Sites of chromosomal instability in the context of nuclear architecture and function.
Chromosomal fragile sites are described as areas within the tightly packed mitotic chromatin that appear as breaks or gaps mostly tracing back to a loosened structure and not a real nicked break within the DNA molecule. Most facts about fragile sites result from studies in mitotic cells, mainly during metaphase and mainly in lymphocytes. Here, we synthesize facts about the genomic regions that are prone to form gaps and breaks on metaphase chromosomes in the context of interphase. We conclude that nuclear architecture shapes the activity profile of the cell, i.e. replication timing and transcriptional activity, thereby influencing genomic integrity during interphase with the potential to cause fragility in mitosis. We further propose fragile sites as examples of regions specifically positioned in the interphase nucleus with putative anchoring points at the nuclear lamina to enable a tightly regulated replication-transcription profile and diverse signalling functions in the cell. Consequently, fragility starts before the actual display as chromosomal breakage in metaphase to balance the initial contradiction of cellular overgrowth or malfunctioning and maintaining diversity in molecular evolution.


Effect of inhaled nitric oxide on gas exchange in patients with congestive heart failure. A randomized, controlled trial.
Conventional vasodilators increase ventilation-perfusion mismatch and do not improve gas exchange even though they reduce pulmonary hypertension. However, the effects of nitric oxide inhalation on ventilatory and gas exchange values in patients with congestive heart failure are not known. To investigate the effect of nitric oxide inhalation on gas exchange in patients with congestive heart failure. Randomized, controlled trial. University hospital. 16 patients with congestive heart failure (New York Heart Association class II or III). Patients inhaled nitric oxide gas at graded concentrations (n = 8) or were given intravenous isosorbide dinitrate, 2.5 mg (n = 8). Hemodynamic and ventilatory variables and blood gases were measured 5 minutes after inhalation of different doses of nitric oxide and 10 minutes after administration of isosorbide dinitrate. Nitric oxide inhalation reduced the mean pulmonary arterial pressure in a dose-dependent manner without altering the mean arterial pressure or cardiac output. At a dose of 40 parts per million, nitric oxide inhalation increased PaO2 (change from baseline, 12.0 mm Hg [95% CI, 2.3 to 21.7 mm Hg]; P = 0.014) and decreased the alveolar-arterial difference in partial pressure of oxygen (change, -8.6 mm Hg [CI, -16.8 to -0.4 mm Hg]; P = 0.038) and the ventilatory equivalent for carbon dioxide output (change, -6.7 [CI, -10.3 to -3.1]; P < 0.001). Although isosorbide dinitrate similarly decreased pulmonary arterial pressure, it did not alter gas exchange or ventilatory variables. Because nitric oxide inhalation improved gas exchange, it may be used as a supportive therapy when other conventional vasodilators worsen gas exchange.


Localization of subrhabdomeric haemolymph lacunae in the retina of Drosophila melanogaster and Calliphora erythrocephala.
The haemolymph of flies and other insects contains tyrosinase (EC 126.96.36.199), the rate-limiting enzyme in mammalian melanogenesis. After incubation with 5 mM L-DOPA for several hours the endogenous tyrosinase of the haemolymph forms an electron dense reaction product. This method was used to localize spaces in the retina of the wild type and the white (w) mutant of Drosophila melanogaster that are filled with haemolymph. A network of subrhabdomeric haemolymph lacunae was found. Moreover it was found that these haemolymph lacunae also form extensions into the photoreceptor cells and are connected with small haemolymph lacunae that cross the retinal basement membrane. In a second set of experiments L-DOPA was injected into the thoraces of Calliphora erythrocephala. Half-an-hour after injections the flies were killed and the eyes were embedded for electron microscopy. The small molecule of DOPA or its product dopachrome, surprisingly, penetrated the retinal basement membrane and reached the subrhabdomeric haemolymph lacunae and the ommatidial cavity.


A phase II trial of weekly chemotherapy with paclitaxel plus gemcitabine as a first-line treatment in advanced non-small-cell lung cancer.
The efficacy and toxicity of combined paclitaxel (PTX) and gemcitabine (GEM) was evaluated as a protocol for first-line chemotherapy in 40 patients with advanced non-small-cell lung cancer (NSCLC). Paclitaxel, 100 mg/m(2), was administered intravenously (IV) as a 1-h infusion, followed by GEM, 1,000 mg/m(2), IV over 30 min on days 1 and 8 of a 21-day cycle. The median age of patients was 66 years with a range of 33-75 years. Nearly all patients (39/40) had an ECOG performance status of 0 or 1. Thirteen patients (32%) had initial stage IIIB disease and 27 patients (68%) had stage IV disease. Histological subtypes were adenocarcinoma (73%) and squamous cell carcinoma (25%). Twenty-two patients (55%) achieved a partial response and none achieved a complete response, giving an overall response rate of 55% (95% confidence interval: 38.2-71.8%). Disease stability was achieved in 14 patients (35%), and 4 patients (10%) had progressive disease. The median survival time was 11.9 months (95% CI: 10.3-14 months), with a 1-year survival rate of 47.5%. Grade 3 or 4 hematological toxicities observed included neutropenia in 37.5%, anemia in 2.5%, and thrombocytopenia in 5.0% of these patients. Non-hematologic toxicities were mild, with the exception of grade 3 and 4 pneumonitis. There were no deaths due to toxicity. Weekly chemotherapy with PTX plus GEM is effective and is acceptable for the first line treatment of advanced NSCLC.


Chromium speciation using sequential injection analysis and multivariate curve resolution.
In this paper we develop a suitable method for the speciation of chromium in tanning and environmental water samples. We use sequential injection analysis (SIA) with a diode array detector linked to chemometric tools such as multivariate curve resolution-alternating least squares (MCR-ALS) to determine Cr(III) and Cr(VI) species. Although Cr(III) is an absorbent species, its sensitivity is much lower than that of Cr(VI). To increase its sensitivity, therefore, it was complexed with EDTA. This method involves generating a pH gradient in the system reactor that converts dichromate into chromate in such a way that, when the sample reaches the detector, selective areas are observed and a data matrix is obtained. Applying MCR enables Cr(III) and Cr(VI) to be successfully determined simultaneously in tanning and environmental wastewater samples.


Polyphenols from whole millet grain (Setaria italica) alleviate glucose and lipid homeostasis in diet-induced obese mice by increasing endogenous GLP-1.
Foxtail millet (Setaria italica) is a whole millet grain that has been considered for improving the disorder of glucose and lipid metabolism. The purpose of the work is to explore the extraction and enrichment of polyphenols from foxtail millets which can regulate the disorder of glucose and lipid metabolism by increasing endogenous GLP-1 (glucagon-like peptide-1). The optimum ultrasound-assisted extraction (UAE) of foxtail millet polyphenols (FMPs) was as follows: 70 °C and 400 W and 70% ethanol concentration, further purification using macroporous resin. In vitro, the FMP eluent of 60% ethanol (FMP-60) has the best effect in promoting GLP-1 secretion from L cells among the different active components of FMP. Millet polyphenols (MPs) were obtained from finishing foxtail millet with the bran removed by the same extraction and purification method. Compared with MP-60, FMP-60 mainly included eight active phenolic constituents and contained more ferulic acid, p-coumaric acid, 2-hydroxycinnamic acid, and coniferaldehyde. After gavage treatment of diet-induced obese (DIO) mice with FMP-60, FMP-60 promoted endogenous GLP-1 secretion in mice and ameliorated disorders of glucolipid metabolism in DIO mice. FMP-60 could improve glucose homeostasis and ameliorates metabolic disease by promoting the endogenous GLP-1 level and preventing weight gain in DIO mice. © 2023 Society of Chemical Industry.


Alterations of high-energy phosphate compounds in the skeletal muscles of rats intoxicated with diisopropylphosphorofluoridate (DFP) and Soman.
The purpose of the present investigation was to determine the changes in high-energy phosphate compounds and to establish their relationship with organophosphate-induced necrotic lesions in skeletal muscles of rats. Following an acute toxicity signs-producing dose of either diisopropylphosphorofluoridate (DFP) (1.5 mg/kg, sc) or soman (0.1 mg/kg, sc), a significant decline in phosphocreatine (PC) was seen as early as within 1 hr, coinciding with the appearance of necrotic lesions, as reported earlier. The maximum decrease in PC was measured after 6 hr. At this time, among the muscles studied, the hemidiaphragm (the muscle which is known to show the greatest number of necrotic lesions with both of the organophosphorus compounds) showed maximum decrease in PC (57%) with soman treatment. A detailed analysis of adenine nucleotides indicated a significant decrease of adenosine triphosphate (ATP) in all three skeletal muscles, with a marked increase in adenosine monophosphate (AMP) and adenosine diphosphate (except in extensor digitorum longus (EDL)). The levels of creatine in all three skeletal muscles remained unaltered throughout the time-course of study. The observed changes in PC, ATP, and AMP were reversed toward control baseline values after 72 hr. Daily administration of DFP (0.5 mg/kg, sc/day) for 14 days caused only a significant decrease of PC in EDL and soleus during the toxic phase (Day 5), with recovery toward the normal value during the tolerance phase (Day 14). It is concluded that both DFP and soman reduced the PC in skeletal muscles, and the time-course for PC reduction correlates well with the previously reported time-course for muscle fiber necrosis.(ABSTRACT TRUNCATED AT 250 WORDS)


Effects of iscador and vincristine and 5-fluorouracil on brain, liver, and kidney element levels in alloxan-induced diabetic mice.
Exposure to substance toxicity is especially dangerous for diabetics because it accelerates and intensifies diabetic complication. Homeostasis of trace elements can be disrupted by diabetes mellitus. On the other hand, disturbance in trace element status in diabetes mellitus may contribute to insulin resistance and development of diabetic complications. The aim of the present study was to compare the concentration of elements in the brain, liver, and kidneys of animals with induced diabetes after the administration of plant preparations (iscador and vincristine) and 5-fluorouracil. The experiments were carried out on male mice. The animals were divided into five groups of ten mice each: one control and four experimental groups. The first experimental group was administered alloxan at 75 mg/kg b.w. for 4 days, the second group was administered both alloxan at 75 mg/kg b.w. and vincristine 1 mg/kg b.w. for 4 days, and the third group was administered both alloxan at 75 mg/kg b.w. and 5-fluorouracil 75 mg/kg b.w. for 4 days. The animals of the fourth group were administered both alloxan at 75 mg/kg b.w. and iscador Qu at 5 mg/kg b.w. for 4 days. Calcium, magnesium, iron, copper, zinc, sodium, and potassium levels in the tissues were analyzed by flame atomic absorption spectrophotometer. We observed that zinc, copper, magnesium, sodium, and potassium were lower in the brain as compared to the control animals. The copper levels in the liver were also lower in diabetic groups than in control groups. However, the iscador and vincristine and 5-fluorouracil did not induce significant differences in the five groups. In conclusion, results of the current study indicated that changes of the investigated essential elements may contribute to explaining the role of impaired element metabolism of some elements in the progression of diabetic complications.


