Characterization of a novel plantain Asr gene, MpAsr, that is regulated in response to infection of Fusarium oxysporum f. sp. cubense and abiotic stresses.
Asr (abscisic acid, stress, ripening induced) genes are typically upregulated by a wide range of factors, including drought, cold, salt, abscisic acid (ABA) and injury; in addition to plant responses to developmental and environmental signals. We isolated an Asr gene, MpAsr, from a suppression subtractive hybridization (SSH) cDNA library of cold induced plantain (Musa paradisiaca) leaves. MpAsr expression was upregulated in Fusarium oxysporum f. sp. cubense infected plantain leaves, peels and roots, suggesting that MpAsr plays a role in plantain pathogen response. In addition, a 581-bp putative promoter region of MpAsr was isolated via genome walking and cis-elements involved in abiotic stress and pathogen-related responses were detected in this same region. Furthermore, the MpAsr promoter demonstrated positive activity and inducibility in tobacco under F. oxysporum f. sp. cubense infection and ABA, cold, dehydration and high salt concentration treatments. Interestingly, transgenic Arabidopsis plants overexpressing MpAsr exhibited higher drought tolerance, but showed no significant decreased sensitivity to F. oxysporum f. sp. cubense. These results suggest that MpAsr might be involved in plant responses to both abiotic stress and pathogen attack.


Complementary DNA encoding the human T-cell FK506-binding protein, a peptidylprolyl cis-trans isomerase distinct from cyclophilin.
The recently discovered macrolide FK506 has been demonstrated to have potent immunosuppressive activity at concentrations 100-fold lower than cyclosporin A, a cyclic undecapeptide that is used to prevent rejection after transplantation of bone marrow and organs, such as kidney, heart, and liver. After the recent discovery that the cyclosporin A-binding protein cyclophilin is identical to peptidylprolyl cis-trans isomerase, a cellular binding protein for FK506 was found to be distinct from cyclophilin but to have the same enzymatic activity. In this study, we isolated a cDNA coding for FK506-binding protein (FKBP) from human peripheral blood T cells by using mixed 20-mer oligonucleotide probes synthesized on the basis of the sequence, Glu-Asp-Gly-Lys-Lys-Phe-Asp, reported for bovine FKBP. The DNA isolated contained an open reading frame encoding 108 amino acid residues. The first 40 residues of the deduced amino acid sequence were identical to those of the reported amino-terminal sequence of bovine FKBP, indicating that the DNA sequence isolated represents the gene coding for FKBP. Computer-assisted analysis of the deduced amino acid sequence indicates that FKBP exhibits no internal homology and does not have significant sequence similarity to any other amino acid sequences of known proteins, including cyclophilin. This result suggests that two catalytically similar proteins, cyclophilin and FKBP, evolved independently. In Northern blot analysis, mRNA species of approximately 1.8 kilobases that hybridized with human FKBP cDNA were detected in poly(A)+ RNAs from brain, lung, liver, and placental cells and leukocytes. Induction of Jurkat leukemic T cells with phorbol 12-myristate 13-acetate and ionomycin did not affect the level of FKBP mRNA. Southern blot analysis of human genomic DNA digested with different restriction enzymes suggests the existence of only a few copies of the DNA sequence encoding FKBP. This is in contrast to the result that as many as 20 copies of the cyclophilin gene and possible pseudogenes may be present in the mammalian genome.


Update on the pharmacologic management of overactive bladder: the present and the future.
Overactive bladder (OAB) is a common condition, affecting approximately 17% of females and males 40 years of age and older. Historically, oxybutynin was the only medication approved for use in the management of OAB. Over the past decade, several new antimuscarinics have been approved for the treatment of OAB. Although all are deemed to be effective in improving the bothersome symptoms of OAB, they differ in their molecular properties, metabolism, and tolerability/side effect profile. A greater understanding of the pathophysiology of OAB has led to approved and investigative therapies to treat refractory OAB, such as neuromodulation and intravesical injection of Botulinum toxin, respectively. A variety of pharmacologic agents are in clinical trials for OAB that target different components of bladder function, such as the urothelium, the afferent sensory nerve pathways, and the central nervous system. It is the intent of this article to highlight these aspects of OAB management.


The antihypertensive effect of taurine in DOCA-salt rats.
We studied the role of the sympathetic nervous system in the antihypertensive actions of taurine in DOCA (deoxycorticosterone acetate)-salt hypertensive rats. Supplementation with 1% taurine could moderate the development of the DOCA-salt hypertension. Norepinephrine turnover was measured from the rate of decline of tissue norepinephrine concentration after the administration of alpha-methyl-p-tyrosine. Cardiac and splenic norepinephrine turnover was markedly accelerated in the DOCA-salt rats compared with the vehicle-treated control rats, but the 1% taurine supplements could normalize this. These results suggest that the normalization of the increased sympathetic activity may be involved in the antihypertensive actions of taurine in DOCA-salt hypertensive rats.


[Antioxidative properties of cardioactive agents].
Calcium entry blockers reduce the ischemia-reperfusion induced damage to the myocardium. Free oxygen radicals play a role in the pathogenesis of this injury. The mechanism of the protective action of calcium entry blockers is unknown in these conditions and appears to be independent of the blockade of slow calcium channels. As demonstrated in this paper, the calcium entry blockers nifedipine, verapamil and diltiazem are effective scavengers of free oxygen radicals and this characteristic may be importantly involved in their protective effect against myocardial damage induced by ischemia and reperfusion. The pro-oxidative capacity of the antineoplastic drug cisplatin is assumed to play a role in the mechanism of its renal toxicity action. The presented study showed that the new antioxidative substance with antiarrhythmic and antihypoxic properties-stobadine-succeeded in inhibiting the pro-oxidative effect of cisplatin. Our findings suggest that administration of cisplatin along with antioxidants may result in a protective effect against the renal toxicity of cisplatin. (Fig. 5, Ref. 38.)


Synthesis and characterization of stimuli-responsive polypropylene containing N-vinylcaprolactam and N-vinylimidazole obtained by ionizing radiation.
Polypropylene films were grafted with thermo-responsive N-vinylcaprolactam and pH-responsive N-vinylimidazole polymers by means of gamma radiation using pre-irradiation and direct methods, in order to functionalize the films with thermo- and/or pH-responsiveness. The dependence of grafting yield on parameters such as co-monomer concentration, pre-irradiation dose, temperature, and reaction time was evaluated. The samples were characterized by Fourier transform infrared and X-ray photoelectron spectroscopies, differential scanning calorimetry, thermogravimetric analysis, swelling studies in different solvents, and water contact angle. The grafted copolymers presented thermo- and pH-sensitiveness, highlighting their potential as advanced biomaterials, capable of providing adequate environment for hosting and sustained release of antimicrobial drugs bearing cationic moieties, such as groups of diclofenac, while still exhibiting good cytocompatibility.


Relationship between CD4+ T-cell counts at baseline and initial periodontal treatment efficacy in patients undergoing treatment for HIV infection: A retrospective observational study.
To retrospectively investigate the relationship between the CD4+ T-cell counts at baseline and the efficacy of the initial periodontal treatment of patients undergoing treatment for human immunodeficiency virus (HIV) infection using the periodontal inflamed surface area (PISA). Thirty-three patients with chronic periodontitis who had undergone periodontal examination at baseline and after the initial periodontal treatment were enrolled. PISA was calculated from the periodontal probing depth and bleeding on probing, and the ratio of PISA after treatment to that at baseline (PISA response ratio) was calculated. Groups with a response ratio of <1 and ≥1 were defined as the improvement and the non-improvement groups, respectively. PISA after the initial periodontal treatment significantly decreased compared with that at baseline (p < .05). A weak negative correlation was found between the PISA response ratio and CD4+ T-cell counts at baseline (p < .05). The CD4+ T-cell counts at baseline were significantly higher in the improvement group than in the non-improvement group (p < .05). Multivariate analysis revealed that the CD4+ T-cell counts at baseline was an independent factor that affects the PISA (p < .05). The higher the CD4+ T-cell counts at baseline in patients undergoing treatment for HIV infection, the more effective the initial periodontal treatment.


A comparison of acoustic radiation force impulse imaging and scintigraphy in the functional evaluation of the major salivary glands.
This study aimed to determine the efficacy of acoustic radiation force impulse (ARFI) imaging for the functional assessment of salivary glands by comparing ARFI with salivary gland scintigraphy. We prospectively evaluated 60 parotid (P) glands and 60 submandibular (SM) glands of 30 patients using salivary gland scintigraphy and ARFI elastography. The average pixel uptake and the excretion fraction (EF) in the P and SM glands were determined scintigraphically. The degree of stiffness in the P and SM glands at prelemon and postlemon stimulation periods were measured elastographically with ARFI. Changes in the degree of stiffness of the P and SM glands were also calculated with lemon stimulation. The scintigraphic and elastographic parameters were then compared statistically. We found a moderate linear correlation between the excretion function and the changes in the degree of stiffness of the P and SM glands induced by lemon stimulation (P<0.001, r=0.661; P<0.001, r=0.530, respectively). We also found a weak positive correlation between the EF and the degree of stiffness of the P and SM glands in the prelemon stimulation period (P=0.001, r=0.405; P<0.001, r=0.480, respectively). However, we did not find any significant correlation between other scintigraphic and elastographic parameters. ARFI imaging may play a role in the determination of the EF of P and SM glands by measuring tissue elasticity changes with lemon stimulation. However, ARFI does not seem to be a suitable substitute for scintigraphy in the evaluation of the parenchymal function of P and SM glands.


Mitochondrion: A Promising Target for Nanoparticle-Based Vaccine Delivery Systems.
Vaccination is one of the most popular technologies in disease prevention and eradication. It is promising to improve immunization efficiency by using vectors and/or adjuvant delivery systems. Nanoparticle (NP)-based delivery systems have attracted increasing interest due to enhancement of antigen uptake via prevention of vaccine degradation in the biological environment and the intrinsic immune-stimulatory properties of the materials. Mitochondria play paramount roles in cell life and death and are promising targets for vaccine delivery systems to effectively induce immune responses. In this review, we focus on NPs-based delivery systems with surfaces that can be manipulated by using mitochondria targeting moieties for intervention in health and disease.


