrian and cyclist safety is unknown and needs to be determined.


Characterization of soil salinization and its driving factors in a typical irrigation area of Northwest China.
Salinization of irrigation areas is a global environmental challenge. The uncertainty in the distribution of salinization is increased by the complexity of the natural environment. This study adopted Yinchuan Plain as a typical irrigation area to study the relationship between soil salinity and the environment from the perspective of macro-environmental elements and micro-ion composition. A Geographic Weighted Regression model (GWR) was used to predict the risk of salinization in the Yinchuan Plain. The results showed obvious spatial variation in soil salinization in the Yinchuan Plain. Farmland accounted for the largest proportion of salinized land area, followed by woodland and "other" land use categories. The main characteristic ions in the salinized area of the Yinchuan Plain were SO42-, K++Na+and Cl-. The rank of ions in terms of change rate with increasing soil salinity was: SO42- > K+ + Na+ > Cl- > Ca2+ > HCO3- > Mg2+ > CO32-. However, the rank of ions in terms of their sensitivity to salinization was: HCO3- > Ca2+ > Mg2+ > SO42- > Cl- > K+ + Na+. On this basis, the geographical indicators of DEM and NDVI, groundwater indicators of groundwater depth and TDS, climate indicators of SPEI, as well as soil indicators of PH and organic matter were taken as the representative ecological drivers of salinization in irrigation areas. These environmental factors were found to control the distribution of salinization, whereas human activity affected the degree of change in salinization. The enrichment of SO42- in the Yinchuan Plain was mainly related to agricultural activities (such as pesticides application and irrigation evaporation), and followed by phreatic evaporation. The salt ions carried by irrigation and rainfall further polluted phreatic water. In the end, the measures of optimizing drainage, combined irrigation, and improving planting layout were recommended for the effectively and economically controlling of salinization.


Cracking the intestinal lymphatic system window utilizing oral delivery vehicles for precise therapy.
Oral administration is preferred over other drug delivery methods due to its safety, high patient compliance, ease of ingestion without discomfort, and tolerance of a wide range of medications. However, oral drug delivery is limited by the poor oral bioavailability of many drugs, caused by extreme conditions and absorption challenges in the gastrointestinal tract. This review thoroughly discusses the targeted drug vehicles to the intestinal lymphatic system (ILS). It explores the structure and physiological barriers of the ILS, highlighting its significance in dietary lipid and medication absorption and transport. The review presents various approaches to targeting the ILS using spatially precise vehicles, aiming to enhance bioavailability, achieve targeted delivery, and reduce first-pass metabolism with serve in clinic. Furthermore, the review outlines several methods for leveraging these vehicles to open the ILS window, paving the way for potential clinical applications in cancer treatment and oral vaccine delivery. By focusing on targeted drug vehicles to the ILS, this article emphasizes the critical role of these strategies in improving therapeutic efficacy and patient outcomes. Overall, this article emphasizes the critical role of targeted drug vehicles to the ILS and the potential impact of these strategies on improving therapeutic efficacy and patient outcomes.


Bis(cinnamato-κO)(1,10-phenanthroline-κ(2) N,N')copper(II).
The title mononuclear Cu(II) complex, [Cu(C9H7O2)2(C12H8N2)], is comprised of a Cu(II) cation, two cinnamate (L (-)) ligands and a 1,10-phenanthroline (phen) ligand. The Cu(II) atom and phen ligand lie on a twofold rotation axis. The Cu(II) atom is coordinated by two O atoms from two carboxyl-ate groups of two (L (-)) ligands and two N atoms from one phen ligand, exhibiting a distorted square-planar geometry. In the crystal, mol-ecules are assembled into supra-molecular chains parallel to the c axis through weak C-H⋯O hydrogen bonds involving the phen and cinnamate ligands.


The economic cost of implementing antigen-based rapid diagnostic tests for COVID-19 screening in high-risk transmission settings: evidence from Germany.
Antigen-based rapid diagnostic tests (Ag-RDT) have been implemented in hospitals and nursing homes to screen for infectious individuals without symptoms suggestive of SARS-CoV-2 infections and to prevent entry into these high-risk settings. Despite their benefits for screening, the cost of large-scale implementation is largely understudied. Our study presents evidence on their implementation costs in high-risk settings. This study aimed to estimate the economic costs of implementing Ag-RDT-based screening for SARS-CoV-2 in two tertiary care hospitals (University Hospital Heidelberg - UKHD, and Charité - Universitätsmedizin Berlin) and one nursing home in Germany. We adopted a health system perspective and followed the three sequential steps to costing: identification of resources, measurement of resource consumption, and valuation of costs. Data on resource consumption were collected between October 2020 and April 2021 through various techniques and data sources. The cost estimation considered all costs along the screening algorithm including PCR confirmation tests for positive cases. We estimated the costs for the two implementation modalities observed: staff dedicated exclusively to screening and staff not dedicated exclusively to screening. Furthermore, cost estimations were performed under both observed capacity use and hypothetical capacity use assumptions (60, 80 and 100%). Our study indicates that the average cost per Ag-RDT is highly dependent on the capacity use and implementation mode. Staff time and test kits are the two main cost drivers of implementing the large-scale screening programs for SARS-CoV-2 using Ag-RDTs. For hospitals, the average cost per test in UKHD was €30.12 (capacity observed); €14.56 (non-dedicated mode); €19.47, €16.37, €14.53 at 60, 80, 100% capacity respectively (dedicated mode); and at Charité €13.10 (non-dedicated mode). For the nursing home the estimated average cost per test was €15.03 (non-dedicated mode). The information on the estimated costs by mode of implementation and capacity use may support the planning of Ag-RDT-based covid-19 screening programs suitable for each institution. Further research is needed to cost this screening strategy for COVID-19 in other high-risk, high-income settings to reach generalizability.


A case of West Nile virus encephalitis accompanied by diabetic ketoacidosis and rhabdomyolysis.
We present here a case of West Nile Virus (WNV) encephalitis that initially presented with diabetic ketoacidosis and rhabdomyolysis. A 35-year-old male with no past medical history presented to the emergency department complaining of polydipsia, generalized weakness, lightheadedness, and visual disturbances of one week duration. He was found to be in diabetic ketoacidosis. His hemoglobin A1c was 11%. The patient was appropriately treated for diabetic ketoacidosis and it resolved on hospital day 1. On hospital day 2, the patient developed a fever of 101.6 °F and his mental status became severely altered. He developed auditory and visual hallucinations. IgM and IgG antibodies to West Nile Virus were positive in the cerebral spinal fluid (CSF). The patient's creatine kinase level rose to 118,400 U/L during his hospitalization and eventually returned to baseline. The patient made a full recovery with no residual neurologic deficits after an 11 day hospital course. In this patient, neuroinvasive WNV was confirmed with positive CSF IgM. The patient's newly diagnosed diabetes likely contributed to his susceptibility to neuroinvasive disease. Furthermore, WNV encephalitis in a background of DKA has not been previously described in the literature and this case demonstrates WNV neuroinvasive disease should be in the differential diagnosis for patients presenting with unexplained neurological symptoms. Diagnosis of neuroinvasive WNV is imperative to stop unnecessary therapies, limit further diagnostic evaluation, help predict patient outcomes, direct public health prevention measures, and further provide investigations into the clinical conditions that define the spectrum of WNV disease.


Contemporary approach to the emergency department management of pediatric asthma.
Asthma continues to be an enormous health problem and economic burden in US society. EDs probably will continue to provide a substantial amount of care for those affected by the disease. Pediatric asthma patients frequently are encountered in EDs. Emergency physicians must remain current in their approach to providing expert care while the management of acute asthma exacerbations continues to evolve, older therapies are challenged and new therapies are developed, tested, and implemented.


A dynamic sandwich assay on magnetic beads for selective detection of single-nucleotide mutations at room temperature.
Single-nucleotide mutation (SNM) has proven to be associated with a variety of human diseases. Development of reliable methods for the detection of SNM is crucial for molecular diagnosis and personalized medicine. The sandwich assays are widely used tools for detecting nucleic acid biomarkers due to their low cost and rapid signaling. However, the poor hybridization specificity of signal probe at room temperature hampers the discrimination of mutant and wild type. Here, we demonstrate a dynamic sandwich assay on magnetic beads for SNM detection based on the transient binding between signal probe and target. By taking the advantage of mismatch sensitive thermodynamics of transient DNA binding, the dynamic sandwich assay exhibits high discrimination factor for mutant with a broad range of salt concentration at room temperature. The beads used in this assay serve as a tool for separation, and might be helpful to enhance SNM selectivity. Flexible design of signal probe and facile magnetic separation allow multiple-mode downstream analysis including colorimetric detection and isothermal amplification. With this method, BRAF mutations in the genomic DNA extracted from cancer cell lines were tested, allowing sensitive detection of SNM at very low abundances (0.1-0.5% mutant/wild type).


An evaluation of Hamiltonian Monte Carlo performance to calibrate age-structured compartmental SEIR models to incidence data.
Hamiltonian Monte Carlo (HMC) is a Markov chain Monte Carlo method to estimate unknown quantities through sample generation from a target distribution for which an analytical solution is difficult. The strength of this method lies in its geometrical foundations, which render it efficient for traversing high-dimensional spaces. First, this paper analyses the performance of HMC in calibrating five variants of inputs to an age-structured SEIR model. Four of these variants are related to restriction assumptions that modellers devise to handle high-dimensional parameter spaces. The other one corresponds to the unrestricted symmetric variant. To provide a robust analysis, we compare HMC's performance to that of the Nelder-Mead algorithm (NMS), a common method for non-linear optimisation. Furthermore, the calibration is performed on synthetic data in order to avoid confounding effects from errors in model selection. Then, we explore the variation in the method's performance due to changes in the scale of the problem. Finally, we fit an SEIR model to real data. In all the experiments, the results show that HMC approximates both the synthetic and real data accurately, and provides reliable estimates for the basic reproduction number and the age-dependent transmission rates. HMC's performance is robust in the presence of underreported incidences and high-dimensional complexity. This study suggests that stringent assumptions on age-dependent transmission rates can be lifted in favour of more realistic representations. The supplementary section presents the full set of results.


