Delayed wound healing in mice associated with viral alteration of macrophages.
Mice acutely and chronically infected with Sendai virus had impaired healing of incisional wounds. This impairment could be overcome by instilling the macrophage-stimulators zymosan and glucan into full-thickness incised wounds, whereas levamisole, an immunomodulator, had no effect on tensile strength of these wounds (breaking strengths). Another commonly occurring murine virus, murine hepatitis virus, also reduced wound tensile strength in infected mice. However, the murine strain of herpes simplex virus, type 1, which caused greater morbidity, did not reduce tensile strength. Although measurements of wound length and wound breaking strength clearly showed the adverse effect of viral infection, histologic evaluation of wounds did not consistently reveal a similar change in composition of wound "cell aggregation centers" for mice infected with the Sendai and murine hepatitis viruses.


The effects of N-allylnormetazocine on electric shock titration in squirrel monkeys.
The effects of the stereoisomers of the prototypic sigma agonist N-allylnormetazocine were evaluated in squirrel monkeys trained to respond on an electric shock titration schedule. The monkeys responded on a fixed-ratio schedule to decrease the level of shock delivered to their tails. The effects of the isomers were compared to the effects of phencyclidine and morphine administered alone and also in combination with a rate-suppressing dose of morphine. Morphine increased the level at which shock was maintained without decreasing rates of responding in the presence of shock. Both the (+)-isomer and PCP produced increases in the levels at which the monkeys maintained the shock, but only in some animals. The (-)-isomer of N-allylnormetazocine resulted in either decreases or no effect on the level at which the monkeys maintained the shock. The isomers were equipotent in decreasing response rates. When tested in combination with morphine, only the (-)-isomer antagonized the shock-level increasing effects of morphine. Thus, the isomers had similar effects on response rates but the (+)-isomer, like PCP, was more effective in increasing the level at which the monkeys maintained electric shock, while only the (-)-isomer was effective as a morphine antagonist. These results suggest analgesic-like effects for the (+)-isomer of N-allylnormetazocine and substantiate the opiate-antagonist properties of the (-)-isomer.


Allergen immunotherapy for asthma.
Allergen specific immunotherapy has long been a controversial treatment for asthma. Although beneficial effects upon clinically relevant outcomes have been demonstrated in randomised controlled trials, there remains a risk of severe and sometimes fatal anaphylaxis. The recommendations of professional bodies have ranged from cautious acceptance to outright dismissal. With increasing interest in new allergen preparations and new methods of delivery, it was time to conduct another systematic review of allergen specific immunotherapy for asthma. The objective of this review was to assess the effects of allergen specific immunotherapy for asthma. We searched the Cochrane Airways Group trials register up to June 2001, MEDLINE, Dissertation Abstracts, Current Contents and reference lists of articles. Randomised controlled trials using various forms of allergen specific immunotherapy to treat asthma and reporting at least one clinical outcome. Three reviewers independently assessed eligibility of studies for inclusion. Two reviewers independently performed quality assessment of studies. Seventy-five trials were included (52 of 54 previously included trials and 23 new trials). A total of 3,506 participants (3,188 with asthma) were involved. There were 36 trials of immunotherapy for house mite allergy; 20 pollen allergy trials; ten animal dander allergy trials; two Cladosporium mould allergy, one latex and six trials looking at multiple allergens. Concealment of allocation was assessed as clearly adequate in only 15 of these trials. Significant heterogeneity was present in a number of comparisons. Overall, there was a significant reduction in asthma symptoms and medication and improvement in bronchial hyper-reactivity following immunotherapy. There was a significant improvement in asthma symptom scores (standardised mean difference -0.72, 95% confidence interval -0.99 to -0.33) and it would have been necessary to treat 4 (95%CI 3 to 5) patients with immunotherapy to avoid one deterioration in asthma symptoms. Overall it would have been necessary to treat 5 (95%CI 4 to 6) patients with immunotherapy to avoid one requiring increased medication. Allergen immunotherapy significantly reduced allergen specific bronchial hyper-reactivity, with some reduction in non-specific bronchial hyper-reactivity as well. There was no consistent effect on lung function. Immunotherapy reduces asthma symptoms and use of asthma medications and improves bronchial hyper-reactivity. One trial found that the size of the benefit is possibly comparable to inhaled steroids. The possibility of adverse effects (such as anaphylaxis) must be considered.


The thiol redox state of lymphoid organs is modified by immunization: role of different immune cell populations.
Resting T lymphocytes can internalize reduced cysteine (Cys) but not cystine, the oxidized form of the amino acid that predominates extracellularly. In vitro studies have shown that DC provide Cys to T cells during antigen presentation, allowing their activation. Here, we show that increased thiol production is a hallmark of immune response in vivo. Indeed, the thiol content of LN increases dramatically after antigen injection. Non-protein thiols co-distribute with DC and are highly abundant in germinal centers. In agreement, activated but not resting B lymphocytes and macrophages release free thiols. Increased thiol release following activation requires thioredoxin and is paralleled by increased thioredoxin expression. The T zones of LN are consistently less stained, and both resting and activated T cells are unable to release thiols. Interestingly, the cystine/glutamate transporter x(c) (-) is absent in resting T lymphocytes but is rapidly induced by TCR triggering in vitro, indicating that the release of T cells from the need of exogenous Cys occurs early after activation. These results indicate that a reducing microenvironment is essential to start the immune response but dispensable for its evolution, and support the emerging concept that extracellular redox is implicated in the control of crucial cellular functions.


Pesticide residues in raspberries (Rubus idaeus L.) and dietary risk assessment.
The aim of this study was to evaluate the residues of 140 pesticides in raspberries from north-eastern Poland (2005-2010). Gas chromatography with electron capture detector (GC-ECD) and nitrogen phosphorous detector (GC-NPD) was used. Among the 128 samples, 66 (51.6%) were found to detect residues: 14.1% contained one pesticide and around 38% multiple pesticide residues. The most frequently detected were pyrimethanil residues (36.0%). Twenty-seven (21.1%) raspberry samples exceeded the maximum residue limits. The estimated daily intakes ranged from 0.003% to 3.183% of the acceptable daily intake (ADI) for adults 0.008% and 9.7% for toddlers, respectively. The most critical case is procymidone, the acute risk was 180.9% of acute reference dose (ARfD) for toddlers and for adults (83% of ARfD) which is high.


Dataset linking free polyunsaturated fatty acid concentrations in erythrocytes with chronic pain conditions in adults.
Circulating polyunsaturated fatty acids (PUFAs) and lipid mediators were extracted from human red blood cells and quantified using liquid chromatography-tandem mass spectrometry (LC-MS/MS). The method encompassed 13 different PUFAs and lipid mediators, however, due to instrument capability only five were confidently quantified (EPA, ALA, AA, DHA, and LA). The extraction focused on free polyunsaturated fatty acids since they have a strong correlation with health in humans. The study design was a secondary analysis of the OPPERA-2 study of chronic overlapping pain conditions in adults. The data included are: a) raw LC-MS/MS data (.raw); b) processed data (.xlsx) including chromatographic peak area for each compound and a concentration (ng/mL) based on external calibration with internal standardization using pure analytical grade standards and heavy-isotope labeled internal standards; c) study participant demographics and phenotypes (.xlsx). This dataset consisting of circulating PUFA quantities measured in 605 humans has been made publicly available for analysis and interpretation.


Influence of transport energization on the growth yield of Escherichia coli.
The growth yields of Escherichia coli on glucose, lactose, galactose, maltose, maltotriose, and maltohexaose were estimated under anaerobic conditions in the absence of electron acceptors. The yields on these substrates exhibited significant differences when measured in carbon-limited chemostats at similar growth rates and compared in terms of grams (dry weight) of cells produced per mole of hexose utilized. Maltohexaose was the most efficiently utilized substrate, and galactose was the least efficiently utilized under these conditions. All these sugars were known to be metabolized to glucose 6-phosphate and produced the same pattern of fermentation products. The differences in growth yields were ascribed to differences in energy costs for transport and phosphorylation of these sugars. A formalized treatment of these factors in determining growth yields was established and used to obtain values for the cost of transport and hence the energy-coupling stoichiometries for the transport of substrates via proton symport and binding-protein-dependent mechanisms in vivo. By this approach, the proton-lactose stoichiometry was found to be 1.1 to 1.8 H+ per lactose, equivalent to approximately 0.5 ATP used per lactose transported. The cost of transporting maltose via a binding-protein-dependent mechanism was considerably higher, being over 1 to 1.2 ATP per maltose or maltodextrin transported. The formalized treatment also permitted estimation of the net ATP yield from the metabolism of these sugars; it was calculated that the growth yield data were consistent with the production of 2.8 to 3.2 ATP in the metabolism of glucose 6-phosphate to fermentation products.


Flualprazolam: Report of an Outbreak of a New Psychoactive Substance in Adolescents.
Flualprazolam is a nonregistered drug in the benzodiazepine family and constitutes a new psychoactive substance (NPS). Since 2014, a growing number of designer benzodiazepines have become available over the Internet and on the counterfeit drug market. In June 2019, a cluster of patients intoxicated with flualprazolam was identified by the Oregon Poison Center. As an emerging drug of abuse, the clinical characteristics of flualprazolam have been poorly characterized thus far. Over a one-week period, 6 teenagers presented to local emergency departments after ingesting illegally obtained counterfeit alprazolam, which led to sedation. Other symptoms included slurred speech, confusion, and mild respiratory depression. All 6 patients had resolution of their symptoms within 6 hours of ingestion. Blood and urine samples, as well as a tablet fragment, were obtained from 3 patients. The tablet and biological samples were analyzed by using liquid chromatography-quadrupole time-of-flight mass spectrometry and were found to contain the NPS flualprazolam without other drugs or intoxicants. With this case series, we add to the medical literature a clinical description of an emerging drug of abuse. Flualprazolam appears to share the clinical properties of other benzodiazepines. As flualprazolam and other NPSs become more common, physicians must be aware of their availability and characteristics. Sedation lasting <6 hours was observed in 6 of 6 patients exposed to flualprazolam. No effects that would be unexpected from benzodiazepine intoxication were seen among the patients. Specifically, none developed prolonged symptoms or required intubation and mechanical ventilation, ICU admission, or antidotal therapy.


