Determination of silica coating efficiency on metal particles using multiple digestion methods.
Nano-sized metal particles, including both elemental and oxidized metals, have received significant interest due to their biotoxicity and presence in a wide range of industrial systems. A novel silica technology has been recently explored to minimize the biotoxicity of metal particles by encapsulating them with an amorphous silica shell. In this study, a method to determine silica coating efficiency on metal particles was developed. Metal particles with silica coating were generated using gas metal arc welding (GMAW) process with a silica precursor tetramethylsilane (TMS) added to the shielding gas. Microwave digestion and Inductively Coupled Plasma-Atomic Emission Spectroscopy (ICP-AES) were employed to solubilize the metal content in the particles and analyze the concentration, respectively. Three acid mixtures were tested to acquire the appropriate digestion method targeting at metals and silica coating. Metal recovery efficiencies of different digestion methods were compared through analysis of spiked samples. HNO(3)/HF mixture was found to be a more aggressive digestion method for metal particles with silica coating. Aqua regia was able to effectively dissolve metal particles not trapped in the silica shell. Silica coating efficiencies were thus calculated based on the measured concentrations following digestion by HNO(3)/HF mixture and aqua regia. The results showed 14-39% of welding fume particles were encapsulated in silica coating under various conditions. This newly developed method could also be used to examine the silica coverage on particles of silica shell/metal core structure in other nanotechnology areas.


Application of solid-phase extraction to the isolation and determination of paracetamol and its metabolites.
A series of clean-up columns for solid-phase extraction (SPE) were packed with various C18 phases of different physico-chemical surface properties. These SPE columns were used for the isolation and determination of paracetamol and its metabolites from biological samples. The packing with a monomeric structure of chemically bonded phase showed the best recovery of tested substances in urine.


A rare mutation of CACNA1C in a patient with bipolar disorder, and decreased gene expression associated with a bipolar-associated common SNP of CACNA1C in brain.
Timothy Syndrome (TS) is caused by very rare exonic mutations of the CACNA1C gene that produce delayed inactivation of Cav1.2 voltage-gated calcium channels during cellular action potentials, with greatly increased influx of calcium into the activated cells. The major clinical feature of this syndrome is a long QT interval that results in cardiac arrhythmias. However, TS also includes cognitive impairment, autism and major developmental delays in many of the patients. We observed the appearance of bipolar disorder (BD) in a patient with a previously reported case of TS, who is one of the very few patients to survive childhood. This is most interesting because the common single-nucleotide polymorphism (SNP) most highly associated with BD is rs1006737, which we show here is a cis-expression quantitative trait locus for CACNA1C in human cerebellum, and the risk allele (A) is associated with decreased expression. To combine the CACNA1C perturbations in the presence of BD in this patient and in patients with the common CACNA1C SNP risk allele, we would propose that either increase or decrease in calcium influx in excitable cells can be associated with BD. In treatment of BD with calcium channel blocking drugs, we would predict better response in patients without the risk allele, because they have increased CACNA1C expression.


[Elevated blood cell counts and vascular disease with the myeloproliferative neoplasms as model diseases].
Recent studies have shown the Philadelphia-negative myeloproliferative neoplasms (MPN) to be massively underdiagnosed and often preceded by a long pre-diagnostic phase of several years, in which many patients suffer serious vascular events. In this review, we focus on the urgent need for earlier diagnosis and treatment of MPN. Such efforts are foreseen to decrease morbidity and mortality for the individual patients and potentially reduce costs for health and social care systems.


On-line identification of trans-resveratrol in red wine using a sweeping technique combined with capillary electrophoresis/77 K fluorescence spectroscopy.
The feasibility of combining the techniques of on-line concentration and capillary electrophoresis/low-temperature fluorescence spectroscopy (CE/LTFS) for the detection and identification of trans-resveratrol in red wine at 77 K is demonstrated for the first time. This technique, involving sweeping-micellar electrokinetic chromatography (sweeping-MEKC), was used for the initial on-line concentration and separation, after which a cryogenic molecular fluorescence experiment was performed at 77 K. In comparison with normal-MEKC mode, a approximately 1500-fold improvement in detection sensitivity could be obtained when the sweeping-MEKC was applied. The proposed method permits not only the separation and detection of trans-resveratrol from red wine extracts but also ensures that the on-line spectrum is readily distinguishable and can be unambiguously assigned at 77 K.


