Influence of reagent rotation on (H-, D2) and (D-, H2) collisions: a quantum mechanical study.
Time-independent quantum mechanical (TIQM) approach (helicity basis truncated at k = 2) has been used for computing differential and integral cross sections for the exchange reaction H- + D2 (v = 0, j = 0-4) --> HD + D- and D- + H2 (v = 0, j = 0-3) --> HD + H- in three dimensions on an accurate ab initio potential energy surface. It is shown that the j-weighted differential reaction cross section values are in good agreement with the experimental results reported by Zimmer and Linder at four different relative translational energies (Etrans = 0.55, 0.93, 1.16 and 1.48 eV) for (H-, D2) and at one relative translational energy (Etrans = 0.6 eV) by Haufler et al. for both (H-, D2) and (D-, H2) collisions. The j-weighted integral reaction cross section values are in good agreement with the crossed beam measurements by Zimmer and Linder in the Etrans range 0.5-1.5 eV and close to the guided ion beam results by Haufler et al. for (H-, D2) in the range 0.8-1.2 eV. Time-dependent quantum mechanical (TDQM) results obtained using centrifugal sudden approximation are reported in the form of integral reaction cross section values as a function of Etrans in the range 0.3-3.0 eV for both reactions in three dimensions on the same potential energy surface. The TDQM reaction cross section values decline more sharply than the TIQM results with increase in the initial rotational quantum number (j) for the D2 molecules in their ground vibrational state (v = 0) for (H-, D2) collisions. The computed j-weighted reaction cross section values are in good agreement with the experimental results reported by Zimmer and Linder for (H-, D2) collisions and guided ion beam results by Haufler et al. for both (H-, D2) and (D-, H2) collisions for energies below the threshold for electron detachment channel.


The response of Golgi tendon organs to single motor unit contractions.
1. Cross-correlation analysis has been used to quantify the responses of cat soleus tendon organs to repetitive twitch contractions of: (a) different motor units within the muscle, (b) single motor units at different muscle lengths, and (c) single motor units when the pulse-train pattern of stimulation delivered to the motor unit axon was altered. 2. Ib afferents were observed which responded to each of several hundred successive motor unit twitches with identical numbers of spikes and with relatively invariant latencies. 3. The present results show that tendon organs are sensitive to subtle alterations in motor unit twitch wave form and amplitude, and that this sensitivity is reflected in the precise timings of their afferent discharge. 4. Examination of these tendon organ responses indicates that the forces produced by single motor units couples to the receptor capsule are well above threshold. Calculations based on these results, and earlier soleus motor unit and muscle fibre data, suggest that the absolute force threshold for tendon organs may be as little as 4 mg, which is less than the estimated minimum twitch force generated by individual soleus muscle fibres. 5. Considering the number of tendon organs in a muscle, and the likelihood that every motor unit is connected with at least one receptor, the sensitivity of tendon organs ensures that every twitch of every motor unit will be reflected in the population of afferent signals projecting to the spinal cord.


Developmental exposure to a commercial PBDE mixture, DE-71: neurobehavioral, hormonal, and reproductive effects.
Developmental effects of polybrominated diphenyl ethers (PBDEs) have been suspected due to their structural similarities to polychlorinated biphenyls (PCBs). This study evaluated neurobehavioral, hormonal, and reproductive effects in rat offspring perinatally exposed to a widely used pentabrominated commercial mixture, DE-71. Pregnant Long-Evans rats were exposed to 0, 1.7, 10.2, or 30.6 mg/kg/day DE-71 in corn oil by oral gavage from gestational day 6 to weaning. DE-71 did not alter maternal or male offspring body weights. However, female offspring were smaller compared with controls from postnatal days (PNDs) 35-60. Although several neurobehavioral endpoints were assessed, the only statistically significant behavioral finding was a dose-by-age interaction in the number of rears in an open-field test. Developmental exposure to DE-71 caused severe hypothyroxinemia in the dams and early postnatal offspring. DE-71 also affected anogenital distance and preputial separation in male pups. Body weight gain over time, reproductive tissue weights, and serum testosterone concentrations at PND 60 were not altered. Mammary gland development of female offspring was significantly affected at PND 21. Congener-specific analysis of PBDEs indicated accumulation in all tissues examined. Highest PBDE concentrations were found in fat including milk, whereas blood had the lowest concentrations on a wet weight basis. PBDE concentrations were comparable among various brain regions. Thus, perinatal exposure to DE-71 leads to accumulation of PBDE congeners in various tissues crossing blood-placenta and blood-brain barriers, causing subtle changes in some parameters of neurobehavior and dramatic changes in circulating thyroid hormone levels, as well as changes in both male and female reproductive endpoints. Some of these effects are similar to those seen with PCBs, and the persistence of these changes requires further investigation.


The discrete adjoint method for parameter identification in multibody system dynamics.
The adjoint method is an elegant approach for the computation of the gradient of a cost function to identify a set of parameters. An additional set of differential equations has to be solved to compute the adjoint variables, which are further used for the gradient computation. However, the accuracy of the numerical solution of the adjoint differential equation has a great impact on the gradient. Hence, an alternative approach is the discrete adjoint method, where the adjoint differential equations are replaced by algebraic equations. Therefore, a finite difference scheme is constructed for the adjoint system directly from the numerical time integration method. The method provides the exact gradient of the discretized cost function subjected to the discretized equations of motion.


MR Image Harmonization with Transformer.
Many clinical applications require medical image harmonization to combine and normalize images from different scanners or protocols. This paper introduces a Transformer-based MR image harmonization method. Our proposed method leverages the self-attention mechanism of the Transformer to learn the complex relationships between image patches and effectively transfer the imaging characteristics from a source image domain to a target image domain. We evaluate our approach to state-of-the-art methods using a publicly available dataset of brain MRI scans and show that it provides superior quantitative metrics and visual quality. Furthermore, we demonstrate that the proposed approach is highly resistant to fluctuations in image modality, resolution, and noise. Overall, the experiment results indicate that our approach is a promising method for medical image harmonization that can improve the accuracy and reliability of automated analysis and diagnosis in clinical settings.


[MiR26a and miR939 regulate the replication of H1N1 influenza virus in MDCK cell].
MicroRNAs (miRNAs) play an important role in the process of infection and replication of virus in host cells. In this study, we cloned two miRNAs expression vectors and examined their effects on the replication of H1N1 type influenza virus in MDCK (Madin dardy canine kidney) cells. We constructed the plasmids expressing miR26a and miR939 and performed the transfection study in MDCK cells. Subsequently, the cells were infected with H1N1 type influenza virus 24 h after transfection. Then we tested the hemagglutination titer at 72 h time point to investigate the effect of miR26a and miR939 on the replication H1N1 type influenza virus in MDCK cells. The transfection study showed that miR26a and miR939 can achieve efficiently expression in MDCK cells. miR26a and miR939 can influence the replication of H1N1 influenza virus differently in two different ways. miR26a inhibits the replication, whereas miR939 stimulates the process. Cellular miRNAs can regulate the replication of H1N1 influenza virus in host cells, and our paper should report the role of miR26a and miR939 in this regulation for the first time.


Recent contributions of in vitro models to our understanding of hepatitis C virus life cycle.
Hepatitis C virus is a human pathogen responsible for liver diseases including acute and chronic hepatitis, cirrhosis and hepatocellular carcinoma. Its high prevalence, the absence of a prophylactic vaccine and the poor efficiency of current therapies are huge medical problems. Since the discovery of the hepatitis C virus, our knowledge of its biology has been largely punctuated by the development of original models of research. At the end of the 1980s, the chimpanzee model led to cloning of the viral genome and the definition of infectious molecular clones. In 1999, a breakthrough was achieved with the development of a robust in vitro replication model named 'replicon'. This system allowed intensive research into replication mechanisms and drug discovery. Later, in 2003, pseudotyped retroviruses harbouring surface proteins of hepatitis C virus were produced to specifically investigate the viral entry process. It was only in 2005 that infectious viruses were produced in vitro, enabling intensive investigations into the entire life cycle of the hepatitis C virus. This review describes the different in vitro models developed to study hepatitis C virus, their contribution to current knowledge of the virus biology and their future research applications.


Sleep apnoea following cervical cord surgery.
Two patients who developed sleep apnoea following upper cervical cord surgery are described. The underlying mechanisms and management of the sleep apnoea syndrome are discussed.


Post-traumatic stress disorder in patients with rheumatic disease during the COVID-19 outbreak: a cross-sectional case-control study in China.
The COVID-19 pandemic is not only a traumatic event, but a collective stressor unfolding over time, causing devastating implications for the mental health. This study aimed to shed light on the mental health status of patients with rheumatic disease (RD) during the massive outbreak of COVID-19 in China, especially the prevalence and severity of post-traumatic stress disorder (PTSD) compared with healthy individuals. A total of 486 patients with RD and 486 age-matched and sex-matched healthy individuals were recruited into the study. For each participant, we collected demographic and clinical characteristics data. The PTSD Checklist for DSM-5 (PCL-5) and four items from the Pittsburgh Sleep Quality Index (PSQI) were used to investigate the prevalence and severity of PTSD and sleep quality, respectively. Compared with healthy control subjects (n=486), patients with RD (n=486) had a higher prevalence of PTSD (12.1% vs 4.1%; p<0.001). Higher total scores on the PCL-5 and on all four items from the PSQI (p≤0.001) were also observed. Female, old age, poor sleep quality, long duration of RD, poor subjective evaluation of the disease and pessimistic subjective perception of the epidemic were identified as risk factors of PTSD in patients with RD during the COVID-19 epidemic. During the COVID-19 outbreak, patients with RD presented a higher prevalence and severity of PTSD and showed more sleep disturbances. Our findings confirm the importance of psychological assessment and mental healthcare out of regular clinical care for patients with RD during the pandemic.


Unexpected biotic resilience on the Japanese seafloor caused by the 2011 Tōhoku-Oki tsunami.
On March 11(th), 2011 the Mw 9.0 2011 Tōhoku-Oki earthquake resulted in a tsunami which caused major devastation in coastal areas. Along the Japanese NE coast, tsunami waves reached maximum run-ups of 40 m, and travelled kilometers inland. Whereas devastation was clearly visible on land, underwater impact is much more difficult to assess. Here, we report unexpected results obtained during a research cruise targeting the seafloor off Shimokita (NE Japan), shortly (five months) after the disaster. The geography of the studied area is characterized by smooth coastline and a gradually descending shelf slope. Although high-energy tsunami waves caused major sediment reworking in shallow-water environments, investigated shelf ecosystems were characterized by surprisingly high benthic diversity and showed no evidence of mass mortality. Conversely, just beyond the shelf break, the benthic ecosystem was dominated by a low-diversity, opportunistic fauna indicating ongoing colonization of massive sand-bed deposits.