Procreative rights denied? Access to assisted reproduction technologies by single women in China.
The Chinese regulatory framework on access to assisted reproduction technologies (hereafter ART) is relatively restrictive, limiting ART exclusively to heterosexual married couples as a medical treatment for infertility. ART clinics across China are prohibited from providing ART services for single women. This creates significant regulatory barrier for single women to exercise their procreative rights. The restriction finds its root in the population and family planning law under which reproduction is tied to marriage and childbirth outside marriage are deemed as illegitimate with punishing consequences. It essentially denies the procreative rights of single women which are recognized by Chinese law. A welcoming development is that in seven out of 10 cases the court is willing to grant exceptions by allowing posthumous implantation procedure for widowed women after the sudden and unexpected death of the husband.


Autologous buccal mucosa graft augmentation for foreshortened vagina.
Vaginal foreshortening after pelvic surgery or radiotherapy may lead to dyspareunia and decreased quality of life. Unfortunately, little literature exists regarding treatment options for this debilitating problem. Autologous buccal mucosal grafting has been previously reported for creation of a total neovagina and the repair of postvaginoplasty vaginal stenosis. Autologous buccal mucosa offers several advantages as a replacement material for vaginal reconstruction. Vaginal and oral buccal mucosa are both hairless, moist, nonkeratinized stratified squamous epithelia. Buccal mucosa has a dense layer of elastic fibers, imparting both elasticity and strength, and acquires a robust neovascularity with excellent graft take. The graft material is readily available and donor site scars are hidden in the mouth. A 60-year-old woman had vaginal foreshortening to 4.5 cm 15 years after radical hysterectomy and brachytherapy for endometrial cancer. She was unable to have intercourse despite attempted vaginal dilation. Her foreshortened vagina was successfully augmented with autologous buccal mucosa grafting at the apex, increasing her vaginal length to 8 cm and permitting pain-free intercourse. Even in the face of an altered surgical field after radical hysterectomy and radiation, autologous buccal mucosa is an option for vaginal reconstruction for vaginal foreshortening.


Callosal warning syndrome.
To report the clinical and imaging findings in a patient with an initial fluctuating disconnection syndrome due to corpus callosal ischemia that ultimately culminated in infarction with persistent symptoms. A 40-year-old, hypertensive, right-handed man presented with transient, stereotyped symptoms of corpus callosal disconnection (intermanual conflict, apraxia, dysgraphia and construction difficulties in his left hand). Serial magnetic resonance imaging scans demonstrated the ischemic nature of the initial fluctuating symptoms and later showed callosal infarction when the symptoms were persistent. Magnetic resonance angiogram did not reveal significant stenosis or occlusion of the internal carotid or proximal portion of anterior cerebral arteries. Patient received standard treatment for ischemic stroke and at follow-up 1 month later, had mild left hand apraxia, dysgraphia and construction difficulties. The case highlights the unusual occurrence of crescendo transient ischemic attacks culminating in infarction in the location of corpus callosum. We have termed this novel stroke syndrome as 'callosal warning syndrome' as the temporal profile was quite indistinguishable from that of relatively well-known stroke warning syndromes in the location of internal capsule and pontine tegmentum.


[Quality control in the treatment and diagnosis in clinics of the Leningrad region].
A systemic review of disease histories delivered from hospitals and outpatient clinics of the Leningrad region in Leningrad region pathoanatomical bureau to examine quality of diagnosis and treatment led to organization of the Expertise Centre of Medical Service Quality at the bureau. The Centre participates in licensing and accreditation of medical activity in the Leningrad region. For the patients this Centre is an instrument of legal control providing help in defencing their rights.


Cystectomy with urinary diversion for benign disease: indications and outcomes.
To analyze what factors contribute to a worse outcome after cystectomy and urinary diversion for benign disease as measured by the frequency of severe complications. A retrospective review was performed of consecutive patients who underwent a cystectomy for benign disease. The primary outcome was the type and severity of complications, according to Clavien-Dindo scale. A total of 139 patients underwent cystectomy with diversion for benign diseases over the study period. The most common indications for surgery were spinal cord injury (32%) and radiation damage to the bladder (18%). The average preoperative age-adjusted Charlson comorbidity index was 4.6. Seventy-four patients (53%) underwent supratrigonal cystectomy. Mean surgery duration was 344±103 minutes, and the mean estimated blood loss was 476±379 mL. The most common complications were perioperative blood transfusion, prolonged ileus, and pyelonephritis. Seventy-nine patients (57%) had a complication grade≥II on the Clavien-Dindo scale. This did not differ based on indication for surgery, age, gender, body mass index, age-adjusted Charlson comorbidity index, estimated blood loss, or type of cystectomy. After adjustment, only duration of surgery in 10-minute increments (odds ratio, 1.07; 95% confidence interval, 1.02-1.12; P=.007) was associated with an increased incidence of serious complication. Most of the patients experience some complication after cystectomy and urinary diversion for benign indications. Duration of surgery is an important variable that can affect outcome.


Molecular mechanisms involved in chemoresistance in paediatric acute lymphoblastic leukaemia.
Acute lymphoblastic leukaemia (ALL) is the most common paediatric cancer. Despite cure rates approaching 80%, resistance to treatment and disease relapse remain a significant clinical problem. Identification of the genes and biological pathways responsible for chemoresistance is therefore crucial for the design of novel therapeutic approaches aiming to improve patient survival. Mutations in the membrane transporter P-glycoprotein genes, genetic variations in drug-metabolising enzymes and defects in apoptotic pathways are mechanisms of chemoresistance common to a wide spectrum of cancers and also play a role in paediatric ALL. In addition, several recent microarray studies have identified transcriptional profiles specifically associated with chemoresistance and pointed to a number of potentially novel therapeutic targets. These microarray studies have shown that genes discriminating between clinically responsive and resistant leukaemias tend to be involved in cellular processes such as regulation of cell cycle, proliferation, and DNA repair. Here we review the outcomes of these microarray studies and also present our own investigations into apoptotic resistance to DNA double strand breaks (DSBs) in paediatric ALL. We present stratification of paediatric ALL by the profile of DNA damage response following ionising radiation (IR) in vitro. This approach allows classification of ALL tumours at presentation into IR-apoptotic sensitive and IR-apoptotic resistant. Furthermore, apoptotic resistant leukaemias exhibit abnormal response of NFkB pathway following irradiation and inhibition of this pathway can sensitise leukaemic cells to IR-induced DSBs.


[Plastic changes in the sensory elements of the spinal cord after decreasing the afferent inflow].
After partial deafferentation of one of the hindlimbs changes of the cord dorsal potential and mass discharge from the anterior-lateral filament of the exposed spinal cord were studied after maximal recovery of function of the deafferented limb in adult cats. Neuronal activity in response to electrical stimulation of the dorsal roots was considerably higher on the deafferented side than on the intact one. This seems to be due to plastic properties of the c. n. s. responsible for the recovery of functions.


Selective effects of mastoparan analogs: separation of G-protein-directed and membrane-perturbing activities.
Mastoparan (MP), a wasp venom peptide, is known both to interact with G-proteins and to alter membrane structure and function. To determine the structural requirements for these two aspects of MP action, we constructed several analogs of the peptide and characterized them using Swiss 3T3 cell membranes. The effects of these peptides were measured on: i) G-protein-mediated stimulation of phospholipase-C activity by GTP gamma S and bombesin and ii) the membrane enzyme activities, calcium-activated phospholipase-C and Na,K-ATPase. MP strongly inhibited all the above activities and caused membrane permeabilization. Substitution of one Lys residue by Gly at either the N- or C-terminal of the MP molecule resulted in peptides which selectively inhibited G-protein stimulated phospholipase-C with no or very slight membrane-perturbing effects. Introduction of additional Lys residues to MP led to the opposite effect. Thus, G-protein modulating and membrane disrupting actions of MP appear to be not necessarily linked, and may be separated.


Failure of extracranial-intracranial arterial bypass to reduce the risk of ischemic stroke. Results of an international randomized trial.
To determine whether bypass surgery would benefit patients with symptomatic atherosclerotic disease of the internal carotid artery, we studied 1377 patients with recent hemisphere strokes, retinal infarction, or transient ischemic attacks who had atherosclerotic narrowing or occlusion of the ipsilateral internal carotid or middle cerebral artery. Of these, 714 were randomly assigned to the best medical care, and 663 to the same regimen with the addition of bypass surgery joining the superficial temporal artery and the middle cerebral artery. The patients were followed for an average of 55.8 months. Thirty-day surgical mortality and major stroke morbidity rates were 0.6 and 2.5 per cent, respectively. The postoperative bypass patency rate was 96 per cent. Nonfatal and fatal stroke occurred both more frequently and earlier in the patients operated on. Secondary survival analyses comparing the two groups for major strokes and all deaths, for all strokes and all deaths, and for ipsilateral ischemic strokes demonstrated a similar lack of benefit from surgery. Separate analyses in patients with different angiographic lesions did not identify a subgroup with any benefit from surgery. Two important subgroups of patients fared substantially worse in the surgical group: those with severe middle-cerebral-artery stenosis (n = 109, Mantel-Haenszel chi-square = 4.74), and those with persistence of ischemic symptoms after an internal-carotid-artery occlusion had been demonstrated (n = 287, chi-square = 4.04). This study thus failed to confirm the hypothesis that extracranial-intracranial anastomosis is effective in preventing cerebral ischemia in patients with atherosclerotic arterial disease in the carotid and middle cerebral arteries.


The Trojan exosome hypothesis.
We propose that retroviruses exploit a cell-encoded pathway of intercellular vesicle traffic, exosome exchange, for both the biogenesis of retroviral particles and a low-efficiency but mechanistically important mode of infection. This Trojan exosome hypothesis reconciles current paradigms of retrovirus-directed transmission with the unique lipid composition of retroviral particles, the host cell proteins present in retroviral particles, the complex cell biology of retroviral release, and the ability of retroviruses to infect cells independently of Envelope protein-receptor interactions. An exosomal origin also predicts that retroviruses pose an unsolvable paradox for adaptive immune responses, that retroviral antigen vaccines are unlikely to provide prophylactic protection, and that alloimmunity is a central component of antiretroviral immunity. Finally, the Trojan exosome hypothesis has important implications for the fight against HIV and AIDS, including how to develop new antiretroviral therapies, assess the risk of retroviral infection, and generate effective antiretroviral vaccines.


