Waiting for change: symptom resolution after adrenalectomy for Cushing's syndrome.
The debilitating symptoms and physical changes from Cushing's syndrome may resolve after treatment, but the time course to resolution is not well established. Between February 1995 and May 2007, 60 patients underwent adrenalectomy for Cushing's syndrome. Pre-operative and operative variables were collected from a prospective database. Long-term follow-up was obtained via patient survey. Unilateral adrenalectomy was performed in 53% and a bilateral adrenalectomy in 47% of patients. Median time to diagnosis was 24 months (range, 1-384). Three percent had intra-operative complications, and 28% developed post-operative complications. Steroids were required post-operatively for a median of 30 months after unilateral adrenalectomy (range, 0-96). At a median follow-up of 3.7 years (range, 0-13.3), 85% of patients are still alive. The majority of the physical changes resolved after adrenalectomy. The time to symptom resolution varied from a few weeks to up to 4 years. Most of the physical changes resolved by a mean of 7-9 months after surgery. Quality of life improved in 78% of patients, with 68% improving dramatically (P < .001). Adrenalectomy can provide excellent palliation of the symptoms of cortisol excess and can dramatically improve patient quality of life, but both patients and physicians must know that these changes may take years.


Repression of zygotic gene expression in the putative germline cells in ascidian embryos.
In germline cells of early C. elegans and Drosophila embryos, repression of zygotic gene expression appears to be essential to maintain the germ cell fate. In these animals, specific residues in the carboxy-terminal domain (CTD) of RNA polymerase II large subunit (RNAP II LS) are dephosphorylated in the germline cells, whereas they are phosphorylated in the somatic cells. We investigated, in early embryos of the ascidian Halocynthia roretzi, the expression patterns of three genes that are essentially expressed in the entire embryo after the 32-cell stage. We found that the expression of these genes was inactive in the putative germline cells during the cleavage stages. Once cells were separated from the germline lineage by cleavages, the expression of the genes was initiated in the cells. These results suggest that repression of transcription in germline cells may also be common in chordate embryos. We then examined the phosphorylation state of the CTD of RNAP II using a phosphoepitope-specific antibody. At cleavage stages after the 32-cell stage, CTD was phosphorylated in every blastomere, including the germline cells. Therefore, in the ascidian, the inactivation of zygotic transcription is not correlated with dephosphorylation of the CTD. These observations indicate that zygotic transcription is inactivated in ascidian germline cells, but the mechanism of the repression may differ from that in C. elegans and Drosophila.


Endurance training in the rat. I. Myocardial mechanics and biochemistry.
The effects of physical training and detraining on cardiac structure and myocardial mechanics were studied in young and adult male rats trained by graded treadmill running for 12 wk and compared with sedentary controls. Detraining was produced by training for 12 wk followed by 6 sedentary wk. A training effect was demonstrated by increased succinate dehydrogenase activity in skeletal muscle (trained 10.0 +/- 1.2 mumol . g-1 . min-1; sedentary 6.4 +/- 0.8 mumol . g-1 . min-1; P less than 0.05). Although heart weight-to-body weight ratios were increased in trained rats of both ages, left ventricular fiber diameters and myocardial RNA, DNA, and collagen content were unchanged by training. Active and passive mechanics (myocardial contractility and stiffness) were studied in left ventricular papillary muscles and did not differ significantly between groups, with the exception of depressed contractility observed in young trained rats [(e.g., papillary peak developed isometric tension at Lmax (length at peak tension)] was 2.64 +/- 0.24 g/mm2 in trained vs. 3.59 +/- 0.22 g/mm2 in sedentary (P less than 0.01). This difference was abolished by detraining. Papillary muscle contractile responses to calcium, norepinephrine, and hypoxia were not altered by training or detraining. In conclusion, moderate endurance training did not result in significant cardiac hypertrophy, altered myocardial stiffness, or consistent changes in myocardial contractility.


Backbone assignments for the SPOUT methyltransferase MTT Tm , a knotted protein from Thermotoga maritima.
The SPOUT family of methyltransferase proteins is noted for containing a deep trefoil knot in their defining backbone fold. This unique fold is of high interest for furthering the understanding of knots in proteins. Here, we report the 1H, 13C, 15N assignments for MTT Tm , a canonical member of the SPOUT family. This protein is unique, as it is one of the smallest members of the family, making it an ideal system for probing the unique properties of the knot. Our present work represents the foundation for further studies into the topology of MTT Tm , and understanding how its structure affects both its folding and function.


[The biological prostheses of Hancock in our experience of 250 subjects underwent a valvular replacement (author's transl)].
In this study we present the results of 5-years Follow-up of Clinical experimentation with biological prostheses of Hancock in 250 patients underwent a valvular replacement at the Cardiovascular Surgery Institute of Padua University in Verona. We report the immediate and long-term results with the death causes and the complications related above all with thrombo-embolic events. For such complications it was done a comparison relatively to the cases with mitral and aortic prostheses, with the results obtained from another Cardiovascular Surgery Center where are always applied artificial prostheses. From this comparison results that Hancock's biological prostheses has a major tendency to give incidence of embolic in the first months following the valvular replacement, but successively it is clearly to be prefered to artificial prostheses.


Genome-wide retinal transcriptome analysis of endotoxin-induced uveitis in mice with next-generation sequencing.
Endotoxin-induced uveitis (EIU) is a well-established mouse model for studying human acute inflammatory uveitis. The purpose of this study is to investigate the genome-wide retinal transcriptome profile of EIU. The anterior segment of the mice was examined with a slit-lamp, and clinical scores were evaluated simultaneously. The histological changes in the posterior segment of the eyes were evaluated with hematoxylin and eosin (H&E) staining. A high throughput RNA sequencing (RNA-seq) strategy using the Illumina Hiseq 2500 platform was applied to characterize the retinal transcriptome profile from lipopolysaccharide (LPS)-treated and untreated mice. The validation of the differentially expressed genes (DEGs) was analyzed with real-time PCR. At the 24th hour after challenge, the clinical score of the LPS group was significantly higher (3.83±0.75, mean ± standard deviation [SD]) than that of the control group (0.08±0.20, mean ± SD; p<0.001). The histological evaluation showed a large number of inflammatory cells infiltrated into the vitreous cavity in the LPS group compared with the control group. A total of 478 DEGs were identified with RNA-seq. Among these genes, 406 were upregulated and 72 were downregulated in the LPS group. Gene Ontology (GO) enrichment showed three significantly enriched upregulated terms. Twenty-one upregulated and seven downregulated pathways were remarkably enriched by Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment. Eleven inflammatory response-, complement system-, fibrinolytic system-, and cell stress-related genes were validated to show similar results as the RNA-seq. We first reported the retinal transcriptome profile of the EIU mouse with RNA-seq. The results indicate that the abnormal changes in the inflammatory response-, complement system-, fibrinolytic system-, and cell stress-related genes occurred concurrently in EIU. These genes may play an important role in the pathogenesis of EIU. This study will lead to a better understanding of the underlying mechanisms and shed light on discovering novel therapeutic targets for ocular inflammation.


On the interconversion pathway of HBO<-->BOH.
The potential energy surfaces have been constructed for the 1A', 3A', and 3A" states of HBO by using the multireference perturbation theory with the basis set cc-pVTZ (6d,10f). Two stationary points and a transition state have been characterized on all the three surfaces, which are in good agreement with available experiments and previous calculations. The interconversion pathways from metastable boron hydroxide BOH to the considerably more stable HBO are expounded based on the nature of the surfaces.


Gut microbiome ADP-ribosyltransferases are widespread phage-encoded fitness factors.
Bacterial ADP-ribosyltransferases (ADPRTs) have been described as toxins involved in pathogenesis through the modification of host proteins. Here, we report that ADPRTs are not pathogen restricted but widely prevalent in the human gut microbiome and often associated with phage elements. We validated their biochemical activity in a large clinical isolate collection and further examined Bxa, a highly abundant ADPRT in Bacteroides. Bxa is expressed, secreted, and enzymatically active in Bacteroides and can ADP-ribosylate non-muscle myosin II proteins. Addition of Bxa to epithelial cells remodeled the actin cytoskeleton and induced secretion of inosine. Bxa-encoding B. stercoris can use inosine as a carbon source and colonizes the gut to significantly greater numbers than a bxa-deleted strain in germ-free and altered Schaedler flora (ASF) mice. Colonization correlated with increased inosine concentrations in the feces and tissues. Altogether, our results show that ADPRTs are abundant in the microbiome and act as bacterial fitness factors.


Rotation of non-spherical micro-particles by amplitude modulation of superimposed orthogonal ultrasonic modes.
Contactless rotation of non-spherical particles has been modeled and experimentally achieved using ultrasonic manipulation. For this purpose an acoustic radiation torque was generated by a time-varying pressure field resulting in a change of orientation of the potential well. The rotation method is based on amplitude modulation of two orthogonal ultrasonic modes. The force potential field has been used to evaluate the different modes and actuations to achieve rotation. Experiments have been performed in micro devices with copolymer particles and glass fibers at frequencies in the megahertz range. A continuous rotation was successfully demonstrated and the method allowed to stop the rotation at arbitrary angular positions.


Synthesis of dual fluorescent encoding magnetic composite nanoparticles.
A new class of high stable, dual fluorescent encoding magnetic composite nanoparticle has been synthesized via reverse microemulsion method. Two kinds of CdTe QDs with different emission wavelengths and magnetic nanoparticles (Fe3O4) were embedded in silica nanoparticles at precisely controlled ratios. In this process, superparamagnetic Fe3O4 nanoparticles and one kind of QDs (573 nm) as cores were coated with silica, forming the first core-shell structure magnetic fluorescent nanoparticles (MFNs); then the MFNs and the other kind of QDs (653 nm) as cores were coated with another silica shell to form the fluorescent, magnetic dual core-shell encoding composite nanoparticles. With the aim of embedding more QDs in MFNs, we use poly(dimethyldiallyl ammonium chloride) to balance the electrostatic repulsion between QDs and silica intermediates. A surface-active reagent, 3-aminopropyltrimethoxysliane was used to link the MFNs with QDs and terminate the surface of composite nanoparticles. Finally, by modifying the surface of composite nanoparticles with amino groups and methylphosphonate groups, biologically functionalized and monodispersed composite nanoparticles were obtained.