[Prediction of depression by locus of control, learned resourcefulness and sociotropy-autonomy in hemodialysis patients].
The aims of the present study were to investigate the effects of various personality variables, namely, the locus of control beliefs, learned resourcefulness and sociotropy-autonomy in the prediction of the level of depressiveness in hemodialysis patients. The dependent variable of the study was not the depression but the level of depressiveness measured by the Beck Depression Inventory. Seventy one permanent hemodialysis outpatients in a treatment center in Ankara participated in the study [43 females and 28 males with mean (+/-SD) ages of 44 (+/-9.68) and 52.6 (+/-7.8), respectively]. Beck Depression Inventory, Rotter's Internal External Locus of Control Scale, Rosenbaum's Learned Resourcefulness Scale, Sociotropy-Autonomy Scale and Demographic Information Form were given to the patients. F test and one way ANOVA were conducted to examine the effects of sex and age groups, respectively, and then Stepwise Multiple Regression Analysis was conducted for prediction of depressiveness levels. The oldest age group (defined as between 56-70 ages) and females had higher depressiveness scores. External locus of control and low level of learned resourcefulness, an indicator of ineffective coping skills were the predictive variables of depressiveness in hemodialysis patients when age, sex, and total length of time on dialysis were controlled. On the other hand, other personality variables, sociotropy and autonomy were not significant predictors. Female patients and patients in the older age group were significantly more depressive, consistent with the literature, and the results were discussed in the light of the related literature.


Increases in orbitofrontal cortex thickness following antidepressant treatment are associated with changes in resting state autonomic function in adolescents with major depression - Preliminary findings from a pilot study.
In adults with major depressive disorder (MDD), effective treatment has been associated with increases in both heart rate variability (HRV) and cortical thickness. However, the impact of treatment on these indices has not yet been examined in adolescents. Cortical thickness and HRV were measured in twelve adolescents with MDD before and after 8 weeks of treatment with a selective serotonin reuptake inhibitor (SSRI). We examined treatment-related changes in depression symptoms, HRV, heart rate (HR), and cortical thickness, and analyzed correlations among these change indices. At follow-up, patients showed significantly decreased depression severity, increased HRV and increased thickness of the left medial orbitofrontal cortex (OFC). Clinical improvement was associated with increased HRV and decreased HR. Increased HRV was associated with increased cortical thickness of left lateral OFC and superior frontal cortex. Due to the small sample size, results represent preliminary findings that need replication. Further, in the absence of a placebo arm, we cannot confirm that the observed effects are due solely to medication. These preliminary findings suggest that SSRI treatment in adolescents impacts both cortical thickness and autonomic functioning. Confirmation of these findings would support OFC thickness and HRV as neurobiological mediators of treatment outcome.


An asymmetric synthesis of all stereoisomers of piclavines A1-4 using an iterative asymmetric dihydroxylation.
The asymmetric synthesis of both enantiomers of piclavines A1, A2, A3, and A4 has been achieved using an iterative asymmetric dihydroxylation with enantiomeric enhancement.


Improved chemotherapy against breast cancer through immunotherapeutic activity of fucoidan decorated electrostatically assembled nanoparticles bearing doxorubicin.
Immunotherapeutic nanoparticles (NPs) could be a viable option for delivering cytotoxic agents in a manner which suppresses their toxic manifestations. Doxorubicin (DOX) loaded NPs were prepared using fucoidan (FCD), an immunomodulatory polysaccharide and evaluated against cancer. FCD was electrostatically assembled with cationic polyethylenimine (PEI) through intermolecular electrostatic interactions to develop an immunomodulatory platform to deliver DOX. FCD NPs offered improved cytotoxicity (2.64 folds), cell cycle arrest in G1-S phase (34.65%) and apoptosis (66.12%) in tumor cells compared to free DOX. The enhanced apoptosis was due to raised mitochondrial depolarization (88.00%). In vivo anticancer activity in 4T1 induced tumor bearing BALB/c mice demonstrated a 2.95 folds enhanced efficacy of NPs. Importantly, NPs treatment generated an immunotherapeutic response indicated by gradual increment of the plasma IL-12 levels and reversed polarization of tumor associated macrophages (TAMs) towards M1 subtype. Furthermore, pharmacokinetic study suggested that NPs administration in tumor infested mice caused serum DOX levels to vary in a biphasic pattern, with twin peaks occurring at 1 h and 6 h which help in maintaining preferential drug localization in tumor. Developed NPs would be an excellent approach for improved immune-chemotherapy (in terms of efficacy, safety and immunocompetency) against cancer.


[Long-term group isolation is a factor of dysregulation of reproductive function in rats].
In the condition of prolonged group sex starvation of rats variations were seen in behavioral reactions, fertility, extent of weight gain, litter, blood alpha-tocopherol level, eosinophil count, lipid peroxidation, evoked brain potentials. All these processes are the sign of stress development in rats. Thus, stress in mature rats influences litter and fertility, newborn rats had underdeveloped nervous system. Changes in the activity of endogenic antioxidant system in this experiment are discussed.