The effect of surface and internal electrodes on the gait of children with cerebral palsy, spastic diplegic type.
The purpose of this study was to determine whether surface and internal fine-wire electromyography electrodes had an effect on gait. The subjects for the experiments were 38 children with the spastic diplegic type of cerebral palsy. The children were filmed using the high-speed cinematographic technique while they walked (a) with no electrodes (unencumbered), (b) with only surface electrodes, and (c) with internal electrodes. Single stance time, step length, cadence, and walking velocity were compared with analysis of variance and Bonferroni t tests. The results included a significant decrease in cadence (-6.3% of unencumbered walking; p less than 0.05) when comparing walking with surface electrodes with walking without any electrodes. The internal electrodes caused significant decreases from normal walking in the following parameters: step length for both the measured leg (-18.6%; p less than 0.005) and the nonmeasured leg (-18.0%; p less than 0.005), cadence (-7.9%; p less than 0.02), and walking velocity (-23.5%; p less than 0.005). Internal electrodes caused significant decreases as compared with surface electrodes in the step length for both the measured leg (15.7%; p less than 0.01) and the nonmeasured leg (15.6%; p less than 0.005) and walking velocity (19.7%; p less than 0.005). Single stance phase did not change significantly in any of the comparisons. It appears that the addition of the surface electrode apparatus does change the normal gait of a subject, causing a large decrease in cadence. The measurement of gait with internal electrodes causes further change in gait, resulting in large decreases in step length and walking velocity.(ABSTRACT TRUNCATED AT 250 WORDS)


A Genotyping Study in Benin Comparing the Carriage of Plasmodium falciparum Infections Before Pregnancy and in Early Pregnancy: Story of a Persistent Infection.
Malaria infections in the first trimester of pregnancy are frequent and deleterious for both mother and child health. To investigate if these early infections are newly acquired or already present in the host, we assessed whether parasites detected before pregnancy and those detected in early pregnancy are the same infection. We used data from the preconceptional "RECIPAL" study (Benin, 2014-2017). Sixty-three pregnant women of 411 included who had a malaria infection detected by quantitative polymerase chain reaction both before pregnancy and at the first antenatal care (ANC) visit were selected for this study. Two highly polymorphic markers, msp-2 and glurp, and a fragment-analysis method were used to enumerate the Plasmodium falciparum genotypes and to quantify their proportions within isolates. An infection was considered as persistent when identical msp-2 and glurp genotypes were found in the corresponding prepregnancy and early-pregnancy samples. The median time between the 2 malaria screenings was 3 months. The median gestational age at the first ANC visit was 6.4 weeks. Most infections before pregnancy were submicroscopic infections. Based on both msp-2 and glurp genotyping, the infection was similar before and in early pregnancy in 46% (29/63) of cases. Almost half of P. falciparum infections detected in the first trimester originate before pregnancy. Protecting young women from malaria infection before pregnancy might reduce the prevalence of malaria in early pregnancy and its related poor maternal and birth outcomes.


A retrospective study of strabismus surgery in a tertiary eye hospital in the Chaoshan area in China from 2014 to 2020.
To investigate the distribution pattern of strabismus surgery at an eye center in southern China. The data of all patients who underwent strabismus surgery at the Joint Shantou International Eye Center of Shantou University /Chinese University of Hong Kong from 2014 to 2020 were retrospectively analyzed. The type of strabismus and its relationship with age and sex were analyzed, and the trend in the number of strabismus surgeries was observed. The data of 4640 patients included a total of 5,282 surgeries. Exotropia surgery was the most common, accounting for 54.0% of all strabismus surgeries, which tended to increase over time, but not significantly (P = 0.109). Constant exotropia was the most common exotropia, but its proportion decreased year by year. The next most common was intermittent exotropia. The percentage of surgeries for intermittent exotropia increased from 2016 to 2020. Surgery for esotropia accounted for 22.1% of all strabismus surgeries and became significantly less common from 2016 to 2020 (P < 0.01). Among patients with intermittent or constant exotropia, the proportion of patients younger than 12 years who underwent surgical intervention increased yearly, while this proportion amoung patients older 12 years old with constant exotropia decreased yearly. Among exotropia surgeries, surgery for constant exotropia was the most common but decreased in prevalence annually. Children under 12 years old were the most affected population.


Listeric meningitis in the non-compromised host.
A small epidemic of listeric infection among non-compromised adults recently occurred in the western part of Sweden. All ten patients survived and the prognosis of listeric meningitis in non-compromised patients would seem to be considerably better than in the compromised host. A rapid initiation of ampicillin treatment (10-20 mg/kg of body weight daily) within 48 hours after onset of symptoms may be contributed to the excellent outcome in the present series besides a well-functioning intracellular killing mechanism which seems to be of the greatest importance in listeric infeciton.


Conditional expression of the transformed phenotype in an "epithelial-like" cell line.
A subclone of ts 14/MNU/2, derived from a heteroploid (epithelial) monkey kidney cell line of BSC-1 and transformed in vitro by methylnitrosourea, expressed the transformed phenotype only at the elevated temperature of 39.5(0)C. Compared to the growth characteristics at 33(0)C, the transformed property was exhibited in the (1) high efficiency of plating at low cell densities, (2) colony morphology, (3) growth in absence of serum and (4) alterations in the quality and the quantity of chromosomal proteins in presence of low concentrations of serum. Such experimental systems may provide an effective control for studying molecular mechanisms related to transformation and neoplasia.


Carcinomatosis under control by osimertinib in EGFR and TP53 mutated lung adenocarcinoma.
Approximately 25%-30% of patients with non-small cell lung cancer (NSCLC) develop central nervous system (CNS) metastases during the course of the disease; this percentage is higher in patients with epidermal growth factor receptor (EGFR) mutations. Leptomeningeal metastases, infrequent in the advanced setting, have a particularly dismal prognosis. Osimertinib, a third-generation EGFR inhibitor, can provide effective and durable response in this setting. We present a 62-year-old man with progressive vomiting, headache, short-term memory impairment, and left lower limb hyposthenia. Computed tomography (CT) showed bilateral lung nodules, multiple lymphadenopathies, liver and bone metastases, and CNS and leptomeningeal dissemination, including multiple parenchymal nodules located at supra- and infratentorial brain. Bone needle biopsy documented TTF1+ lung adenocarcinoma. Whole brain radiotherapy (WBRT) and symptomatic treatments were started. Next-generation sequencing reported deletion of exon 19 of EGFR and mutation 8 of TP53. Osimertinib 80 mg was promptly started and WBRT interrupted. Some days after the patient experienced repetitive seizures and neurologic worsening, antiepileptic drugs and dexamethasone were implemented, with gradual improvement. Radiologic evaluation, including brain MRI and thorax-abdominal CT, showed partial response on CNS as well as extracranial sites, which was sustained. First-line treatment with osimertinib can be safe and effective in EGFR-mutated NSCLC even in presence of multiple negative predictive factors (poor Performance Status, diffuse leptomeningeal involvement, TP53 comutation), suggesting that deferring local treatments can be feasible in this setting, allowing the patient to maintain a good quality of life.


A peptide that mimics the Vth region of beta-2-glycoprotein I reverses antiphospholipid-mediated thrombosis in mice.
Antiphospholipid (aPL) antibodies bind to beta2glycoprotein I (beta2GPI) and cause endothelial cell (EC) activation and thrombosis in mice. beta2GPI binds to EC through its Vth domain and induces their activation. TIFI is a 20 amino acid synthetic peptide that shares similarity with the Vth domain of beta2GPI. Our objectives were to examine the ability of TIFI to affect aPL-mediated thrombosis in mice and the interactions of TIFI, beta2GPI with phospholipid surfaces and target cells. CD1 mice were injected with IgG from a patient with antiphospholipid syndrome (IgG-APS) or with control IgG-NHS and with either TIFI or with control peptide (VITT). Size of induced thrombi was determined. Inhibition and competition studies were done using aPL antibodies, cardiolipin (CL) liposomes in the presence of varying amounts of TIFI and beta2GPI. Binding of fluorescinated beta2GPI to human ECs and to murine macrophages in the presence or absence of TIFI, was also examined. TIFI significantly decreased thrombus size in mice injected with IgG-APS. TIFI reverted the beta2GPI-dependent binding of aPL antibodies to CL liposomes in a dose-dependent fashion. This effect was abrogated by addition of beta2GPI, suggesting that TIFI displaces the binding of beta2GPI to phospholipids. TIFI inhibited the binding of fluorescinated beta2GPI to human EC and to murine macrophages. The data indicate that TIFI abrogates thrombogenic properties of aPL in mice by competing with beta2GPI and preventing its binding to target cells. This may be important in designing new modalities for the treatment of thrombosis in APS.


