Functional anatomy and volume-pressure characteristics of immature lungs.
The mechanical behavior of immature rabbit fetal lungs in situ was assessed by air and saline volume-pressure diagrams. All lungs were in their natural fetal state, i.e., filled with fetal pulmonary fluid, prior to inflation. Anatomic correlates were determined by continuous stereomicroscopic monitoring of the lungs. We found the following to be characteristic of immature lungs: (1) Tissue retractive forces are similar to adults. (2) Fetal lungs are not 'plastic' above functional residual capacity. (3) Initial aeration is by 'axial filling' in which airways are distended several times their resting size. (4) Invariably, peripheral rather than central saccules are the first to be aerated and saccules are recruited by both pressure- and time-dependent processes. (5) Pressure-dependence is related to surface forces and terminal orifice size, while time-dependent processes include orifice enlargement, liquid flow through terminal conduits, and the formation of very short-lived, labile bubbles. (6) 'Opening pressure' inflection in the VP diagram is not coincidental with, but follows the onset of saccular aeration. (7) Negative compliance at the onset of deflation is due to saccular enlargement and recruitment. (8) Hysteresis is due to tissue conformational characteristics at high pressures and air entrapment at low pressures. (9) Surface tension cannot be measured reliably from the saline and air VP diagrams.


Kidney transplantation from a living donor with renal artery fibromuscular dysplasia: A case report on arterial grafting of the donor renal artery.
Renal artery fibromuscular dysplasia is generally considered a contraindication of kidney transplantation, since fibromuscular dysplasia occasionally induces hypertension or renal insufficiency in the recipient and/or donor. To date, limited information remains available with respect to whether kidneys with renal arterial fibromuscular dysplasia can be successfully transplanted. A 53-year-old potential donor was diagnosed with fibromuscular dysplasia of the right renal artery. Laparoscopic right nephrectomy was performed, and the affected portion was resected and reconstructed using the harvested internal iliac artery. Transplantation was successful and the serum creatinine level was <2 mg/dL for 3 years after surgery. If reconstruction of the diseased artery could be safely performed, transplantation using a kidney from a donor with renal artery fibromuscular dysplasia may be considered.


[Metabolic products of microorganisms. 175. Tetracenomycin C (author's transl)].
Streptomyces glaucescens, strain Tü 49 = ETH 22794, produces hydroxystreptomycin as well as the tetracenomycins, a mixture of several lipophilic antibiotics. The main component and the most active one is tetracenomycin C. Tetracenomycin C has a molecular formula C23H20O11 and is chemically related to tetracyclines and anthracyclinones. The pale yellow antibiotic is active against some gram-positive bacteria, especially against streptomycetes. Gram-negative bacteria and fungi are not inhibited. In considering the differences of biological activity and the functional groups of the molecule, tetracenomycin C is not a member of the tetracycline or anthracyclinone group of antibiotics.


Assessment of the potential of progenitor stem cells extracted from human peripheral blood for seeding a novel vascular graft material.
A novel nanocomposite has recently been developed based on polyhedral oligomeric silsesquioxane attached by direct reaction onto a urethane segment, as a potential vascular graft material; its trade name is UCL-Nano. The UCL-Nano has been demonstrated to have similar viscoelastic properties to the walls of a natural artery, to be resistant to degradation and to be able to sustain endothelial cell seeding. Human peripheral blood contains both circulating endothelial cells and endothelial progenitor cells, which may be suitable for conduit seeding. The aim of this study was to develop a system with the potential to deliver an endothelial cell-seeded bypass graft in a realistic time frame. Endothelial progenitor cells and circulating endothelial cells were isolated from human peripheral blood and were characterized by fluorescent-activated cell sorting, reverse transcriptase-polymerase chain reaction and immunohistochemistry. Isolated cells were seeded on nanocomposite and were maintained in culture for 35 days. The UCL-Nano was successfully seeded with cells and a confluent cell layer was achieved after 14-day culture. Cells remained viable and confluent on the nanocomposite for 35 days. In conclusion, these results suggest that this process has potential both for a realistic and achievable two-stage seeding process for vascular bypass grafts and for the potential development of a device, with the aim of achieving in situ seeding once implanted.


Spiritual Well-being May Reduce the Negative Impacts of Cancer Symptoms on the Quality of Life and the Desire for Hastened Death in Terminally Ill Cancer Patients.
Spirituality is a central component of the well-being of terminally ill cancer patients. The aim of this study was to examine the mediating or moderating role of spiritual well-being in reducing the impact of cancer-related symptoms on quality of life and the desire for hastened death in terminally ill cancer patients. Eighty-five terminally ill cancer patients were assessed using the Taiwanese version of the M. D. Anderson Symptom Inventory, the Functional Assessment of Cancer Therapy-General, the Functional Assessment of Chronic Illness Therapy-Spiritual Well-being, the Beck Hopelessness Scale, and the Schedule of Attitudes Toward Hastened Death. Spiritual well-being was significantly negatively correlated with symptom severity (r = -0.46, P < .01). Symptom severity negatively correlated with quality of life (r = -0.54) and positively correlated with hopelessness (r = 0.51, P < .01) and the desire for hastened death (r = 0.61, P < .01). Spiritual well-being was a partial mediator and moderator between symptom severity and quality of life. Spiritual well-being was a partial mediator between symptom severity and the desire for hastened death. The meaning subscale of spiritual well-being was a more significant predictor of the desire for hastened death and quality of life than the faith subscale was. Spiritual well-being may reduce the negative impacts of cancer on quality of life and the desire for hastened death. Appropriate spiritual care may reduce the negative impact of severe cancer symptoms on quality of life and the desire for hastened death in terminally ill cancer patients.


Zero-valent iron supported on expanded graphite from spent lithium-ion battery anodes and ferric chloride for the degradation of 4-chlorophenol in water.
Zero-valent iron supported with expanded graphite (ZVI/EG) were successfully prepared from ferric chloride and the graphite of spent lithium-ion battery (LIB) using carbothermic reduction as a new approach for recycling spent LIB. ZVI/EG composites synthesized with different ZVI mass ratios were used as catalysts for the 4-chlorophenol (4-CP) removal from water by heterogeneous Fenton reactions. ZVI/EG composites showed a BET specific surface area of 11.295 m2 g-1. ZVI/EG synthesized from expandable graphite and ferric chloride with mass ratio of 2:1 (ZVI/EG-2) showed the highest removal percentage of 4-CP, being 97% in 1 h. The degradation rate fitted to a pseudo first-order model better, and reached 0.0527 min-1 for ZVI/EG-2. Moreover, ZVI/EG-2 showed high reactivity for 4-CP removal even in the sixth reuse cycle, being 82%. Hydroquinone and 4-chlorocatechol were identified as the intermediate products of 4-CP degradation. Increasing the ZVI/EG-2 dosage can enhance the 4-CP removal percentage through offering more reactive sites and Fe2+ ions. Acidic pH values favorited the 4-CP removal due to the high H+ concentrations, while Alkaline pH value inhabited the 4-CP removal. A higher temperature increased the rate of •OH formation and enhanced the 4-CP removal percentage. At a fixed dosage of the ZVI/EG-2, the ratio of available reactive sites was less at higher initial concentrations. These results prove the possibility of synthesizing high active and stable ZVI/EG catalysts using graphite from spent LIB and ferric chloride. These catalysts show promising prospective for the 4-CP removal in water, with comparable activities to others previously reported.


Preemptive Pharmacogenomic Testing for Precision Medicine: A Comprehensive Analysis of Five Actionable Pharmacogenomic Genes Using Next-Generation DNA Sequencing and a Customized CYP2D6 Genotyping Cascade.
Significant barriers, such as lack of professional guidelines, specialized training for interpretation of pharmacogenomics (PGx) data, and insufficient evidence to support clinical utility, prevent preemptive PGx testing from being widely clinically implemented. The current study, as a pilot project for the Right Drug, Right Dose, Right Time-Using Genomic Data to Individualize Treatment Protocol, was designed to evaluate the impact of preemptive PGx and to optimize the workflow in the clinic setting. We used an 84-gene next-generation sequencing panel that included SLCO1B1, CYP2C19, CYP2C9, and VKORC1 together with a custom-designed CYP2D6 testing cascade to genotype the 1013 subjects in laboratories approved by the Clinical Laboratory Improvement Act. Actionable PGx variants were placed in patient's electronic medical records where integrated clinical decision support rules alert providers when a relevant medication is ordered. The fraction of this cohort carrying actionable PGx variant(s) in individual genes ranged from 30% (SLCO1B1) to 79% (CYP2D6). When considering all five genes together, 99% of the subjects carried an actionable PGx variant(s) in at least one gene. Our study provides evidence in favor of preemptive PGx testing by identifying the risk of a variant being present in the population we studied.


Review of ultrasound appearance in inflammatory breast cancer: A pictorial essay.
Inflammatory breast cancer (IBC) is a rare malignancy accounting for 1-2% of breast cancers. It has an aggressive clinical presentation and poor prognosis. The sonographic findings in 41 patients with a clinical diagnosis of IBC and biopsy-proven breast malignancy are presented in this study. The most common finding was the presence of skin thickening (92%). Multiple small anechoic spaces within the dermis, correlating with the presence of dermal lymphatic invasion by tumour emboli on histopathology were noted in approximately one-third of cases. Other sonographic findings included single or multiple masses, parenchymal oedema, axillary lymphadenopathy, echogenic foci consistent with microcalcifications and increased vascularity.


Consultation within the nephroblastoma trial SIOP 2001/GPOH as part of the workload in the trial office.
More than 90% of children with cancer are treated in prospective clinical trials and studies in Germany. Consultations are part of the daily work in every study centre. Nevertheless little is known about the kind of requests, the time needed to handle these, and the effect on outcome due to an optimized treatment. 763 consultations were carried out in 257 patients between the 1st of January 2003 and the 31st of December 2005. 237 of these patients were enrolled in the nephroblastoma trials SIOP 93-01/GPOH (33) and SIOP 2001/GPOH. 20 patients were not registered in any trial at the time of consultation. 61% of all newly diagnosed patients had a consultation by the trial centre during the three year period. The number of consultations per patient was higher in non-university hospitals compared to university hospitals. The mean duration for a consultation was 27 min with a standard deviation of 53.5 min. Most of the requests were related to chemotherapy, 36% to the general management of patients and 15% of all consultations concerned relapsed patients. A highly significant improved 5 year overall survival rate was found for relapsed patients with consultation (65 vs. 10%). This difference may be partly explained by other risk factors for relapse. Trial centres are competence centres for a specific disease. Consultations are an important task and help to increase the quality of care for patients enrolled in clinical trials and studies. For consultation purposes about 25% of a person month was needed for every 100 new patients enrolled in the SIOP 2001/GPOH trial and study. We estimate this effort to be comparable to other studies.