Reaction Chemistry at Discrete Organometallic Fragments on Black Phosphorus.
Black phosphorus (bP) is a two-dimensional van der Waals material unique in its potential to serve as a support for single-site catalysts due to its similarity to molecular phosphines, ligands quintessential in homogeneous catalysis. However, there is a scarcity of synthetic methods to install single metal centers on the bP lattice. Here, we demonstrate the functionalization of bP nanosheets with molecular Re and Mo complexes. A suite of characterization techniques, including infrared, X-ray photoelectron and X-ray absorption spectroscopy as well as scanning transmission electron microscopy corroborate that the functionalized nanosheets contain a high density of discrete metal centers directly bound to the bP surface. Moreover, the supported metal centers are chemically accessible and can undergo ligand exchange transformations without detaching from the surface. The steric and electronic properties of bP as a ligand are estimated with respect to molecular phosphines. Sterically, bP resembles tri(tolyl)phosphine when monodentate to a metal center, and bis(diphenylphosphino)propane when bidentate, whereas electronically bP is a σ-donor as strong as a trialkyl phosphine. This work is foundational in elucidating the nature of black phosphorus as a ligand and underscores the viability of using bP as a basis for single-site catalysts.


Prevention of bleomycin-induced pulmonary fibrosis in the hamster by cis-4-hydroxy-l-proline.
We investigated the effect of the proline analogue cis-hydroxyproline on pulmonary fibrosis produced by intratracheal administration of bleomycin in hamsters. Two groups of animals received a single dose of bleomycin; one of these groups was also injected with cis-hydroxyproline twice daily for 30 days. Control animals received intratracheal saline. Lungs were examined on day 30. In the bleomycin group, the collagen content of lungs was 131% of the control value (p less than 0.05). Administration of cis-hydroxyproline decreased collagen accumulation to 114% of the control value (p less than 0.05). Pressure-volume curves were significantly shifted downward and to the right of control in the bleomycin group; this shift was partially prevented by cis-hydroxyproline. Morphometric studies showed that alveolar walls comprised 15% of the lung parenchyma in the control group and 19% in the bleomycin group (p less than 0.05). Administration of cis-hydroxyproline significantly decreased alveolar walls to 16% of the lung parenchyma (p less than 0.05). We conclude that cis-hydroxyproline partially prevents the chemical, structural, and functional changes of bleomycin-induced pulmonary fibrosis in the hamster.


Validation of Balance Map Analysis of Walking at Different Speeds.
Walking balance about falling in the forward direction is associated with the body's center of mass and placement of the swing foot during the swing phase. Balance map analysis evaluates walking balance based on the prediction of the reachability of an appropriate foot placement using a simple biomechanical model during the swing phase without active joint torque (ballistic walking model). The ballistic walking model can be justified in terms of the preferred walking speed because the metabolic energy consumption associated with muscle activity in faster and slower walking is higher than that in preferred speed walking. Therefore, the assumption that the active joint torque is sufficiently small during the swing phase may not hold in faster or slower walking, which can be a significant limitation of balance map analysis. In this study, it was hypothesized that steady-state walking at various walking speeds would be evaluated as stable for validation of the balance map analysis, and the gait patterns for three types of walking speeds (slow, normal, and fast) were examined. The results showed that the trajectories during the swing phase were within stable regions for all conditions, with a sufficient margin from the forward balance loss region. In addition, the margin from forward balance was reduced with an increase in walking velocity. The decrease in the margin during fast walking resulted from an increase in the forward velocity of the body's center of mass in relation to the velocity of the swing leg. These results suggest that balance map analysis effectively measures walking balance at various speeds.


Can we assess the changes of ventricular filling resulting from acute allograft rejection with Doppler echocardiography?
We investigated the value of several Doppler echocardiographic measurements for the diagnosis of acute allograft rejection after orthotopic heart transplantation. In all, 144 transmitral flow velocity curves and 159 internal jugular venous flow velocity curves were recorded by continuous wave Doppler echocardiography, and the results were compared with the histologic findings. The recordings were evaluated with a computer-aided analysis system. The Doppler measurements did not show any significant correlation with the biopsy results. Only one recording obtained during a moderate acute rejection episode supported the hypothesis about the relation between jugular venous flow and cardiac rejection. We conclude that these Doppler echocardiographic measurements are not suitable to detect acute allograft rejection noninvasively.


Embedding entropy: a nonlinear measure of dynamical causality.
Research on concepts and computational methods of causality has a long history, and there are various concepts of causality as well as corresponding computing algorithms based on measured data. Here, by considering causes and effects from a dynamical perspective, we present a unified mathematical framework for the so-called dynamical causality (DC), which can detect causal interactions over time; notably, this framework covers Granger causality, transfer entropy, embedding causality and their conditional versions. Based on this framework, we further propose a causality criterion called embedding entropy (EE) to measure the DC between two variables. Moreover, its conditional version, conditional embedding entropy (cEE), is also derived for detecting conditional/direct causality. The significant advantages of EE and cEE are that they can be employed for solving not only nonlinear causal inference but also the non-separability problem, and they can reduce the scale bias in numerical calculation. The performance and robustness of EE and cEE were demonstrated through numerical simulations, and causal inference on various real-world datasets validated their effectiveness.


Brain metabolic correlates of decision making in amnestic mild cognitive impairment.
Persons with amnestic mild cognitive impairment (MCI) have subtle impairments in medical decision-making capacity (MDC). We examined the relationship between proton magnetic resonance spectroscopy (MRS) and MDC in MCI. Twenty-nine MCI patients and 42 controls underwent MRS to obtain ratios of N-acetylaspartate (NAA)/Creatine (Cr), Choline (Cho)/Cr, and myo-Inositol (mI)/Cr of the posterior cingulate. They also completed the Capacity to Consent to Treatment Instrument (CCTI), a vignette-based instrument measuring decisional standards of expressing choice, appreciating consequences of choice, providing rational reasons for choice, and understanding treatment choices. Patients showed abnormal MRS ratios of mI/Cr and Cho/Cr compared to controls, and impairments on the CCTI understanding and reasoning Standards. Performance on the reasoning standard of the CCTI was correlated with NAA/Cr (r = .46, p < .05). The relationship of NAA/Cr with decision-making suggests a role for posterior cortical neuronal functioning in performance of complex IADLs in MCI.


The impact of acute changes of inflammation on appetite and food intake among older hospitalised patients.
The present study aimed to investigate the effect of acute changes in serum C-reactive protein (CRP) on appetite and food intake among older hospitalised patients. A total of 200 patients (age range 65-94 years, 62·5 % women) participated in this prospective longitudinal observational study. Risk of malnutrition was measured according to the Mini Nutritional Assessment Short Form. The Simplified Nutritional Appetite Questionnaire (SNAQ) and Edmonton Symptom Assessment System (ESAS) were used to evaluate patients' appetite at the time of hospital admission (baseline) and after 7 d (follow-up). Food intake was measured according to the plate diagram and serum CRP was analysed at baseline and follow-up. At baseline, 30·5 % of the patients had moderate to severe inflammation, 31·0 % were malnourished and 48·0 % had food intake <75 % of the meals offered. Also, 32·5 and 23·5 % reported poor and very poor appetite or severe loss of appetite according to the SNAQ and ESAS, respectively. Of the patients, 40 % displayed a pronounced reduction in median CRP levels by -1·2 mg/dl and 19 % demonstrated an increase in median CRP levels by +1·2 mg/dl. Appetite significantly improved (P = 0·006) in patients with a decrease in CRP level and deteriorated in those with an increase in CRP level (P = 0·032). Changes in CRP levels did not show any significant impact on food intake. In a regression analysis, changes of inflammation were the major independent predictor for changes of patients' appetite. We conclude that inflammation has a significant impact on appetite and should therefore be considered in the diagnosis and treatment of malnutrition.


How GroES regulates binding of nonnative protein to GroEL.
At present, it is still enigmatic how the reaction cycle by which the Escherichia coli GroE chaperones mediate protein folding in the cell is coordinated with respect to the sequential order of binding and release of GroES, nucleotide, and nonnative protein. It is generally assumed that the asymmetric GroEL.GroES complex is the acceptor state for substrate protein. Nevertheless, this species is poorly understood in its binding characteristics for nucleotide and nonnative protein. We show here that this species has a high affinity binding site for nonnative protein. In addition to this, binding of nucleotide to one GroEL ring is strongly favored by GroES binding to the other ring. However, the slow rate of release of substrate protein from the unproductive trans-position kinetically favors the binding of a second GroES, thereby forming a symmetric GroEL14.(GroES7)2 complex and simultaneously ensuring that substrate protein is sequestered in a position underneath GroES. Our results demonstrate that the intrinsic binding characteristics of the trans-bullet complex determine the sequence of events during the reaction cycle.


A Case of Pirfenidone-Induced Photosensitive Drug Eruption.
A 75-year-old male was diagnosed with idiopathic pulmonary fibrosis and treated with pirfenidone. He presented with an erythematous thick scaly patch on his face, neck, and both hands and arms. He had a history of significant exposure to sunlight without using sunscreen. All lesions were restricted to sun-exposed areas and appeared one month ago. Histopathological examination revealed necrotic keratinocytes, epidermal spongiosis, liquefaction degeneration of the basal layer, interface dermatitis, solar elastosis, and upper dermal perivascular lympho-histiocytic infiltration. Based on clinical and histopathological findings, the skin lesion could be diagnosed as photosensitive drug eruption induced by pirfenidone. Pirfenidone was discontinued for a month, and the patient was treated with oral and topical corticosteroids. Consequently, the skin lesion almost fully cleared, leaving mild postinflammatory hyperpigmentation. Although there are many reports of photosensitivity reactions to pirfenidone, dermatologists are still not familiar with this drug. Through this case presentation, clinicians should be aware of the potential phototoxic effects of pirfenidone and provide the necessary precautionary information to patients who take pirfenidone.


The electrical axis of the heart in nigerian patients with chronic obstructive lung disease in Benin City.
Of the electrocardiographic changes in chronic obstructive lung disease (COLD) patients, a shift of the P wave axis greater than 900 which is highly characteristic, is said to be due to hyperinflation and does not occur in interstitial lung disease. To describe the electrocardiographic changes in chronic obstructive lung disease patients. The electrical axis of the various waves of the ECG using the hexiaxial reference system in 92 Nigerian patients with COLD were examined, 39 of whom had associated cor pulmonale. P wave axis greater than 900 was present in 2(19.1%) of 17 patients with COLD alone and 15(41.7%) out of 36 with development of corpulmonale (p<0.001). The mean P wave axis was 64.7 ± 10.6 0 in those without cor pulmonale while it was significantly shifted to the right (83.90) in those with cor pulmonale. The mean QRS axis was 53.50 ± 21.20 and 89.0 ±12.40 in those without and with cor pulmonale respectively (p=0.7716). The QRS axis was normal in all but one of those without cor pulmonale while there was a right axis deviation in 51.7% of those with it. ST and T wave changes were mainly present in those with associated cor pulmonale. The study shows that a shift of the electrical axis of the heart occurs in COLD patients mainly with the development of right ventricular hypertrophy (cor pulmonale), rather than the hyperinflation.