Simultaneous aortic and renal artery reconstruction for acute arterial occlusion in solitary kidney.
A case is described of the onset of acute renal failure due to renal artery occlusion in a solitary kidney of a sixty-six-year-old woman. She had been treated for severe hypertension due to renal artery stenosis. An aortorenal bypass to revascularized the kidney was combined with repair of an abdominal aortic aneurysm. There was early and full recovery of renal function in the single kidney, and the patient was completely rehabilitated. Review of the literature shows that an aggressive surgical approach to the management of renal artery occlusion is usually followed by excellent results. The pre-existence of renal artery stenosis encourages the formation of a collateral arterial supply which maintains the nutrition of the kidney almost indefinitely, after renal artery occlusion. Revascularization will result in prompt recovery of renal function.


Oral thromboprophylaxis following total hip replacement: the issue of compliance.
Thirty-five to 40 days' thromboprophylaxis is recommended following total hip replacement (THR). Low molecular weight heparin (LMWH) injected by a health professional ensures good compliance. Compliance with recent oral anticoagulants has not been precisely assessed. Oral self-administration, without coagulation monitoring tests, may be a worrying issue in the management of what is a potentially catastrophic adverse event, without prodromal symptoms alerting the patient to the need for regular intake throughout the prescription period. It was hypothesized that compliance with these new oral anticoagulants is good over the entire treatment period. The present cohort study prospectively assessed compliance with oral medication (two capsules of dabigatran etexilate [Pradaxa(®)] per day in a single dose at a set time) following THR. An electronic device continuously monitored the day and time of extraction of capsules from the package. All included patients underwent clinical and echo-Doppler examination at day 30±5 after the start of the study. Fifty-six patients were included at their discharge home. Overall compliance was 98.1% (3,188/3246 capsules correctly taken), falling off slightly over time but never below 97.1%. One patient was diagnosed with symptomatic thrombophlebitis 34 days postoperatively, associated with non-compliance at day 11. End of follow-up echo-Doppler found four cases of asymptomatic distal venous thrombosis. There were no hemorrhagic complications. The risk of thromboembolic complications diminishes over time, while oral anticoagulants have a wide therapeutic window and relatively long half-life (15-17 hrs). Efficacy was demonstrated, with improved patient comfort and cost-saving. Compliance in the present series was satisfactory. This, however, should not mean that patients not be appropriately informed, as in the present study, so as to improve compliance. Level III, prospective diagnostic.


Highly sensitive and selective separation of intact parathyroid hormone and variants by sheathless CE-ESI-MS/MS.
Parathyroid hormone (PTH) is a common clinical marker whose quantification relies on immunoassays, giving variable results as batch, brand, or target epitope changes. Sheathless CE-ESI-MS, combining CE resolution power and low-flow ESI sensitivity, was applied to the analysis of PTH in its native conformation in the presence of related forms. Fused silica and neutral-coated capillaries were investigated, as well as preconcentration methods such as transient isotachophoresis, field-amplified sample injection (FASI), and electrokinetic supercharging (EKS). The method for the separation of PTH and its variants was first developed using fused-silica capillary with UV detection. An acidic BGE was used to separate 1-84 PTH (full length), 7-84 PTH, and 1-34 PTH. Acetonitrile was added to the BGE to reduce peptide adsorption onto the capillary wall and transient isotachophoresis was used as analyte preconcentration method. The method was then transferred to a sheathless CE-ESI-MS instrument. When using a fused silica capillary, CE-MS was limited to μg/mL levels. The use of a neutral coating combined with FASI or EKS allowed a significant increase in sensitivity. Under these conditions, 1-84 PTH, 7-84 PTH, and 1-34 PTH were detected at concentrations in the low ng/mL (FASI) or pg/mL (EKS) range.


Drivers of Cost for Pancreatic Surgery: It's Not About Hospital Volume.
Outcomes for pancreatic resection have been studied extensively due to the high morbidity and mortality rates, with high-volume centers achieving superior outcomes. Ongoing investigations include healthcare costs, given the national focus on reducing expenditures. Therefore, we sought to evaluate the relationships between pancreatic surgery costs with perioperative outcomes and volume status. We performed a retrospective analysis of 27,653 patients who underwent elective pancreatic resections from October 2013 to June 2017 using the Vizient database. Costs were calculated from charges using cost-charge ratios and adjusted for geographic variation. Generalized linear modeling adjusting for demographic, clinical, and operation characteristics was performed to assess the relationships between cost and length of stay, complications, in-hospital mortality, readmissions, and hospital volume. High-volume centers were defined as hospitals performing ≥ 19 operations annually. The unadjusted mean cost for pancreatic resection and corresponding hospitalization was $20,352. There were no differences in mean costs for pancreatectomies performed at high- and low-volume centers [- $1175, 95% confidence interval (CI) - $3254 to $904, p = 0.27]. In subgroup analysis comparing adjusted mean costs at high- and low-volume centers, there was no difference among patients without an adverse outcome (- $99, 95% CI - $1612 to 1414, p = 0.90), one or more adverse outcomes (- $1586, 95% CI - $4771 to 1599, p = 0.33), or one or more complications (- $2835, 95% CI - $7588 to 1919, p = 0.24). While high-volume hospitals have fewer adverse outcomes, there is no relationship between surgical volume and costs, which suggests that, in itself, surgical volume is not an indicator of improved healthcare efficiency reflected by lower costs. Patient referral to high-volume centers may not reduce overall healthcare expenditures for pancreatic operations.


Unilateral contraction of facial muscles do effect emotions: a "failed replication's" failure to perform a replication.
Kop, Merckelbach and Muris (1991) reported a failure to replicate Schiff and Lamon's (1989) finding that unilateral muscle contractions induce emotions and influence cognitions in a manner which reflect those emotions. However, the procedures they used were different from the original experiment in substantive ways. These differences are described and it is explained how they account for the failure to replicate. This discussion helps illustrate the nature of the phenomenon which has been shown to be both robust and clinically relevant.


Tight-binding approach to penta-graphene.
We introduce an effective tight-binding model to discuss penta-graphene and present an analytical solution. This model only involves the π-orbitals of the sp(2)-hybridized carbon atoms and reproduces the two highest valence bands. By introducing energy-dependent hopping elements, originating from the elimination of the sp(3)-hybridized carbon atoms, also the two lowest conduction bands can be well approximated - but only after the inclusion of a Hubbard onsite interaction as well as of assisted hopping terms. The eigenfunctions can be approximated analytically for the effective model without energy-dependent hopping elements and the optical absorption is discussed. We find large isotropic absorption ranging from 7.5% up to 24% for transitions at the Γ-point.


Unilateral optic neuritis, scleritis and exudative retinal detachment due to recurrent orbital pseudotumor.
Idiopathic orbital inflammation, also known as orbital pseudotumor, describes a spectrum of idiopathic, non-neoplastic, non-infectious, space-occupying orbital lesions without identifiable local or systemic cause. The condition occurs mainly in young adults who may present with acute pain, proptosis, chemosis and limitations of extraocular movements. Decreased vision due to optic nerve infiltration and macular edema as a result of scleritis is less common sequel of orbital pseudotumor. Herein, we present a case of unilateral orbital pseudotumor in a young male who presented with chief complaints of painful decreased vision which was attributed to optic neuritis and macular edema as a result of scleritis. Imaging studies were helpful in the establishment of the correct diagnosis and patient's complaints improved with administration of systemic corticosteroids.


Facile ultrathin film of silver nanoparticles for bacteria sensing.
Silver nanoparticles (AgNPs) exhibit excellent anti-microbial and bactericidal properties. Due to bacterial abhorrence for AgNPs, it is difficult to develop a label-free, sensitive and low-cost bacteria sensor using them. In the present article, we report that an ultrathin and uniform Langmuir-Schaefer (LS) film of AgNPs can be employed for bacteria sensing effectively as compared to that of non-uniform and randomly distributed AgNPs in spin coated film. The uniformly distributed AgNPs in the LS film offer a relatively larger contact surface for bacteria as compared to that of spin coated film. Due to higher contact surface, adsorption of the bacteria on LS film is strongly preferable as compared to that of spin coated film leading to an enhanced sensing performance of the LS film than that of spin coated film. Soil bacteria was grown by the standard protocol and were utilized as model system for bacteria sensing application. The soil bacteria sensing was done by monitoring the piezoresponse and dissipation parameters using a quartz crystal microbalance, simultaneously. Our study indicates that the LS film of AgNPs not only facilitates the adsorption of the soil bacteria but also kills them.


Partners in Crime: Phenolic Glycolipids and Macrophages.
Two recent articles advance our understanding of mycobacterial pathogenesis, revealing key roles for bacterially derived phenolic glycolipids (PGLs). In leprosy, Mycobacterium leprae PGL-1 uniquely subverts local macrophages to produce neurotoxic nitric oxide (NO), leading to nerve demyelination. In a related model, Mycobacterium marinum PGL stimulates the recruitment of growth-conducive monocytes to sites of initial infection as an early immune evasion strategy.


In vivo efficiency of praziquantel treatment of single-sex Schistosoma japonicum aged three months old in mice.
Schistosomiasis is a major neglected tropical disease mainly caused by Schistosoma haematobium, S. japonicum and S. mansoni, and results in the greatest disease burden. Mass drug administration (MDA) with praziquantel (PZQ), a single drug only available for the disease, has played a vital role in schistosomiasis control. Therefore, any possibility of selection of the parasites for PZQ resistance or low sensitivity may hamper the 2030's target of global disease elimination. We had experimentally demonstrated the long-term survival and reproductive potential of single-sex (of either sex) S. japonicum infections in definitive hosts mice. What has not yet been adequately addressed is whether the long live single-sex schistosomes remain sensitive to PZQ, and what reproduction potential for those schistosomes surviving treatment may have. We therefore performed experimental mice studies to explore the treatment effectiveness of PZQ (at total doses of 200 or 400 mg/kg, corresponding to the sub-standard or standard treatment doses in humans) for single-sex S. japonicum aged three months old. The results showed that no treatment efficiency was observed on female schistosomes, whereas on male schistosomes only at PZQ 400 mg/kg a significant higher efficiency in reducing worm burdens was observed. Moreover, either schistosome males or females surviving PZQ treatment remained their reproduction potential as normal. The results indicate that long (i.e., three months) live single-sex S. japonicum can easily survive the current treatment strategy, and moreover, any schistosomes, if with PZQ resistance or low sensitivity, could be easily transmitted in nature. Therefore, in order to realize the target for the national and the global schistosomiasis elimination, there is undoubtedly a great need for refining PZQ administration and dosage, looking for alternative therapies, and/or developing vaccines against schistosome.