Antibiotics Are Recommended, for the Urgent Management of Pulpal- and Periapical-Related Dental Pain and Intraoral Swelling, Only When There Is Systematic Involvement.
Evidence-based clinical practice guideline on antibiotic use for the urgent management of pulpal- and periapical-related dental pain and intraoral swelling: A report from the American Dental Association. Lockhart PB, Tampi MP, Abt E, et al. J Am Dent Assoc 2019;150(11):906-921.e12. The American Dental Association. Systematic review with meta-analysis of data.


Prevalence of moderately increased albuminuria among individuals with normal HbA1c level but impaired glucose tolerance: Results from the LIFE-Adult-Study.
Diabetes screening strategies using glycated haemoglobin (HbA1c) as first-instance diagnostic parameter may cause failure to detect individuals with abnormal glucose regulation and possible signs of microvascular complications despite "rule-out" HbA1c levels. This cross-sectional study examined the diagnostic performance of HbA1c in relation to fasting and two-hour postload plasma glucose (FPG/2 h-PG), and investigated whether individuals with normal HbA1c but abnormal FPG/2 h-PG have a higher prevalence of moderately increased albuminuria as possible sign of early stage kidney damage. A total of 2695 individuals (age 40-79 years, 48% men) without prior diagnosis of diabetes and complete measurement of HbA1c, FPG, 2 h-PG and urine albumin-creatinine ratio (UACR) were taken from a large population-based epidemiological study in the City of Leipzig, Germany. A total of 2439 individuals (90.5%, 95% CI: 89.4-91.6) had normal HbA1c levels, <39 mmol/mol (<5.7%), while 234 (8.7%, 95% CI: 7.7-9.8) had prediabetes, HbA1c ≥39 and <48 mmol/mol (≥5.7 and <6.5%), and 22 (0.8%, 95% CI: 0.5-1.2) had diabetes, HbA1c ≥48 mmol/mol (≥6.5%), according to HbA1c. Among individuals with normal HbA1c, 35.6% (95% CI: 33.7-37.5) had impaired fasting glucose or impaired glucose tolerance and 1.8% (95% CI: 1.4-2.4) had diabetes according to FPG/2 h-PG. Individuals with normal HbA1c but prediabetic or diabetic FPG/2 h-PG had a significantly higher prevalence of moderately increased albuminuria (9.4%, 95% CI: 7.6-11.5 and 13.3%, 95% CI: 5.8-25.4, respectively) than individuals with normal HbA1c and normal FPG/2 h-PG (3.9%, 95% CI: 3.0-5.0). The prevalence of prediabetes according to FPG/2 h-PG among individuals with normal HbA1c is considerably high, and the prevalence of moderately increased albuminuria in this group is significantly elevated. Risk factors for diabetes such as age, gender and BMI may help to better identify this at-risk group.


[Images in cardiology after clinical observation - aortic dissection in Marfan syndrome].
Stanford type A aortic dissection is a rare phenomenon with high short-term mortality and clinical manifestations that can make differential diagnosis a lengthy process requiring several diagnostic examinations. Based on a case report, the aim is to highlight the importance of physical examination in the initial management of these patients and of rapid access to a surgical center. A brief review follows on the diagnosis and treatment of ascending aortic dissection, and its specific nature in Marfan syndrome. A 33-year-old man was admitted to the emergency department of a district hospital with chest and back pain associated with vomiting, 20 hours after symptom onset. Initial physical examination revealed an aortic systolic murmur and musculoskeletal morphological abnormalities compatible with Marfan syndrome. Given suspected aortic dissection, a transthoracic echocardiogram was immediately performed, which showed an extensive intimal flap originating at the sinotubular junction. He was transferred to the cardiothoracic surgery department of a referral hospital where he was treated by a Bentall procedure. In this case, careful physical examination during initial assessment raised the suspicion that this patient was in a high-risk group for aortic dissection, thus avoiding unnecessary and lengthy exams. This diagnosis requires emergent surgical treatment, and so direct contact in real time between those making in the diagnosis and the surgeon is essential, as well as protocols governing immediate access to a surgical center.


Addiction and Chronic Pain: Training Addiction Psychiatrists.
Addiction psychiatrists are increasingly asked to address chronic pain in patients with addiction. Because of historic "divisions of labor" between physicians who manage pain and addiction psychiatrists who manage addiction, limited guidance exists for preparing addiction psychiatry trainees to address this comorbidity. A 1-h focus group composed of five geographically well-distributed addiction psychiatry fellowship directors/faculty was conducted to explore existing curricula, identify themes, and build consensus regarding educational goals for addiction psychiatry fellows in the area of chronic pain management. Discussion resulted in five broad categories of themes involving perceptions of the importance of chronic pain training for addiction psychiatrists; barriers to curriculum development (one notably being that the addiction psychiatrist's role in managing chronic pain is poorly articulated); facilitators to such development; and potential curricular content and roles of addiction psychiatrists in relation to chronic pain training. Educators in addiction psychiatry should clarify their role in the management of chronic pain and prioritize training in this area.


Lysosome-mitochondria-mediated apoptosis specifically evoked in cancer cells induced by gold nanorods.
The main aim of this article is to explain the apoptosis mechanisms of cancer cells specifically triggered by gold nanorods (GNRs). GNRs were synthesized and optimized, the lysosome damage, cathepsin D, mitochondrial membrane potential, caspase-9, cleaved caspase-9, caspase-3 and intracellular GNRs location related to apoptosis was systematically evaluated. GNRs specifically induce cancer cell apoptosis while posing a negligible impact on normal cells. After incubation with GNRs, the lysosomal permeability in cancer cells as indicated by cathepsin D was markedly higher than that in normal cells and resulted in an obvious decrease in mitochondrial membrane potential. Western blot analysis further confirmed that apoptosis occurred through caspase-9 and caspase-3 activation following mitochondrial damage. Transmission electron microscope images showed that GNRs did not appear in most of the damaged mitochondria but mainly accumulated in lysosomes. These findings indicated that GNR-induced apoptosis specifically in cancer cells by affecting lysosomes and mitochondria.


Early outcome prediction for out-of-hospital cardiac arrest with initial shockable rhythm using machine learning models.
Early outcome prediction for out-of-hospital cardiac arrest with initial shockable rhythm is useful in selecting the choice of resuscitative treatment by clinicians. This study aimed to develop and validate a machine learning-based outcome prediction model for out-of-hospital cardiac arrest with initial shockable rhythm, which can be used on patient's arrival at the hospital. Data were obtained from a nationwide out-of-hospital cardiac arrest registry in Japan. Of 43,350 out-of-hospital cardiac arrest patients with initial shockable rhythm registered between 2013 and 2017, patients aged <18 years and those with cardiac arrest caused by external factors were excluded. Subjects were classified into training (n = 23,668, 2013-2016 data) and test (n = 6381, data from 2017) sets for validation. Only 19 prehospital variables were used for the outcome prediction. The primary outcome was death at 1 month or survival with poor neurological function (cerebral performance category 3-5; "poor" outcome). Several machine learning models, including those based on logistic regression, support vector machine, random forest, and multilayer perceptron classifiers were compared. In validation analyses, all machine learning models performed satisfactorily with area under the receiver operating characteristic curve values of 0.882 [95% confidence interval [CI]: 0.869-0.894] for logistic regression, 0.866 [95% CI: 0.853-0.879] for support vector machine, 0.877 [95% CI: 0.865-0.890] for random forest, and 0.888 [95% CI: 0.876-0.900] for multilayer perceptron classifiers. A favourable machine learning-based prognostic model available to use on patient arrival at the hospital was developed for out-of-hospital cardiac arrest with initial shockable rhythm.


Childhood of a phoenix: modern biology in Eastern and South-Eastern Europe.
With the expanding unification of Europe, the face of European science is changing. For some countries these changes are more pronounced than for others. Here, we survey the present state of science, most notably molecular biology research, in Eastern and South-Eastern European countries. We focus on the strategies these countries are taking in their quest for scientific excellence, discuss some of the acute challenges they face and explore several success stories in the making.


NADP-malate dehydrogenase from leaves of Zea mays: purification and physical, chemical, and kinetic properties.
NADP-malate dehydrogenase (NADP-MDH) from leaves of Zea mays has been purified and has a specific activity of 600-1000 mumol/min/mg protein. The native, inactive form of the enzyme is an 87.4-kDa, dimeric protein with a sedimentation coefficient of 5.5 S and a Stokes' radius of 3.62 nm. Isofocus analysis reveals the native enzyme preparation to contain two proteins of pI 4.88 and 4.90. The uv-visible absorbance spectrum reveals no chromophores on the protein. The inactive form of the enzyme contains three thiols and three disulfides per subunit. 2-Mercaptoethanol can reduce two of the three subunit disulfides without concomitant activation of the enzyme. Treating the enzyme with dithiothreitol reduces all three subunit disulfides and fully activates the enzyme. These results show that NADP-MDH activation is dependent on the reduction of a critical disulfide bond. The enzyme can use both NADPH and NADH for oxaloacetate (OAA) reduction and NADP and NAD for malate oxidation at the following measured specific activities (eu/mg protein) at pH 8.5 in Tris buffer: NADPH plus OAA (690), NADH plus OAA (260), NADP plus malate (82), and NAD plus malate (37). These activities vary as a function of pH and buffer composition. Km values for the substrate pairs are NADPH (24 microM) plus OAA (56 microM); NADH (0.83 mM) plus OAA (61 microM); NADP (73 microM) plus malate (32 mM); and NAD (0.80 mM) plus malate (29 mM). The enzyme shows allosteric kinetics for NADP with a Hill number of 1.56. The enzyme is substrate-inhibited by malate for both NADP- and NAD-dependent activities.


Influence of plasma triglycerides on lipoprotein patterns in normal subjects and in patients with coronary artery disease.
This study examined the correlation of plasma triglyceride levels with concentrations of intermediate, low and high density lipoproteins (IDL, LDL, and HDL, respectively) and to particle sizes of LDL in 93 normal men and 106 men with coronary artery disease. Plasma triglyceride concentrations were in the normal range for all persons in both groups. Analysis of lipoproteins of density less than 1.063 g/ml was carried out by analytical ultracentrifugation. The analytical pattern gave the peak Sf for LDL as well as an indication of heterogeneity of particle sizes in the density range of LDL. In both normal subjects and patients with coronary artery disease, a positive correlation was found between peak Sf for LDL and concentrations of plasma triglycerides. Plasma triglyceride levels also were correlated positively with concentrations of Sf 20 to 60 lipoproteins and total IDL mass, and inversely with HDL cholesterol levels. Furthermore, the value for peak Sf for LDL correlated inversely with the IDL mass concentration and IDL/LDL mass ratio, and positively with the HDL cholesterol levels. The results indicate that the lipoprotein pattern, including lipoprotein concentrations and particle sizes, is sensitive to concentrations of plasma triglycerides even when the latter are within the normal range.


