Combined Drug with Antibacterial Effect Supports the Normal Intestinal Microflora.
Widespread use of antibiotics leads to an imbalance of normal intestinal microflora and to the development of multidrug resistance. The problem can be solved by administration of the antibiotics in combination with the drugs that have an immunotropic effect. We studied the effect of the drug containing technologically processed affinity purified antibodies to IFNγ, CD4 receptor, β2-microglobulin of MHC class I, and β2-domain of MHC II combined with antibiotics on the composition of intestinal microflora of pigs and the total number of microbiome resistance genes. Using the methods of NGS sequencing and quantitative PCR, we found that the drug contributes to the maintenance of normal microflora and, consequently, to the symbiotic relationship of the host with microflora, and prevents the reproduction of pathogenic bacterial species. Analysis for the presence of the resistance genes of gastrointestinal microorganisms showed that the drug does not affect the qualitative and quantitative composition of these genes of the intestinal microbiome.


Genetic characterization of H1N1, H1N2 and H3N2 swine influenza virus in Thailand.
Swine have been known to be a suitable host for influenza A virus. In Thailand, phylogenetic analysis on swine influenza virus (SIV) has as yet not been attempted. The present report presents molecular and phylogenetic analysis performed on SIV in Thailand. In this study, 12 SIV isolates from the central and eastern part of Thailand were subtyped and the molecular genetics of hemagglutinin and neuraminidase were elucidated. Three subtypes, H1N1, H1N2 and H3N2, are described. Phylogenetic analysis of the SIV hemagglutinin and neuraminidase genes shows individual clusters with swine, human or avian influenza virus at various global locations. Furthermore, amino acid substitutions were detected either at the receptor binding site or the antigenic sites of the hemagglutinin gene.


Room Temperature Synthesis Mediated Porphyrinic NanoMOF Enables Benchmark Electrochemical Biosensing.
Leveraging size effects, nanoparticles of metal-organic frameworks, nanoMOFs, have recently gained traction, amplifying their scopes in electrochemical sensing. However, their synthesis, especially under eco-friendly ambient conditions remains an unmet challenge. Herein, an ambient and fast secondary building unit (SBU)-assisted synthesis (SAS) route to afford a prototypal porphyrinic MOF, Fe-MOF-525 is introduced. Albeit the benign room temperature conditions, Fe-MOF-525(SAS) nanocrystallites obtained are of ≈30 nm size, relatively smaller than the ones conventional solvothermal methods elicit. Integrating Fe-MOF-525(SAS) as a thin film on a conductive indium tin oxide (ITO) surface affords Fe-MOF-525(SAS)/ITO, an electrochemical biosensor. Synergistic confluence of modular MOF composition, analyte-specific redox metalloporphyrin sites, and crystal downsizing contribute to its benchmark voltammetric uric acid (UA) sensing. Showcasing a wide linear range of UA detection with high sensitivity and low detection limit, this SAS strategy coalesces ambient condition synthesis and nanoparticle size control, paving a green way to advanced sensors.


Effect of pretreatment reagent and hydrogen peroxide on enzymatic hydrolysis of oak in percolation process.
The effect of pretreatment reagent and hydrogen peroxide on enzymatic digestibility of oak was investigated to compare pretreatment performance. Pretreatment reagents used were ammonia, sulfuric acid, and water. These solutions were used without or in combination with hydrogen peroxide in the percolation reactor. The reaction was carried out at 170 degrees C for the predetermined reaction time. Ammonia treatment showed the highest delignification but the lowest digestibility and hemicellulose removal among the three treatments. Acid treatment proved to be a very effective method in terms of hemicellulose recovery and cellulose digestibility. Hemicellulose recovery was 65-90% and digestibilities were >90% in the range of 0.01-0.2% acid concentration. In both treatments, hydrogen peroxide had some effect on digestibility but decomposed soluble sugars produced during pretreatment. Unlike ammonia and acid treatments, hydrogen peroxide in water treatment had a certain effect on hemicellulose recovery as well as delignification. At 1.6% hydrogen peroxide concentration, both hemicellulose recovery and digestibility were about 90%, which were almost the same as those of 0.2% sulfuric acid treatment. Also, digestibility was investigated as a function of hemicellulose removal or delignification. It was found that digestibility was more directly related to hemicellulose removal rather than delignification.


The modified Pereyra procedure in recurrent stress urinary incontinence: a 15-year review.
To assess the effectiveness and perioperative morbidity of the modified Pereyra procedure in the treatment of recurrent stress urinary incontinence. Data of 54 patients who underwent a modified Pereyra procedure for the treatment of recurrent stress urinary incontinence between January 1, 1978, and August 1, 1992, were analyzed retrospectively regarding presenting symptoms, preoperative evaluation, surgical procedure, complications, and cure and failure rates. The patients were divided into two groups depending on the preoperative absence (group I) or presence (group II) of risk factors for repeated failure (detrusor instability, low-pressure urethra, fibrotic urethra, negative Q-tip test, and neurogenic incontinence). After a mean follow-up of 36.3 months, the cure rate of 81.6% in group I (N = 38) was significantly (P = .005) higher than that in group II (N = 16; 43.8% cured). The mean time of occurrence of failure was 11.9 months for group I and 6.8 months for group II. The incidence of intraoperative complications (Pereyra suture in bladder, hemorrhage) for both groups was 7.4%. Immediate postoperative complications were found in 25.9% of all patients; these were mainly infectious processes. Late postoperative complications occurred in 33.3%, with the most prevalent being new-onset urge incontinence and de novo detrusor instability (11.1%) and obstructive voiding dysfunction (9.3%). The rates of perioperative morbidity were not significantly different between the groups. The modified Pereyra procedure is well suited for the treatment of uncomplicated recurrent stress urinary incontinence, with a long-term cure rate of over 80%. However, success rates are significantly lower for recurrent stress incontinence in association with persistent risk factors for failure. In either instance, the procedure is associated with appreciable perioperative morbidity.


Functional characterization of kurtz, a Drosophila non-visual arrestin, reveals conservation of GPCR desensitization mechanisms.
The arrestins are a family of molecules that terminate signaling from many different G protein-coupled receptors, by inhibiting the association between receptor and downstream effectors. We recently employed a human betaarrestin2-GFP fusion protein to explore the dynamics of different neuropeptide receptors in Drosophila and have previously used a betaarrestin translocation assay to identify ligands at orphan receptors. Here, we report that the Drosophila arrestin encoded by kurtz functions in a similar fashion and can be employed to investigate GPCR-arrestin associations. Specifically, a GFP-krz fusion protein, upon co-expression with various Drosophila peptide receptors, an amine receptor, and a mammalian peptide receptor translocates to the plasma membrane in specific response to ligand application. This molecular phenotype is exhibited in a mammalian cell line as well as in a Drosophila cell line. Notably, the details of receptor-arrestin associations in terms of endocytotic patterns are functionally conserved between the mammalian arrestins and kurtz. Furthermore, we report that kurtz mutants exhibit hypersensitivity to osmotic stress, implicating GPCR desensitization as an important feature of the endocrine events that shape this stress response.


Combined Effect of Genotype, Housing System, and Calcium on Performance and Eggshell Quality of Laying Hens.
The objective of this study was to evaluate hen performance and eggshell quality response to genotype, housing system, and feed calcium (Ca) level. For this purpose, an experiment was conducted on 360 laying hens of ISA Brown, Bovans Brown (commercial hybrids), and Moravia BSL (traditional Czech hybrid). Laying hens were kept in enriched cages and on littered floor and fed similar feed mixtures with different Ca content (3.00% vs. 3.50%). In terms of hen performance, ISA Brown had the highest egg production (84.2%) compared to Moravia BSL (74.3%) and Bovans Brown (71.4%). Regarding eggshell quality, Bovans Brown showed the highest values of all eggshell quality parameters. Increasing feed Ca level augmented egg production (p ≤ 0.001) but had no effect on other performance parameters. Except eggshell thickness, all eggshell quality parameters were affected by the three-way interaction of genotype, housing, and Ca. Bovans Brown, which had the strongest eggshells (5089 g/cm2) when housed on a littered floor system and fed 3.00% Ca, while Moravia BSL housed on a littered floor had the weakest eggshells (4236 g/cm2) at 3.50% Ca. The study pointed out the importance of the interactions between studied factors on performance and eggshell quality compared to an individual factor effect.


Estimated GFR Accuracy When Cystatin C- and Creatinine-Based Estimates Are Discrepant in Older Adults.
Serum creatinine and cystatin C are used to estimate glomerular filtration rate, but creatinine-based estimated glomerular filtration rate (eGFRcr), cystatin C-based estimated glomerular filtration rate (eGFRcys), and combined creatinine- and cystatin C-based estimated glomerular filtration rate (eGFRcr-cys) are often divergent, particularly in older adults. We investigated which estimated glomerular filtration rate (eGFR) was more accurate and less biased compared with measured glomerular filtration rate (mGFR). A diagnostic test study from the Berlin Initiative Study. The study population included 657 individuals aged 70 years or older with iohexol plasma clearance (mGFR) and serum creatinine and cystatin C measurements: 567 community-dwelling participants and 90 with a serum creatinine of ≥1.5 mg/dL. We defined 3 groups on the basis of the difference eGFRcys - eGFRcr: whether < -5 mL/min/1.73 m2 (lower eGFRcys), within 5 mL/min/1.73 m2 (reference), or ≥ 5 mL/min/1.73 m2 (lower eGFRcr). eGFRcr, eGFRcys, and eGFRcr-cys were compared to mGFR to assess bias and accuracy. Median bias (eGFR minus mGFR) with 95% CIs and accuracy (percentage of eGFR values within ±30% of mGFR). The mean ± standard deviation age was 78 ± 6 years; the mean eGFRcys, eGFRcr, and eGFRcr-cys were 59 ± 23, 64 ± 20, and 61 ± 22 mL/min/1.73 m2, respectively, and the mean mGFR was 56 ± 19 mL/min. Half of the participants were in the lower eGFRcys group (n=337, 51%). Among them, the median bias for eGFRcys was the lowest (median bias, -2.7; 95% CI, -3.8 to -1.9) compared with the other eGFR equations. Conversely, in the lower eGFRcr group (n=121, 18%), the median bias for eGFRcr was the lowest compared with those for eGFRcys and eGFRcr-cys (2.9; [95% CI, 0.9-4.8] vs 13.8 [95% CI, 11.4-15.6] and 9.5 [95% CI, 7.7-11.0], respectively). Accuracy (percentage of eGFR values within ±30% of mGFR) was 93% for eGFRcr in the lower eGFRcr group and 92% for eGFRcys and 94% for eGFRcr-cys in the lower eGFRcys group. Untested generalizability in younger populations. Among older adults, the lower eGFR between eGFRcys and eGFRcr was a more accurate and less biased estimate of mGFR when comparing the groups.