Nephrotoxicity of xenobiotics.
Nephrotoxicity can be grouped by the xenobiotics place of action, by the clinical presentation or by the generic toxic effect. The latter can be dose related, indirect, idiosyncratic or allergic. Nephrotoxicity of lithium, demeclocycline, aminoglycosides, cyclosporine, mercuric ion, nonsteroidal anti-inflammatory drugs, methoxyflurane, ethylene glycol, D-penicillamine and methicillin is reviewed in light of all these three viewpoints, but emphasis is on toxic mechanisms.


The regulatory subunit of the type II cAMP-dependent protein kinase in rabbit ovaries is the RII beta isoform.
Based on RII autophosphorylation, photoaffinity labeling with 8-N3[32P]cAMP, and Western blot analysis we have identified the RII isoform found in rabbit corpora lutea as RII beta. The RII beta subunit found in rabbit corpora lutea differs from the RII beta found in rat follicles and corpora lutea in that it migrates at Mr 52,500 on SDS-PAGE and shifts to Mr 53,000 when phosphorylated.


Effect of aprotinin (Trasylol) on aorta-coronary bypass graft patency.
To determine the effect on aorta-coronary bypass grafts of high-dose aprotinin, a drug known to be effective in reducing bleeding after all forms of heart operations, a prospective double-blind study was performed. Graft patency was assessed noninvasively 7 to 12 days (median 9 days) postoperatively in 90 patients. In the aprotinin group, 38 of 43 patients had all grafts patent compared with 43 of 47 in the placebo group. In each group, respectively, 126 of 131 grafts versus 134 of 138 grafts were patent. Neither difference was statistically significant (p > 0.05). Blood loss and homologous blood use were significantly reduced in the aprotinin-treated patients. In this study, high-dose aprotinin did not result in early saphenous vein graft occlusion after aorta-coronary bypass operations. This is further evidence that aprotinin reduces hemostatic derangement during cardiopulmonary bypass without creating a "prothrombotic" situation.


Competition of milrinone, a non-iodinated cardiac inotropic agent, with thyroid hormone for binding sites on human serum prealbumin (TBPA).
Milrinone [2-methyl-5-cyano-(3,4'-bipyridin)-6(1H)-one] is a positive cardiac inotropic agent recently shown to have thyromimetic activity in vitro in a rabbit myocardial membrane Ca2+-ATPase system [K. M. Mylotte et al., Proc. natn. Acad. Sci. U.S.A. 82, 7974 (1985)]. In the present studies, milrinone was examined for activity as an inhibitor of iodothyronine binding by human serum thyroid hormone transport proteins, thyroxine-binding globulin (TBG), prealbumin (TBPA) and albumin. Polyacrylamide gel electrophoresis at pH 9.0 of sera equilibrated with [125I]thyroxine showed that milrinone competed with L-thyroxine (T4) for binding sites on TBPA (10 and 100 microM milrinone caused 61 and 73% reductions, respectively, in T4 binding to TBPA, P less than 0.01); T4 displaced from TBPA was bound by TBG and albumin. Comparable reductions in T4 binding to TBPA were observed in electrophoretic studies conducted at pH 7.4. Binding of triiodo-L-thyronine (T3) to TBPA was electrophoretically confirmed and shown to be decreased in the presence of milrinone. Electrophoresis of purified TBPA also demonstrated that [14C]milrinone co-migrated with this transport protein and that milrinone displaced tracer T4 from TBPA. Amrinone, the 2-H-5-NH2 analog of milrinone, had less than 5% of the activity of milrinone as an inhibitor of T4 binding in electrophoretic studies. Scatchard analysis of T4 and milrinone binding to purified TBPA, measured by equilibrium dialysis, showed two classes of binding sites, with association constants, respectively, of 6.1 X 10(7) M-1 and 1.6 X 10(6) M-1 for T4, and 1.7 X 10(6) M-1 and 8.9 X 10(2) M-1 for milrinone. Computer graphic modeling of the binding of milrinone to the T4 site in the crystal structure of TBPA showed that milrinone best occupied this site when the substituted bipyridine ring overlapped the phenolic ring of T4. In this orientation the 5-cyano group, which has an electronegativity similar to that of iodine, occupied the same volume as the 5'-iodine of T4. The 5-amino group of amrinone lacks these characteristics. In this orientation, the keto function of milrinone overlapped the T4 4'-hydroxyl and could participate in similar intermolecular interactions. Thus, milrinone, a non-iodinated bipyridine, and thyroid hormone share structural and biochemical homologies and compete for the same binding site on TBPA.