A Simpler, Modified Frailty Index Weighted by Complication Occurrence Correlates to Pain and Disability for Adult Spinal Deformity Patients.
The Miller et al adult spinal deformity frailty index (ASD-FI) correlates with complication risk; however, its development was not rooted in clinical outcomes, and the 40 factors needed for its calculation limit the index's clinical utility. The present study aimed to develop a simplified, weighted frailty index for ASD patients METHODS: This study is a retrospective review of a single-center database. Component ASD-FI parameters contributing to overall ASD-FI score were assessed via Pearson correlation. Top significant, clinically relevant factors were regressed against ASD-FI score to generate the modified ASD-FI (mASD-FI). Component mASD-FI factors were regressed against incidence of medical complications, and factor weights were calculated from regression of these coefficients. Total mASD-FI score ranged from 0 to 21, and was calculated by summing weights of expressed parameters. Linear regression and published ASD-FI cutoffs generated corresponding mASD-FI frailty cutoffs: not frail (NF, <7), frail (7-12), severely frail (SF, >12). Analysis of variance assessed the relationship between frailty category and validated baseline measures of pain and disability at baseline. The study included 50 ASD patients. Eight factors were included in the mASD-FI. Overall mean mASD-FI score was 5.7 ± 5.2. Combined, factors comprising the mASD-FI showed a trend of predicting the incidence of medical complications (Nagelkerke R 2 = 0.558; Cox & Snell R 2 = 0.399; P = .065). Breakdown by frailty category is NF (70%), frail (12%), and SF (18%). Increasing frailty category was associated with significant impairments in measures of pain and disability: Oswestry Disability Index (NF: 23.4; frail: 45.0; SF: 49.3; P < .001), SRS-22r (NF: 3.5; frail: 2.6; SF: 2.4; P = .001), Pain Catastrophizing Scale (NF: 41.9; frail: 32.4; SF: 27.6; P < .001), and NRS Leg Pain (NF: 2.3; frail: 7.2; SF: 5.6; P = .001). This study modifies an existing ASD frailty index and proposes a weighted, shorter mASD-FI. The mASD-FI relies less on patient-reported variables, and it weights component factors by their contribution to adverse outcomes. Because increasing mASD-FI score is associated with inferior clinical measures of pain and disability, the mASD-FI may serve as a valuable tool for preoperative risk assessment.


Gastric mucosal lesions in influenza virus infected mice: role of gastric lipid peroxidation.
The present study provides direct experimental proof that the combination of influenza virus infection A/Aichi/2/68 (H3N3) with different models of oxidative stress, such as immobilization, cold and cold-restraint, is associated with graduated oxidative disturbances in the stomach of mice, despite the absence of virus replication and inflammation in this tissue. It was found that experimental influenza virus infection is accompanied with significant changes in gastric mucosal integrity, as well as an increase in the products of lipid peroxidation in the stomachs of mice. Preliminary exposure of mice to immobilization stress and subsequent inoculation of influenza virus did not significantly influence gastric ulceration or lipid peroxidation compared with infected mice. Cold stress resulted in a significant decrease in the index of stomach ulceration and did not influence the fluorescent products of lipid peroxidation and MDA compared with infected animals. The simultaneous application of cold-restraint stress and influenza virus infection provoked synergism in the activity of all factors on the parameters under investigation. Ulceration increased approximately two-fold, as did the amount of fluorescent products of lipid peroxidation and MDA, compared with influenza virus-infected and non-stressed animals.


Wake-induced oscillation behaviour of twin bundle conductor transmission lines.
A numerical method to simulate air flow around a bundle conductor line by means of the FLUENT software is presented and verified by a wind tunnel test for aerodynamic characteristics of a twin bundle conductor line. The lift and drag coefficients of the leeward sub-conductor of a twin bundle conductor varying with its relative position in the wake zone to the windward one under different wind velocities are numerically determined by the presented method. A user-defined subroutine of ABAQUS software is developed to apply the aerodynamic loads on each sub-conductor and the electromagnetic force between sub-conductors. The numerical simulation method for wake-induced oscillation of a bundle conductor line is proposed. By means of the numerical method, wake-induced oscillation processes of twin bundle conductor transmission lines under different parameters, including current intensity, spacer layout, span length and wind velocity, are numerically simulated. Moreover, the effects of those parameters on the oscillation characteristics of the lines, such as vibration mode, frequency, amplitude and motion trace, are discussed. The results obtained provide a fundamental basis for the understanding of wake-induced oscillation behaviour of twin bundle conductor transmission lines and the development of control technique for wake-induced oscillation.


[Hyperlipidemias: new data and new concepts].
Strategy for management of patients displaying hyperlipidemia has changed since the the first statin has been launched in France more than ten years ago. Following the first primary and secondary prevention studies conducted with hyperlipidemic subjects, results have been extended to patients with cholesterol levels within normal range both in primary (AFCAPS/TexCAPS) and secondary (CARE) prevention. Drug therapy has been simplified with targets tailored to the patient's risk. Despite these important results from intervention studies with statins, other crucial questions remain. Among these questions the first one concerns the possibility that cardiovascular benefits demonstrated with statins are also partly due to other (pleiotropic) effects. This was first hypothesised when statins were proven to be efficacious after short term treatments (one year in the regression studies). The second question is whether we can extend the benefit observed in populations included in published trials to primary prevention of stroke and to the groups less well represented in previous trials including women, elderly patients. The current trends and economic strains of every health care systems have focused on evidence-based medicine and cost-efficacy studies. ROLE OF TRIGLYCERIDES: Beyond LDL-cholesterol there is clear emergence of a role of triglyceride in cardiovascular disease as well as new data on pathophysiology of the so-called reverse cholesterol transport. Recent trials including patients with hypertriglyceridemia as well as a decline of the benefit observed in hypertriglyceridemic patients strongly suggest that the use of statins may have its own limitation. IMPORTANCE OF DIET: Finally, translating results of recent trials in clinical practice remains a challenge for treating physicians who face poor compliance and difficulties in implementing diet in patients.


The accuracy of color Doppler flow imaging for the detection of symptomatic deep venous thrombosis in Chinese patients.
To evaluate the ability of color Doppler flow imaging (CDFI) to detect deep venous thrombosis (DVT), which is difficult to diagnose clinically, 67 limbs of 60 patients who presented with clinical signs strongly indicative of DVT during the period between June 1988 and June 1992, were examined. The iliac, common femoral, and superficial femoral veins were assessed with the patient in the supine position, and the popliteal vein was examined with the patient prone. Gentle but firm compression with the transducer probe was used to test for the presence of DVT. Ascending contrast venograms were also obtained within 24 h after the ultrasound procedure, with venography being used as the standard for comparison with CDFI. DVT was identified in 63 limbs by contrast venography and in 62 limbs by CDFI. The sensitivity and specificity of CDFI were 98.4% and 100%, respectively, while the positive and negative predictive values were 100% and 80%, respectively. The thromboses were classified into three patterns: the filling type, the local type, and mural thrombus, detected in 63%, 27%, and 10%, of the limbs respectively, with the filling type being the most common in this series. The results of our study illustrated that CDFI is highly sensitive and specific for detecting symptomatic DVT and that it should be gradually substituted for venography in such patients.


Identification of functionally distinct domains of human granulocyte-macrophage colony-stimulating factor using monoclonal antibodies.
Granulocyte-macrophage colony-stimulating factor (GM-CSF) is a glycoprotein that is required for the survival, growth, and differentiation of hematopoietic progenitor cells. Although the primary structure of GM-CSF is known from cDNA cloning, the relationship between structure and function of GM-CSF is not fully understood. Fifteen different monoclonal antibodies (MoAbs) to human GM-CSF were generated to map immunologically distinct areas of the molecule. Each of the MoAbs was biotinylated and shown by enzyme-linked immunosorbent assay to bind to recombinant GM-CSF that had been affixed to a solid phase. Each of the 15 unconjugated MoAbs was then used to compete with each biotinylated MoAb for binding to GM-CSF. These cross-blocking studies identified eight distinct epitopes of native GM-CSF. Seven of these epitopes were also present in denatured GM-CSF by Western blotting, and four of the epitopes were at least partially conserved on GM-CSF that was reduced in beta-mercaptoethanol. MoAbs to four of eight epitopes neutralized both recombinant (glycosylated and nonglycosylated) and natural human GM-CSF in a GM colony-forming unit (CFU-GM) assay and blocked GM-CSF-induced activation of neutrophils. For most of the antibodies there was a good correlation between neutralizing activity and the capacity to block binding of 125I-GM-CSF to neutrophils or blasts. Non-neutralizing antibodies to one epitope partially blocked binding of 125I-GM-CSF to neutrophils. None of the MoAbs neutralized interleukin-3, G-CSF, or M-CSF. The locations of seven of the epitopes could be partially mapped with regard to the amino acid structure by determining reactivity to GM-CSF synthetic peptides or to human-mouse chimeric GM-CSFs. The neutralizing antibodies were found to map to amino acids 40-77, 78-94, or 110-127. Thus, these MoAbs are useful to identify functional domains of GM-CSF and in identifying regions that are likely to be involved in receptor interaction.


Development of hybrid scaffolds with natural extracellular matrix deposited within synthetic polymeric fibers.
A major challenge of tissue engineering is to generate materials that combine bioactivity with stability in a form that captures the robust nature of native tissues. Here we describe a procedure to fabricate a novel hybrid extracellular matrix (ECM)-synthetic scaffold biomaterial by cell-mediated deposition of ECM within an electrospun fiber mat. Synthetic polymer fiber mats were fabricated using poly(desamino tyrosyl-tyrosine carbonate) (PDTEC) co-spun with poly(ethylene glycol) (PEG) used as a sacrificial polymer. PEG removal increased the overall mat porosity and produced a mat with a layered structure that could be peeled into separate sheets of about 50 μm in thickness. Individual layers had pore sizes and wettability that facilitated cell infiltration over the depth of the scaffold. Confocal microscopy showed the formation of a highly interpenetrated network of cells, fibronectin fibrils, and synthetic fibers mimicking a complex ECM as observed within tissues. Decellularization did not perturb the structure of the matrix or the fiber mat. The resulting hybrid ECM-scaffold promoted cell adhesion and spreading and stimulated new ECM assembly by stem cells and tumor cells. These results identify a new technique for fabricating highly porous synthetic fibrous scaffolds and an approach to supplement them with natural biomimetic cues. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 2162-2170, 2017.