Cortisol-mediated regulation of uterine artery contractility: effect of chronic hypoxia.
We previously demonstrated that cortisol regulated alpha(1)-adrenoceptor-mediated contractions differentially in nonpregnant and pregnant uterine arteries. Given that chronic hypoxia during pregnancy has profound effects on maternal uterine artery reactivity, the present study investigated the effects of chronic hypoxia on cortisol-mediated regulation of uterine artery contractions. Pregnant (day 30) and nonpregnant ewes were divided between normoxic control and chronically hypoxic [maintained at high altitude (3,820 m), arterial Po(2): 60 mmHg for 110 days] groups. Uterine arteries were isolated and contractions measured. In hypoxic animals, cortisol (10 ng/ml for 24 h) increased norepinephrine-induced contractions in pregnant, but not in nonpregnant, uterine arteries. The 11beta-hydroxysteroid dehydrogenase inhibitor carbenoxolone did not change cortisol effects in nonpregnant uterine arteries, but abolished it in pregnant uterine arteries by increasing norepinephrine pD(2) (-log EC(50)) in control tissues. The dissociation constant of norepinephrine-alpha(1)-adrenoceptors was not changed by cortisol in nonpregnant, but decreased in pregnant uterine arteries. There were no differences in the density of glucocorticoid receptors between normoxic and hypoxic tissues. Cortisol inhibited the norepinephrine-induced increase in Ca(2+) concentrations in nonpregnant arteries, but potentiated it in pregnant arteries. In addition, cortisol attenuated phorbol 12,13-dibutyrate-induced contractions in normoxic nonpregnant and pregnant uterine arteries, but had no effect on the contractions in hypoxic arteries. The results suggest that cortisol differentially regulates alpha(1)-adrenoceptor- and PKC-mediated contractions in uterine arteries. Chronic hypoxia suppresses uterine artery sensitivity to cortisol, which may play an important role in the adaptation of uterine vascular tone and blood flow in response to chronic stress of hypoxia during pregnancy.


Formation, characterization, and analysis of curcumin nanoformulation for evaluating its in vitro cytotoxicity.
Nanotechnology holds significance in all fields of research, and the formation and surface alterations of nanomaterials are particularly important in this discipline. Nanoformulations synthesized with bioactive plant components play a crucial role in the improvement of several therapeutics and diagnostics. In the present study, we reported the synthesis of a curcumin nanoformulation (CN) by using curcumin and D-α-tocopheryl polyethylene glycol 1000 succinate (TPGS). The synthesized CN was characterized using dynamic light scattering, UV-Visible spectrophotometry, Fourier-transform infrared spectroscopy, field-emission scanning electron microscopy, and X-ray diffraction. Furthermore, it was evaluated for solubility, drug loading, encapsulation efficiency, stability, in vitro release, and anticancer potentials. The role of TPGS in the synthesis of CN was validated. The synthesized CN exhibited a size of 6.2 ± 1.9 nm, needle-shaped morphology, a polydispersity index of 0.164, and zeta potential of - 10.1 ± 3.21 mV, as determined by characterization techniques. Its water solubility was 2.5 × 104 times higher than that of pure curcumin. The encapsulation efficiency and curcumin loading efficiency of the synthesized CN were found to be 80 and 10%, respectively, with storage stability exceeding 30 days. Moreover, the synthesized CN demonstrated significant in vitro anticancer activity against the colorectal cancer cell line HCT-116, with an IC50 value of 12.74 ± 0.54 μM at 24 h.


Comparison of polycyclic aromatic hydrocarbon uptake pathways and risk assessment of vegetables from waste-water irrigated areas in northern China.
Atmospheric deposition is the dominant pathway for PAH uptake by vegetables grown in peri-urban areas. Different polycyclic aromatic hydrocarbon (PAH) uptake pathways and the associated health risk were investigated in vegetable samples collected from the Beijing-Tianjin city cluster, China, where irrigation with waste or reclaimed water has been practised for many decades. Sampling comprised 23 diverse sites and the roots and shoots of six types of vegetables. Among the different edible vegetable parts, the highest PAH concentrations were found in radish roots and the lowest in cauliflower heads. Bioconcentration factors (BCFs) for individual PAHs showed a weakly decreasing trend with increasing log K(OW). To investigate whether the air-leaf or soil-root-shoot uptake dominates, the measured values were compared with estimations from a generic one-compartment model. The results and related observations are more consistent with an atmospheric uptake pathway than a soil-uptake pathway. The PAH isomeric ratios are consistent with pyrogenic sources (from combustion of fossil fuel and biomass). A health risk assessment on the consumption of the edible parts of vegetables revealed that all studied vegetables, except for 16% of Chinese cabbage samples, are safe for consumption. The results of this study indicate the potential health risk of consuming vegetables from waste-water irrigated areas of this city cluster and provide new insights regarding the transfer of PAHs in vegetables grown in this region.


[Hypothyroidism and aging: the search for protective factors].
Searching for aging key points is one of the main problems in geriatrics. More and more research in recent years has been devoted to the study of geroprotective mechanisms, the impact of various conditions and diseases on aging in general. Of particular importance is the determination of age-related involutive processes in the human body, whether they are part of normal aging or a condition that needs to be corrected to improve the functioning of organs and systems. An important mechanism of aging starts is a change in hormonal activity of endocrine glands, in particular in hormonal activity of thyroid. Frequency of hypothyroidism in advanced age explains relevance of the chosen topic. The aim of the review was to find out the role hypothyroidism in aging. The main task was to define, whether thyroid hormones decrease in older age was a protective factor or pathological process. A review of the literature over the past 10 years on subclinical treatment was carried out and we identified the most pressing issues associated with hypothyroidism and aging. We studied data on the relationship between hypothyroidism and major geriatric syndromes, with special attention paid to cognitive diseases and emotional disorders.


Effectiveness of photobiomodulation for people with age-related cognitive impairment: a systematic review and meta-analysis.
The increasing incident of age-related cognitive impairment worldwide and the lack of pharmaceutical treatments emphasizes the value of non-pharmaceutical therapy. Emerging evidence suggested photobiomodulation (PBM) is a popular intervention to brain disorder; however, it remains unclear the efficacy of PBM for patients with age-related cognitive impairment. The purpose of this systematic review is to compare the different parameters used in PBM, analyze the beneficial effects of PBM as a potential therapy for age-related cognitive impairment. Five electronic database, PubMed, Web of Science, Cochrane Library, CINAHL, and PsycINFO, were systematically searched from inception to November 2021. Relevant randomized controlled trials (RCTs) were screened and assessed for risk of bias. Eleven RCTs evaluating PBM interventions were included. The systematic review and meta-analysis has been registered in PROSPERO(CRD42022374562). Results showed that PBM had a significant moderated effect on global cognition function (SMD=0.51, 95% CI [0.162, 0.864], p=0.004). We found that multiple wavelength PBM (SMD=0.648, 95% CI [0.220, 1.075], p=0.003) had significant effects while single wavelength PBM was non-significant (SMD=0.385, 95% CI [-0.168, 0.987], p=0.172). Laser effect (SMD=0.682, 95% CI [0.37, 0,994], p<0.001) was larger than LED effect (SMD=0.582, 95% CI [0.269, 0.895], p<0.001). PBM in clinical setting (SMD=0.468, 95% CI [0.050, 0.887], p=0.028) had significant effect, but there was no significant effect of home-used PBM (SMD=0.616, 95% CI [-0.121, 1.354], p=0.101). The pool effect of multi-modality PBM (SMD=0.720, 95% CI [0.027, 1.414], p=0.040) was significantly higher in the studies of transcranial irradiation (SMD=0.616, 95% CI [-0.121, 1.354], p=0.010). Cumulative irradiation time was a moderator between the PBM and cognitive function improvement. Photobiomodulation have the potential to improve cognitive function in aging adults. Cumulative irradiation duration, light source, device type, penetration modality, and intervention site can affect the effectiveness of PBM intervention.


A New N-methoxypyridone from the Co-Cultivation of Hawaiian Endophytic Fungi Camporesia sambuci FT1061 and Epicoccum sorghinum FT1062.
A new N-methoxypyridone analog (1), together with four known compounds, was isolated from the co-culture of Hawaiian endophytic fungi Camporesia sambuci FT1061 and Epicoccum sorghinum FT1062. The structure of the new compound was elucidated as 11S-hydroxy-1-methoxyfusaricide (1) by extensive spectroscopic analysis and comparison with the literature. The absolute configuration of 1 was determined by comparison with the experimental and calculated ECD spectra. The absolute configuration of compound 3 was investigated and renamed as (+)-epipyridone by comparison of the optical rotation and CD spectrum with those of 1. The other known compounds were identified as epicoccarine B (2), D8646-2-6 (4), and iso-D8646-2-6 (5). Compounds 4 and 5 showed modest inhibitory activity towards pathogenic fungi. Epicoccarine B (2) inhibited A2780 and TK-10 with an IC50 value of 22 μM.


St. John's wort and its constituent hyperforin concordantly regulate expression of genes encoding enzymes involved in basic cellular pathways.
The effects of St. John's wort and hyperforin on gene expression were analysed in HepG2 cells by Affymetrix microarray hybridization and real time reverse transcription-PCR. Both compounds increased mRNAs of the drug metabolizing enzymes CYP3A4, CYP1A1, CYP1A2 and the flavin containing monooxygenase FMO5, and of the multidrug resistance protein MRP2. CYP4F2 and the reduced nicotinamide adenine dinucleotide dehydrogenase NQO1 were downregulated. Expression of genes mediating cholesterol biosynthesis was decreased, while facilitated glucose transporters and glycolysis genes were induced, indicating increased glucose metabolism. Changes of a considerable number of additional transcripts corresponded to reports on gene regulation by hypoxia. Endoplasmic reticulum stress-regulated genes involved in unfolded protein response and in protection of cells from apoptosis were downregulated. Other calcium binding proteins were affected by both treatments, suggesting an increase in intracellular calcium. St. John's wort and hyperforin concordantly affected expression of genes not only mediating metabolism and transport of exogenous and endogenous compounds, but also involved in energy metabolism, intracellular calcium regulation, cell proliferation and apoptosis.