Regional cerebral blood flow correlates of the severity of writer's cramp symptoms.
Writer's cramp is a type of idiopathic focal dystonia with incompletely understood pathophysiology. Recent studies provide evidence that one element might be a sensory processing defect. We performed a PET study with O(15) H(2)O to find out in which brain areas activity correlates with the severity of writer's cramp symptoms. We studied 10 patients with writer's cramp and 10 age- and gender-matched control subjects. There were seven conditions, each repeated twice: rest, writing, tapping with index finger for 2, 3, 4, and 5 min. For each scan, we obtained EMG recordings from the flexor digitorum superficialis (FDS), extensor indicis proprius (EIP) muscles, and a subjective score of severity of dystonia. Scans were realigned, normalized, smoothed, and analyzed using SPM99. Analysis included both intra- and intergroup comparisons and a correlation analysis where we used EMG recordings and subjective dystonia score as covariates. Random effect analysis of the writing task showed overactivity of the primary sensory cortex and no significant underactivity. Correlation analysis of dystonia patients showed activation of SI when we used the subjective dystonia score as a covariate, and activation of both the SI and primary motor cortex when the normalized EMG score of FDS was used. While some overactivity of MI is not surprising, overactivity of SI is more dramatic and suggests a primary deficit in processing sensory feedback. Writer's cramp may arise in part as a dysfunction of sensory circuits, which causes defective sensorimotor integration resulting in co-contractions of muscles and overflow phenomena.


Differences in outcomes of bilateral adrenalectomy in patients with ectopic ACTH producing tumor of known and unknown origin.
Endogenous Cushing syndrome (CS) can be caused by ectopic corticotropin-producing tumors of known (EK) and unknown origin (EU). Bilateral adrenalectomy (BA) can be used as definite treatment of hypercortisolism in such cases. This study compared patients undergoing BA for CS secondary to EK vs EU. Retrospective review (1995-2017) of patients undergoing BA due to EK or EU. We analyzed demographic characteristics, laboratory values, intraoperative variables, surgical outcomes, and survival. 48 patients (26 EU, 22 EK) were identified. Serum cortisol and ACTH concentrations were similar. 92% of BA for EU were performed minimally invasively vs 77% for EK, P = 0.22. Complications occurred in 19% of EU and 4.5% EK, P = 0.2. Mean survival was 4.3 years for EU and 4.0 years for EK without difference in all-cause mortality P = 0.63. BA cure rate was 100% for CS in EU and EK. Morbidity, long term and all-cause mortality differences were not statistically significant between EK and EU.


Presurgical psychiatric evaluations of candidates for bariatric surgery, part 1: reliability and reasons for and frequency of exclusion.
Many bariatric surgery programs include psychiatric evaluations as part of the pre-operative screening procedure. Surveys of surgeons and mental health professionals have found variability in opinion regarding what psychosocial problems warrant denial of clearance for surgery. Few studies have reported the number of patients who are not cleared for surgery due to psychiatric reasons, and no study has reported the reliability of decision making. The goals of the present study were to examine the reliability of decisions to clear candidates for surgery, determine the percentage of candidates who were not cleared for surgery, and detail the reasons candidates were not cleared for surgery. Five hundred candidates for bariatric surgery were evaluated from July 2004 until July 2006 with semistructured diagnostic interviews for DSM-IV Axis I and Axis II disorders supplemented by a module specific to this population. Reliability for determining clearance was evaluated in 73 patients. Reasons for not clearing patients were recorded on the Surgery Clearance Form. Eighteen percent (N = 92) of the patients were not cleared for surgery. The kappa coefficient of reliability of determining surgical clearance was 0.83. The most common reasons for the negative recommendation were overeating to cope with stress or emotional distress, current eating disorder, uncontrolled psychopathology, and the presence of significant life stressors. Only 1 patient was excluded for a lack of understanding of the potential risks of surgery. The decision whether to clear candidates for bariatric surgery can be made reliably. Approximately 1 in 5 surgical candidates did not pass the initial psychiatric screening, usually because of current eating pathology, other forms of uncontrolled psychopathology, or difficulty coping with current life stressors.


Intervention for children with severe speech disorder: a comparison of two approaches.
Children with speech disorder are a heterogeneous group (e.g. in terms of severity, types of errors and underlying causal factors). Much research has ignored this heterogeneity, giving rise to contradictory intervention study findings. This situation provides clinical motivation to identify the deficits in the speech-processing chain that underlie different subgroups of developmental speech disorder. Intervention targeting different deficits should result in a differential response to intervention across these subgroups. To evaluate the effect of two different types of therapy on speech accuracy and consistency of word production of children with consistent and inconsistent speech disorder. Eighteen children (aged 4;08-6;05 years) with severe speech disorder participated in an intervention study comparing phonological contrast and core vocabulary therapy. All children received two 8-week blocks of each intervention. Changes in consistency of production and accuracy (per cent consonants correct) were used to measure the effect of each intervention. All of the children increased their consonant accuracy during intervention. Core vocabulary therapy resulted in greater change in children with inconsistent speech disorder and phonological contrast therapy resulted in greater change in children with consistent speech disorder. The results provide evidence that treatment targeting the speech-processing deficit underlying a child's speech disorder will result in efficient system-wide change. Differential response to intervention across subgroups provides evidence supporting theoretical perspectives regarding the nature of speech disorders: it reinforces the concept of different underlying deficits resulting in different types of speech disorder.