Pulsed Electromagnetic Fields Reduce Postoperative Interleukin-1β, Pain, and Inflammation: A Double-Blind, Placebo-Controlled Study in TRAM Flap Breast Reconstruction Patients.
Pulsed electromagnetic fields have been shown to reduce postoperative pain, inflammation, and narcotic requirements after breast reduction and augmentation surgical procedures. This study examined whether pulsed electromagnetic field therapy could produce similar results in patients undergoing unilateral transverse rectus abdominis myocutaneous (TRAM) flap breast reconstruction, a significantly more complex and painful surgical procedure. In this double-blind, placebo-controlled, randomized study, 32 patients undergoing unilateral TRAM flap breast reconstruction received active or sham pulsed electromagnetic field therapy. Pain levels were measured by using a visual analogue scale; narcotic use and wound exudate volume were recorded starting 1 hour postoperatively. Wound exudates were analyzed for interleukin-1β. Mean visual analogue scale pain scores were 2-fold higher in the sham cohort at 5 hours and 4-fold higher at 72 hours (p < 0.01), along with a concomitant 2-fold increase in narcotic use in sham patients (p < 0.01). Wound exudate volume was 2-fold higher in the sham cohort at 24 hours (p < 0.01), and mean interleukin-1β concentration in wound exudates of sham patients was 5-fold higher at 24 hours (p < 0.001). Pulsed electromagnetic field therapy significantly reduced postoperative pain, inflammation, and narcotic use following TRAM flap breast reconstruction, paralleling its effect in breast reduction patients. Both studies also report a significant reduction of interleukin-1β in the wound exudate, supporting a mechanism involving a pulsed electromagnetic field effect on nitric oxide/cyclic guanosine monophosphate signaling, which modulates the body's antiinflammatory pathways. Adjunctive pulsed electromagnetic field therapy could impact the speed and quality of wound repair in many surgical procedures. Therapeutic, I.


Multicenter study of compliance and drop administration in glaucoma.
Poor compliance with medication is a major concern in the management of glaucoma. Improper administration technique can lead to contamination and inaccurate dosing. This study estimates the prevalence and predictors of noncompliance and improper administration technique among Canadian glaucoma patients. Data were collected using a standardized questionnaire. Noncompliance was defined as missing at least 1 drop of medication per week and (or) the inability to accurately describe the medication regimen. Patients were asked to indicate the most common reason for missing medication. Study personnel assessed drop administration technique as patients were applying eye drops. Physicians provided information, including measures of disease stability, regarding the patient's glaucoma. Predictors were assessed using odds ratios from a logistic regression model. 500 patients from 10 centers across Canada participated in the study. Of these, 25.6% reported missing at least 1 drop of medication per week, and 4.2% were unable to accurately describe their medication regimen. The overall proportion of noncompliance was 27.9%. With regard to drop administration, 6.8% missed their eye and 28.8% contaminated the bottle tip; overall, 33.8% demonstrated improper technique. The most common reasons given for missing eye drops were "forgetfulness" and "being away from drops." Formal education limited to elementary school and treatment duration of <5 years increased patient-reported noncompliance. Factors associated with improper administration technique were age 60 years and older and formal education limited to elementary school. Over 50% of the patients surveyed were either noncompliant or demonstrated improper administration technique. Glaucoma patients should be educated on the importance of compliance and instructed on proper drop administration.


Did you hear the one about the policeman, the doctor and the pharmacist at 30000 feet?
This is the remarkable story of survival against all the odds. A passenger had a myocardial infarction complicated by a witnessed cardiac arrest while on a commercial flight through some of the most remote airspace on the planet. Immediate cardiopulmonary resuscitation and use of an automatic external defibrillator achieved rapid return of spontaneous circulation. Passengers and crew worked effectively together, under the guidance of a physician, to provide critical care to the patient while the flight diverted so he could be transferred to an emergency hospital in Beijing for eventual thrombolysis and postresuscitation care. He made a rapid and full recovery to be discharged from hospital, neurologically intact, 10 days later.


Experimental third ventriculostomy performed using endovascular surgical techniques and their adaptation to percutaneous intradural neuronavigation: proof of concept cadaver study.
Endoscopic third ventriculostomy has developed into a therapeutic alternative to shunting for the management of carefully selected patients with primarily noncommunicating hydrocephalus. This procedure, however, requires a general anesthetic and necessitates violation of the brain parenchyma and manipulation near vital neural structures to access the floor of the third ventricle. Using two cadavers and off-the-shelf angiographic catheters, we sought to determine whether it was possible to navigate a catheter, angioplasty balloon, and stent percutaneously through the subarachnoid space from the thecal sac into the third ventricle so as to perform a third ventriculostomy from below. Using biplane angiography and off-the-shelf angiographic catheters along with angioplasty balloons and stents, we were able to pass a stent coaxially from the thecal sac to and across the floor of the third ventricle so as to achieve a third ventriculostomy from below. Coaxial catheter techniques allowed for the percutaneous insertion of a stent across the floor of the third ventricle. Ventriculostomy was confirmed by injecting contrast medium into the lateral ventricle and seeing it pass through the stent and into the chiasmatic cistern. We describe the performance of third ventriculostomies in two cadavers by use of the new concept of percutaneous intradural neuronavigation. This procedure may obviate the need for general anesthetic and minimize the potential for brain and vascular injury, especially if ultimately combined with magnetic resonance fluoroscopy.


[Pleiotropic effects of small dozes simvastatin in patients of senile age with chronic heart failure].
The pleiotropic effects of simvastatin in a daily doze of 20 mg in persons of senile age with chronic heart failure were studied in the submitted work. The practical opportunity to reduce the risk of acute vascular events, improvement of vascular endothelium function and relative safety of application of the preparation in the specified dosage at persons of senile age is shown.


Making Sense of Burnout: A Reflexive Thematic Analysis of How Teachers in England Discuss and Encounter the Term Burnout.
Despite extensive research looking at the phenomenon of burnout, little is known about how individuals working in traditionally high-burnout occupations understand the term. Interviews were conducted with six teachers working in state schools in England centring on how the term burnout was understood and how it was used or encountered. Reflexive thematic analysis was employed from a critical realist perspective to analyse the data generated. All participants described burnout as a stress-related condition, yet for some participants the point at which stress became burnout was unclear leading to an understanding that burnout was the point at which one was unable to work. Many participants highlighted an individualistic understanding of burnout, perceiving it as representing an individual deficit rather than an organisational failing. This was often reinforced by where the term was encountered (at work or in the media) and was linked to the stigma many participants associated with burnout. This paper concludes that individualistic framings of burnout obscure its organisational determinants while reinforcing notions that mental well-being is something which should be personally - and privately - managed by individuals.


Two-dimensional silicon photonic crystal based biosensing platform for protein detection.
We theoretically and experimentally demonstrate an ultrasensitive two-dimensional photonic crystal microcavity biosensor. The device is fabricated on a silicon-on-insulator wafer and operates near its resonance at 1.58 microm. Coating the sensor internal surface with proteins of different sizes produces a different amount of resonance redshift. The present device can detect a molecule monolayer with a total mass as small as 2.5 fg. The device performance is verified by measuring the redshift corresponding to the binding of glutaraldehyde and bovine serum albumin (BSA). The experimental results are in good agreement with theory and with ellipsometric measurements performed on a flat oxidized silicon wafer surface.


Delusions beyond beliefs: a critical overview of diagnostic, aetiological, and therapeutic schizophrenia research from a clinical-phenomenological perspective.
Delusions are commonly conceived as false beliefs that are held with certainty and which cannot be corrected. This conception of delusion has been influential throughout the history of psychiatry and continues to inform how delusions are approached in clinical practice and in contemporary schizophrenia research. It is reflected in the full psychosis continuum model, guides psychological and neurocognitive accounts of the formation and maintenance of delusions, and it substantially determines how delusions are approached in cognitive-behavioural treatment. In this Review, we draw on a clinical-phenomenological framework to offer an alternative account of delusion that incorporates the experiential dimension of delusion, emphasising how specific alterations to self-consciousness and reality experience underlie delusions that are considered characteristic of schizophrenia. Against that backdrop, we critically reconsider the current research areas, highlighting empirical and conceptual issues in contemporary delusion research, which appear to largely derive from an insufficient consideration of the experiential dimension of delusions. Finally, we suggest how the alternative phenomenological approach towards delusion could offer new ways to advance current research and clinical practice.


Modified Masaoka stage and size are independent prognostic predictors in thymoma and modified Masaoka stage is superior to histopathologic classifications.
The prognostic value of histopathologic classifications of thymoma is debated. Problematic reproducibility might cause this controversy. We studied the prognostic significance of three histopathologic classifications of thymomas after three thoracic pathologists agreed upon thymoma subtype and invasion. We also compared the outcome to established prognostic parameters. Patients, surgically treated for thymic epithelial neoplasm at Mayo Clinic (1942-2008), were staged according to the modified Masaoka staging and the recently proposed staging by Moran. Three thoracic pathologists independently classified all cases according to the World Health Organization, Bernatz, and proposed Suster and Moran classification. Only thymoma that all three pathologists diagnosed as the same histopathologic subtype and extent of invasion were included in outcome analysis. In 214 (proposed Suster and Moran classification), 145 (World Health Organization classification), and 120 cases (Bernatz classification), reviewers agreed upon subtype of thymoma and invasion and follow-up was available. Median follow-up time was 7.5-7.7 years (range between classifications). All histopathologic classifications were associated with overall survival (OS) and disease-free survival (p ≤ 0.0001 to p = 0.048); only Bernatz classification was independent of modified Masaoka staging associated with OS (p = 0.04). Modified Masaoka stage predicted outcome independent of all histopathologic classifications and resection status and strongly correlated with the proposed Moran stage (correlation coefficient, 0.95). Thymoma size and age were prognostic parameters for OS independent of any histopathologic classification. Histopathologic classifications of thymomas are associated with prognosis but are in general not independent predictors of outcome. Modified Masaoka stage and proposed Moran staging are independent prognostic parameters for thymoma and superior to histopathologic classifications.