Survival outcomes and prognostic factors of surgical therapy for all potentially resectable intrahepatic cholangiocarcinoma: a large single-center cohort study.
Surgical resection is currently indicated for all potentially resectable intrahepatic cholangiocarcinoma (ICC), but the survival outcomes and the prognostic factors have not been well-documented due to its rarity. This study aims to assess these in a large, consecutive series of patients with ICC treated surgically. A retrospective study was conducted on 1,333 ICC patients undergoing surgery between January 2007 and December 2011. Surgical results and survival were evaluated and compared among different subgroups of patients. Univariate and multivariate analyses were performed to identify prognostic factors. R0, R1, R2 resection and exploratory laparotomy were obtained in 34.8, 44.9, 16.4, and 3.9% of the patients, respectively. The overall 1-, 3-, and 5-year survival rates for the entire cohort were 58.2, 25.2, and 17.0%, respectively, with corresponding rates of 79.1, 42.6, and 28.7% for patients with R0 resection; 60.5, 20.1, and 13.9% for patients with R1 resection; 20.5, 7.4, and 0% for patients with R2 resection; and 3.8, 0, and 0% for patients with an exploratory laparotomy. Independent factors for poor survival included positive resection margin, lymph node metastasis, multiple tumors, vascular invasion, and elevated CA19-9 and/or CEA, whereas hepatitis B virus infection and cirrhosis were independently favorable prognosis indicators. R0 resection offers the best possibility of long-term survival, but the chance of a R0 resection is low when surgery is performed for potential resectable ICC. Further randomized trials are warranted to refine indications for surgery in the management of ICC.


Tunable time-resolved tick-tock pulsed digital holographic microscopy for ultrafast events.
This study presents a time-resolved imaging technique for detecting ultrafast events in the sample with tunable tick-tock pulses in common-path digital holographic microscopy. The tick-tock pulses are generated from the same single femtosecond pulse source and manipulated through a spatial-multiplexing encoding/decoding scheme with two complementary binary codes for digital hologram recording and reconstruction. The spatial-multiplexing encoding/decoding scheme with compressive sensing on the Fresnel digital hologram is used to recover missing data and achieve high-fidelity wavefront reconstruction. The elapsed time of tick-tock pulses can be adjusted by changing the optical path difference between the pulse pair arms for dynamic observation at various timescales. The proposed method is applied to explore the ultrafast physical phenomenon by quantitative phase imaging with a stopwatch-like tunable timescale ranging from nanoseconds to femtoseconds.


A sparse neural code for some speech sounds but not for others.
The precise neural mechanisms underlying speech sound representations are still a matter of debate. Proponents of 'sparse representations' assume that on the level of speech sounds, only contrastive or otherwise not predictable information is stored in long-term memory. Here, in a passive oddball paradigm, we challenge the neural foundations of such a 'sparse' representation; we use words that differ only in their penultimate consonant ("coronal" [t] vs. "dorsal" [k] place of articulation) and for example distinguish between the German nouns Latz ([lats]; bib) and Lachs ([laks]; salmon). Changes from standard [t] to deviant [k] and vice versa elicited a discernible Mismatch Negativity (MMN) response. Crucially, however, the MMN for the deviant [lats] was stronger than the MMN for the deviant [laks]. Source localization showed this difference to be due to enhanced brain activity in right superior temporal cortex. These findings reflect a difference in phonological 'sparsity': Coronal [t] segments, but not dorsal [k] segments, are based on more sparse representations and elicit less specific neural predictions; sensory deviations from this prediction are more readily 'tolerated' and accordingly trigger weaker MMNs. The results foster the neurocomputational reality of 'representationally sparse' models of speech perception that are compatible with more general predictive mechanisms in auditory perception.


Limb lengthening promotes muscle growth.
Studies of limb lengthening have demonstrated successful bone formation in the distraction gap. Failure of the muscle units to lengthen leads to many complications that significantly limit the success of this approach; it is, therefore, of paramount importance to characterize the behavior of the muscle during limb lengthening. In this study, tibiae of adult rabbits were lengthened for 10 days at a rate of 1 mm/day. The proliferative ability of the lengthened muscle was characterized using bromodeoxyuridine, a thymidine analogue that is incorporated during cell division, and desmin, a muscle-specific marker. We observed a large number of proliferating cells, specifically in the lengthened muscle, that were co-localized with many desmin-positive cells. The presence of bromodeoxyuridine nuclei inside desmin-positive muscle fibers suggests that limb lengthening promotes muscle growth by triggering myoblast proliferation and fusion into the lengthened muscle. Our findings are consistent with those of other studies in the reviewed literature that also suggest that limb lengthening promotes muscle growth.


The fermentation, isolation and characterization of a macromolecular peptide antibiotic: AN-1.
A new macromolecular peptide antibiotic, named AN-1, was isolated from the culture broth of Streptomyces albus AJ9003. From 18 liters of culture broth (110 units/ml activity) a 300 mg sample of AN-1 was obtained with a specific activity of 1,160 units/mg was obtained. AN-1 is a basic polypeptide with a molecular weight of 12,000, isoelectric point of pH 8.3, and gives a single band on SDS polyacrylamide gel electrophoresis. It is soluble in water but insoluble in ethanol, butanol and acetone. It was stable at pH 6 approximately 9 but very unstable at pH 2. The UV absorption spectrum shows a maximum at 280 nm. AN-1 had no antibacterial activity against the Gram-positive and Gram-negative bacteria tested, but shows strong inhibitory activity toward Escherichia coli MP2, a macromolecule permeable mutant. In addition to being highly mutagenic, AN-1 inhibits the in vitro cell growth of L1210 (ED50 0.41 micrograms/ml). However, AN-1 had no antitumor activity against mouse leukemia L1210 or Lewis lung carcinoma in mouse.


Two-step pH-modulated rapid assembly of trace-element-doped calcium-phosphate nanocrystals into giant porous beads in gelatin hydrosol for biomedical applications.
Biomolecule-ion interactions that occur during changes in pH value are a crucial but poorly investigated area that underlies the aggregation of inorganic nanocrystals. Meanwhile, the disorderly growth of calcium phosphate (CaP) nanocrystals is an obstacle that limits its practical applications. Herein, we have demonstrated for the first time that a simple two-step pH-adjustment process for a gelatin hydrosol reaction medium can modulate the ordered self-assembly of trace-element-doped CaP nanocrystals into porous beads. Two methods are used to adjust the initial pH value of gelatin hydrosol: One is to firstly adjust the pH value to 3.0 and then to 4.0 with acid/base solutions, whilst the other is to directly adjust the pH value to 4.0 with acid. Spherical CaP porous beads are rapidly produced through the two-step pH-adjustment process, whereas the one-step pathway results in disorderly CaP aggregates. We believe that the introduction of additives for pH adjustment is the dominant factor in disturbing the electrokinetic parameters and for driving the self-assembly of nanocrystals, whereas the nucleation of CaP nanocrystals prior to assembly is caused by the relaxation/condensation of the polypeptide network, owing to the increase in pH value on the introduction of the basic calcium salt. This method is facile and rapid and these highly bioactive porous beads are particularly promising for use in hard-tissue repair, tissue engineering, and drug delivery.


Sporotrichosis in renal transplant patients: two case reports and a review of the literature.
Sporotrichosis is a rare fungal infection in transplant patients; among these patients, it occurs mostly in renal transplant patients. Sporothrix schenkii is the primary pathogen responsible. A high index of suspicion is required to make the diagnosis keeping important differential diagnoses in mind. History of trauma through recreational or occupational exposure to the fungus may assist in making the diagnosis. Treatment is difficult, with long-term use of potentially nephrotoxic and cytochrome P450 inhibitor antifungal agents leading to potential calcineurin inhibitors toxicity. We describe two renal transplant patients presenting with distinct sporotrichosis infection: "Case 2" being only the second reported case ever of meningeal sporotrichosis. We subsequently review the general aspects of sporotrichosis, specifically in renal transplant patients as described in the medical literature. Case 1, a 43-year-old mixed ancestry male patient presented with a non-healing ulcer on the left arm for 1 year, he was diagnosed with cutaneous sporotrichosis and was successfully treated with itraconazole monotherapy. Case 2, a 56-year-old mixed ancestry male patient presented with a slow decline in functions, confusion, inappropriate behavior, rigors and significant loss of weight and appetite over the past 4 months, he was diagnosed with meningeal sporotrichosis and was successfully treated with a combination of deoxycholate amphotericin B and itraconazole. Physicians taking care of renal transplant patients should have a high index of suspicion for sporotrichosis infection particularly when conventional therapy for common conditions fails. Susceptibility testing is recommended to identify the most effective antifungal agent and its dose. The slow nature of growth of Sporothrix schenkii necessitates patients to be on amphotericin B until the time results are available. Finally, there is a need to be aware of potential drug-drug interactions of the azoles with calcineurin inhibitors and the required dose adjustments to prevent therapy related adverse events.


Carnitine increases glucose disposal in humans.
The goal of this work is to assess the effect of L-carnitine on glucose disposal, particularly on insulin sensitivity, in healthy volunteers. Fourteen healthy human volunteers were subjected to the intravenous glucose tolerance test (analyzed by means of the minimal model technique), together with indirect calorimetry and measurement of serum free fatty acids, after a bolus of glucose plus carnitine (C) or a bolus of glucose plus saline (P). The minimal model demonstrated a significant increase in glucose disposal from plasma with carnitine: Glucose effectiveness passed from 2.7%/min to 3.8%/min. No significant changes were observed in the Insulin Sensitivity Index or in Insulin/C-Peptide secretion. Calorimetry showed a significant increase in respiratory quotient, resulting from a significant increase in carbohydrate oxidation rate during carnitine administration by an average of 0.0176+/-0.0118 g/min (p=0.015). Energy expenditure was not modified by treatment. A smaller decrease in plasma fatty acid concentrations was noted with carnitine plus glucose than after glucose alone. From these data it appears that carnitine stimulates glucose disposal and oxidation in the healthy volunteer. Therefore, carnitine might be useful as an adjunct in the therapy of diabetes mellitus.