The concomitance of learning disabilities and emotional/behavioral disorders: a conceptual model.
Although research has documented overlapping and coexisting characteristics of learning disabilities and emotional/behavioral disorders, little attention has been paid to the subset of students who manifest symptoms of both disorders (LD/EBD). This gap in our professional knowledge/research base may be due to (a) exclusive language in federal definitions that promotes differentiation of disabilities rather than recognition of symptom overlap; (b) the lack of a conceptual model of concomitant learning and emotional/behavioral disorders; and (c) the absence of a research focus on this population. In this article, we construct a conceptual model involving six critical domains of relevance to students with LD/EBD. After describing the utility of this interactive and functional model, we highlight critical issues in screening, assessment, and programming for children with concomitant LD/EBD.


Bonding of restorative resins to enamel.
The bond between restorative resin and enamel may be likened to a chain with a series of links. The potentially weakest link is the interface between the resin and the tissue. This link is established by the clinician and is considered to be technique sensitive. An understanding of the steps in clinical method provide a rationale and an aim for each step. A thorough dental prophylaxis to remove deposits, including calculus from enamel, is important in allowing the acidic conditioning agent, namely phosphoric acid, to exert its optimal effect. Conditioning of the enamel raises its surface energy, creates increased surface area and enhances tissue porosity in the outermost enamel. These conditions are achieved through careful isolation of the teeth and thorough washing to remove the acid and reaction products. A dry field is also of paramount importance in obtaining the micromechanical retention of the resin within the enhanced tissue micropores. The polymerized resin within the tissue serves to retain the bulk of resin located upon the enamel surface. The method is a clinically conservative, non-traumatic, biocompatible means by which resins, polymerizable under oral conditions, can be bonded durably to enamel.


The Mediation Role of Moral Personality Between Childhood Psychological Abuse and Cyberbullying Perpetration Attitudes of College Students.
Guided by social learning theory and general aggression model, this work aims to explore the impact of childhood psychological abuse on cyberbullying perpetration attitudes of college students and the mediating role of moral personality. Using stratified cluster random sampling method, 527 college students were tested by using the Childhood Psychological Abuse Scale, Moral Personality Adjective Evaluation Questionnaire for college students, and the revised Chinese version of Cyberbullying Attitude Questionnaire. Results: (1) Childhood psychological abuse was significantly positively correlated with cyberbullying perpetration attitudes and showed a significant negative correlation with positive moral personality traits. (2) Positive moral personality traits had a significant negative correlation with cyberbullying perpetration attitudes. (3) Positive moral personality traits had a significant mediating effect between childhood psychological abuse and cyberbullying attitudes of college students. The mediating effect accounted for 11.11% of the total effect.


Deep Encrypted Traffic Detection: An Anomaly Detection Framework for Encryption Traffic Based on Parallel Automatic Feature Extraction.
With an increasing number of network attacks using encrypted communication, the anomaly detection of encryption traffic is of great importance to ensure reliable network operation. However, the existing feature extraction methods for encrypted traffic anomaly detection have difficulties in extracting features, resulting in their low efficiency. In this paper, we propose a framework of encrypted traffic anomaly detection based on parallel automatic feature extraction, called deep encrypted traffic detection (DETD). The proposed DETD uses a parallel small-scale multilayer stack autoencoder to extract local traffic features from encrypted traffic and then adopts an L1 regularization-based feature selection algorithm to select the most representative feature set for the final encrypted traffic anomaly detection task. The experimental results show that DETD has promising robustness in feature extraction, i.e., the feature extraction efficiency of DETD is 66% higher than that of the conventional stacked autoencoder, and the anomaly detection performance is as high as 99.998%, and thus DETD outperforms the deep full-range framework and other neural network anomaly detection algorithms.


Comparison of the Olfactory Functions in Conventional Endoscopic Sinus Surgery to the Balloon Sinuplasty in Frontal Sinus Surgery.
Balloon sinuplasty is being used worldwide, however the olfactory functions after balloon sinuplasty are underestimated. The authors aimed to study the effects of conventional endoscopic sinus surgery (ESS) compared to the balloon sinuplasty on olfactory function. Forty-four subjects were randomly divided into 2 groups as ESS and balloon sinuplasty. The olfactory functions of each subject were recorded preoperatively and at the 1st, 3rd, 6th, and 12th months postoperatively. The initial assessments of olfaction were the same in both groups. After the surgery, the olfactory functions were significantly better in those of ESS group (P < 0.05). The olfactory function is preserved better in the conventional surgery compared to the balloon catheter dilation of the frontal sinus.


Crystallization and preliminary X-ray diffraction analysis of the BRPF1 bromodomain in complex with its H2AK5ac and H4K12ac histone-peptide ligands.
The bromodomain-PHD finger protein 1 (BRPF1) is an essential subunit of the monocytic leukemia zinc (MOZ) histone acetyltransferase (HAT) complex and is required for complex formation and enzymatic activation. BRPF1 contains a structurally conserved bromodomain, which recognizes specific acetyllysine residues on histone proteins. The MOZ HAT plays a direct role in hematopoiesis, and deregulation of its activity is linked to the development of acute myeloid leukemia. However, the molecular mechanism of histone-ligand recognition by the BRPF1 bromodomain is currently unknown. The 117-amino-acid BRPF1 bromodomain was overexpressed in Escherichia coli and purified to homogeneity. Crystallization experiments of the BRPF1 bromodomain in complex with its H4K12ac and H2AK5ac histone ligands yielded crystals that were suitable for high-resolution X-ray diffraction analysis. The BRPF1 bromodomain-H4K12ac crystals belonged to the tetragonal space group P43212, with unit-cell parameters a = 75.1, b = 75.1, c = 86.3 Å, and diffracted to a resolution of 1.94 Å. The BRPF1 bromodomain-H2AK5ac crystals grew in the monoclinic space group P21, with unit-cell parameters a = 60.9, b = 55.6, c = 82.1 Å, β = 93.6°, and diffracted to a resolution of 1.80 Å. Complete data sets were collected from both crystal forms using synchrotron radiation on beamline X29 at Brookhaven National Laboratory (BNL).


Effects of propofol and inhaled anesthetics on postoperative complications for the patients undergoing one lung ventilation: A meta-analysis.
With the widespread use of one-lung ventilation (OLV) in thoracic surgery, it is unclear whether maintenance anesthetics such as propofol and inhaled anesthetics are associated with postoperative complications. The purpose of this study was to compare the effects of propofol and inhaled anesthetics on postoperative complications in OLV patients. PubMed, EMBASE, Medline, and Cochrane Library were searched for relevant randomized controlled trials until 09/2021. All randomized controlled trials comparing the effect of propofol versus inhaled anesthetics on postoperative complications in OLV patients were included. All randomized controlled trials comparing:(a) major complications (b) postoperative pulmonary complications (c) postoperative cognitive function (MMSE score) (d) length of hospital stay (e) 30-day mortality, were included. Thirteen randomized controlled trials involving 2522 patients were included in the analysis. Overall, there was no significant difference in major postoperative complications between the inhaled anesthetic and propofol groups (OR 0.78, 95%CI 0.54 to 1.13, p = 0.19; I2 = 0%). However, more PPCs were detected in the propofol group compared to the inhalation anesthesia group (OR 0.62, 95%CI 0.44 to 0.87, p = 0.005; I2 = 37%). Both postoperative MMSE score (SMD -1.94, 95%CI -4.87 to 0.99, p = 0.19; I2 = 100%) and hospital stay (SMD 0.05, 95%CI -0.29 to 0.39, p = 0.76; I2 = 73%) were similar between the two groups. The 30-day mortality rate was also not significantly different between groups (OR 0.79, 95%CI 0.03 to 18, p = 0.88; I2 = 63%). In patients undergoing OLV, general anesthesia with inhaled anesthetics reduced PPC compared to propofol, but did not provide clear benefits on other major complications, cognitive function, length of hospital stay, or mortality.


[Compartment syndrome of the foot].
Severe compression trauma of the foot predisposes to development of compartment syndrome. Special problems in complex lesions of the foot arise because of the thin layer of soft tissue coverage and the diminished blood supply to the bones of the foot, resulting in difficulties in estimate correctly the severity of the injury. Subfascial pressure monitoring is the most valuable diagnostic tool for establishing the diagnosis. The technique of decompression and fracture stabilization by K-wire osteosynthesis is described and emphasis is placed on tibial-metatarsal transfixation. Follow-up after open-wound treatment consists of a planned "second look" operation with delayed wound closure.


Neuroprotective hypothermia - Why keep your head cool during ischemia and reperfusion.
Targeted temperature management (TTM) is the induced cooling of the entire body or specific organs to help prevent ischemia and reperfusion (I/R) injury, as may occur during major surgery, cardiac resuscitation, traumatic brain injury and stroke. Ischemia and reperfusion induce neuronal damage by mitochondrial dysfunction and oxidative injury, ER stress, neuronal excitotoxicity, and a neuroinflammatory response, which may lead to activation of apoptosis pathways. The aim of the current review is to discuss TTM targets that convey neuroprotection and to identify potential novel pharmacological intervention strategies for the prevention of cerebral ischemia and reperfusion injury. TTM precludes I/R injury by reducing glutamate release and oxidative stress and inhibiting release of pro-inflammatory factors and thereby counteracts mitochondrial induced apoptosis, neuronal excitotoxicity, and neuroinflammation. Moreover, TTM promotes regulation of the unfolded protein response and induces SUMOylation and the production of cold shock proteins. These advantageous effects of TTM seem to depend on the clinical setting, as well as type and extent of the injury. Therefore, future aims should be to refine hypothermia management in order to optimize TTM utilization and to search for pharmacological agents mimicking the cellular effects of TTM. Bundling knowledge about TTM in the experimental, translational and clinical setting may result in better approaches for diminishing I/R damage. While application of TTM in the clinical setting has some disadvantages, targeting its putative protective pathways may be useful to prevent I/R injury and reduce neurological complications.


Simple and accurate method to evaluate tunneling splitting in polyatomic molecules.
A practical and accurate semiclassical method for calculating the tunneling splitting of the ground state in polyatomic molecules is presented based on a recent version of the instanton theory [J. Chem. Phys. 115, 6881 (2001)]. The method uses ab initio quantum chemical data for the potential energy surface without any concomitant extrapolation and requires only a small number of ab initio data points to get convergence even for large molecules. This enables one to use an advanced level of electronic structure theory and achieve a high accuracy of the result. The method is applied to the 9-atomic malonaldehyde molecule by making use of the potential energy surface at the level of CCSD(T) with the hybrid basis set of aug-cc-pVTZ (for oxygen atoms and the transferred hydrogen atom) and cc-pVTZ (for other atoms).