A continuous quality improvement program to focus a college of pharmacy on programmatic advancement.
To enhance the achievement of a college of pharmacy's goals for education, research, and service missions by implementing an excellence program based on the Studer Group model for continuous quality improvement. The Studer model was combined with university strategic planning for a comprehensive quality-improvement program that was implemented over 5 years. The program included identifying and measuring key performance indicators, establishing specific "pillar" goals, aligning behaviors with goals and values, and training leaders. Assessment of key performance indicators over 5 years demonstrated progress toward achieving college goals for student and faculty satisfaction, research funding, numbers of students seeking formal postgraduate training, and private giving. Implementation of a continuous quality-improvement program based on the Studer program enabled the college to focus on and meet its yearly and strategic goals for all components of its mission.


Genetic polymorphisms in the cytochrome P450 1A1 and 2E1 genes, smoking, drinking and prostate cancer susceptibility: a case-control study in a Han nationality population in Southern China.
To investigate the association among the polymorphisms of the cytochrome P450 1A1 and 2E1 genes, smoking, drinking and the risk of prostate cancer (PCa) in a Han nationality population in Southern China. A case-control study including 225 PCa patients and 250 age-matched controls was conducted. The six polymorphic sites of the CYP 1A1 and CYP2E1 genes were analysed by polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) or allele-specific PCR technique using genomic DNA isolated from peripheral blood lymphocytes. We found that the CYP1A1 Val/Val genotype significantly increased the risk for PCa (OR, 2.26; 95% CI, 1.09-4.68). In contrast, the CYP2E1 C1/C2 (OR, 0.67; 95% CI, 0.46-0.99) or C2/C2 genotype (OR, 0.31; 95% CI, 0.10-1.00) significantly decreased the risk. Furthermore, the individuals carrying the CYP1A1 Val allele and the CYP2E1 C1/C1 genotype showed the highest risk (OR, 2.50; 95% CI, 1.45-4.29). Though there was no significant difference with smoking history (P = 0.237) or drinking habit (P = 0.499) between cases and controls, a deep smoking habit (OR, 2.02; 95% CI, 1.28-3.17) and heavy smoking history (OR, 1.61; 95% CI, 1.04-2.50) significantly increased the susceptibility of PCa after stratification by smoking method and accumulative smoking amount. Moreover, both the CYP1A1 Val allele (OR, 2.82; 95% CI, 1.49-5.35) and CYP2E1 C1/C1 genotype (OR, 2.57; 95% CI, 1.31-5.02) had obvious interaction with heavy smoking history that significantly raised the risk. We also discovered a significant interaction between the CYP2E1 C1/C1 genotype and drinking (OR, 1.85; 95% CI, 1.04-3.28). Individuals carrying the CYP1A1 Val allele or the CYP2E1 C1/C1 genotype with a smoking or drinking habit were at increased risk of PCa, which also showed a positive correlation with exposure dose of tobacco.


Comparison of Intranasal Dexmedetomidine with Intranasal Clonidine as a Premedication in Surgery.
To compare effectiveness of intranasal dexmedetomidine and clonidine as anxiolytics and sedatives in pediatric patients undergoing various surgeries. This double blind randomized placebo controlled study was conducted on 105 surgical patients of American Society of Anesthesiologist (ASA) physical status І-ІІ, aged between 2 and 9 y in a tertiary-care hospital (February 2014 to September 2015). Participants were randomly allocated to three groups to receive either intranasal dexmedetomidine 2 μg/kg (Group І) or intranasal clonidine 3 μg/kg (Group ІІ) or intranasal saline 0.5 ml (Group ІІІ). The primary outcome measure was proportion of patients with satisfactory anxiolysis and sedation at 30 min after drug administration. Secondary outcome measures included time taken to achieve Aldrete score of 9 and number of doses of rescue analgesia required in 12 h after surgery. Satisfactory anxiolysis was achieved by 88.5% in Group І vs. 60% in Group ІІ (p = 0.001) and satisfactory sedation by 57.1% in Group І vs. 25.7% in Group ІІ (p = 0.001) 30 min after premedication. Rescue analgesia requirement was significantly less in Group І as compared to Group ІІ (p = 0.001) while time taken to achieve Aldrete score was comparable between the study groups (p = 0.185). Intranasal dexmedetomidine is a better anxiolytic and sedative as compared to clonidine. Postoperative analgesic requirement was also significantly decreased after intranasal dexmedetomidine. Thus, it can be preferred as compared to clonidine for premedication in pediatric surgical patients.


The influence of 2- chlorodeoxyadenosine in combination with tumour necrosis factor-alpha or its mutein on murine leukaemias L1210 and P388.
We investigated the influence of 2-chlorodeoxyadenosine (2-CdA) in combination with tumour necrosis factor-alpha (TNFalpha) or its mutein VI, which differs from the native molecule by N-terminal amino acid composition, on the survival time of mice inoculated with leukaemia L1210 or P388. Groups of mice with leukaemia L1210 and P388 receiving 2-CdA combined with TNFalpha had shorter survival times than animals treated with these agents separately. In contrast, the administration of 2-CdA in conjunction with mutein VI, prolonged the survival of mice inoculated with these leukaemias as compared with animals receiving these agents separately. The results of the present study emphasize the importance of the biological activity of the TNFalpha molecule N-terminus.


Presynaptic dendrites and serial synapses in the intermediate and deep layers of the cat superior coliculus.
Presynaptic dendrites (PSDs) which participate in the serial synapses have frequently been found in the intermediate and deep layers of the cat superior colliculus. The PSDs are presynaptic to small dendritic shafts or spines with symmetrical membrane thikening, and postsynaptic to axon terminals with asymmetrical synaptic contact. Two types of the axon terminals are observed, both of which contain pleomorphic vesicles.


Probiotics in non-alcoholic fatty liver disease: which and when.
Non-alcoholic fatty liver disease (NAFLD) is a common and serious disease. Literature reports the central role of the gut-liver axis in the pathogenesis of NAFLD, and recently suggests that the microbiota is a casual factor of the disease, involved in the interactions between intestinal lumen and liver. Probiotic are commensal bacteria, able to modulate the microbiota with benefits for the health of humans. Several data suggest a range of potentially beneficial medicinal uses for probiotics, in particular in NAFLD patients. However, the species with higher efficacy in this disease are not identified. The present review focuses on the role of gut-liver axis in the pathogenesis, and on the potential therapeutic role of probiotics in the managing of NAFLD.


SARS-CoV-2 Infection During Pregnancy and Associated Perinatal Health Outcomes: A National US Cohort Study.
Although severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has been associated with increased risk of adverse perinatal health outcomes, few large-scale, community-based epidemiological studies have been conducted. We conducted a national cohort study using deidentified administrative claims data for 78 283 pregnancies with estimated conception before 30 April 2020 and pregnancy end after 11 March 2020. We identified SARS-CoV-2 infections using diagnostic and laboratory testing data, and compared the risk of pregnancy outcomes using Cox proportional hazard models treating coronavirus disease 2019 (COVID-19) as a time-varying exposure and adjusting for baseline covariates. Of the pregnancies, 2655 (3.4%) had a documented SARS-CoV-2 infection. COVID-19 during pregnancy was not associated with risk of miscarriage, antepartum hemorrhage, or stillbirth, but was associated with 2-3 fold higher risk of induced abortion (adjusted hazard ratio [aHR], 2.60; 95% confidence interval [CI], 1.17-5.78), cesarean delivery (aHR, 1.99; 95% CI, 1.71-2.31), clinician-initiated preterm birth (aHR, 2.88; 95% CI, 1.93-4.30), spontaneous preterm birth (aHR, 1.79; 95% CI, 1.37-2.34), and fetal growth restriction (aHR, 2.04; 95% CI, 1.72-2.43). Prenatal SARS-CoV-2 infection was associated with increased risk of adverse pregnancy outcomes. Prevention could have fetal health benefits.


Effect of cicloxilic acid on the bile lipid composition in cholelithiasis.
5 patient with cholesterol gallstones were treated with cis-2-hydroxy-2-penyl-cyclohexanecarboxilic acid (cicloxilic acid) 240 mg daily for one year. Before treatment and after 1 month's, 3 months' and 1 year's treatment gallbladder bile was withdrawn by duodenal tube after i.v. cerulein stimulation. The bile was assayed for lipids and the lithogenic index was determined. The pool of bile acids was also determined and liver function tests performed. The results show a gradual lowering of the mean lithogenic index in the course of treatment. The blood chemistry values remained within strictly normal limits.


A fly GWAS for purine metabolites identifies human FAM214 homolog medusa, which acts in a conserved manner to enhance hyperuricemia-driven pathologies by modulating purine metabolism and the inflammatory response.
Elevated serum urate (hyperuricemia) promotes crystalline monosodium urate tissue deposits and gout, with associated inflammation and increased mortality. To identify modifiers of uric acid pathologies, we performed a fly Genome-Wide Association Study (GWAS) on purine metabolites using the Drosophila Genetic Reference Panel strains. We tested the candidate genes using the Drosophila melanogaster model of hyperuricemia and uric acid crystallization ("concretion formation") in the kidney-like Malpighian tubule. Medusa (mda) activity increased urate levels and inflammatory response programming. Conversely, whole-body mda knockdown decreased purine synthesis precursor phosphoribosyl pyrophosphate, uric acid, and guanosine levels; limited formation of aggregated uric acid concretions; and was sufficient to rescue lifespan reduction in the fly hyperuricemia and gout model. Levels of mda homolog FAM214A were elevated in inflammatory M1- and reduced in anti-inflammatory M2-differentiated mouse bone marrow macrophages, and influenced intracellular uric acid levels in human HepG2 transformed hepatocytes. In conclusion, mda/FAM214A acts in a conserved manner to regulate purine metabolism, promotes disease driven by hyperuricemia and associated tissue inflammation, and provides a potential novel target for uric acid-driven pathologies.