Regulation of the intracellular calcium level in human blood platelets: cyclic adenosine 3',5'-monophosphate dependent phosphorylation of a 22,000 dalton component in isolated Ca2+-accumulating vesicles.
Two protein kinase activities have been separated from the supernatants of homogenized human blood platelets by DEAE cellulose chromatography. One of them (peak I enzyme) is an efficient stimulator of the uptake of Ca2+ into isolated membrane vesicles in the presence of cyclic AMP and ATP. The second (peak II enzyme), although equally active towards histone, exerts only about one third of the activity of the peak I enzyme. The stimulation of Ca2+ uptake is accompanied by the phosphorylation of a membrane protein with an apparent molecular weight of 22 000, which appears to play an essential role in the regulation of the intracellular Ca2+ level and hence of platelet activity.


Gallic Acid Exerts Nephroprotective, Anti-Oxidative Stress, and Anti-Inflammatory Effects Against Diclofenac-Induced Renal Injury in Malerats.
Diclofenac (DIC) is a Nonsteroidal anti-inflammatory drug (NSAID) and consumption of this drug creates side effects such as renal injury. The purpose of this work was to assess the influences of gallic acid (GA) on DIC-induced renal injury in rats. Rats were segregated into five groups. Group 1, control group; Group 2 received DIC-only (50 mg/kg bw, i.p.) for 7 consecutive days; Groups 3, received GA-only (100 mg/kg bw, po) for 7 consecutive days; group 4 received DIC (50 mg/kg bw, i.p.) plus GA (50 mg/kg, po) for 7 consecutive days and group 5 received DIC (50 mg/kg bw, i.p.) plus GA (100 mg/kg, po) for 7 consecutive days. The data indicated that the levels of the serum protein carbonyl, sGOT, sGPT, urea, creatinine, uric acid, nitrite content, MDA, serum IL-1β, and the renal IL-1β gene expression were remarkably increased in DIC-only treated animals compared to control group. In the other hand, treatment with gallic acid led to significant improvements in abnormalities of DIC-induced oxidative stress and serum biochemical parameters. Histological changes were also ameliorated by GA oral administration. The results indicated that oral injection of GA could alleviate the noxious effects of DIC on the antioxidant defense system and renal tissue.


Bilingualism in infancy: first steps in perception and comprehension.
Many children grow up in bilingual families and acquire two first languages. Emerging research is advancing the view that the capacity to acquire language can be applied equally to two languages as to one but that bilingual and monolingual acquisition nonetheless differ in some nontrivial ways. To probe the first steps toward acquisition, researchers recently have begun to use experimental methods to study preverbal bilingual infants. We review the literature in this growing field, focusing on how infants growing up bilingual use surface acoustic information to separate, categorize and begin to learn their two languages. These new data invite the expansion of standard linguistic theories to account for how a single architecture can support the acquisition of two languages simultaneously.


A collaborative approach to reducing stress among staff.
Stress has been identified as an important issue among residential carers looking after individuals with learning disabilities. This article describes the implementation of a stress-management programme on a residential site for people with learning disabilities, which significantly reduced levels of anxiety and burnout.


Populations of the Minor α-Conformation in AcGXGNH2 and the α-Helical Nucleation Propensities.
Intrinsic backbone conformational preferences of different amino acids are important for understanding the local structure of unfolded protein chains. Recent evidence suggests α-structure is relatively minor among three major backbone conformations for unfolded proteins. The α-helices are the dominant structures in many proteins. For these proteins, how could the α-structures occur from the least in unfolded to the most in folded states? Populations of the minor α-conformation in model peptides provide vital information. Reliable determination of populations of the α-conformers in these peptides that exist in multiple equilibriums of different conformations remains a challenge. Combined analyses on data from AcGXPNH2 and AcGXGNH2 peptides allow us to derive the populations of PII, β and α in AcGXGNH2. Our results show that on average residue X in AcGXGNH2 adopt PII, β, and α 44.7%, 44.5% and 10.8% of time, respectively. The contents of α-conformations for different amino acids define an α-helix nucleation propensity scale. With derived PII, β and α-contents, we can construct a free energy-conformation diagram on each AcGXGNH2 in aqueous solution for the three major backbone conformations. Our results would have broad implications on early-stage events of protein folding.


Predictive value of CD8/FOXP3 ratio combined with PD-L1 expression for radiosensitivity in patients with squamous cell carcinoma of the larynx receiving definitive radiation therapy.
Little is known about immune-related radiosensitivity in patients with squamous cell carcinoma of the larynx (SCC-L) treated with radiation therapy (RT). We retrospectively reviewed 91 patients with SCC-L treated with RT or chemoradiation therapy and performed immunohistochemical examination to analyze PD-L1 level on tumor cells, CD4+ tumor-infiltrating lymphocytes (TILs), CD8+ TIL, and FOXP3+ TIL using pretreated biopsy specimens. The association between these immune-related parameters and radiosensitivity was evaluated. Multivariate analyses showed that high CD8/FOXP3 ratio combined with negative PD-L1 expression was an independent and significant favorable predictive factor for local control, compared with the other groups. We showed that high CD8/FOXP3 ratio combined with negative PD-L1 expression might be a useful biomarker of radiosensitivity in patients with SCC-L receiving definitive RT. We propose that coassessment of CD8/FOXP3 ratio and PD-L1 expression level in tumor cells can help predict potential radiosensitivity in patients with SCC-L.


Development and characterization of a highly selective neuropeptide Y Y5 receptor agonist radioligand: [125I][hPP1-17, Ala31, Aib32]NPY.
(1) The existence of multiple classes of neuropeptide Y (NPY) receptors (Y(1), Y(2), Y(4), Y(5) and y(6)) is now well established. However, one of the major difficulties in the study of these various receptor subtypes is the current lack of highly selective probes to investigate a single receptor class. Up to most recently, this was particularly true for the Y(4) and Y(5) subtypes. (2) [hPP(1-17), Ala(31), Aib(32)]NPY, the first highly selective Y(5) agonist, was iodinated using the chloramine T method and purified by high-pressure liquid chromatography. (3) Binding performed in rat brain homogenates revealed that equilibrium was reached after 120 min (t(1/2)=21 min) and 60 min (t(1/2)=12 min) at 25 and 100 pM [(125)I][hPP(1-17), Ala(31), Aib(32)]NPY, respectively. (4) Isotherm saturation binding experiments demonstrated that [(125)I][hPP(1-17), Ala(31), Aib(32)]NPY binds to an apparent single population with high-affinity (K(D) of 1.2 and 1.7 nM) and low-capacity (B(max) of 14+/-3 fmol/100,000 cells and 20+/-5 fmol/mg protein) sites in Y(5) receptor HEK293-transfected cells and rat brain membrane homogenates, respectively. No specific [(125)I][hPP(1-17), Ala(31), Aib(32)]NPY binding sites could be detected in Y(1), Y(2) or Y(4) receptors transfected HEK293 cells, demonstrating the high selectivity of this ligand for the Y(5) subtype. (5) Competition binding experiments performed in rat brain membrane homogenates and Y(5)-receptor transfected HEK293 cells demonstrated that specific [(125)I][hPP(1-17), Ala(31), Aib(32)]NPY binding was competed with high affinity by Y(5) agonists and antagonists such as [Ala(31), Aib(32)]NPY, [hPP(1-17), Ala(31), Aib(32)]NPY, hPP, CGP71683A and JCF109, but not by Y(1) (BIBP3226), Y(2) (BIIE0246) and Y(1)/Y(4) (GR231118) preferential ligands. (6) Taken together, these data demonstrate that [(125)I][hPP(1-17), Ala(31), Aib(32)]NPY is the first highly selective Y(5) radioligand to be developed. This new probe should prove most useful for further detailed studies of the molecular and pharmacological properties of this receptor subtype in brain and peripheral tissues.


Oncological effectiveness of bladder-preserving trimodal therapy versus radical cystectomy for the treatment of muscle-invasive bladder cancer: a system review and meta-analysis.
Radical cystectomy (RC) is the gold standard treatment for muscle-invasive bladder cancer (MIBC). As a bladder-preservation option recommended in guidelines, trimodal therapy (TMT) has become increasingly popular in recent years. However, it is still uncertain whether TMT can provide comparable oncologic outcomes to RC. Therefore, it is imperative to evaluate whether TMT yields comparable outcomes to RC. We conducted a systematic search of Web of Science, MEDLINE, the Cochrane Library, and EMBASE databases up to June 2023 to identify studies that met our inclusion criteria. The primary outcome measures evaluated in this study were overall survival (OS) and cancer-specific survival (CSS). The study quality was evaluated independently by two authors, and data were extracted accordingly. After excluding duplicates and ineligible articles, our meta-analysis included seven studies involving 3,489 and 13,877 patients in the TMT and RC groups, respectively. Short-term overall survival rates were comparable between the groups, but beyond 5 and > 10-years, the RC group had significantly higher overall survival rates compared to the TMT group. In terms of cancer-specific survival, there was no significant difference between the groups at 1-year follow-up, but from the second year onwards, including the 5-year and > 10-year nodes, the RC group had significantly better outcomes compared to the TMT group. The treatment effect of RC is better than that of TMT. Unless the patient can't tolerate RC or has a strong desire to preserve the bladder, RC should be chosen over TMT in treatment, and patients undergoing TMT should be closely followed up.


Apolipoprotein B is a globular protein--morphological studies by electron microscopy.
Water-soluble apolipoprotein B was prepared from fresh plasma by quick isolation of low density lipoproteins and immediate delipidization under non-oxidative conditions. The denatured protein in 6 M guanidine X HCl was reduced and carboxymethylated, dialyzed through 6 M urea/preservatives and to 1% ammonium acetate/0.05% EDTA/0.13% epsilon-amino caproic acid, pH 7.3 under N2 at 4 degrees C. The morphological studies were carried out by electron microscopy with negative staining and freeze fracture. Both these techniques showed that apolipoprotein B is a globular protein with average diameter of 11.48 +/- 1.25 nm (n = 978). The M.W. of apolipoprotein B calculated from this particle size was comparable to that from amino acid sequence.