Evolutionary and expression analysis of a MADS-box gene superfamily involved in ovule development of seeded and seedless grapevines.
MADS-box transcription factors are involved in many aspects of plant growth and development, such as floral organ determination, fruit ripening, and embryonic development. Yet not much is known about grape (Vitis vinifera) MADS-box genes in a relatively comprehensive genomic and functional way during ovule development. Accordingly, we identified 54 grape MADS-box genes, aiming to enhance our understanding of grape MADS-box genes from both evolutionary and functional perspectives. Synteny analysis indicated that both segmental and tandem duplication events contributed to the expansion of the grape MADS-box family. Furthermore, synteny analysis between the grape and Arabidopsis genomes suggested that several grape MADS-box genes arose before divergence of the two species. Phylogenetic analysis and comparisons of exon-intron structures provided further insight into the evolutionary relationships between the genes, as well as their putative functions. Based on phylogenetic tree analysis, grape MADS-box genes were divided into type I and type II subgroups. Tissue-specific expression analysis suggested roles in both vegetative and reproductive tissue development. Expression analysis of the MADS-box genes following gibberellic acid (GA3) treatment revealed their response to GA3 treatment and that seedlessness caused by GA3 treatment underwent a different mechanism from that of normal ovule abortion. Expression profiling of MADS-box genes from six cultivars suggests their function in ovule development and may represent potential ovule identity genes involved in parthenocarpy. The results presented provide a few candidate genes involved in ovule development for future study, which may be useful in seedlessness-related molecular breeding programs.


The impact of August Krogh on the insulin treatment of diabetes and our present status.
The influence of August Krogh on the introduction of insulin preparations in Scandinavia is mentioned, and his outstanding physiological background is outlined. Developments in preparation of insulin depending on the progress in protein-chemistry are summarized. The latest step in the purification of insulin extracted from pork pancreas now allows treatment of diabetics with protamine-pork-insulin without causing formation of insulin-antibodies in at least 90 per cent treated with insulin through several months. In only 3 out of 51 diabetics was it possible to demonstrate insulin-antibodies. This new step may be of great interest in two ways 1) it is now possible to make insulin-estimations in the plasma of insulin-treated cases and 2) it will be possible to find out whether elimination of insulin-antibody-formation will reduce the degree of vascular lesions in diabetics, such lesions being the greatest problem in clinical diabetes.


Hybrid shear force feedback/scanning quantitative phase microscopy applied to subsurface imaging.
Quantitative phase microscopy allows for the study of the surface morphology and dynamics of transparent biological specimens. Although phase data often contains coupled subsurface information, decoupling the surface and subsurface components is often very difficult or impossible. We hereby present a simple procedure which exploits simultaneous obtained quantitative phase and shear-force feedback topography data to extract subsurface sample information. Our results reveal subsurface features in fabricated samples and fish erythrocytes.


Iridium Complexes with BIAN-Type Ligands: Synthesis, Structure and Redox Chemistry.
A series of iridium complexes with bis(diisopropylphenyl)iminoacenaphtene (dpp-bian) ligands, [Ir(cod)(dpp-bian)Cl] (1), [Ir(cod)(NO)(dpp-bian)](BF4)2 (2) and [Ir(cod)(dpp-bian)](BF4) (3), were prepared and characterized by spectroscopic techniques, elemental analysis, X-ray diffraction analysis and cyclic voltammetry (CV). The structures of 1-3 feature a square planar backbone consisting of two C = C π-bonds of 1,5-cyclooctadiene (cod) and two nitrogen atoms of dpp-bian supplemented with a chloride ion (for 1) or a NO group (for 2) to complete a square-pyramidal geometry. In the nitrosyl complex 2, the Ir-N-O group has a bent geometry (the angle is 125°). The CV data for 1 and 3 show two reversible waves between 0 and -1.6 V (vs. Ag/AgCl). Reversible oxidation was also found at E1/2 = 0.60 V for 1. Magnetochemical measurements for 2 in a range from 1.77 to 300 K revealed an increase in the magnetic moment with increasing temperature up to 1.2 μB (at 300 K). Nitrosyl complex 2 is unstable in solution and loses its NO group to yield [Ir(cod)(dpp-bian)](BF4) (3). A paramagnetic complex, [Ir(cod)(dpp-bian)](BF4)2 (4), was also detected in the solution of 2 as a result of its decomposition. The EPR spectrum of 4 in CH2Cl2 is described by the spin Hamiltonian Ĥ = gβHŜ with S = 1/2 and gxx = gyy = 2.393 and gzz = 1.88, which are characteristic of the low-spin 5d7-Ir(II) state. DFT calculations were carried out in order to rationalize the experimental results.


Spatial coincidence modulates interaction between visual and somatosensory evoked potentials.
The time course of interaction between concurrently applied visual and somatosensory stimulation with respect to evoked potentials (EPs) was studied. Visual stimuli, either in the left or right hemifield, and electric stimuli to the left wrist were delivered either alone or simultaneously. Visual and somatosensory EPs were summed and compared to bimodal EPs (BiEP, response to actual combination of both modalities). Temporal coincidence of stimuli lead to sub-additive or over-additive amplitudes in BiEPs in several time windows between 75 and 275 ms. Additional effects of spatial coincidence (left wrist with left hemifield) were found between 75 and 300 ms and beyond 450 ms. These interaction effects hint at a temporo-spatial pattern of multiple brain areas participating in the process of multimodal integration.


[Expression of netrin-1 in placenta from patients with pre-eclampsia and the relation to placental angiogenesis].
To investigate the expression of netrin-1 in placenta from patients with pre-eclampsia and the relation to placental angiogenesis. Twenty patients with pre-eclampsia (12 mild cases and 8 severe cases) and 20 normal late pregnant women were investigated. The expression of netrin-1 mRNA and protein was determined with RT-PCR and Western blotting respectively. The placenta vascular density was examined by immunohistochemical F8 staining. (1) The values of netrin-1 mRNA in normal group and pre-eclampsia groups were 0.51 +/- 0.08 and 0.41 +/- 0.06; The values of netrin-1 protein in normal group and pre-eclampsia groups were 26.4 +/- 1.8 and 20.5 +/- 1.3 (P < 0.01). The values of netrin-1 mRNA in mild and severe pre-eclampsia groups were 0.48 +/- 0.08 and 0.34 +/- 0.07; The values of netrin-1 protein in mild and severe pre-eclampsia groups were 22.8 +/- 1.3 and 18.2 +/- 1.0 (P < 0.01). (2) The placenta vascular density in pre-eclampsia (54 +/- 8) was significantly reduced than in normal group (65 +/- 10) (P < 0.01); the decrease was even more obvious in severe group (48 +/- 7) than in mild group (60 +/- 9) (P < 0.01). (3) There was positive correlation between the expression of netrin-1 mRNA and protein and placenta vascular density in normal pregnancy (r = 0.67 and 0.71, P < 0.01), as well as in pre-eclampsia group (r = 0.61 and 0.70, P < 0.01), in mild pre-eclampsia group (r = 0.69 and 0.73, P < 0.01), and in severe pre-eclampsia group (r = 0.71 and 0.75, P < 0.01). The study shows that the decrease of netrin-1 in placenta of patients with pre-eclampsia is one of the possible reasons for the reduction of placenta vascular density.


[Influenza vaccination present and future].
In healthy adults younger than 65 years the effectiveness of influenza vaccination is up to 90% for laboratory confirmed influenza, but is far less in elderly individuals over 65 years and those with comorbidities. However the vaccination in elderly people is effective in preventing complications of influenza infection: pneumonia, hospital admission and death from influenza or pneumonia. This effect is larger for elderly individuals living in nursing homes than in those living in the community. Recommendations at present include vaccination of all people over the age of 65, of high-risk groups, and of those who can transmit influenza to high-risk individuals (healthcare workers). Since 2005 it is recommended that people with occupational contact with wild or domestic birds should be vaccinated to reduce the risk of simultaneous infection with a human and an avian influenza virus. Influenza vaccination is considered to be safe: side effects are reversible within 1-2 days, severe complications are exceedingly rare. Most frequently inactivated vaccines are used, but in the USA there is also an attenuated live vaccine available. They all contain surface antigens of two influenza A strains and one influenza B strain. The world health organization (WHO) selects every year the strains to be included in the vaccine and the viruses are then grown on embryonated chicken eggs. This process requires detailed planning up to 6 months. Because a pandemic event cannot be predicted, this period is too long and there is an urgent need to develop techniques to reduce the vaccine production time and enhance its efficacy. Additionally, several researchers are exploring the possibility of generating a universal vaccine against influenza A virus that does not require reformulation on an annual basis.


Polymer brush-induced depletion interactions and clustering of membrane proteins.
We investigate the effect of mobile polymer brushes on proteins embedded in biological membranes by employing both Asakura-Oosawa type of theoretical model and coarse-grained molecular dynamics simulations. The brush polymer-induced depletion attraction between proteins changes non-monotonically with the size of brush. The depletion interaction, which is determined by the ratio of the protein size to the grafting distance between brush polymers, increases linearly with the brush size as long as the polymer brush height is shorter than the protein size. When the brush height exceeds the protein size, however, the depletion attraction among proteins is slightly reduced. We also explore the possibility of the brush polymer-induced assembly of a large protein cluster, which can be related to one of many molecular mechanisms underlying recent experimental observations of integrin nanocluster formation and signaling.


Silencing of the VHL tumor-suppressor gene by DNA methylation in renal carcinoma.
Mutational inactivation and allelic loss of the von Hippel-Lindau (VHL) gene appear to be causal events for the majority of spontaneous clear-cell renal carcinomas. We now show that hypermethylation of a normally unmethylated CpG island in the 5' region provides another potentially important mechanism for inactivation of the VHL gene in a significant portion of these cancers. This hypermethylation was found in 5 of 26 (19%) tumors examined. Four of these had lost one copy of VHL while one retained two heavily methylated alleles. Four of the tumors with VHL hypermethylation had no detectable mutations, whereas one had a missense mutation in addition to hypermethylation of the single retained allele. As would be predicted for the consequence of methylation in this 5' CpG island, none of the 5 tumors expressed the VHL gene. In contrast, normal kidney and all tumors examined with inactivating VHL gene mutations but no CpG island methylation had expression. In a renal cell culture line, treatment with 5-aza-2'-deoxycytidine resulted in reexpression of the VHL gene. These findings suggest that aberrant methylation of CpG islands may participate in the tumor-suppressor gene inactivations which initiate or cause progression of common human cancers.