Suicidal communication signifies suicidal intent in Chinese completed suicides.
Recognizing suicidal communication from the distressful catharsis in a high-risk group with suicidal tendencies is essential for suicide prevention. This study analyzes whether suicidal communication can indicate the severity of suicidal intent. Various types of suicidal communication are defined, and their clinical significance is further explored. A comprehensive analysis of the psychological autopsy data of 200 victims of completed suicide, including their general socio-demographic status, suicidal communication methods, previous suicide attempts, mental disorders, and psychosocial situation. Our results showed that 39.5% of all the subjects were suicidal communicators, 23.0% had previously attempted suicide, and 14.0% left suicide notes; 32.4% of 142 subjects free of physical disease suffered from mental disorders. Suicidal communication included verbal communication, behavioral communication, and suicidal notes. Younger people with a higher level of education were more inclined to communicate their suicidal intent by leaving a suicide note. Suicide notes, but not previous suicide attempts or psychosocial situation, were significantly correlated with suicidal intent. Suicidal communicators showed higher depression scores than non-communicators. Those who suffered from mood disorders with higher levels of both depression and suicidal intent were more likely to expose their intent through behavioral communication. The present study provides strong evidence that suicidal communication can indicate the severity of suicidal intent. Current findings help interpret high-risk, self-destructive behavior and consequently provide the theoretical basis for a feasible suicide prevention program.


[Changes in UDP-glucuronosyl-, glutathione-S-transferase and lipid peroxidation in rat liver microsomes during gamma-irradiation and protective effect of alpha-tocopherol].
Stimulation of lipid peroxidation, accompanied by a decrease in activity of UDP-glucuronyl- and glutathione-S-transferases, was observed in rat liver microsomes within one day after gamma-irradiation. Maximal alteration of the patterns studied was detected within 5 days. Preadministration of alpha-tocopherol, within 14 days at a dose of 200 mg/kg of body mass, prevented distinctly the impairing effect of irradiation.


Whole exome sequencing for non-selective pediatric patients with hyperlipidemia.
Hyperlipidemia is a group of conditions with abnormally elevated levels of any or all lipids or lipoproteins in the blood. It is highly heterogeneous both genetically and clinically, which contributes to diagnostic challenges and results in many patients to be underdiagnosed and undertreated in China. Precise diagnosis and early management are critical to reduce the incidence of potential coronary artery disease and cardiovascular disease. We performed a single center study to demonstrate the clinical utility of the genome-first approach by whole exome sequencing (WES) for 12 pediatric patients with abnormal lipids or lipoproteins levels. In vitro experiments were performed in COS-7 cells to further evaluate the biological function of the novel variants. We identified ten pathogenic and likely pathogenic variants and three of them were novel. Molecular cause was uncovered in five (41.7%) patients including three lipoprotein lipase deficiency patients, one hypercholesterolemia patient and one sitosterolemia patient. We also found three patients with rare variants of uncertain significance. Copy number variant (CNV) analysis with WES data did not reveal any potential hyperlipidemia related CNVs in all patients. We expanded the mutation and phenotype spectra of familial hyperlipidemia. Our study demonstrated the effectiveness of genome-first approach for evaluation pediatric hyperlipidemia patients and showed that WES can be used as the first-tier test for patients with suspected Mendelian hyperlipidemia disorder.


Arteriolization of capillaries and FGF-2 upregulation in skeletal muscles of patients with chronic peripheral arterial disease.
Microvascular changes in ischemic skeletal muscle are described derived from patients with long-lasting peripheral arterial disease (PAD). Skeletal muscles from the lower limb of 17 patients (obtained after amputation) with chronic PAD and 4 asymptomatic controls (obtained from biopsies after bypass surgery) were evaluated by electron microscopy and immunohistochemistry. The capillaries in skeletal muscles of PAD patients were surrounded by a more than 1 microm-thick coat, which was positively stained for basement membrane pericapillary coat collagen type IV. Thickness of the coat correlated with presence of PAD (p < .0001), and less strongly with diabetes mellitus (p = .023) and age of patients (p = .019). The majority of the capillaries in skeletal muscles of PAD patients (71.1 +/- 15.3%) were covered with cells positive for smooth muscle cell actin (sma) as compared to samples from asymptomatic controls (22.8% +/- 9.6%; p < .0001) suggesting advanced arteriolization. Semiquantitative analysis revealed that patients with PAD demonstrate a higher expression of FGF-2 in capillary endothelial cells (67.8 +/- 17.5%) as compared to controls (10.2 +/- 8.4%; p < .0001), whereas VEGF immunoreactivity was only occasionally present in extravascular cells. Thickened collagen type IV-positive basement membranes in combination with a significant increase in sma-coverage indicate arteriolization of capillaries characteristic for chronic PAD, what may be related to high FGF-2 expression in capillary endothelial cells.


Effects of dopamine modulation on chronic stress-induced deficits in reward learning.
Anhedonia is characteristically preceded by chronic stress, likely involving downstream effects of glucocorticoid alterations on dopamine (DA) function. To elucidate the neural underpinnings of this interaction, we examined whether acute pharmacological modulation of DA alters reward learning after chronic mild stress (CMS). Forty-eight male Wistar rats were exposed to a 21-day CMS regime (n = 48 no stress controls) before completing the probabilistic reward task (PRT), a well-validated cross-species test of reward learning. We first examined whether stress-induced reward dysfunction could be restored by systemic injections of low-dose amisulpride (AMI), which increases DA transmission via D2-like autoreceptor blockade. Then, we investigated region-specific effects through bilateral infusions of quinpirole (QUIN), a D2-like receptor agonist, into either the nucleus accumbens core (NAcc) or medial prefrontal cortex (mPFC). Blunted reward learning in CMS animals was reversed by acute AMI administration, but this treatment did not alter reward learning in the no stress group. Elevated adrenal gland weight, a proxy for stress reactivity, predicted lower reward learning in the untreated CMS group. This effect was extinguished following AMI treatment. These findings might be attributed to significantly higher D2 receptor density in the NAcc of high stress reactive animals. To this end, NAcc QUIN infusions potentiated reward learning relative to mPFC QUIN infusions in CMS rats, but there was no effect in no stress control rats. Collectively, these findings suggest that DA modulation reverses stress-induced reward dysfunction, even among the most stress-reactive animals. The effect might depend on D2-like receptor activation in the mesolimbic system.


Identification of linear B-cell epitopes on the phosphoprotein of canine distemper virus using four monoclonal antibodies.
The highly contagious canine distemper virus (CDV) is a non-segmented single-stranded negative-sense RNA virus, which belongs to the Morbillivirus genus of the Paramyxoviridae family. The phosphoprotein (P) of CDV plays the important role in the virus replication and pathogenesis. In this study, we characterized four monoclonal antibodies (MAbs), designated as Pc7, Pc8, Pc11 and Pc25 MAbs against the P protein of CDV-PS strain. A series of overlapping P protein-derived peptides representing the CDV-PS phosphoprotein (aa232-507) were screened to identify linear peptide epitopes recognized by each MAb. Finally, four epitopes, 238SHGMGIVAGSTN249 (E2-9), 264GPSVSAENVRQ274 (E6-2), 390INPELRPIIGR400 (E27-2) and 252TQSALKSTG260 (E4-9), are minimal linear epitopes recognized by the Pc7, Pc8, Pc11 and Pc25 MAbs, respectively. Each identified B-cell epitope was able to be recognized by CDV positive dog serum. Alignment analysis of the amino acid sequences indicated that the linear B-cell epitope of the Pc11 MAb is relatively conserved among different CDV strains, but the linear B-cell epitopes recognized by Pc7, Pc8 and Pc25 MAbs are not conserved among CDV strains. Our results revealed that the E27-2 peptide might be a common B-cell binding epitope of CDV antibodies. These findings may provide a useful basis for the development of new diagnostic assays for CDV.


The role of free fatty acids in pulmonary fat embolism.
Pulmonary embolism was produced in rabbits by the intravenous injection of 0-5 ml/kg body-weight of glycerol trioleate and mineral oil. Lung weight, pulmonary total lipid, esterified and free fatty acids content increased in both groups, but the concentration of free fatty acids increased only in the animals injected with neutral fat. Mineral oil injection produced stasis and haemorrhage; neutral fat produced exudation of serous liquid into the alveoli and an inflammatory reaction. There are definite differences between the pulmonary effects of mineral oil embolism and neutral fat embolism. The observations support the assumption that pulmonary changes in fat embolism are due to the toxic effect of free fatty acids liberated from the embolized neutral fat.


Long-term prognosis in patients with clipped unruptured cerebral aneurysms--increased cerebrovascular events in patients with surgically treated unruptured aneurysms.
We retrospectively investigated surgical immediate and long-term overall results after clipping of the unruptured aneurysms. Between 1991 and 2008, 166 patients underwent neck clipping of unruptured saccular aneurysms at our institute. Patients were subsequently followed to clarify the occurrence of subarachnoid hemorrhage (SAH), and stroke other than SAH, aneurysm recurrence, cerebrovascular death, all-cause death, and risk factors. Surgical complication was noted in 14 patients (8.4%) and surgical morbidity in two patients (1.2%). Of 164 patients except for these two patients who suffered surgical morbidity, we could obtain more than 3 years follow-up information for 144 patients (87.8%). There were 49 men and 95 women. The mean age was 58.5 years, and mean follow-up period was 7.9 years. Eight cases had died during follow-up (hepatic insufficiency in one, renal insufficiency in one, suicide in one, intracerebral hemorrhage (ICH) in two, SAH in one, and pneumonia after stroke in two). Therefore, the cause of death was stroke and late effects of stroke. Twelve symptomatic cerebrovascular events (cerebral infarction in seven, ICH in four, and SAH in one) occurred in ten patients. Consequently, annual risk of SAH after clipping of unruptured aneurysms was 0.085%. Besides, annual risk of stroke in those patients was 1.06%, and this incidence was higher than that in the general population. Although this study confirmed the good surgical result, annual risk of stroke after clipping of unruptured aneurysms was much higher than that in the general population. The long-term periodic examination to detect recurrent aneurysms and appropriate management to prevent stroke should be performed for patients with surgically treated unruptured aneurysm.


Tertiary lymphoid structures in pulmonary metastases of microsatellite stable colorectal cancer.
Tertiary lymphoid structures (TLSs) are ectopic lymphoid aggregates located at sites of chronic inflammation and recognized as prognosticators in several cancers. We aimed to analyse the prognostic effect of TLSs in colorectal cancer (CRC) pulmonary metastases and primary tumours, with a comparison to the CD3+ and CD8+ cell density-based immune cell score (ICS). For TLS density and TLS maximum diameter analysis, 67 pulmonary metastases and 63 primary tumours were stained with haematoxylin and eosin. For ICS scoring and analysis, CD3 and CD8 immunohistochemistry was performed. Excellent interobserver agreement was achieved in all TLS measurements. Of all patients, 36 patients had low TLS density (< 0.222 follicles/mm) and 31 patients had high TLS density (≥ 0.222 follicles/mm) in the first resected pulmonary metastases. TLS density (adjusted HR 0.91, 0.48-1.73) or maximum diameter (adjusted HR 0.78, 0.40-1.51) did not have prognostic value in pulmonary metastases. In primary tumours, higher TLS density (adjusted HR 0.39, 0.18-0.87) and maximum diameter (adjusted HR 0.28, 0.11-0.73) were associated with lower mortality. In the pulmonary metastases, ICS had superior prognostic value to TLSs; however, TLSs and ICS were significantly associated. In conclusion, TLSs in CRC pulmonary metastases had no prognostic value but correlated with the ICS. TLSs in primary tumours associated with favourable prognosis.