Value of fluoroscopy in the detection of coronary stenosis: influence of age, sex, and number of vessels calcified on diagnostic efficacy.
Although fluoroscopically detected coronary artery calcification is known to correlate with the presence of coronary artery stenosis, age, sex, and extent of calcification influence the strength of this association. To clarify its diagnostic potential, we performed fluoroscopy before coronary angiography in 600 patients and analyzed the results according to all three factors simultaneously. The sensitivity of fluoroscopy for significant stenosis exceeded 65% in all groups except women less than 45 years of age. Specificity exceeded 90% in patients less than 45 years and 85% in patients less than 55 years of age, and declined significantly with age. The number of vessels calcified was an important determinant of predictive value, except in those less than 45 years of age in whom even a single mild calcification markedly increased the chance of stenosis. In patients aged 45 to 64 years, calcification of two or three vessels substantially increased the chances of stenosis, but single-vessel calcification increased the risk only slightly. In patients more than 65 years of age, fluoroscopy was not helpful in detecting stenosis, regardless of the number of vessels calcified. Our findings were similar in men and women. We conclude that if both age and the number of vessels calcified are considered, fluoroscopy can provide useful information regarding the presence of stenosis in young and middle-aged patients.


Feasibility of reduced-intensity cord blood transplantation as salvage therapy for graft failure: results of a nationwide survey of adult patients.
To evaluate whether rescue with cord blood transplantation (CBT) could improve the poor survival after graft failure (GF), we surveyed the data of 80 adult patients (median age, 51 years) who received CBT within 3 months of GF (primary 64, secondary 16), with fludarabine-based reduced-intensity regimens with or without melphalan, busulfan, cyclophosphamide, and/or 2-4 Gy total-body irradiation (TBI). A median number of 2.4 × 10(7)/kg total nucleated cells (TNC) were infused, and among the 61 evaluable patients who survived for more than 28 days, 45 (74%) engrafted. The median follow-up of surviving patients was 325 days, and the 1-year overall survival rate was 33% despite poor performance status (2-4, 60%), carryover organ toxicities (grade 3/4, 14%), and infections (82%) prior to CBT. Day 100 transplantation-related mortality was 45%, with 60% related to infectious complications. Multivariate analysis showed that the infusion of TNC ≥2.5 × 10(7)/kg and an alkylating agent-containing regimen were associated with a higher probability of engraftment, and that high risk-status at the preceding transplantation and grade 3/4 organ toxicities before CBT were associated with an increased risk of mortality. In conclusion, in an older population of patients, our data support the feasibility of CBT with a reduced-intensity conditioning regimen for GF.


Development of a direct mapping model between hedonic rating and facial responses by dynamic facial expression representation.
Consumer tests are one of the most important activities in product development. More evidence indicates that consumer emotions in real life are mostly driven by unconscious mechanisms, and implicit measurements are regarded as beneficial by an increasing number of sensory and consumer scientists. Nonverbal manner such as facial expression analysis is a supplement to the declarative method and brings very insightful results. Up until now, the facial expression analysis for consumers' acceptance identification is limited to investigate the relationship between hedonic rating and facial expression descriptors, such as facial coding system (FACS or MAX), discrete facial expressions (i.e. happiness, sadness, surprise, fear, anger, and disgust), and affective dimensional model (valence and activation). In this study, we attempt to develop a direct mapping model between the hedonic rating and facial responses evoked by various taste stimuli. Basic taste solutions (sourness, sweetness, bitterness, umami, and saltiness) with six levels, and five types of juice are used as stimuli. Firstly, the hedonic rating categories are defined based on the nine-point hedonic scale, with a coarse-to-fine division of scale levels based on two directions of like and dislike. Secondly, the facial dynamic optical flow method is employed to analyze facial characteristics of the subjects' facial responses evoked by taste stimuli. And the genetic algorithm is conducted to select facial regions that have high contribution to hedonic rating identification. It indicates that the texture changes of eye area, wrinkles at the nasal root, and mouth area can effectively reflect the facial reaction corresponding to hedonic rating. The research shows that it is feasible to establish a direct mapping model between hedonic rating and facial responses. The hedonic rating can be predicted through automatic facial reading technology, without extra transformation from predefined emotional models. In general, this is the first try to discuss the direct prediction of hedonic rating through facial expressions up to now, and it is a complex problem due to various influence factors.


Acute obstruction of the renal collecting system: the intrarenal resistive index is a useful yet time-dependent parameter for diagnosis.
The aim of this study was to determine whether the intrarenal resistive index (RI) can be used for the diagnosis of acute obstruction in patients with renal colic and to determine whether the index is time-related. Seventy patients referred to the Emergency Department with acute renal colic and without known associated renal disease underwent duplex Doppler ultrasonography to determine the intrarenal RI at the symptomatic and asymptomatic side. The age range of the patients was 18-72 years. An RI greater than 0.68 and/or an interrenal difference in RI greater than 0.06 and/or an increase in RI of more than 11% compared with the normal side proved reliable cut-off values to diagnose acute renal obstruction. In addition, time dependency of the increase in RI was noted. No significant differences were observed within the first 6 h after the onset of symptoms. From 6 to 48 h, however, the mean RI in the affected kidney (0.70 +/- 0.06; mean +/- SD) was significantly different from that in the normal kidney (0.59 +/- 0.04) (P < 0.001). In the same period the mean difference in RI was 0.08-0.13 (P < 0.001). After 48 h the sensitivity of RI dropped substantially. It is concluded that renal duplex Doppler ultrasonography is useful for diagnosing acute renal obstruction between 6 and 48 h after the onset of symptoms.


Design of mechanical-robust phosphorescence materials through covalent click reaction.
It remains a great challenge to engineer materials with strong and stable interactions for the simultaneously mechanical-robust and room temperature phosphorescence-efficient materials. In this work, we demonstrate a covalent cross-linking strategy to engineer mechanical-robust room temperature phosphorescence materials through the B-O click reaction between chromophores, polyvinyl alcohol matrix and inorganic layered double hydroxide nanosheets. Through the covalent cross-linkage between the organic polyvinyl alcohol and inorganic layered double hydroxide, a polymeric composite with ultralong lifetime up to 1.45 s is acquired based on the inhibited non-radiative transition of chromophores. Simultaneously, decent mechanical strength of 97.9 MPa can be realized for the composite materials due to the dissipated loading stress through the covalent-bond-accommodated interfacial interaction. These cross-linked composites also exhibit flexibility, processability, scalability and phosphorescence responses towards the mechanical deformation. It is anticipated that the proposed covalent click reaction could provide a platform for the design and modulation of composites with multi-functionality and long-term durability.


The imprinted Igf2-Igf2r axis is critical for matching placental microvasculature expansion to fetal growth.
In all eutherian mammals, growth of the fetus is dependent upon a functional placenta, but whether and how the latter adapts to putative fetal signals is currently unknown. Here, we demonstrate, through fetal, endothelial, hematopoietic, and trophoblast-specific genetic manipulations in the mouse, that endothelial and fetus-derived IGF2 is required for the continuous expansion of the feto-placental microvasculature in late pregnancy. The angiocrine effects of IGF2 on placental microvasculature expansion are mediated, in part, through IGF2R and angiopoietin-Tie2/TEK signaling. Additionally, IGF2 exerts IGF2R-ERK1/2-dependent pro-proliferative and angiogenic effects on primary feto-placental endothelial cells ex vivo. Endothelial and fetus-derived IGF2 also plays an important role in trophoblast morphogenesis, acting through Gcm1 and Synb. Thus, our study reveals a direct role for the imprinted Igf2-Igf2r axis on matching placental development to fetal growth and establishes the principle that hormone-like signals from the fetus play important roles in controlling placental microvasculature and trophoblast morphogenesis.


Immune induction strategies to enhance responses to PD-1 blockade: lessons from the TONIC trial.
Programmed cell death protein 1 (PD-1) blockade is only effective in a minority of patients, prompting the search for combinatorial therapies that increase responses. Identifying effective combinations requires lengthy testing and so far has shown few successes. To accelerate progress Voorwerk and colleagues (Nat Med. 25(6):920-8, 2019) used an adaptive trial design to compare 4 short-course therapies (radiotherapy, cyclophosphamide, cisplatin and doxorubicin) for their ability to improve the tumor immune microenvironment and enhance responses to subsequent PD-1 blockade in women with metastatic triple negative breast cancer, a disease with low response rate to PD-1 blockade. They reported the first phase of the trial that enrolled 12 to 17 patients per arm to "pick the winner" induction treatment. Higher objective response rates (ORR) compared to no induction were observed only in the arm containing doxorubicin, which proceeded to phase II. These results raise a number of questions about testing local versus systemic induction treatments and whether sequencing with PD-1 blockade is appropriate in light of evidence supporting concomitant treatment, at least for radiotherapy. Small imbalances in baseline characteristics can also influence results obtained with limited numbers of patients per arm. We hope that these considerations will help future adaptive, signal-finding combination immunotherapy studies.


Asymptomatic carotid stenosis. Immediate and long-term results after prophylactic endarterectomy.
1. A review of the immediate and long-term results of prophylactic carotid endarterectomy for asymptomatic lesions of 78 carotid arteries in 72 patients between 1961 and 1976 is presented. 2. The inhospital operative mortality was zero. Two patients experienced postoperative transient neurologic deficit with complete recovery (2.6 per cent). There were no postoperative strokes. 3. Late follow-up data demonstrated that in only one patient did a stroke subsequently develop appropriate to the operative side, and it occurred 4 years after operation. Life table analysis for neurologic events carried out for up to 15 years indicated a 96 per cent stroke-free status of the surviving patients. 4. A 42 month survival rate of 83 per cent in patients treated by prophylactic carotid endarterectomy represented a statistically significant improvement over the 67 per cent survival of a comparable group of patients reported on in the literature. 5. Prophylactic carotid endarterectomy in the experience of vascular surgeons who can offer a low operative morbidity and mortality appears to be reasonable therapy in preventing stroke and prolonging survival until a randomized controlled study comparing surgery with the natural history of untreated patients shows evidence to the contrary.


Strength training as superior, dose-dependent and safe prevention of acute and overuse sports injuries: a systematic review, qualitative analysis and meta-analysis.
This review aims to analyse strength training-based sports injury prevention randomised controlled trials (RCT) and present best evidence recommendations for athletes and future research. A priori PROSPERO registration; CRD42015006970. Systematic review, qualitative analysis and meta-analysis. Sorting of studies and quality assessments were performed by two independent authors. Qualitative analyses, relative risk (RR) estimate with robustness and strength of evidence tests, formal tests of publication bias and post-hoc meta-regression were performed. PubMed, Embase, Web of Science and SPORTDiscus were searched to July 2017. RCTs on strength training exercises as primary prevention of sports injuries. Six studies analysed five different interventions with four distinct outcomes. 7738 participants aged 12-40 years were included and sustained 177 acute or overuse injuries. Studies were published in 2003-2016, five from Europe and one from Africa. Cluster-adjusted intention-to-treat analysis established RR 0.338 (0.238-0.480). The result was consistent across robustness tests and strength of evidence was high. A 10% increase in strength training volume reduced the risk of injury by more than four percentage points. Formal tests found no publication bias. The included studies were generally well designed and executed, had high compliance rates, were safe, and attained consistently favourable results across four different acute and overuse injury outcomes despite considerable differences in populations and interventions. Increasing strength training volume and intensity were associated with sports injury risk reduction. Three characteristically different approaches to prevention mechanisms were identified and incorporated into contemporary strength training recommendations.