Educational Overview of the Concept and Application of Computer Vision in Arthroplasty.
Image data has grown exponentially as systems have increased their ability to collect and store it. Unfortunately, there are limits to human resources both in time and knowledge to fully interpret and manage that data. Computer Vision (CV) has grown in popularity as a discipline for better understanding visual data. Computer Vision has become a powerful tool for imaging analytics in orthopedic surgery, allowing computers to evaluate large volumes of image data with greater nuance than previously possible. Nevertheless, even with the growing number of uses in medicine, literature on the fundamentals of CV and its implementation is mainly oriented toward computer scientists rather than clinicians, rendering CV unapproachable for most orthopedic surgeons as a tool for clinical practice and research. The purpose of this article is to summarize and review the fundamental concepts of CV application for the orthopedic surgeon and musculoskeletal researcher.


Restoration and recovery of hurricane-damaged mangroves using the knickpoint retreat effect and tides as dredging tools.
In 2001, a hurricane moved a large sand dune, blocking the sole outlet channel of a mangrove. In the absence of daily tidal flow, the two ponds containing the mangrove vegetation evaporated, the secondary drainage channels were lost, and a salt crust formed on the bed of the ponds. The mangrove lost most of its trees and the remaining suffered from osmotic shock that led to defoliation. Restoration involved creating a knickpoint retreat (waterfall retreat effect) and tidal flow as a dredging mechanism to restore the outlet and form secondary channels in the ponds. During a very low tide, we deepened the mouth of the outlet channel by 1 m below high tide level to form a small waterfall when high tides receded. During successive tides, this one-step knickpoint deteriorated and formed a series of low rapids. With a steep gradient, the rapids retreated upstream into the ponds, first reopening the outlet channel and then carving new secondary channels in the pond mud flat. The excavation process of the outlet channel was repeated three times and was sufficient to effectively improve the hydrology of the entire pond system; allowing adequate flooding and draining of the mangrove ponds. Hydrology analysis tested by the Engelund-Hansen sediment transport formula established that the output of sediment from the ecosystem is greater than the input of sand into the mangroves. This is keeping the main channel continuously open. After eight years, tidal flow continues to keep the channels open; the salt crust has disappeared; the trees have recovered, and a large area of new vegetation has emerged.


Highly sensitive analysis of substituted aniline compounds in water samples by using oxidized multiwalled carbon nanotubes as an in-tube solid-phase microextraction medium.
An automated on-line method for the determination of the substituted aniline compounds was developed using in-tube solid-phase microextraction coupling to high-performance liquid chromatography (HPLC). In this work, oxidized multiwalled carbon nanotubes (MWCNTs-COOH) coated on the outer surface of the fused-silica tube and inserted in the polyether ether ketone (PEEK) tubing, which was fixed directly on the six-port injection valve to substitute for the sample loop. The extraction procedure was performed by a constant flow pump frequently driving the sample solution through the PEEK tubing and the analytes were adsorbed onto MWCNTs-COOH materials when the six-port valve set to load position. After extraction, the valve switched to inject position and the extracted analytes were desorbed by mobile phase in dynamic mode. High extraction capacity was achieved for the investigated analytes and great improvement of the limits of detection was obtained in comparison with other methods. The calibration plots were linear (r(2)> or =0.9949) over the concentration range of 1.04-104ngmL(-1) for 4-nitroaniline, 1.02-102ngmL(-1) for 2-nitroaniline, 1.68-168ngmL(-1) for 2-chloroaniline and 1.09-109ngmL(-1) for 2,4-dichloroaniline. The detection limit ranged from 0.04ngmL(-1) to 0.13ngmL(-1) (at S/N=3). The possibility of applying the established method to water samples analysis was also studied.


Gestational diabetes mellitus and the role of intercurrent type 2 diabetes on long-term risk of cardiovascular events.
Recent studies have shown that gestational diabetes mellitus (GDM) is associated with an increased risk for cardiovascular disease. GDM has also been shown to be a risk factor for type 2 diabetes (T2DM) after pregnancy. However, there is limited evidence regarding the role of intercurrent T2DM on the relationship between GDM and future CVD. Thus, we investigated the risks of incident cardiovascular events among women with GDM during pregnancy compared to women without GDM and whether the increased CVD risk is dependent on intercurrent development of T2DM. We conducted a population-based retrospective cohort study using the Korean National Health Insurance Service claims database. Outcomes were the first occurrence of any CVD (myocardial infarction, treatment with coronary revascularization, heart failure, and cerebrovascular disease). Cox proportional hazard models were used to assess the association between GDM and incident CVD events, using landmark analysis at 4 years. A total of 1,500,168 parous women were included in the analysis, of which 159,066 (10.60%) had GDM. At a median follow-up of 12.8 years, 13,222 incident cases of total CVD were observed. Multivariable-adjusted hazard ratio for total CVD among women with prior GDM, compared with those without GDM, was 1.08 (95% CI 1.02-1.14). Further classifying GDM by progression to T2DM in relation to total CVD risk indicated a positive association for GDM with progression to T2DM vs no GDM or T2DM (HR 1.74; 95% CI 1.40-2.15), and no statistically significant association for GDM only (HR 1.06; 95% CI 1.00-1.12). GDM with subsequent progression to T2DM were linked with an increased risk of cardiovascular diseases. These findings highlight the need for more vigilant postpartum screening for diabetes and the implementation of diabetes interventions in women with a history of GDM to reduce future CVD risk.


Factors influencing the development of periventricular lucencies in patients with raised intracranial pressure.
Sixty patients with raised intracranial pressure and lowered attenuation areas around the lateral ventricles ('periventricular lucency', PVL) on CT scanning were reviewed, and compared with a control group of 90 similar patients who did not have PVL. It was confirmed that PVL tends to occur in patients with acute or subacute obstructive hydrocephalus due to a tumour, and is more common in the presence of papilloedema and/or a decreased level of consciousness. Patients with very dilated lateral ventricles did not in general have PVL, but it was frequently seen in association with diastasis of the sutures. Twelve patients with PVL had no other clinical or radiological indication of raised intracranial pressure. Comparison with the control cases did not reveal any reason as to why some patients should develop PVL while others did not.


Technology for mobility in SCI 10 years from now.
To identify technological advances and that are likely to have a great impact on the quality of life and participation in individuals with spinal cord injury (SCI). In this paper we use the International Classification of Function to frame a discussion on how technology is likely to impact SCI in 10 years. In addition, we discuss the implication of technological advances on future research. Although technology advances are exciting, a large challenge for the research community will be how to effectively apply and deploy this technology. Advances occurring in the next 10 years that reduce cost of technology may be more important to the population with SCI than brand new technologies. Social context is everything. As a research community we must advocate for better systems of care. Advocating now for better care will lead to a world in 2020 that is ready to adopt new technologies that are truly transformative.


Cellular neurothekeoma of the upper lip in an infant.
Cellular neurothekeoma is an uncommon benign skin neoplasm and also a variant of neurothekeoma. Cellular neurothekeomas usually occur in the skin of the upper trunk, head, or neck of children and young adults; however, they rarely occur in infants or involve the lip. A 6-month-old male infant was incidentally found to have a tumor in the upper lip. The tumor was elastic, nontender, and movable, and the overlying mucosa and skin were normal without discoloration. The tumor was excised from the mucosal side of the upper lip, and a pathological examination revealed cellular neurothekeoma. Cellular neurothekeoma in the lip of an infant without overlying skin discoloration might delay the diagnosis and lead to wrong preoperative diagnosis. No similar case has been reported in the literature.


Intra coronary freshly isolated bone marrow cells transplantation improve cardiac function in patients with ischemic heart disease.
Autologous bone marrow cell transplantation (BMCs-Tx) is a promising novel option for treatment of cardiovascular disease. In this study we analyzed whether intracoronary autologous freshly isolated BMCs-Tx have beneficial effects on cardiac function in patients with ischemic heart disease (IHD). In this prospective nonrandomized study we treated 12 patients with IHD by freshly isolated BMCs-Tx by use of point of care system and compared them with a representative 12 control group without cell therapy. Global ejection fraction (EF) and infarct size area were determined by left ventriculography.Intracoronary transplantation of autologous freshly isolated BMCs led to a significant reduction of infarct size (p < 0.001) and an increase of global EF (p = 0.003) as well as infarct wall movement velocity (p < 0.001) after 6 months follow-up compared to control group. In control group there were no significant differences of global EF, infarct size and infarct wall movement velocity between baseline and 6 months after coronary angiography. Furthermore, we found significant decrease in New York Heart Association (NYHA) as well as significant decrease of B-type natriuretic peptide (BNP) level 6 months after intracoronary cell therapy (p < 0.001), whereas there were no significant differences in control group 6 months after coronary angiography. These results demonstrate that intracoronary transplantation of autologous freshly isolated BMCs by use of point of care system is safe and may lead to improvement of cardiac function in patients with IHD. ISRCTN54510226.


Change of peripapillary retinal nerve fiber layer and choroidal thickness during 4-year myopic progress: Boramae Myopia Cohort Study Report 4.
To investigate the longitudinal changes of peripapillary retinal nerve fibre layer (RNFL) and choroidal thickness during myopic axial elongation. Peripapillary RNFL and choroidal thickness were prospectively evaluated by spectral-domain optical coherence tomography (SD-OCT) in 46 eyes of 23 myopic children over the course of 4 years. Using serial OCT images acquired based on a fixed scan circle in the glaucoma progression analysis mode, general and sectoral RNFL thicknesses were acquired at the same position and the angular location of the peak was measured. The peripapillary choroidal thickness likewise was measured at eight positions in serial OCT images. The mean age at the baseline was 9.6±1.7 years. The mean axial length increased from 24.80±1.28 mm to 25.64±1.35 mm. The global peripapillary RNFL thickness was 98.54±12.06 µm at baseline. The global and sectoral RNFL thicknesses did not change during the 4 years. The angular location of RNFL peaks was also stable and was located in the superotemporal (64.18±10.85°) and inferotemporal (293.98±11.62°) sectors. The global peripapillary choroidal thickness was 145.40±28.67 µm at the baseline. The global and sectoral choroidal thicknesses did not change during the 4 years. The peripapillary RNFL and choroidal thicknesses as well as the locations of the RNFL peaks had been preserved, during the 4-year follow-up on myopic children, when traced and measured from the same location.