Increased prevalence of Helicobacter pylori infection in gastric cardia of patients with reflux esophagitis: a study from Jordan.
The role of H. pylori infection in GERD is highly controversial. Our aim was to investigate the relationship between reflux esophagitis and H. pylori infection in Jordanian subjects and to examine the gastric site for H. pylori that is most strongly associated with reflux esophagitis. During endoscopy two biopsies from the cardia and another two biopsies from the antrum were taken from 100 consecutive patients with reflux esophagitis (RE group) and from a sex- and age-matched group of 50 patients, who were referred to the endoscopy unit for evaluation of upper gastrointestinal symptoms and whose endoscopic findings were normal (control group). The biopsies were examined histologically for the presence of gastritis and H. pylori. Antral histological gastritis, Barrett's esophagus and hiatus hernia were significantly more common in the RE group than in the control group. Out of the 100 patients, 68 (68%) in the RE group and 26 of 50 (52%) in the control group were found to have H. pylori infection. The presence of H. pylori in both antral and cardiac biopsies was significantly more frequent in patients of the RE group. Forty-four patients in the RE group had positive H. pylori in both antral and cardiac biopsies (44%), while only 12 out of 50 patients of the control group (24%) had positive H. pylori in both biopsies. In the control group the prevalence of H. pylori in the antrum was similar to that of patients of the RE group (52% vs. 59%), but colonization of H. pylori in the cardia was significantly much lower than that of the RE group (24% vs. 53%; P = 0.0007). The increased prevalence of H. pylori colonization in the cardia is associated with reflux esophagitis and further controlled clinical study is required to show the impact of H. pylori eradication in patients with reflux esophagitis.


Role of organic matter in framboidal pyrite oxidation.
An experimental system has been set up to investigate the reaction kinetics of framboidal pyrite oxidation in real, reactive acid sulfate soil assemblages. This study was undertaken to determine the degree to which pyrite oxidation rates are reduced by bacteriological reactions and organic matter, which both modify the net reaction mechanisms and compete for available oxygen. The results from these experimental runs not only confirm the role of organic matter in mitigating pyrite oxidation but indicate that at least initially, the acidity produced is consumed or otherwise ameliorated by parallel reactions. Tracking pH or [H+] in both a reactor and in soil does not accurately reflect reaction progress and may not correctly indicate the true level of risk. In comparison, the tracking of pyrite oxidation with the concentration of sulfate in solution is not affected by side reactions or precipitation and is therefore a better indicator for the rate of pyrite destruction.


A preventative approach to emotional illness in psychiatric residents.
Emotional illness in psychiatric residents and its relationship to psychiatric postgraduate training is examined. First, the pertinent literature is reviewed. Psychological and social factors which predispose, precipitate, and perpetuate these emotional disturbances are discussed. The significance of emotional illness in psychiatric residents to the teaching and learning of psychiatry and to the psychiatric profession is clarified. Second, the currently unresolved dilemma of the psychiatric resident "Teach or Treat?" is presented. It is the author's contention that by redefining "treatment" in terms of the goals and philosophy of public health this dilemma can be resolved to the satisfaction of resident, faculty, and the psychiatric profession.


Fetal Flow Quantification in Great Vessels Using Motion-Corrected Radial Phase Contrast MRI: Comparison With Cartesian.
Phase contrast MRI in the great vessels is a potential clinical tool for managing fetal pathologies. One challenge is the uncontrollable fetal motion, potentially corrupting flow quantifications. To demonstrate improvements in fetal blood flow quantification in great vessels using retrospectively motion-corrected golden-angle radial phase contrast MRI relative to Cartesian phase contrast MRI. Method comparison. Computer simulation. Seventeen pregnant volunteers. 1.5T and 3T. Cartesian and golden-angle radial phase contrast MRI. Through computer simulations, radial (with and without retrospective motion correction) and Cartesian phase contrast MRI were compared using flow deviations. in vivo Cartesian and radial phase contrast MRI measurements and reconstruction qualities were compared in pregnancies. Cartesian data were reconstructed into gated reconstructions (CINEs) after cardiac gating with metric optimized gating (MOG). For radial data, real-time reconstructions were performed for motion correction and MOG followed by CINE reconstructions. Wilcoxon signed-rank test. Linear regression. Bland-Altman plots. Student's t-test. Simulations showed significant improvements (P < 0.05) in flow accuracy and reconstruction quality with motion correction ([mean/peak] flow errors with ±5 mm motion corruption: Cartesian [35 ± 1/115 ± 7] mL/s, motion uncorrected radial [25 ± 1/75 ± 2] mL/s and motion-corrected radial [1.0 ± 0.5/-5 ± 1] mL/s). in vivo Cartesian reconstructions without motion correction had lower quality than the motion-corrected radial reconstructions (P < 0.05). Across all fetal mean flow measurements, the bias [limits of agreement] between the two measurements were -0.2 [-76, 75] mL/min/kg, while the linear regression coefficients were (Mradial = 0.81 × MCartesian + 29.8 [mL/min/kg], r2 = 0.67). The corresponding measures for the peak fetal flows were -23 [-214, 167] mL/min/kg and (Pradial = 0.95 × PCartesian -1.2 [mL/min/kg], r2 = 0.80). Cartesian reconstructions of low quality showed significantly higher estimated mean and peak (P < 0.05) flows than the corresponding radial reconstructions. Simulations showed that radial phase contrast MRI with motion compensation improved flow accuracy. For fetal measurements, motion-corrected radial reconstructions showed better image quality than, and different flow values from, Cartesian reconstructions. Level of Evidence 1. Technical Efficacy Stage 1. J. MAGN. RESON. IMAGING 2021;53:540-551.


[Biological capabilities of the thymus of human fetus during normal development and during constant exposure to small doses of radiation after the accident at the Chernobyl power plant].
The literature information and the authors's data are presented on the lability of human fetus thymus changes under extremal conditions. In particular, the source of the thymus development is discussed determining its morphogenetic potencies, the sequences of its endocrine and lymphocytopoietic function appearance. Lymphocytes composition and kinetics of their quantity in the process of fetus development and thymus response to the unfavourable conditions of the mother are presented.


Identification of two amino acid residues on Ebola virus glycoprotein 1 critical for cell entry.
Using site-directed mutagenesis and retroviral vector pseudotyping of the wild type or mutated glycoprotein of Zaire ebolavirus (ZEBOV), we analyzed 15 conserved residues in the N-terminus of the filovirus glycoprotein 1 (GP1) in order to identify residues critical for cell entry. Results from infectivity assays and Western blot analyses identified two phenylalanine residues at positions 88 and 159 that appear to be critical for ZEBOV entry in vitro. We extended this observation by introduction of alanines at either position 88 or 159 of Ivory Coast Ebolavirus (CIEBOV) and observed the same phenotype. Further, we showed that introduction of each of the two mutations in a recombinant full-length clone of ZEBOV (Mayinga strain) that also carried the coding sequence for GFP could not be rescued, suggesting the mutants rendered the virus non-infectious. The two phenylalanines that are critical for both ZEBOV and CIEBOV entry are found in two linear domains of GP1 that are highly conserved among filoviruses, and thus could provide a target for rational development of broadly cross-protective vaccines or antiviral therapies.


Measurement of macrophage marker in hyperhaemolytic transfusion reaction: a case report.
Hyperhaemolytic transfusion reaction (HHTR) has been well described in patients with sickle cell disease (SCD). It is characterised by a decrease in haemoglobin concentration to levels below those before transfusion and a fall in the absolute reticulocyte count. As red blood cells (RBC) alloantibodies are typically not detected in post-transfusion samples in acute forms of HHTR, we have previously proposed that both the transfused and autologous RBCs cells (HbSS/reticulocytes) are destroyed by activated macrophages. We report a patient with SCD who presented with vaso-occlusive sickle cell crisis and developed a severe HHTR attributable to anti-Fy3. In addition to the usual supportive measures, the patient was treated with intravenous immunoglobulin (IVIG) and steroids. Serum ferritin levels were measured as an aspecific marker of macrophage activation. Steroids and IVIG were effective in managing HHTR. Ferritin levels were high at the time of haemolysis, (>10000 µg L(-1)) whereas recovery and cessation of haemolysis correlated with a decrease in ferritin levels. Serum ferritin values >10,000 µg L(-1) are considered pathognomic for conditions characterised by abnormal macrophage activation. In our case, serum ferritin levels correlate well with the disease activity and clinical response. This further supports our previous proposal that the activated macrophages play an important role in HHTR. Serum ferritin is a nonspecific marker of inflammation. A rapid specific bio-marker to measure the activity of macrophages in SCD in HHTR is desirable, and this area warrants further investigation.


Investigating the therapeutic potential of cognitive bias modification for high anxiety sensitivity.
Individuals with high anxiety sensitivity (AS) display negative interpretive biases in response to uncomfortable but nondangerous physical sensations. Research suggests that modifying interpretation biases associated with AS leads to changes in AS. The present study sought to replicate and extend this research by addressing limitations of previous studies, increasing the amount of training and adding a follow-up period. Participants high in AS were randomly assigned to four sessions of computerized interpretation bias modification (CBM-I) training or four sessions of computerized "sham" training (control condition) over a 2-week period. The outcomes were AS, interpretive biases, and reactions to induced physical sensations. Assessments occurred at baseline, during training, immediately after the final training session, and 2 weeks after the final training; number of re-assessments varied by outcome. The CBM-I condition did not outperform the control condition. At the end of the training period, the CBM-I condition displayed limited reductions in AS and interpretation biases. There were no changes in reactions to induced physical sensations. Similar results were found in the control condition for all outcomes. The control task and the dose of training may have obscured potential effects of CBM-I. When considered within the context of previous research, the experimental effects and therapeutic potential of CBM-I for high AS appear to be minimal. However, methodological questions need to be resolved before such a conclusion can be considered definitive.