Aboriginal spirituality: symbolic healing in Canadian prisons.
Symbolic healing is a complex phenomenon that is still relatively poorly understood. This paper documents a process of symbolic healing which is occurring in Canadian penitentiaries, and which involves Aboriginal offenders in cultural awareness and educational programs. The situation is compounded, however, by the existence of offenders from diverse Aboriginal cultural backgrounds with differing degrees of orientation to Aboriginal and Euro-Canadian cultures. Participants must first receive the necessary education to allow them to identify with the healing symbols so that healing may ensue, and both the healers and the patients must engage in a process of redefining their cultures in search of a common cultural base.


Acute confusional states and depression treated with maprotiline mesylate. Report of 4 patients successfully treated in an intensive care unit.
Four patients admitted to hospital with multiple injuries developed psychiatric symptoms after an initially favourable response to intensive therapy. Alterations in the level of consciousness and behavioural pattern were observed, associated with the presence of acute depression, possibly endogenous in origin. Within 24--48 hours of intravenous administration of maprotiline mesylate (Ludiomil, Ciba), a tetracyclic antidepressant drug, considerable improvement was noted in all 4 patients, with regard to both the depressive state and the clouding of consciousness. The importance of recognizing psychiatric disorders in severely ill patients in an intensive therapy environment is stressed.


(3,3'-{(1E,1'E)-1,1'-[Ethane-1,2-diylbis(azan-1-yl-1-yl-idene-κN)]bis-(ethan-1-yl-1-yl-idene)}di-pyrazine 1-oxide-κN (4))bis-(nitrato-κO)nickel(II) monohydrate.
In the title complex, [Ni(NO3)2(C14H16N6O2)]·H2O, the Ni(II) atom, lying on a twofold rotation axis, is coordinated by a tetra-dentate 3,3'-{(1E,1'E)-1,1'-[ethane-1,2-diylbis(azan-1-yl-1-yl-idene)]bis-(ethan-1-yl-1-yl-idene)}di-pyrazine 1-oxide ligand and two mutually trans monodentate nitrate anions in a distorted o-cta-hedral geometry. The lattice water mol-ecule is located on a twofold rotation axis. The complex mol-ecules are linked by the water mol-ecules through O-H⋯O hydrogen bonds into a chain along [001]. Further C-H⋯O hydrogen bonds lead to the formation of a three-dimensional network.


Health management and patients who lack capacity: forms of guardianship in European health policy.
The focus of healthcare debate has in recent years shifted from doctors and healthcare professionals in general to patients and the principle of patient self-determination. Patient competence therefore plays an increasingly central role in the legal framework of many Europeans countries. Consequently, healthcare policy has to address the possible repercussions of a non-systematic approach to cases of patient incapacity. The diverse nature of the experiences of the mentally or physically disadvantaged clearly raises problems for the healthcare professional. In this setting, we examine Italy's Law no. 6/2004 from a comparative perspective, in particular analysing legislation in the same area from Spain, France, Great Britain and the Netherlands.


External radiotherapy for prostatic cancers.
We present the update of the recommendations of the French society of oncological radiotherapy on external radiotherapy of prostate cancer. External radiotherapy is intended for all localized prostate cancers, and more recently for oligometastatic prostate cancers. The irradiation techniques are detailed. Intensity-modulated radiotherapy combined with prostate image-guided radiotherapy is the recommended technique. A total dose of 74 to 80Gy is recommended in case of standard fractionation (2Gy per fraction). Moderate hypofractionation (total dose of 60Gy at a rate of 3Gy per fraction over 4 weeks) in the prostate has become a standard of therapy. Simultaneous integrated boost techniques can be used to treat lymph node areas. Extreme hypofractionation (35 to 40Gy in five fractions) using stereotactic body radiotherapy can be considered a therapeutic option to treat exclusively the prostate. The postoperative irradiation technique, indicated mainly in case of biological recurrence and lymph node involvement, is detailed.


Efficacy and safety of 1% and 2% rebamipide clear solution in dry eye disease: a multicenter randomized trial.
To evaluate the efficacy of 1% and 2% rebamipide clear solution in the treatment of dry eye disease (DED). Two hundred twenty patients with DED were randomly assigned to one of three groups: the 1% rebamipide, 2% rebamipide, or placebo (eye drops containing the same ingredients, except for the active components). Each eye drop was instilled four times daily for 12 weeks. Changes in tear film break-up time (TBUT), corneal and conjunctival staining score, Schirmer 1 test, and the Ocular Surface Disease Index (OSDI) from baseline to 12-week visit between the study groups were compared for efficacy assessment. The mean age of study patients was 43.8±14.2 years. The 1% and 2% rebamipide groups showed greater improvement in TBUT (1.99±1.87 and 2.02±2.21 s) at 12 weeks from baseline than the placebo group (1.25±2.93 s). The 2% rebamipide group showed greater improvement in the corneal staining score (- 3.15±2.00) at 12 weeks from baseline than the placebo group (- 2.85±1.80). The 1% and 2% rebamipide groups showed improvement in Schirmer 1 test (1.27±3.86 and 1.50±4.14 mm) at 12 weeks of treatment, but not the placebo group (0.55±2.99 mm). Both the rebamipide groups and the placebo group showed significantly improved OSDI after treatment for 12 weeks; however, there was no significant difference among the three groups. 1% and 2% rebamipide clear solutions are an effective therapeutic option for improving TBUT and tear volume, and stabilizing the corneal staining score in DED.


COVID-19-related knowledge influences mental health, self-care behaviors, and quality of life among elderly with non-communicable diseases in Northern Thailand.
A growing body of research shows that individuals with non-communicable diseases (NCDs), such as hypertension, diabetes, hypercholesterolemia, and heart disease, are more likely to suffer from severe COVID-19 and, subsequently, death. The purpose of this study was to assess the influence of COVID-19-related knowledge on mental health, healthcare behaviors, and quality of life among the elderly with NCDs in Northern Thailand. In this cross-sectional study, the participants were 450 elderly people with NCDs, living in the Chiang Rai province, Northern Thailand. Random sampling was applied to select the subjects. Data collection included demographic information, COVID-19-related knowledge, healthcare behaviors, the Suanprung Stress Test-20, the Thai General Health Questionnaire (GHQ-28) for the assessment of mental health, and the Thai version of the World Health Organization Quality of Life-BREF. Almost half of the participants (45.6%) had poor knowledge about COVID-19. More than half of the sample had high stress (52.0%) and a low score in healthcare behaviors (64.9%), while approximately one-third of the participants had mental health problems (34.0%). The overall quality of life during the COVID-19 pandemic was moderate (70.7%). The score of COVID-19-related knowledge was significantly correlated with scores of stress (r = -0.85), mental health (r = -0.74), healthcare behaviors (r = 0.50), and quality of life (r = 0.33). Multiple linear regression found that history of COVID-19 detection and COVID-19-related knowledge were associated with scores of stress and quality of life (p < 0.05). Multiple logistic regression showed that history of COVID-19 detection (OR = 4.48, 95% CI = 1.45-13.84) and COVID-19-related knowledge (OR = 0.23, 95% CI = 0.17-0.31) were associated with mental health problem (p < 0.05). The findings emphasize the importance of COVID-19-related knowledge concerning the improvement of self-care behaviors and quality of life in the elderly population with NCDs during the pandemic, especially due to the high rate of stress and mental health problems documented in our sample. Health education interventions for this vulnerable population should be organized.


Clinical response to peroral endoscopic myotomy in patients with idiopathic achalasia at a minimum follow-up of 2 years.
The recently developed technique for peroral endoscopic myotomy (POEM) has been shown to be effective in several short-term studies. Longer term outcome data are largely non-existent. To systematically report clinical outcome with a minimum post-POEM follow-up of 2 years. All patients treated consecutively by POEM for achalasia at three centres were retrospectively analysed, with a minimum follow-up of 2 years. The main outcome was the rate of POEM failures (Eckardt score >3) related to follow-up time. Of 85 patients treated, five (5.9%) cases were excluded due to protocol violation or loss to follow-up; the remaining 80 patients (mean age 44.9 years, 54% men) were followed clinically for 29 months (range 24-41). Initial clinical response was observed in 77 cases (96.3%). Clinical recurrences (later failures) were seen in a further 14 cases (17.7%), accounting for a total failure rate of 21.5%. In a multivariate analysis, age and endoscopic reflux signs were independent predictors of treatment success. Of the 17 failures, eight were among the first 10 cases treated in the participating centres. Reflux-associated sequelae included one case of a severe reflux-associated stricture requiring dilatation, and two patients with minor transient Eckardt score elevations curable by proton pump inhibitor (PPI) treatment. Endoscopic signs of reflux oesophagitis, mostly Los Angeles grade A/B, were seen in 37.5% (37/72) at the 2-year control. In this multicentre retrospective analysis, a high initial success rate of POEM is followed by a mid-term recurrence rate of 18%. Reflux oesophagitis, albeit mild, is frequent and should probably be treated by regular low-dose PPI therapy. NCT 01405417 (UKE study).


Metagenomic analysis reveals the size effect of magnetite on anaerobic digestion of waste activated sludge after thermal hydrolysis pretreatment.
Although magnetite has been widely investigated in anaerobic digestion (AD), its role in the practical AD of waste-activated sludge (WAS) after thermal hydrolysis pretreatment (THP) and its size effect remain unclear. In this study, magnetite with four different particle sizes was added during the AD of WAS after THP. With the reduction of magnetite particle size, cumulative methane production was increased, while the optimal dosage of magnetite decreased, with 0.1 μm magnetite at an optimal dosage of 2 g/L achieving the highest cumulative methane production increase of 111.97 % compared with the blank group (without magnetite). Smaller magnetite particles increased α-glucosidase and protease activities, coenzyme F420 concentration, and electron-transport system activity (20.30 %, 173.02 %, 60.39 % and 158.08 % higher respectively than the blank group). The size of magnetite also influenced the establishment of direct interspecies electron transfer (DIET) during AD. Based on the analysis of the pilA gene abundance, magnetite with a large particle size could promote the formation of e-pili in syntrophic electroactive bacteria (Clostridium, Syntrophomonas, and Pseudomonas) and methanogens (Methanospirillum), thereby completing electron transfer. However, small-sized magnetite particles stimulated DIET by enhancing the secretion of conductive proteins in extracellular polymeric substances and membrane-bound enzymes (Fpo) in Methanosarcina.