Frequency of administration of recombinant human erythropoietin for anaemia of end-stage renal disease in dialysis patients.
The benefits of recombinant human erythropoietin (rHuEPO) administration in dialysis patients have been demonstrated, however the optimal frequency regimen have yet to be established. To assess the effects of different frequency regimens of rHuEPO administration in dialysis patients on anaemia correction, quality of life and optimal use. We searched 13 electronic databases (1980 to May 2001) the internet (August 1997), handsearched Kidney International (1983 to May 1997), contacted known investigators, biomedical companies, and screened reference lists of relevant articles. Most recent search: The Cochrane Renal Group's specialised register (June 2004) and The Cochrane Library (Issue 3, 2004). Randomised controlled trials (RCTs) or quasi-RCTs comparing different frequencies of rHuEPO administration in dialysis patients. We compared haemodialysis and CAPD patients and subcutaneous and intravenous administration. Quality assessment was performed by two assessors. Data were abstracted by a single author onto a standard form, and a sample was checked by another author. Results were expressed as relative risk (RR) or weighted mean difference (WMD) with 95% confidence intervals (CI). Eleven studies (719 patients) were included. There was no significant difference in maintaining target haemoglobin for once versus twice weekly administration (one study, 20 patients: RR 1.00, 95% CI 0.42 to 2.40) or mean haemoglobin after 12 weeks of therapy between haemodialysis and CAPD patients (two studies: WMD -0.21 g/dL, 95% CI -0.98 to 0.56) At the end of study for once versus thrice weekly administration (three studies: SMD -0.31, 95% CI -0.67 to 0.06) and at the end of maintenance phase (one study: WMD -0.2 g/dL, 95% CI -0.65 to 0.25) there was no significant difference. More rHuEPO was required by haemodialysis patients receiving once weekly versus twice weekly doses (WMD 12.0 U/kg, 95% CI 0.24 to 23.76). No difference was found for CAPD patients alone or combined (WMD 4.38 U/kg, 95% CI -11.28 to 20.04). Once versus thrice weekly administration was not significant (WMD 10.00 U/kg, 95% CI -80.87 to 100.87). There was no difference in the frequency of adverse events. There is no significant difference between once weekly versus thrice weekly subcutaneous administration of rHuEPO. Once weekly administration would require an additional 12 U/kg/wk for patients on haemodialysis, however this is based on one very small study. Cost of additional rHuEPO needs to assessed with regard to patient preference and compliance.


Drug Repurposing Approach in Developing New Furosemide Analogs as Antimicrobial Candidates and Anti-PBP: Design, Synthesis, and Molecular Docking.
Multidrug-resistant microorganisms have become a global health problem, prompting research into new antimicrobials. Drug repurposing is a new technique in drug discovery used to improve drug development success. As a well-studied medication with a sulfonamide moiety, furosemide was chosen to study its antimicrobial effect on different microbial strains. In addition, a new family of furosemide analogs was investigated for their antimicrobial efficacy. According to the obtained results, the majority of the examined molecules exhibited potential antimicrobial activity. Compounds 3b and 4a had the best anti-MRSA results, with an MIC = 7.81 µg/mL. They also demonstrated potent anti-gram-negative activity against E. coli (MIC = 1.95 µg/mL and 3.91 µg/mL, respectively). A time-killing kinetics study against E. coli and MRSA showed bactericidal actions of 3b and 4a within 120-150 min. Moreover, an anti-PBP activity and an in vitro cytotoxicity evaluation were performed. Furosemide decreased the PBP2a levels in MRSA by 21.5% compared to the control. However, the furosemide analogs 3b and 4a demonstrated superior anti-PBP activity (55.9 and 57.1 % reduction in the expression of PBP2a, respectively). In addition, compound 4a was nearly nontoxic to normal WI-38 cells (IC50 = 248.60 μg /mL) indicating its high safety profile. Finally, the ability of furosemide and compounds 3b and 4a to bind to the target PBP2a enzyme has also been supported by molecular docking research.


[Effects of skin infiltration with ropivacaine 0,75% on postoperative pain after caesarean section].
Evaluate the effects of skin infiltration with ropivacaine 0,75% on postoperative pain after caesarean section in the first 24h. A prospective randomized double blind study was realized during three months in Auxerre Hospital. All ASA 1-2 patients presenting for elective caesarean section under spinal anesthesia were enrolled in the study. Drug addicts and patients with chronic pain were excluded from the study. The patients were randomly divided into two groups to receive skin infiltration 20 ml of ropivacaine 0,75% (Gr R) or skin infiltration of 20 ml of 0,9% saline solution. All patients received systematically propacetamol 1g per six hours and ketoprofen 50mg per six hours. Intravenous morphine titration was delivered to patients with a simple numerical scale greater or equal to three (SNS> or =3). Postoperative pain (SNS), morphine consumption and adverse reactions were compared. From July to September 2005, 42 patients were enrolled in the study. The SNS was lower in the Gr R. Total morphine consumption was reduced in the Gr R. The incidence of the adverse effects were higher in the Gr P. One case of parietal haematoma was detected in the Gr P, the evolution of which was favorable. Skin infiltration of ropivacaine 0,75% is a simple technique able to reduce postoperative pain score and morphine consumption after caesarean section.


Adam-Gibbs model in the density scaling regime and its implications for the configurational entropy scaling.
To solve a long-standing problem of condensed matter physics with determining a proper description of the thermodynamic evolution of the time scale of molecular dynamics near the glass transition, we have extended the well-known Adam-Gibbs model to describe the temperature-volume dependence of structural relaxation times, τα(T, V). We also employ the thermodynamic scaling idea reflected in the density scaling power law, τα = f(T(-1)V(-γ)), recently acknowledged as a valid unifying concept in the glass transition physics, to differentiate between physically relevant and irrelevant attempts at formulating the temperature-volume representations of the Adam-Gibbs model. As a consequence, we determine a straightforward relation between the structural relaxation time τα and the configurational entropy SC, giving evidence that also SC(T, V) = g(T(-1)V(-γ)) with the exponent γ that enables to scale τα(T, V). This important findings have meaningful implications for the connection between thermodynamics and molecular dynamics near the glass transition, because it implies that τα can be scaled with SC.


Burnout and associated occupational stresses among Chinese nurses: A cross-sectional study in three hospitals.
There is literature scarcity relating to burnout and other work stresses in relation to Chinese nursing-workforce performance. To assess the relationship between self-esteem versus burnout; and effort-reward ratio versus favorability to the work environment, among Chinese nurses. We employed four validated questionnaires in the assessment burnout, self-esteem, effort-reward ratio, and favorability of nursing workplace; Maslach-Burnout Inventory (MBI), Rosenberg's self-esteem (RS), Effort-Reward imbalance (ERI) and Work-Environment Scale questionnaires (WES). Linear and ordinal regression models were utilized to assess the relationships between the variables. Analyses were conducted by using SPSS at a 95% level of significance. We assessed 487 (Mean age: 38.8±7.1 years) nurses from three hospitals. Higher self-esteem was associated with a lower level of emotional exhaustion (Unstandardized coefficient: -0.579, p-Value<0.001); and a lower level of depersonalization (Unstandardized coefficient: -0.212, p-Value = 0.001). The relationship between self-esteem and personal achievement did not reach statistical significance. A higher effort-reward ratio was associated with less likelihood that nurses would consider their work environment favorable (Logit estimate of -0.832, p-Value = 0.014). Lower self-esteem is associated with increased burnout. A higher effort-reward ratio is associated with an enhanced perception work environment as unfavorable. We recommend psychosocial intervention programs and amendments in nursing policies to improve effort-reward imbalance among Chinese nurses.


Recombinant baculovirus-based multiple protein expression platform for Drosophila S2 cell culture.
A platform for selective and controllable expression of multiple foreign protein types was developed in insect cell culture. Based on the fact that baculovirus cannot replicate in nonpermissive Drosophila melanogaster Schneider line 2 (S2) cells, S2 cells that stably express human erythropoietin (hEPO) under the control of the S2-derived inducible metallothionein (MT) promoter were infected with three types of recombinant baculoviruses, each of which expressed a different fluorescent protein gene under the control of MT promoter. Addition of copper sulfate as an inducer to infected, stably transfected S2 cells resulted in simultaneous expression of hEPO and three fluorescent proteins. Expression profiles and levels of the three induced fluorescent proteins were similar in all single infected cells. Importantly, expression profiles and levels of hEPO were similar in both non-infected and infected cells, indicating that baculovirus expressed recombinant proteins do not adversely affect expression of host cell recombinant proteins. Expressions of the three fluorescent proteins were able to be selectively regulated by altering combination ratios of the three types of recombinant baculoviruses. Collectively, these data indicate that the baculovirus/stably transfected S2 cell system can be successfully used to express multiple foreign proteins in a controlled and selective manner without the burden of additional selection markers. Such a system would be expected to be attractive as a multiple protein expression platform for engineering metabolic or glycosylation pathways.


Potential immune escape mutations under inferred selection pressure in HIV-1 strains circulating in Medellín, Colombia.
The introduction of highly active antiretroviral therapy (HAART) has significantly improved life expectancy of HIV-infected patients; nevertheless, it does not eliminate the virus from hosts, so a cure for this infection is crucial. Some strategies have employed the induction of anti-HIV CD8+ T cells. However, the high genetic variability of HIV-1 represents the biggest obstacle for these strategies, since immune escape mutations within epitopes restricted by Human Leukocyte Antigen class I molecules (HLA-I) abrogate the antiviral activity of these cells. We used a bioinformatics pipeline for the determination of such mutations, based on selection pressure and docking/refinement analyses. Fifty HIV-1 infected patients were recruited; HLA-A and HLA-B alleles were typified using sequence-specific oligonucleotide approach, and viral RNA was extracted for the amplification of HIV-1 gag, which was bulk sequenced and aligned to perform selection pressure analysis, using Single Likelihood Ancestor Counting (SLAC) and Fast Unconstrained Bayesian Approximation (FUBAR) algorithms. Positively selected sites were mapped into HLA-I-specific epitopes, and both mutated and wild type epitopes were modelled using PEP-FOLD. Molecular docking and refinement assays were carried out using AutoDock Vina 4 and FlexPepDock. Five positively selected sites were found: S54 at HLA-A*02 GC9, T84 at HLA-A*02 SL9, S125 at HLA-B*35 HY9, S173 at HLA-A*02/B*57 KS12 and I223 at HLA-B*35 HA9. Although some mutations have been previously described as immune escape mutations, the majority of them have not been reported. Molecular docking/refinement analysis showed that one combination of mutations at GC9, one at SL9, and eight at HY9 epitopes could act as immune escape mutations. Moreover, HLA-A*02-positive patients harbouring mutations at KS12, and HLA-B*35-positive patients with mutations at HY9 have significantly higher plasma viral loads than patients lacking such mutations. Thus, HLA-A and -B alleles could be shaping the genetic diversity of HIV-1 through the selection of potential immune escape mutations.