Appraisal of existing evidences of competition law and policy: Bilateral legislative developments of Sino-Pak.
Developing nations use contemporary competition laws based on international models for reasons ranging from achieving international legitimacy to achieving domestic economic objectives. Although passing such laws gives these nations competition regimes more legitimacy, doing so does not guarantee that their economic goals will be met unless the laws are also effectively implemented. Comparative legal scholarship suggests that effective enforcement requires, among other things, a positive link between the passed laws and the nation's pre-existing legal systems in light of development economics. The globalization of national competition laws, particularly the application of international soft law, is responsible for the existence of modern competition law. Secondly, the competition regimes in Pakistan and China face a number of long-term difficulties, many of which are the product of globalization, which must be addressed as soon as possible. In order to examine the aims and objectives, this study employs qualitative data analysis. The results of this research suggest that for both nations to successfully implement competition law, innovation and unconventionality are required. Although the goal of competition law is to prevent anti-competitive activities and practices by promoting fair and open market competition, this goal is achieved through protecting consumers from businesses' use of unfair business practices. Because of this, the act encourages the formation of agreements that limit and restrict market dominance. In addition, the law specifies how investigations, acquisitions, mergers, penalties, leniency, and other aspects of law enforcement should be handled. As a result, this law can be seen as extremely important for regulating firms while maintaining consumer and producer welfare. It eventually supports economic growth and social justice. As a result, Voluntary adherence to competition law, rules, and regulations is essential since doing so would significantly lower the societal costs of enforcing the law.


Procalcitonin (PCT) is useful in predicting the bacterial origin of an acute circulatory failure in critically ill patients.
To evaluate the accuracy of procalcitonin (PCT) in predicting bacterial infection in ICU medical and surgical patients. A 10-bed medical surgical unit. PCT, C-reactive protein (CRP), interleukin 6 (IL-6) dosages were sampled in four groups of patients: septic shock patients (SS group), shock without infection (NSS group), patients with systemic inflammatory response syndrome related to a proven bacterial infection (infect. group) and ICU patients without shock and without bacterial infection (control group). Sixty patients were studied (SS group:n=16, NSS group,n=18, infect. group,n=16, control group,n=10). The PCT level was higher in patients with proven bacterial infection (72+/-153 ng/ml vs 2.9+/-10 ng/ml,p=0.0003). In patients with shock, PCT was higher when bacterial infection was diagnosed (89 ng/ml+/-154 vs 4.6 ng/ml+/-12,p=0.0004). Moreover, PCT was correlated with severity (SAPS:p=0.00005, appearance of shock:p=0.0006) and outcome (dead: 71.3 g/ml, alive: 24.0 g/ml,p=0.006). CRP was correlated with bacterial infection (p<10(-5)) but neither with SAPS nor with day 28 mortality. IL-6 was correlated with neither infection nor day 28 mortality but was correlated with SAPS. Temperature and white blood cell count were unable to distinguish shocked patients with or without infection. Finally, when CRP and PCT levels were introduced simultaneously in a stepwise logistic regression model, PCT remained the unique marker of infection in patients with shock (PCT> or =5 ng/ml, OR: 6.2, 95% CI: 1.1-37,p=0.04). The increase of PCT is related to the appearance and severity of bacterial infection in ICU patients. Thus, PCT might be an interesting parameter for the diagnosis of bacterial infections in ICU patients.


Bootstrapped DEPICT for error estimation in PET functional imaging.
Basis pursuit denoising is a new approach for data-driven estimation of parametric images from dynamic positron emission tomography (PET) data. At present, this kinetic modeling technique does not allow for the estimation of the errors on the parameters. These estimates are useful when performing subsequent statistical analysis, such as, inference across a group of subjects or when applying partial volume correction algorithms. The difficulty with calculating the error estimates is a consequence of using an overcomplete dictionary of kinetic basis functions. In this paper, a bootstrap approach for the estimation of parameter errors from dynamic PET data is presented. This paper shows that the bootstrap can be used successfully to compute parameter errors on a region of interest or parametric image basis. Validation studies evaluate the methods performance on simulated and measured PET data ([(11)C]Diprenorphine-opiate receptor and [(11)C]Raclopride-dopamine D(2) receptor). The method is presented in the context of PET neuroreceptor binding studies, however, it has general applicability to a wide range of PET/SPET radiotracers in neurology, oncology and cardiology.


Slurry Erosion-Corrosion Characteristics of As-Built Ti-6Al-4V Manufactured by Selective Laser Melting.
Erosion and erosion-corrosion tests of as-built Ti-6Al-4V manufactured by Selective Laser Melting were investigated using slurries composed of SiO2 sand particles and either tap water (pure water) or 3.5% NaCl solution (artificial seawater). The microhardness value of selective laser melting (SLM)ed Ti-6Al-4V alloy increased as the impact angle increased. The synergistic effect of corrosion and erosion in seawater is always higher than erosion in pure water at all impact angles. The seawater environment caused the dissolution of vanadium oxide V2O5 on the surface of SLMed Ti-6Al-4V alloy due to the presence of Cl- ions in the seawater. These findings show lower microhardness values and high mass losses under the erosion-corrosion test compared to those under the erosion test at all impact angles.


Captopril renal scintigraphy--an advance in the detection and treatment of renovascular hypertension.
Despite the risks associated with renovascular hypertension and the durable benefits of revascularization, the detection of patients with renovascular hypertension and the selection of those who will benefit from interventional therapy remains a challenge. We have previously documented the reliability of captopril renal scintigraphy in predicting angiographically significant renal artery stenosis in patients suspected of having renovascular hypertension. In the present study we report our recent experience with this noninvasive technique in predicting outcome after revascularization. Captopril renal scintigraphy involves the administration of 50 mg of captopril 3 hours after a baseline technitium-99m diethylenetriaminepentaacetic acid renal scan and 1 hour before a repeat captopril renal scintigraphy scan. Nineteen of the last 70 patients with clinically suspected renovascular hypertension undergoing captopril renal scintigraphy had abnormal renal scan outcomes, and 17 had a decrease in flow or function after captopril (positive captopril renal scintigraphy). Eight of these 17 with abnormal findings on captopril renal scintigraphy underwent revascularization, and the hypertension was cured or improved in six of the eight: two of three after surgical bypass grafting and four of five after angioplasty. In the seven surviving patients with abnormal renal scan results but no change with captopril (negative captopril renal scintigraphy), improvement in hypertension after treatment occurred in only one: one of two after nephrectomy, zero of three after bypass surgery, and zero of two after angioplasty (p less than 0.05). We conclude that captopril renal scintigraphy is an accurate predictor of hypertension response to revascularization. Further evaluation of this new noninvasive technique for assessing patients with suspected renovascular hypertension appears warranted.


Maternal intraguild predation risk affects offspring anti-predator behavior and learning in mites.
Predation risk is a strong selective force shaping prey morphology, life history and behavior. Anti-predator behaviors may be innate, learned or both but little is known about the transgenerational behavioral effects of maternally experienced predation risk. We examined intraguild predation (IGP) risk-induced maternal effects on offspring anti-predator behavior, including learning, in the predatory mite Phytoseiulus persimilis. We exposed predatory mite mothers during egg production to presence or absence of the IG predator Amblyseius andersoni and assessed whether maternal stress affects the anti-predator behavior, including larval learning ability, of their offspring as protonymphs. Protonymphs emerging from stressed or unstressed mothers, and having experienced IGP risk as larvae or not, were subjected to choice situations with and without IG predator traces. Predator-experienced protonymphs from stressed mothers were the least active and acted the boldest in site choice towards predator cues. We argue that the attenuated response of the protonymphs to predator traces alone represents optimized risk management because no immediate risk existed. Such behavioral adjustment could reduce the inherent fitness costs of anti-predator behaviors. Overall, our study suggests that P. persimilis mothers experiencing IGP risk may prime their offspring to behave more optimally in IGP environments.


Poly_NumtS_430 or HSA_NumtS_587 observed in massively parallel sequencing of the mitochondrial HV1 and HV2 regions.
An increasing number of studies on massively parallel sequencing of mitochondrial DNA (mtDNA) have been reporting identification of various types of noise or off-target sequences. Herein, we report that an off-target haplotype (sequence length 192 bp) observed in MiSeq data of mtDNA at nucleotide position 16,209-16,400 was likely caused by polymorphic nuclear mitochondrial DNA sequences (NumtS). Buccal DNA samples from Volunteers #001-004 and Control DNA 007 were amplified with our multiplex system of the B (15,998-16,172), C (16,209-16,400), and E (30-289) regions using 2000 copies of mtDNA. A sample index was added using a Nextera XT index kit, and MiSeq Reagent Nano Kit v2 was used in 2 × 251 cycles on a MiSeq FGx. FASTQ files were analyzed by CLC Genomics Workbench 21.0.3. The extracted SAM files were analyzed using our original Excel macro to sum up the read counts as the phased variant calls for each region. An off-target haplotype differing at 19 sites against the revised Cambridge reference sequence was observed in Volunteer #001 (4 in 10 MiSeq data), Volunteer #002 (2 in 9), and Control DNA 007 (6 in 9). In a BLAST search, the sequence of the off-target haplotype matched perfectly to three polymorphic NumtS (Poly_NumtS_430 [KM281528.1], HSA_NumtS_587 [HE613849.1], and nuclear fossil [S80333.1]) and BAC clone of chromosome 11 (AC107937.2). The sequence also matched perfectly to a Filipino mtDNA (KC993973.1) which was inferred as a chimeric sequence of mtDNA and the HSA_NumtS_587. The sequence of the off-target haplotype was not contained in the latest human reference genome sequence (GRCh38.p13). In a phylogenetic tree, the off-target haplotype was genetically distant from modern human mtDNA and not directly connected to them. In conclusion, observed off-target haplotype amplified by our multiplex system was likely caused by Poly_NumtS_430 or HSA_NumtS_587.