Understanding Heterogeneity in Patients' Conceptualisation of Treatment for Rheumatoid Arthritis: A Cluster Analysis.
Uptake of treat-to-target (TTT) strategies for rheumatoid arthritis (RA) management is low. Our objective was to understand the heterogeneity in patients' conceptualisation of RA treatment to inform interventions improving TTT uptake. Eligible participants recruited from an online research registry rated 56 items (on 5-point scales) reflecting concepts raised from patient interviews. Using items describing adhering to physician recommendations to create a binary criterion variable for medication adherence, we conducted a principal components analysis on the remaining items using Varimax rotation, describing how these factors predict adherence over and above demographic characteristics. We further use optimal sets in regression to identify the individual concepts that are most predictive of medication adherence. We found significant heterogeneity in patients' conceptualisation of RA treatment among 621 persons with RA. A scree plot revealed a four-factor solution explained 38.4% of the variance. The four factors expected to facilitate TTT uptake were (% variance explained): (1) Access to high quality care and support (11.3%); (2) low decisional conflict related to changing disease-modifying antirheumatic drugs (DMARDs) (10.1%); (3) endorsement of a favourable DMARD risk/benefit ratio (9.9%); and (4) confidence that testing reflects disease activity (7.2%). These factors account for 13.8% of the variance in full medication adherence, fully explaining the only significant demographic predictor, age of the patient. The individual items most predictive of poor adherence centre on the lack of effective patient-physician communication, specifically insufficient access to information from rheumatologists, along with the need to seek information elsewhere. Patients' conceptualisation of RA treatment varies; however, almost all patients have difficulty escalating DMARDs, even with access to quality information and an understanding of the benefits of TTT. Tailored interventions are needed to address patient hesitancy to escalate DMARDs.


Prognostic role of different PD-L1 expression patterns and tumor-infiltrating lymphocytes in high-grade serous ovarian cancer: a systematic review and meta-analysis.
The prognostic value of programmed cell death ligand 1 (PD-L1) expression and tumor-infiltrating lymphocytes (TILs) in high-grade serous ovarian cancer (HGSOC) remains a controversial topic in the research field. To comprehensively assess the importance of PD-L1 and TILs in this particular subtype of ovarian cancer, we performed a meta-analysis. We conducted a comprehensive search of PubMed, Embase, Scopus, Web of Science, and Cochrane Library databases up to December 25, 2022. The association between PD-L1, TILs, and survival outcomes was evaluated using the combined hazard ratios (HRs) and their corresponding 95% confidence intervals (CIs). This meta-analysis comprised 11 trials involving a total of 1746 cases. The results revealed no significant association between PD-L1 expression in tumor cells (TCs) and overall survival (OS, HR = 0.76, 95% CI: 0.52-1.09, p = 0.136) or progression-free survival (PFS, HR = 0.71, 95% CI: 0.4 -1.24, p = 0.230). Nevertheless, a correlation was observed between PD-L1 expression in immune cells (ICs) and OS (HR = 0.73, 95% CI: 0.55-0.97, p = 0.031). Furthermore, the presence of CD8+ and PD-1+ TILs was found to significantly enhance OS (HR = 0.70, 95% CI = 0.55-0.87, p = 0.002; HR = 0.57, 95% CI = 0.40-0.80, p = 0.001, respectively) and PFS (HR = 0.62, 95% CI = 0.41-0.92, p = 0.019; HR = 0.52, 95% CI = 0.35-0.78, p = 0.002, respectively), whereas the presence of CD3+ and CD4+ TILs was positively associated with OS (HR = 0.50, 95% CI = 0.29-0.87, p = 0.014; HR = 0.55, 95% CI = 0.34-0.91, p = 0.020, respectively). This study indicates a positive correlation between ICs-derived PD-L1 and survival, while no significant correlation was observed between TCs-derived PD-L1 and prognosis. These results highlight the importance of studying PD-L1 expression in ICs as a prognostic predictor. In addition, the presence of TILs was found to significantly improve patient survival, suggesting that TILs may be a valuable prognostic biomarker. https://www.crd.york.ac.uk/prospero/, identifier CRD42022366411.


Claimed effects, outcome variables and methods of measurement for health claims proposed under European Community Regulation 1924/2006 in the area of blood glucose and insulin concentrations.
Most requests for authorization to bear health claims under Articles 13(5) and 14 related to blood glucose and insulin concentration/regulation presented to the European Food Safety Authority (EFSA) receive a negative opinion. Reasons for such decisions are mainly ascribable to poor substantiation of the claimed effects. In this scenario, a project was carried out aiming at critically analysing the outcome variables (OVs) and methods of measurement (MMs) to be used to substantiate health claims, with the final purpose to improve the quality of applications provided by stakeholders to EFSA. This manuscript provides a position statement of the experts involved in the project, reporting the results of an investigation aimed to collect, collate and critically analyse the information relevant to claimed effects (CEs), OVs and MMs related to blood glucose and insulin levels and homoeostasis compliant with Regulation 1924/2006. The critical analysis of OVs and MMs was performed with the aid of the pertinent scientific literature and was aimed at defining their appropriateness (alone or in combination with others) to support a specific CE. The results can be used to properly select OVs and MMs in a randomized controlled trial, for an effective substantiation of the claims, using the reference method(s) whenever available. Moreover, results can help EFSA in updating the guidance for the scientific requirements of health claims.


Men's health promotion: a new frontier in Australia and the UK?
The field of men's health has grown markedly over the past few decades. Increased activity specifically relating to men's health promotion in both Australia and the UK has been noted during this period. There has, however, been a reticence to critically examine men's health promotion work within a broader discourse relating to gender and gender relations. Indeed, the vast majority of health-related gender discussion to date has been focused on women's health experiences and their health practices. In this paper, we argue that grounding men's health within this broad gender discourse is important for building an evidence base in, and advancing, men's health promotion work at a range of levels. We specifically explore the research, practice and policy contexts relating to men's health in Australia and the UK, and describe the facilitators for, and barriers to, promoting men's health. We conclude by suggesting that a critical gender lens ought to be applied to current men's health promotion work and provide strategies for researchers, practitioners and policy makers to move towards this new frontier.


[Nodular fasciitis of the orbit].
A 46-year-old patient is described who presented with a pea-sized painless tumor in the upper eyelid. Surgical excision and histologic diagnosis revealed a proliferating spindle cell tumor with an inflammatory reaction, which was identified as nodular fasciitis. Differential diagnosis, incidence of such tumors in the orbit and treatment are discussed.


Factors influencing proxy online health information seeking among the elderly: A study from the perspective of the elderly with chronic illnesses.
With the ageing population in China and an increasing number of the elderly developing chronic illnesses, health services for the elderly have become a major concern. They have significant needs for health information (HI) such as online medical consultation, disease prevention, and medical insurance. To explore the influencing factors and their relative significance in proxy online health information (OHI) seeking among the elderly with chronic illnesses so as to provide a reference for enriching theoretical research and optimizing care for the elderly with chronic illness. Twenty-three elderly people with chronic illnesses participated in semi-structured in-depth interviews in this study. The interview transcripts were subject to three levels of coding (open, axial, and selective coding) based on grounded theory to determine the factors influencing proxy OHI seeking among the elderly and to understand how the main categories are interconnected. We used the interpretive structural modeling (ISM) process to analyze the hierarchy and associated pathways among the factors influencing proxy OHI seeking. From our analysis, we identified four main categories affecting proxy HI seeking: the health status, emotional needs, electronic HI literacy, and self-efficacy of the elderly. There were six subcategories that could be further subclassified into direct factors, key factors, and root factors, which constituted the hierarchical model of influencing factors. We found that proxy HI seeking among the elderly was directly triggered by self-efficacy and emotional needs following changes in their evaluation of health information and emotional needs, which originates from their perceptions of their health, concerns about their health, and information retrieval capability.


Comparison of structural architecture of HCV NS3 genotype 1 versus Pakistani genotype 3a.
This study described the structural characterization of Pakistani HCV NS3 GT3a in parallel with genotypes 1a and 1b NS3. We investigated the role of amino acids and their interaction patterns in different HCV genotypes by crystallographic modeling. Different softwares were used to study the interaction pattern, for example, CLCBIO sequence viewer, MODELLER, NMRCLUST, ERRAT score, and MODELLER. Sixty models were produced and clustered into groups and the best model of PK-NCVI/Pk3a NS3 was selected and studied further to check the variability with other HCV NS3 genotypes. This study will help in future to understand the structural architecture of HCV genome variability and to further define the conserved targets for antiviral agents.


Limited compatibility of polymerase subunit interactions in influenza A and B viruses.
Despite their close phylogenetic relationship, natural intertypic reassortants between influenza A (FluA) and B (FluB) viruses have not been described. Inefficient polymerase assembly of the three polymerase subunits may contribute to this incompatibility, especially because the known protein-protein interaction domains, including the PA-binding domain of PB1, are highly conserved for each virus type. Here we show that substitution of the FluA PA-binding domain (PB1-A(1-25)) with that of FluB (PB1-B(1-25)) is accompanied by reduced polymerase activity and viral growth of FluA. Consistent with these findings, surface plasmon resonance spectroscopy measurements revealed that PA of FluA exhibits impaired affinity to biotinylated PB1-B(1-25) peptides. PA of FluB showed no detectable affinity to biotinylated PB1-A(1-25) peptides. Consequently, FluB PB1 harboring the PA-binding domain of FluA (PB1-AB) failed to assemble with PA and PB2 into an active polymerase complex. To regain functionality, we used a single amino acid substitution (T6Y) known to confer binding to PA of both virus types, which restored polymerase complex formation but surprisingly not polymerase activity for FluB. Taken together, our results demonstrate that the conserved virus type-specific PA-binding domains differ in their affinity to PA and thus might contribute to intertypic exclusion of reassortants between FluA and FluB viruses.