[The bronchodilator action of berodual spray compared to fenoterol and ipratropium bromide sprays].
Berodual (Duovent) was tested in 40 bronchial asthma patients in comparison with a similar group treated with fenoterol. The results of FEV1.0 investigation showed no significant differences: increases of 15% were noted in both groups. In two other groups (40 bronchial asthma cases each) treated with berodual and Atrovent, respectively FEV1.0 values were significantly different: increased by 5% in the Atrovent group, and by 15% in the berodual one. Berodual showed the advantage of inducing the same strong bronchodilation of similar duration, though applied in doses by far smaller than fenoterol or Atrovent. A diminution of the clinical evolution score from 3 to 0.7, an increase by 15%; in FEV1.0, and no changes as regards the immunological tests (IgA, IgG, IgM, Clq, C3) were obtained in the group treated with berodual for 4 weeks.


Towards density functional approximations from coupled cluster correlation energy densities.
(Semi)local density functional approximations (DFAs) are the workhorse electronic structure methods in condensed matter theory and surface science. The correlation energy density ϵc(r) (a spatial function that yields the correlation energy Ec upon integration) is central to defining such DFAs. Unlike Ec, ϵc(r) is not uniquely defined, however. Indeed, there are infinitely many functions that integrate to the correct Ec for a given electron density ρ. The challenge for constructing useful DFAs is thus to find a suitable connection between ϵc(r) and ρ. Herein, we present a new such approach by deriving ϵc(r) directly from the coupled-cluster (CC) energy expression. The corresponding energy densities are analyzed for prototypical two-electron systems. As a proof-of-principle, we construct a semilocal functional to approximate the numerical CC correlation energy densities. Importantly, the energy densities are not simply used as reference data but guide the choice of the functional form, leading to a remarkably simple and accurate correlation functional for the helium isoelectronic series. While the resulting functional is not transferable to many-electron systems (due to a lack of same-spin correlation), these results underscore the potential of the presented approach.


Congenital and Hereditary Diseases of the Spinal Cord.
Congenital anomalies of the spinal cord can pose a diagnostic dilemma to the radiologist. Several classification systems of these anomalies exist. Antenatal ultrasound and fetal magnetic resonance imaging is playing an increasingly important role in the early diagnosis and management of patients. Understanding the underlying anatomy as well as embryology of these disorders can be valuable in correctly identifying the type of spinal cord dysraphic defect. Hereditary spinal cord diseases are rare but can be devastating. When the onset is in adulthood, delay in diagnosis is common. Although the spine findings are nonspecific, some imaging features combined with brain imaging findings can be distinctive. Sometimes, the radiologist may be the first to raise the possibility of these disorders.


Biomass energy from crop and forest residues.
Residues remaining after the harvest of crop and forestry products are being proposed as a substantial energy source for the nation. An estimated 22 percent of the residues might be utilized, providing a renewable source of high-grade energy with the potential of supplying 1 percent of the current U.S. gasoline consumption as ethanol or 4 percent of the total electrical energy used. These net energy benefits are limited by high energy costs to collect, transport, and process the residues. Environmental threats include soil erosion, water runoff, and nutrient loss.


Alcohol's contribution to fatal injuries: a report on public perceptions.
We determine whether members of the public understand that alcohol contributes to each of the leading causes of unintentional-injury death in the United States and not just to motor vehicle-related fatalities. Public opinions of selected alcohol control policies were also assessed. We used a national telephone survey of 943 adults, who were selected by random-digit dialing techniques. Respondents' mean estimates of alcohol's involvement in fatal injuries were compared with published data from a meta-analysis of medical examiner data. The study population accurately estimated the proportion of fatal fall, drowning, and poisoning victims who were legally drunk when they died. Respondents overestimated the proportion of drivers killed in motor vehicle crashes who were intoxicated and underestimated the proportion of fire/burn victims. Fifty-seven percent of participants endorsed the myth that alcohol intoxication is protective against injury in the event of a motor vehicle crash. Participants were divided over whether increasing the legal drinking age to 21 had resulted in fewer injury deaths. Seventy-eight percent of participants did not believe that raising alcohol taxes would reduce fatal injuries. A majority (58%) of respondents supported taking blood alcohol levels on all "seriously injured" patients brought to the hospital. This report suggests that public awareness of alcohol's contribution to the breadth of the injury problem in the United States is high. Conversely, public understanding of whether prevention strategies have proven to be effective is poor. Emergency medicine practitioners can serve as credible sources of more accurate information for patients and the community at large.


[Reactivity of Candida albicans in the system of the alternative way of complement activation].
The neutrophil-stimulating activity of C. albicans before and after opsonization in the system of the alternative way of complement activation (AWCA) was studied. The study revealed that, in comparison with zymosan, C. albicans exhibited a considerably lower index of AWCA-dependent opsonic effect in reaction with neutrophils. This did not correlate with the capacity of substrates to activate the alternative cascade and with the intensity of phagocytosis. The suggestion on the involvement of C. albicans thermolabile cell-wall components into the negative regulation AWCA-dependent opsonic effect was substantiated.


Heat-stimuli-enhanced osteogenesis using clinically available biomaterials.
A recent study reported that heat stress stimulates osteogenesis in an in vivo rat model using alginate gel and magnetite cationic liposomes. However, for clinical use, the efficacy for promoting osteogenesis needs to be investigated using clinically approved materials, and preferably with animals larger than rats. The aim of this study was to evaluate multiple heat stimuli-triggered osteogenesis in rat tibial defect models using already clinically applicable materials (Resovist® and REGENOS®) and determine the efficacy also in the rabbit. Fifty-eight rats and 10 rabbits were divided into two groups, respectively, with or without hyperthermia treatment at 45°C for 15 min. (hyperthermia; 20 rats once a week, 8 rats three times a week, 5 rabbits once a week, control; 30 rats and 5 rabbits). Micro-CT assessment at 4 weeks revealed that a significantly stimulated osteogenesis was observed in the once a week group of both rats and rabbits as compared to the control group (p = 0.018 and 0.036, respectively). In contrast, the three times a week group did not show enhanced osteogenesis. Histological examination and image analysis showed consistent results in which the area of mineralized bone formation in the once a week hyperthermia group was significantly increased compared with that in the control group at four weeks (rat; p = 0.026, rabbit; p = 0.031). Newly formed bone was observed in the grafted materials from the periphery toward the center, and more osteoclasts were found in the once a week group. Heat stress also induced enhanced alkaline phosphatase expression in cultured osteoblastic cells, MC3T3, in vitro (p = 0.03). On the other hand, heat stress had no obvious effects on chondrogenic differentiation using ATDC5 cells. Our study demonstrates that heat-stimuli with clinically applicable novel heating materials can promote significant osteogenesis, and may thus be a promising treatment option for diseases associated with bone defects.


The HIV oligonucleotide database (HIVoligoDB).
The human immunodeficiency virus (HIV) is associated with one of the most widespread infectious disease, the acquired immunodeficiency syndrome (AIDS). The development of antiretroviral drugs and methods for virus detection requires a comprehensive analysis of the HIV genomic diversity, particularly in the binding sites of oligonucleotides. Here, we describe a versatile online database (HIVoligoDB) with oligonucleotides selected for the diagnosis of HIV and treatment of AIDS. Currently, the database provides an interface for visualization, analysis and download of 380 HIV-1 and 65 HIV-2 oligonucleotides annotated according to curated reference genomes. The database also allows the selection of the most conserved HIV genomic regions for the development of molecular diagnostic assays and sequence-based candidate therapeutics. http://portugene.com/HIVoligoDB.


Single-incision laparoscopic surgery for intersigmoid hernia.
Intersigmoid hernia is a rare form of internal hernia. Here, we report a case of intersigmoid hernia and provide a brief review of the 62 cases involving the mesosigmoid reported in Japan from 2000 to 2013. In the current case, a 26-year-old man with no previous history of abdominal surgery presented with abdominal pain and vomiting. Abdominal computed tomography revealed an extensively dilated small bowel and a closed loop of small bowel in the mesosigmoid. The patient was diagnosed with an intestinal obstruction due to an incarcerated internal hernia involving the mesosigmoid. There was no blood flow obstruction at the incarcerated bowel. An elective single-incision laparoscopic surgery was performed after decompression of the bowel using ileus tube. As the ileum herniated into the intersigmoid fossa, the patient was diagnosed with an intersigmoid hernia. The incarcerated small bowel was reduced in order to make it viable, and the hernial defect was closed with interrupted sutures. The patient had an uneventful recovery and was discharged on postoperative day five.


Clinical use of the membrane oxygenator.
Since April 1973 we have treated nine patients with extracorporeal membrane oxygenation (ECMO), utilizing the spiral coil membrane lung. One patient is a long-term survivor. All patients except one showed substantial improvement in peripheral arterial oxygen tension. Four adults and two neonates were treated for critical hypoxia. Two patients were treated for cardiac failure but failed to show improved myocardial function. Complications involving perfusion circuitry, cannulation, chronic systemic heparinization, thrombocytopenia, and renal failure have been managed with minimal difficulty. However, irreversible pulmonary, neurologic, hepatic, or gastrointestinal damage due to hypoxia present before the institution of ECMO was associated with lethal complications. The ECMO has supplied adequate oxygenation to this group of nine critically hypoxic patients. Institution of ECMO at an earlier date in patients with critical hypoxia would provide a higher likelihood of survival.