Implantation of automatic cardioverter-defibrillators via median sternotomy.
15 AICD (automatic implantable cardioverter-defibrillator) Model B units were implanted in 10 patients. The median sternotomy is our preferred surgical approach using a right atrial patch electrode, a left ventricular apex patch electrode, and two closely placed epicardial sensing electrodes. Follow-up is 109 patient months and all patients are alive. AICD units discharged for ventricular tachycardia, ventricular flutter, and ventricular fibrillation. Discharges also occurred for sinus tachycardia and atrial fibrillation above the rate limit in three units. Premature pulse generator depletion has occurred in four AICD-B units 3 to 18 months postimplant and appears due to a defect in original battery design. Discharge of the AICD for supraventricular tachycardia is a problem that will remain until a better means of differentiating supraventricular tachycardia from ventricular tachyarrhythmias is found. The AICD appears to prevent sudden death from ventricular tachyarrhythmias.


A simple microplate-based method for the determination of α-amylase activity using the glucose assay kit (GOD method).
For the first time, a reliable, simple, rapid and high-throughput analytical method for the detection and quantification of α-amylase inhibitory activity using the glucose assay kit was developed. The new method facilitates rapid screening of a large number of samples, reduces labor, time and reagents and is also suitable for kinetic studies. This method is based on the reaction of maltose with glucose oxidase (GOD) and the development of a red quinone. The test is done in microtitre plates with a total volume of 260μL and an assay time of 40min including the pre-incubation steps. The new method is tested for linearity, sensitivity, precision, reproducibility and applicability. The new method is also compared with the most commonly used 3,5-dinitrosalicylic acid (DNSA) method for determining α-amylase activity.


Two-Stage En Bloc Resection of Multilevel Cervical Chordomas With Vertebral Artery Preservation: Operative Technique.
En bloc excision of cervical chordoma is a technically complex procedure, due to the involvement and closeness of the tumor to the spinal cord, cervical nerve roots, and vertebral arteries. Studies have previously shown that en bloc excision of chordomas with negative margins improves local control and prolongs disease-free survival compared with intralesional excision. True en bloc spondylectomy in the cervical spine is not feasible since bilateral vertebral artery sacrifice is not possible. However, for lateralized tumors, en bloc excision of chordoma can be performed with unilateral vertebral artery preservation by parasagittal osteotomy. To describe the operative technique of performing en bloc excision of cervical chordoma via parasagittal osteotomy. Four patients underwent en bloc excision of multilevel cervical chordomas via parasagittal osteotomy between 2008 and 2016. These 4 cases of chordoma were at the upper-cervical, mid-cervical, and cervicothoracic regions. We analyzed the tumor location, oncological staging, surgical technique, and perioperative complications. All 4 patients underwent en bloc excision of chordoma with expandable cage reconstruction and posterior instrumentation. Cervical nerve roots were sacrificed in 2 patients, and vertebral artery ligation was performed in 3 patients. Complications include new neurologic deficit, implant failure, and pharyngeal erosion after radiation. No tumor recurrence was seen. Parasagittal osteotomy is a useful alternative to en bloc spondylectomy in the treatment of lateralized multilevel cervical chordoma, preserving one vertebral artery while still achieving an en bloc resection.


Galactomannan detection in Geotrichum capitatum invasive infections: report of 2 new cases and review of diagnostic options.
We report 2 cases of Geotrichum capitatum infection in leukemia patients for which Aspergillus galactomannan (GM) assay was positive. The diagnostic options of G. capitatum infections in hematologic patients were reviewed. Although the pathogen was isolated from blood in 77% of cases, diagnostic difficulties remain and GM assay may have a role.


Virtual screening of the multi-gene regulatory molecular mechanism of Si-Wu-tang against non-triple-negative breast cancer based on network pharmacology combined with experimental validation.
Si-Wu-Tang (SWT), a prestigious herbal formula from China, has been extensively used for centuries for female-related diseases. It has been documented that SWT has a significant inhibitory effect on non-triple-negative breast cancer (non-TNBC) cells. However, there has been limited comprehensive analysis of the targeted effects of the anticancer components of SWT and its exact biological mechanism. This study aims to uncover the mechanism by which SWT treats non-TNBC by applying a network pharmacological method combined with experimental validation. First, SWT compounds were collected from the Traditional Chinese Medicines Systems Pharmacology database (TCMSP) and The Encyclopedia of Traditional Chinese Medicine (ETCM), and then the targets related to SWT were obtained from the TCMSP and SwissTarget databases. Second, a target data set of non-TNBC proteins was established by using the Online Mendelian Inheritance in Man (OMIM), GeneCards and Gene Expression Omnibus (GEO) databases. Third, based on the overlap of targets between SWT and non-TNBC, a protein-protein interaction (PPI) network was built to analyse the interactions among these targets, which focused on screening for hub targets by topology. On these hub genes, we conducted a meta-analysis and survival analysis to screen the best match targets, ESR1, PPARG, CAT, and PTGS2, which had a strong correlation with the ingredients of SWT in our verification by molecular docking. In vitro experiments further proved the reliability of the network pharmacology findings. Finally, FunRich software and the ClusterProfiler package were utilized for the enrichment analysis of Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) data. A total of 141 active ingredients and 116 targets of SWT were selected. GO enrichment analysis showed that the biological processes through which SWT acted against non-TNBC (FDR<0.01) mainly involved modulating energy metabolism and apoptosis. According to RT-qPCR and Western blotting, the mRNA and protein expression of ESR1, PPARG and PTGS2 were upregulated (P < 0.01), and the mRNA and protein levels of CAT were downregulated (P < 0.01), suggesting a multi-gene regulatory molecular mechanism of SWT against non-triple-negative breast cancer. This research explored the multi-gene pharmacological mechanism of action of SWT against non-TNBC through network pharmacology and in vitro experiments. The findings provide new ideas for research on the mechanism of action of Chinese medicine against breast cancer.


[The everyday life of survivors. The quality of life of hospice workers].
Each year, the number of hospice services and terminally ill patients increase while the number of hospice workers is falling. The intensification of the physical and mental burdens of the latter can lead to burnout and the fluctuation of the workers. The aim of the authors was to survey the physical and mental state of hospice workers, as well as the risk of burnout and coping strategies. A questionnaire survey in hospice experts and volunteers (n ≈ 1500) based on the Hungarostudy survey was performed. Those who filled in the questionnaire (n = 195) had on average 1.86 workplaces and 45.8% of them reported working 12 or more hours a day. Most often, they suffered from lack of energy (65.1%), disturbing physical pain (46.9%), sleeping (56.9%) and digestion (35%), they considered themselves overweight (56.9%) and they were occupied with work problems even at bedtime (72.8%). Hospice workers are overloaded, they have physical and mental symptoms and they are characterized by compassion fatigue. At the same time, they are also characterized by compassion satisfaction as an ability to accept appreciation for the caretaking.


Chemical composition of halophytes from the Neusiedler Lake region in Austria.
The ionic relations in halophytes from the region east of Neusiedler Lake in Austria have been investigated. The study encompasses the following compounds: Na, K, Mg, Ca; Cl, SO4, phosphate, nitrate, and organic acids.The ionic composition varies substantially among the species investigated. Frequently a specific pattern of ion content can be found within a specific taxon. a) Dicotyledons: Extraordinary accumulation of sodium, high intake of inorganic ions (mainly Cl, less SO4), and regular occurrence of free oxalate, causing low Ca-concentrations, are typical for Chenopodiaceae and Caryophyllaceae (Spergularia media). Lepidium crassifolium shows similar sodium preponderance accompanied by high levels of SO4, Cl, and organic anions other than oxalate (mainly citrate and malate). The remaining dicotyledons show rather moderate salt content; Asteraceae and Cichoriaceae prefer Cl, and Plantago maritima accumulates high amounts of SO4 as well as Cl. Malate and citrate are, without exception, the main organic anions. The K:Na ratios in dicotyledons (esp. Chenopodiaceae and Lepidium-Brassicaceae) lie far below unity. b) Monocotyledons: In marked contrast, Poaceae, Cyperaceae, and Juncaceae are characterized by a general low salt status. With few exceptions, Cl is stored as the main inorganic anion, phosphate reaches higher levels than in dicotyledons and in many cases lies in nearly the same concentration range as SO4. The pattern of organic anions with malate and citrate as the main acids, does not basically differ from nonhalophilous species. In any case, K:Na ratio exceeds unity. Triglochin maritimum is the only monocotyle species exhibiting as high salt content and low K:Na ratios as dicotyledons. Nitrate and phosphate are of minor quantitative importance with regard to their osmotic efficiency; their mEq percentage of the total anion concentration range between 0.03 to 2.6 (NO3) and 0.5 to 13.6 (phosphate), respectively.The results are discussed from different points of view: on the one hand, the general problems of salt tolerance, on the other hand, the taxonomical and ecological aspects. beneficial to plant growth in view of salt sensitivity of enzymatic reactions. However, low osmotic potential of cell sap, and consequently, the acquisition of water is guaranteed by storing high amounts of sugars: according to our data (Albert and Popp, in preparation) total sugar concentration in halophilous Poaceae, Cyperaceae, and Juncaceae amounts to up to 200 mmol·l-1 fresh water, whereas in salt rich dicotyle species the sugar content is comparatively low (up to 50 mmol).


Effect of Microdissection of Inferior Thyroid Artery on Post-operative Hypocalcemia in Total Thyroidectomy.
Hypocalcemia is one of the most common complication after bilateral thyroid surgery. Reported rates range from 5 to 35% and 0.5 to 4.4% for transient and permanent hypocalcemia respectively. Various methods have been devised to reduce the post-operative hypocalcemia and range from modification of surgical techniques to use of loops and avoidance of inadverant neck dissections. We conducted a randomised control trial of 50 patients divided into two groups, to evaluate the effect of microdissection and ligation of distal branches of inferior thyroid artery (group B) on incidence of temporary and permanent hypocalcaemia in patients of total thyroidectomy versus its ligation distally close to the thyroid capsule(group A). Postoperative mean total serum calcium levels were lower in group A as compared to group B (9.13 mg/dl vs. 9.33 mg/dl at 24 h; 8.77 vs. 9.10 at 3rd day and 8.58 vs. 8.96 mg/dl on 10 th day) with p > 0.05. The value of ionized serum calcium as recorded on 3rd day was 4.39 mg/dl for group A and 4.72 mg/dl for group B with p value ≤ 0.001 (Table 2). 19 patients in group A required calcium supplementation for 6 months with incidence of transient hypocalcemia at 76% while 11 patients in group B had calcium supplementation for 6 months with incidence of 40% and difference was significant statistically. Microdissection technique is better for preventing the temporary hypocalcemia and hence decreasing the hospital visits of the patient when compared to the ligation of inferior thyroid artery distally close to the thyroid gland. The incidence of permanent hypocalcemia doesn't varies significantly between both techniques.