Peptide vaccines for hepatocellular carcinoma.
Immunotherapy is a potentially attractive treatment option for patients with hepatocellular carcinoma (HCC). We have reported that glypican-3 (GPC3) is an ideal target for anticancer immunotherapy against HCC because its expression is specifically detected in > 80% of HCCs, even during the early stages. Further, increased GPC3 expression is correlated with a poor prognosis. Based on results obtained from a preclinical study using mice, we conducted a phase I clinical trial using a GPC3-derived peptide vaccine. Phase I results showed that the GPC3-derived peptide vaccine was well tolerated. Furthermore, this was the first study to show that the frequency of peptide-specific cytotoxic T lymphocytes was correlated with overall survival in patients with HCC receiving a peptide vaccine. Next, we conducted a phase II clinical trial using the GPC3-derived peptide vaccine in patients with HCC after surgery or radiofrequency ablation (adjuvant setting). We are currently evaluating a third trial involving liver biopsies removed from patients with advanced HCC before and after GPC3-derived peptide vaccination. We expect that the results of these trials will result in future drug development.


Inhibition of Glycolysis in Prostate Cancer Chemoprevention by Phenethyl Isothiocyanate.
We have shown previously that dietary administration of phenethyl isothiocyanate (PEITC), a small molecule from edible cruciferous vegetables, significantly decreases the incidence of poorly differentiated prostate cancer in Transgenic Adenocarcinoma of Mouse Prostate (TRAMP) mice without any side effects. In this study, we investigated the role of c-Myc-regulated glycolysis in prostate cancer chemoprevention by PEITC. Exposure of LNCaP (androgen-responsive) and 22Rv1 (castration-resistant) human prostate cancer cells to PEITC resulted in suppression of expression as well as transcriptional activity of c-Myc. Prostate cancer cell growth inhibition by PEITC was significantly attenuated by stable overexpression of c-Myc. Analysis of the RNA-Seq data from The Cancer Genome Atlas indicated a significant positive association between Myc expression and gene expression of many glycolysis-related genes, including hexokinase II and lactate dehydrogenase A Expression of these enzyme proteins and lactate levels were decreased upon PEITC treatment in prostate cancer cells, and these effects were significantly attenuated by ectopic expression of c-Myc. A normal prostate stromal cell line (PrSC) was resistant to lactic acid suppression by PEITC treatment. Prostate cancer chemoprevention by PEITC in TRAMP mice was associated with a significant decrease in plasma lactate and pyruvate levels. However, a 1-week intervention with 10 mg PEITC (orally, 4 times/day) was not sufficient to decrease lactate levels in the serum of human subjects. These results indicated that although prostate cancer prevention by PEITC in TRAMP mice was associated with suppression of glycolysis, longer than 1-week intervention might be necessary to observe such an effect in human subjects. Cancer Prev Res; 11(6); 337-46. ©2018 AACR.


Endovascular covered stenting for visceral artery pseudoaneurysm rupture: report of 2 cases and a summary of the disease process and treatment options.
We present 2 cases of hemorrhage from a visceral artery pseudoaneurysm, managed successfully with endovascular covered stent placement. The first case was a 59-year-old man, 3 months after a laparoscopic distal pancreatectomy for adenoma, presenting with diffuse abdominal pain. The patient was evaluated with a computed tomography scan revealing a splenic artery pseudoaneurysm (PA) bleeding into a pancreatic pseudocyst. He was emergently taken to the angiography suite where a covered stent was deployed at the level of splenic artery PA. The second case was a 52-year-old woman with recurrent left retroperitoneal mass 5 years after distal pancreatectomy and splenectomy for a nonfunctional neuroendocrine tumor. She underwent resection of the mass in the left upper quadrant. Postoperative course was complicated by hematoma, abscess formation, reexploration, and repair of the duodenotomy and the portal vein. Subsequently, she was noted to have intermittent gastrointestinal hemorrhage, which prompted an angiogram revealing a hepatic artery PA that was repaired with a covered balloon-expandable stent. A completion angiogram was obtained in each case demonstrating exclusion of the PA. Our experience with these 2 cases supports the notion that endovascular covered stenting is a safe and effective therapy for exclusion of visceral artery aneurysm.


Long-term follow-up of intraocular lens implants: the first 127 compared with the latest 100 of the same style in a span of 9 years.
The long-term follow up of the first 127 patients (127 eyes) treated by one surgeon with cataract extraction and Federov I lens implantation is reported. The proportion of patients achieving visual acuity of 6/12 or better had decreased since the one year follow-up. Corneal oedema was the most serious long-term complication. This group of patients is compared with the latest 100 patients (100 eyes) operated on by the same surgeon using the same type of implant. There was a reduction of some operative complications, and improvement in surgical techniques had resulted in a lower sample endothelial cell loss at one month.


Development and Validation of the Standard Chinese Version of the CARE Item Set (CARE-C) for Stroke Patients.
The Continuity Assessment Record and Evaluation (CARE) item set is a standardized, integrative scale for evaluation of functional status across acute and postacute care (PAC) providers. The aim of this study was to develop a Chinese version of the CARE (CARE-C) item set and to examine its reliability and validity for assessment of functional outcomes among stroke patients.The CARE-C was administered in two samples. Sample 1 included 30 stroke patients in the outpatient clinic setting for the purpose of examining interrater and test-retest reliabilities and internal consistency. Sample 2 included 138 stroke patients admitted to rehabilitation units for the purpose of investigating criterion-related validity with the Barthel index, Lawton Instrumental Activities of Daily Living (IADL) scale, EuroQOL five dimensions questionnaire (EQ-5D), and Mini-Mental State Examination (MMSE).The CARE-C was categorized into 11 subscales, 52 items of which were analyzed. At the subscale level, the interrater reliability and test-retest reliability expressed by intraclass correlation coefficient (ICC) ranged from 0.72 to 0.99 and 0.60 to 1.00, respectively. Six of the 11 subscales met acceptable levels of internal consistency (Cronbach alpha > 0.7). The criterion-related validity of the CARE-C showed moderate to high correlations of its subscales of cognition and basic and instrumental activities of daily living with the Barthel index, IADL scale, and MMSE.The CARE-C is a useful instrument for evaluating functional quality metrics in the Chinese stroke population. The development of the CARE-C also facilitates the assessment of the PAC program in Taiwan and future research is warranted for validating the capability of CARE-C to identify patients' functional change over time and its generalizability for nonstroke populations.


The Value of Sleep on Athletic Performance, Injury, and Recovery in the Young Athlete.
Adequate sleep can easily become compromised as student-athletes try to balance the multiple demands on their time. People with sleep deficiency are at increased risk for acute illnesses, traumatic sports injuries, and development of chronic diseases. Training sessions or competitions during extremely early or late hours can interfere with circadian and homeostatic rhythms. Adjusting the training schedule to improve sleep duration has a significantly positive impact on several aspects of athletic performance. Pediatricians should increase the time dedicated in well-child visits for sleep hygiene and evaluate for sleep disorders at all ages. Parents, coaching staff, teachers, and pediatricians should advocate for improved education on the importance of sleep during adolescence. Future sleep research specific to adolescent athletes can further delineate requirements specific to sport, gender, training times, and surrounding competitions. [Pediatr Ann. 2017;46(3):e106-e111.].


AP-MALDI Mass Spectrometry Imaging of Gangliosides Using 2,6-Dihydroxyacetophenone.
Matrix-assisted laser/desorption ionization (MALDI) mass spectrometry imaging (MSI) is widely used as a unique tool to record the distribution of a large range of biomolecules in tissues. 2,6-Dihydroxyacetophenone (DHA) matrix has been shown to provide efficient ionization of lipids, especially gangliosides. The major drawback for DHA as it applies to MS imaging is that it sublimes under vacuum (low pressure) at the extended time necessary to complete both high spatial and mass resolution MSI studies of whole organs. To overcome the problem of sublimation, we used an atmospheric pressure (AP)-MALDI source to obtain high spatial resolution images of lipids in the brain using a high mass resolution mass spectrometer. Additionally, the advantages of atmospheric pressure and DHA for imaging gangliosides are highlighted. The imaging of [M-H]- and [M-H2O-H]- mass peaks for GD1 gangliosides showed different distribution, most likely reflecting the different spatial distribution of GD1a and GD1b species in the brain. Graphical Abstract .


Impact of patient knowledge, patient-pharmacist relationship, and drug perceptions on adverse drug therapy outcomes.
The purpose of this project was to determine the relationship between adverse drug outcomes and knowledge of drugs, quality of a counseling relationship, and perceptions about drugs in an ambulatory clinic population. The presence of these three factors and other indicators of adverse outcomes were identified through a structured interview of 78 patients. Medical records were reviewed 3, 6, and 12 months after the initial interview to determine the presence of adverse drug outcomes. Four outcomes-hospitalizations, unscheduled clinic visits, emergency room visits, and changes in drug regimen-were assessed and categorized according to drug-related problem. Demographics of the group were recorded. Responses to the interview were analyzed to determine differences in counseling relationships between pharmacists and other health professionals. Logistic regression analysis was performed to determine the influence of independent variables on outcome. Relative risks for developing adverse outcomes given the presence of certain independent variables were calculated for significant associations. Significant relationships between predictor variables and adverse drug outcomes were identified for the following independent variables: female gender (RR = 5.2, CI 1.11, 24.31), three or more diseases (RR = 3.3, CI 1.13, 9.75), more drug knowledge and better perceptions (RR = 0.29, CI 0.10, 0.84), perception of no or low drug interference (RR = 0.18, CI 0.044, 0.745), and inadequate data collection by nurses and physicians as perceived by the patient (RR = 3.08, CI 1.09, 8.70). More knowledge and better perceptions about drugs were associated with a reduced risk of therapy changes due to drug-related problems. No association was found between the quality of the pharmacist-patient counseling relationship and adverse drug outcomes.


Multiomic analysis of malignant pleural mesothelioma identifies molecular axes and specialized tumor profiles driving intertumor heterogeneity.
Malignant pleural mesothelioma (MPM) is an aggressive cancer with rising incidence and challenging clinical management. Through a large series of whole-genome sequencing data, integrated with transcriptomic and epigenomic data using multiomics factor analysis, we demonstrate that the current World Health Organization classification only accounts for up to 10% of interpatient molecular differences. Instead, the MESOMICS project paves the way for a morphomolecular classification of MPM based on four dimensions: ploidy, tumor cell morphology, adaptive immune response and CpG island methylator profile. We show that these four dimensions are complementary, capture major interpatient molecular differences and are delimited by extreme phenotypes that-in the case of the interdependent tumor cell morphology and adapted immune response-reflect tumor specialization. These findings unearth the interplay between MPM functional biology and its genomic history, and provide insights into the variations observed in the clinical behavior of patients with MPM.