Physiognomy, familism and consumerism: preferences among Jewish-Israeli recipients of donor insemination.
This paper examines the physiological preferences of Jewish-Israeli donor insemination (DI) recipients regarding the desirable donor. (1) By comparing recipients' own physiognomy with that of a hypothetical donor, we explore some of the social potentials of DI in its emerging democratized form. We examine prevailing notions regarding the 'natural family' and 'family resemblance' and query the relative weight of the natural vs. the consumer model as applied to one's own family through considerations regarding physical appearance. While examining the 'natural family' concept as a limit in the making of actual Israeli families, we consider the meanings of choice in the context of procreative technologies. The study may also provide practitioners with relevant information for donor matching. The paper is based on questionnaires delivered in four sperm banks during the years 1995-1998. It is important to note that the preferences we study are hypothetical, as in Israel no choice is offered and donor matching is performed exclusively by doctors. (2) Three comparisons serve as vehicles for characterizing the gaps between the natural and the consumer model: women's preferences regarding the donor's appearance vs. their male partners' appearance; men's preferences vs. their own features; single women's preferences vs. those of married ones. The paper ends with a discussion of the social implications of democratized DI on family, gender power relations and social hegemony.


ER proteostasis addiction in cancer biology: Novel concepts.
Endoplasmic reticulum (ER) stress is generated by various physiological and pathological conditions that induce an accumulation of misfolded proteins in its lumen. ER stress activates the unfolded protein response (UPR), an adaptive reaction to cope with protein misfolding to and restore proteostasis. However, chronic ER stress results in apoptosis. In solid tumors, the UPR mediates adaptation to various environmental stressors, including hypoxia, low in pH and low nutrients availability, driving positive selection. Recent findings support the concept that UPR signaling also contributes to other relevant cancer-related event that may not be related to ER stress, including angiogenesis, genomic instability, metastasis and immunomodulation. In this article, we overview novel discoveries highlighting the impact of the UPR to different aspects of cancer biology beyond its known role as a survival factor to the hypoxic environment observed in solid tumors.


[Prevention and early management of immediate postpartum haemorrhage: policies in six perinatal networks in France].
Postpartum haemorrhage (PPH) constitutes the leading cause of maternal deaths in France, and the majority of these deaths are preventable. The objective of this study was to ascertain policies for prevention and early management of PPH in maternity units, and to compare the results with scientific evidence. The survey was part of the Euphrates European project, and was conducted in France in 2003 before national recommendations for clinical practice related to PPH were launched. A cross-sectional declarative survey was conducted in six perinatal networks representing 132 maternity units. A postal questionnaire was sent to all units. Main outcomes measured were stated policies for prevention, diagnosis and management of PPH. There was no definition of PPH in one out of four units, and no written protocol for PPH management in one out of six. Policies of using preventive uterotonics were widespread, but variation was observed concerning the timing of administration, and association with the other components of active management of the third stage of labour. Policies about drugs used for management of PPH also varied. Variations in policies show firstly that evidence-based improvement in practice is possible, and secondly that further research is needed on poorly documented aspects of PPH management.


Study design and protocol of a stepped wedge cluster randomized trial using a practical implementation strategy as a model for hypertension-HIV integration - the MAP-IT trial.
As people living with HIV (PLWH) experience earlier and more pronounced onset of noncommunicable diseases (NCDs), advancing integrated care networks and models in low-resource-high-need settings is critical. Leveraging current health system initiatives and addressing gaps in treatment for PLWH, we report our approach using a late-stage (T4) implementation research study to test the adoption and sustainability of a proven-effective implementation strategy which has been minimally applied in low-resource settings for the integration of hypertension control into HIV treatment. We detail our protocol for the Managing Hypertension Among People Living with HIV: an Integrated Model (MAP-IT) trial, which uses a stepped wedge cluster randomized trial (SW-CRT) design to evaluate the effectiveness of practice facilitation on the adoption of a hypertension treatment program for PLWH receiving care at primary healthcare centers (PHCs) in Akwa Ibom State, Nigeria. In partnership with the Nigerian Federal Ministry of Health (FMOH) and community organizations, the MAP-IT trial takes place in 30 PHCs. The i-PARiHS framework guided pre-implementation needs assessment. The RE-AIM framework will guide post-implementation activities to evaluate the effect of practice facilitation on the adoption, implementation fidelity, and sustainability of a hypertension program, as well as blood pressure (BP) control. Using a SW-CRT design, PHCs sequentially crossover from the hypertension program only (usual care) to hypertension plus practice facilitation (experimental condition). PHCs will recruit and enroll an average of 28-32 patients to reach a maximum of 960 PLWH participants with uncontrolled hypertension who will be followed longitudinally for BP outcomes. Given the need for integrated NCD-HIV care platforms in low-resource settings, MAP-IT will underscore the challenges and opportunities for integrating hypertension treatment into HIV care, particularly concerning adoption and sustainability. The evaluation of our integration approach will also highlight the potential impact of a health systems strengthening approach on BP control among PLWH. Clinicaltrials.gov ( NCT05031819 ). Registered on 2nd September 2021.


Respiratory responses of the air-breathing fish Hoplosternum littorale to hypoxia and hydrogen sulfide.
The present study analyzes the respiratory responses of the neotropical air-breathing fish Hoplosternum littorale to graded hypoxia and increased sulfide concentrations. The oxygen uptake (VO2), critical O2 tension (PcO2), respiratory (fR) and air-breathing (fRA) frequencies in response to graded hypoxia were determined for fish acclimated to 28 degrees C. H. littorale was able to maintain a constant VO2 down to a PcO2 of 50 mm Hg, below which fish became dependent on the environmental O2 even with significant increases in fR. The fRA was kept constant around 1 breath h(-1) above 50 mm Hg and increased significantly below 40 mm Hg, reaching maximum values (about 4.5 breaths h(-1)) at 10 mm Hg. The lethality to sulfide concentrations under normoxic and hypoxic conditions were also determined along with the fRA. For the normoxic fish the sulfide lethal limit was about 70 microM, while in the hypoxic ones this limit increased to 87 muM. The high sulfide tolerance of H. littorale may be attributed to the air-breathing capability, which is stimulated by this compound.


Phosphate transport in mitochondria: past accomplishments, present problems, and future challenges.
The requirement of inorganic phosphate (Pi) for oxidative phosphorylation in eukaryotic cells is fulfilled through specific Pi transport systems. The mitochondrial proton/phosphate symporter (Pic) is a membrane-embedded protein which translocates Pi from the cytosol into the mitochondrial matrix. Pic is responsible for the very rapid transport of most of the Pi used in ATP synthesis. During the past five years there have been advances on several fronts. Genomic and cDNA clones for yeast, bovine, rat, and human Pic have been isolated and sequenced. Functional expression of yeast Pic in yeast strains deficient in Pi transport and expression in Escherichia coli of a chimera protein involving Pic and ATP synthase alpha subunit have been accomplished. Pic, in contrast to other members of the family of transporters involved in energy metabolism, was demonstrated to have a presequence, which optimizes the import of the precursor protein into mitochondria. Six transmembrane segments appear to be a structural feature shared between Pic and other mitochondrial anion carriers, and recent-site directed mutagenesis studies implicate structure-functional relationships to bacteriorhodopsin. These recent advances on Pic will be assessed in light of a more global interpretation of transport mechanism across the inner mitochondrial membrane.


Neutrophil dysfunction in guanosine 3',5'-cyclic monophosphate-dependent protein kinase I-deficient mice.
The regulation of neutrophil functions by Type I cGMP-dependent protein kinase (cGKI) was investigated in wild-type (WT) and cGKI-deficient (cGKI-/-) mice. We demonstrate that murine neutrophils expressed cGKIalpha. Similar to the regulation of Ca2+ by cGKI in other cells, there was a cGMP-dependent decrease in Ca2+ transients in response to C5a in WT, but not cGKI-/- bone marrow neutrophils. In vitro chemotaxis of bone marrow neutrophils to C5a or IL-8 was significantly greater in cGKI-/- than in WT. Enhanced chemotaxis was also observed with cGKI-/- peritoneal exudate neutrophils (PE-N). In vivo chemotaxis with an arachidonic acid-induced inflammatory ear model revealed an increase in both ear weight and myeloperoxidase (MPO) activity in ear punches of cGKI-/- vs WT mice. These changes were attributable to enhanced vascular permeability and increased neutrophil infiltration. The total extractable content of MPO, but not lysozyme, was significantly greater in cGKI-/- than in WT PE-N. Furthermore, the percentage of MPO released in response to fMLP from cGKI-/- (69%) was greater than that from WT PE-N (36%). PMA failed to induce MPO release from PE-N of either genotype. In contrast, fMLP and PMA released equivalent amounts of lysozyme from PE-N. However, the percentage released was less in cGKI-/- (approximately 60%) than in WT (approximately 90%) PE-N. Superoxide release (maximum velocity) revealed no genotype differences in responses to PMA or fMLP stimulation. In summary, these results show that cGKIalpha down-regulates Ca2+ transients and chemotaxis in murine neutrophils. The regulatory influences of cGKIalpha on the secretagogue responses are complex, depending on the granule subtype.


The Epilepsy Foundation's 4th Biennial Epilepsy Pipeline Update Conference.
On June 5 and 6, 2014, the Epilepsy Foundation held its 4th Biennial Epilepsy Pipeline Update Conference, an initiative of the Epilepsy Therapy Project, which showcased the most promising epilepsy innovations from health-care companies and academic laboratories dedicated to pioneering and advancing drugs, biologics, technologies, devices, and diagnostics for epilepsy. Speakers and attendees included emerging biotech and medical technology companies, major pharmaceutical and device companies, as well as investigators and innovators at the cutting-edge of epilepsy. The program included panel discussions on collaboration between small and large companies, how to get products in need of funding to the marketplace, who is currently funding epilepsy and CNS innovation, and how the NIH facilitates early-stage drug development. Finally, the conference featured the third annual "Shark Tank" competition. The presentations are summarized in this paper, which is followed by a compilation of the meeting poster abstracts.