Acute red eye. Differentiating viral conjunctivitis from other, less common causes.
Adenoviral conjuctivitis is one of the most common causes of acute red eye. Other diagnostic considerations include herpes virus conjunctivitis, chlamydial conjunctivitis, allergic conjunctivitis, and various other less common infections. Careful history taking can help in identifying a viral cause. The presentation may range from a minor conjunctivitis resulting from an upper respiratory tract infection to a serious, debilitating epidemic keratoconjunctivitis. Local care and interventions to minimize transmission are the cornerstones of management. Infection is usually self-limiting. Warm soaks and artificial tear lubricants may relieve itching and burning. Patients should be instructed to avoid touching their eyes, wash hands often, use disposable towels, and avoid group activities for as long as an ocular discharge is present. Use of topical corticosteroids or antibacterial preparations can lead to complications, and injudicious use of topical corticosteroids may mask serious conditions that require other interventions.


Nectar quality perception by honey bees (Apis mellifera ligustica).
In exploring how foragers perceive rewards, we often find that well-motivated individuals are not too choosy and unmotivated individuals are unreliable and inconsistent. Nevertheless, when given a choice we see that individuals can clearly distinguish between rewards. Here we develop the logic of using responses to two-choice problems as a derivative function of perceived reward, and utilize this model to examine honey bee perception of nectar quality. Measuring the derivative allows us to deduce the perceived reward function. The derivative function of the perceived reward equation gives the rate of change of the reward perceived for each reward value. This approach depends on presenting free-flying foragers with a series of two different rewards presented simultaneously (i.e., two-choice, binomial tests). We also examine how honey bees integrate information from a range of reward qualities to formulate a functional response. Results suggest that honey bees overestimate higher quality rewards and that direct comparison is an important step in the integration of information from a range of rewards.


Bradycardia after pulse methylprednisolone therapy in a child-Uncommon side effect of a frequently used drug: A case report.
Corticosteroids are potent anti-inflammatory agents used as a mainstay of therapy in most of the rheumatologic disorders. Common side effects of pulse steroid therapy include hypertension, hyperglycemia, seizure, hypokalemia, and infection. We report a case of an 11-year-old girl with polyarticular Juvenile idiopathic arthritis who developed bradycardia following pulse methylprednisolone therapy. On day 2 of methylprednisolone infusion, she developed bradycardia with a heart rate between 50 and 60/min. ECG was suggestive of sinus bradycardia. There was no evidence of dyselectrolytemia (Na-141 mmol/l, K-3.54 mmol/l, Ca-8.72 mg/l) or sepsis. The patient did not receive methylprednisolone on day 3 and vitals continued to be monitored. Her heart rate improved after 12 hours. In the mid of infusion on day 4, again the patient had bradycardia with a heart rate of 50-60/minute. Since she was hemodynamically stable, we continued the infusion, and bradycardia resolved in the next 8 hours. On follow-up after 2 weeks, she had some improvement in joint symptoms and normal heart rate. As per Naranjo adverse drug reaction probability scale, the adverse reaction in our case was probable with a score of 8. Although bradycardia associated with pulse steroid therapy is benign and is usually reversible following cessation of therapy, a baseline heart rate, ECG, and electrolyte level are suggested before infusion as a cautionary measure to minimize serious adverse events.


Contribution of the Platelia Candida-specific antibody and antigen tests to early diagnosis of systemic Candida tropicalis infection in neutropenic adults.
The Platelia Candida-specific antigen and antibody assays (Bio-Rad Laboratories) were used to test serial serum samples from seven neutropenic adult patients with hematological malignancies who had developed systemic Candida tropicalis infections. The diagnosis of candidiasis was based on a positive blood culture (all seven patients) and the isolation of C. tropicalis from a normally sterile site (six patients). All patients received early antifungal therapy with amphotericin B and/or an azole derivative and had successful outcomes. When the combined assays were applied to sera collected at different time points before and after the first positive blood culture, all patients tested positive. In six patients, at least one positive test was obtained with sera collected, on average, 5 days (range, 2 to 10 days) prior to the first positive blood culture, while blood cultures were constantly negative. High and persistent mannanemias were detected in all patients during the neutropenic period. In five patients, an increased antibody response was detected when the patients recovered from aplasia. Controls consisted of 48 serum samples from 12 febrile neutropenic patients with aspergillosis (n = 4), bacteremia (n = 4), or no evidence of infection (n = 4). A low level of mannanemia was detected in only one serum sample, and none showed significant Candida antibody titers. Our data thus confirm the value of the combined detection of mannanemia and antimannan antibodies in individuals at risk of candidemia and suggest that in neutropenic patients, an approach based on the regular monitoring of both markers could contribute to the earlier diagnosis of C. tropicalis systemic infection.


Use of single-nucleotide polymorphisms in the search for genetic modifiers of the uremic phenotype.
As the modern nephrology community continues to be burdened with growing numbers of patients with end-stage renal disease (ESRD) and exceptionally high mortality rates, it is obvious that progress in the development of preventive and therapeutic strategies has not been sufficient. This urges nephrologists to focus on the underlying mechanisms for ESRD morbidity and mortality, and in particular on cardiovascular disease (CVD), which is the major contributor to premature death in this patient group. The high prevalence of inflammation, vascular ossification, and oxidative stress in ESRD predisposes these patients to CVD. Because genetic risk factors may modulate the pathophysiologic response, genotype-phenotype association studies may provide ways of predicting individual disease progression and may shed some light on key regulatory pathways. Indeed, recent genetic association studies show that polymorphisms in candidate genes related to inflammatory signaling, vascular ossification, and oxidative stress response influence the uremic phenotype. DNA polymorphisms may also be used as nonconfounded tools in observational studies conducted to test causality, as stated by the mendelian randomization approach. To date, the collection of genetic data is no longer a limitation because genetic information is easily accessible in public databases and high-throughput genotyping technologies are available. Advanced bioinformatic tools are now warranted to facilitate the integration of accumulating genetic information with clinical and biochemical end points and, finally, to implement genotype-phenotype data in the care of patients with renal failure to better identify patients at high risk and to design novel personalized therapeutic and preventive strategies.


Effects of propolis extract on growth performance and health condition of dairy calves.
The aim of this study was to evaluate the effect of propolis ethanol extract, on performance, fecal structure, and general health status of calves during the preweaning phase. For this purpose, 24 Simmental calves that were given colostrum for the first 3 days after birth were enrolled in the study. The study started when the calves were 4 days old and finished when they were 60 days old. These calves were divided into two groups as propolis and control groups according to their weight and gender. Both groups were given the same ration and housed in individual calf huts under the same environmental conditions. Differently from the control group, the calves in the propolis group were given 4 mL of propolis extract (300 mg/mL) with an oral feeding syringe for 56 days after morning feeding. The amounts of feed intake and fecal scores of the calves were recorded daily. Health scores, rectal body temperature, fecal pH, body weight, and body measurements were recorded weekly. For the determination of the counts of Lactobacillus spp. and Bifidobacterium spp., fecal samples were collected at the beginning and at the end of the study. The results indicated that oral administration of propolis had positive effects in terms of some performance parameters, the number of days with diarrhea, and fecal scores. In this study, it was concluded that propolis extract had the potential to positively affect the growth performance and health status of preweaning calves.


Volume overload in patients treated with continuous ambulatory peritoneal dialysis associated with reduced circadian blood pressure variation.
While a high blood pressure (BP) in patients receiving maintenance ambulatory peritoneal dialysis (CAPD) is associated with congestive heart failure and an increased mortality, the relevance of diurnal variations in BP is unknown. In a prospective study, we enrolled 76 prevalent patients receiving stable CAPD (age 60.4 +/- 13.8 years; 37 males). BP was measured over 24 h using an automated device. We also performed routine clinical and biochemical measurements, as well as the Karnofsky index to evaluate physical activity. Volume status was assessed using bioimpedance analysis. 69 patients (with an average time on dialysis of 24.4 +/- 22.5 months) completed the study. Of these, 16 patients experienced a drop in BP >10% at night (dippers), while 53 patients did not (non-dippers). Comparing these two groups, dippers had significantly lower extracellular water (ECW) (13.8 +/- 2.1 vs. 15.9 +/- 3.3 l; p < 0.05), normalized extracellular water (nECW) (0.22 +/- 0.05 vs. 0.26 +/- 0.04 l/m; p < 0.05), and serum albumin (38.2 +/- 2.9 vs. 35.9 +/- 3.7 g/l; p < 0.05). Age, Karnofsky index, vintage, residual renal Kt/V and peritoneal Kt/V, total Kt/V, dose of antihypertensive drugs, mean systolic and diastolic BP did not significantly differ between these groups. Correlation analysis showed the coefficient of variation (CV) of BP positively correlated with E/T (r(2) = 0.292; p < 0.05), diabetic (r(2) = 0.267; p < 0.05), male (r(2) = 0.257; p < 0.05), nECW (r(2) = 0.278; p < 0.05) and ECW (r(2) = 0.249; p < 0.05) negatively correlated with albumin (r(2) = -0.280; p < 0.05). Furthermore, in a multivariate linear regression model, E/T, albumin and sex were independently associated with CV for BP. We show that reduced BP variation is common in CAPD patients and associated with volume overload and hypoalbuminemia. Furthermore, the relationship between nutritional, inflammatory status and dipping needs further studies.


Polymyalgia rheumatica and temporal arteritis in a married couple.
A husband suffering from temporal arteritis and his wife afflicted with polymyalgia rheumatica are reported. The possibility of the existence of an environmental factor rather than a genetic etiology is discussed.


[Mycobacterium marinum infection. Case report and review of the literature].
Atypical mycobacterial infections are increasingly important in immunosuppressed patients as well as in healthy hosts. The atypical mycobacterium that most commonly affects the skin is Mycobacterium marinum. The infection should be suspected upon the presence of ulcers, nodules or chronic plaques and a history of contact with fresh or salt water. Optimal therapy is yet to be established. We report a case of Mycobacterium marinum infection in a patient receiving immunosuppressive therapy that responded favourably to treatment with doxicycline. We review the different antibiotic regimens prescribed in the past years for the treatment of Mycobacterium marinum infection.