The effects of Staphylococcus aureus leukotoxins on the host: cell lysis and beyond.
The success of Staphylococcus aureus as a leading cause of deadly hospital-acquired and community-acquired infections is attributed to its high-level resistance to most antibiotics, and the multitude of virulence factors it elaborates. Most clinical isolates produce up to four bi-component pore-forming toxins capable of lysing cells of the immune system. Subtle differences in activity and target range of each leukotoxin suggest that these toxins are not redundant, but instead may have specialized functions in attacking and/or evading host defenses. In turn, the host has developed countermeasures recognizing sublytic levels of leukotoxins as signals to activate protective immune defenses. The opposing cytotoxic and immune-activating effects of leukotoxins on host cells make for a complex dynamic between S. aureus and the host.


[Peripheral thrombophlebitis. "Paratuberculous syndrome" (author's transl)].
The authors relate the case of a young North-African man who presented during one month several peripheral thrombophlebitis before a ganglionary tuberculosis of the mediastinum appear. With specific antibiotherapy, the cutaneous lesions disappear and can be so considered as a paratuberculous syndroma.


miR-488 mediates negative regulation of the AKT/NF-κB pathway by targeting Rac1 in LPS-induced inflammation.
Endometritis is an inflammatory change in the structure of the endometrium due to various causes and is a common cause of infertility. Studies have confirmed that microRNAs (miRNAs) play a key regulatory role in various inflammatory diseases. However, the miRNA-mediated mechanism of endometrial inflammation induced by lipopolysaccharides (LPS) remains unclear. In this study, real-time quantitative polymerase chain reaction, Western blot analysis, immunofluorescence and Rac family small GTPase 1 (Rac1) interference were used to reveal the overexpression of miR-488 in the LPS-induced bovine uterus, and the effect of protein kinase B κ-light chain enhancement of the nuclear factor-activated B cells (AKT/NF-κB) pathway in intimal epithelial cells. The results showed that the expression of inflammatory cytokines such as interleukin-1β (IL-1β), IL-6, and tumor necrosis factor-α in the experimental group was significantly lower than that in the control group when miR-488 was overexpressed. Similar results were observed in the expression levels of p-AKT, p-IKK, and p-p65 proteins. In addition, the dual-luciferase reporter system confirmed that miRNA-488 may directly target the 3'-untranslated region of Rac1. In turn, the expression of Rac1 was inhibited. Moreover, the nuclear translocation of NF-κB was inhibited, and meanwhile, the accumulation of reactive oxygen species (ROS) in the cells was reduced. Thus, we provide basic data for the negative regulation of miR-488 in LPS-induced inflammation by inhibiting ROS production and the AKT/NF-kB pathway in intimal epithelial cells.


Immunolocalization of beta-catenin in pleomorphic adenomas and carcinomas ex-pleomorphic adenomas of salivary glands.
Beta-catenin plays a central role in cadherin/catenin cell-cell adhesion complex and is involved in cell signaling pathway. Change in beta-catenin distribution has been associated with several human cancers including salivary gland tumors. We studied the immunolocalization of beta-catenin in a series of pleomorphic adenomas (PA) and carcinomas ex-pleomorphic adenomas (Ca ex-PA). Ten samples of PA and ten of Ca ex-PA were evaluated by immunohistochemistry using streptavidin-biotin-peroxidase technique and a monoclonal antibody against beta-catenin (E-5). Cell membrane/cytoplasmic staining of beta-catenin was observed in normal gland parenchyma, PA, and in well-differentiated Ca ex-PA. Cytoplasmic/nuclear beta-catenin staining was observed in poorly differentiated carcinomas and, interestingly, in one case of PA. Our data showed decreased cell membrane beta-catenin expression in higher-grade tumors suggesting that beta-catenin may play an important role in histologic differentiation and transition to malignant phenotype of Ca ex-PA.


Decreased INPP5B expression predicts poor prognosis in lung adenocarcinoma.
Inositol Polyphosphate-5-Phosphatase B (INPP5B), a inositol 5-phosphatase, plays an important role in many biological processes through phosphorylating PI(4,5)P2 and/or PI(3,4,5)P3 at the 5-position. Nevertheless, little is known about its function and cellular pathways in tumors. This study aims to investigate the potential role of INPP5B as a diagnostic and prognostic biomarker for lung adenocarcinoma (LUAD), as well as its biological functions and molecular mechanisms in LUAD. TCGA, GEO, CTPAC, and HPA datasets were used for differential expression analysis and pathological stratification comparison. The prognostic and diagnostic role of INPP5B was determined by Kaplan-Meier curves, univariate and multivariate Cox regression analysis, and receiver operating characteristics (ROC) curve analyses. The potential mechanism of INPP5B was explored through GO, KEGG, and GSEA enrichment analysis, as well as GeneMANIA and STRING protein-protein interaction (PPI) network. PicTar, PITA, and miRmap databases were used for exploring miRNA targeting INPP5B. In molecular biology experiments, immunohistochemical analyses and Western blot analyses were used to determine protein expression. Co-immunoprecipitation assay was used to detect protein-protein interactions. CCK8 assays and colony formation assays were used for the measurement of cell proliferation. Cell cycle was assessed by PI staining with flow cytometry. Cell migration was performed by Transwell assays and wound healing assays. INPP5B was decreased in LUAD tissues compared with normal adjacent tissues. And the low expression of INPP5B was associated with late-stage pathological features. In addition, INPP5B was found to be a significant independent prognostic and diagnostic factor for LUAD patients. Hsa-miR-582-5p was predicted as a negative regulator of INPP5B mRNA expression. INPP5B was significantly correlated with the expression of PTEN and the activity of PI3K/AKT signaling pathways, as determined by enrichment analysis and PPI network. In vitro experiments partially confirmed the aforementioned findings. INPP5B could interact directly with PTEN. INPP5B overexpression inhibited LUAD cell proliferation and migration while downregulating the AKT pathway. Our results demonstrated that INPP5B could inhibit the proliferation and metastasis of LUAD cells. It could serve as a novel diagnostic and prognostic biomarker for LUAD patients. Trial registration LUAD tissues and corresponding para-cancerous tissues were collected from 10 different LUAD patients at Hangzhou First People's Hospital. The Ethics Committee of Hangzhou First People's Hospital has approved this study. (registration number: IIT-20210907-0031-01; registration date: 2021.09.13).


Corticomuscular coherence in the acute and subacute phase after stroke.
Stroke is one of the leading causes of physical disability due to damage of the motor cortex or the corticospinal tract. In the present study we set out to investigate the role of adaptations in the corticospinal pathway for motor recovery during the subacute phase after stroke. We examined 19 patients with clinically diagnosed stroke and 18 controls. The patients had unilateral mild to moderate weakness of the hand. Each patient attended two sessions at approximately 3days (acute) and 38days post stroke (subacute). Task-related changes in the communication between motor cortex and muscles were evaluated from coupling in the frequency domain between EEG and EMG during movement of the paretic hand. Corticomuscular coherence (CMC) and intermuscular coherence (IMC) were reduced in patients as compared to controls. Paretic hand motor performance improved within 4-6weeks after stroke, but no change was observed in CMC or IMC. CMC and IMC were reduced in patients in the early phase after stroke. However, changes in coherence do not appear to be an efficient marker for early recovery of hand function following stroke. This is the first study to demonstrate sustained reduced coherence in acute and subacute stroke.


The interconnections among the intensity of social network use, anxiety, smartphone addiction and the parent-child relationship of adolescents: A moderated mediation effect.
To explore the mediation role of smartphone addiction on the relationship between parent-child relationships and the intensity of use of social network sites (SNSs), as well as the moderation effect of anxiety, this research conducted self-report questionnaires of the Social networking site (SNS) Usage Questionnaire, Self-Rating Anxiety Scale, Smartphone Addiction Scale and Inventory of Parent and Peer Attachment with 719 adolescents. The results showed that (1) the parent-child relationship negatively predicts SNS usage and (2) smartphone addiction plays a mediating role in the link between the parent-child relationship and SNS usage. (3) The relationship between the parent-child relationship and SNS usage is moderated by anxiety (on the first mediation path), and low levels of anxiety can mitigate the negative impact of the parent-child relationship on smartphone addiction, thus also mitigating the negative effects of the parent-child relationship on SNS usage. Our conclusion highlighted the vital role of the parent-child relationship and anxiety on the influence of smartphone addiction and the intensity of use of SNSs among adolescents. Our research also provides clinical implications: (1) teachers in high school can adopt family group counseling or emotion regulation workshop to help adolescents to prevent addiction to smartphones and social network sites; (2) we can reduce addictive behaviors by designing a series of intervention sessions to improve parent-child relationships and reduce anxiety for adolescents who have been addicted to smartphone and social network sites.


A solvent tolerant isolate of Enterobacter aerogenes.
A solvent tolerant strain of Enterobacter aerogenes was isolated from soil by cyclohexane enrichment. Presence of cyclohexane (20%) in culture media prolonged the lag phase and caused reduction in biomass. Transmission electron micrographs showed convoluted cell membrane and accumulation of solvent in case of the cells grown in cyclohexane. The Enterobacter isolate was able to grow in the range of organic solvents having log P above 3.2 and also in presence of mercury, thus showing potential for treatment of solvent rich wastes.


Improving 1-year outcome in first-episode psychosis: OPUS trial.
Because early illness course and outcome may affect the long-term outcome of schizophrenia-spectrum disorders, it is especially important to address poor outcome in this early critical period. To evaluate whether integrated treatment compared with standard treatment reduced the proportion of patients with poor clinical and social outcome after 1 year. A total of 547 patients with first-episode psychosis were included in the study, 275 randomly assigned to integrated treatment and 272 to standard treatment. Measures assessed psychotic symptoms and social functioning. There was a significant beneficial effect of integrated treatment v. standard treatment on "any poor outcome". Integrated treatment had a significantly better effect on "any poor outcome" in patients with schizophrenia compared with patients in standard treatment. The integrated treatment significantly reduced the proportion of patients with poor clinical and social outcome compared with standard treatment.