A new approach to smiling deformity: cutting of the superior part of the orbicularis oris.
A diagnosis of an aesthetic smiling deformity, which is functional rather than anatomic, is essential for provision of the best treatment in rhinoplasty. Smiling deformity consists of three elements: (a) the nasal tip tending to retrodisplace and rotate inferiorly; (b) the lower part of the upper lip moving superiorly; and (c) a horizontal groove occurring in the midphiltral area. An active depressor septi and orbicularis muscle can accentuate a drooping nasal tip and shorten the upper lip during smiling. Downward movement of the nasal tip and a sharper nasolabial angle usually are aesthetically unpleasant. During the study period (January 2000 to January 2004), the authors identified 38 patients with smiling deformities, 16 of whom underwent dissection and transposition of the paired depressor septi during rhinoplasty. The remaining 22 patients experienced hyperactivity of both the depressor septi and orbicularis muscles, as diagnosed by a descending nasal tip and a shortened upper lip at animation. These patients underwent a modification of the depressor septi and orbicularis muscles. No relapse was evident up to 2 years postoperatively. Repositioning of the depressor septi nasi muscle improved only mild cases. However, modification of the orbicularis and depressor septi muscles was a valuable adjunct to rhinoplasty for moderate and severe forms of smiling deformity. The new approach for smiling deformity provided an aesthetically pleasant appearance for the patient both at rest and when smiling.


New insights into drug resistance in cancer.
New findings by Kavallaris et al. characterize mechanisms of resistance to epothilones and paclitaxel in cell lines. One significant discovery is a novel tubulin point mutation positioned outside the paclitaxel binding site, which confers a high degree of drug resistance.


Epidemiologic Features, Risk Factors, and Outcomes of Respiratory Infection in Patients with Acute Stroke.
The objective of this study is to explore risk factors for stroke-associated pneumonia (SAP) and their impact on prognosis. The data collected from a retrospective review of 257 patients with acute cerebral infarction between January 2014 and December 2016 were included in this study. Data were collected for clinical, demographic, and coexisting parameters. Univariate and multivariate logistic regression analyses were performed. Elderly age (odds ratio [OR]: 1.096, 95% confidence interval [CI]: 1.023-1.174), dysphagia (OR: 2.805, 95% CI: 1.614-4.875), and long-term bedridden status (OR: 120.425, 95% CI: 29.689-488.466) were significantly associated with SAP. Among these risk factors, long-term bedridden status had the highest prognostic value (area under the curve = 0.908) for developing SAP. Furthermore, pneumonia, in turn, strongly predicted poor prognosis at discharge and after 3 years. Pneumonia seems to be a major complication in stroke patients. A better understanding of its risk factors is important for prevention and early recognition. Further studies are needed to clarify the optimal preventive treatment for SAP patients.


AFM nanoindentation of protein shells, expanding the approach beyond viruses.
The archetypical protein nanoshell is the capsid that surrounds viral genomes. These capsids protect the viral RNA or DNA and function as transport vehicle for their nucleic acid. The material properties of a variety of viral capsids have been probed by Atomic Force Microscopy. In particular nanoindentation measurements revealed the complex mechanics of these shells and the intricate interplay of the capsid with its genomic content. Furthermore, effects of capsid protein mutations, capsid maturation and the effect of environmental changes have been probed. In addition, biological questions have been addressed by AFM nanoindentation of viruses and a direct link between mechanics and infectivity has been revealed. Recently, non-viral protein nanoshells have come under intense scrutiny and now the nanoindentation approach has been expanded to such particles as well. Both natural as well as engineered non-viral protein shells have been probed by this technique. Next to the material properties of viruses, therefor also the mechanics of encapsulins, carboxysomes, vault particles, lumazine synthase and artificial protein nanoshells is discussed here.


Inhibition of novel β coronavirus replication by a combination of interferon-α2b and ribavirin.
The identification of a novel β coronavirus, nCoV, as the causative agent of severe respiratory illness in humans originating in Saudi Arabia, Qatar and Jordan has raised concerns about the possibility of a coronavirus pandemic similar to that of SARS-CoV. As a definitive treatment regimen has never been thoroughly evaluated for coronavirus infections, there is an urgent need to rapidly identify potential therapeutics to address future cases of nCoV. To determine an intervention strategy, the effect of interferon-α2b and ribavirin on nCoV isolate hCoV-EMC/2012 replication in Vero and LLC-MK2 cells was evaluated. hCoV-EMC/2012 was sensitive to both interferon-α2b and ribavirin alone in Vero and LLC-MK2 cells, but only at relatively high concentrations; however, when combined, lower concentrations of interferon-α2b and ribavirin achieved comparable endpoints. Thus, a combination of interferon-α2b and ribavirin, which are already commonly used in the clinic, may be useful for patient management in the event of future nCoV infections.


Traumatic incarceration of the small bowel: case report.
While bowel injuries associated with blunt abdominal trauma are a well recognized entity, entrapment of bowel between vertebral bodies has seldom been described. The unusual case of traumatic jejunal incarceration between two lumbar vertebrae is presented.


Incidence of Workers' Compensation Claims in Opioid-Using Truck Drivers.
This study examines the relationship between opioid use prevalence and subsequent filing of workers' compensation claims. A retrospective cohort study design was utilized to examine data from drivers' initial commercial driver medical exam, employment data, and workers' compensation claims data. Data from 57,733 over 7 years were analyzed. Drivers who reported opioid use at their initial medical exam visit filed subsequent workers' compensation claims 1.81 times sooner (P = 0.0001; 95% CI 1.34, 2.44) than drivers who did not report opioid use at their CDME when controlling for age, gender, BMI, and diastolic blood pressure. These findings provide information that may aid in improving regulations to control for incidents, training programs to inform professional drivers of factors that increase accident risk and educating prescribers about increased risks of injury among opioid-using drivers.


Three-stage intelligent support of clinical decision making for higher trust, validity, and explainability.
The paper presents a conceptual framework for building practically applicable clinical decision support systems (CDSSs) using data-driven (DD) predictive modelling. With the proposed framework we have tried to fill the gap between experimental CDSS implementations widely covered in the literature and solutions acceptable by physicians in daily practice. The framework is based on a three-stage approach where DD model definition is accomplished with practical norms referencing (scales, clinical recommendations, etc.) and explanation of the prediction results and recommendations. The approach is aimed at increasing the applicability of CDSSs based on DD models through better integration into decision context and higher explainability. The approach has been implemented in software solutions and tested within a case study in type 2 diabetes mellitus (T2DM) prediction, enabling us to improve known clinical scales (such as FINDRISK) while keeping the problem-specific reasoning interface similar to existing applications. A survey was performed to assess and investigate the acceptance level and provide insights on the influences of the introduced framework's element on physicians' behavior.


Survival of cancer cells is maintained by EGFR independent of its kinase activity.
Expression of the epidermal growth factor receptor (EGFR), a receptor tyrosine kinase associated with cell proliferation and survival, is overactive in many tumors of epithelial origin. Blockade of the kinase activity of EGFR has been used for cancer therapy; however, by itself, it does not seem to reach maximum therapeutic efficacy. We report here that in human cancer cells, the function of kinase-independent EGFR is to prevent autophagic cell death by maintaining intracellular glucose level through interaction and stabilization of the sodium/glucose cotransporter 1 (SGLT1).


The Radiological Complications of Short-Segment Pedicle Screw Fixation Combined with Transforaminal Interbody Fusion in the Treatment of Unstable Thoracolumbar Burst Fracture: A Retrospective Case Series Study in Vietnam.
The radiological complications including correction loss and hardware failure of short segment posterior pedicle screw fixation in the treatment of unstable thoracolumbar burst fractures remain a main concern. Several procedures aiming to reinforce the anterior column have been introduced to solve these limitations, including transforaminal interbody fusion (TIF). The purposes of this study were to evaluate the radiological complications of short-segment pedicle screw fixation in combination with transforaminal interbody fusion in the treatment of unstable thoracolumbar burst fractures. This retrospective case series study enrolled patients with isolated unstable thoracolumbar burst fractures, who were treated by posterior short fixation with TIF between January 2013 and January 2017. Patients were followed up for a minimum of one and half years. For evaluation of correction loss, % loss of anterior vertebral body height (%AVB), vertebral kyphotic angle (VA) and regional kyphotic angle (RA) were collected preoperatively, postoperatively and at the final follow-up. Hardware failure was assessed on radiological images at the last follow-up. There were 36 patients who met the inclusion criteria with a mean follow-up duration of 53 months. The mean correction loss of %AVB, VA and RA were 10.2%, 2.9° and 5.6°, respectively. There were 6 patients (16.7%) with hardware failure at the final follow-up. Short-segment posterior pedicle screw fixation with TIF using bone chip grafts does not completely prevent hardware failure and progressive kyphosis in the treatment of unstable thoracolumbar burst fractures.


[From chronic disease to multimorbidity: Which impact on organization of health care].
Healthcare systems are concerned with the growing prevalence of chronic diseases. Single disease approach, based on the Chronic Care Model, is known to improve specific indicators for the targeted disease. However, the co-existence of several chronic disease, or multimorbidity, within a same patient is the most frequent situation. The fragmentation of care, as consequence of the single disease approach, has negative impact on the patient and healthcare professionals. A person centred approach is a method addressing the combination of health issues of each patient. The coordination and synthesis role is key to ensure continuity of care for the patient within a network of healthcare professionals from several settings of care. This function is the main characteristic of an organized first level of care.


Deep learning radiomics of ultrasonography for comprehensively predicting tumor and axillary lymph node status after neoadjuvant chemotherapy in breast cancer patients: A multicenter study.
Neoadjuvant chemotherapy (NAC) can downstage tumors and axillary lymph nodes in breast cancer (BC) patients. However, tumors and axillary response to NAC are not parallel and vary among patients. This study aims to explore the feasibility of deep learning radiomics nomogram (DLRN) for independently predicting the status of tumors and lymph node metastasis (LNM) after NAC. In total, 484 BC patients who completed NAC from two hospitals (H1: 297 patients in the training cohort and 99 patients in the validation cohort; H2: 88 patients in the test cohort) were retrospectively enrolled. The authors developed two deep learning radiomics (DLR) models for personalized prediction of the tumor pathologic complete response (PCR) to NAC (DLR-PCR) and the LNM status (DLR-LNM) after NAC based on pre-NAC and after-NAC ultrasonography images. Furthermore, they proposed two DLRNs (DLRN-PCR and DLRN-LNM) for two different tasks based on the clinical characteristics and DLR scores, which were generated from both DLR-PCR and DLR-LNM. In the validation and test cohorts, DLRN-PCR exhibited areas under the receiver operating characteristic curves (AUCs) of 0.903 and 0.896 with sensitivities of 91.2% and 75.0%, respectively. DLRN-LNM achieved AUCs of 0.853 and 0.863, specificities of 82.0% and 81.8%, and negative predictive values of 81.3% and 87.2% in the validation and test cohorts, respectively. The two DLRN models achieved satisfactory predictive performance based on different BC subtypes. The proposed DLRN models have the potential to accurately predict the tumor PCR and LNM status after NAC. In this study, we proposed two deep learning radiomics nomogram models based on pre-neoadjuvant chemotherapy (NAC) and preoperative ultrasonography images for independently predicting the status of tumor and axillary lymph node (ALN) after NAC. A more comprehensive assessment of the patient's condition after NAC can be achieved by predicting the status of the tumor and ALN separately. Our model can potentially provide a noninvasive and personalized method to offer decision support for organ preservation and avoidance of excessive surgery.