Iron regulatory proteins: players or pawns in ferroptosis and cancer?
Cells require iron for essential functions like energy production and signaling. However, iron can also engage in free radical formation and promote cell proliferation thereby contributing to both tumor initiation and growth. Thus, the amount of iron within the body and in individual cells is tightly regulated. At the cellular level, iron homeostasis is maintained post-transcriptionally by iron regulatory proteins (IRPs). Ferroptosis is an iron-dependent form of programmed cell death with vast chemotherapeutic potential, yet while IRP-dependent targets have established roles in ferroptosis, our understanding of the contributions of IRPs themselves is still in its infancy. In this review, we present the growing circumstantial evidence suggesting that IRPs play critical roles in the adaptive response to ferroptosis and ferroptotic cell death and describe how this knowledge can be leveraged to target neoplastic iron dysregulation more effectively.


Recent research and clinical progress of CTLA-4-based immunotherapy for breast cancer.
Breast cancer is characterized by a high incidence rate and its treatment challenges, particularly in certain subtypes. Consequently, there is an urgent need for the development of novel therapeutic approaches. Immunotherapy utilizing immune checkpoint inhibitors (ICIs) is currently gaining momentum for the treatment of breast cancer. Substantial progress has been made in clinical studies employing cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) inhibitors for breast cancer, but the cure rates are relatively low. To improve the efficacy of CTLA-4-based therapy for breast cancer, further research is imperative to explore more effective immune-based treatment strategies. In addition to monotherapy, CTLA-4 inhibitors are also being investigated in combination with other ICIs or alternative medications. However, it should be noted that immune-based treatments may cause adverse events. This review focuses on the mechanisms of CTLA-4 inhibitor monotherapy or combination therapy in breast cancer. We systematically summarize the latest research and clinical advances in CTLA-4-based immunotherapy for breast cancer, providing new perspectives on the treatment of breast cancer. In addition, this review highlights the immune-related adverse events (irAEs) associated with CTLA-4 inhibitors, providing insights into the development of appropriate clinical tumor immunotherapy regimens and intervention strategies.


[Lung transplanted patient climbing a mountain higher than 4,000 metres. Comparison with healthy climbers].
To ascertain if a bilaterally lung transplanted patient can climb a mountain higher than 4,000 metres and to compare the evolution of his physiological parameters during the ascent with those of healthy mountaineers. Heart rate, blood pressure, arterial oxygen saturation (SaO2), forced vital capacity, forced expiratory volume in one second, Tiffenau test, 25-75 mesoexpiratory flow, peak flow, severity of dyspnoea (analogic score) and symptoms and signs of acute mountain sickness (lake Louise and Serrano-Alcócer scores) were measured in a bilaterally lung transplanted patient and in 4 healthy mountaineers at sea level and at different altitudes during the ascent of Breithorn (4,164 m) from Zermatt in 3 days. All subjects attained the summit. The transplanted patient suffered from an acute mountain sickness at 2,700 m but recovered spontaneously. No other substantial differences were found during the climb between the patient's physiological parameters and those of the healthy controls. On the summit (third day) the patient's SaO2 (90%) was higher than the figure which should be theoretically expected for this altitude among non-acclimatised subjects (81%). Our study confirms that it is possible for a bilaterally lung transplanted patient to climb by his own effort a mountain higher than 4,000 m with no physiological changes other than those experienced by healthy mountaineers. Considering the spontaneous recovery from the acute mountain sickness and the high SaO2 on the summit of Breithorn, we conclude that lung transplantation does not necessarily prevent altitude acclimatisation.


Surfactant inhibits cationic liposome-mediated gene transfer.
We have demonstrated that tracheal insufflation of recombinant plasmid DNA results in transfection of rat lungs to the same extent as insufflation of plasmid-cationic liposome complex. To understand this observation better, we investigated the in vitro gene transfer of plasmid DNA in the presence and absence of cationic liposome and the effect of surfactant on gene transfer. The chloramphenicol acetyltransferase (CAT) expression plasmids pBL-CAT and pSV-CAT were studied in three cell types: rat fetal lung fibroblast (RFL-6), calf pulmonary artery endothelial cell (CPAE), and rat type II alveolar epithelial cell (type II AE). Three cationic liposomes were tested: DDAB (dimethyl-dioctadecyl ammonium bromide)-liposome, DOTAP (dioleoyltrimethyl ammonium propane)-liposome, and lipofectin. The results revealed that (i) plasmid DNA alone caused a dose-dependent, low-level transfection, most efficiently in RFL-6 followed by CPAE and type II AE, (ii) DDAB-liposome markedly enhanced gene transfer, most efficiently in RFL-6 followed by CPAE and type II AE, (iii) Survanta, a naturally derived surfactant preparation, and Exosurf, a synthetic surfactant, while having no effect on in vitro gene transfer by plasmid DNA alone, markedly inhibited cationic liposome-mediated gene transfer, (iv) dipalmitoyl phosphatidylcholine was responsible for the inhibitory effect of Exosurf, and (v) inhibition of cationic liposome-mediated gene transfer by Exosurf was not due to inhibition of plasmid DNA-cationic liposome complex uptake or interference with the promoter and enhancer. The observed inhibition of cationic liposome-mediated gene transfer by surfactant may in part explain our previous observation that tracheal insufflation of plasmid DNA and plasmid-cationic liposome complex results in equal lung gene transfer.


Study on attitudes of students of Islamic Azad University Tehran Medical Branch toward food safety, 2016.
Given the importance of high-quality healthy food for humans, contamination control is the most important concern for healthy staff. To determine the attitudes of students at Islamic Azad University (Tehran Medical Branch) toward food safety. This cross-sectional and analytic-descriptive study was conducted on 326 students of Azad University of Medical Sciences in 2016. A self-made questionnaire consisting of 40 questions was used. The reliability of the questionnaire was confirmed using internal consistency method (Cronbach's alpha coefficient of 0.80). After collecting data, we use descriptive statistical indexes (mean and standard deviation) among demographic variables and the level of knowledge to describe and analyze the data. The participants' attitudes and operation are measured by Spearman tests, and the analytical results are given using SPSS version 20. According to the findings, 55.3, 30 and 14.7 percent of students had high, moderate and low attitude scores toward food safety, respectively. In addition, male and female students had equal attitudes toward food safety, and no significant relationship between sex and attitude was observed a significant difference (p>0.05), but between educational levels (p=0.008) and ages (p=0.001) of students significance was a positive correlation. Due to the low attitudes score of about half of the students of Islamic Azad University Tehran Medical Branch toward food safety, it can be claimed, food safety training in this community is required.


Characterization of Stromatolite Organic Sedimentary Structure Based on Spectral Image Fusion.
This paper evaluates the potential application of Raman baselines in characterizing organic deposition. Taking the layered sediments (Stromatolite) formed by the growth of early life on the Earth as the research object, Raman spectroscopy is an essential means to detect deep-space extraterrestrial life. Fluorescence is the main factor that interferes with Raman spectroscopy detection, which will cause the enhancement of the Raman baseline and annihilate Raman information. The paper aims to evaluate fluorescence contained in the Raman baseline and characterize organic sedimentary structure using the Raman baseline. This study achieves spectral image fusion combined with mapping technology to obtain high spatial and spectral resolution fusion images. To clarify that the fluorescence of organic matter deposition is the main factor causing Raman baseline enhancement, 5041 Raman spectra were obtained in the scanning area of 710 μm × 710 μm, and the correlation mechanism between the gray level of the light-dark layer of the detection point and the Raman baseline was compared. The spatial distribution of carbonate minerals and organic precipitations was detected by combining mapping technology. In addition, based on the BI-IHS algorithm, the spectral image fusion of Raman fluorescence mapping and reflection micrograph, polarization micrograph, and orthogonal polarization micrograph are realized, respectively. A fusion image with high spectral resolution and high spatial resolution is obtained. The results show that the Raman baseline can be used as helpful information to characterize stromatolite organic sedimentary structure.


Elucidating the Effect of Accelerated Carbonation on Porosity and Mechanical Properties of Hydrated Portland Cement Paste Using X-Ray Tomography and Advanced Micromechanical Testing.
Carbonation of hydrated cement paste (HCP) causes numerous chemo-mechanical changes in the microstructure, e.g., porosity, strength, elastic modulus, and permeability, which have a significant influence on the durability of concrete structures. Due to its complexity, much is still not understood about the process of carbonation of HCP. The current study aims to reveal the changes in porosity and micromechanical properties caused by carbonation using micro-beam specimens with a cross-section of 500 μm × 500 μm. X-ray computed tomography and micro-beam bending tests were performed on both noncarbonated and carbonated HCP micro-beams for porosity characterization and micromechanical property measurements, respectively. The experimental results show that the carbonation decreases the total porosity and increases micromechanical properties of the HCP micro-beams under the accelerated carbonation. The correlation study revealed that both the flexural strength and elastic modulus increase linearly with decreasing porosity.


Efficacy and safety of intracoronary prourokinase during percutaneous coronary intervention in treating ST-segment elevation myocardial infarction patients: a randomized, controlled study.
Prourokinase is a single-chain plasminogen activator presenting with fewer hemorrhagic complications and reduced reocclusion rate compared with the conventional fibrinolytic agents in patients with coronary artery disease. However, prourokinase intracoronary injection during PCI for treating patients with ST-segment elevation myocardial infarction (STEMI) is rarely investigated. Therefore, this study aimed to evaluate the efficacy and safety of intracoronary prourokinase during the percutaneous coronary intervention (PCI) in treating STEMI patients. Fifty STEMI patients who underwent primary PCI were consecutively enrolled and randomly assigned to intracoronary prourokinase group (N = 25) or control group (N = 25). During the primary PCI procedure, patients in the intracoronary prourokinase group received 10 ml prourokinase injection, while patients in control group received 10 ml saline injection as control. The primary endpoints were coronary physiological indexes, the secondary endpoints were angiographic assessments, myocardial infarct size/reperfusion assessment, cardiac function evaluations, major adverse coronary events (MACEs) and hemorrhagic complications. All patients were followed up for 3 months. Post PCI, the index of microcirculatory resistance (IMR) was decreased in intracoronary prourokinase group than that in control group (34.56 ± 7.48 vs. 49.00 ± 8.98, P < 0.001), while no difference of coronary flow reserve (CFR) (2.01 ± 0.32 vs. 1.88 ± 0.23, P = 0.267) or fractional flow reserve (FFR) (0.89 ± 0.05 vs. 0.87 ± 0.04, P = 0.121) was found between the two groups. The thrombolysis in myocardial infarction myocardial perfusion grade (TMPG) (P = 0.024), peak values of creatine kinase (CK) (P = 0.028), CK isoenzyme-MB (CK-MB) (P = 0.016), cardiac troponin I (cTnI) (P = 0.032) and complete ST-segment resolution (STR) (P = 0.005) were better in intracoronary prourokinase group compared with control group. At 3-months post PCI, left ventricular ejection fraction (LVEF) and wall motion score index (WMSI) were higher, while left ventricular end-diastolic diameter (LVEDd) was lower in intracoronary prourokinase group compared with control group (all P < 0.05). There was no difference in hemorrhagic complication or total MACE between the two groups. Intracoronary prourokinase during PCI is more efficient and equally tolerant compared with PCI alone in treating STEMI patients. Chinese Clinical Trial Registry ChiCTR1800016207 . Prospectively registered.