Interpretation of the interaction between cesium ion and some clay minerals based on their structural features.
Cesium (Cs+) is known to have a strong interaction with various clay minerals; however, it is not interpreted from the structure of clay minerals and the adsorption isotherm. The adsorption interactions between Cs+ and hydrobiotite (H-Bio), biotite (Bio), vermiculite (Verm), and exfoliated vermiculite (E-Verm) were evaluated by analyzing adsorption isotherm, basal spacing, and adsorption/desorption experiments. The Cs+ adsorption of H-Bio and Verm fitted well to the Langmuir adsorption isotherm, while the Cs+ adsorption of Bio and E-Verm fitted well to the Freundlich adsorption isotherm. The basal spacing of H-Bio and Verm was approximately 1.4 nm, while Bio and E-Verm basal spacing was 1.0 nm. The adsorption experiment results for Cs+ under the coexistence of Ca2+ and K+ indicated that the contribution of the interlayer sites to Cs+ adsorption on H-Bio and Verm was 25-40%, while the contribution of the interlayer sites to that on Bio and E-Verm was almost 0%. The adsorption isotherms reflected this interlayer contribution to Cs+ adsorption, which was dependent on the basal spacing. Therefore, the basal spacing of clay minerals is one of the key structural properties controlling both the adsorption capacity and the adsorption mechanism of Cs+ in clay minerals.


The clinical utility of reticular basement membrane thickness measurements in asthmatic children.
Reticular basement membrane (RBM) thickness is one of the pathological features of asthma and can be measured in endobronchial biopsies. We assessed the feasibility of endobronchial biopsies in a routine clinical setting and investigated the clinical value of RBM thickness measurements for asthma diagnosis in children. We included all children who underwent bronchoscopy with endobronchial mucosal biopsies for clinical reasons and divided them into three subgroups: (1) no asthma, (2) mild-moderate asthma, and (3) problematic severe asthma. In 152/214 (71%) patients, mean age 9.5 years (SD 4.6; range 0.1-18.7) adequate biopsies were retrieved in which RBM thickness could be measured. Mean (SD) RBM thickness differed significantly among children without asthma, with mild-moderate asthma, and with problematic severe asthma (p = 0.04), 4.68 (1.24) µm, 4.56 (0.89) µm, and 5.21 (1.10) µm respectively. This difference disappeared after adding exhaled nitric oxide to the multivariate model. This study confirms the difference in RBM thickness between children with and without asthma and between asthma severities in a routine clinical care setting. However, quantifying the RBM thickness appeared to have no added clinical diagnostic value for asthma in children.


Severe fetal thrombocytopenia in Rhesus D alloimmunized pregnancies.
The objective of the study was to evaluate the incidence of fetal thrombocytopenia and association with hydrops in Rhesus D alloimmunization. The study was a retrospective chart review of 914 intrauterine transfusions in 314 pregnancies performed between 1988 and 2005 in a single institution. The incidence of thrombocytopenia and severity of hydrops at cordocentesis were assessed and correlated with perinatal mortality. Thrombocytopenia (less than 150 x 10(9)/L) was found in 241 of 914 (26%) and severe thrombocytopenia (less than 50 x 10(9)/L) in 25 of 914 (3%) cordocentesis. Twenty-three percent of severely hydropic fetuses had severe thrombocytopenia, compared with 3% and 1% of mildly hydropic and nonhydropic fetuses, respectively. Thrombocytopenia was an independent risk factor for perinatal mortality. Mortality in fetuses that were severely thrombocytopenic and severely hydropic was 67%. Thrombocytopenia is common in hydropic anemic fetuses. Severe thrombocytopenia is associated with a poor prognosis, irrespective of the presence of hydrops. The option of platelet transfusion in severely hydropic anemic fetuses needs further study.


Bladder Sparing Approaches for Muscle-Invasive Bladder Cancers.
Organ preservation has been increasingly utilised in the management of muscle-invasive bladder cancer. Multiple bladder preservation options exist, although the approach of maximal TURBT performed along with chemoradiation is the most favoured. Phase III trials have shown superiority of chemoradiotherapy compared to radiotherapy alone. Concurrent chemoradiotherapy gives local control outcomes comparable to those of radical surgery, but seemingly more superior when considering quality of life. Bladder-preserving techniques represent an alternative for patients who are unfit for cystectomy or decline major surgical intervention; however, these patients will need lifelong rigorous surveillance. It is important to emphasise to the patients opting for organ preservation the need for lifelong bladder surveillance as risk of recurrence remains even years after radical chemoradiotherapy treatment. No randomised control trials have yet directly compared radical cystectomy with bladder-preserving chemoradiation, leaving the age-old question of superiority of one modality over another unanswered. Radical cystectomy and chemoradiation, however, must be seen as complimentary treatments rather than competing treatments. Meticulous patient selection is vital in treatment modality selection with the success of recent trials within the field of bladder preservation only being possible through this application of meticulous selection criteria compared to previous decades. A multidisciplinary approach with radiation oncologists, medical oncologists, and urologists is needed to closely monitor patients who undergo bladder preservation in order to optimise outcomes.


ATF1/miR-214-5p/ITGA7 axis promotes osteoclastogenesis to alter OVX-induced bone absorption.
The dynamic balance of osteoblast and osteoclast is critical for bone homeostasis and overactive osteoclastic function may lead to osteoporosis. Activating transcription factor 1 (ATF1) is involved in osteoclastogenesis. However, the detailed mechanisms remain to be explored. RAW264.7 cells were used and induced toward osteoclast by RANKL administration. We performed flow cytometry, CCK-8 assay and tartrate-resistant acid phosphatase (TRAP) staining to examine cell apoptosis, proliferation and differentiation of RAW264.7 cells, respectively. Mice were subjected to ovariectomy to induce osteoporosis. Micro CT, HE staining and TRAP staining were performed to evaluate bone loss in the OVX mouse model. Bioinformatics methods, luciferase assays and Chromatin Immunoprecipitation (ChIP) were used to predict and validate the interaction among ATF1, miR-214-5p, and ITGA7. ATF1 and miR-214-5p were up-regulated while ITGA7 was inhibited in RANKL-induced osteoclasts. MiR-214-5p was transcriptionally activated by ATF1. ATF1 knockdown suppressed osteoclast formation by miR-214-5p inhibition. ITGA7 was the direct target of miR-214-5p. Knockdown of miR-214-5p abolished osteoclastogenesis, which was reversed by ITGA7 knockdown. In OVX model, miR-214-5p knockdown suppressed osteoclast differentiation and prevented bone loss. ATF1/miR-214-5p/ITGA7 axis regulated osteoclast formation both in vivo and in vitro, thereby affecting OVX-induced bone resorption in mice. Knockdown of ATF1 might be a promising strategy to manage osteoporosis.


Benign and Malignant Lesions of Jaw.
Benign and malignant neoplasm of oral cavity is usually presented as swellings or ulcerations of affected tissue. The lesions are broadly categorized as potentially malignant disorders, benign and malignant neoplasm of epithelial and connective tissue origin for the convenience of learning. Neoplasm of oral cavity has a significantly lower incidence. Because of uncommon occurrence of oral neoplasm, retention of diagnostic skills is a challenging task. However, comprehensive understanding on clinical and pathologic details will help in correlating and presenting complaint and assisting in formulation of possible diagnosis. The key for successful therapeutic management depends on achieving right and timely diagnosis.


Seasonal serotonin uptake changes in healthy subjects.
Platelet 5-hydroxytryptamine (5HT) uptake was measured in 12 healthy subjects in the spring, summer, and late autumn. The uptake was performed according to the method of Arora and Meltzer (1981). The maximal velocity of 5HT uptake was higher in the spring and in summer than in the autumn. In addition, a significant negative correlation between the Michaelis constant and the photoperiod was observed in spring. These findings seem to indicate the possible evidence of physiological season-related changes of platelet 5HT uptake that may be linked to the photoperiod.


Effect of tranexamic acid on choroidal melanoma.
Four cases of malignant choroidal melanoma have been treated with the antifibrinolytic agent tranexamic acid (Cyklocapron). One patient treated for six months showed no progression in tumor growth. Three eyes have been enucleated, and the histological examination revealed that the tumours were surrounded by fibrin. No side-effects of the treatment were observed.


[Preliminary results of burn treatment using an autograft of cultured epidermis].
Transplantation of autologous cultured epidermal sheets is a recent advance in the treatment of burn patients. A small skin biopsy is sufficient to produce large epidermal sheets within 3 weeks which provide transplants to cover extensive burn wounds. First clinical experience with this method is described.


Educational strategies in the health professions to mitigate cognitive and implicit bias impact on decision making: a scoping review.
Cognitive and implicit biases negatively impact clinicians' decision-making capacity and can have devastating consequences for safe, effective, and equitable healthcare provision. Internationally, health care clinicians play a critical role in identifying and overcoming these biases. To be workforce ready, it is important that educators proactively prepare all pre-registration healthcare students for real world practice. However, it is unknown how and to what extent health professional educators incorporate bias training into curricula. To address this gap, this scoping review aims to explore what approaches to teaching cognitive and implicit bias, for entry to practice students, have been studied, and what are the evidence gaps that remain. This scoping review was guided by the Joanna Briggs Institute (JBI) methodology. Databases were searched in May 2022 and included CINAHL, Cochrane, JBI, Medline, ERIC, Embase, and PsycINFO. The Population, Concept and Context framework was used to guide keyword and index terms used for search criteria and data extraction by two independent reviewers. Quantitative and qualitative studies published in English exploring pedagogical approaches and/or educational techniques, strategies, teaching tools to reduce the influence of bias in health clinicians' decision making were sought to be included in this review. Results are presented numerically and thematically in a table accompanied by a narrative summary. Of the 732 articles identified, 13 met the aim of this study. Most publications originated from the United States (n=9). Educational practice in medicine accounted for most studies (n=8), followed by nursing and midwifery (n=2). A guiding philosophy or conceptual framework for content development was not indicated in most papers. Educational content was mainly provided via face-to-face (lecture/tutorial) delivery (n=10). Reflection was the most common strategy used for assessment of learning (n=6). Cognitive biases were mainly taught in a single session (n=5); implicit biases were taught via a mix of single (n=4) and multiple sessions (n=4). A range of pedagogical strategies were employed; most commonly, these were face-to-face, class-based activities such as lectures and tutorials. Assessments of student learning were primarily based on tests and personal reflection. There was limited use of real-world settings to educate students about or build skills in biases and their mitigation. There may be a valuable opportunity in exploring approaches to building these skills in the real-world settings that will be the workplaces of our future healthcare workers.