Bipolar disorder and bone health: A case-control study.
Bipolar disorder (BD) is associated with significant psychological and physical comorbidity. Yet little is known about the bone health of individuals with BD. Thus, we aimed to investigate the association between BD and bone health in a population-based sample of women. Women with a history of BD (cases; n = 117) were recruited from public and private health care settings and controls, without BD, were drawn from the Geelong Osteoporosis Study (n = 909). BD was identified using a semi-structured clinical interview (SCID-I/NP). Bone mineral density (BMD) was measured at the spine, femoral neck and total body using dual energy x-ray absorptiometry, and bone quality by quantitative heel ultrasound and included the following parameters: Speed of Sound (SOS), Broadband Ultrasound Attenuation (BUA) and Stiffness Index (SI). Weight and height were measured and information on medication use and lifestyle was obtained. Adjusted mean BMD among the cases was 4.3% lower at the hip and 1.6% lower at the total body compared to controls. Age was an effect modifier at the spine. Among women <50 years, mean spine BMD for cases was 3.5% lower than controls. No differences in spine BMD for those ≥50 years were detected. Cases also had a 1.0%, 3.2% and 7.8% lower adjusted mean SOS, BUA and SI compared to controls, respectively. Course, chronicity and recovery of BD were not explored in relation to bone health. These data suggest BD is associated with low bone quantity and quality in women. Replication and research into underlying mechanisms is warranted.


Achieving hip fracture surgery within 36 hours: an investigation of risk factors to surgical delay and recommendations for practice.
The UK hip fracture best practice tariff (BPT) aims to deliver hip fracture surgery within 36 h of admission. Ensuring that delays are reserved for conditions which compromise survival, but are responsive to medical optimisation, would help to achieve this target. We aimed to identify medical risk factors of surgical delay, and assess their impact on mortality. Prospectively collected patient data was obtained from the National Hip Fracture Database (NHFD). Medical determinants of surgical delay were identified and analysed using a multivariate regression analysis. The mortality risk associated with each factor contributing to surgical delay was then calculated. A total 1361 patients underwent hip fracture surgery, of which 537 patients (39.5 %) received surgery within 36 h of admission. Following multivariate analyses, only hyponatraemia was deduced to be a significant risk factor for delay RR = 1.24 (95 % CI 1.06-1.44). However, following a validated propensity score matching process, a Pearson chi-square test failed to demonstrate a statistical difference in mortality incidence between the hypo- and normonatraemic patients [χ (2) (1, N = 512) = 0.10, p = 0.757]. Hip fracture surgery should not be delayed in the presence of non-severe and isolated hyponatraemia. Instead, surgical delay may only be warranted in the presence of medical conditions which contribute to mortality and are optimisable. III.


Getting closer: Synchronous interpersonal multisensory stimulation increases closeness and attraction toward an opposite-sex other in female participants.
Experiencing tactile facial stimulation while seeing synchronous stimulations delivered to another's face induces enfacement, i.e. the subjective experience of ownership over the other's face. The synchronous Interpersonal Multisensory Stimulation (IMS) procedure leading to enfacement induces changes beyond the bodily sense of self, such as increased feeling of closeness between self and other. However, evidence for such an influence of IMS on higher-level self-other representations remains limited. Moreover, research has been restricted to settings involving a same-sex other. The current study tested, in female participants, whether IMS could promote social closeness and attraction toward an opposite-sex other. Across two experiments, enfacement with an opposite-sex face was successfully obtained. Synchronous (vs. asynchronous) IMS yielded greater closeness with the other and induced greater Liking and Attraction scores. These novel findings add further evidence to the existence of a link between body representation and social cognition. Implications for interpersonal attraction are discussed.


Functional regulation of an ancestral RAG transposon ProtoRAG by a trans-acting factor YY1 in lancelet.
The discovery of ancestral RAG transposons in early deuterostomia reveals the origin of vertebrate V(D)J recombination. Here, we analyze the functional regulation of a RAG transposon, ProtoRAG, in lancelet. We find that a specific interaction between the cis-acting element within the TIR sequences of ProtoRAG and a trans-acting factor, lancelet YY1-like (bbYY1), is important for the transcriptional regulation of lancelet RAG-like genes (bbRAG1L and bbRAG2L). Mechanistically, bbYY1 suppresses the transposition of ProtoRAG; meanwhile, bbYY1 promotes host DNA rejoins (HDJ) and TIR-TIR joints (TTJ) after TIR-dependent excision by facilitating the binding of bbRAG1L/2 L to TIR-containing DNA, and by interacting with the bbRAG1L/2 L complex. Our data thus suggest that bbYY1 has dual functions in fine-tuning the activity of ProtoRAG and maintaining the genome stability of the host.


Life satisfaction, loneliness and related factors during female midlife.
Studies assessing life satisfaction and feelings of loneliness in mid-aged women are scarce. To assess loneliness, life satisfaction and related factors in mid-aged Spanish women. This was a cross sectional study in which 182 women aged 40 to 65 completed the menopause rating scale (MRS), the University of California at Los Angeles loneliness scale (UCLA-LS), the life satisfaction index A (LSI-A), and a general socio-demographic questionnaire containing personal/partner data. Internal consistency of each tool was also computed. Median [interquartile range] age of the sample was 51 [9.0] years. A 55.5% were postmenopausal, 47.3% had increased body mass index (BMI) values, 57.7% were abdominally obese, 1.6% had hypertension and 86.3% had a stable partner. In addition, 4.9% used hormone therapy and 19.2% psychotropic drugs. Multiple linear regression analysis found that higher UCLA-LS scores (more loneliness) correlated with MRS psychological scores, partner alcohol abuse, living in urban areas, lower LSI-A scores (less life satisfaction) and not having a stable partner. Lower LSI-A scores (worse life satisfaction) correlated with severe female economical problems, BMI values and UCLA-LS and MRS psychological scores. Loneliness and life satisfaction in this mid-aged female sample was influenced by personal and partner issues which seem to play a much more relevant role than biological aspects. More research is warranted in this regard.


Initial mercury evaporation from experimental Ag-Sn-Cu amalgams containing Pd.
This study examined the Hg evaporation during setting from experimental Ag-Sn-Cu alloy powders with and without Pd. Four series of alloy powders were fabricated to examine the effect on the Hg evaporation of the alloy compositions (all percentages in this report are weight percents): Pd (0-1.5), Cu (9.0-14.0), Ag (57.0-63.7), and Sn (24.9-29.5). These variations in composition produced alloy powders with gamma-Ag3Sn to beta-AgSn ratios varying from 0.0 to 23.9. The total amounts of Hg released from 10 min after trituration were measured from cylindrical specimens (4 x 8mm; n = 4 ) at 37 degrees C using a Hg vapor analyzer. The results were compared to those from commercial alloys (one high-Cu and one low-Cu alloy). All amalgams made from alloys containing 1.5% Pd exhibited lower Hg vapor release than any other amalgams, with the exception of the low-Cu amalgam. The results clearly showed that the alloy formulation affected the mercury evaporation behavior during setting of the resultant amalgams. A small addition of Pd to the alloy can produce amalgams with 50-60% less Hg vapor release during setting than a leading commercial high-Cu amalgam, Tytin.


Swelling of Penicillium digitatum conidia by a Fusarium acuminatum NRRL 6227 metabolite.
Fusarium acuminatum NRRL 6227 produces an antifungal metabolite that causes incubating conidia of several Penicillium species to swell 5-10 diameters while inhibiting germination. The swollen conidia are spherical, translucent, nonviable and easily shattered with a slight physical pressure; however, they remain resistant to osmotic shock. This antibiotic has been identified as a cyclic peptide composed of alanine, glutamic acid, leucine, threonine and tyrosine.


Immunobiology of pregnancy: from basic science to translational medicine.
Embryo implantation failure and spontaneous abortions represent the main causes of infertility in developed countries. Unfortunately, incomplete knowledge of the multiple factors involved in implantation and fetal development keeps the success rate of medically assisted procreation techniques relatively low. According to recent literature, cellular and molecular mechanisms of 'immunogenic tolerance' towards the embryo are crucial to establish an 'anti-inflammatory' state permissive of a healthy pregnancy. In this review we dissect the role played by the immune system in the endometrial-embryo crosstalk, with a particular emphasis towards the fork-head-box-p3 (Foxp3+) CD4+CD25+ regulatory T (Treg) cells and discuss the most recent therapeutic advances in the context of early immune-mediated pregnancy loss.


The perchlorosoluble proteins of the serum of the rainbow trout (Salmo gairdnerii Richardson): albumin like and hemoglobin binding fraction.
1. The main perchlorosoluble fraction of rainbow trout serum has some physico-chemical characters kindred to those of human serum albumin (low molecular weight, solubility with ammonium sulfate, electrophoretic mobility, no glycoproteinic staining). 2. However, on account of obvious differences (heterogeneity and existence of various phenotypes, lack of bromophenol blue or bilirubin binding, low concentration, solubility in perchloric acid), the term "para-albumin" seems more suitable to name this compound. 3. The perchlorosoluble fraction binds hemoglobin causing an increase of peroxidasic activity. But, unlike to human haptoglobin, hemoglobin binding is partial, reversible and labile.


Dendritic cells in lung immunopathology.
Dendritic cells (DCs) lie at the heart of the innate immune system, specialised at recognising danger signals in many forms including foreign material, infection or tissue damage and initiating powerful adaptive immune and inflammatory responses. In barrier sites such as the lung, the instrumental role that DCs play at the interface between the environment and the host places them in a pivotal position in determining the severity of inflammatory disease. The past few years has seen a significant increase in our fundamental understanding of the subsets of DCs involved in pulmonary immunity, as well as the mechanisms by which they are activated and which they may use to coordinate downstream inflammation and pathology. In this review, we will summarise current understanding of the multi-faceted role that DCs play in the induction, maintenance and regulation of lung immunopathology, with an emphasis on allergic pulmonary disease.


Maternal morbidity, mortality, and risk assessment.
Maternal deaths in developed countries continue to decline and are rare. Maternal mortality statistics are essentially similar in the United States and United Kingdom. However, the situation is completely different in developing countries, where maternal mortality exceeds 0.5 million every year. This article not only assesses morbidity risks in some of the leading causes of maternal death but also highlights strategies to minimize the risks and to prevent maternal morbidity and mortality.


Muscarinic receptors of the pancreas: a correlation between displacement of (3 H)-quinuclidinyl benzilate binding and amylase secretion.
(3H)-quinuclidinyl benzilate [(3H)-QNB], A potent muscarinic antagonist, was used as a tool to reveal the presence of muscarinic receptors in rat pancreas. Binding assays were performed on a 49,000 g pellet. Known muscarinic antagonists and agonists were used for competition assays on (3N)-QNB binding and studies on amylase secretion in vitro. A correlation was established between the binding assays and the studies on amylase release which suggests that the binding sites and those involved in the cholinergic control of pancreatic enzyme secretion are similar.