Situation of mycotoxins in milk, dairy products and human milk in Egypt.
ABSTACT: Milk and dairy products purchased at Egyptian markets and breast milk from lactating mothers in Cairo and Giza governorates were analyzed for some mycotoxins. Three of 15 cows' milk samples were found positive for Afl. M1 with mean value 6.3 ppb. Only one sample of dried milk was positive (5 ppb). Two of 10 hard cheese samples contained detectable levels of Afl. M1 (3and 6 ppb), whereas one sample containing Afl. B1 and G1 (10 and 4 ppb resp.). For soft cheese one sample of 10 was positive for Afl. M1 (0.5 ppb). Blue veined cheeses were free of Afl. M1 and PR-toxins.For breast milk two of 10 samples were positive for Afl. M1 (20%) with mean value 2.75 ppb, while 3 of 10 samples were positive for Ochratoxin A (30 %).


Jejunal perforation associated with cytomegalovirus infection in a patient with adult T-cell leukemia-lymphoma.
A patient with adult T-cell leukemia-lymphoma suffered a jejunal perforation, which we believe was directly attributable to cytomegalovirus (CMV) infection. In the areas of ulceration and perforation in the small bowel, blood vessels penetrating the muscularis propria showed extensive lining of cytomegalic endothelial cells with CMV inclusions, accompanied by occasional disruption of the walls, partial occlusion of the lumina, fibrin thrombi, and hemorrhage. The CMV-induced vascular damage seemed to be closely related to the occurrence of ulcers and perforation. The recognition of CMV as a cause of lethal gastrointestinal lesions in immunocompromised hosts has become more important with the advent of anti-CMV therapy.


The optimized quantum dot mediated thermometry reveals isoform specific differences in efficiency of myosin extracted from muscle mini bundles.
The biophysical function of myosin in vitro has been extensively investigated in different motility assays, but the study of myosin ATPase properties at the fiber level is insufficiently investigated. In this study, quantum dot (QD) mediated thermometry measurements were optimized to measure the efficiency of myosin extracted from muscle mini bundles. A reduction in fluorescent intensity of QD reflects an increase in temperature caused by the heat released during ATP hydrolysis and denotes the efficiency of the motor protein myosin. The procedure for extracting myosin was similar to the single fiber in vitro motility assay with some small modifications, and the concentration of myosin was represented by the extracted total protein since the ratio of extracted myosin to total protein was constant. Moreover, the efficiencies of myosin extracted from preparations containing different myosin heavy chain isoforms reveal lower efficiency of slow compared to fast myosin isoforms. Specifically, more heat was released in slow myosin enzymatic reaction, resulting in faster decay of QD fluorescence intensity. Hence, the optimized QD mediated thermometry provides a novel and sensitive approach to evaluate efficiency of myosin ATPase obtained from small muscle samples, representing a significant advantage in the clinical evaluation of neuromuscular disorders.


Core and Lumbopelvic Stabilization in Runners.
Core muscles provide stability that allows generation of force and motion in the lower extremities, as well as distributing impact forces and allowing controlled and efficient body movements. Imbalances or deficiencies in the core muscles can result in increased fatigue, decreased endurance, and injury in runners. Core strengthening should incorporate the intrinsic needs of the core for flexibility, strength, balance, and endurance, and the function of the core in relation to its role in extremity function and dysfunction. Specific exercises are effective in strengthening the core muscles.


MyoD promotes porcine PPARγ gene expression through an E-box and a MyoD-binding site in the PPARγ promoter region.
Peroxisome proliferator-activated receptor γ (PPARγ) is a key transcription factor in adipogenesis and can be regulated by adipogenesis-related factors. However, little information is available regarding its regulation by myogenic factors. In this study, we found that over-expression of MyoD enhanced porcine adipocyte differentiation and up-regulated PPARγ expression, whereas small interfering RNA against MyoD significantly attenuated porcine adipocyte differentiation and inhibited PPARγ expression. The MyoD-binding sites in the PPARγ promoter region at -412 to -396 and -155 to -150 were identified by promoter deletion analysis and site-directed mutagenesis. Electrophoretic mobility shift assays and chromatin immunoprecipitation further showed that these two regions are MyoD-binding sites, both in vitro and in vivo, indicating that MyoD directly interacts with the porcine PPARγ promoter. Thus, our results demonstrate that an Enhancer box and a binding site for a cooperative co-activator of MyoD are present in the promoter region of porcine PPARγ; furthermore, MyoD up-regulates PPARγ expression and promotes porcine adipocyte differentiation.


Does Mechanical Bowel Preparation Reduce the Risk of Developing Infectious Complications in Pediatric Colorectal Surgery? A Systematic Review and Meta-Analysis.
To evaluate whether the application of mechanical bowel preparation (MBP) before colorectal surgery reduces the risk of developing infectious complications in children. In this systematic review and meta-analysis, PubMed, Embase, and the Cochrane Library were systematically searched to identify all articles comparing pediatric patients receiving MBP with pediatric patients not receiving MBP before colorectal surgery. Results are presented with weighted risk differences based on the number of events and sample size per study. Six original studies were included comparing MBP (n = 810) and no MBP (n = 1167). The overall risk of developing infectious complications was 10.1% in patients with MBP, compared with 9.1% in patients without MBP, resulting in a nonsignificant risk difference of -0.03% (95% CI, -0.09% to 0.03%). Concerning the number of wound infections and anastomotic leaks, we found nonsignificant risk differences of -0.03% (95% CI, -0.08% to 0.02%) and 0.01% (95% CI, -0.01% to 0.02%), respectively. Based on the current literature, there is insufficient evidence to indicate that the use of MBP leads to a significant difference in the risk of developing infectious complications in pediatric colorectal surgery.


The role of copper in drug-resistant murine and human tumors.
Multidrug resistance (MDR) is still a major threat to successful clinical application of cancer chemotherapy. Copper plays an important role in biological systems, and copper is also involved in carcinogenesis. In the present investigation, we addressed the question whether metal copper might be involved in drug resistance of murine and human tumors. By means of atomic absorption spectroscopy, we determined serum copper concentrations. We found that the blood serum of tumor-bearing mice contained higher amounts of copper than healthy mice with tumors. Secondly, mice bearing doxorubicin-resistant Ehrlich ascites carcinoma- or cyclophosphamide-resistant Lewis lung carcinoma contained more copper in their serum than mice bearing the corresponding drug-sensitive parental tumors. Furthermore, the analysis of patients with breast cancer, colon carcinoma or lung cancer showed that the serum copper contents were higher in patients not responding to chemotherapy when compared to patients whose tumors responded to treatment. The copper levels in serum of healthy volunteers were lower than in cancer patients irrespective of their response to chemotherapy. Our results imply that the level of serum copper may be considered as a biomarker for treatment response.


[Effects of repeated lower g exposures on high-G induced memory and balance changes in rats].
To study the protective effects of repeated +4 Gz/3 min exposures on memory and balance changes induced by +10 Gz/5 min exposure in rats. 32 male SD rats were randomly divided into 4 groups: control group (C) ; +10 Gz/5 min group (10 Gz); 3 d training group (3 d) ; 5 d training (5 d) group (exposed to +4 Gz/3 min per day for 3 or 5 days before +10 Gz/5 min exposure). Changes of memory and balance in rats of all the 4 groups were observed after +10 Gz/5 min exposure. In +10 Gz group, the percentage of correct reaction (CR) decreased significantly at all times after +10 Gz exposure (P<0.01), and the reaction time (RT) lengthened significantly at all times after +10 Gz exposure (P<0.01); as compared with control group. In 3 d training group, CR decreased significantly at 1 d, 2 d and 6 d after +10 Gz exposure (P<0.05), RT lengthened significantly at all times after +10 Gz exposure (P<0.05); as compared with control group. CR increased significantly at 2 d, 4 d and 6 d after +10 Gz exposure (P<0.01), RT shortened significantly at 1 d, 2 d, 4 d and 6 d after +10 Gz exposure (P<0.01) as compared with +10 Gz group. In 5 d training group, there were no apparent changes compared to control group; but CR increased significantly and RT shortened significantly at the time of 1 d, 2 d, 4 d and 6 d after +10 Gz exposure (P<0.01) as compared with +10 Gz group. Balancing function (BF) of +10 Gz group decreased significantly immediately and 2 d after +10 Gz exposure (P<0.01) as compared with control group. BF in 3 d and 5 d training group improved significantly immediately and 2 d after +10 Gz exposure as compared with +10 Gz group (P<0.01). It is suggested that repeated low +Gz exposures could provide protective effect on memory and balance changes induced by high +Gz exposure in rats.