A qualitative exploration of patients' experience of mobile telephone-delivered contingency management to promote adherence to supervised methadone.
Despite an increasing evidence base for mobile telephone-delivered contingency management (mCM), there had been no previous qualitative exploration of patients' experience of receiving mCM and the factors that might influence that experience and outcome in a UK setting. The aim of this study was to understand patients' views and experience of receiving mCM by exploring their beliefs, expectations and perceived benefits within the context of the UK's first mCM intervention. Qualitative interviews (N = 15) were conducted with patients undergoing opioid agonist treatment in a UK drug treatment service and receiving mCM to encourage adherence with supervised methadone as part of an existing study. Interviews were conducted at two time points and analysed using Framework to explore patients' expectations and beliefs during the early stage of the intervention (2 weeks) and their perceived benefits and experience at the end of the intervention (12 weeks). The mCM was perceived as a motivator, providing validation of achievement, and involving discreet and positive interactions. Perceived benefits included enhanced methadone adherence, reduced drug use and the development of a supportive and non-judgemental connection that resembled a therapeutic alliance. The mechanisms underpinning contingency management appeared to operate in the absence of human interaction, and the mCM intervention was deemed to be meaningful, acceptable and well received by patients. These findings not only provide support for the application of mCM in this context but also offer insight into the factors that influence outcomes and should be considered in the development of future mCM interventions.


The management of croup.
Croup is a common paediatric respiratory illness involving inflammation and narrowing of the subglottic region of the larynx, frequently precipitated by viral infections. Treatment is aimed at decreasing symptoms and reducing inflammation. Glucocorticoids are effective by oral, parenteral or nebulized routes, and continue to provide the mainstay of therapy. The common oral dexamethasone dose (0.6 mg/kg) may exceed the dose required for good clinical efficacy. Nebulized epinephrine provides effective additional therapy for more severe cases. L-epinephrine appears to be comparable to racemic epinephrine, although further study is warranted. Limited data suggest that heliox is also effective in the short-term management of refractory croup. The use of humidified oxygen remains controversial, as good data are lacking.


Enhancement of tetrel bond involving tetrazole-TtR3 (Tt = C, Si; R = H, F). Promotion of SiR3 transfer by a triel bond.
When attached to a tetrazole, a TtR3 group (Tt = C, Si; R = H, F) engages in a Tt⋯N tetrel bond (TtB) with the Lewis base NCM (M = Li, Na). MP2/aug-cc-pVTZ calculations find that the Si⋯N TtB is rather strong, more than 20 kcal mol-1 for SiH3, and between 46 and 53 kcal mol-1 for SiF3. The C⋯N TtBs are relatively weaker, less than 8 kcal mol-1. All of these bonds are intensified when a BH3 or BF3 molecule forms a triel bond to a N atom of the tetrazole ring, particularly for the C⋯N TtB, up to 11 kcal mol-1. In these triads, the SiR3 group displaces far enough along the line toward the base that it may be thought of as half transferred.


Automatic microarray image segmentation with clustering-based algorithms.
Image segmentation, as a key step of microarray image processing, is crucial for obtaining the spot expressions simultaneously. However, state-of-art clustering-based segmentation algorithms are sensitive to noises. To solve this problem and improve the segmentation accuracy, in this article, several improvements are introduced into the fast and simple clustering methods (K-means and Fuzzy C means). Firstly, a contrast enhancement algorithm is implemented in image preprocessing to improve the gridding precision. Secondly, the data-driven means are proposed for cluster center initialization, instead of usual random setting. The third improvement is that the multi features, including intensity features, spatial features, and shape features, are implemented in feature selection to replace the sole pixel intensity feature used in the traditional clustering-based methods to avoid taking noises as spot pixels. Moreover, the principal component analysis is adopted for various feature extraction. Finally, an adaptive adjustment algorithm is proposed based on data mining and learning for further dealing with the missing spots or low contrast spots. Experiments on real and simulation data sets indicate that the proposed improvements made our proposed method obtains higher segmented precision than the traditional K-means and Fuzzy C means clustering methods.


Effect of monensin, estradiol controlled release implants and supplement on performance in grazing steers.
Five trials in five locations in the United States involving 512 steers were conducted to evaluate the effect of monensin [200 mg/d in .9 kg of supplement (Ru mensin )] and estradiol-controlled release implants ( Compudose ) administered alone and in combination on average daily gain (ADG) in steers on pasture. The effect of energy supplementation on rate of gain was also evaluated in these same trials. The initial weight of steers averaged 250 kg and the average duration of the five trials was 124 d. Estradiol-controlled release implants increased ADG by 15.6% (.095 kg/d; P less than .0001) and monensin increased ADG by 8.1% (.054 kg/d; P less than .05). The combination of estradiol-controlled release implant and monensin increased ADG by 27.4% (.168 kg/d). Treatment responses were additive relative to ADG response, with no interaction observed between the treatments. Nine-tenths kilograms of an energy supplement/d increased ADG by 12.4% (.073 kg/d; P less than .01).


Arrested development: understanding v-abl.
The protein tyrosine kinase activity of the v-abl oncogene has been demonstrated to subvert the normal second messenger systems used by lymphoid cells for growth and differentiation. Transformation of bone marrow with the Abelson murine leukemia virus results in the appearance of B cell lineage cells arrested at the pre-B cell stage. Recent reports have characterized these cells expressing high v-abl kinase activity as deficient in detectable NF-kappaB DNA binding activity and low level RAG gene expression. These observations suggest that v-abl may be inhibiting the differentiation of B cells by blocking these two crucial elements in the maturation pathway.


Vascular complications and associated comorbidities in newly diagnosed pre-diabetes: is it the tip of the iceberg?
The aim of this study was to investigate the prevalence of microvascular and macrovascular diabetic complications and the associated comorbidities in newly diagnosed pre-diabetic individuals. This cross-sectional study includes 100 newly diagnosed pre-diabetic individuals. Fasting plasma glucose, HbA1c, and oral glucose tolerance (OGTT) were tested according to the American Diabetes Association's diagnostic criteria for pre-diabetes, besides anthropometric measurements, lipid profiles, and demographic and biochemical parameters. Comorbidities like hypertension, obesity, dyslipidemia etc., were evaluated. All participants were screened for microvascular (retinopathy, nephropathy, neuropathy) and macrovascular [coronary artery disease (CAD) and cerebrovascular event-peripheral artery disease] complications. Microvascular complications were found in 12% of the participants (neuropathy: 4%, nephropathy: 8%) and 19% had macrovascular complications. Of the participants, 21% of the cases presented hypertension, 21% dyslipidemia and 48% obesity. A high probability of developing non-alcoholic fatty liver disease-related fibrosis [estimated using non-alcoholic fatty liver disease fibrosis score (NFS)] was found in 68% of cases. History of dyslipidemia (OR: 5.00, 95% CI: 1.10-22.56; p=0.037) was an independent risk factor for the development of vascular complications. Diabetic vascular complications were found in approximately one-third of pre-diabetic cases. Dyslipidaemia was found to be an important risk factor for the development of vascular complications in these individuals.


Early identification of autism spectrum disorder in children with CHD attending a Cardiac Developmental Outcomes Program.
To determine the prevalence and timing of autism spectrum disorder diagnosis in a cohort of congenital heart disease (CHD) patients receiving neurodevelopmental follow-up and identify associated risk factors. Retrospective single-centre observational study of 361 children undergoing surgery for CHD during the first 6 months of life. Data abstracted included age at autism spectrum disorder diagnosis, child and maternal demographics, and medical history. Autism spectrum disorder was present in 9.1% of children with CHD, with a median age at diagnosis of 34 months and 87.9% male. Prematurity, history of post-operative extracorporeal membrane oxygenation, and seizures were higher among those with autism (p = 0.013, p = 0.023, p = 0.001, respectively). Infants with autism spectrum disorder were older at the time of surgery (54 days vs 13.5 days, p = 0.002), and infants with surgery at ≥ 30 days of age had an increased risk of autism spectrum disorder (OR 2.31; 95% CI =1.12, 4.77, p = 0.023). On multivariate logistic regression analysis, being male (OR 4.85, p = 0.005), surgery ≥ 30 days (OR 2.46, p = 0.025), extracorporeal membrane oxygenation (OR 4.91, p = 0.024), and seizures (OR 4.32, p = 0.003) remained associated with increased odds for autism spectrum disorder. Maternal age, race, ethnicity, and surgical complexity were not associated. Children with CHD in our cohort had more than three times the risk of autism spectrum disorder and were diagnosed at a much earlier age compared to the general population. Several factors (male, surgery at ≥ 30 days, post-operative extracorporeal membrane oxygenation, and seizures) were associated with increased odds of autism. These findings support the importance of offering neurodevelopmental follow-up after cardiac surgery in infancy.


Estimated costs of postoperative wound infections. A case-control study of marginal hospital and social security costs.
A cohort of 4515 surgical patients in ten selected intervention groups was followed. Three hundred and seventeen developed postoperative wound infections, and 291 of these cases were matched 1:1 to controls by operation, sex and age. In comparison to the controls the cases stayed longer in hospital after the intervention and had more contact after discharge with the social security system. Using data from a national sentinel reference database of the incidence of postoperative wound infections, and using national activity data, we established an empirical cost model based on the estimated marginal costs of hospital resources and social sick pay. It showed that the hospital resources spent on the ten groups, which represent half of the postoperative wound infections in Denmark, amounted to approximately 0.5% of the annual national hospital budget. This stratified model creates a better basis for selecting groups of operations which need priority in terms of preventive measures.


Genistein and resveratrol: mammary cancer chemoprevention and mechanisms of action in the rat.
The environment, including diet, plays a critical role in a woman's subsequent risk of breast cancer. Two dietary polyphenols that have received attention from the health and research communities for their ability to protect against breast cancer are: genistein, a component of soy; and resveratrol, a phytoalexin found in red grapes and red wine. We and others have shown that both genistein and resveratrol can protect against mammary cancer in rodents. The timing of exposure to genistein appears critical for its mammary protective effects. It has been reported that genistein early in life causes enhanced mammary gland differentiation, alterations in cell proliferation and apoptosis, and upregulation of tumor-suppressor genes. With resveratrol in the diet, changes in cell proliferation and apoptosis in terminal ductal structures of the mammary gland might help to explain its protective effects. We conclude that genistein and resveratrol can protect against breast cancer by regulating important mammary growth and differentiation pathways.


Treatment of Morton's neuroma by neurolysis.
Thirty-five patients who had undergone neurolysis for Morton's neuroma were reviewed at a mean of 21.4 months. Those patients who had received diagnostic lidocaine (local anesthetic) injections as an evaluation tool before the operation did extremely well after this operation. Overall patient satisfaction was found to be extremely high, with 17 of 35 patients enjoying complete relief of their pain and 12 of 35 reporting minimal discomfort with activity. The likelihood of persistent symptoms seemed to be related to the presence of associated foot disorders.