Spontaneous hemobilia in a hemophiliac treated by factor VIII replacement and nasobiliary drainage.
We report a case of spontaneous hemobilia in a hemophilia patient presenting with classical Sandblom's triad of symptoms. Endoscopic retrograde cholangiography was helpful in establishing the diagnosis. Hemobilia subsided with factor VIII replacement and endoscopic nasobiliary drainage. Endoscopic nasobiliary drainage resulted in lysis of the clots in the biliary tree and relief of obstructive jaundice.


Impact of time to antibiotic on hospital stay, intensive care unit admission, and mortality in febrile neutropenia.
To determine if time to antibiotics (TTA) improves outcomes of hospital length of stay, admission to the intensive care unit, and 30-day mortality in adult patients with febrile neutropenia. This retrospective cohort study evaluated the impact of time to antibiotic, in the treatment of febrile neutropenia, on hospital length of stay, admission to the intensive care unit, and 30-day mortality. Cases included were patients 18 years or older hospitalized with febrile neutropenia from August 1, 2006 to July 31, 2016. To adjust for other characteristics associated with hospital length of stay, admission to the intensive care unit, and 30-day mortality, a multivariate analysis was performed. A total of 3219 cases of febrile neutropenia were included. The median hospital length of stay was 7.0 days (IQR 4.1-13.3), rate of intensive care unit admission was 13.6%, and 30-day mortality was 6.6%. Multivariate analysis demonstrated time to antibiotics was not associated with hospital length of stay but was associated with admission to the intensive care unit admission and 30-day mortality. Delays in time to antibiotic of up to 3 hours did not impact outcomes. A shorter time to antibiotic is important in treatment of febrile neutropenia; however, moderate delays in antibiotic administration did not impact outcomes. Further investigation is needed in order to determine if other indicators of infection, in addition to fever, or other supportive management, in addition to antibiotics, are indicated in the early identification and management of infection in patients with neutropenia.


Aucubin promotes bone-fracture healing via the dual effects of anti-oxidative damage and enhancing osteoblastogenesis of hBM-MSCs.
Aucubin (AU), an iridoid glucoside isolated from many traditional herbal medicines, has anti-osteoporosis and anti-apoptosis bioactivities. However, the effect of AU on the treatment of bone-fracture remains unknown. In the present study, the aims were to investigate the roles and mechanisms of AU not only on osteoblastogenesis of human bone marrow-derived mesenchymal stromal cells (hBM-MSCs) and anti-oxidative stress injury in vitro, but also on bone-fracture regeneration by a rat tibial fracture model in vivo. CCK-8 assay was used to assess the effect of AU on the viability and proliferation of hBM-MSCs. The expression of specific genes and proteins on osteogenesis, apoptosis and signaling pathways was measured by qRT-PCR, western blotting and immunofluorescence analysis. ALP staining and quantitative analysis were performed to evaluate ALP activity. ARS and quantitative analysis were performed to evaluate calcium deposition. DCFH-DA staining was used to assess the level of reactive oxygen species (ROS). A rat tibial fracture model was established to validate the therapeutic effect of AU in vivo. Micro-CT with quantitative analysis and histological evaluation were used to assess the therapeutic effect of AU locally injection at the fracture site. Our results revealed that AU did not affect the viability and proliferation of hBM-MSCs. Compared with control group, western blotting, PCR, ALP activity and calcium deposition proved that AU-treated groups promoted osteogenesis of hBM-MSCs. The ratio of phospho-Smad1/5/9 to total Smad also significantly increased after treatment of AU. AU-induced expression of BMP2 signaling target genes BMP2 and p-Smad1/5/9 as well as of osteogenic markers COL1A1 and RUNX2 was downregulated after treating with noggin and LDN193189. Furthermore, AU promoted the translocation of Nrf2 from cytoplasm to nucleus and the expression level of HO1 and NQO1 after oxidative damage. In a rat tibial fracture model, local injection of AU promoted bone regeneration. Our study demonstrates the dual effects of AU in not only promoting bone-fracture healing by regulating osteogenesis of hBM-MSCs partly via canonical BMP2/Smads signaling pathway but also suppressing oxidative stress damage partly via Nrf2/HO1 signaling pathway.


Abnormal sympathoadrenal development and systemic hypotension in PHD3-/- mice.
Cell culture studies have implicated the oxygen-sensitive hypoxia-inducible factor (HIF) prolyl hydroxylase PHD3 in the regulation of neuronal apoptosis. To better understand this function in vivo, we have created PHD3(-/-) mice and analyzed the neuronal phenotype. Reduced apoptosis in superior cervical ganglion (SCG) neurons cultured from PHD3(-/-) mice is associated with an increase in the number of cells in the SCG, as well as in the adrenal medulla and carotid body. Genetic analysis by intercrossing PHD3(-/-) mice with HIF-1a(+/-) and HIF-2a(+/-) mice demonstrated an interaction with HIF-2alpha but not HIF-1alpha, supporting the nonredundant involvement of a PHD3-HIF-2alpha pathway in the regulation of sympathoadrenal development. Despite the increased number of cells, the sympathoadrenal system appeared hypofunctional in PHD3(-/-) mice, with reduced target tissue innervation, adrenal medullary secretory capacity, sympathoadrenal responses, and systemic blood pressure. These observations suggest that the role of PHD3 in sympathoadrenal development extends beyond simple control of cell survival and organ mass, with functional PHD3 being required for proper anatomical and physiological integrity of the system. Perturbation of this interface between developmental and adaptive signaling by hypoxic, metabolic, or other stresses could have important effects on key sympathoadrenal functions, such as blood pressure regulation.


The constitutive K+ pump in Serratia marcescens.
Transport of K+ and H+ in the anaeronically and aerobically grown bacterium Serratia marcescens has been studied. The volumes of one cell of the anaerobically and aerobically grown bacterium were 3.7 X 10(-13) cm3 and 2.4 X 10(-13) cm3, respectively. Irrespective of the growth conditions the bacteria manifested the same respiration rate. However, the values of membrane potential for the anaerobically and aerobically grown bacterium were different and equal to -130 mV and -175 mV (interior negative), respectively, in the absence of an exogenic energy source. KCN + DCCD decreases delta psi down to almost zero in both species. DCCD alone decreases delta psi partially in anaerobes and increases delta psi in aerobes, whereas KCN alone reduces delta psi partially in both species. The introduction of glucose into the medium containing K+ reduces the absolute value of delta psi to [-160] mV in aerobes and to [-20] mV in anaerobes. The effect is not observed without external K+. In the presence of arsenate a delta psi is not reduced after the addition of glucose. At pH 7.5-7.8 the ATP level in aerobes grows notably faster than in anaerobes. The H+ extrusion becomes intensified when K+ uptake is activated by the increase in external osmotic pressure. Apparent Km and Vmax for K+ accumulation are 1.2 mM and 0.4 mM.min-1.g-1. The decrease of delta psi by glucose or KCN + DCCD have no effect on the K+ uptake whereas CCCP inhibits potassium accumulation. At the same time, arsenate stabilizes the delta psi value, but blocks K+ uptake. The accumulation of K+ correlates with the potassium equilibrium potential of -200 mV calculated according to the Nernst equation, whereas the delta psi measured was not more than [-25] mV. The calculated H+/ATP stoichiometry was 3.3 for aerobes. It was assumed that a constitutive K+ pump having a K+/ATP ratio equal to 2 or 3 operates in S. marcescens membranes.


Mesenchymal stromal cell-derived secretome-based therapy for neurodegenerative diseases: overview of clinical trials.
Over the past few years, mesenchymal stromal cells (MSCs) have attracted a great deal of scientific attention owing to their promising results in the treatment of incurable diseases. However, there are several concerns about their possible side effects after direct cell transplantation, including host immune response, time-consuming cell culture procedures, and the dependence of cell quality on the donor, which limit the application of MSCs in clinical trials. On the other hand, it is well accepted that the beneficial effects of MSCs are mediated by secretome rather than cell replacement. MSC secretome refers to a variety of bioactive molecules involved in different biological processes, specifically neuro-regeneration. Due to the limited ability of the central nervous system to compensate for neuronal loss and relieve disease progress, mesenchymal stem cell products may be used as a potential cure for central nervous system disorders. In the present study, the therapeutic effects of MSC secretome were reviewed and discussed the possible mechanisms in the three most prevalent central nervous system disorders, namely Alzheimer's disease, multiple sclerosis, and Parkinson's disease. The current work aimed to help discover new medicine for the mentioned complications. The use of MSC-derived secretomes in the treatment of the mentioned diseases has encouraging results, so it can be considered as a treatment option for which no treatment has been introduced so far.


Coarctation of aorta with special reference to infants. Long-term results of operation in 126 cases.
A review of 126 cases of coarctation of the aorta confirms the need for surgical resection in infants with intractable congestive cardiac failure. The high association with additional cardiovascular abnormalities in patients presenting in early infancy contributes significantly to the mortality. Patients with large ventricular septal defects and coarctation of the aorta are at risk and may require pulmonary artery banding at the time of resection of the aortic coarctation. Long-term complications included restenosis (18 cases) and persistent hypertension (10 cases). In order to prevent persistent hypertension, it is suggested that elective resection of the coarctation be done at 1 year of age.


[Prevention and therapy of hemostatic disorders in massive transfusion].
Adequate periop. analysis of hemostasis taking into account also disorders of primary hemostasis considerably contributes to prevention, early detection and appropriate treatment of hemostatic disturbances. Standard transfusion protocols are advisable in massive transfusion with respect to logistic problems. We describe an effective standard protocol based on the initial administration of blood components (red cells, plasma, platelets) in a certain fixed ratio which then is adapted according to the laboratory test results and the clinical situation of the patient. In addition, as soon as the hemostasis shows critical values, coagulation factor concentrates (prothrombin complex, fibrinogen, seldom single coagulation factors) are administered. Furthermore, desmopressin and antifibrinolytics can be successfully used in disorders of primary hemostasis, and additionally antifibrinolytics in hyperfibrinolysis or unclear diffuse bleeding.