A fatal case of acute hepatitis E among pregnant women, Central African Republic.
Hepatitis E virus (HEV) is a major public health problem in developing countries. HEV infection in pregnant women is more common and more often fatal in the third trimester. The mortality rate due to HEV-induced hepatitis is as high as 15-20 per cent. The present study was designed to determine the potential factors responsible for high mortality rate among pregnant women. Twenty one pregnant women attended the Maternity Center of Begoua in the Central African Republic during an outbreak of hepatitis E virus between July and October 2002 with symptoms of acute liver disease. Their mean gestational period was 29.9 (SD 8.3 weeks) and they were aged from 15 to 39 years old. The serology IgM showed that seven women (33%) had acute hepatitis E. Among them, one woman, aged 35 and her newborn died after an apparently normal preterm delivery. The 6 remaining young women, age 18 - 22, had preterm deliveries which included three live babies and three stillborn with one macerated. These results suggest that maternal age, in addition to hormonal, immunological and environmental factors, may be a risk factor for fatal outcome.


SIX1 acts synergistically with TBX18 in mediating ureteral smooth muscle formation.
Dysfunction of the ureter often leads to urine flow impairment from the kidney to the bladder, causing dilation of the ureter and/or renal pelvis. Six1 is a crucial regulator of renal development: mutations in human SIX1 cause branchio-oto-renal (BOR) syndrome and Six1(-/-) mice exhibit renal agenesis, although the ureter is present. It remains unclear whether Six1 plays a role in regulating ureter morphogenesis. We demonstrate here that Six1 is differentially expressed during ureter morphogenesis. It was expressed in undifferentiated smooth muscle (SM) progenitors, but was downregulated in differentiating SM cells (SMCs) and had disappeared by E18.5. In Six1(-/-) mice, the ureteral mesenchymal precursors failed to condense and differentiate into normal SMCs and showed increased cell death, indicating that Six1 is required for the maintenance and normal differentiation of SM progenitors. A delay in SMC differentiation was observed in Six1(-/-) ureters. A lack of Six1 in the ureter led to hydroureter and hydronephrosis without anatomical obstruction when kidney formation was rescued in Six1(-/-) embryos by specifically expressing Six1 in the metanephric mesenchyme, but not the ureter, under control of the Eya1 promoter. We show that Six1 and Tbx18 genetically interact to synergistically regulate SMC development and ureter function and that their gene products form a complex in cultured cells and in the developing ureter. Two missense mutations in SIX1 from BOR patients reduced or abolished SIX1-TBX18 complex formation. These findings uncover an essential role for Six1 in establishing a functionally normal ureter and provide new insights into the molecular basis of urinary tract malformations in BOR patients.


The Health-promoting Potential of Edible Mushroom Proteins.
Edible mushrooms have been classified as "next-generation food" due to their high nutritional value coupled with their biological and functional potential. The most extensively studied and reported mushroom macromolecules are polysaccharides. However, macrofungi proteins and peptides are also a representative and significant bioactive group. Several factors such as species, substrate composition and harvest time significantly impact the mushroom protein content, typically ranging between 19 and 35% on a dry weight basis. Proteins work based on their shape and structure. Numerous extraction methods, including chemical and non-conventional, and their implications on protein yield and stability will be discussed. Beyond their biological potential, a great advantage of mushroom proteins is their uniqueness, as they often differ from animal, vegetable, and microbial proteins. According to recently published reports, the most relevant mushroom bioactive proteins and peptides include lectins, fungal immunomodulatory proteins, ubiquitin-like proteins, and proteins possessing enzymatic activity such as ribonucleases laccases, and other enzymes and ergothioneine. These are reported as antioxidant, antiviral, antifungal, antibacterial, antihypertensive, immunomodulatory, antitumour, antihypercholesterolemic or antihyperlipidemic, antidiabetic and anti-inflammatory properties, which improved proteins and peptides research interest and contributed to the increase of mushroom market value. This review provides an overview of the most relevant biochemical and biological properties of the main protein groups in edible mushrooms, explicitly focusing on their biomedical potential. Although mushrooms are a rich source of various proteins, many of these molecules have yet to be identified and characterised. Accordingly, it is crucial to identify and characterise new macromolecules of macrofungi origin, which opens an opportunity for further investigation to identify new bioactives for food, nutraceutical, or medicinal applications.


Influence of social relationship domains and their combinations on incident dementia: a prospective cohort study.
Social relationships consist of mutually related but distinct dimensions. It remains unclear how these domains independently contribute to incident dementia. This large-scale, prospective cohort study examines associations between the social relationship domains as well as their combinations and incident dementia among community-dwelling older adults. We analysed data from 13 984 community-dwelling adults aged 65+ without long-term care needs living in Aichi prefecture in Japan. Incident dementia was assessed based on the Long-term Care Insurance records, followed for 3436 days from the baseline survey conducted in 2003. Three social relationships domains (social support, social networks and social activities) were further divided into a total of eight subdomains. A social relationship diversity score was calculated using the social relationship domains which were significantly related to incident dementia. A Cox proportional hazards model showed that being married, exchanging support with family members, having contact with friends, participating in community groups and engaging in paid work were related to a lower likelihood of developing incident dementia, controlling for covariates and other social relationship domains. The diversity scores, ranging from 0 to 5, were linearly associated with incident dementia (p<0.001), and those who scored highest were 46% less likely to develop incident dementia compared with those in the lowest category. Our findings revealed five social relationship subdomains which were negatively related to incident dementia, suggesting that dementia may potentially be prevented by enhancing these social relationships. Future studies should examine independent pathways between each social relationship domain and incident dementia.


Enhancing Triplet-Triplet Annihilation Upconversion of Pyrene Derivatives for Photoredox Catalysis via Molecular Engineering.
Triplet-triplet annihilation upconversion (TTA-UC) has the potential to enhance photoredox catalysis yield. It includes a sensitizer and an annihilator. Efficient and stable annihilators are essential for photoredox catalysis, yet only a few examples are reported. Herein, we designed four novel pyrene annihilators (1, 2, 3 and 4) via introducing aryl-alkynyl groups onto pyrene to systematically modulate their singlet and triplet energies. Coupled with platinum octaethylporphyrin (PtOEP), the TTA-UC efficiency is enhanced gradually as the number of aryl-alkynyl group increases. When combining 4 with palladium tetraphenyl-tetrabenzoporphyrin (PdTPTBP), we achieved the highest red-to-green upconversion efficiency (22.4±0.3 %) (out of a 50 % maximum) so far. Then, this pair was used to activate photooxidation of aryl boronic acid under red light (630 nm), which achieved a great improved reaction yield compared to that activated by green light directly. The results not only provide a design strategy for efficient annihilators, but also show the advantage of applying TTA-UC into improving the photoredox catalysis yield.


Suppression of the temperature-sensitive phenotype of a mutant of reovirus type 3.
A revertant of a reovirus group A temperature-sensitive mutant was crossed with wild type. More than 50 percent of the progeny were temperature sensitive. In all of the temperature-sensitive progeny examined by recombination tests, the temperature-sensitive lesion was in group A. The results indicate that the revertant was phenotypically suppressed.


Optimising fluorescein diacetate sputum smear microscopy for assessing patients with pulmonary tuberculosis.
Assessing Mycobacterium tuberculosis (TB) viability by fluorescein diacetate (FDA) microscopy can predict TB culture results, treatment response and infectiousness. However, diverse methods have been published. We aimed to optimise FDA microscopy, minimising sputum processing, biohazard and complexity for use in resource-constrained settings. Optimization: Patients with smear-positive pulmonary TB before treatment and healthy control participants provided sputa. These were divided into equal aliquots that were tested directly or after NaOH centrifuge-decontamination. Each aliquot was cultured and used to prepare slides (n = 80). FDA microscopy used: 1 or 3 drops of sputum; with/out acid-alcohol wash; with/out phenol sterilization; with 0/30/60 seconds KMnO4 quenching. Control samples all had negative culture and microscopy results. FDA microscopy had higher sensitivity when performed directly (without centrifuge-decontamination) on 1 drop of sputum (P<0.001), because 3 drops obscured microscopy. Acid-alcohol wash and KMnO4 quenching made bacilli easier to identity (P = 0.005). Phenol sterilization did not impair microscopy (P>0.1). Validation: The 2 protocols that performed best in the optimization experiments were reassessed operationally by comparing duplicate slides (n = 412) stained with KMnO4 quenching for 30 versus 60 seconds. FDA microscopy results were similar (P = 0.4) and highly reproducible, with 97% of counts agreeing within +/-1 logarithm. Storage: Smear microscopy slides and aliquots of the sputum from which they were made were stored for 4 weeks. Twice-weekly, paired slides (n = 80) were stained with freshly prepared versus stored FDA and read quantitatively. Storing sputum, microscopy slides or FDA solution at 4°C or room temperature had no effect on FDA microscopy results (all P>0.2). Cost: Material costs for each slide tested by FDA microscopy using reagents purchased locally were USD $0.05 and required the same equipment, time and skills as auramine acid-fast microscopy. We recommend a simple, bio-secure protocol for FDA microscopy that provides sensitive and repeatable results without requiring centrifugation.


Systematic review of robotic liver resection.
Robotic liver resection has emerged as a new modality in the field of minimally invasive surgery. However, the effectiveness of this approach for liver resection is not yet known. A literature survey was performed using specific search phrases in PubMed. Case series that focused on biliary reconstruction were excluded. Characteristics, such as patient demographics, perioperative outcomes, and oncological results for colorectal liver metastasis and hepatocellular carcinoma were analyzed. Nineteen series that described the cases of 217 eligible patients were reviewed. The most commonly performed procedures were wedge resection and segmentectomy. Right hepatectomy was performed in a few specialized centers. The conversion and complication rates were 4.6 and 20.3 %, respectively. The most common reason for conversion was unclear tumor margin. Intra-abdominal fluid collection was the most frequently occurring morbidity. Mean operation time was 200-507 min. Mean intraoperative blood loss was 50-660 mL, with a tendency toward increased blood loss observed in series that included major hepatectomies. Mean postoperative hospital stay was 5.5-11.7 days. The longest mean follow-up time was 36 months for colorectal liver metastasis and 25.1 months in hepatocellular carcinoma. Disease-free survival for mixed malignancies was comparable to that after laparoscopic procedures. Overall survival was not reported. Robotic liver resection is safe and feasible for experienced surgeons with advanced laparoscopic skills. Long-term oncologic outcomes are unclear, but short-term perioperative results seem comparable to those of conventional laparoscopic liver resection.