Magnetic resonance differential analysis for different hormone receptor expression status in HER-2-positive breast cancer.
Currently, it is difficult to assess the expression status of hormone receptor (HR) in breast malignant tumors with human epidermal growth factor receptor 2 (HER-2)-positive in the early preoperative stage, and it is difficult to predict whether it is non-invasively. This study aims to explore the value of MRI on the different HR expression status (HR+/HR-) in HER-2 positive breast cancer. Thirty patients with HR+ HER-2-positive breast cancer (HR+ group) and 23 patients with HR-HER-2-positive breast cancer (HR- group) from the First Hospital of Hunan University of Traditional Chinese Medicine between January 7, 2015 and November 26, 2021 were selected as subjects, and all the patients were examined by MRI and all were confirmed by surgery or pathological biopsy puncture. The immunohistochemical staining results were used as the gold standard to analyze the basic clinical conditions, peri-lesion conditions and MRI sign characteristics in the 2 groups. There were all significant differences in terms of mass margins, internal reinforcement features, and apparent diffusion coefficient (ADC) values between the HR+ group and the HR- group (all P<0.05). The logistic multivariate regression model showed that: when the lesion presented as a mass-type breast cancer on MRI, the internal enhancement features of the lesion were an independent predictor for differentiation in the 2 types of breast cancer [odds ratio (OR)=5.95, 95% CI: 1.223 to 28.951, P<0.05], and the mass margin (OR=0.386, 95% CI: 0.137 to 1.082, P>0.05) and ADC value (OR=0.234, 95% CI: 0.001 to 105.293, P>0.05) were not the independent predictors in distinguishing the 2 types of breast cancer. Multiparametric MRI has good diagnostic value for HR expression status in HER-2-positive breast cancer. Combined logistic regression analysis to construct a predictive model may be helpful to the identical diagnosis.


Primary Amine Functionalization of Alkoxysilanes: Synthesis, Selectivity, and Mechanistic Insights.
We report a highly selective substitution of silicon-bound methoxy groups by primary lithium amides. This unusual reactivity is possible because of the formation of particularly stable lithium methoxide, which compensates for the decreased Si-N bond enthalpy compared to Si-O bonds. In contrast to substitution reactions on halosilanes, highly selective monosubstitutions under mild conditions are possible, even in the presence of further reactive methoxy groups. A combination of experiments and density functional theory calculations was carried out in order to get an extensive understanding of the reaction. The calculations reveal a possible reaction mechanism with considerably low activation barriers and the entry of the nucleophile to be the rate-determining step. The low activation energies allow for the substitutions to be carried out at low temperatures, therefore preventing side reactions from occurring. The presented investigations expand the view of fundamental transformation processes on silicon and give access to a wide variety of functionalized silicon-based building blocks for various fields of chemistry.


Assessing computational genomics skills: Our experience in the H3ABioNet African bioinformatics network.
The H3ABioNet pan-African bioinformatics network, which is funded to support the Human Heredity and Health in Africa (H3Africa) program, has developed node-assessment exercises to gauge the ability of its participating research and service groups to analyze typical genome-wide datasets being generated by H3Africa research groups. We describe a framework for the assessment of computational genomics analysis skills, which includes standard operating procedures, training and test datasets, and a process for administering the exercise. We present the experiences of 3 research groups that have taken the exercise and the impact on their ability to manage complex projects. Finally, we discuss the reasons why many H3ABioNet nodes have declined so far to participate and potential strategies to encourage them to do so.


Retro-inverso forms of gastrin5-12 are as biologically active as glycine-extended gastrin in vitro but not in vivo.
Non-amidated gastrin peptides such as glycine-extended gastrin (Ggly) are biologically active in vitro and in vivo and have been implicated in the development of gastric and colonic cancers. Previous studies have shown that the truncated form of Ggly, the octapeptide LE5AY, was still biologically active in vitro, and that activity was dependent on ferric ion binding but independent of binding to the cholecystokinin 2 (CCK2) receptor. The present work was aimed at creating more stable gastrin-derived 'super agonists' using retro-inverso technology. The truncated LE5AY peptide was synthesized using end protecting groups in three forms with l-amino acids (GL), d-amino acids (GD) or retro-inverso (reverse order with d-amino acids; GRI). All of these peptides bound ferric ions with a 2:1 (Fe: peptide) ratio. As predicted, Ggly, GL and GRI were biologically active in vitro and increased cell proliferation in mouse gastric epithelial (IMGE-5) and human colorectal cancer (DLD-1) cell lines, and increased cell migration in DLD-1 cells. These activities were likely via the same mechanism as Ggly since no CCK1 or CCK2 binding was identified, and GD remained inactive in all assays. Surprisingly, unlike Ggly, GL and GRI were not active in vivo. While Ggly stimulated colonic crypt height and proliferation rates in gastrin knockout mice, GL and GRI did not. The apparent lack of activity may be due to rapid clearance of these smaller peptides. Nevertheless further work designing and testing retro-inverso gastrins is warranted, as it may lead to the generation of super agonists that could potentially be used to treat patients with gastrointestinal disorders with reduced mucosal function.


Mesoscopic helical architectures via self-assembly of porphyrin-based discotic systems.
Mesoscopic super-helices with preferred helicity have been serendipitously formed from the self-assembly of electroactive extended core discotic molecules. The investigation at dilute concentrations reveals intramolecular hydrogen-bonding and π-π stacking interactions as the driving force of the chiral self-assembly at different length scales.


The IL-15/IL-15Ralpha on cell surfaces enables sustained IL-15 activity and contributes to the long survival of CD8 memory T cells.
We previously described unique features of the IL-15 receptor (IL-15R)alpha. IL-15Ralpha by itself forms stable complexes with IL-15 on cell surfaces and presents IL-15 in trans to neighboring natural killer/T cells. Moreover, the membrane IL-15/IL-15Ralpha complexes (membIL-15) undergo endosomal internalization but survive lysosomal degradation, allowing the complexes to recycle back to the cell surface. Here, we show that membIL-15+ cells act as a persistent source of IL-15 for the surrounding microenvironment (intercellular reservoir effect). Additionally, membIL-15+ cells give rise to augmented retention of IL-15 in the circulation as well as in tissues. Curiously, IL-15 retention was particularly associated with lungs, rather than with lymph nodes, in normal unstimulated mice, which correlated with the preferential homing of antigen-specific CD8 T cells to lungs during their contraction phase in an IL-15Ralpha-dependent manner. Furthermore, membIL-15, unlike soluble IL-15, caused sustained IL-15 signal transduction in the target cells. Collectively, these characteristics define IL-15 as a unique cytokine with prolonged in vivo survival and sustained biological action on the target cells, which may account for the proposed persistent action of IL-15 that helps the long-term survival of functional CD8 memory T cells in vivo.


Rare entity: Ectopic liver tissue in the wall of the gallbladder - A case report.
Ectopic liver tissue (ELT) is a rare condition, which is usually not diagnosed preoperatively, but coincidentally during abdominal surgery. While the location of ELT can vary, it is usually localized on the gallbladder wall or in close proximity. ELT is associated with various complications, a major complication being extrahepatic hepatocellular carcinoma. A 59-year-old female underwent elective surgery for chronic cholecystitis with stones. During laparoscopic exploration, a 2-cm-diameter ELT was detected in the anterior gallbladder wall and a laparoscopic cholecystectomy was performed. The case is presented due to the rare nature of ELT and as a reminder of ELT-related complications.


Dynamics of ocular surface pH.
We studied ocular surface pH in 161 subjects. The mean pH for 133 normal volunteers was 7 . 11, SD 1 . 5. We found that older women had a more alkaline pH than other subjects, that the pH shifted from acid to alkaline during the day, that one hour of eyelid closure caused an acid shift in pH, and that pH recovered to baseline values within 40 minutes after acid drop instillation. We explored the mechanism of pH regulation, and we believe that pH changes could affect contact lens toleration, drug effectiveness, and clinical signs in disease processes.


Regulation of immediate early gene expression by exercise: short cuts for the adaptation of immune function.
Onset of physical activity induces a wide variety of rapid biophysical and biochemical responses that act on cells and lead to a wide range of phenotypic adaptations. Here we elucidate the role of immediate early gene (IEG) expression as a first line of transcriptional response that mediates protein neosynthesis and leads to adaptation of immune function. New posttranscriptional mechanisms have been described that speed up transcriptional responses. These include RNA-RNA interactions such as those exploited by miRNAs and stimulus-dependent cytoplasmic polyadenylation. We describe these shortcuts that modulate expression and discuss the challenges of accurately measuring them using various transcriptomic screening and quantification approaches. Although there is high complexity of the upstream as well as the downstream pathways that lead to IEG expression, IEG expression itself may only show a limited number of response patterns. Focusing transcriptomic approaches in exercise immunology at the IEG-level may facilitate the discovery of exercise-specific transcriptional signatures.


Effect of antenatal care on low birth weight: a systematic review and meta-analysis in Africa, 2022.
Risk identification, as well as the prevention and management of diseases associated with pregnancy or other conditions that may occur concurrently, is the essential component of ANC. The observational follow-up and cross-sectional studies on the effect of antenatal care on low birth weight in Africa were conducted according to the Preferred Reporting Items for Systematic reviews and Meta-Analyses guidelines. Five computerized bibliographic databases: Google Scholar, PubMed, Scopus, Cochrane Library, and Hinari Direct were searched for published studies written in English till May 2022. The risk of bias assessment tools developed by the Joanna Briggs Institute for cross-sectional and observational follow-up research was used, and the caliber of each included study was assessed. Seven papers were included, with a total of 66,690 children participating in the study. Seven studies met the selection criteria. Prenatal care and low birth weight were linked in four of the seven studies included in the review. The pooled odd ratio for low birth weight in the random-effects model was 0.46 (95% CI: 0.39, 0.53). The pooled odds ratio for low birth weight was 0.21 (95% CI: 0.19, 0.22) and 0.21 (95% CI: 0.19, 0.22), respectively, among pregnant women who had no antenatal care follow-up and those who had antenatal care follow up. Women who attended at least one antenatal care appointment were more likely than their counterparts to have a baby of normal weight. Interventions to reduce low birth weight in Africa should focus on providing adequate antenatal care and quality healthcare services to women with low socioeconomic status.


Strong Associations Between Early Tubular Damage and Urinary Cytokine, Chemokine, and Growth Factor Levels in Elderly Males and Females.
Acute tubular necrosis is associated with high mortality rates and it is important to develop new biomarkers for tubular damage. The aim of this study was to investigate the effect of early tubular damage on a large number of urinary cytokines, chemokines, and growth factors. We selected 90 urine samples from the Prospective Investigation of the Vasculature in Uppsala Seniors Study (41 males and 49 females). The tubular damage markers cystatin C, neutrophil gelatinase-associated lipocalin (NGAL), and kidney injury molecule-1 (KIM-1) were analyzed in the urine samples and urinary cytokine levels were analyzed with 2 multiplex assays (proximity extension assay). After adjustment for sex, body mass index, estimated glomerular filtration rate, smoking, and multiplicity testing using the false discovery rate approach, there remained 26 cytokines that correlated significantly with urine cystatin C, 27 cytokines that correlated with NGAL, and 66 cytokines that correlated with KIM-1. Tubular damage shows a strong association with urinary cytokines, chemokines, and growth factors. Our findings indicate that multiplex proteomics could be a promising new approach to explore the complex effects of tubular damage.