Effects of Abeta1-42 on the subunits of KATP expression in cultured primary rat basal forebrain neurons.
ATP-sensitive potassium channels (KATP) play a crucial role in coupling metabolic energy to the membrane potential of cells, thereby functioning as cellular "metabolic sensors." Recent evidence has showed a connection between the amyloid neurotoxic cascade and metabolic impairment. With regard to their neuroprotection in other neuronal preparations, KATP channels may mediate a potential neuroprotective role in Alzheimer's disease (AD). To investigate the effects of Abeta1-42 on the subunits of KATP expression in cultured primary rat basal forebrain cholinergic neurons, primary rat basal forebrain neurons were cultured and evaluated. The subunits of KATP: Kir6.1, Kir6.2, SUR1 and SUR2 expressing changes were observed by double immunofluorescence and immunoblotting when the neurons were exposed to Abeta1-42(2 microM) for different time (0, 24, 72 h). We found a significant increase in the expression of Kir6.1 and SUR2 in the cultured neurons being exposed to Abeta1-42 for 24 h, while Kir6.2 and SUR1 showed no significant change. However, after being treated with Abeta1-42 for 72 h, the expression of the four subunits was all increased significantly compared with the control. These findings suggest that being exposed to Abeta1-42 for different time (24 and 72 h) induces differential regulations of KATP subunits expression in cultured primary rat basal forebrain cholinergic neurons. The change in composition of KATP may contribute to resist the toxicity of Abeta1-42.


Twenty years of transcriptomics, 17alpha-ethinylestradiol, and fish.
In aquatic toxicology, perhaps no pharmaceutical has been investigated more intensely than 17alpha-ethinylestradiol (EE2), the active ingredient of the birth control pill. At the turn of the century, the fields of comparative endocrinology and endocrine disruption research witnessed the emergence of omics technologies, which were rapidly adapted to characterize potential hazards associated with exposures to environmental estrogens, such as EE2. Since then, significant advances have been made by the scientific community, and as a result, much has been learned about estrogen receptor signaling in fish from environmental xenoestrogens. Vitellogenin, the egg yolk precursor protein, was identified as a major estrogen-responsive gene, establishing itself as the premier biomarker for estrogenic exposures. Omics studies have identified a plethora of estrogen responsive genes, contributing to a wealth of knowledge on estrogen-mediated regulatory networks in teleosts. There have been ~40 studies that report on transcriptome responses to EE2 in a variety of fish species (e.g., zebrafish, fathead minnows, rainbow trout, pipefish, mummichog, stickleback, cod, and others). Data on the liver and testis transcriptomes dominate in the literature and have been the subject of many EE2 studies, yet there remain knowledge gaps for other tissues, such as the spleen, kidney, and pituitary. Inter-laboratory genomics studies have revealed transcriptional networks altered by EE2 treatment in the liver; networks related to amino acid activation and protein folding are increased by EE2 while those related to xenobiotic metabolism, immune system, circulation, and triglyceride storage are suppressed. EE2-responsive networks in other tissues are not as comprehensively defined which is a knowledge gap as regulated networks are expected to be tissue-specific. On the horizon, omics studies for estrogen-mediated effects in fish include: (1) Establishing conceptual frameworks for incorporating estrogen-responsive networks into environmental monitoring programs; (2) Leveraging in vitro and computational toxicology approaches to identify chemicals associated with estrogen receptor-mediated effects in fish (e.g., male vitellogenin production); (3) Discovering new tissue-specific estrogen receptor signaling pathways in fish; and (4) Developing quantitative adverse outcome pathway predictive models for estrogen signaling. As we look ahead, research into EE2 over the past several decades can serve as a template for the array of hormones and endocrine active substances yet to be fully characterized or discovered.


Intracranial extension of sphenoid sinusitis.
The incidence of sphenoid sinusitis has decreased significantly since the pre-antibiotic era. Intracranial complications from isolated sphenoid sinusitis are rare but have a high morbidity and mortality. A case of intracranial extension of sphenoid sinusitis in a 64-year-old woman is reported. A 64-year-old woman was initially seen unconscious with bacterial meningitis and cerebrospinal fluid (CSF) fistula. Imaging suggested sphenoid sinusitis with intracranial extension. She underwent a sinus drainage procedure, was placed on antibiotic therapy, and underwent a definitive sphenoid sinus obliteration. The patient made a satisfactory recovery. Despite the low incidence of intracranial complications of sphenoid sinusitis, the potential morbidity and mortality from such complications is high. We advocate aggressive management consisting of antibiotic therapy, sinus drainage, and definitive CSF fistula repair.


Assessment of antibiotic prescription in acute urinary tract infections in adults.
To assess the appropriateness of antibiotic prescription for urinary tract infections in several hospital emergency services and to evaluate the variability of antibiotic prescription among these services. A cross-sectional study was carried out in the emergency services of 10 hospitals from different Spanish regions. The sample was composed of patients diagnosed with acute urinary infection, aged> or =14 years. A Consensus Conference, held by a panel of experts, established first-choice, second-choice and inappropriate antibiotic treatments for each type of urinary tract infection, based on the available scientific evidence. All the observed prescriptions in our study were classified according to this pattern. The main variables were: type of urinary infection, antibiotic prescription, urine culture request, comorbidity and hospital admission. A sample of 3797 acute urinary tract infections was studied. Eighty-one percent were lower urinary tract infections. The most commonly used antibiotics were ciprofloxacin and amoxicillin-clavulanate. The global percentages of first-choice, alternative-choice and inappropriate antibiotic prescriptions were: 42.4% (95% CI: 40.8-43.9), 44.1 (95% CI: 42.5-45.7) and 13.6% (95% CI: 12.5-14.7), respectively. We observed a significant variability in appropriateness of antibiotic prescriptions among the participating centres (p<0.001). Physicians at Spanish emergency rooms prescribe an excessive number of second-choice antibiotics for urinary tract infection treatment. There exists a high variability in antibiotic prescription among hospitals from different regions.


Cutaneous and Systemic Findings in Mosaic Neurofibromatosis Type 1.
Mosaic neurofibromatosis type 1 (MNF1) is a variant of neurofibromatosis type 1 (NF1) in which clinical manifestations are limited to one or several body segments. The objective was to characterize the cutaneous features and associated systemic findings in a cohort of children with MNF1. We performed a retrospective study of 40 children diagnosed with MNF1 at the Department of Dermatology, Hospital Infantil Niño Jesús, Madrid, Spain, from January 1, 1986, to October 31, 2015. All patients had pigmentary changes, alone (n = 39) or in combination with neurofibromas (n = 1). Twenty-four cases fulfilling the definition of MNF1 had six or more café au lait spots with or without freckling within the affected segment. They all lacked any other National Institutes of Health criteria of NF1. No patient had juvenile xanthogranuloma (JXG) or nevus anemicus (NA). Two children with MNF1 had epilepsy and two others developed malignancy (Hodgkin's lymphoma and ganglioneuroblastoma). Pigmentary changes are the most frequent presentation of MNF1 in children. MNF1 must be considered with segmentary distribution of freckling and café au lait spots. Other frequent cutaneous findings in NF1, such as JXG or NA, seem to be exceptional in MNF1. Although the possibility of systemic complications and cancer risk seem to be low, patients must be followed up.


A Soft-Reference Breast Ultrasound Image Quality Assessment Method That Considers the Local Lesion Area.
The quality of breast ultrasound images has a significant impact on the accuracy of disease diagnosis. Existing image quality assessment (IQA) methods usually use pixel-level feature statistical methods or end-to-end deep learning methods, which focus on the global image quality but ignore the image quality of the lesion region. However, in clinical practice, doctors' evaluation of ultrasound image quality relies more on the local area of the lesion, which determines the diagnostic value of ultrasound images. In this study, a global-local integrated IQA framework for breast ultrasound images was proposed to learn doctors' clinical evaluation standards. In this study, 1285 breast ultrasound images were collected and scored by experienced doctors. After being classified as either images with lesions or images without lesions, they were evaluated using soft-reference IQA or bilinear CNN IQA, respectively. Experiments showed that for ultrasound images with lesions, our proposed soft-reference IQA achieved PLCC 0.8418 with doctors' annotation, while the existing end-to-end deep learning method that did not consider the local lesion features only achieved PLCC 0.6606. Due to the accuracy improvement for the images with lesions, our proposed global-local integrated IQA framework had better performance in the IQA task than the existing end-to-end deep learning method, with PLCC improving from 0.8306 to 0.8851.


Purification and characterization of the invertase from Pycnoporus sanguineus.
A constitutive invertase (EC 220.127.116.11) was isolated and purified by the first time from Pycnoporus sanguineus. The enzyme is a glycoprotein. Its relative molecular mass is about 84,000 and its structure is dimeric, with two identical subunits (about 41,000). The enzyme is able to attack sucrose, raffinose, stachyose, inulin and levan, being sucrose the preferred substrate (Km 4.89 +/- 0.13 mM). Fructose was a classical competitive inhibitor, but glucose was not an inhibitor of the enzyme. Lectins with specificity toward glucose are inhibitors of the enzyme. Glucose was present in invertase acid hydrolysates. Unlike higher plant invertases, bovine serum albumin is not an effector of the Pycnoporus sanguineus enzyme, and the inhibition by fructose is not suppressed by this protein. The properties of the Pycnoporus sanguineus enzyme are discussed with reference to higher plant invertases.


Voltage-sensor movements in the Eag Kv channel under an applied electric field.
Voltage-dependent ion channels regulate the opening of their pores by sensing the membrane voltage. This process underlies the propagation of action potentials and other forms of electrical activity in cells. The voltage dependence of these channels is governed by the transmembrane displacement of the positive charged S4 helix within their voltage-sensor domains. We use cryo-electron microscopy to visualize this movement in the mammalian Eag voltage-dependent potassium channel in lipid membrane vesicles with a voltage difference across the membrane. Multiple structural configurations show that the applied electric field displaces S4 toward the cytoplasm by two helical turns, resulting in an extended interfacial helix near the inner membrane leaflet. The position of S4 in this down conformation is sterically incompatible with an open pore, thus explaining how movement of the voltage sensor at hyperpolarizing membrane voltages locks the pore shut in this kind of voltage-dependent K+ (Kv) channel. The structures solved in lipid bilayer vesicles detail the intricate interplay between Kv channels and membranes, from showing how arginines are stabilized deep within the membrane and near phospholipid headgroups, to demonstrating how the channel reshapes the inner leaflet of the membrane itself.