Ablation efficiency and relative thermal confinement measurements using wavelengths 1,064, 1,320, and 1,444 nm for laser-assisted lipolysis.
Laser-assisted lipolysis is routinely used for contouring the body and the neck while modifications of the technique have recently been advocated for facial contouring. In this study, wavelength-dependence measurements of laser lipolysis effect were performed using different lasers at 1,064, 1,320, and 1,444 nm wavelengths that are currently used clinically. Fresh porcine skin with fatty tissue was used for the experiments with radiant exposure of 5-8 W with the same parameters (beam diameter = 600 μm, peak power = 200 mJ, and pulse rate = 40 Hz) for 1,064, 1,320 and 1,444 nm laser wavelengths. After laser irradiation, ablation crater depth and width and tissue mass loss were measured using spectral optical coherence tomography and a micro-analytical balance, respectively. In addition, thermal temporal monitoring was performed with a thermal imaging camera placed over ex vivo porcine fat tissue; temperature changes were recorded for each wavelength. This study demonstrated greatest ablation crater depth and width and mass removal in fatty tissue at the 1,444 nm wavelength followed by, in order, 1,320 and 1,064 nm. In the evaluation of heat distribution at different wavelengths, reduced heat diffusion was observed at 1,444 nm. The ablation efficiency was found to be dependent upon wavelength, and the 1,444 nm wavelength was found to provide both the highest efficiency for fatty tissue ablation and the greatest thermal confinement.


Maxillary canine-lateral incisor transposition--orthodontic management.
A case of maxillary canine-lateral incisor complete transposition is presented. Treatment options for transposed teeth, including alignment in their transposed positions, extraction of one or both transposed teeth, and orthodontic alignment to their normal positions in the arch, are discussed. The orthodontic technique and sequence used in this challenging case to align the fully transposed teeth to their normal position in the dental arch are described.


Mild hyperphenylalaninemia (hpa) presenting as orthostatic tremor: a case report.
Orthostatic tremor (OT) is a type of postural tremor of the lower extremities that has not been described in either phenylketonuria (PKU) or hyperphenylalaninemia (HPA). Because little is known about the clinical features and therapeutic responses of OT in mild HPA, we describe a mild HPA patient who presented with OT as an initial symptom. A 22-year-old male was admitted for bilateral leg tremor while standing, with symptom onset eight months prior. One month before admission, the tremor disappeared in the left leg but persisted in the right leg. Electromyography recorded from the right gastrocnemius revealed a 6-8 Hz tremor, which appeared when the patient was standing and disappeared when he was resting or walking. Blood screening showed a phenylalanine/tyrosine ratio of 2.06 and a phenylalanine level of 140 μmol/L. Urine metabolic screening was negative. Whole-exome sequencing confirmed the presence of a compound heterozygous mutation, c.158G > A and c.728G > A, in phenylalanine hydroxylase (PAH) gene. After three months of levodopa/benserazide tablets (250 mg, tid) and a low-phenylalanine diet treatment, the tremor disappeared. Young-onset mild HPA is a relatively rare autosomal recessive metabolic disease, and slow OT is a rare clinical feature. Metabolic screening and genetic testing are the keys to early diagnosis and treatment. For adolescents and young adults, appropriate medication and long-term dietary therapy remain important treatments. This case expanded the disease spectrum of slow OT.


[Use of serum tumor markers in the diagnosis of malignant tumors of the digestive system].
The article is devoted to the main OncoMarkers, which are used in the case of malignant growth in digestal organs, their efficient administration in the medical practise and diagnostic importance.


Pentoxyphylline and propentophylline are inhibitors of TNF-alpha release in monocytes activated by advanced glycation endproducts.
Non-enzymatic glycation of proteins with reducing sugars and subsequent transition metal-catalyzed oxidation leads to the formation of protein-bound "advanced glycation endproducts" (AGEs). They accumulate on long-lived protein deposits inducing senile plaques in Alzheimer's disease. AGE-modified proteins are able to activate microglia and astroglia and can cause chronic inflammation. The aim of the present study was to confirm the stimulatory effect of different AGEs on TNF-alpha release in human monocytes. Furthermore, the effects of four xanthine derivatives on AGE-induced TNF-alpha release were investigated. We show that chicken egg albumin-AGEs prepared with glucose and chicken egg albumin-AGEs prepared with methylglyoxal dose-dependently induce TNF-alpha release. The xanthine derivatives pentoxyphylline and propentophylline attenuate AGE-induced TNF-alpha release in a dose-dependent manner. Theophylline at low concentrations slightly stimulated TNF-alpha release whereas caffeine had no effect. The inhibition of the AGE-induced TNF-alpha release by pentoxyphylline and propentophylline provides interesting pharmacological strategies for diseases with local neuroinflammation such as Alzheimer's disease.


[Management of colorectal resections for treatment of neoplastic intestinal occlusions. Experience of surgery clinic No III, Cluj-Napoca].
We analyzed the clinical results of different techniques of resection for malignant colorectal (primary or staged) obstruction. The subjects of this retrospective nonrandomized clinical study were 165 patients with malignant colorectal occlusion who underwent surgery treatment in our Department between 2002-2006. Patients with peritonitis or treated by means of permanent colostomy, palliative anastomosis, primary Hartman resection and rectal excision were excluded. Patients with large bowel obstruction caused by obstructive malignant colorectal lesions underwent either one-stage primary resection with anastomosis (77 patients) or staged interventions (88 patients). There were no differences in age, sex, comorbidities, tumor staging, serum preoperative levels of hemoglobin and proteins between the two groups of patients defined by the different surgical techniques. Regarding mortality and morbidity following surgical treatment for large bowel obstruction no significant difference among the two groups (p > 0.05) or the fistula rate (p = 0.435) was obtained. Moreover, results showed a higher incidence of mortality (11.8% vs 7.8%), morbidity (13.6 vs 10.4) and increased hospitalization period (p = 0.03) among the patients that undergone series resections. One stage primary resections with anastomosis of the large bowel can be performed safely in case of emergency whenever patient comorbidities and local conditions do not stand as major restrictions.


Sensitivity of a neoplastic epithelial duct cell line from a human submandibular salivary gland to human leukocyte interferon as assessed by an in vitro semi-solid agar technique.
A neoplastic epithelial duct cell line from a human submandibular salivary gland, HSG, was assayed by an in vitro semi-solid agar technique for sensitivity to human leukocyte interferon (HuIFN-alpha). The clone which showed the most stable growth and the greatest ability of colony formation in the agar medium, was isolated from the colonies of HSG cells and used in the present study. This clone was designated as HSG-1. As a consequence, cultivation of HSG-1 cells in the agar medium containing HuIFN-alpha of 1000 units/ml resulted in the inhibition of 47.6% of the colony-forming ability of HSG-1 cells, as compared with the untreated control. Addition of increasing concentrations of HuIFN-alpha (between 100 units/ml and 1000 units/ml) in the agar medium caused a linear reduction in the number of the colonies, ranging from 5.2% to 47.6%. Moreover, addition of HuIFN-alpha showed an inhibitory effect on the multiplication of HSG-1 cells in the monolayer culture. These observations strongly suggest that HuIFN-alpha has antineoplastic and antiproliferative effects on HSG-1 cells.


Extradural Remodeling in Empty Sella Syndrome: 3-Dimensional Operative Video.
Sellar arachnoidocele is a term used to define the herniation of the subarachnoid space to the sella.1 This is a rare radiologic finding that, in most cases, does not require treatment.2-5 When symptoms appear, the term empty sella syndrome is used. Two varieties exist: primary and secondary empty sella syndrome.2 The aim of this 3-dimensional operative video (Video 1) is to demonstrate the extradural microsurgical remodeling of the sellar fossa with autologous bone in 2 cases of primary empty sella syndrome. Both patients signed an informed consent for the procedures and agree with the use of their images for research purposes. In both cases, magnetic resonance imaging scans showed herniation of the subarachnoid space into the pituitary fossa and an anchor-like silhouette on coronal view. Patients evolved favorably, improving their visual deficit after the surgery, as can be observed in the postoperative visual field study. If surgery is indicated due to visual loss, the procedure is known as chiasmapexy. Recently, Guinto et al3 described a technique for chiasmapexy. Our team considers this procedure to be useful, technically simple, and low cost. Being autologous, rejection possibilities are almost null. This 3D video serves as a complement to illustrate the technique.


The rationale and potential of combining novel biologic therapies with radiotherapy: focus on non-small cell lung cancer.
There are a number of novel, biologically targeted therapies, including anti-epidermal growth factor receptor agents (eg, ZD1839 and C225 [cetuximab]), anti-angiogenic agents (eg, vascular endothelial growth factor receptor inhibitors endostatin and angiostatin), and vascular targeting agents (eg, ZD6126), currently undergoing clinical development for a range of human cancers. These agents generally have milder toxicity profiles than conventional cytotoxic agents, and have the potential to be combined effectively with radiotherapy and other conventional modalities in the treatment of malignancies. In this review we consider the mechanistic rationale for combining biologically targeted agents with radiotherapy, present preclinical data to validate this hypothesis, and discuss early clinical investigations of these novel combination therapies, with an emphasis on ongoing trials in non-small cell lung cancer.


Normative segment-specific axial and coronal angulation corridors of subaxial cervical column in axial rotation.
In contrast to clinical studies wherein loading magnitudes are indeterminate, experiments permit controlled and quantifiable moment applications, record kinematics in multiple planes, and allow derivation of moment-angulation corridors. Axial and coronal moment-angulation corridors were determined at every level of the subaxial cervical spine, expressed as logarithmic functions, and level-specificity of range of motion and neutral zones were evaluated. segmental primary axial and coupled coronal motions do not vary by level. Although it is known that cervical spine responses are coupled, segment-specific corridors of axial and coronal kinematics under axial twisting moments from healthy normal spines are not reported. Ten human cadaver columns (23-44 years, mean: 34 +/- 6.8) were fixed at the ends and targets were inserted to each vertebra to obtain kinematics in axial and coronal planes. The columns were subjected to pure axial twisting moments. Range of motion and neutral zone for primary-axial and coupled-coronal rotation components were determined at each spinal level. Data were analyzed using factorial analysis of variance. Moment-rotation angulations were expressed using logarithmic functions, and mean +/-1 standard deviation corridors were derived at each level for both components. Moment-angulations responses were nonlinear. Each segmental curve for both components was well represented by a logarithmic function (r2 > 0.95). Factorial analysis of variance indicated that the biomechanical metrics are spinal level-specific (P < 0.05). Axial and coronal angulations of cervical spinal columns show statistically different level-specific responses. The presentation of moment-angulation corridors for both metrics forms a dataset for the normal population. These segment-specific nonlinear corridors may help clinicians assess dysfunction or instability. These data will assist mathematical models of the spine in improved validation and lead to efficacious design of stabilizing systems.