Insect pest control, approximate dynamic programming, and the management of the evolution of resistance.
Ecological decision problems, such as those encountered in agriculture, often require managing conflicts between short-term costs and long-term benefits. Dynamic programming is an ideal method for optimally solving such problems but agricultural problems are often subject to additional complexities that produce state spaces intractable to exact solutions. In contrast, look-ahead policies, a class of approximate dynamic programming (ADP) algorithm, may attempt to solve problems of arbitrary magnitude. However, these algorithms focus on a temporally truncated caricature of the full decision problem over a defined planning horizon and as such are not guaranteed to suggest optimal actions. Thus, look-ahead policies may offer promising means of addressing detail-rich ecological decision problems but may not be capable of fully utilizing the information available to them, especially in scenarios where the best short- and long-term solutions may differ. We constructed and applied look-ahead policies to the management of a hypothetical, stage-structured, continually reproducing, agricultural insect pest. The management objective was to minimize the combined costs of management actions and crop damage over a 16-week growing season. The manager could elect to utilize insecticidal sprays or one of six release ratios of male-selecting transgenic insects where the release ratio determines the number of transgenic insects to be released for each wild-type male insect in the population. Complicating matters was the expression of insecticide resistance at non-trivial frequencies in the pest population. We assessed the extent to which look-ahead policies were able to recognize the potential threat of insecticide resistance and successfully integrate insecticides and transgenic releases to capitalize upon their respective benefits. Look-ahead policies were competent at anticipating and responding to ecological and economic information. Policies with longer planning horizons made fewer, better-timed insecticidal sprays and made more frequent transgenic releases, which consequently facilitated lower resistance allele frequencies. However, look-ahead policies were ultimately inefficient resistance managers, and directly responded to resistance only when it was dominant and prevalent. Effective long-term agricultural management requires the capacity to anticipate and respond to the evolution of resistance. Look-ahead policies can accommodate all the information pertinent to making the best long-term decision but may lack the perspective to actually do so.


Hydrogen bonding and the conformations of poly(alkyl acrylamides).
The conformations of poly(alkyl acrylamide) oligomers in nonpolar solvents were studied using molecular dynamics techniques. Poly(methyl acrylamide) was found to collapse to a globule-like conformation at low temperatures; however, excluded volume effects inhibited the collapse of poly(octadecyl acrylamide). A high density of structured units, characterized by a trans-gauche-trans-trans-gauche-trans torsional sequence along the backbone, was noted in all simulations. Such units were found to create a particularly stable set of intramolecular hydrogen bonds. An oligomer constructed with these stable units was found to have significantly lower minimized energy than both the all-trans and the helical backbone conformations. The constructed conformation had lower Coulomb energy (more hydrogen bonds) than the all-trans conformation and lower dihedral energy (less backbone distortion) than the helical conformation. The propensity for poly(octadecyl acrylamide) to form hydrogen bonds introduced significant disorder into the orientation of the alkyl side chains. This disorder would inhibit crystallization and restrict the ability of such polymers to form epitaxial seeds for nucleating paraffin crystals.


Best practice in critical care: anaemia in acute and critical illness.
Anaemia is common in critical illness, and standard treatment is red blood cell (RBC) transfusion, typically using a restrictive transfusion threshold of 70 g L-1 . However, there are subgroups of patients in whom it is biologically plausible that a higher transfusion threshold may be beneficial, namely, acute sepsis, traumatic brain injury and coexisting cardiovascular disease. In this review article, we will discuss the pathophysiology of anaemia, as well as its prevalence and time course. We will explore the limitations of using haemoglobin concentration as a surrogate for oxygen delivery and the concept of the critical haemoglobin concentration. We will then discuss transfusion thresholds for the general intensive care unit (ICU) population and specific subgroups.


Association of lipophilic opioids and hyperbaric bupivacaine in spinal anesthesia for elective cesarean section. Randomized controlled study.
To evaluate the efficacy and side-effects of fentanyl and sufentanil combined with hyperbaric spinal bupivacaine in elective cesarean section. A prospective, randomized, double-blind study with 64 term parturients, distributed into 2 groups according to the opioid combined with hyperbaric bupivacaine 0.5% (10mg): GF - fentanyl (25 µg) and GS - sufentanil (5.0 µg). The latency and maximum sensory block level; degree and duration of motor block; duration and quality of analgesia; maternal-fetal repercussions were evaluated. This was an intention-to-treat analysis with a 5% significance level. The latency period, maximum sensory block level, motor block degree and perioperative analgesia were similar in both groups. Motor block and analgesia had a longer duration in the sufentanil group. Maternal adverse effects and neonatal repercussions were similar. The incidence of hypotension was higher in the fentanyl group. In both groups, there was a predominance of patients who were awake and either calm or sleepy. The addition of fentanyl and sufentanil to hyperbaric subarachnoid bupivacaine was shown to be effective for the performance of cesarean section, and safe for the mother and fetus. Analgesia was more prolonged with sufentanil.


[Comparison of biological characteristics of placenta mesenchymal stem cells derived from fetus].
Mesenchymal stem cells (MSCs) have broad application potentials in regenerative medicine and translational medicine. Obtaining large quantities of primary-cultured MSCs and select the most suitable cell origin for targeted diseases are critical to research. To select the most suitable seed cells of MSCs from different origins for clinical treatment and research, biological characteristics of MSCs from human umbilical cord and placenta were compared. These include cell morphology, surface marker expression, differentiation and karyotype. Transcriptome sequencing of four MSCs from fetus were performed and the results were analyzed from the perspective of proliferation and cytokine secretion. The results revealed that MSCs from umbilical cord (UC), amniotic membrane (AM), chorionic membrane (CM), chorionic villi (CV) and deciduae (DC) met the minimum standards of the International Society of Cell Therapy (ISCT) in 2006 and had the general characteristics of stem cells. Karyotype analysis showed that MSCs derived from UC, AM, CM and CV were all from fetus except that the DC-MSCs were from mother. Transcriptome sequencing analysis showed that hMSCs from umbilical cord and placenta had similar gene expression patterns, while different expression patterns were observed in specific genes involved in cell cycle, cell division, cell death, cell growth and development. These genes play important roles in transcriptional regulation, DNA repair, DNA replication and chromosome stability, which were momentous components of cellular or subcellular fraction movement, cell communication, cell tissue protrusions, cytokine secretion and hormone metabolism. Transcriptome sequencing analysis explained the differences in biological characteristics among MSCs from different sources, while verification experiments based on the transcriptome sequencing results showed that the proliferation and cytokine secretion capabilities of MSCs from different sources were significantly different. In all, UC-MSCs and CV-MSCs with stronger proliferation and higher levels of paracrine factors secretion may show their respective advantages in treating diseases.


Impact of mobile health applications on self-management in patients with type 2 diabetes mellitus: protocol of a systematic review.
The emergence of mobile health (mHealth) solutions, particularly mHealth applications (apps), has shown promise in self-management of chronic diseases including type 2 diabetes mellitus (T2DM). While majority of the previous systematic reviews have focused on the effectiveness of mHealth apps in improving treatment outcomes in patients with T2DM, there is a need to also understand how mHealth apps influence self-management of T2DM. This is crucial to ensure improvement in the design and use of mHealth apps for T2DM. This protocol describes how a systematic review will be conducted to determine in which way(s) mHealth apps might impact on self-management of T2DM. The following electronic databases will be searched from inception to April 2019: PubMed, MEDLINE, EMBASE, Global Health, PsycINFO, CINAHL, The Cochrane Central Register of Controlled Trials, Scopus, Web of Science, ProQuest Dissertations & Theses Global, Health Management Information Consortium database, Google Scholar and ClinicalTrials.gov. The Cochrane risk of bias tool will be used to assess methodological quality. The primary outcome measures to be assessed will be 'change in blood glucose'. The secondary outcomes measures will be 'changes in cardiovascular risk markers' (including blood pressure, body mass index and blood lipids), and self-management practices. Others will include: health-related quality of life, economic data, social support, harms (eg, death or complications leading to hospital admissions or emergency unit attendances), death from any cause, anxiety or depression and adverse events (eg, hypoglycaemic episodes). This study will not involve the collection of primary data and will not require ethical approval. The review will be published in a peer-reviewed journal and a one-page summary of the findings will be shared with relevant organisations. Presentation of findings will be made at appropriate conferences. CRD42017071106.


Inhibition of proliferation and invasion of hepatocellular carcinoma cells by lncRNA-ASLNC02525 silencing and the mechanism.
One of the most differentially expressed long non-coding RNAs (lncRNAs) that we identified by high throughput screening from liver cancer and para-carcinoma tissues, ASLNC02525, was highly expressed in the tissues and cell lines of liver cancer but not in adjacent tissues or normal hepatic cells. Knockdown of ASLNC02525 in hepatocellular carcinoma cells inhibited the proliferation and invasion. In the process, expression level of transcription factor twist1 (twist‑related protein 1) was reduced, but no change at transcription level was observed. According to bioinformatics analysis, ASLNC02525 may play a crucial role in inactivation of regulation of twist1 by hsa-miRNA-489-3p. The mechanism study revealed that ASLNC02525, as an RNA sponge, broke the negative regulation of twist1 by hsa-miRNA-489-3p, and once ASLNC02525 was silenced, the highly expressed hsa-miRNA‑489-3p regained its regulation on twist1 and inhibited the proliferation and invasion. The importance of this study lies in shedding light on the potential for lncRNAs to become targets for gene therapy, by demonstrating that lncRNAs can suppress tumor inhibiting activity of miRNAs via breaking regulation of some miRNA target genes.


Abnormal sperm in mice with targeted deletion of the act (activator of cAMP-responsive element modulator in testis) gene.
ACT [activator of cAMP-responsive element modulator (CREM) in testis] is a LIM-only protein that interacts with transcription factor CREM in postmeiotic male germ cells and enhances CREM-dependent transcription. CREM regulates many crucial genes required for spermatid maturation, and targeted mutation of the Crem gene in the mouse germ-line blocks spermatogenesis. Here we report the phenotype of mice in which targeted disruption of the act gene was obtained by homologous recombination. Whereas the seminiferous tubules of the act(-/-) mice contain all of the developmental stages of germ cells and the mice are fertile, the amount of mature sperm in the epididymis is drastically reduced. The residual sperm display severe abnormalities, including fully folded tails and aberrant head shapes. These results indicate that numerous postmeiotic genes under CREM control require the coactivator function of ACT. Thus, the fine-tuning of sperm development is achieved by the coordinated action of two transcriptional regulators.