Comparison of allogeneic transplant outcomes between matched sibling donors and alternative donors in patients over 50 years of age with acute myeloid leukemia: 8/8 allele-matched unrelated donors and unrelated cord blood provide better leukemia-free survival compared with matched sibling donors during non-remission status: MSD vs alternative donors transplant for patients over 50 years of age with AML.
Acute myeloid leukemia (AML) is the most common indication for allogeneic hematopoietic cell transplantation (HCT). The increased availability of alternative donor sources has broadened donor types for older patients without HLA-matched sibling donors (MSD). It is uncertain if an MSD should be the first option for allogeneic HCT in patients with AML over 50 years of age. The objective of this study was to compare survival and other posttransplant outcomes between MSDs, 8/8 allele-matched unrelated donors (MUDs), 7/8 allele-MUDs, unrelated cord blood (UCB), and haploidentical donors for patients with AML over 50 years of age. We conducted a retrospective study to compare outcomes in 5,704 patients with AML over 50 years of age and receiving allogeneic HCT between 2013 and 2021, using either MSD, 8/8 allele-MUD, 7/8 allele-MUD, UCB, or haploidentical donors in Japan. Complete remission (CR) and non-remission at HCT were analyzed separately for all analyses. In total, 3041 patients were CR, and 2663 patients were non-remission at the time of HCT. In multivariate analysis, donor type did not determine overall survival, irrespective of disease status at HCT. Leukemia-free survival (LFS) was significantly better for 8/8 allele-MUD (hazard ratio [HR], 0.77; 95% confidence interval [CI], 0.64 to 0.93; P = 0.005) and UCB (HR, 0.76; 95% CI, 0.65 to 0.88; P = 0.001), but not for 7/8 allele-MUD (HR, 0.97; 95% CI, 0.79 to 1.19; P=0.794), and haploidentical donor (HR, 0.86; 95% CI, 0.70 to 1.05; P=0.146) compared to the MSD group in non-remission status. However, donor type did not determine LFS among CR status. Relapse rates were significantly lower for 8/8 allele-MUD and UCB, whereas non-relapse mortality was higher for UCB compared to the MSD group among both CR and non-remission status. Our registry-based study demonstrated that MSDs do not lead to superior survival compared to alternative donors for patients with AML over 50 years of age. Furthermore, 8/8 allele-MUDs and UCB provide better LFS compared with MSDs during non-remission status. Therefore, MSD is not necessarily the best donor option for allogeneic HCT in this population.


[Precarious situation of obstetric practice in Gabon].
In 1993, 2,008 deliveries were recorded at the Provincial Maternity Hospital at Franceville in Gabon. The frequency of cesarean section was 3%. The perinatal mortality of children born by cesaraean section was high, 213 per thousand. The principal indications for cesarean section were the baby being too large to pass through the pelvis, bicicatricial uterus, breech presentation and toxemia during pregnancy. The maternal mortality rate was 200 per 100,000, similar to the rates of most African countries, and 75% of the women that died had undergone cesarean section. The mortality rate for cesarean section was high (4.9%), so the indications for cesarean section in underdeveloped countries are limited. Malaria was the principal reason for the hospitalization of pregnant women, because it is endemic and is a serious condition for pregnant women. The next most frequent causes of hospitalization were a high risk of premature labor and hyperemesis gravidarum, the frequency of which is high among pregnant African women, particularly those of West Africa. Toxemia in pregnancy was the fourth most important cause of hospitalization. The rate of cesarean section rupture was 2.5 per thousand. Only 20% of these cases involved a cicatricial uterus, with no maternal deaths but a fetal mortality rate of 100%. The frequency of premature birth was 4.23% and the perinatal mortality rate was 48 per thousand, with 37 stillbirths per thousand and an early neonatal mortality rate of 11 per thousand. The perinatal mortality of breech presentations was high (330 per thousand), with 13.9 delivered by cesarean section. These levels are similar to those for other African countries. Maternal health could be improved by introducing several consultations during pregnancy, improving hospital hygiene and making antibiotics more widely available. Fetal survival could be improved by preventing premature births, providing more help with delivery, decreasing the time to intervention and improving neonatal resuscitation techniques.


The blood-stage malaria antigen PfRH5 is susceptible to vaccine-inducible cross-strain neutralizing antibody.
Current vaccine strategies against the asexual blood stage of Plasmodium falciparum are mostly focused on well-studied merozoite antigens that induce immune responses after natural exposure, but have yet to induce robust protection in any clinical trial. Here we compare human-compatible viral-vectored vaccines targeting ten different blood-stage antigens. We show that the full-length P. falciparum reticulocyte-binding protein homologue 5 (PfRH5) is highly susceptible to cross-strain neutralizing vaccine-induced antibodies, out-performing all other antigens delivered by the same vaccine platform. We find that, despite being susceptible to antibody, PfRH5 is unlikely to be under substantial immune selection pressure; there is minimal acquisition of anti-PfRH5 IgG antibodies in malaria-exposed Kenyans. These data challenge the widespread beliefs that any merozoite antigen that is highly susceptible to immune attack would be subject to significant levels of antigenic polymorphism, and that erythrocyte invasion by P. falciparum is a degenerate process involving a series of parallel redundant pathways.


Human performance consequences of stages and levels of automation: an integrated meta-analysis.
We investigated how automation-induced human performance consequences depended on the degree of automation (DOA). Function allocation between human and automation can be represented in terms of the stages and levels taxonomy proposed by Parasuraman, Sheridan, and Wickens. Higher DOAs are achieved both by later stages and higher levels within stages. A meta-analysis based on data of 18 experiments examines the mediating effects of DOA on routine system performance, performance when the automation fails, workload, and situation awareness (SA). The effects of DOA on these measures are summarized by level of statistical significance. We found (a) a clear automation benefit for routine system performance with increasing DOA, (b) a similar but weaker pattern for workload when automation functioned properly, and (c) a negative impact of higher DOA on failure system performance and SA. Most interesting was the finding that negative consequences of automation seem to be most likely when DOA moved across a critical boundary, which was identified between automation supporting information analysis and automation supporting action selection. Results support the proposed cost-benefit trade-off with regard to DOA. It seems that routine performance and workload on one hand, and the potential loss of SA and manual skills on the other hand, directly trade off and that appropriate function allocation can serve only one of the two aspects. Findings contribute to the body of research on adequate function allocation by providing an overall picture through quantitatively combining data from a variety of studies across varying domains.


Adolescents Presenting with Mental Health Crises.
Aims The aim of the study is to examine emergency mental health (MH) presentations and assessments of adolescents (16-18) presenting to a Dublin adult emergency department (ED). Methods Clinical data was collected on all patients over a 12 month period. Results Seventy seven adolescents presented, the majority out of hours (n=58, 75%) and with either self-harm (n=34, 44%) or suicidal ideation (n=28, 36%), where females significantly outnumbered males (89% vs 66%; p=.028). Other presentations included low mood, anxiety and behavioural problems, and following assessment from an adult mental health service team member, 55% (n=39) were given an Axis I psychiatric diagnosis. Almost all adolescents were discharged following assessment (n=68, 96%), the majority being referred on to Child and Adolescent Mental Health Service (CAMHS) (55, 78%). Conclusion Crisis presentations to EDs often occur in adolescents with co-existing psychiatric disorders, and require skilled and therapeutic assessment. Knowledge of appropriate services for onward referral is essential, and highlight the importance of a close collaborative between adult EDs and CAMHS.


Expression Levels of Interferon Regulatory Factor 5 (IRF5) and Related Inflammatory Cytokines Associated with Severity, Prognosis, and Causative Pathogen in Patients with Community-Acquired Pneumonia.
BACKGROUND Community-acquired pneumonia (CAP) is a common disease with significant morbidity and mortality. Interferon regulatory factor 5 (IRF5), which induces type I interferons (IFNs) and cytokines such as interleukin (IL)-6, tumor necrosis factor (TNF)-α, IL-10, and interferon gamma-induced protein (IP)10, is a key transcription factor involved in controlling the expression of proinflammatory cytokines and responses to infection. Here, we carefully investigated the role of IRF5 in regulating immune responses to CAP. MATERIAL AND METHODS QRT-PCR was used to detect the mRNA levels of IRF5, IL-6, IL-10, IP10, TNF-α, and IFN-α in the peripheral blood of 71 CAP patients and 31 healthy controls, as well as in the bronchoalveolar lavage cells of 20 patients with CAP and 23 patients with lung cancer (using samples from the unaffected lung). Flow cytometry was performed to detect the protein level of IRF5, and a CBA flex set was used to detect the levels of these cytokines in the volunteers. RESULTS The expression levels of IRF5 and its related cytokines were significantly increased in CAP patients compared with the controls. Additionally, IRF5, IL-6, IL-10, and IP10 levels were found to be related with the severity of CAP. Furthermore, the levels of IRF5 and IFN-a increased significantly in the early phase of pneumonia caused by influenza virus infection. CONCLUSIONS IRF5 and its related inflammatory cytokines are associated with the severity, prognosis, and causative pathogen of CAP patients. This finding may provide new drug targets for the prevention and treatment of severe pneumonia caused by influenza virus.


Immunity and Protection Provided by Live Modified Vaccines Against Paratyphoid Salmonella in Poultry-An Applied Perspective.
Several serotypes of non-host-specific or paratyphoid Salmonella have been linked with contamination of poultry meat, and eggs, resulting in foodborne outbreaks in humans. Vaccination of poultry against paratyphoid Salmonella is a frequent strategy used to reduce the levels of infection and transmission, which ultimately can lead to lower rates of human infections. Live vaccines have been developed and used in poultry immediately after hatching as a result of their ability to colonize the gut, stimulate a mucosal immune response, induce a competitive inhibitory effect against homologous wild strains, and reduce colonization and excretion of Salmonella. Furthermore, vaccines can competitively exclude some heterologous strains of Salmonella from colonizing the gastrointestinal tract when young poultry are immunologically immature. In addition, various studies have suggested that booster vaccination with live vaccines a few weeks after initial vaccination is essential to increase the level of protection and achieve better cross-protective immunity. Vaccination of breeders, broilers, layers, and turkeys with modified live Salmonella vaccines is a common intervention that has become an important component in poultry companies' multistep prevention programs to meet increasingly demanding customer and regulatory food safety requirements. Both live and inactivated vaccines play a critical role in a comprehensive control program for chicken and turkey breeders and commercial layers. This review examines the response and protection conferred by live modified vaccines against non-host-specific Salmonella that can be considered for the design and implementation of vaccination strategies in poultry.