[Surgical classification of the diabetic foot syndrome].
Surgical classification of the diabetic foot syndrome was proposed, permitting to formulate pathogenetic diagnosis with working out in detail the foot pathologic process depth and expansion, taking into account the microflora presence in the purulent-necrotic affection zone, basing on own experience of treatment of 490 patients. This permits to formulate tactic and volume of necessary pathogenetic surgical and conservative treatment.


Hydrophilic contact lenses for wound stabilization in keratoplasty.
Hydrophilic contact lenses may be used in selected cases in which penetrating keratoplasty is complicated by partial wound dehiscence and anterior slippage of the donor tissue. We report five cases and describe a technique in which, rather than resuturing, a soft contact lens is used as a corneal stent to realign the graft-host interface. This technique allows for non-surgical correction of a potentially serious complication, with preservation of good vision during the treatment period. In the present series, no serious complications were encountered, and all wounds were adequately reapposed. Successful application of this technique requires appropriate patient selection and careful monitoring during the course of treatment.


[Comparison of perioperative complications between simultaneous and staged bilateral total knee arthroplasty].
To compare the rates of perioperative complications in matched patients undergoing simultaneous bilateral total knee arthroplasty, or staged bilateral total knee arthroplasty. A total of 219 cases of bilateral total knee arthroplasty were performed from October 1996 to October 2006. It consisted 171 simultaneous and 48 staged (group B) bilateral total knee arthroplasty. Forty-eight patients were matched with group B for age and sex from simultaneous group (group A). A retrospective review of each group was conducted to compare the rates of perioperative complications. No significant differences between the two matched groups were found with regard to preoperative co-morbidities (P > 0.05). The percentage of patients who had cardiovascular and cerebrovascular complications was significantly higher in the simultaneous group than in the staged group (P < 0.05). Preoperative health status must be assessed carefully. Patients must be fully informed of the risks of simultaneous bilateral total knee arthroplasty before surgery. Active prevention of perioperative complications must be applied after surgery.


Perceptions of undereaters: a matter of perspective?
We assume that people, to convey positive impressions of themselves, use the amounts eaten by others as limits beyond which their eating may be deemed excessive. One should, therefore, prefer eating partners who eat a lot because others' large intake renders one's own eating nonexcessive. Two studies were conducted to test this hypothesis. As predicted, participants liked confederates who ate more than they did better than those who ate less than they did, and they also rated their own intake as more appropriate when it had been exceeded by confederates than they did when it had been undercut by confederates. Noneating observers, instead, did not display a preference for eaters who ate more. Both noneating observers and active participants, however, rated eaters who ate less more positively than eaters who ate more on self-control-related items. We conclude that the nature of the behavior-impression association depends critically on the perspective of the rater.


Interim results: influenza A (H1N1) 2009 monovalent and seasonal influenza vaccination coverage among health-care personnel - United States, August 2009-January 2010.
Since 1986, the Healthcare Infection Control Practices Advisory Committee (HICPAC) and the Advisory Committee on Immunization Practices (ACIP) have recommended that all health-care personnel (HCP) be vaccinated annually for influenza. Since 1989, overall influenza vaccination coverage among HCP has never exceeded 49% in any season, according to estimates from the National Health Interview Survey. In August 2009, ACIP recommended that HCP be one of five initial target groups to receive the influenza A (H1N1) 2009 monovalent vaccine when it first became available. This report summarizes results of a population-based panel survey administered via the Internet during January 2010 to a nationally representative sample of 1,417 HCP to assess vaccination coverage. By mid-January 2010, estimated vaccination coverage among HCP was 37.1% for 2009 pandemic influenza A (H1N1) and 61.9% for seasonal influenza. Overall, 64.3% received either of these influenza vaccines, higher coverage than any previous season, but only 34.7% of HCP reported receiving both vaccines. The existence of an employer requirement for vaccination at the facility where the respondent was employed was associated with an eightfold greater likelihood of 2009 H1N1 vaccination compared with respondents employed by facilities with neither requirement nor recommendations; likewise, the existence of a recommendation for vaccination was associated with a fourfold greater probability of 2009 H1N1 vaccination. Health-care administrators should consider influenza vaccination coverage among employees an important measure of patient safety and make appropriate efforts to increase coverage in future seasons.


Pineal germinoma in a young adult: A case report.
Intracranial germinomas (GN) are rare cancers that primarily affect children, making them rarer still in adults. Standard treatment for this neoplasm includes neoadjuvant chemotherapy (NC) followed by radiotherapy (RT) or RT at a higher dose and larger field. These recommendations are based on studies focused mostly on children; it is currently unclear whether this treatment is applicable to adults. We present a case of a 23-year-old adult male with no underlying pathologies, drug allergies, or family history of cancer, who presented for medical evaluation with blurred vision, diplopia, forgetfulness, and weight loss starting 3-4 months before the evaluation. Clinical examination indicated Parinaud's Syndrome. Magnetic resonance imaging (MRI) and computed tomography (CT) revealed a pineal tumor with ependymal dissemination in both lateral ventricles, which was causing obstructive hydrocephalus. The patient had surgery consisting of ventriculostomy, Holter shunt insertion, cisternal ventricular intubation, and cisterna magna anastomosis to improve ventricular drainage. Pathology confirmed pineal germinoma. Cerebrospinal fluid cytology and MRI of the axis were negative. Four cycles of NC were given to the patient (carboplatin, etoposide, and ifosfamide), with reduced dosage. Once a partial volumetric response was confirmed, whole-ventricular radiotherapy (WVR) was initiated with a total tumor bed dose of 45 Gy over 25 sessions in 5 weeks. Optimum clinical results were observed, and no short-term (<90 day) radiation toxicity was observed. The patient was able to resume his normal activities soon after treatment. Follow-ups over 2 years post-surgery indicated continued control of the lesion and absence of symptoms except for mild diplopia. Although this is a case report, these data suggest that a reduced NC course and WVR may effectively treat adult GN. This protocol likely decreases the risk of undesirable NC and RT secondary effects, while providing excellent local control; however, using a narrower RT field is not recommended.


Spirituality as experienced by Muslim oncology nurses in Iran.
Spirituality, as an essential part of holistic care, is concerned with faith and meaning, and is usually conceptualised as a 'higher' experience or a transcendence of oneself. A resurgence of interest in this area is evident in post modern culture because of the effects that spirituality and religious beliefS may have on health. Up until the last two decades, spirituality and spiritual care, although vital, were invisible aspects of nursing. However, now that these concepts have made their way into the mainstream, literature in this area has burgeoned. In addition, modern nursing grew out of spiritual roots, and spiritual care is a component of holistic care. In the Islamic Republic of Iran,little information exists documenting the expressed spirituality of nurses in general and of oncology nurses in particular. This article presents spirituality as it is experienced by Muslim oncology nurses.The investigation involved a qualitative analysis of the spirituality of 24 participants, using semi-structured interviews. Participants were oncology nurses at 12 hospitals in two educational universities of medical sciences in Tehran. The main categories of spirituality as experienced by oncology nurses included religious and existential dimensions in an Iranian Muslim context. Findings are consistent with the holistic view of Islam, that considers all dimensions of personhood simultaneously. This study is important to transcultural nursing because of the benefits of increasing nursing knowledge through research that examines nurses' spirituality in diverse cultures.


Epigenetics of autism spectrum disorders.
The autism spectrum disorders (ASD) comprise a complex group of behaviorally related disorders that are primarily genetic in origin. Involvement of epigenetic regulatory mechanisms in the pathogenesis of ASD has been suggested by the occurrence of ASD in patients with disorders arising from epigenetic mutations (fragile X syndrome) or that involve key epigenetic regulatory factors (Rett syndrome). Moreover, the most common recurrent cytogenetic abnormalities in ASD involve maternally derived duplications of the imprinted domain on chromosome 15q11-13. Thus, parent of origin effects on sharing and linkage to imprinted regions on chromosomes 15q and 7q suggest that these regions warrant specific examination from an epigenetic perspective, particularly because epigenetic modifications do not change the primary genomic sequence, allowing risk epialleles to evade detection using standard screening strategies. This review examines the potential role of epigenetic factors in the etiology of ASD.


Obesity--a critical issue in preventive cardiology: the Bogalusa Heart Study.
Obesity has become a major public health problem in the United States, with a marked upward trend occurring over the past three decades. It plays a critical role in the development of cardiovascular risk factors that mediate the evolution of asymptomatic cardiovascular disease. Longitudinal observations of children, adolescents, and young adults enrolled in the Bogalusa Heart Study show that obesity persists over time and is linked to the clustering of components of metabolic syndrome including hyperinsulinemia/insulin resistance, dyslipidemia, and hypertension, thereby creating a long-term burden of cardiovascular risk beginning in childhood. This burden is associated with subclinical and adverse structural and functional changes of the cardiovascular system in youth. Ultimately, these changes can result in morbidity from disease, as exemplified in the Framingham Heart Study. Obesity is governed by the interplay of both genetic and environmental factors. Unlike genetic factors, lifestyle behaviors are amenable to modification. Since obesity is so widespread and underlying cardiovascular disease is so prevalent, health education beginning in childhood is suggested as an approach to prevention.