Stanniocalcin 2 enhances mesenchymal stem cell survival by suppressing oxidative stress.
To overcome the disadvantages of stem cell-based cell therapy like low cell survival at the disease site, we used stanniocalcin 2 (STC2), a family of secreted glycoprotein hormones that function to inhibit apoptosis and oxidative damage and to induce proliferation. STC2 gene was transfected into two kinds of stem cells to prolong cell survival and protect the cells from the damage by oxidative stress. The stem cells expressing STC2 exhibited increased cell viability and improved cell survival as well as elevated expression of the pluripotency and self-renewal markers (Oct4 and Nanog) under sub-lethal oxidative conditions. Up-regulation of CDK2 and CDK4 and down-regulation of cell cycle inhibitors p16 and p21 were observed after the delivery of STC2. Furthermore, STC2 transduction activated pAKT and pERK 1/2 signal pathways. Taken together, the STC2 can be used to enhance cell survival and maintain long-term stemness in therapeutic use of stem cells.


Antigens produced in plants by infection with chimeric plant viruses immunize against rabies virus and HIV-1.
The coat protein (CP) of alfalfa mosaic virus was used as a carrier molecule to express antigenic peptides from rabies virus and HIV. The antigens were separately cloned into the reading frame of alfalfa mosaic virus CP and placed under the control of the subgenomic promoter of tobacco mosaic virus CP in the 30BRz vector. The in vitro transcripts of recombinant virus with sequences encoding the antigenic peptides were synthesized from DNA constructs and used to inoculate tobacco plants. The plant-produced protein (virus particles) was purified and used for immunization of mice. Both antigens elicited specific virus-neutralizing antibodies in immunized mice.


Perioperative use of oxygen: variabilities across age.
Enormous interest has emerged in the perioperative use of high concentrations of inspired oxygen in an attempt to increase tissue oxygenation and thereby improve postoperative outcome. An extensive debate has arisen regarding the risk/benefit ratio of oxygen therapy, with some researchers advocating the benefits of perioperative hyperoxia, particularly with regard to surgical site infection, whereas others emphasize its detrimental consequences on multiple organs, particularly the lungs and the brain. As one aspect of this debate, there is increased awareness of effects of reactive oxygen metabolites, a feature that contributes to the complexity of achieving consensus regarding optimum oxygen concentration in the perioperative period. Many reviews have discussed the pros and cons in the use of perioperative oxygen supplementation, but the potential importance of age-related factors in hyperoxia has not been addressed. The present narrative review provides a comprehensive overview of the physiological mechanisms and clinical outcomes across the age range from neonates to the elderly. Risks greatly outweigh the benefits of hyperoxia both in the very young, where growth and development are the hallmarks, and in the elderly, where ageing increases sensitivity to oxidative stress. Conversely, in middle age, benefits of short-term administration of perioperative oxygen therapy exceed potential adverse change effects, and thus, oxygen supplementation can be considered an important therapy to improve anaesthesia management.


The usefulness and limitations of hand-held refractometers in veterinary laboratory medicine: an historical and technical review.
Medical hand-held refractometers have been used in veterinary practice since their development in the 1960s. They have become ubiquitous for the measurement of protein and urine solute concentrations because of their rapidity of analysis, ease of use, and relatively low cost. Refraction of light offers advantages for the determination of solute concentrations because the measurement requires no chemical alteration of the specimen. Numerous authors have reported that the results of protein estimation by refractometry for domestic mammals correlate well with those obtained by the biuret method, although others have reported both higher and lower refractometric results compared with biuret results. Major discrepancies between biuret and refractometric results have been reported for avian samples. Some of the variation in reported results may be due to differences in design by refractometer manufacturers. Another possible source may be variation in the biuret reagent mixture and assay conditions. Refractometers also can be used to calculate serum water concentration. A table that converts index of refraction to serum water concentration can be used to convert electrolyte concentration from mmol/L of serum to mmol/L of serum water, a more accurate indicator of effective electrolyte concentration. Refractometers are especially useful for determining urine specific gravity on veterinary samples because they require relatively small sample volumes. Specific gravity continues to be the most common unit for reporting total solids concentration. Some solutes, such as acetone, may cause false increases in specific gravity by refractometry, as they increase refraction but are less dense than water.


Bub1p kinase activates the Saccharomyces cerevisiae spindle assembly checkpoint.
Saccharomyces cerevisiae BUB1 encodes a protein kinase required for spindle assembly checkpoint function. In the presence of spindle damage, BUB1 is required to prevent cell cycle progression into anaphase. We have identified a dominantly acting BUB1 allele that appears to activate the spindle assembly checkpoint pathway in cells with undamaged spindles. High-level expression of BUB1-5 did not cause detectable spindle damage, yet it delayed yeast cells in mitosis at a stage following bipolar spindle assembly but prior to anaphase spindle elongation. Delayed cells possessed a G2 DNA content and elevated Clb2p mitotic cyclin levels. Unlike cells delayed in mitosis by spindle damage or MPS1 kinase overexpression, hyperphosphorylated forms of the Mad1p checkpoint protein did not accumulate. Similar to cells overexpressing MPS1, the BUB1-5 delay was dependent upon the functions of the other checkpoint genes, including BUB2 and BUB3 and MAD1, MAD2, and MAD3. We found that the mitotic delay caused by BUB1-5 or MPS1 overexpression was interdependent upon the function of the other. This suggests that the Bub1p and Mps1p kinases act together at an early step in generating the spindle damage signal.


Estradiol suppresses NF-kappa B activation through coordinated regulation of let-7a and miR-125b in primary human macrophages.
Previous findings suggest that 17beta-estradiol (estradiol) has a suppressive effect on TNF-alpha, but the mechanism by which estradiol regulates TNF-alpha expression in primary human macrophages is unknown. In this article, we demonstrate that pretreatment of human macrophages with estradiol attenuates LPS-induced TNF-alpha expression through the suppression of NF-kappaB activation. Furthermore, we show that activation of macrophages with LPS decreases the expression of kappaB-Ras2, an inhibitor of NF-kappaB signaling. Estradiol pretreatment abrogates this decrease, leading to the enhanced expression of kappaB-Ras2 with LPS stimulation. Additionally, we identified two microRNAs, let-7a and miR-125b, which target the kappaB-Ras2 3' untranslated region (UTR). LPS induces let-7a and inhibits miR-125b expression in human macrophages, and pretreatment with estradiol abrogates these effects. 3'UTR reporter assays demonstrate that let-7a destabilizes the kappaB-Ras2 3'UTR, whereas miR-125b enhances its stability, resulting in decreased kappaB-Ras2 in response to LPS. Our data suggest that pretreatment with estradiol reverses this effect. We propose a novel mechanism for estradiol inhibition of LPS-induced NF-kappaB signaling in which kappaB-Ras2 expression is induced by estradiol via regulation of let-7a and miR-125b. These findings are significant in that they are the first to demonstrate that estradiol represses NF-kappaB activation through the induction of kappaB-Ras2, a key inhibitor of NF-kappaB signaling.


A multiperspective on the broad dissemination of research findings to past research participants and the community-at-large.
Dissemination of research findings to past research participants and the community-at-large is a critical element to improving health outcomes, yet it is often overlooked by researchers. Few studies have explored how to provide study findings to the community, and no studies have investigated how community members can be involved in this process. This study explored views on the broad dissemination of research findings to community members and the role of the community in the dissemination process. We conducted a comparative analysis from the perspective of researchers, community members, and program officers (POs) from national health research funding agencies. Semistructured interviews were conducted with community members (African American, N = 10; Latino, N = 10), academic researchers (N = 10), and POs (N = 5). Thematic analysis was utilized in which codes and themes were created. One cross-cutting theme was identified, Views on Disseminating Research Findings to Communities. There were three additional themes identified among community members, five among researchers, and four among POs. All groups perceived the value of dissemination to communities as meaningful and ethical. Groups differed in their perceptions of prioritization of dissemination audiences. This study highlighted consensus on the value of broad dissemination to the community-at-large and identified areas of insufficiency in the translational research continuum that could be expanded or improved to ensure targeted groups receive the intended benefits of positive research findings. The long-term benefit of disseminating findings to the community-at-large is increased acceptability of interventions and reduced mistrust in research and researchers.


[Preclinical left ventricular diastolic dysfunction in insulin-dependent diabetes].
Isolated alterations of the left ventricular diastolic function have been described in diabetic insulin-dependent patients (IDDM), even in the absence of old age, hypertension, ischemic heart disease, left ventricular hypertrophy. Such alterations have been associated with microangiopathy but it is not known whether it is reversible or if there is a relation with the way the therapy is given. Fifty-five subjects have been studied, of which 15 were healthy, 30 recently diagnosed IDDM without microangiopathy and 10 IDDM with microangiopathy. All the patients were under 35 years old and did not present risk factors for coronary artery disease, hypertension or autonomic neuropathy. The maximal exercise stress test proved negative. The diastolic function was studied using the results of Doppler echocardiography of the mitral flow and of isovolumetric relaxation time, with continuous and discrete parameters. The velocity of wave A and E, the relationship between them and their integrals are significantly greater in diabetics with microangiopathy than in those without it and in healthy subjects. There are no significant differences between healthy and diabetic subjects without microangiopathy using continuous parameters. Using discrete parameters diastolic damage is absent in the healthy subjects and is present in 48% of diabetics without microangiopathy and in 90% of those with it. Slight preclinical diastolic dysfunction is present in young recently diagnosed IDDM without microangiopathy. More severe dysfunction is present when there is also microangiopathy.


Polymorphisms in nucleotide excision repair genes and DNA repair capacity phenotype in sisters discordant for breast cancer.
Interindividual differences in DNA repair capacity (DRC) may play a critical role in breast cancer risk. Previously, we determined that DRC measured via removal of in vitro-induced benzo[a]pyrene diolepoxide-DNA adducts in lymphoblastoid cell lines was lower in cases compared with controls among sisters discordant for breast cancer from the Metropolitan New York Registry of Breast Cancer Families. We have now determined genotypes for seven single nucleotide polymorphisms in five nucleotide excision repair genes, including Xeroderma pigmentosum complementation group A (XPA +62T>C), group C (XPC Lys939Gln and Ala499Val), group D (XPD Asp312Asn and Lys751Gln), and group G (XPG His1104Asp) and ERCC1 (8092 C>A) in a total of 160 sister pairs for whom DRC phenotype data were available. Overall, there were no statistically significant differences in average DRC for most of the genotypes. A final multivariate conditional logistic model, including three single nucleotide polymorphisms (XPA +62T>C, XPC Ala499Val, and XPG His1104Asp) and smoking status, only modestly predicted DRC after adjusting for case-control status and age of blood donation. The overall predictive accuracy was 61% in the model with a sensitivity of 78% and specificity of 39%. These findings suggest that those polymorphisms we have investigated to date in nucleotide excision repair pathway genes explain only a small amount of the variability in DRC.