HIV enteropathy: crypt stem and transit cell hyperproliferation induces villous atrophy in HIV/Microsporidia-infected jejunal mucosa.
The study aim was to analyse the kinetics of stem and transit cells in the crypts of jejunal mucosa infected with HIV and Microsporidia. The size of villi, depth of crypts and proliferative activity of transit and stem cells in jejunal mucosa were measured using morphometric techniques. The surface area/volume ratio (S/V) of jejunal biopsies was estimated under light microscopy using a Weibel graticule. Crypt length was measured by counting enterocytes along the crypt side from the base to the villus junction, and the mean crypt length was calculated. The S/V and crypt lengths of the jejunal mucosa of 21 HIV and Microsporidia-infected test cases were compared with 14 control cases. The labelling index in relation to the crypt cell position of 10 of the test cases was analysed compared with 13 control cases. Differences were found in the S/V and crypt length, and there was a negative correlation between S/V and crypt length in test and control cases combined. Cell labelling indices fell into low and high proliferation groups. There were significant differences in labelling indices between low proliferation test cases and controls, between high proliferation test cases and controls, and between high and low proliferation test cases. Villous atrophy induced by HIV and Microsporidia is attributed to crypt cell hyperplasia and the encroachment of crypt cells onto villi. These infections induce crypt hypertrophy by stimulating cell mitosis predominantly in transit cells but also in stem cells. Increased stem cell proliferation occurs only in high proliferation cases.


Protein synthesis by rice coleoptiles during prolonged anoxia: implications for glycolysis, growth and energy utilization.
Anoxia-tolerant plant tissues synthesize a number of proteins during anoxia, in addition to the 'classical anaerobic proteins' involved in glycolysis and fermentation. The present study used a model system of rice coleoptile tips to elucidate patterns of protein synthesis in this anoxia-tolerant plant tissue. Coleoptile tips 7-11 mm long were excised from intact seedlings exposed to anoxia, or excised from hypoxically pre-treated seedlings and then exposed to anoxia for 72 h. Total proteins or 35S-labelled proteins were extracted, separated using two-dimensional isoelectric focusing/SDS-polyacrylamide gel electrophoresis and analysed using mass spectrometry. The coleoptile tips excised after intact seedlings had been exposed to anoxia for 72 h had a similar proteome to tips that were first excised and then exposed to anoxia. After 72 h anoxia, Bowman-Birk trypsin inhibitors and a glycine-rich RNA-binding protein decreased in abundance, whereas a nucleoside diphosphate kinase and several proteins with unknown functions were strongly enhanced. Using [35S]methionine as label, proteins synthesized at high levels in anoxia, and also in aeration, included a nucleoside diphosphate kinase, a glycine-rich RNA-binding protein, a putative elicitor-inducible protein and a putative actin-depolymerizing factor. Proteins synthesized predominately in anoxia included a pyruvate orthophosphate dikinase (PPDK), alcohol dehydrogenase 1 and 2, fructose 1,6-bisphosphate aldolase and a protein of unknown function. The induction of PPDK in anoxic rice coleoptiles might, in combination with pyruvate kinase (PK), enable operation of a 'substrate cycle' producing PPi from ATP. Production of PPi would (a) direct energy to crucial transport processes across the tonoplast (i.e. the H+-PPiase); (b) be required for sucrose hydrolysis via sucrose synthase; and (c) enable acceleration of glycolysis, via pyrophosphate:fructose 6-phosphate 1-phosphotransferase (PFP) acting in parallel with phosphofructokinase (PFK), thus enhancing ATP production in anoxic rice coleoptiles; ATP production would need to be increased if there was a substantial requirement for PPi.


Migratory hosts can maintain the high-dose/refuge effect in a structured host-parasite system: The case of sea lice and salmon.
Migration can reduce parasite burdens in migratory hosts, but it connects populations and can drive disease dynamics in domestic species. Farmed salmon are infested by sea louse parasites, often carried by migratory wild salmonids, resulting in a costly problem for industry and risk to wild populations when farms amplify louse numbers. Chemical treatment can control lice, but resistance has evolved in many salmon-farming regions. Resistance has, however, been slow to evolve in the north-east Pacific Ocean, where large wild-salmon populations harbour large sea louse populations. Using a mathematical model of host-macroparasite dynamics, we explored the roles of domestic, wild oceanic and connective migratory host populations in maintaining treatment susceptibility in associated sea lice. Our results show that a large wild salmon population, unexposed to direct infestation by lice from farms; high levels of on-farm treatment; and a healthy migratory host population are all critical to slowing or stopping the evolution of treatment resistance. Our results reproduce the "high-dose/refuge effect," from the agricultural literature, with the added requirement of a migratory host population to maintain treatment susceptibility. This work highlights the role that migratory hosts may play in shared wildlife/livestock disease, where evolution can occur in ecological time.


Applications of evidence-based medicine: cranial cruciate ligament injury repair in the dog.
To evaluate the literature reporting surgical interventions pertaining to canine cranial cruciate ligament (CCL) injury using an evidence-based medicine paradigm. Systematic literature review. An on-line bibliographic search through Medline, PubMed, Veterinary Information Network, and Commonwealth Agricultural Bureau Abstracts was performed during August 2004. Two hundred and forty resources of information were identified. Studies were compared and evaluated with regard to study design (retrospective, prospective, randomization), surgical technique, short- and long-term follow-up, and evidence classification. Twenty-eight resources qualified to assist with evidence classification. No class I or class II studies were present, 5 studies were categorized as a class III and 23 studies were categorized as a class IV. Seventeen studies were retrospectively designed and 11 studies were prospectively designed. Proposed results ranged from a wide variety of subjective findings including clinical impression, radiographic analysis, synovial fluid analysis, gross pathology, and histopathology. Objective results, although infrequent, included force plate analysis and cadaveric biomechanical testing. At this time, the application of evidence-based medicine in analyzing the current available evidence suggests that there is not a single surgical procedure that has enough data to recommend that it can consistently return dogs to normal function after CCL injury. The requirement for assessing and categorizing the available evidence becomes increasingly important as more data becomes available and the quality of research improves. An evidence-based medicine paradigm did not provide sufficient evidence favoring 1 surgical technique for management of canine CCL injury.


Impact of clinical response to neoadjuvant endocrine therapy on patient outcomes: a follow-up study of JFMC34-0601 multicentre prospective neoadjuvant endocrine trial.
Neoadjuvant endocrine therapy (NET) has been demonstrated to improve breast-conserving rate and is a widely accepted treatment option for postmenopausal patients with hormone receptor-positive breast cancer. There are few reports on the association of NET response and long-term outcomes. To investigate the prognostic value of clinical response to NET. Long-term outcomes of NET were examined in 107 patients who participated in the multicentre prospective neoadjuvant exemestane study, JFMC34-0601. Patients were treated with 25 mg/day exemestane for 16 weeks followed by an 8-week extension depending on the treatment response. Clinical response included partial response (PR) in 58 patients, stable disease in 41 patients and progressive disease (PD) in 8 patients. Clinical response was significantly associated with disease-free survival (DFS), distant disease-free survival (DDFS) and overall survival (OS) (P<0.0001 for all). Especially, patients with PD showed markedly poor outcomes with median DFS=17.8 months (HR (vs PR): 7.7 (95% CI 1.6 to 33)) and median OS=37.7 months (HR (vs PR): 26.3 (95% CI 2.4 to 655)). Preoperative endocrine prognostic index (PEPI) were associated with DFS and marginally with OS (P=0.022 and 0.066, respectively). PEPI=0 indicated an excellent prognosis with 95% 5-year DFS (95% CI 73 to 99). In the multivariate analysis including T stage, nodal status and Ki67, clinical response was an independent prognostic factor for DFS, DDFS and OS (P=0.032, 0.0007 and 0.020, respectively), whereas PEPI was marginally associated with DFS and OS (P=0.079 and 0.068, respectively). Clinical response to NET showed an independent prognostic value. Patients with PD had markedly poor prognosis, indicating a need of additional therapy. PEPI=0 indicated an excellent prognosis. The integration of clinical response and PEPI would improve decision-making with regard to treatment options for endocrine-responsive breast cancer when these results are validated in a larger clinical trial. UMIN C000000345.


RecA protein of Mycobacterium tuberculosis possesses pH-dependent homologous DNA pairing and strand exchange activities: implications for allele exchange in mycobacteria.
To gain insights into inefficient allele exchange in mycobacteria, we compared homologous pairing and strand exchange reactions promoted by RecA protein of Mycobacterium tuberculosis to those of Escherichia coli RecA protein. The extent of single-stranded binding protein (SSB)-stimulated formation of joint molecules by MtRecA was similar to that of EcRecA over a wide range of pH values. In contrast, strand exchange promoted by MtRecA was inhibited around neutral pH due to the formation of DNA networks. At higher pH, MtRecA was able to overcome this constraint and, consequently, displayed optimal strand exchange activity. Order of addition experiments suggested that SSB, when added after MtRecA, was vital for strand exchange. Significantly, with shorter duplex DNA, MtRecA promoted efficient strand exchange without network formation in a pH-independent fashion. Increase in the length of duplex DNA led to incomplete strand exchange with concomitant rise in the formation of intermediates and networks in a pH-dependent manner. Treatment of purified networks with S1 nuclease liberated linear duplex DNA and products, consistent with a model in which the networks are formed by the invasion of hybrid DNA by the displaced linear single-stranded DNA. Titration of strand exchange reactions with ATP or salt distinguished a condition under which the formation of networks was blocked, but strand exchange was not significantly affected. We discuss how these results relate to inefficient allele exchange in mycobacteria.


[Clinical pattern of tuberculosis in patients with mental disorders in Sverdlovsk region].
The clinical pattern was first studied in 153 new cases of tuberculosis with mental disorders. Most patients were admitted from psychoneurological boarding houses. Prophylactic survey revealed tuberculosis in most patients. There were prevalent infiltrative and focal forms of a specific process. Proper therapy provided benefits in the majority of patients. However every six patients had worsening tuberculosis.