Maturational changes in rabbit renal brush border membrane vesicle urea permeability.
Urea transport in the proximal tubule is thought to occur by passive diffusion through the lipid bilayers of the cell membranes. The lipid composition of cell membranes changes during maturation and may directly affect urea permeability of proximal tubule membranes. The present study examined the maturation of urea transport in rabbit renal brush border membrane vesicles (BBMV). BBMV from adult and neonatal (9- to 11-d-old) New Zealand white rabbits were loaded with 500 mM urea and mixed with an iso-osmotic mannitol solution using a stop-flow instrument. Vesicle shrinkage, due to efflux of urea, was followed with light scattering and urea permeability was calculated from an exponential fit of the data. Urea permeability was significantly lower in the neonatal BBMV than the adult at 25 degrees C (0.34+/-0.04 x 10(-6) versus 0.56+/-0.03 x 10(-6) cm/sec;p < 0.001, n=7) and 37 degrees C (0.45+/-0.04 x 10(-6) versus 0.66+/-0.03 x 10(-6) cm/sec; p=0.001, n=7). There was no effect of 250 microM phloretin on urea permeability in either adult or neonatal BBMV at either temperature. The activation energy for urea diffusion was higher in the neonatal than the adult BBMV. Because the maturational increase in urea permeability could potentially be due to a sodium-dependent urea transporter in the adult BBMV, the sodium dependence of urea uptake in adult BBMV was examined. There was no difference in urea permeability in the presence or absence of 20 mM NaCl. Permeability of the lipid-soluble molecule, glycerol, was also found to be the same in the neonatal and adult BBMV. Urea transport in the apical membrane of neonatal and adult proximal tubules is not phloretin sensitive, a finding consistent with diffusion of urea via the lipid bilayer. The rate of urea diffusion is lower in neonatal membranes and may be an important factor in overall urea excretion. This may also play a role in developing and maintaining a high medullary urea concentration and thus the ability to concentrate the urine during renal maturation.


Enhanced enzyme activity after incubation with zinc can be used to distinguish heterozygotes of Pompe's disease.
In an attempt to identify heterozygotes for Pompe's disease, the acid alpha-D-glucosidase activity at pH 4 in phytohemagglutinin-stimulated lymphocytes was measured. In the standard assay an overlap in the enzyme activity between normal controls and obligate heterozygotes was demonstrated. When the assay was modified by adding zinc chloride into the incubation mixture, the enzyme activity of the lymphocyte homogenates did not change. However, the enzyme activity increased dramatically after intact lymphocytes were preincubated with zinc chloride. There was no more overlap in the acid alpha-D-glucosidase activity between normal controls and obligate heterozygotes when lymphocytes were incubated 1 h with 10(-4) mol/liter zinc chloride or 2 h with 10(-3) or 10(-4) mol/liter zinc chloride. This modified enzyme activity should facilitate improved heterozygote detection.


Esterase and acid phosphatase polymorphism in the fig tree (Ficus carica L.).
The genetics of two enzymatic loci, esterase (Est-D) and acid phosphatase (AcP-A), were studied by means of polyacrylamide gel electrophoresis in the fig tree (Ficus carica L.). Two codominant alleles are described at the Est-D locus and four codominant alleles at the AcP-A locus. Heterozygotes at the AcP-A locus have a hybrid band, thus showing that the AcP-A allozymes, are at least dimer molecules. Both loci are independent of the male sterility factor in F. carica. The polymorphism in four natural populations was investigated for both loci. A significant deficiency of heterozygotes was observed.


Retrospective study assessing efficacy of treatment of large colonic impactions.
Cases with a history of colic due to a large colonic impaction were recruited retrospectively to assess the treatment efficacy and complications of oral and parenteral fluid therapy regimes for correction of primary large colon impactions. Oral isotonic fluids had been administered at varying intervals following initial treatment with magnesium sulphate and water. There was no significant difference in complication rates between groups. Considering complication rates with impaction clearance, hourly administration of oral fluids appears to be the most appropriate treatment regime of those investigated.


Anaerobic fermentation of organic solid waste: Recent updates in substrates, products, and the process with multiple products co-production.
The effective conversion and recycling of organic solid waste contribute to the resolution of widespread issues such as global environmental pollution, energy scarcity and resource depletion. The anaerobic fermentation technology provides for the effective treatment of organic solid waste and the generation of various products. The analysis, which is based on bibliometrics, concentrates on the valorisation of affordable and easily accessible raw materials with high organic matter content as well as the production of clean energy substances and high value-added platform products. The processing and application status of fermentation raw materials such as waste activated sludge, food waste, microalgae and crude glycerol are investigated. To analyse the status of the preparation and engineering applications of the products, the fermentation products biohydrogen, VFAs, biogas, ethanol, succinic acid, lactic acid, and butanol are employed as representatives. Simultaneously, the anaerobic biorefinery process with multiple product co-production is sorted out. Product co-production can reduce waste discharge, enhance resource recovery efficiency, and serve as a model for improving anaerobic fermentation economics.


Mepolizumab in allergic bronchopulmonary aspergillosis complicated by infection.
Allergic bronchopulmonary aspergillosis (ABPA) is an allergic reaction caused by the fungus Aspergillus, and it is often treated with steroids or antifungal agents. However, long-term use of these medications can lead to infections and drug interactions. We present the case of a 71-year-old woman with ABPA who was diagnosed with hepatitis B and active hepatitis C, and sputum analysis revealed the presence of bacteria. Oral steroids were initially administered, but the patient was switched to mepolizumab because of numerous infectious complications. The early introduction of mepolizumab is effective in patients with ABPA complicated by infectious diseases.


Lower esophageal rings as a cause of dysphagia in progressive systemic sclerosis--coincidence or consequence?
Lower esophageal rings were found in five of 40 consecutive patients seen with progressive systemic sclerosis. Three of these five patients had diffuse skin involvement and two had the CREST variant of progressive systemic sclerosis. All of the patients with lower esophageal rings had intermittent esophageal obstruction (initially attributed to esophageal dysmotility), but so did five of seven patients with esophageal strictures without lower esophageal rings. Esophageal bougienage relieved this symptom in four of the five patients with rings in which it was performed. Persistent relief of these obstructive symptoms (6-36 months) in the patients with rings was in contrast to the recurrent dilatations that have been needed in the group of patients with peptic strictures. In contrast to esophageal aperistalsis and/or stricture formation, the lower esophageal ring, perhaps as a consequence of chronic gastroesophageal reflux, may be a more treatable cause of dysphagia in patients with progressive systemic sclerosis.


Robust vessel segmentation in laser speckle contrast images based on semi-weakly supervised learning.
Objective.The goal of this study is to develop a robust semi-weakly supervised learning strategy for vessel segmentation in laser speckle contrast imaging (LSCI), addressing the challenges associated with the low signal-to-noise ratio, small vessel size, and irregular vascular aberration in diseased regions, while improving the performance and robustness of the segmentation method.Approach.For the training dataset, the healthy vascular images denoted as normal-vessel samples were manually labeled, while the diseased LSCI images involving tumor or embolism were denoted as abnormal-vessel samples and annotated as pseudo labels by the traditional semantic segmentation methods. In the training phase, the pseudo labels were constantly updated to improve the segmentation accuracy based on DeepLabv3+. Objective evaluation was conducted on the normal-vessel test set, while subjective evaluation was performed on the abnormal-vessel test set.Main results.The proposed method achieved an IOU of 0.8671, a Dice of 0.9288, and a mean relative percentage difference (mRPD) with supervised learning of 0.5% in the objective evaluation. In the subjective evaluation, our method significantly outperformed other methods in main vessel segmentation, tiny vessel segmentation, and blood vessel connection. Additionally, our method exhibited robustness when abnormal-vessel style noise was added to normal-vessel samples using a style translation network.Significance.The proposed semi-weakly supervised learning strategy demonstrates high efficiency and excellent robustness for vascular segmentation in LSCI, providing a potential tool for assessing the morphological and structural features of vessels in clinical applications.


MiR-101 inhibits melanoma cell invasion and proliferation by targeting MITF and EZH2.
The microRNA miR-101 has been reported to be a tumor suppressor. Here we show that low expression of miR-101 is associated with poor survival in stage IV melanoma patients. We identified microphthalmia-associated transcription factor (MITF) as a direct target of miR-101. In melanoma cells, overexpression of miR-101 downregulated protein levels of MITF and a previously reported target protein, enhancer of zeste homolog 2 (EZH2). Functional assays showed that miR-101 suppressed invasion and proliferation - an outcome that could be phenocopied by siRNA knockdown of MITF and EZH2. Our data suggest that miR-101 might have a beneficial role in melanoma.


Development of an intervention program to prevent childhood obesity targeted to Mexican mothers of school-aged children using intervention mapping and social cognitive theory.
In Mexico, data from the last National Health and Nutrition Survey (2016) described the increase in the prevalence of overweight and obesity in school-aged children (33.2%). Obesity prevention strategies have not been effective, and currently, Mexico has one of the highest prevalence of childhood obesity. Thus, there is an urgent need to develop strategies that can prevent childhood obesity and also to avoid these children to remain overweight/obese through adulthood. The objective of this study was to provide a step-by-step description of the design, implementation and evaluation of an intervention plan for Mexican mothers of school aged children to promote healthy eating and to prevent childhood obesity. The program Niño Sano Adulto Sano was developed using the Intervention Mapping Approach and the Social Cognitive Theory frameworks to provide Mexican mothers with knowledge and skills to positively modify their children's food behavior, thus preventing future weight gain. The program was developed, piloted and delivered to the target population with positive results on the mothers' nutrition knowledge and children's BMI. Intervention Mapping and Social Cognitive Theory are useful models to design and deliver an intervention that provides a holistic approach to promote healthy eating.


Synthesis of dinucleoside tetraphosphates by RNA polymerase B (II) from calf thymus.
Highly purified RNA polymerase B (II) from calf thymus catalyses the synthesis of dinucleoside tetraphosphates from ribonucleoside triphosphates in the absence of an oligonucleotide primer or additional protein factors. The reaction requires a DNA template and bivalent cations such as Mn2+ or Mg2+. It is strongly inhibited by heparin and high concentrations of alpha-amanitin but not by rifampicin. On a given template various dinucleoside tetraphosphates of different sequence are formed although the yield depends on the nature of the template.


Soft drinks and dental health: a review of the current literature.
In recent years there has been increased interest in the role of commercial soft drinks in dental diseases namely as dental caries and erosion. The objective of this paper has been to review the past and current literature to determine the present knowledge on this subject. The literature related to dental caries, erosion, drinks, soft drinks and fruit juices was reviewed. The literature shows efforts have been taken to modify soft drinks by either adding or deleting certain components so as to reduce their harmful effects on teeth. A rational protocol to encourage the sensible use of drinks and the modification of drinks to render them less harmful would be advisable.