EQ-5D health utilities: exploring ways to improve upon responsiveness in psoriasis.
To determine if EuroQoL 5-Dimension Health Questionnaire (EQ-5D) health utility scores were able to discriminate among different levels of improvement in psoriasis severity following therapy. Data were from three placebo-controlled phase 3 ixekizumab studies (UNCOVER-1, UNCOVER-2, and UNCOVER-3) with patients who had baseline Dermatology Life Quality Index scores >10 (DLQI >10). Psoriasis severity (Psoriasis Area and Severity Index [PASI]), general health utility (EQ-5D), and psoriasis-specific utility (EQ-PSO, UNCOVER-3 only) were assessed. EQ-5D-5L utility scores were generated using the England EQ-5D-5L value set, a crosswalk applied to the EQ-5D-3L United States (US) and United Kingdom (UK) value sets, and a regression-based exploratory scoring function for the EQ-PSO (UK). Analysis of variance was used to estimate change in EQ-5D-5L from baseline to Week 12 per PASI improvement level: PASI <50, PASI 50 to <75, PASI 75 to <90, PASI 90 to <100, and PASI 100. Missing data were imputed using the last observation carried forward method. Value sets for the UK, England, and the US were applied. In total, 2085 patients across UNCOVER-1, UNCOVER-2, and UNCOVER-3 had baseline DLQI >10 and available utility scores. At Week 12, mean EQ-5D utility scores increased with increasing PASI improvement levels (p < 0.001, all analyses). Mean health utilities for PASI 90 to <100 and PASI 100 were similar when based on the generic classifier, whereas a clear differentiation between PASI 90 to <100 and PASI 100 was observed for EQ-PSO mean scores (UNCOVER-3 only, n = 645; PASI 90 to <100: 0.141, PASI 100: 0.200; adjusted p = 0.043). EQ-5D-5L index-based scores have limited ability to differentiate among psoriasis patients at the highest PASI improvement levels. ConclusionsL Adding psoriasis-specific EQ-PSO dimensions to the EQ-5D may enhance responsiveness to improvement in skin clarity at the highest PASI levels, and, therefore, generate utility scores that better reflect treatment benefit in cost-utility models.


Improving immunological tumor microenvironment using electro-hyperthermia followed by dendritic cell immunotherapy.
The treatment of intratumoral dentritic cells (DCs) commonly fails because it cannot evoke immunity in a poor tumor microenvironment (TME). Modulated electro-hyperthermia (mEHT, trade-name: oncothermia) represents a significant technological advancement in the hyperthermia field, allowing the autofocusing of electromagnetic power on a cell membrane to generate massive apoptosis. This approach turns local immunogenic cancer cell death (apoptosis) into a systemic anti-tumor immune response and may be implemented by treatment with intratumoral DCs. The CT26 murine colorectal cancer model was used in this investigation. The inhibition of growth of the tumor and the systemic anti-tumor immune response were measured. The tumor was heated to a core temperature of 42 °C for 30 min. The matured synergetic DCs were intratumorally injected 24 h following mEHT was applied. mEHT induced significant apoptosis and enhanced the release of heat shock protein70 (Hsp70) in CT26 tumors. Treatment with mEHT-DCs significantly inhibited CT26 tumor growth, relative to DCs alone or mEHT alone. The secondary tumor protection effect upon rechallenging was observed in mice that were treated with mEHT-DCs. Immunohistochemical staining of CD45 and F4/80 revealed that mEHT-DC treatment increased the number of leukocytes and macrophages. Most interestingly, mEHT also induced infiltrations of eosinophil, which has recently been reported to be an orchestrator of a specific T cell response. Cytotoxic T cell assay and ELISpot assay revealed a tumor-specific T cell activity. This study demonstrated that mEHT induces tumor cell apoptosis and enhances the release of Hsp70 from heated tumor cells, unlike conventional hyperthermia. mEHT can create a favorable tumor microenvironment for an immunological chain reaction that improves the success rate of intratumoral DC immunotherapy.


Early Energy Intake and Amino Acid Profile in Preterm Newborns: A Quasi-Experimental Study.
(1) Background: An increased protein intake via parenteral nutrition (PN) in early life is associated with an improvement of the nitrogen balance in preterm newborns. However, the role of energy intake on amino acid (AA) utilization provided by PN remains to be defined. We investigated the effects of energy intake on blood AA levels and profiles. (2) Methods: Quasi-experimental study including preterm very low birth weight newborns who received an energy enhanced PN (Cohort A) or an energy standard PN (Cohort B), with a similar protein amount in the first week of life. Blood AA levels were measured between three and seven days of life (T0) and at fifteen days of life (T1) and compared between the two study cohorts. (3) Results: AA levels of 40 newborns from each group were analyzed. No difference was found for total essential and non-essential blood AA concentration at T0 between the two study cohorts. At T1, we found a significantly higher blood concentration of leucine, isoleucine and proline, and a significantly lower concentration of tyrosine in Cohort B. However, multivariate analysis did not confirm this result. (4) Conclusions: An enhanced PN protocol in terms of energy but not of protein did not influence AA levels and profiles. Considering the high risk of side effects, we suggest exercising caution when administering high energy intake via PN in the first week of life.


miR-542-3p-Targeted PDE4D Regulates cAMP/PKA Signaling Pathway and Improves Cardiomyocyte Injury.
To investigate the protective effect of miR-542-3p on cardiomyocyte injury and related mechanisms. A cardiomyocyte hypoxia/reoxygenation model was established. The expression levels of miR-542-3p and PDE4D were detected using qRT-PCR; the luciferase reporter assay system was used to detect the targeting relationship between miR-542-3p and PDE4D; overexpressing miR-542-3p was transfected into cardiomyocytes, and ROS release was detected by immunofluorescence while cellular apoptosis was detected by TUNEL; and the western blot assay was applied to detect the expression of PDE4D, phosphorylated protein kinase A (p-PKA), and phosphorylated cyclic adenosine monophosphate (cAMP) response element-binding protein (p-CREB). Compared with the control group, the miR-542-3p expression level was decreased and the PDE4D expression level was increased in the cardiomyocyte hypoxia/reoxygenation model group. The dual-luciferase reporter assay system confirmed that miR-542-3p could target and regulate PDE4D; the transfection with cardiomyocytes using the overexpressing miR-542-3p could downregulate PDE4D expression, attenuate ROS release during cardiomyocyte injury, and reduce cellular apoptosis rate, while upregulating the expression of p-PKA and p-CREB. The miR-542-3p can negatively regulate PDE4D protein expression and attenuate cardiomyocyte injury through a mechanism related to the activation of the cAMP/PKA signaling pathway.


A double blind controlled trial of a new anorectic agent AN448.
AN448 is a new anorectic agent, which in the dose used, is without the CNS stimulant properties of the amphetamines. Patients entering the trial were a highly resistant group at least 20 percent above ideal weight chosen from an ischaemic-hyperlipidaemic clinic population. In a double blind trial of 12 patients on the active drug and nine patients on placebo, a highly significant weight loss occurred over 12 weeks in the active group only. A significant reduction in serum cholesterol occurred independently of weight loss but there was no reduction in the serum triglycerides and no change in the lipoprotein electrophoretic pattern. The drug is shown to be effective for this group of patients and may also be useful as a cholesterol lowering agent.


Understanding vaginal microbiome complexity from an ecological perspective.
The various microbiota normally associated with the human body have an important influence on human development, physiology, immunity, and nutrition. This is certainly true for the vagina wherein communities of mutualistic bacteria constitute the first line of defense for the host by excluding invasive, nonindigenous organisms that may cause disease. In recent years much has been learned about the bacterial species composition of these communities and how they differ between individuals of different ages and ethnicities. A deeper understanding of their origins and the interrelationships of constituent species is needed to understand how and why they change over time or in response to changes in the host environment. Moreover, there are few unifying theories to explain the ecological dynamics of vaginal ecosystems as they respond to disturbances caused by menses and human activities such as intercourse, douching, and other habits and practices. This fundamental knowledge is needed to diagnose and assess risk to disease. Here we summarize what is known about the species composition, structure, and function of bacterial communities in the human vagina and the applicability of ecological models of community structure and function to understanding the dynamics of this and other ecosystems that comprise the human microbiome.


Histomorphogenesis of cranial nerves in Huso huso larvae.
In this study the cranial nerves development of H. huso are explained from 1 to 54-days-old (1, 3, 6, 15, 21 and 54 days). Despite all the researches on fish brain, there are no study on nerves evolution on H. huso during their larvae life. For this research 40 samples of larvae H. huso were obtained (from each age, about six samples were selected). The specimens were maintained in fiberglass tank, then histological samples were taken from tissues and stained with hematoxylin and eosin for general histological studies using light microscope. According to the results, on 1 and 3-days-old, no nerve was observed. The terminal nerve and their dendrites were observed around the nasal cavity and the axons projected to different areas in forebrain especially around olfactory bulb diffusely, on 6-day-old fish. Also, olfactory, optic, oculomotor, trochlear, trigeminal, lateral line and vagus nerves were detected on 6-day-old fish, however two parts of lateral line nerve were separated on 54-day-old. Three nerves, profundus, facial and octaval were observed on 54-day-old, however, up to this age, epiphysial nerve was not observed.


Complexation in situ of 1-methylpiperidine, 1,2-dimethylpyrrolidin, and 1,2-dimethylpiperidine with rhodium(II) tetracarboxylates: Nuclear magnetic resonance spectroscopy, chiral recognition, and density functional theory studies.
Complexation in situ of 1-methylpiperidine, racemic 1,2-dimethylpyrrolidin, and racemic 1,2-dimethylpiperidine with rhodium(II) tetracarboxylates in chloroform was studied by 1 H and 13 C nuclear magnetic resonance (NMR) spectroscopy and density functional theory (DFT) methods. As substrates, three dirhodium(II) compounds were applied, tetraacetate, tetrakistrifluoroacetate, and a derivative of optically pure Mosher's acid. Due to conformational flexibility, free and complexed ligands can adopt potentially various conformations. The NMR titration experiments revealed the subsequent formation of 1:1 and 1:2 complexes, depending on the molar ratio of substrate to ligand. Conformations of free and complexed ligands were examined by the comparison of experimental and DFT gauge-independent atomic orbital (GIAO) calculated chemical shifts and by the analysis of the internal energy of the compounds. For some ligand and substrate combinations, a mixture of complexes differing in ligand conformations was formed. Complexes of Mosher's acid derivative of rhodium(II) with racemic 1,2-dimethylpyrrolidin and 1,2-dimethylpiperidine exhibited NMR chiral recognition phenomenon, manifested by splitting of signals in 13 C NMR and 1 H,13 C HSQC spectra.