Fatty Acid and Lipid Transport in Plant Cells.
Fatty acids (FAs) and lipids are essential - not only as membrane constituents but also for growth and development. In plants and algae, FAs are synthesized in plastids and to a large extent transported to the endoplasmic reticulum for modification and lipid assembly. Subsequently, lipophilic compounds are distributed within the cell, and thus are transported across most membrane systems. Membrane-intrinsic transporters and proteins for cellular FA/lipid transfer therefore represent key components for delivery and dissemination. In addition to highlighting their role in lipid homeostasis and plant performance, different transport mechanisms for land plants and green algae - in the model systems Arabidopsis thaliana, Chlamydomonas reinhardtii - are compared, thereby providing a current perspective on protein-mediated FA and lipid trafficking in photosynthetic cells.


The narrow subspine space and relatively large labrum are radiographic features of subspine impingement: a case-control study.
Subspine impingement is considered a source of residual hip symptoms after primary hip arthroscopy, and the role of the subspine space and soft tissue is not clear. The purpose of this study was to analyze the relationship between the subspine space and labrum size in subspine impingement patients. We performed a retrospective study of patients with femoroacetabular impingement between July 2016 and July 2020. Sixteen patients without hip symptom relief after primary hip arthroscopic treatment of femoroacetabular impingement and undergoing revision surgery for anterior inferior iliac spine compression were included as the study group. Forty-eight matched patients who underwent only primary surgery and whose hip discomfort was relieved without a diagnosis of subspine impingement were included as the control group. The patients' preoperative computerized tomography data were reviewed, and the anterior inferior iliac spine dimensions and the size of the subspine space were measured. The size of the labrum at the 11:30, 1:30, and 3 o'clock positions was measured with the use of magnetic resonance imaging. The ratio of the subspine space to the labrum was also calculated. There was no significant difference in anterior inferior iliac spine dimensions between these two groups (p > 0.05). A relatively narrow subspine space was found in the study group, especially in the direction of the anterior inferior iliac spine. Compared with the control group, subspine impingement patients were identified with larger labrums at 11:30 (8.20 ± 1.95 mm vs. 6.81 ± 0.50 mm, p = 0.016), 1:30 (7.83 ± 1.61 mm and 6.25 ± 0.78 mm, p = 0.001) and 3:00 (9.50 ± 1.73 mm vs. 7.48 ± 0.99 mm, p = 0.001). A relative mismatch between the subspine space and the labrum was also identified in the study group. The ratios of the labrum width to the subspine area were significantly larger in the study group than in the control group. This study reported potential additional criteria for subspine impingement-a large labrum and a relatively narrow subspine space-instead of abnormal anterior inferior iliac spine dimensions. For those with a large labrum and narrow subspine space, the diagnosis of subspine impingement should be carefully made, and arthroscopic anterior inferior iliac spine decompression may be important.


Reduction of nuclear peroxisome proliferator-activated receptor gamma expression in methamphetamine-induced neurotoxicity and neuroprotective effects of ibuprofen.
We examined changes in nuclear peroxisome proliferator-activated receptor gamma (PPAR gamma) in the striatum in methamphetamine (METH)-induced dopaminergic neurotoxicity, and also examined effects of treatment with drugs possessing PPAR gamma agonistic properties. The marked reduction of nuclear PPAR gamma-expressed cells was seen in the striatum 3 days after METH injections (4 mg/kg x 4, i.p. with 2-h interval). The reduction of dopamine transporter (DAT)-positive signals and PPAR gamma expression, and accumulation of activated microglial cells were significantly and dose-dependently attenuated by four injections of a nonsteroidal anti-inflammatory drug and a PPAR gamma ligand, ibuprofen (10 or 20 mg/kg x 4, s.c.) given 30 min prior to each METH injection, but not by either a low or high dose of aspirin. Either treatment of ibuprofen or aspirin, that showed no effects on METH-induced hyperthermia, significantly blocked the METH-induced striatal cyclooxygenase (COX) expression. Furthermore, the treatment of an intrinsic PPAR gamma ligand 15d-PG J2 also attenuated METH injections-induced reduction of striatal DAT. Therefore, the present study suggests the involvement of reduction of PPAR gamma expression in METH-induced neurotoxicity. Taken together with the previous report showing protective effects of other PPAR gamma ligand, these results imply that the protective effects of ibuprofen against METH-induced neurotoxicity may be based, in part, on its anti-inflammatory PPAR gamma agonistic properties, but not on its COX-inhibiting property or hypothermic effect.


Arthroscopic Synovectomy and Removal of Loose Bodies in Synovial Osteochondromatosis of the Knee.
Synovial osteochondromatosis is a benign process that most commonly affects the knee joint (70%). It is characterized by proliferative metaplasia of synovial membrane into chondrocytes, resulting in the formation of multiple cartilaginous nodules, which can detach from the synovium to become multiple intra-articular loose bodies. It usually involves the anterior compartment, including infrapatellar fat pad, suprapatellar pouch, and anterior interval, and rarely involves the posterior compartment of the knee. Treatment for synovial osteochondromatosis usually involves surgery, especially in the presence of locking symptoms or decreased range of motion. Arthroscopy has gradually replaced a traditional open approach, resulting in low morbidity, low postoperative pain, better cosmetic results, early recovery of range of motion, short rehabilitation course, and an early return to previous function. In case of involvement of the posterior compartment of the knee joint, arthroscopic access may be difficult. In this Technical Note, the technical details of arthroscopic synovectomy and removal of loose bodies in synovial osteochondromatosis of the knee is described. This arthroscopic technique can deal with the disease, involving both the anterior and posterior compartments of the knee joint.


Antioxidant enzymes in periodontitis.
Periodontitis is basically an inflammatory disease initiated by the subgingival biofilm and modified by the individual's aberrant inflammatory/immune response. Various studies have pointed toward the role of oxidative stress in periodontitis. As the reactive oxygen species and antioxidants are in dynamic equilibrium, any disturbance in one would lead to changes in the other. As studying, individual antioxidants is a vast field, this review focuses on the role of antioxidant enzymes in periodontitis and in other related systemic conditions. It is highlighted that oxidative stress may be the missing link in these associations of periodontitis and other conditions. Also, the antioxidant enzymes may be considered a useful biomarker for periodontal diseases and antioxidant supplementation may be of help to reduce the burden of periodontal destruction without having much extra effort.


Inhibition of enteropathogenic Escherichia coli (EPEC) adherence to HEp-2 cells by bovine colostrum and milk.
enteropathogenic Escherichia coli (EPEC) is the main etiological agent of infantile diarrhea in Brazil and other developing countries. Human milk IgA protects newborn intestinal mucosa by inhibiting bacterial adhesion to epithelial cells and this effect is shown by in vitro assays of EPEC adhesion to HEp-2 cultured cells. Bovine milk, if effective in promoting this protection, could be an useful tool in the absence of the natural breastfeeding, in high-risk nurseries or in hospital infections. the effect of colostrum, milk, and serum from dairy cows on the adherence to EPEC to HEp-2 cells was investigated. Colostrum from immunized and control animals and industrialized milk formulas were fractionated through a membrane device with a molecular weight cut off 10 kDa. The high molecular weight fraction (HMWF) of bovine colostrum was depleted of IgG through an affinity column and absorbed with an EPEC adherent strain. Antibodies were searched by ELISA and immunoblotting (IB). colostrum and milk from EPEC-immunized animals showed and inhibitory activity on adherence similar to that of control non-immunized animals. The inhibitory effect on adhesion was related to the HMWF. IgG-depleted colostrum partially retained the inhibitory effect, whereas IgG-rich eluate lost this property. The EPEC-absorbed fraction retained the inhibitory property. Industrialized milk formulas and respective HMWF also inhibited bacterial adherence. In IB assays, colostrum and milk samples from immunized animals recognized proteins of 30-40 kDa and 94 kDa, a molecular weight consistent with the adhesin intimin, in EPEC extracts. the inhibitory effect of EPEC adherence may be mediated by HMWF components, and IgG was not the only component responsible for this phenomenon.


SEC22B inhibition attenuates colorectal cancer aggressiveness and autophagic flux under unfavorable environment.
Autophagy has bidirectional functions in cancer by facilitating cell survival and death in a context-dependent manner. Soluble N-ethylmaleimide-sensitive factor attachment protein receptors (SNAREs) are a large family of proteins essential for numerous biological processes, including autophagy; nevertheless, their potential function in cancer malignancy remains unclear. Here, we explored the gene expression patterns of SNAREs in tissues of patients with colorectal cancer (CRC) and discovered that SEC22B expression, a vesicle SNARE, was higher in tumor tissues than in normal tissues, with a more significant increase in metastatic tissues. Interestingly, SEC22B knockdown dramatically decreased CRC cell survival and growth, especially under stressful conditions, such as hypoxia and serum starvation, and decreased the number of stress-induced autophagic vacuoles. Moreover, SEC22B knockdown successfully attenuated liver metastasis in a CRC cell xenograft mouse model, with histological signs of decreased autophagic flux and proliferation within cancer cells. Together, this study posits that SEC22B plays a crucial role in enhancing the aggressiveness of CRC cells, suggesting that SEC22B might be an attractive therapeutic target for CRC.


Urinary biomarkers for the differentiation of prerenal and intrinsic pediatric acute kidney injury.
Urinary calprotectin and neutrophil gelatinase-associated lipocalin (NGAL) have recently been identified as promising biomarkers for the differentiation of prerenal and intrinsic acute kidney injury (AKI) in adults. In the study reported here we examined the diagnostic accuracy of calprotectin, NGAL, and kidney injury molecule 1 (KIM-1) in pediatric patients. Urinary calprotectin, NGAL, and KIM-1 concentrations were assessed in a study population of 139 pediatric subjects including 39 patients with intrinsic AKI, 14 with prerenal AKI, and 86 non-AKI subjects. Median urinary calprotectin and NGAL concentrations were higher in patients with intrinsic AKI than in those with prerenal AKI (calprotectin by 22-fold, NGAL by 9-fold). Receiver operating characteristic (ROC) curve analyses for the differentiation of intrinsic and prerenal AKI resulted in an area under the curve (AUC) of 0.90 [95 % confidence interval (CI) 0.81-0.98] for calprotectin and 0.73 (95 % CI 0.58-0.87) for NGAL. Median urinary KIM-1 concentrations were not significantly different between patients with prerenal AKI and those with intrinsic disease (P = 0.98; AUC 0.50, 95 % CI, 0.35-0.65). The AUC for the fractional excretion of sodium (FENa) and proteinuria was 0.78 (95 % CI 0.63-0.92) and 0.77 (CI 0.65-0.90), respectively. Urinary calprotectin outperforms NGAL, KIM-1, FENa, and proteinuria as a biomarker for the differentiation of prerenal and intrinsic AKI in pediatric patients with a high diagnostic accuracy.