Identification of fluid overload in elderly patients with chronic kidney disease using bioimpedance techniques.
Diagnosis of fluid overload (FO) in early stage is essential to manage fluid balance of patients with chronic kidney disease (CKD) and to prevent cardiovascular disease (CVD). However, the identification of fluid status in patients with CKD is largely dependent on the physician's clinical acumen. The ratio of fluid overload to extracellular volume (FO/ECV) has been used as a reference to assess fluid status. The primary aim of this study was to compare FO/ECV with other bioimpedance methods and clinical assessments in patients with CKD. Whole body ECV, intracellular volume (ICV), total body water (TBW), and calf normalized resistivity (CNR) were measured (Hydra 4200). Thresholds of FO utilizing CNR and ECV/TBW were derived by receiver operator characteristic (ROC) analysis based on data from pooled patients with CKD and healthy subjects (HSs). Clinical assessments of FO in patients with CKD were performed by nephrologists. Patients with CKD (stage 3 and stage 4) (n = 50) and HSs (n = 189) were studied. The thresholds of FO were ≤14.3 (10-2 Ωm3/kg) for females and ≤13.1 (10-2 Ωm3/kg) for males using CNR and ≥0.445 in females and ≥0.434 in males using ECV/TBW. FO was diagnosed in 78%, 62%, and 52% of patients with CKD by CNR, FO/ECV, and ECV/TBW, respectively, whereas only 24% of patients with CKD were diagnosed to be FO by clinical assessment. The proportion of FO in patients with nondialysis CKD was largely underestimated by clinical assessment compared with FO/ECV, CNR, and ECV/TBW. CNR and FO/ECV methods were more sensitive than ECV/TBW in identifying fluid overload in these patients with CKD.NEW & NOTEWORTHY We found that fluid overload (FO) in patients with nondialysis CKD was largely underestimated by clinical assessment compared with bioimpedance methods, which was majorly due to lack of appropriate techniques to assess FO. In addition, although degree of FO by bioimpedance markers positively correlated with the age in healthy subjects (HSs), no difference was observed in the three hydration markers between groups of 50 ≤ age <70 yr and age ≥70 yr in the patients with CKD.


MiR-181b regulates cisplatin chemosensitivity and metastasis by targeting TGFβR1/Smad signaling pathway in NSCLC.
MicroRNAs (miRNAs) have been identified as important post-transcriptional regulators involved in various biological and pathological processes of cells, but their underlying mechanisms in chemosensitivity and metastasis have not been fully elucidated. The objective of this study was to identify miR-181b and its mechanism in the chemosensitivity and metastasis of NSCLC. We found that miR-181b expression levels were lower in A549/DDP cells compared with A549 cells. Functional assays showed that the overexpression of miR-181b inhibited proliferation, enhanced chemosensitivity to DDP, attenuated migration and metastatic ability in NSCLC cell lines in vitro and in vivo. TGFβR1 was subsequently identified as a novel functional target of miR-181b. TGFβR1 knockdown revealed similar effects as that of ectopic miR-181b expression, whereas overexpression of TGFβR1 rescued the function of miR-181b-mediated growth, chemosensitivity and metastasis in NSCLC cells. In addition, miR-181b could inactivate the TGFβR1/Smad signaling pathway. We also observed that decreased miR-181b expression and increased TGFβR1 expression were significantly associated with chemosensitivity to DDP and tumor metastasis in NSCLC patients. Consequently, miR-181b functions as a tumor suppressor and has an important role in proliferation, chemosensitivity to DDP and metastasis of NSCLC by targeting TGFβR1/Smad signaling pathway.


Bioinspired Au/TiO2 photocatalyst derived from butterfly wing (Papilio Paris).
The reticular hierarchical structure of butterfly wings (Papilio Paris) is introduced as template for Au/TiO(2) photocatalyst by depositing the Au nanoparticles on TiO(2) matrix, which is carried out by a water-ethanol sol-gel procedure combined with subsequent calcination. The obtained Au/TiO(2) nanocomposites present the reticular hierarchical structure of butterfly wings, and Au nanoparticles with an average size of 7 nm are homogeneously dispersed in TiO(2) substrate. Benefiting from such unique reticular hierarchical structure and composition, the biomorphic Au/TiO(2) exhibits high-harvesting capability and presents superior photocatalytic activity. Especially, the biomorphic Au/TiO(2) at the nominal content of gold to titanium of 8 wt% shows the highest photocatalytic activity and can completely decompose methyl orange within 80 min, which is obviously higher than that of commercial Degussa P25 powders.


[Status of collective immunity to hepatitis A virus in urban residents in Byelorussia].
The large immune stratum and intense collective immunity to virus hepatitis A among the urban population of Byelorussia are characteristic of hyperendemic territory. The geometric mean of the antibody titer has been noted to increase with age, which is probably due to repeated infections of persons who have already had the disease. The use of this value for the characterization of collective immunity and epidemiological situation has been proposed.