Tumor burden influences exposure and response to rituximab: pharmacokinetic-pharmacodynamic modeling using a syngeneic bioluminescent murine model expressing human CD20.
Clinical studies have shown a large interindividual variability in rituximab exposure and its significant influence on clinical response in patients receiving similar doses of antibody. The aim of this study was to evaluate the influence of tumor burden on dose-concentration-response relationships of rituximab. Murine lymphoma cells (EL4, 8 x 10(3)), transduced with human CD20 cDNA and transfected with luciferase plasmid (EL4-huCD20-Luc), were intravenously injected into C57BL/6J mice. Tumor burden detection, dissemination, and progression were evaluated quantitatively by in vivo bioluminescence imaging. Different doses of rituximab (6, 12, 20, or 40 mg/kg) were infused 13 days after lymphoma cell inoculation, and rituximab serum concentrations were measured by enzyme-linked immunosorbent assay. Without rituximab, all mice developed disseminated lymphoma and died within 30 days, whereas a significant dose-response relationship was observed in mice receiving rituximab. The 20-mg/kg dose was adequate to study interindividual variability in response because 23% of mice were cured, 59% had partial response, and 18% had disease progression. Rituximab concentrations were inversely correlated with tumor burden; mice with low tumor burden had high rituximab concentrations. Furthermore, rituximab exposure influenced response and survival. Finally, using a pharmacokinetic-pharmacodynamic model, we demonstrated that tumor burden significantly influenced rituximab efficacy.


Technique of parathyroidectomy.
The goal of the surgical treatment of primary hyperparathyroidism is ablation of the proper amount of hyperfunctioning tissue. This paper presents our operative technique based on an experience in the treatment of 190 patients with primary hyperparathyroidism. The technique is based on a complete knowledge of the anatomy of the normal parathyroid gland as well as the pathology in primary hyperparthyroidism. We also propose a systematic and methodical search for possible abnormal locations incorporating a thorough knowledge of the specific embryology.


High-Quality GaSe Single Crystal Grown by the Bridgman Method.
A high-quality GaSe single crystal was grown by the Bridgman method. The X-ray rocking curve for the studied GaSe sample is symmetric and the Full Width at Half Maximum (FWHM) is only 46 arcs, which is the smallest value ever reported for GaSe crystals. The IR-transmittance is about 66% in the range from 500 to 4000 cm-1. The photoluminescence spectrum at 9.2 K shows a symmetric and sharp excition peak in 2.1046 eV. The results indicate that the as-grown GaSe crystal is of high crystalline quality. The as-grown ε -GaSe crystal has a p-type conductance with the resistivity of 10³ Ω/cm, and the Hall mobility is ~25 cm² V-1 s-1. Few-layer GaSe crystals were prepared through mechanical exfoliation from this high-quality crystal sample. Few-layer GaSe-based photodetectors were fabricated, which exhibit an on/off ratio of 10⁴, a field-effect differential mobility of 0.4 cm² V-1 s-1, and have a fast response time less than 60 ms under light illumination.


The novel Tau mutation G335S: clinical, neuropathological and molecular characterization.
Mutations in Tau cause the inherited neurodegenerative disease, frontotemporal dementia and Parkinsonism linked to chromosome 17 (FTDP-17). Known coding region mutations cluster in the microtubule-binding region, where they alter the ability of tau to promote microtubule assembly. Depending on the tau isoforms, this region consists of three or four imperfect repeats of 31 or 32 amino acids, each of which contains a characteristic and invariant PGGG motif. Here, we report the novel G335S mutation, which changes the PGGG motif of the third tau repeat to PGGS, in an individual who developed social withdrawal, emotional bluntness and stereotypic behavior at age 22, followed by disinhibition, hyperorality and ideomotor apraxia. Abundant tau-positive inclusions were present in neurons and glia in the frontotemporal cortex, hippocampus and brainstem. Sarkosyl-insoluble tau showed paired helical and straight filaments, as well as more irregular rope-like filaments. The pattern of pathological tau bands was like that of Alzheimer disease. Experimentally, the G335S mutation resulted in a greatly reduced ability of tau to promote microtubule assembly, while having no significant effect on heparin-induced assembly of recombinant tau into filaments.


Altered Uncinate Fasciculus Microstructure in Childhood Anxiety Disorders in Boys But Not Girls.
Anxiety disorders are common, can result in lifelong suffering, and frequently begin before adolescence. Evidence from adults suggests that altered prefrontal-limbic connectivity is a pathophysiological feature of anxiety disorders. More specifically, in adults with anxiety disorders, decreased fractional anisotropy (FA), a measure of white matter integrity, has been observed in the uncinate fasciculus, the major tract that connects limbic and prefrontal regions. Because of the early onset of anxiety disorders and the increased incidence in anxiety disorders in females during their reproductive years, it is important to understand whether the reduction in uncinate fasciculus FA exists in children with anxiety disorders and the extent to which this alteration is sex related. To address these issues, the authors assessed FA in the uncinate fasciculus in unmedicated boys and girls with anxiety disorders. FA measures were derived from diffusion tensor images that were acquired from 98 unmedicated children (ages 8-12); 52 met criteria for generalized anxiety disorder, separation anxiety disorder, social anxiety disorder, or anxiety disorder not otherwise specified, and 46 were matched control subjects. Tract-based results demonstrated that children with anxiety disorders have significant reductions in uncinate fasciculus FA. A significant sex-by-group interaction and post hoc testing revealed that this effect was evident only in boys. No other main effects or sex-by-group interactions were found for other white matter tracts. These findings provide evidence of uncinate fasciculus white matter alterations in boys with anxiety disorders. The data demonstrate that anxiety disorder-related alterations in prefrontal-limbic structural connectivity are present early in life, are not related to psychotropic medication exposure, and are sex specific. Building on these findings, future research has the potential to provide insights into the genesis and sexual dimorphism of the pathophysiology that leads to anxiety disorders, as well as to identify sex-specific early-life treatment targets.


Outsourcing in Iranian hospitals: Findings from a qualitative study.
Outsourcing is used as a strategy to improve efficiency, quality, and satisfaction of beneficiaries in hospitals. This study aimed to determine the reasons for outsourcing, outsourced services, achieved objectives, and outsourcing challenges. This qualitative study was conducted through 58 face-to-face semi-structured interviews with chief executive officers (CEOs), chief financial officers (CFOs), and contracting experts (CEs) in 42 public hospitals in Tehran, Iran. Purposive and snowball sampling techniques were used. Interviews were recorded digitally and transcribed verbatim. Data analysis was performed based on an inductive-deductive approach via MAXQDA-10. The Participants included 26 CEOs, 15 CFOs, and 17 CEs. The most important reasons for outsourcing were divided into four main categories including financial resources and funding, customers, management, and factors related to the hospitals. Accessing to up-to-date knowledge and technology, improving service quality and accountability, focusing on strategic points, reducing workload, and increasing patient satisfaction turned out to be the positive outcomes of outsourcing. Weakness in laws and regulations, monitoring and assessment of an outsourced unit, creating dependency and changing organizational culture, as well as human resource issues were introduced as the main pitfalls and challenges of outsourcing. Based on the results, it was suggested that the hospital managers must attempt to outsource services by realistic analysis of the organization's current status. They should specify the reasons and objectives of outsourcing and make decisions based on outsourcing potentials. By taking the current challenges of outsourcing in Iranian hospitals into account, the authorities can make the most efficient decisions with regard to outsourcing.


Skeletal Muscle Mitochondrial Dysfunction Is Present in Patients with CKD before Initiation of Maintenance Hemodialysis.
Patients with CKD suffer from frailty and sarcopenia, which is associated with higher morbidity and mortality. Skeletal muscle mitochondria are important for physical function and could be a target to prevent frailty and sarcopenia. In this study, we tested the hypothesis that mitochondrial dysfunction is associated with the severity of CKD. We also evaluated the interaction between mitochondrial function and coexisting comorbidities, such as impaired physical performance, intermuscular adipose tissue infiltration, inflammation, and oxidative stress. Sixty-three participants were studied, including controls (n=21), patients with CKD not on maintenance hemodialysis (CKD 3-5; n=20), and patients on maintenance hemodialysis (n=22). We evaluated in vivo knee extensors mitochondrial function using 31P magnetic resonance spectroscopy to obtain the phosphocreatine recovery time constant, a measure of mitochondrial function. We measured physical performance using the 6-minute walk test, intermuscular adipose tissue infiltration with magnetic resonance imaging, and markers of inflammation and oxidative stress in plasma. In skeletal muscle biopsies from a select number of patients on maintenance hemodialysis, we also measured markers of mitochondrial dynamics (fusion and fission). We found a prolonged phosphocreatine recovery constant in patients on maintenance hemodialysis (53.3 [43.4-70.1] seconds, median [interquartile range]) and patients with CKD not on maintenance hemodialysis (41.5 [35.4-49.1] seconds) compared with controls (38.9 [32.5-46.0] seconds; P=0.001 among groups). Mitochondrial dysfunction was associated with poor physical performance (r=0.62; P=0.001), greater intermuscular adipose tissue (r=0.44; P=0.001), and increased markers of inflammation and oxidative stress (r=0.60; P=0.001). We found mitochondrial fragmentation and increased content of dynamin-related protein 1, a marker of mitochondrial fission, in skeletal muscles from patients on maintenance hemodialysis (0.86 [0.48-1.35] arbitrary units (A.U.), median [interquartile range]) compared with controls (0.60 [0.24-0.75] A.U.). Mitochondrial dysfunction is due to multifactorial etiologies and presents prior to the initiation of maintenance hemodialysis, including in patients with CKD stages 3-5.


Pyoderma gangrenosum after cardiac surgery.
Pyoderma gangrenosum (PG) can mimic early postoperative sternal wound infections. Steroid therapy is the only method of treatment for this condition, which recognizes the fact that steroids can lead to immunosuppression and potentially inhibit healing after major surgery.