Can we influence medical students' approaches to learning?
Students use three approaches to learning and studying: deep, surface and strategic. These are influenced by the learning environment. In response to the General Medical Council's report 'Tomorrow's Doctors', the second year of the medical course at the University of Edinburgh was changed to promote deep learning, with learning objectives constructed according to the SOLO taxonomy, learning methods such as problem-based learning and constructively aligned written assignments and examinations. The Approaches to Study Skills Inventory for Students (ASSIST) was used to evaluate the effect of these changes. Scores were highest for deep approaches and lowest for surface approaches and showed almost no change during the course. There are various possible explanations. The students already scored highly on deep approaches at the beginning of Year 2 and it may be difficult to increase the deep scores further, particularly over the relatively short period of the study. Alternatively, the effect of the changes in learning environment may not be strong enough to change entrenched approaches which have hitherto been successful.


Influence of large peritumoral vessels on outcome of radiofrequency ablation of liver tumors.
The effect of large vessels (>/=3 mm) contiguous to hepatic tumors was evaluated with respect to clinical tumor recurrence rates after radiofrequency (RF) ablation. The first 105 malignant liver tumors treated by RF ablation therapy at our institution with pathologic analysis or a minimum of 6 months of clinical follow-up were reviewed. The original pretreatment imaging studies were reviewed by a radiologist who was blinded to the cases, and, based on lesion contiguity to vessels of at least 3 mm, the lesions were categorized as perivascular or nonperivascular. Treatment outcomes with respect to local tumor recurrence between these two groups were then compared. Logistic regression analysis was performed to take into account other variables and to determine whether this categorization was an independent predictor of treatment outcome. There were 74 nonperivascular tumors and 31 perivascular tumors. Mean tumor size was 2.4 cm and mean follow-up was 11.3 months. Residual or locally recurrent tumors were documented in 20 of 105 cases (19%). In the nonperivascular group, five of 74 (7%) had either incompletely treated tumor (manifested within 6 months) or local recurrence beyond 6 months. In the perivascular group, 15 of 31 (48%) had incompletely treated or locally recurrent tumor (P <.001). Subanalysis of lesion size (61 tumors </=2.5 cm, 33 tumors 2.6-4 cm, and 11 tumors >4 cm), tumor type (40 hepatocellular carcinomas, 48 colorectal metastases, and 17 other metastases), access (53 intraoperative, 52 percutaneous), and RF device (45 Radiotherapeutics electrodes, 18 Rita electrodes, and 42 Radionics electrodes) showed similar results. Multivariate logistic regression analysis showed that presence or absence of a large peritumoral vessel is an independent, and the dominant, predictor of treatment outcome. The presence of vessels at least 3 mm in size contiguous to hepatic tumors is a strong independent predictor of incomplete tumor destruction by RF ablation. Modified ablation strategies should be considered to improve destruction of these tumors.


Heme oxygenase-1 deficiency accelerates formation of arterial thrombosis through oxidative damage to the endothelium, which is rescued by inhaled carbon monoxide.
Heme oxygenase (HO)-1 (encoded by Hmox1) catalyzes the oxidative degradation of heme to biliverdin and carbon monoxide. HO-1 is induced during inflammation and oxidative stress to protect tissues from oxidative damage. Because intravascular thrombosis forms at sites of tissue inflammation, we hypothesized that HO-1 protects against arterial thrombosis during oxidant stress. To investigate the direct function of HO-1 on thrombosis, we used photochemical-induced vascular injury in Hmox1-/- and Hmox1+/+ mice. Hmox1-/- mice developed accelerated, occlusive arterial thrombus compared with Hmox1+/+ mice, and we detected several mechanisms accounting for this antithrombotic effect. First, endothelial cells in Hmox1-/- arteries were more susceptible to apoptosis and denudation, leading to platelet-rich microthrombi in the subendothelium. Second, tissue factor, von Willebrand Factor, and reactive oxygen species were significantly elevated in Hmox1-/- mice, consistent with endothelial cell damage and loss. Third, following transplantation of Hmox1-/- donor bone marrow into Hmox1+/+ recipients and subsequent vascular injury, we observed rapid arterial thrombosis compared with Hmox1+/+ mice receiving Hmox1+/+ bone marrow. Fourth, inhaled carbon monoxide and biliverdin administration rescued the prothrombotic phenotype in Hmox1-/- mice. Fifth, using a transcriptional analysis of arterial tissue, we found that HO-1 determined a transcriptional response to injury, with specific effects on cell cycle regulation, coagulation, thrombosis, and redox homeostasis. These data provide direct genetic evidence for a protective role of HO-1 against thrombosis and reactive oxygen species during vascular damage. Induction of HO-1 may be beneficial in the prevention of thrombosis associated with vascular oxidant stress and inflammation.


Biomarkers for chronic kidney disease in dogs: a comparison study.
The aim of this study was to determine whether serum symmetric dimethylarginine (SDMA) and cystatin C (CysC) levels can be utilized as more accurate markers of early kidney dysfunction in dogs. Forty-one client-owned dogs with chronic kidney disease (CKD), which were clinically stable, and ten beagles as healthy controls were included. All dogs underwent physical examination, systemic blood pressure measurement, complete blood cell count, and plasma biochemistry analyses. Frozen serum was used for SDMA and CysC analyses. Data analysis was performed using Kruskal Wallis, Pearson's correlation, Bland-Altman plots, and receiver operating characteristic curve. SDMA and CysC levels were significantly higher in patients with CKD at various International Renal Interest Society (IRIS) stages than in the healthy controls. In particular, CysC level was the only biomarker that could indicate the earliest stage of CKD (IRIS stage I). Similar to these results, CysC level showed better sensitivity and specificity compared to the other biomarkers in early CKD dogs.


Three-year experience with interventional neuroradiology for management of cerebral aneurysms at a single Australian centre.
Over the last decade interventional neuroradiology (NR) has become the mainstay of managing cerebral aneurysms. The aim of our study was to review our growing experiences with interventional NR and quantify morbidity and mortality associated with these procedures. The electronic medical records of all patients admitted to the Gold Coast (University) Hospital Intensive Care Unit following subarachnoid haemorrhage (SAH) or elective interventional NR management of cerebral aneurysms between January 2012 and December 2014 were retrieved. Primary outcomes of interest were death, thromboembolic and haemorrhagic events during hospital admission. One hundred and fifty-two patients underwent interventional NR procedures for cerebral aneurysms. This consisted of 92 (60.5%) elective cases and 60 (39.5%) emergency cases following SAH. The all-cause mortality rate and the rate of thromboembolic and haemorrhagic events for the entire cohort were 5.9%, 11.2% and 7.2% respectively. Intra-procedural complications occurred in 6.6% of the entire cohort. Median length of follow-up was 448 days, with 91.6% of the entire cohort followed up. At follow-up, 64.1% of patients had no neurological deficits, 29% had mild non-specific deficits and 6.9% had significant disability. Interventional NR represents the primary treatment modality for all patients presenting to our service with cerebral aneurysm. Our results are encouraging and are comparable to published data in the international literature. Reducing the burden of thromboembolism in patients undergoing endovascular treatment of their aneurysmal disease is our main research focus currently, and we aim to improve outcomes for this patient group.


A Novel Betabaculovirus Isolated from the Monocot Pest Mocis latipes (Lepidoptera: Noctuidae) and the Evolution of Multiple-Copy Genes.
In this report, we described the genome of a novel baculovirus isolated from the monocot insect pest Mocis latipes, the striped grass looper. The genome has 134,272 bp in length with a G + C content of 38.3%. Based on the concatenated sequence of the 38 baculovirus core genes, we found that the virus is a betabaculovirus closely related to the noctuid-infecting betabaculoviruses including Pseudaletia unipuncta granulovirus (PsunGV), Trichoplusia ni granulovirus (TnGV), Helicoverpa armigera granulovirus (HearGV), and Xestia c-nigrum granulovirus (XecnGV). The virus may constitute a new Betabaculovirus species tentatively named Mocis latipes granulovirus (MolaGV). After gene content analysis, five open reading frames (ORFs) were found to be unique to MolaGV and several auxiliary genes were found including iap-3, iap-5, bro-a, bro-b, and three enhancins. The virus genome lacked both chitinase and cathepsin. We then looked at the evolutionary history of the enhancin gene and found that betabaculovirus acquired this gene from an alphabaculovirus followed by several duplication events. Gene duplication also happened to an endonuclease-like gene. Genomic and gene content analyses revealed both a strict collinearity and gene expansion into the genome of the MolaGV-related species. We also characterized the granulin gene using a recombinant Autographa californica multiple nucleopolyhedrovirus (AcMNPV) and found that occlusion bodies were produced into the nucleus of infected cells and presented a polyhedral shape and no occluded virions within. Overall, betabaculovirus genome sequencing is of importance to the field as few genomes are publicly accessible. Mocislatipes is a secondary pest of maize, rice, and wheat crops in Brazil. Certainly, both the discovery and description of novel baculoviruses may lead to development of greener and safer pesticides in order to counteract and effectively control crop damage-causing insect populations.


Understanding the Catalytic Mechanism of Xanthosine Methyltransferase in Caffeine Biosynthesis from QM/MM Molecular Dynamics and Free Energy Simulations.
S-Adenosyl-l-methionine (SAM) dependent xanthosine methyltransferase (XMT) is the key enzyme that catalyzes the first methyl transfer in the caffeine biosynthesis pathway to produce the intermediate 7-methylxanthosine (7mXR). Although XMT has been a subject of extensive discussions, the catalytic mechanism and nature of the substrate involved in the catalysis are still unclear. In this paper, quantum mechanical/molecular mechanical (QM/MM) molecular dynamics (MD) and free energy (potential of mean force or PMF) simulations are undertaken to determine the catalytic mechanism of the XMT-catalyzed reaction. Both xanthosine and its monoanionic form with N3 deprotonated are used as the substrates for the methylation. It is found that while the methyl group can be transferred to the monoanionic form of xanthosine with a reasonable free energy barrier (about 17 kcal/mol), that is not the case for the neutral xanthosine. The results suggest that the substrate for the first methylation step in the caffeine biosynthesis pathway is likely to be the monoanionic form of xanthosine rather than the neutral form as widely adopted. This conclusion is supported by the pKa value on N3 of xanthosine both measured in aqueous phase and calculated in the enzymatic environment. The structural and dynamics information from both the X-ray structure and MD simulations is also consistent with the monoanionic xanthosine scenario. The implications of this conclusion for caffeine biosynthesis are discussed.