Regulation of phosphodiesterase and ornithine decarboxylase by cAMP is cell cycle independent.
Cyclic AMP (cAMP) causes growth arrest in G1 and induction of cAMP phosphodiesterase and decrease of ornithine decarboxylase in S49 mouse lymphoma cells. Dibutyryl cAMP treatment of partially synchronized cells causes similar changes in activities of both enzymes, regardless of position in the cell cycle. This suggests that cAMP regulation of these enzymes is not mediated by growth perturbation.


Indocyanine green-based fluorescence imaging improved by deep learning.
Intraoperative identification of malignancies using indocyanine green (ICG)-based fluorescence imaging could provide real-time guidance for surgeons. Existing ICG-based fluorescence imaging mostly operates in the near-infrared (NIR)-I (700-1000 nm) or the NIR-IIa' windows (1000-1300 nm), which is not optimal in terms of spatial resolution and contrast as their light scattering is higher than the NIR-IIb window (1500-1700 nm). It is highly desired to achieve ICG-based fluorescence imaging in the NIR-IIb window, but it is hindered by its ultra-low NIR-IIb emission tail of ICG. Herein, we employ a generative adversarial network to generate NIR-IIb ICG images directly from the acquired NIR-I ICG images. This approach was investigated by in vivo imaging of sub-surface vascular, intestine structure, and tumors, and their results demonstrated significant improvement in spatial resolution and contrast for ICG-based fluorescence imaging. It is potential for deep learning to improve ICG-based fluorescence imaging in clinical diagnostics and image-guided surgery in clinics.


Gas chromatographic determination of pemoline as 5-phenyl-2,4-oxazolidinedione in human urine.
A simple gas chromatographic assay of the psychostimulant pemoline in human urine has been developed. Instead of extraction of the drug from urine, it is hydrolysed to 5-phenyl-2,4-oxazolidinedione with 1 N hydrochloric acid. After the extraction, this compound is methylated with diazomethane and determined by gas-liquid chromatography using a nitrogen-selective detector and a solid injection system. The method has been applied in preliminary human pharmacokinetic studies, by measuring the urinary excretion rate of pemoline following oral administration. At present, the screening procedures for doping control do not involve the detection of pemoline, but the method described can easily be incorporated in such procedures.


Reactions of the carcinogen N-acetoxy-4-acetamidostilbene with nucleosides.
The carcinogen N-acetoxy-4-acetamidostilbene (N-AcO-AAS) yields multiple products in reactions with guanosine, adenosine or cytidine in aqueous acetone. The major product from the reaction with cytidine is a deamination product, 1-(4-acetamidophenyl)-1-(3-uridyl)-2-hydrosy-2-phenylethane. Three minor products were unstable and were characterized only by their UV spectra and pK values. Adenosine yielded two major products, one of them 1-(4-acetamidophenyl)-1-(N6-adenoxyl)-2-hydroxy-2-phenylethane, and the second 3-(beta-D-ribosyl)-7-phenyl-8-(4-acetamidophenyl)-7,8 dihydroimidazo [2,1-i] purine. The major adduct with guanosine is 1-(4-acetamidophenyl)-1-(1-guanosyl)-2-hydroxy-2-phenylethane. One minor adduct also appears to be a guanosine-N-1 derivative, while two other minor adducts yield 1-(4-acetamidophenyl)-2-phenyl-1, 2-ethanediol on acid hydrolysis, and thus appear to be O6-derivatives. None of the guanine adducts isolated had the properties of N-7, C-8 or N2 adducts. In this respect, N-Aco-AAS appears to behave more like a classical alkylating agent than like previously studied N-acetoxy-N-arylacetamides, although the target organs of 4-acetamidostilbene are the same as those of other N-arylacetamides.


Methods and tips for the purification of human histone methyltransferases.
Recently developed biochemical techniques have enabled researchers to study histone modifications more easily and accurately. One of these modifications, histone lysine methylation, has been shown to be highly stable and to represent an epigenetic alteration. Extensive biochemical analyses have led to discoveries about the nature and functions of this modification, thus accelerating our understanding of this crucial epigenetic event. Here we describe basic methods for purification and biochemical analysis of lysine-directed, histone methyltransferases from HeLa cell-derived extracts. In the section on substrate preparation, we describe a simple method for the preparation of recombinant substrates, although we recommend using native substrates for initial detection of the activities. The purification protocols for several histone methyltransferases have been streamlined so that those researchers with a basic understanding of biochemistry can perform them. We also describe many tips and provide suggestions to avoid common pitfalls in the biochemical analysis of histone methyltransferases.