Sesquiterpenes and neolignans from the roots of Illicium dunnianum.
Two new sesquiterpenes, dunnianoside I (1) and 8'-oxo-6-hydroxy-dihydrophaseic acid methyl ester (2), a new glycoside, dunnianoside J (3), two new neolignans, dunnianeolignans A-B (4, 5), together with 10 known compounds (6-15), were isolated from the roots of Illicium dunnianum. The structures of these new compounds were elucidated by spectroscopic methods including 1D and 2D NMR, HR-ESI-MS, and chemical methods. Compounds 7, 8, and 13-15 exhibited potent antioxidant activities against Fe²⁺-cystine-induced rat liver microsomal lipid peroxidation, with IC₅₀ values ranging from 4.2 ± 0.4 to 38.4 ± 2.6 μM.


Diagnostic value of anti-cyclic citrullinated peptide antibody for rheumatoid arthritis in a Chinese population: a meta-analysis.
To use meta-analysis to determine the accuracy of anti-cyclic citrullinated peptide (CCP) antibody in diagnosis of patients with rheumatoid arthritis (RA) in a Chinese population, we searched MEDLINE and CNKI databases for studies published in English or Chinese between January 2000 and June 2010. Two investigators independently evaluated studies for inclusion, data extraction, and quality assessment. We used a random-effects model to combine estimates of sensitivity, specificity, positive likelihood ratio (LR+), negative likelihood ratio (LR-), and diagnostic odds ratio (DOR). One hundred and eighteen studies met our inclusion criteria. All studies were of high quality. The summary estimates for anti-CCP antibody in the diagnosis of RA in a Chinese population were as follows: sensitivity 0.65 (95% confidence interval (CI) 0.65-0.66), specificity 0.95 (95% CI 0.95-0.96), positive likelihood ratio (LR+) 15.84 (95% CI 13.55-18.54), negative likelihood ratio (LR-) 0.33 (95% CI 0.31-0.35), and diagnostic odds ratio (DOR) 51.60 (95% CI 43.64-61.01). With high specificity and moderate sensitivity, anti-CCP antibody tests play an important role in conforming the diagnosis of RA in a Chinese population.


Oral health-related quality of life and parental anxiety in chinese children undergoing Dental General Anesthesia: a prospective study.
Dental general anesthesia (DGA) is an effective treatment for very young children or those who have severe dental fear and mental or physical disabilities. However, the long-term impacts of DGA on oral health-related quality of life (OHRQoL) and parents' anxiety in China are still questionable. This study aimed to assess the influence of DGA on OHRQoL in Chinese children and their parents' psychological status. A total of 204 children and their parents participated in this study. The ECOHIS was applied to evaluate OHRQoL in children. The parents' anxiety was analyzed using the Chinese version of the Kessler 10 scale. The internal consistency was evaluated with Cronbach's alpha coefficient, and Wilcoxon signed-rank test was used for statistical analyses. The scores of each section of ECOHIS decreased one month after the procedure except for the self-image and social sections (P < 0.05). The scores of the Kessler 10 scale decreased one month after DGA and kept decreasing six months later (P < 0.05). The parents' Kessler 10 scores exhibited a moderately positive correlation with the children's ECOHIS scores (r = 0.480, P < 0.05). After DGA, the OHRQoL of Chinese children and their parents' mental health continued to improve. And they exhibited positive correlation.


Molecular characterization of lung carcinomas: A study on diagnostic, predictive, and prognostic markers using immunohistochemical analysis at a Tertiary Care Center in Uttarakhand, India.
Focused studies in different geographic regions would delineate the underlying biological differences and molecular alterations in non-small cell lung cancer (NSCLC) worldwide. Previous studies in literature have documented limited characterization by studying a minimal number of biological markers. This study was done to evaluate expression of multiple immunomarkers including diagnostic, prognostic, and predictive markers in NSCLC for its characterization. This was an observational study conducted on 60 consecutive cases of NSCLC. Immunomarkers comprising of p63, p40, TTF-1, napsin A, B-Raf, c-Met, phospho-AKT (P-AKT), PTEN, anaplastic lymphoma kinase (ALK), epidermal growth factor receptor (EGFR) and K-Ras, synaptophysin, chromogranin and pan-cytokeratin were evaluated on paraffin-embedded tissue sections of NSCLC. Age of patients with NSCLC in our study ranged from 35 to 90 years, and 93.3% of them were chronic smokers. 93.3% of cases presented in late stages (Stages III and IV) and 78% of cases were squamous cell carcinoma (SCC). EGFR positivity was noted in 83.3% of cases. ALK was positive in one case while C-Met and PTEN immunopositivity was noted in only two cases. Ten cases showed positivity for K-Ras and 90% of these were SCC. Ten cases were positive for B-Raf and 80% of these were SCC. 30% of cases showed immunopositivity for P-AKT. None of the molecular markers was found to have statistically significant correlation with clinicopathological parameters. SCC is the predominant histological subtype of NSCLC in the region of Uttarakhand, India, with a high proportion of cases harboring EGFR mutation. Variable expression of K-Ras, P-AKT, ALK 1, and PTEN in NSCLC signifies that molecular profile of every case is individualistic and independent. We attribute this to ethnicity, influence of implicated substance or metabolite in tobacco, and variable mutations incurred in tumor cells over a period of time.


Use of anti-infective agents during lactation: Part 2--Aminoglycosides, macrolides, quinolones, sulfonamides, trimethoprim, tetracyclines, chloramphenicol, clindamycin, and metronidazole.
Because many antibiotics are excreted into breast milk, it can be difficult for a practitioner to choose an antibiotic for a lactating patient that will have minimal risks to her nursing infant. This article is the second of a three-part series discussing the use of anti-infective agents during lactation. The authors review general information regarding use and common side effects for several classes of antibiotics. They also summarize information, including documented milk concentrations, milk-to-plasma ratios, and other pharmacokinetic properties, in a table that can help practitioners choose antibiotics that may be considered safe to use in the lactating mother.


Changes in heart rate variability after sitting following interscalene block.
Hypotensive bradycardic events (HBEs) occur in 5-28% of patients undergoing arthroscopic shoulder surgery in the sitting position after an interscalene brachial plexus block (ISBPB). The objective of this study was to investigate the effects of the sitting position following ISBPB on heart rate variability (HRV). In this prospective case-control study, we evaluated 64 patients undergoing arthroscopic shoulder surgery under ISBPB and 49 nonsurgical control subjects. HRV power spectral analysis parameters were measured (and natural log-transformed) before ISBPB and after changing to the sitting position. The patients experiencing HBEs were assigned to the HBE group, and the remaining patients were assigned to the non-HBE group. HBEs developed in 18 patients (28.1%). Changing from the supine position to the sitting position after ISBPB did not induce a significant increase in the natural log-transformed ratio of low-frequency to high-frequency power (lnLF/HF). A significant decrease in natural log-transformed high-frequency power (lnHF) was observed compared to the control group, who presented a significant increase in lnLF/HF and an insignificant change in lnHF. lnHF was found to be significantly higher in the HBE group compared to the non-HBE group. Sustained vagal activity with a failed shift in the sympathovagal balance toward sympathetic predominance in response to sitting after ISBPB is associated with the development of HBE.


Response of micropenis to topical testosterone and gonadotropin.
Five patients were treated with gonadotropin and topical testosterone for micropenis associated with hypothalamic hypogonadotropic hypogonadism. All patients received 1,000 units of gonadotropin weekly for 3 weeks, with a 6-week interval followed by 10% topical testosterone cream twice daily for 3 weeks. Serum testosterone levels were measured and remained equivalent for both modes of therapy. Average penile growth response with gonadotropin was 14.3% increase in length and 5.0% increase of girth. Topical testosterone produced an average increase of 60% in penile length and 52.9% in girth. The greatest growth response occurred in prepubertal male subjects with a minimal response in postpubertal male subjects. This study suggests that 10% topical testosterone cream twice daily will produce effective penile growth. The response appears to be greater in younger children, which is consistent with previously published studies of age-related 5 reductase activity.


GABA and glutamate-like immunoreactivity in processes presynaptic to afferents from hair plates on the proximal joints of the locust leg.
Hair plate afferents from coxal group 1 on the meso- and prothoracic legs of the locust were backfilled with cobalt salts or HRP for light and electron microscopy. The distribution of the terminal branches of the afferents is described from wholemount preparations and from 150 microns thick slices through the ganglion. Identified branches from the slices were sectioned for electron microscopy and examined for the presence of input and output synapses. Both were found in close proximity on small-diameter varicose branches in all parts of the arborization. Immunocytochemistry using antibodies against GABA and glutamate was used to try to identify putative transmitters in processes presynaptic to the afferents. Ninety-three percent of processes presynaptic to the hair plate afferents were clearly immunoreactive for GABA and only 7% appeared unlabelled. Most neuronal processes in the vicinity of afferent terminals were also immunoreactive for GABA, but a small number of glutamate-immunoreactive processes were found in intimate contact with afferents and one of these was demonstrated to be presynaptic. Processes postsynaptic to the afferents were of small diameter (mean = 0.28 micron) and were not found to be immunoreactive for GABA.