Correction of hyperopia with intracorneal implants.
To evaluate the safety and efficacy of intracorneal lenses as a surgical alternative for the correction of hyperopia. Al-Azhar University, Cairo, Egypt, and Louisiana State University Eye Center, New Orleans, Louisiana, USA. PermaVision lenses (Anamed Inc.) were implanted in the left eye of 20 albino rabbits that were followed for 6 months by confocal microscopy. The lenses are made of a highly permeable hydrogel with 70% water content and a refractive index close to that of corneal tissue (1.376). The Carriazo-Barraquer microkeratome (Moria) was used to create a 150 microm corneal flap with a diameter of 8.5 mm or larger. The intracorneal lens was placed under the flap after minimal interface irrigation. At 3 days, confocal microscopy showed interface edema that resolved after 1 week. No flap melting or excursion of the lens was noted. In 1 eye, a deep lamellar keratitis was seen. At 6 months, the edge of the lens showed excellent compatibility, with no keratocytic activity or intrastromal fibrosis. Intracorneal hydrogel lenses were well tolerated by stromal tissue in rabbits. They are potentially safe and can be considered as an alternative for the correction of hyperopia. Further clinical studies are required to confirm their safety in humans.


Determination of acetamiprid partial-intercalative binding to DNA by use of spectroscopic, chemometrics, and molecular docking techniques.
Acetamiprid (ACT) is an insecticide widely used for controlling a variety of insect pests. The binding mode associated with calf thymus DNA (ctDNA) upon interaction with ACT was determined using spectroscopic, chemometrics, and molecular docking techniques to clarify the interaction mechanism at the molecular level. Fluorescence titration suggested that the fluorescence quenching of ACT by ctDNA is a static procedure. The binding constants between ACT and ctDNA at different temperatures were calculated to be of the order 10(3)-10(4) L mol(-1). The positive values of enthalpy and entropy change suggested that the binding process is primarily driven by hydrophobic interactions. Multivariate curve resolution-alternating least squares (MCR-ALS), a chemometrics approach, was used to resolve the expanded UV-visible spectral data matrix. The concentration profiles and the spectra for the three reaction components (ACT, ctDNA, and ACT-ctDNA complex) of the system, which formed a highly overlapping composite response, were then successfully obtained and used to evaluate the progress of ACT interacting with ctDNA. The results of the single-stranded ctDNA and iodide quenching experiments, ctDNA-melting investigations, and viscosity measurements indicated that ACT binds to ctDNA by means of a partial intercalation. Molecular docking studies showed that the specific binding site is mainly located between the ACT and G-C base pairs of ctDNA. This docking prediction was confirmed by use of Fourier-transform infrared (FT-IR) spectral analysis. Results from circular dichroism (CD) spectroscopy revealed that ACT induced a conformational change from the B-ctDNA form to the A-ctDNA form.


Longest gallbladder: A case report.
A gallbladder mucocele is the distention of the gallbladder by an inappropriate accumulation of mucus. Decreased bile flow, decreased gallbladder motility, and altered absorption of water from the gallbladder lumen are predisposing factors to biliary sludge. However, it is more likely to be a small part of a complex disease process involving inflammation of the gallbladder wall and changes to the lining of the gallbladder changing the consistency of its secretions. We would like to present a case of mucocele gallbladder operated successfully by laparoscopic cholecystectomy. Herein, we present a case of 46year old female presenting with symptoms of pain in right hypochondrium with ultrasonographic diagnosis of cholelithiasis undergone successful laparoscopic cholecystectomy with Intraoperative findings of: 1. The length of the gallbladder was measured to be 30cm. 2. A large stone was impacted at the neck of gallbladder, which was leading to mucocele formation. Mucocele of gallbladder present an important hurdle in successful laparoscopic cholecystectomy. A habit of calm and slow dissection with precautions should be developed. Clearance of the calot's triangle with limited use of electro cautery should be done before proceeding towards ligation or clip application to various structures.


Lower-extremity dynamics of walking in neuropathic diabetic patients who wear a forefoot-offloading shoe.
A forefoot-offloading shoes has a negative-heel rocker outsole and is used to treat diabetic plantar forefoot ulcers, but its mechanisms of action and their association with offloading and gait stability are not sufficiently clear. Ten neuropathic diabetic patients were tested in a forefoot-offloading shoe and subsequently in a control shoe with no specific offloading construction, both worn on the right foot (control shoe on left), while walking at 1.2m/s. 3D-instrumented gait analysis and simultaneous in-shoe plantar pressure measurements were used to explain the shoe's offloading efficacy and to define centre-of-pressure profiles and left-to-right symmetry in ankle joint dynamics (0-1, 1:maximum symmetry), as indicators for gait stability. Compared to the control shoe, peak forefoot pressures, vertical ground reaction force, plantar flexion angle, and ankle joint moment, all in terminal stance, and the proximal-to-distal centre-of-pressure trajectory were significantly reduced in the forefoot-offloading shoe (P<0.01). Peak ankle joint power was 51% lower in the forefoot-offloading shoe compared to the control shoe: 1.61 (0.35) versus 3.30 (0.84) W/kg (mean (SD), P<0.001), and was significantly associated with forefoot peak pressure (R2=0.72, P<0.001). Left-to-right symmetry in the forefoot-offloading shoe was 0.39 for peak ankle joint power. By virtue to their negative-heel rocker-outsole design, forefoot-offloading shoes significantly alter a neuropathic diabetic patient's gait towards a reduced push-off power that explains the shoe's offloading efficacy. However, gait symmetry and stability are compromised, and may be factors in the low perceived walking discomfort and limited use of these shoes in clinical practice. Shoe modifications (e.g. less negative heel, a more cushioning insole) may resolve this trade-off between efficacy and usability.


Hepatocellular carcinoma in patients listed for liver transplantation: Current and future allocation policy and management strategies for the individual patient.
Liver transplantation can provide definitive cure for patients with cirrhosis and hepatocellular carcinoma (HCC) when used appropriately. Advances in the management of HCC have allowed improved control of HCC while waiting for liver transplantation and new approaches to candidate selection particularly with regard to tumor burden and downstaging protocols. Additionally, there have been recent changes in allocation policy related to HCC in the U.S. that cap the HCC MELD exception at 34 points and implement a 6-month delay in a HCC MELD exception. This review examines the U.S. liver transplant allocation policy related to HCC, comprehensively details locoregional therapy options in HCC patients awaiting liver transplantation, and considers the impact of an increasing burden of HCC on future liver graft allocation policy.


The efficacy of corticosteroid therapy in inflammatory bowel disease: analysis of a 5-year UK inception cohort.
Corticosteroids remain the mainstay of first-line therapy in active inflammatory bowel disease. To determine the clinical outcome after the first corticosteroid-therapy and to identify factors which predict response/failure. 216 (136 ulcerative colitis and 80 Crohn's disease) patients were identified in this 5-year inception cohort. The outcomes of early (30 days) and late (1 year) responses were used. Multivariate analyses were performed to identify factors associated with outcome. 86 (63%) and 60 (75%) ulcerative colitis and Crohn's disease required corticosteroid therapy, respectively. In ulcerative colitis, at 30 days, 69 (51%), 42 (31%) and 25 (18%) patients demonstrated complete response, partial response and no response, respectively. For Crohn's disease, these outcomes were observed in 32 (40%), 28 (35%) and 20 (25%). After 1 year, 75 (55%), 23 (17%) and 29 (21%) patients with ulcerative colitis demonstrated prolonged response, corticosteroid-dependence or required surgery, respectively. For Crohn's disease, these outcomes were observed in 30 (38%), 19 (24%) and 27 (35%) patients. Extensive ulcerative colitis was a predictor of surgery (P = 0.001, OR: 15.2). In Crohn's disease, inflammatory disease behaviour was negatively associated with surgery (P = 0.02, OR: 0.13). Although corticosteroids are effective, dependence/resistance remains common. Patients with extensive ulcerative colitis and fistulizing/stricturing Crohn's are most at risk of failing corticosteroid therapy.


Influence of age on the frequency characteristics of the soleus muscle response to Achilles tendon vibration during standing.
Proprioceptive sensory information from the ankle joint is critical for the control of upright posture and balance. We examined the influence of age (n = 54 healthy adults, 20-82 years old) on lower limb muscle responses to proprioceptive perturbations evoked by Achilles tendon vibration during standing. The frequency bandwidth of the muscle response became narrower, and the gain (the muscle response relative to the stimulus) and scaling (increases in response amplitude with increases in stimulus amplitude) decreased with age. Mechanics of the muscle-tendon unit (mechanical admittance) did not differ with age during standing, and thus probably did not mediate the age-related changes observed in soleus muscle responses to vibration. These findings add to our understanding of how altered proprioceptive responses may contribute to impaired mobility and falls with ageing. Proprioceptive information from the ankle joint plays an important role in the control of upright posture and balance. Ageing influences many components of the sensorimotor system, which leads to poor mobility and falls. However, little is known about the influence of age on the characteristics of short latency muscle responses to proprioceptive stimuli during standing across frequencies that are encoded by muscle spindles. We examined the frequency characteristics of the soleus muscle response to noisy (10-115 Hz) Achilles tendon vibration during standing in 54 healthy adults across a broad age range (20-82 years). The results showed the frequency bandwidth of the soleus response (vibration-electromyography coherence) became progressively narrower with ageing. Coherence was significantly lower in middle-aged relative to young adults between ∼7-11 and 28-62 Hz, lower in older relative to middle-aged adults between ∼30-50 Hz and lower in older relative to young adults between ∼7-64 Hz. Muscle response gain was similar between age groups at low frequencies, although gain was lower in older relative to young adults between ∼28-54 Hz. Across the age range, the response amplitude (peak-to-peak cross-covariance) and the scaling of the response with stimulus amplitude were both negatively correlated with age. Muscle-tendon mechanics (admittance) did not differ with age, suggesting this did not mediate differences in soleus responses. Our findings suggest there is a progressive change in the soleus response to proprioceptive stimuli with ageing during standing, which could contribute to poorer mobility and falls.


Arrhythmias in a long-term adult survivor with uncorrected tetralogy of Fallot: Case report and review of the literature.
We present a case of a middle-aged adult with uncorrected Tetralogy of Fallot (TOF) with pulmonary atresia who developed symptomatic supraventricular and ventricular arrhythmias. The lack of data regarding management of electrical and other complications in adults with uncorrected TOF is highlighted and emphasizes the need for a registry to better understand the medical management of long-standing adult survivors.