Translation and validation of the Greek version of the Modified Weight Bias Internalization Scale in an adult population.
Weight bias internalization (WBI) has been identified as a global public health concern, which is associated with significant psychological and physical consequences. Despite increased interest in WBI worldwide, cross-cultural research is limited by the lack of availability of validated measures. The aim of the current study was therefore to translate into Greek and validate the Modified Weight Bias Internalization Scale (WBIS-M), the most widely used instrument in the measurement of WBI. An online convenience sample of 642 participants (364 women and 278 men) completed the Greek translation of the WBIS-M and validated the measures of satisfaction with appearance, investment in appearance, weight/appearance anxiety, body appreciation, dysfunctional eating habits and global self-esteem to assess convergent validity. Principal factor and confirmatory analyses revealed that the WBIS-M upheld its one-factor structure. The WBIS-M showed adequate internal consistency, convergent validity and 3-week test-retest reliability. These findings provide support for the cross-cultural equivalence of the WBIS-M and for the utility of this measure in Greek-speaking populations.


Evaluation of factors controlling net photosynthetic rate in Scots pine seedlings under field conditions without water stress.
The ecological importance of different factors generating variation in the photosynthetic rate of a pine seedling (Pinus sylvestris) under nonstressing conditions are evaluated. The data consists of 1,300 observations of the photosynthetic rate and environmental factors possibly affecting photosynthesis. Statistical analysis of the data gave the following results: 1. light solely explained about 90% of the variance of photosynthetic rate during a day, 2. light and temperature together explained about 94% of it and 3. the other factors studied (leakage from the cuvette, different spectral sensitivity of photosynthesis and the monitoring apparatus, high transpiration rate, circadian rhythm and inhibition of photosynthesis by carbohydrates) were not found to be significant from the ecological point of view, since they explain less than 0.5% of the variance.


[Factors causing fatigue in female industrial workers].
In 1698 female workers aged 18-45 a relationship was sought between subjective symptoms of fatigue and factors which directly or indirectly could affect them: age, Hb level, relative body weight, health status, abundance of menstrual bleedings. In 199 women the number of sleep hours and stress in occupational work was taken into account. A strong relation was found between fatigue and age of women. The role of the remaining factors was evaluated after standardisation for age. The occurrence of fatigue was highly statistically dependent on the health status and abundance of menstrual bleedings. The other relations were less pronounced.


Intracerebral hemorrhage models in rat: comparing collagenase to blood infusion.
Many therapies have shown promise in preclinical stroke studies, but few benefit patients. A greater understanding of stroke pathophysiology is needed to successfully develop therapies, and this depends on appropriate animal models. The collagenase and blood infusion models of intracerebral hemorrhage (ICH) are widely used; yet, investigators often prefer using one model for a variety of reasons. Thus, we directly compared these to highlight advantages and limitations of each as well as the assessment approach. An ICH was created by infusing blood or bacterial collagenase into the rats' striatum. We matched initial hematoma volume in each model (Experiment 1) and assessed the time course of bleeding (Experiment 2). Functional deficits and the progression of injury were tracked over 6 weeks using behavior, magnetic resonance imaging, and histology (Experiment 3). Despite similar initial hematoma volumes, collagenase-induced ICH resulted in a greater blood-brain barrier breakdown and more damage to the striatum, substantia nigra, white matter, and cortex. Magnetic resonance imaging revealed faster hematoma resolution in the blood model, and little increase in the volume of tissue lost from 1 to 6 weeks. In contrast, tissue loss continued over 4 weeks in the collagenase model. Finally, functional deficits recovered more quickly and completely in the blood model. This study highlights key differences between these models and that neither closely replicates the human condition. Thus, both should be used whenever possible taking into account the significant differences between these models and their limitations. Furthermore, this work illustrates significant weaknesses with several outcome measures.


Initial analysis of the spatial correlation between the incidence of COVID-19 and human development in the municipalities of the state of Ceará in Brazil.
To analyze the spatial distribution of the incidence of COVID-19 and its correlation with the municipal human development index (MHDI) of the municipalities of Ceará. This is an ecological study with data recovered from the 15th epidemiological week and the 19th one of the year 2020 using the MHDI and the COVID-19 incidence coefficient for each municipality as variables. The univariate spatial correlation and the bivariate one were analyzed using the TerraView and GeoDa softwares. The incidence of COVID-19 has spatial dependence with moderate positive correlation and the formation of high-high clusters located in the metropolitan region of Fortaleza and municipalities in the north region. The lowest incidence was a low-low cluster in the south and west regions. There was a positive bivariate correlation between MHDI and the incidence of COVID-19 with the formation of a cluster in the metropolitan region of Fortaleza. The uneven mapping of COVID-19 and its relationship with MHDI in Ceará can contribute to actions to regional combat the pandemic.