RTF: a rapid and versatile tissue optical clearing method.
Tissue optical clearing enables imaging deeper in large volumes with high-resolution. Clear T2 is a relatively rapid clearing method with no use of solvents or detergents, hence poses great advantage on preservation of diverse fluorescent labels. However, this method suffers from insufficient tissue transparency, especially for adult mouse brain blocks. In this work, we develop a rapid and versatile clearing method based on Clear T2 , termed RTF (Rapid clearing method based on Triethanolamine and Formamide), aiming for better clearing capability. The results show that RTF can not only efficiently clear embryos, neonatal brains and adult brain blocks, but also preserve fluorescent signal of both endogenous fluorescent proteins and lipophilic dyes, and be compatible with virus labeling and immunostaining. With the good transparency and versatile compatibility, RTF allows visualization and tracing of fluorescent labeling cells and neuronal axons combined with different imaging techniques, showing potentials in facilitating observation of morphological architecture and visualization of neuronal networks.


Behavioral effect of herbal glycoside in the forced swimming test.
We investigated the behavioral effects of Chinese herbal medicines in the forced swimming test. One of these medicines, Kami-shoyo-san, induced an antidepressive climbing behavior in mice. An effective substance detected to be an O-linked glycoside with the sugar chain structure GalNAc alpha 1-3GalNAc was separated. The behavioral effect was dose-dependently decreased by the dopamine 2 antagonist sulpiride, but not by the dopamine 1 antagonist SCH-233960. Investigated Chinese herbal medicines, including Kami-shoyo-san, have been used for human depression. These facts suggest that glycoside is one of the antidepressant-like substances of Chinese herbal medicines.


What's new in lipid management?
Statins are the principal agents for managing hyperlipidemia because of their ability to reduce low-density lipoprotein cholesterol (LDL) and triglyceride levels, increase high-density lipoprotein cholesterol (HDL) levels slightly, and decrease clinical events. Nevertheless, not all patients can tolerate the statins or achieve their treatment goals with these drugs. In addition, available statins have only modest effects on HDL, and clinical events still occur despite the best current lipid-lowering agents. Thus, new lipid-lowering agents are required to improve clinical outcomes. These recently or soon to be released agents are stanol esters, which can be incorporated into spreads and other foods and reduce LDL levels up to 15%; colesevelam, a new bile acid sequestrant with a higher potency, fewer adverse effects, and less drug interactions than those of older agents in this class; rosuvastatin, a new statin that reduces LDL levels and increases HDL levels at least more effectively than atorvastatin; and a new class of agents that inhibit cholesterol absorption and are likely to be used in combination with statins. Low-density lipoprotein cholesterol apheresis is another, nonpharmacologic option for patients with severe hyperlipidemia despite maximal medical therapy.


Prenatal cystic fibrosis screening in Mexican Americans: an economic analysis.
We evaluated the cost benefit of cystic fibrosis screening in Mexican American gravid women. With the use of decisions analysis techniques, a cost-benefit analysis was performed. Baseline assumptions were based on published references. Sensitivity analyses were performed. Under the baseline assumptions, screening was not cost beneficial. Threshold analysis showed that, if the test was priced under 53.00 dollars, screening became cost beneficial. Sensitivity analysis demonstrated that lower acceptance rates of amniocentesis or termination made the screening strategy less attractive. If the test sensitivity was raised to 90%, which required testing of >60 mutations, the cost of screening would need to be <100.00 dollars for the program to be cost beneficial. Cystic fibrosis screening is not cost beneficial in Mexican American women over a wide range of assumptions. This is principally due to the poor sensitivity of the test in this population. Cultural factors, such as lower acceptance of amniocentesis and pregnancy termination of affected fetuses, further lower the cost-benefit ratio of screening.


Optical encoding and hiding scheme for a double image based on chaotic fingerprint phase masks and phase-shifting digital holography.
This paper proposes a novel, to the best of our knowledge, double-image hiding scheme based on the chaotic fingerprint phase masks (CFPMs) and three-step phase-shifting digital holography (PSDH). First, the two images to be hidden are encoded into a complex amplitude image, and then with the help of the CFPM located in the Fresnel transform (FrT) domain and the three-step PSDH, the complex amplitude image can be encoded into three noise-like interference holograms. Finally, the three noise-like interference holograms are hidden into the texture part of the host image by the discrete wavelet transform based fusion approach and variational image decomposition technique. This scheme can simultaneously hide two images into one host image, and the invisibility and robustness of the hiding scheme can be well balanced by embedding the secret image in the texture of the host image. Additionally, the introduction of a biometric feature increases the association of the key and the authorized user, and the parameters of the chaotic map and FrT can also provide additional security to the proposed scheme. We have verified the scheme's feasibility, security, and robustness through extensive experiments.


Total synthesis of (15R)- and (15S)-F(2t)-isoprostanes by a biomimetic process using the cyclization of acyclic dihydroxylated octa-5,7-dienyl radicals.
We report a new route to F(2t)-IsoP (formerly named 8-epi-PGF(2alpha)) using a biomimetic radical cyclization of a highly functionalized C20 precursor. The strategy employed gives a beta-hydroxy free radical followed by molecular oxygen trapping, which is an unusual method for quenching carbon free radicals. We observed the formation of unique diastereoisomers (15R)- and (15S)-F(2t)-IsoP. This result is consistent with a strong stereoelectronic control associated with a steric effect initiated by the side chains alpha and omega on the cyclopentane ring.


Effect of Distance From Fertility Center on Utilization of Fertility Preservation Referral in Men.
Fertility preservation (FP) is underutilized in males with cancer or other diseases requiring gonadotoxic therapies. We sought to evaluate whether patient distance from FP center affected rates of providing a semen analysis after referral. We performed a retrospective analysis of all males who were referred for FP at a single institution between 2013 and 2021. A multiple logistic regression model was conducted with semen sample submission as the variable of interest. Predictor variables were disease type, distance, and payment method. Secondary outcomes were number of semen samples submitted and number of vials collected. Records of 461 males referred to our center were analyzed. Of these patients, 326 (71%) provided a semen sample after referral and 135 (30%) did not. Further distance from our center was associated with lower odds of submitting a semen sample (OR, 0.85; 95% CI, 0.75 to 0.97; P < .05). For patients who submitted at least one sample, distance did not affect the total number of samples submitted but was associated with a small increase in total vials cryopreserved. Men referred for FP exhibit a high rate of sperm cryopreservation. Further distance from FP center was associated with decreased odds to provide semen sample after referral. Our model estimated a 15% decrease in odds of collection with every doubling of distance from our center. Efforts must be made to improve FP utilization for patients traveling far distances, but distance alone should not preclude referral.


Rolapitant: first global approval.
Rolapitant (Varubi™) is an orally active neurokinin-1 receptor antagonist developed by TESARO and approved in the USA for use in combination with other antiemetic agents for the prevention of delayed chemotherapy-induced nausea and vomiting (CINV) in adults. Unlike other approved agents in this class, rolapitant does not interact with cytochrome P450 (CYP) enzyme CYP3A4. It also has a long elimination half-life which means that a single dose could prevent CINV during the entire at-risk period (0-120 h). An intravenous formulation of rolapitant is under clinical development in the USA. Phase II development of rolapitant in postoperative nausea and vomiting, and cough appears to have been discontinued. This article summarizes the milestones in the development of rolapitant leading to the first approval for the prevention of CINV.


[Post-translational proteolytic maturation of prosomatostatin. Cellular and molecular approach].
Somatostatins -14 and -28 are generated from a single (mammals) or two distinct (teleostean fishes) biosynthetic precursors by selective cleavage at either a dibasic (Arg-Lys) or a monobasic (Arg) site. This prohormone obviously constitutes an excellent model to study post-translational proteolytic events both at the cellular and molecular levels. Using a combination of techniques including subcellular fractionation, intracellular transport blockage and electron microscopy immunocytochemical observations, we have demonstrated unequivocally that both monobasic and dibasic proteolytic maturation occur in the Golgi apparatus of either rat brain cortex or hypothalamic cells or for somatostatin producing cells of Lophius piscatorius Brockmann organs. An arginine selective endoprotease, putative converting enzyme of prosomatostatin into somatostatin -28, has been purified and characterized from the rat intestinal mucosa.


Traumatic subcutaneous emphysema after liposuction.
Traumatic subcutaneous emphysema, which is the infiltration of air into subcutaneous tissues due to trauma, is caused by various factors such as chest and/or abdominal trauma, facial fractures, and barotrauma caused by mechanical ventilation. In this case report, a 32-year-old woman developed traumatic subcutaneous emphysema after undergoing abdominal liposuction at a local clinic. She was subsequently admitted to Busan Paik Hospital, and with early diagnosis and conservative treatment, she was discharged on the seventh day of hospitalization with no complications. However, because traumatic subcutaneous emphysema may accompany other injuries for various reasons, radiological examination and various tests should be performed to prevent serious complications and sequelae.


Trajectories of perceived discrimination from adolescence to emerging adulthood and substance use among Hispanic youth in Los Angeles.
Previous studies have documented associations between perceptions of racial/ethnic discrimination and adverse health outcomes among Hispanics and other minority groups. However, these studies have not examined change in perceived discrimination over the lifecourse and whether trajectories of perceived discrimination affect outcomes differently. This study of 2722 Hispanic students identified trajectories of perceived discrimination from 9th grade through emerging adulthood (approximately ages 14-23), and compared these trajectory groups on substance use outcomes. Four distinct trajectory groups were identified: (1) low and stable discrimination, (2) increasing discrimination, (3) initially high but decreasing discrimination, and (4) high and stable discrimination. Compared with the low and stable discrimination group, the groups that experienced higher levels of discrimination were at higher risk of cigarette, alcohol, marijuana, and hard drug use. Specifically, the group with increasing discrimination (group 2) had a higher risk of alcohol, marijuana, and hard drug use; the group with initially high but decreasing discrimination (group 3) had a higher risk of cigarette smoking and alcohol use; and the group with high and stable discrimination (group 4) had a higher risk of alcohol, marijuana, and hard drug use. Results indicate that experiencing discrimination during adolescence, emerging adulthood, or both, regardless of whether the discrimination increases or decreases, could place Hispanic youth at risk for substance use. Health education programs are needed to help Hispanic youth learn effective skills to cope with discrimination without resorting to substance use.