Peripheral blood absolute lymphocyte/monocyte ratio recovery during ABVD treatment cycles predicts clinical outcomes in classical Hodgkin lymphoma.
The peripheral blood absolute lymphocyte/monocyte count ratio at diagnosis (ALC/AMC-DX) predicts survival in classical Hodgkin lymphoma (cHL). However, a limitation of the ALC/AMC-DX is the inability to assess sequentially the host/tumor interaction during treatment. Therefore, we retrospectively examined the ALC/AMC ratio, as a surrogate marker of host immunity (ALC) and tumor microenvironment (AMC), at each adriamycin, bleomycin, vinblastine and dacarbazine treatment cycle as a predictor for clinical outcomes. From 1990 until 2008, 190 cHL patients were diagnosed, treated and followed at Mayo Clinic Rochester and qualified for the study. The ALC/AMC ratio at each treatment cycle was a predictor for overall survival (OS) and progression-free survival (PFS). An ALC/AMC ratio 1.1 versus ALC/AMC <1.1 during treatment cycles was an independent predictor for OS (hazard ratio (HR)=0.14; 95% confidence interval (CI): 0.04-0.40; P<0.0002) and for PFS (HR=0.19; 95% CI: 0.05-0.82; P<0.03). The ALC/AMC ratio during treatment cycles is a predictor for survival and provides a platform to develop therapeutic modalities to manipulate the ALC/AMC ratio during chemotherapy to improve clinical outcomes in cHL.


Spontaneous disclosure of BRCA1/2 genetic test results to employers: a French prospective study.
The aim of this study was to examine the patterns of disclosure of BRCA1/2 genetic test results to employers by unaffected carriers. In a national prospective cohort study on unaffected BRCA1/2 mutation carriers, disclosure to employers was assessed prospectively, using self-administered questionnaires, up to 2 years after their test results were delivered by cancer geneticists. Kaplan-Meier curves and Cox-regression analysis were used to assess the factors associated with time to disclosure to the employer. Mean age of the 146 women BRCA1/2 carriers who were employed when their test results were delivered was 37.1 years (range: 19-57). At the end of the second year of follow-up, 47 of them (32.2%) had disclosed their results to their employers; median time to disclosure was 6 months. Reasons spontaneously expressed were first to inform the employer that medical surveillance/surgery was necessary for cancer risk management although these carriers did not actually have cancer. After multivariate adjustment on age, women with a lower educational level (HRadj=2.00, P=0.026) and those who had undergone prophylactic surgery during the 2 years of follow-up (HRadj=2.18, P=0.019) had disclosed their BRCA status to their employers earlier and more frequently. One-third of the female carriers not affected by breast/ovarian cancer disclosed their BRCA1/2 genetic test results spontaneously to their employers, mainly to inform them that they were disease-free but required medical surveillance or a surgical intervention to reduce the risk of cancer.


Effect of 5-HT2C receptor agonist and antagonist on chronic unpredictable stress (CUS) - Mediated anxiety and depression in adolescent Wistar albino rat: Implicating serotonin and mitochondrial ETC-I function in serotonergic neurotransmission.
Anxiety and depression are among the major neuropsychiatric disorders worldwide, and yet the etiologies of these disorders remain unclear to date. Chronic unpredictable stress (CUS) procedure mimics several behavioral characteristics such as anxiety and depression in rodents. Using this animal model, we have attempted to understand the serotonergic system in the hippocampus and prefrontal cortex, while using the 5-HT2CR agonist and antagonist in evaluating 5-HT2C receptor neurotransmission. A decrease in serotonin (5-HT) level, tryptophan hydroxylase-2 activity and, 5-HT2CR receptor protein down-regulation in the CUS exposed group, explains the involvement of 5-HT and 5-HT2CR neurotransmission in the genesis of anxiety and depression. Besides, the oxidative stress - attenuated electrolyte imbalance via decrease ATPase pump activity, and compromised oxidative phosphorylation via decrease ETC-I activity are some of the underlying factors affecting neuronal cell survival and serotonergic neurotransmission. To complement our finding, altered behavioral performance scored in the open field test, elevated plus maze test, and the forced swim test, when exposed to CUS is indicative or consistent with anxiety, depression, emotional and locomotor status of the animals. Keeping these findings in mind, treatment with 5-HT2CR agonist (1-Methylpsilocin at 0.7 mg/kg), and 5-HT2CR antagonist (RS-102221 hydrochloride at 1 mg/kg) displayed varying results. One prominent finding was the anxiolytic ability of the 5-HT2CR agonist and the anti-depressive ability of the 5-HT2CR antagonist on the 7th-day treatment. Though the exact mechanism of action is not clear, their ability to equilibrate brain redox status, restoring Ca2+ level via Ca2+ATPase pump activity, and sustaining the mitochondrial bioenergetics can all be accounted for facilitating neurogenesis and the serotonergic system.


Synthesis and in vitro cancer cell growth inhibitory activity of monocyclic model compounds containing spongistatin triene side-chains.
Two monosaccharides embodying triene side-chains of the spongistatins display significant in vitro activity against human cancer cell lines.


Does a Bayesian model of V1 contrast coding offer a neurophysiological account of human contrast discrimination?
The dipper effect for contrast discrimination provides strong evidence that the underlying neural response is accelerating at low contrasts and saturating at high contrasts. The contrast-response functions of V1 neurons do have this sigmoidal shape, but individual neurons do not generally have a dynamic range wide enough to account for the dipper effect. This paper presents a Bayesian model of neurons in monkey V1, whose contrast-response function is described by a modified Naka-Rushton with multiplicative noise. It is shown that a model of groups of twelve or more neurons gives a reasonable explanation of the psychophysical data of two observers, but there is a large systematic error which is apparently due to the shape of the distribution of the monkey's sensitivity parameter, c50. A further model provides a better fit to the data by sacrificing strict adherence to V1 neuronal parameters and, instead using an arbitrary bimodal c50 distribution, perhaps reflecting differences between M- and P-cells.


Noncovalently functionalized multi-wall carbon nanotubes in aqueous solution using the hydrophobin HFBI and their electroanalytical application.
A novel noncovalent approach was developed for the functionalization of multi-wall carbon nanotubes (MWNTs) using the hydrophobin, HFBI. Owing to the amphipathic nature, HFBI can be adopted onto the surface of MWNTs to form HFBI-MWNTs nanocomposite with good dispersion in water. The HFBI-MWNTs nanocomposite was characterized by scanning electron microscopy (SEM), transmission electron microscopy (TEM) and water contact angle measurements (WCA). Furthermore, a glucose biosensor was developed based on HFBI-MWNTs by a one-step casting method. The resulting biosensor displayed high sensitivity, wider linear range, low detection limit, and fast response for glucose detection, which implicated that the HFBI-MWNTs nanocomposite film holds great promise in the design of electrochemical devices, such as sensors and biosensors.


Angiopoietin-2 is associated with capillary leak and predicts complications after cardiac surgery.
Patients undergoing cardiac surgery are prone to numerous complications. Increased vascular permeability may be associated with morbidity and mortality due to hemodynamic instability, fluid overload, and edema formation. We hypothesized that markers of endothelial injury and inflammation are associated with capillary leak, ultimately increasing the risk of postoperative complications. In this prospective, observational, multidisciplinary cohort study at our tertiary academic medical center, we recruited 405 cardiac surgery patients. Patients were assessed daily using body impedance electrical analysis, ultrasound, sublingual intravital microscopy, and analysis of serum biomarkers. Multivariable models, as well as machine learning, were used to study the association of angiopoietin-2 with extracellular water as well as common complications after cardiac surgery. The majority of patients underwent coronary artery bypass grafting, valvular, or aortic surgeries. Across the groups, extracellular water increased postoperatively (20 ± 6 preoperatively to 29 ± 7L on postoperative day 2; P < 0.001). Concomitantly, the levels of the biomarker angiopoietin-2 rose, showing a strong correlation based on the time points of measurements (r = 0.959, P = 0.041). Inflammatory (IL-6, IL-8, CRP) and endothelial biomarkers (VE-Cadherin, syndecan-1, ICAM-1) suggestive of capillary leak were increased. After controlling for common risk factors of edema formation, we found that an increase of 1 ng/mL in angiopoietin-2 was associated with a 0.24L increase in extracellular water (P < 0.001). Angiopoietin-2 showed increased odds for the development of acute kidney injury (OR 1.095 [95% CI 1.032, 1.169]; P = 0.004) and was furthermore associated with delayed extubation, longer time in the ICU, and a higher chance of prolonged dependence on vasoactive medication. Machine learning predicted postoperative complications when capillary leak was added to standard risk factors. Capillary leak and subsequent edema formation are relevant problems after cardiac surgery. Levels of angiopoietin-2 in combination with extracellular water show promising potential to predict postoperative complications after cardiac surgery. German Clinical Trials Registry (DRKS No. 00017057), Date of registration 05/04/2019, www.drks.de.


Remote after-care using smartphones: A feasibility study of monitoring children's pain with automated SMS messaging.
Monitoring children's recovery postoperatively is important for routine care, research, and quality improvement. Although telephone follow-up is common, it is also time-consuming and intrusive for families. Using SMS messaging to communicate with families regarding their child's recovery has the potential to address these concerns. While a previous survey at our institution indicated that parents were willing to communicate with the hospital by SMS, data on response rates for SMS-based postoperative data collection is limited, particularly in pediatric populations. We conducted a feasibility study with 50 completed pain profiles obtained from patients at Perth Children's Hospital to examine response rates. We collected and classified daily average pain (0-10 parent proxy score) on each day after tonsillectomy until pain-free for two consecutive days. We enrolled 62 participants and recorded 50 (81%) completed pain profiles, with 711 (97.9%) of 726 requests for a pain score receiving a response. Two families (3%) opted out of the trial, and 10 (16%) were lost to follow-up. Responses received were classified automatically in 92% of cases. No negative feedback was received, with a median (range) satisfaction score of 5 on a 5-point Likert scale (1 = very unhappy, 5 = very happy). This methodology is likely to generalize well to other simple clinical questions and produce good response rates in further similar studies. We expect SMS messaging to permit expanded longitudinal data collection and broader investigation into patient recovery than previously feasible using telephone follow-up at our institution.


PD 176252--the first high affinity non-peptide gastrin-releasing peptide (BB2) receptor antagonist.
In this paper we describe the development of a novel series of non-peptide, "balanced" neuromedin-B preferring (BB1)/gastrin-releasing peptide preferring (BB2) receptor ligands as exemplified by PD 176252. PD 176252, which exhibits nanomolar affinity for both the BB1 (Ki = 0.15 nM) and BB2 (Ki = 1.0 nM) receptors, has been demonstrated to be a competitive antagonist at these bombesin receptor subtypes.


Genetic effects on physical health: lower at higher income levels.
Given the robust finding that people in higher income groups tend to experience better physical health, there is interest in identifying mechanisms underlying this gradient. Using a nationwide sample of 719 twin pairs from the National Survey of Midlife Development in the United States, we investigated the possibility that gene-environment interaction underlies the income-health gradient. We observed that genetic variance associated with 2 measures of physical health, number of chronic illnesses and body mass index, each declined significantly with increasing income. This interaction effect could not be removed by adjusting income for the presence of health insurance coverage and education, suggesting that the interaction is not simply a result of differences in levels of those characteristics with income.