Brightness and shadows of mitochondrial ROS in the brain.
Mitochondrial reactive oxygen species (mROS) have been generally considered harmful byproducts wanted to clear when elevated to avoid brain damage. However, the abundance of mROS in astrocytes is very high -about one order of magnitude above that in neurons-, despite they are essential to preserve cell metabolism and animal behavior. Here, we have focused on this apparent ambiguity by discussing (i) the intrinsic mechanisms accounting for the higher production of mROS by the mitochondrial respiratory chain in astrocytes than in neurons, (ii) the specific molecular targets of astrocytic beneficial mROS, and (iii) how decreased astrocytic mROS causes excess neuronal mROS leading to cellular and organismal damage. We hope that this mini-review serves to clarifying the apparent controversy on the beneficial versus deleterious faces of ROS in the brain from molecular to higher-order organismal levels.


Comparison of FDG-PET scans to conventional radiography and bone scans in management of Langerhans cell histiocytosis.
We evaluated the effectiveness of FDG-PET scans in identifying sites of active disease and assessing response to therapy in patients with Langerhans cell histiocytosis (LCH). Changes in standardized uptake value (SUV) indicated increased or decreased disease activity before changes are evident by plain films or bone scans. One hundred and two PET scans for 44 patients (41 children, 3 adults) with biopsy-proven LCH were compared with 83 corollary imaging modalities and were rated for overall clinical utility: false positive or negative ("inferior"), confirming lesions identified by another imaging modality ("confirmatory"), or showing additional lesions, response to therapy or recurrence of disease activity ("superior"), in comparison to bone scans, MRI, CT or plain films. FDG-PET was rated superior in that 90/256 (35%) new, recurrent, or lesions responding to therapy were identified via change in standard uptake value (SUV) before other radiographic changes. PET scans confirmed active LCH in 146/256 (57%). FDG-PET was superior to bone scans in that 8/23 (34%) lesions, 11/53 (21%) comparisons to lesions found by MRI, 13/64 (20%) CT, and 58/116 (50%) plain films. PET scans confirmed lesions found by: 14/23 (61%) bone scans, 33/53 (62%) MRI, 45/64 (65%) CT, and 54/116 (46%) of plain films. Whole body FDG-PET scans can detect LCH activity and early response to therapy with greater accuracy than other imaging modalities in patients with LCH lesions in the bones and soft tissues. Whole-body FDG-PET scanning is an important and informative study at diagnosis and for following disease course in patients with LCH.


NERVTRACK--a neuroanatomical data bank.
To provide the neurologist with a detailed and easily accessible neuroanatomical reference, we have developed a data bank including all relevant efferent and many afferent neuroanatomical pathways. NERVTRACK contains 4000 anatomical data items arranged in a tree-like manner reflecting structural and functional relationships. The program is able to address problems like the following: (1) What is the spinal, radicular, and peripheral innervation of a given muscle? (2) Which muscles are affected by a lesion of a given peripheral nerve, a root, or a segment of the spinal cord? (3) For a given muscle, what are synergists and antagonists, and which clinical test is applicable to evaluate its strength? NERVTRACK runs on IBM-compatible microcomputers, even on lap tops. It is a fast and comfortable reference for clinical practice and serves as a readily accessible teaching aid.


Reversal of the effects of focal suppression on pharyngeal corticobulbar tracts by chemesthesis coupled with repeated swallowing.
Previous reports suggested the potential benefit of chemesthesis in the form of carbonated water (CW) integrated within dysphagia rehabilitation protocols. Here, we examined the effects of CW within a repeated swallowing protocol following focal suppression to pharyngeal cortical representation as a prelude to its application in dysphagic patients. Fourteen healthy volunteers participated in a 3-arm study. Each participant underwent baseline corticobulbar pharyngeal and thenar motor-evoked potential (MEP) measurements with Transcranial Magnetic Stimulation (TMS). Subjects were then conditioned with 1Hz repetitive (r)TMS to induce focal unilateral suppression of the corticopharyngeal hotspot before randomization to each of three arms with 40 swallows of CW, non-CW and saliva swallowing on separate days. Corticobulbar and thenar MEPs were collected for up to 1 h and analyzed using repeated measures (rm)ANOVA. A 2-way rmANOVA for Intervention x Time showed a significant effect of Intervention (F(1,13) = 7.519, p = 0.017) in both ipsi- and contra-lesional corticopharyngeal projections. Carbonation showed superiority in facilitating change by increasing pharyngeal cortical MEPs compared to non-CW (z = -3.05, p = 0.002) and saliva swallowing (z = -2.6, p = 0.008). No change in thenar representation (control) was observed nor in MEP latencies from both pharyngeal and thenar musculature. We conclude that interventional paradigms with CW have the capacity to reverse the effects of a focal suppression with 1Hz rTMS more strongly than non-CW or saliva swallowing alone, producing site specific bi-hemispheric changes in corticopharyngeal excitability. Our data suggest that carbonation produces the effects through a mainly cortical mechanism.


A Prospective Study of Cosmetic Outcomes for Patients Treated with Breast Conservation and Radiation Therapy using Shorter Fractionation Schedules at Auckland Hospital, New Zealand.
Breast cosmesis is an important outcome for women after breast conservation. It has been shown to be correlated with better patient satisfaction, sexuality and self-esteem. This study reports the subjective and objective breast cosmesis outcomes for women treated at Auckland Hospital Radiation Oncology Department using hypofractionated radiation therapy. Breast cosmesis was evaluated using a subjective questionnaire and standardised photographs before radiation, at 6 weeks, 1 year, 3 years and 5 years after radiation. Objective evaluation of the photographs and completion of questionnaires were undertaken by clinicians at the same time points. The questionnaire evaluated global cosmesis on a four-point scale - excellent (E), good (G), fair (F) and poor (P). Patient, tumour and treatment factors were evaluated to assess the impact on cosmesis. Three hundred and fifty-eight patients completed the baseline assessments and two hundred and two patients completed the 5-year assessments. Sixty-eight per cent of patients at baseline and 70% at 5 years scored their cosmesis as E/G compared with 52% and 51%, respectively, by clinician assessment. Age >50 years, separation ≤25 cm, non-diabetic, T1 tumours, node negative, quadrant of the scar, no boost and no adjuvant endocrine therapy were correlated with E/G cosmesis. On multivariate analysis at baseline, the individual breast factors that were significantly associated with a score of E/G cosmesis were breast shape (P = 0.028) and scar appearance (P = 0.001). At 5 years, breast shape (P = 0.003), nipple shape (P = 0.019) and scar appearance (P = 0.001) were found to be significant. This study shows that most women reported no significant change in their breast cosmesis after hypofractionated radiation treatment over 5 years and that a number of patient, tumour and treatment factors may impact on breast cosmesis.


Implications of the accumulation of CXCR5+ NK cells in lymph nodes of HIV-1 infected patients.
B cell follicles are immune-privileged sites where intensive HIV-1 replication and latency occur, preventing a permanent cure. Recent study showed that CXCR5+ NK cells in B cell follicles can inhibit SIV replication in African green monkeys, but this has not been reported in HIV-1 infected patients. Lymphocytes and tissue sections of lymph node were collected from 11 HIV-1 positive antiretroviral therapy (ART)-naive and 19 HIV-1 negative donors. We performed immunofluorescence and RNA-scope to detect the location of CXCR5+ NK cells and its relationship with HIV-1 RNA, and performed flow cytometry and RNA-seq to analyze the frequency, phenotypic and functional characteristics of CXCR5+ NK cells. The CXCL13 expression were detected by immunohistochemistry. CXCR5+ NK cells, which accumulated in LNs from HIV-1 infected individuals, expressed high levels of activating receptors such as NKG2D and NKp44. CXCR5+ NK cells had upregulated expression of CD107a and β-chemokines, which were partially impaired in HIV-1 infection. Importantly, the frequency of CXCR5+NK cells was inversely related to the HIV-1 viral burden in LNs. In addition, CXCL13-the ligand of CXCR5-was upregulated in HIV-1 infected individuals and positively correlated with the frequency of CXCR5+ NK cells. During chronic HIV-1 infection, CXCR5+ NK cells accumulated in lymph node, exhibit altered immune characteristics and underlying anti-HIV-1 effect, which may be an effective target for a functional cure of HIV-1.


Effects of progressive muscle relaxation on health-related outcomes in cancer patients: A systematic review and meta-analysis of randomized controlled trials.
Progressive muscle relaxation training (PMRT) has been widely applied to improve the physical and mental health of patients. The aim of this study was to evaluate the effects of PMRT on the symptoms and quality of life (QOL) of cancer patients. Nine databases (Web of Science, CENTRAL, PubMed, Embase, CINAHL, OpenGrey, CNKI, Wanfang, and VIP database) were searched to identify randomized controlled trials (RCTs) that assessed the effects of PMRT on health-related outcomes for cancer patients. The risk of bias of the included studies and the evidence quality were appraised using the Cochrane Risk of Bias 2.0 tool and the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach, respectively. Meta-analysis was performed using RevMan 5.4. Twelve RCTs sampling 1147 patients were included. PMRT showed significant effects of alleviating anxiety [standardized mean difference (SMD) = -1.32, 95% CI (-1.88, -0.75), P < 0.001] and pain [SMD = -1.02, 95% CI (-1.93, -0.11), P = 0.030], and improving QOL [SMD = 1.65, 95% CI (0.53, 2.76), P = 0.004] in cancer patients. Regarding depression, self-esteem, nausea, and vomiting, PMRT showed better effects compared to the control group. However, no significant effect of reducing fatigue was detected [SMD = -1.00, 95% CI (-2.27, 0.27), P = 0.120]. The overall quality of evidence was moderate to very low. PMRT is a promising complementary therapy that may improve the health-related outcomes of cancer patients. Future studies with rigorous research design are needed to obtain valid conclusions.