Body mass index kinetics around adiposity rebound in Anorexia nervosa: A case-control study.
Anorexia nervosa (AN) is associated with parameters involved in body mass index (BMI) regulation. Contrary to obesity, BMI kinetics around the adiposity rebound is not documented in AN. This study aimed at investigating which characteristics of BMI kinetics around the adiposity rebound are associated with AN. Multicentre case-control study with 101 inpatient women with AN onset after 10 years of age, and 101 healthy women, all free of overweight history and matched for age, level of education and fathers' socio-professional status. Age at adiposity rebound, pre- and post-adiposity rebound BMI velocities and accelerations (change in velocity over time) were estimated with linear mixed models using data recorded between 2 and 10 years of age. Patients had an earlier adiposity rebound (mean (standard deviation (SD)): 5.3 (1.3) vs 5.7 (1.1) years), a larger BMI at adiposity rebound (mean (SD): 15.3 [1] vs 14.9 (0.9) kg/m2) and 29% lower BMI acceleration after adiposity rebound than controls. After adjustment, only BMI at adiposity rebound and BMI acceleration after adiposity rebound were associated with a higher risk of AN (Odds ratio [95% confidence interval]: 2.15 [1.41-3.46] for an increase of 1 kg/m2 and 2.44 [1.56-4.02] for an increase of 0.1 kg/(m2*years2) respectively). These two factors were not correlated in patients (r = 0.007, p = 0.96). A flattened evolution of BMI after adiposity rebound and higher BMI at adiposity rebound were associated with AN. Further prospective study is needed to confirm these findings.


Low-Temperature Postfunctionalization of Highly Conductive Oxide Thin-Films toward Solution-Based Large-Scale Electronics.
Although transparent conducting oxides (TCOs) have played a key role in a wide range of solid-state electronics from conventional optoelectronics to emerging electronic systems, the processing temperature and conductivity of solution-processed materials seem to be far exceeding the thermal limitations of soft materials and insufficient for high-perfomance large-area systems, respectively. Here, we report a strategy to form highly conductive and scalable solution-processed oxide materials and their successful translation into large-area electronic applications, which is enabled by photoassisted postfunctionalization at low temperature. The low-temperature fabrication of indium-tin-oxide (ITO) thin films was achieved by using photoignited combustion synthesis combined with photoassisted reduction process under hydrogen atmosphere. It was noteworthy that the photochemically activated hydrogens on ITO surface could be triggered to facilitate highly crystalline oxygen deficient structure allowing significant increase of carrier concentration and mobility through film microstructure modifications. The low-temperature postfunctionalized ITO films demonstrated conductivity of >1607 S/cm and sheet resistance of <104 Ω/□ under the process temperature of less than 300 °C, which are comparable to those of vacuum-deposited and high-temperature annealed ITO films. Based on the photoassisted postfunctionalization route, all-solution-processed transparent metal-oxide thin-film-transistors and large-area integrated circuits with the ITO bus lines were demonstrated, showing field-effect mobilities of >6.5 cm2 V-1 s-1 with relatively good operational stability and oscillation frequency of more than 1 MHz in 7-stage ring oscillators, respectively.


Angular and internal state distributions of H2 (+) generated by (2 + 1) resonance enhanced multiphoton ionization of H2 using time-of-flight mass spectrometry.
We report direct measurement of the anisotropy parameter β for the angular distribution of the photoelectron and photoion in (2 + 1) resonance enhanced multiphoton ionization process of H2 X (1)Σg (+) (v = 0, J = 0) molecules through the intermediate H2 E,F (1)Σg (+) (v' = 0, J' = 0) level (λ = 201.684 nm) using a time-of-flight mass spectrometer. The time-of-flight spectra were recorded as the direction of polarization of the ionizing laser was varied with respect to the flight axis of the H2 molecular beam and were fitted to an angular distribution in an appropriately rotated coordinate system with the z-axis oriented along the time-of-flight axis. The anisotropy parameter β was found to be 1.72 ± 0.13 by fitting the time-of-flight spectra and agreed with previous measurements. Using secondary ionization with a delayed laser pulse of different wavelength, we also determined the vibrational energy distribution of the ions, showing that 98% ± 4% of the ions are generated in their ground vibrational state, in agreement with the calculated Franck-Condon factors between the H2 E,F (1)Σg (+) (v' = 0) and H2 (+) X (1)Σg (+) (v″) vibrational levels.


Covalent analogues of nucleobase-pairs.
Covalently linked base pairs analogues consisting of purine-purine or purine-pyrimidine conjugates linked by carbon linkages of diverse length and configuration (ethylene, vinylene, acetylene and phenylene) were prepared.


In vitro differentiation of epithelial cells from cervical neoplasias resembles in vivo lesions.
Cell lines derived from cervical neoplasias, as well as cells from normal cervix and neonatal foreskin were examined in an in vitro culture system (raft system) that allows for stratification and differentiation of epithelial cells at an air-liquid interface. Epithelial cells from human foreskin and ectocervix were observed to differentiate in a manner histologically similar to normal epithelium in vivo as indicated by a single layer of basal cells with a defined mid and upper zone. In contrast, cells expanded from cervical squamous carcinoma explants showed total absence of normal differentiation in the raft system with numerous cells in the upper portion of the stratum exhibiting mitotic figures. Cell cultures derived from low grade cervical intraepithelial neoplasia and condyloma acuminata exhibited partial differentiation in addition to perinuclear clearing, binucleate cells and individual cell keratinization. These studies show that in the raft system, cultured cells derived from tissue biopsies can duplicate many of the histological features observed in cervical neoplasias. In addition, epithelial cells derived from normal fetal ectocervix and electroporated with cloned human papillomavirus (HPV) type 16 DNA exhibited abnormal differentiation patterns similar to those of cervical intraepithelial neoplasia in vivo. This model system will thus be useful for examining the effects of HPV infection on epithelial maturation and for investigating the role of other factors in the progression of cervical malignancies.


Interleukin-1 beta-mediated metallothionein induction and cytoprotection against cadmium and cis-diamminedichloroplatinum.
Metallothioneins (MTs) are major intracellular protein thiols that have been associated with resistance to the cytotoxicity of heavy metals and some cytotoxic anticancer drugs. The accumulation and subcellular location of MT and its functionality were examined in a human hormone-independent prostatic tumor cell line (DU-145) exposed to cytokines that participate in autocrine growth and the acute phase response. Incubation of DU-145 cells with interleukin-1 beta (IL-1 beta) caused a concentration-dependent increase in MT protein reaching a 2- to 3-fold maximum increase 24 to 48 hr after treatment with 10 U of IL-1 beta/ml; smaller increases were seen with human recombinant IL-1 alpha and tumor necrosis factor alpha. DU-145 cells constitutively expressed only MT-IIa and MT-Ie mRNA and the IL-1 beta-mediated increase in MT protein was preceded by a marked elevation solely in MT-IIa mRNA. Basal MT was immunolocalized by confocal microscopy primarily to the nucleus of DU-145 cells with some granular deposits near the cell surface. IL-1 beta treatment increased nuclear MT. DU-145 cells pretreated with IL-1 beta were 2- to 3-fold resistant to the toxicity of CdCl2 and cis-diamminedichloroplatinum(II) (cisplatin). Both MT induction and cytoprotection against CdCl2 and cisplatin were blocked by concomitant incubation with a recombinant human IL-1 receptor antagonist protein. These results suggest the responsiveness of human prostatic tumor cells to cytotoxic electrophilic anticancer drugs can be diminished by direct exposure to the cytokine IL-1 beta, possibly by a mechanism involving MT.


Association analyses of depression and genes in the hypothalamus-pituitary-adrenal axis.
Dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis has been reported in depression. The aim was to investigate the potential association between depression and seven genes regulating or interfering with the HPA axis, including the gene encoding angiotensin converting enzyme (ACE). In total, 78 single nucleotide polymorphisms (SNPs) and one insertion/deletion polymorphism were genotyped. The study included 408 individuals with depression and 289 controls. In a subset of cases, the interaction between genetic variants and stressful life events (SLEs) was investigated. After quality control, 68 genetic variants were left for analyses. Four of nine variants within ACE were nominally associated with depression and a gene-wise association was likewise observed. However, none of the SNPs located within AVP, CRH, CRHR1, CRHR2, FKBP5 or NC3C1 were associated with depression. One nominally significant interaction, most likely due to chance, was identified. The results indicate that ACE could be a potential candidate gene for depression.


Recent progress in flexor tendon healing.
Although advances in the treatment of flexor tendon injuries have led to improved clinical outcomes during the past several decades, a subset of patients continue to experience a loss of function. Using a canine model of sharp transection of the flexor digitorum profundus tendon followed by repair and rehabilitation using clinically relevant techniques, we have examined the influence of multistrand suture and postoperative rehabilitation variables on digital function and tendon strength. Our findings highlight the critical role of repair technique in providing a stiff and strong repair and indicate that continued refinement of suture techniques is warranted in order to minimize repair-site elongation (gap). Gap formation continues to occur at a high frequency, and the formation of gaps greater than 3 mm delays the accrual of repair-site strength that occurs with time. Furthermore, our results indicate that passive-motion rehabilitation that produces a moderate amount of tendon excursion (2 mm) at low levels of tendon force (5 N) is sufficient to inhibit adhesion formation and to promote healing. Increases in excursion or force beyond these levels do not accelerate the healing process. These findings suggest that we are approaching the limit of the extent to which we can modulate healing by manipulating rehabilitation variables such as tendon excursion and force. Future advances will probably require manipulation of the biological factors that promote healing.


Trial of long-term anticoagulant therapy in the treatment of small stroke associated with a normal carotid arteriogram.
The clinical features of 49 patients who had sustained small strokes in the internal carotid artery territory, who were normotensive, free from cardiac or other relevant disease, and who each had a normal appropriate single vessel angiogram are presented. These were randomized into two groups: group A, 25 patients, who received only supportive treatment; group B, 24 patients who were treated with anticoagulants for an average period of 18 months. There was a reduced incidence of neurological episodes during the administration of anticoagulant therapy but, after treatment was discontinued, there was no significant difference between the two groups. In view of the relatively benign prognosis for this syndrome, unless special facilities exist for the personal control of anticoagulant treatment, the dangers may outweigh the benefits.