The psychometric properties of the 16-item version of the Prodromal Questionnaire (PQ-16) as a screening instrument for perinatal psychosis.
Psychiatric illness can pose serious risks to pregnant and postpartum women and their infants. There is a need for screening tools that can identify women at risk for postpartum psychosis, the most dangerous perinatal psychiatric illness. This study used exploratory factor analysis (EFA) and Rasch item response theory (IRT) models to evaluate the psychometric properties and construct validity of the Spanish language version of the 16-item Prodromal Questionnaire (PQ-16) as a screening tool for psychosis in a population of pregnant Peruvian women. The EFA yielded a four-factor model, which accounted for 44% of the variance. Factor 1, representing "unstable sense of self," accounted for 22.1% of the total variance; factor 2, representing "ideas of reference/paranoia," for 8.4%; factor 3, representing "sensitivity to sensory experiences," accounted for 7.2%; and factor 4, possibly representing negative symptoms, accounted for 6.3%. Rasch IRT analysis found that all of the items fit the model. These findings support the construct validity of the PQ-16 in this pregnant Peruvian population. Also, further research is needed to establish definitive psychiatric diagnoses to determine the predictive power of the PQ-16 as a screening tool.


Effectiveness of a Rapid Lumbar Spine MRI Protocol Using 3D T2-Weighted SPACE Imaging Versus a Standard Protocol for Evaluation of Degenerative Changes of the Lumbar Spine.
Reducing lumbar spine MRI scanning time while retaining diagnostic accuracy can benefit patients and reduce health care costs. This study compares the effectiveness of a rapid lumbar MRI protocol using 3D T2-weighted sampling perfection with application-optimized contrast with different flip-angle evolutions (SPACE) sequences with a standard MRI protocol for evaluation of lumbar spondylosis. Two hundred fifty consecutive unenhanced lumbar MRI examinations performed at 1.5 T were retrospectively reviewed. Full, rapid, and complete versions of each examination were interpreted for spondylotic changes at each lumbar level, including herniations and neural compromise. The full examination consisted of sagittal T1-weighted, T2-weighted turbo spin-echo (TSE), and STIR sequences; and axial T1- and T2-weighted TSE sequences (time, 18 minutes 40 seconds). The rapid examination consisted of sagittal T1- and T2-weighted SPACE sequences, with axial SPACE reformations (time, 8 minutes 46 seconds). The complete examination consisted of the full examination plus the T2-weighted SPACE sequence. Sensitivities and specificities of the full and rapid examinations were calculated using the complete study as the reference standard. The rapid and full studies had sensitivities of 76.0% and 69.3%, with specificities of 97.2% and 97.9%, respectively, for all degenerative processes. Rapid and full sensitivities were 68.7% and 66.3% for disk herniation, 85.2% and 81.5% for canal compromise, 82.9% and 69.1% for lateral recess compromise, and 76.9% and 69.7% for foraminal compromise, respectively. Isotropic SPACE T2-weighted imaging provides high-quality imaging of lumbar spondylosis, with multiplanar reformatting capability. Our SPACE-based rapid protocol had sensitivities and specificities for herniations and neural compromise comparable to those of the protocol without SPACE. This protocol fits within a 15-minute slot, potentially reducing costs and discomfort for a large subgroup of patients.


The complex interactions between the cellular and non-cellular components of the brain tumor microenvironmental landscape and their therapeutic implications.
Glioblastoma (GBM), an aggressive high-grade glial tumor, is resistant to therapy and has a poor prognosis due to its universal recurrence rate. GBM cells interact with the non-cellular components in the tumor microenvironment (TME), facilitating their rapid growth, evolution, and invasion into the normal brain. Herein we discuss the complexity of the interactions between the cellular and non-cellular components of the TME and advances in the field as a whole. While the stroma of non-central nervous system (CNS) tissues is abundant in fibrillary collagens, laminins, and fibronectin, the normal brain extracellular matrix (ECM) predominantly includes proteoglycans, glycoproteins, and glycosaminoglycans, with fibrillary components typically found only in association with the vasculature. However, recent studies have found that in GBMs, the microenvironment evolves into a more complex array of components, with upregulated collagen gene expression and aligned fibrillary ECM networks. The interactions of glioma cells with the ECM and the degradation of matrix barriers are crucial for both single-cell and collective invasion into neighboring brain tissue. ECM-regulated mechanisms also contribute to immune exclusion, resulting in a major challenge to immunotherapy delivery and efficacy. Glioma cells chemically and physically control the function of their environment, co-opting complex signaling networks for their own benefit, resulting in radio- and chemo-resistance, tumor recurrence, and cancer progression. Targeting these interactions is an attractive strategy for overcoming therapy resistance, and we will discuss recent advances in preclinical studies, current clinical trials, and potential future clinical applications. In this review, we also provide a comprehensive discussion of the complexities of the interconnected cellular and non-cellular components of the microenvironmental landscape of brain tumors to guide the development of safe and effective therapeutic strategies against brain cancer.


Serum protein changes during exposure to ozone.
Serial measurements of serum proteins in rabbits exposed to 0.4 ppm and 1.0 ppm of ozone revealed progressive changes in the concentrations of the various fractions: albumine concentration declined while alpha- and gamma-globulin concentrations increased.


Current development in the formulations of non-injection administration of paclitaxel.
Paclitaxel (PTX) belongs to a class of taxane anti-tumor drug used for the clinic treatment of breast cancer, ovarian cancer, non-small-cell lung cancer, and so on. PTX has poor water solubility and oral bioavailability. It is generally administered via intravenous (i.v.) infusion. Traditional PTX injectable preparations contain Cremophor-EL and ethanol to improve its solubility, which would result in adverse reactions like severe hypersensitivity, neutropenia, etc. Adverse reactions can be reduced only by complicated pretreatment with glucocorticoid and antihistamines drugs and followed by PTX slow infusion for three hours, which has brought significant inconvenience to the patients. Though, a new-generation PTX formulation, Abraxane, free of Cremophor-EL and ethanol, is still being administrated by frequent i.v. infusions and extremely expensive. Therefore, non-injection administration of PTX is urgently needed to avoid the side effects as well as reduce inconvenience to the patients. Recently, a variety of non-injection drug delivery systems (DDSs) of PTX have been developed. This review aims to discuss the progress of non-injectable administration systems of PTX, including oral administration systems, vaginal administration systems, implantable DDSs, transdermal DDSs and intranasal administration for the future study and clinical applications.


Challenges in reversing esophageal discontinuity operations.
After catastrophic esophageal or gastric disruption results in esophageal discontinuity, operations to restore swallowing are surgical challenges. A retrospective review and assessment of functional results was performed in 40 patients (average age 59.9 years) who had 42 operations to reverse esophageal discontinuity between 1973 and 2002. Esophageal discontinuity resulted from gastric necrosis after esophagectomy and esophagogastrostomy (n = 10) or hiatal hernia repair (n = 4), esophageal perforation complicating dilatation (n = 5), failed colonic or jejunal interpositions (n = 5), caustic ingestion (n = 4), Boerhaave syndrome (n = 4), esophagogastric anastomotic leak (n = 3), and other causes (n = 6). Eighteen patients (43.9%) required prolonged mechanical ventilation. Thirty-one (75.6%) had an end cervical esophagostomy; 6, an anterior thoracic esophagostomy; 2, lateral esophagostomy and in situ native esophagus stapled and divided distally; and 1 each, a stapled, divided esophagus without esophagostomy and a stapled undivided esophagus without esophagostomy. Twenty-six patients (63.4%) had undergone partial or total gastrectomy. Ten (24.4%) had vocal cord paralysis. Operations reestablishing continuity included colonic interposition in 23 (56.1%), substernal gastric interposition in 7 (17.1%), esophagectomy and cervical anastomosis in 6, esophageal reanastomosis in 3, staged jejunal interposition in 1, and Roux-en-Y esophagojejunostomy in 1. There were no hospital deaths. Twenty-eight patients (68.3%) had postoperative complications. Length of stay averaged 20.6 days. Follow-up for 40 patients averaged 54.5 months. Functional results (39 patients) were excellent in 12 (30.8%), good in 15 (38.5%), fair in 10 (25.6%), and poor in 2 (5.1%). Successful reversal of esophageal discontinuity requires individualized assessment and ingenuity. Despite appreciable morbidity, the ultimate result is generally gratifying.


Gold nanostructure matrices by diffraction mask-projection laser ablation: extension to previously inaccessible substrates.
Gold nanodot matrices made by diffraction mask-projection laser ablation (DiMPLA) are presented. The nanodots are well ordered and can be synthesized on so far not accessible substrates by virtue of intermediate thin AlO(x) layers deposited by pulsed-laser deposition (PLD). Investigations were made on the influence of layer thickness, roughness and type of substrate on the nanodots and their fabrication. It is shown that all of these parameters are crucial for the generation of nanodots on thin AlO(x) layers. The roughness of the layer and the substrate material determine whether the layer cracks upon laser patterning. The layer thickness, on the other hand, influences the size of gold nanodots on top. Extinction spectra show that the particle size is the dominant contribution that shifts the plasmon resonance peak.


[A case of highly atypical hyperplasia--difficult to differentiate from carcinoma].
We present a 51-year-old nulliparous woman with highly atypical hyperplasia of the uterus induced by the prolonged use of exogenous estrogen. The patient was given nearly 1,415 mg of estradiol dipropionate intramuscularly for over 23 years after operation for bilateral ovarian cysts. She complained of vaginal bleeding and diagnostic endometrial curettage revealed highly atypical hyperplasia which was difficult to differentiate from well differentiated adenocarcinoma. On hysterectomy, atypical tissues were limited to the upper part of the posterior wall of the uterus with no muscle invasion.


LGMD2E is the most common type of sarcoglycanopathies in the Iranian population.
Sarcoglycanopathies (SGCs) which are caused by mutations in SGCA, SGCB, SGCG or SGCD genes are a subgroup of autosomal-recessive limb-girdle-muscular-dystrophies (LGMD2). Although frequencies of mutations in these genes are different among populations, mutations in SGCA and SGCD, respectively, have the highest and lowest frequencies in most populations. Here, we report the proportion of mutations in SGC genes among a group of Iranian SGCs patients. Clinical features and results of SGC genes screening of 25 SGCs probands are presented. Large deletion mutations are confirmed with MLPA assays. In total, 15 candidate disease causing mutations were observed in the SGCA, SGCB, SGCG and SGCD genes; ten were novel. Fourteen (56%), seven (28%), three (12%) and one (4%) patient, respectively, carried mutations in SGCB, SGCG, SGCD and SGCA. The findings suggest that LGMD2E is the most common form of SGCs in the Iranian population and that LGMD2D is the rarest. Twelve LGMD2E cases carried the same mutation. To the best of knowledge, the mutation spectrum in SGCs is being reported for the first time in Iranian population. The finding will be beneficial for screening and genetic-counseling of SGCs patients in Iran.