Sleep in pediatric neuromuscular disorders.
Sleep disordered breathing (SDB) is prevalent among children with neuromuscular disorders (NMD). The combination of respiratory muscle weakness, altered drive, and chest wall distortion due to scoliosis make sleep a stressful state in this population. Symptomatology can range from absent to snoring, nocturnal awakenings, morning headaches, and excessive daytime sleepiness. Sequelae of untreated SDB includes cardiovascular effects, metabolic derangements, and neurocognitive concerns which can be compounded by those innate to the NMD. The clinician should have a low threshold for obtaining polysomnography and recognize the nuances of individual disorders due to disproportionately impacted muscle groups such as hypoventilation in ambulating patients from diaphragm weakness. Non-invasive or invasive ventilation are the mainstay of treatment. In this review we explore the diagnosis and treatment of SDB in children with various NMD.


Active dendrites enhance neuronal dynamic range.
Since the first experimental evidences of active conductances in dendrites, most neurons have been shown to exhibit dendritic excitability through the expression of a variety of voltage-gated ion channels. However, despite experimental and theoretical efforts undertaken in the past decades, the role of this excitability for some kind of dendritic computation has remained elusive. Here we show that, owing to very general properties of excitable media, the average output of a model of an active dendritic tree is a highly non-linear function of its afferent rate, attaining extremely large dynamic ranges (above 50 dB). Moreover, the model yields double-sigmoid response functions as experimentally observed in retinal ganglion cells. We claim that enhancement of dynamic range is the primary functional role of active dendritic conductances. We predict that neurons with larger dendritic trees should have larger dynamic range and that blocking of active conductances should lead to a decrease in dynamic range.


Mesotrypsin Has Evolved Four Unique Residues to Cleave Trypsin Inhibitors as Substrates.
Human mesotrypsin is highly homologous to other mammalian trypsins, and yet it is functionally unique in possessing resistance to inhibition by canonical serine protease inhibitors and in cleaving these inhibitors as preferred substrates. Arg-193 and Ser-39 have been identified as contributors to the inhibitor resistance and cleavage capability of mesotrypsin, but it is not known whether these residues fully account for the unusual properties of mesotrypsin. Here, we use human cationic trypsin as a template for engineering a gain of catalytic function, assessing mutants containing mesotrypsin-like mutations for resistance to inhibition by bovine pancreatic trypsin inhibitor (BPTI) and amyloid precursor protein Kunitz protease inhibitor (APPI), and for the ability to hydrolyze these inhibitors as substrates. We find that Arg-193 and Ser-39 are sufficient to confer mesotrypsin-like resistance to inhibition; however, compared with mesotrypsin, the trypsin-Y39S/G193R double mutant remains 10-fold slower at hydrolyzing BPTI and 2.5-fold slower at hydrolyzing APPI. We identify two additional residues in mesotrypsin, Lys-74 and Asp-97, which in concert with Arg-193 and Ser-39 confer the full catalytic capability of mesotrypsin for proteolysis of BPTI and APPI. Novel crystal structures of trypsin mutants in complex with BPTI suggest that these four residues function cooperatively to favor conformational dynamics that assist in dissociation of cleaved inhibitors. Our results reveal that efficient inhibitor cleavage is a complex capability to which at least four spatially separated residues of mesotrypsin contribute. These findings suggest that inhibitor cleavage represents a functional adaptation of mesotrypsin that may have evolved in response to positive selection pressure.


Survival from tumours of the central nervous system in Danish children: Is survival related to family circumstances?
Little is known about social inequalities in childhood cancer survival. We investigated the impact of family circumstances on survival from paediatric central nervous system (CNS) tumours in a nationwide, register-based cohort of Danish children. All children born between 1973 and 2006 and diagnosed with a CNS tumour before the age of 20 years (N = 1,261) were followed until 10 years from diagnosis. Using Cox proportional hazards models, the impact of various family characteristics on overall survival was estimated. Hazard ratios (HRs) for all CNS tumours combined did not show strong associations between survival and any family characteristic. Analyses by CNS tumour subtypes showed reduced survival for children with glioma when living outside of Copenhagen (HR 1.55; CI 1.03; 2.35). For embryonal CNS tumours, the number of full siblings was associated with worse survival (HR for having 3+ siblings 3.60; CI 1.52; 8.53) and a trend of better survival was observed for children with parents of younger age at child's diagnosis and poorer survival of children with parents of older age. Despite free and uniform access to health care services, some family circumstances appear to affect survival from specific CNS tumour types in Danish children. Further research is warranted to gain a more comprehensive understanding of the impact of family factors on childhood cancer survival in other populations and to elaborate underlying mechanisms and pathways of those survival inequalities observed.


Catalyst-proximity protein chemical labelling on affinity beads targeting endogenous lectins.
Magnetic affinity beads functionalized with lactose and ruthenium/dcbpy complexes were developed. Using MAUra, a catalyst-proximity labelling reagent, the catalytic labeling of lactose-binding proteins was achieved with high selectivity on the beads. The first unbiased identification of cellular endogenous lectins bound to lactose (galectin-1 and galectin-3) was achieved with chemical labelling on the affinity beads.


Voluntary Running Suppresses Tumor Growth through Epinephrine- and IL-6-Dependent NK Cell Mobilization and Redistribution.
Regular exercise reduces the risk of cancer and disease recurrence. Yet the mechanisms behind this protection remain to be elucidated. In this study, tumor-bearing mice randomized to voluntary wheel running showed over 60% reduction in tumor incidence and growth across five different tumor models. Microarray analysis revealed training-induced upregulation of pathways associated with immune function. NK cell infiltration was significantly increased in tumors from running mice, whereas depletion of NK cells enhanced tumor growth and blunted the beneficial effects of exercise. Mechanistic analyses showed that NK cells were mobilized by epinephrine, and blockade of β-adrenergic signaling blunted training-dependent tumor inhibition. Moreover, epinephrine induced a selective mobilization of IL-6-sensitive NK cells, and IL-6-blocking antibodies blunted training-induced tumor suppression, intratumoral NK cell infiltration, and NK cell activation. Together, these results link exercise, epinephrine, and IL-6 to NK cell mobilization and redistribution, and ultimately to control of tumor growth.


The Efficacy of Complementary and Alternative Medicine in the Treatment of Female Infertility.
Female infertility is a state of fertility disorder caused by multiple reasons. The incidence of infertility for females has significantly increased due to various factors such as social pressure, late marriage, and late childbirth, and its harm includes heavy economic burden, psychological shadow, and even marriage failure. Conventional solutions, such as hormone therapy, in vitro fertilization (IVF), and embryo transfer, have the limitations of unsatisfied obstetric outcomes and serious adverse events. Currently, complementary and alternative medicine (CAM), as a new treatment for infertility, is gradually challenging the dominant position of traditional therapies in the treatment of infertility. CAM claims that it can adjust and harmonize the state of the female body from a holistic approach to achieve a better therapeutic effect and has been increasingly used by infertile women. Meanwhile, some controversial issues also appeared; that is, some randomized controlled trials (RCTs) confirmed that CAM had no obvious effect on infertility, and the mechanism of its effect could not reach a consensus. To clarify CAM effectiveness, safety, and mechanism, this paper systematically reviewed the literature about its treatment of female infertility collected from PubMed and CNKI databases and mainly introduced acupuncture, moxibustion, and oral Chinese herbal medicine. In addition, we also briefly summarized psychological intervention, biosimilar electrical stimulation, homeopathy, hyperbaric oxygen therapy, etc.


Spatially distinct atrophy is linked to β-amyloid and tau in preclinical Alzheimer disease.
To determine whether an MRI-based Alzheimer disease (AD) signature biomarker can detect tau-related neurodegeneration in preclinical AD, and to assess whether AD signature cortical thinning is associated with cognitive changes in cognitively normal (CN) older individuals. In a large cohort of CN individuals (n = 188), we measured the hippocampal volume and cortical thickness within independently defined AD signature regions. We cross-sectionally assessed the associations between AD signature cortical thinning or hippocampal atrophy with CSF biomarkers of tau (increased tau) and β-amyloid (Aβ) (decreased Aβ42). We also examined the impact of AD signature cortical thinning or other biomarker changes (i.e., hippocampal atrophy, reduced CSF Aβ42, or increased CSF tau) on cognitive performance in CN individuals. Elevated CSF tau was associated with AD signature cortical thinning but not hippocampal atrophy. In contrast, decreased CSF Aβ42 was associated with hippocampal loss but not AD signature cortical thinning. In addition, AD signature cortical thinning was associated with lower visuospatial performance. Reduced CSF Aβ42 was related to poorer performance on episodic memory. Spatially distinct neurodegeneration is associated with Aβ and tau pathology in preclinical AD. Aβ deposition and AD signature cortical atrophy independently affect cognition in CN older individuals.


[Salivary gland choristoma (hamartoma) of the middle ear: a case report].
Middle ear salivary gland choristoma are extremly rare. We report a case, describe the clinical management and review the literature. A 12 year old boy presented with unilateral conductive hearing loss associated with a large inferior retraction pocket on otoscopy. CT scan demonstrated a large mass in the left middle ear cavity. The incus was absent and the stapes was partially eroded. Middle ear exploration demonstrated an 8 mm yellow/red mass in the region of the fallopian canal. This mass was comptly removed and histopathology confirmed salivary gland choristoma. These lesions result from an abnormal development of the second branchial arch. It is important to consider these lesions as part of the differential diagnosis for any unilateral hearing loss associated with a middle ear mass in children.


Evolution of primate chromosomes.
Human and higher primate chromosomes have been compared by general and regional banding methods, including hybridization in situ. The general banding patterns of the chromosomes of gorilla, chimpanzee, and orangutan, but not gibbon, are similar to those of the human. Preliminary results show that chromosomes with similar banding patterns in different species often carry the same genes. Repetitious DNA's have undergone changes in structure and distribution which are reflected in changes in the regional banding patterns. These studies confirm that the evolutionary distance between the gibbon and the orangutan is relatively great compared to the distance between the orangutan and the other great apes, and suggest that man is more closely related to the gorilla than to the chimpanzee.