Paramagnetic Properties of Fullerene-Derived Nanomaterials and Their Polymer Composites: Drastic Pumping Out Effect.
The evolution of paramagnetic properties of the fullerene soot (FS), fullerene black (FB), and their polymer composites Phenylon C-2/FS, FB has been studied using the electron paramagnetic resonance (EPR) method. For the first time, a drastic growth of the EPR signals in the FB, FS, and composite samples was observed under pumping out at temperatures T = 20 ÷ 300 °C, which is attributed to the interaction between carbon defects and adsorbed gas molecules, mainly oxygen.It is shown that the ensemble of paramagnetic centers in the FB, FS, and the composite is heterogeneous. This ensemble consists of three spin subsystems 1, 2, and 3 related with different structural elements. The subsystems give three corresponding contributions, L 1, L 2 and L 3, into the overall contour of the EPR signal. The most intensive and broad signal L 3 is caused by 2D electrons from the surface of carbon flakes. Theoretical calculations of the L 3 signal line shape were carried out, and the decay rate of the integral intensity has been obtained for each component L 1, L 2, and L 3 after the contact of the sample with the ambient air. The signal decay process in the bulk composite samples is much slower due to their low gas permeability at room temperature (RT).


Design and synthesis of a novel family of semi-rigid ligands: versatile compounds for the preparation of 99mTc radiopharmaceuticals.
Synthetic pathways to a range of novel semi-rigid tetradentate ligands, with sulfur, amido or amino donor groups, designed to coordinate technetium 99m have been developed. The technetium-99m complexes have been prepared and their stabilities in serum and by metathesis reaction via cysteine exchange reactions were compared. HPLC comparison of two (99m)Tc-complexes and their rhenium analogues led to the first proof of the nature of our radioactive complexes.


Conditions of the calcaneus in skeletally immature patients.
Most conditions of the calcaneus in children, including calcaneal apophysitis, calcaneal fractures, and even intra-articular displaced fractures can be treated successfully with nonoperative methods. Calcaneal bone cysts require surgery only if symptomatic or at risk for pathologic fracture. Calcaneal osteomyelitis must be recognized and treated promptly to prevent severe complications.


Cigarette Smoking Prevalence Among Adults Working in the Health Care and Social Assistance Sector, 2008 to 2012.
The primary objective of this study was to estimate current smoking among workers in the health care and social assistance sector. We analyzed the 2008 to 2012 National Health Interview Survey data for adults (age 18 years or more) working in health care and social assistance sector who reported current cigarette smoking. Of the approximately 18.9 million health care and social assistance workers, 16.0% were current cigarette smokers. Smoking prevalence was highest in women (16.9%) and among workers: age 25 to 44 years (17.7%); with a high school education or less (24.4%); with income less than $35,000 (19.5%); with no health insurance (28.5%); in the nursing and residential care facilities (26.9%) industry; and in the material recording, scheduling, dispatching, and distributing (34.7%) occupations. These findings suggest that specific group of workers in the health care and social assistance sector might particularly benefit from cessation programs and incentives to quit smoking.


Ciliary neurotrophic factor as an injury factor.
This article reviews recent evidence suggesting that endogenous ciliary neurotrophic factor may be involved in neural responses to injury, and discusses the possibility that ciliary neurotrophic factor could have therapeutic applications in a clinical setting. The functional relevance of ciliary neurotrophic factor in non-injury situations is also evaluated, with emphasis on its possible roles in embryonic development.


Psychotropic medicines use in Residents And Culture: Influencing Clinical Excellence (PRACTICE) tool©. A development and content validation study.
Psychotropic medicines are often prescribed in nursing homes to manage behavioral and psychological symptoms of dementia despite marginal clinical effects alongside harmful adverse events. Organizational culture has been identified as a key factor that contributes to the high-level prescribing of psychotropic medicines in nursing homes. There are gaps in existing tools used to link organizational culture to the use of psychotropic medicines. The aim of this research was to develop and content validate a tool that evaluates organizational culture specific to the use of psychotropic medicines, named the Psychotropic medicines use in Residents And Culture: Influencing Clinical Excellence (PRACTICE) tool©. Schein's theory of organizational culture was used to guide the development and content validation of the PRACTICE tool©. The PRACTICE tool© was developed based on a comprehensive systematic review, qualitative research and generated by the research team. Content validity was assessed using the CVI (Content Validity Index). The content relevance and importance of the PRACTICE tool© items were rated by an expert panel with relevant knowledge and experience. Any modified or re-worded items were presented to the panel members in a subsequent survey for re-rating. Across the two rounds, the PRACTICE tool© had 68 items that assessed all aspects of culture according to Schein's theory. Sixty-two items out of 68 (91%) met predefined cut-off values (≥0.78) for the I -CVI. The remaining six items (9%) did not fully meet the cut-off values but were deemed important to be included in the tool based on the systematic review, qualitative research and discussions with the research team. The PRACTICE tool© is a step forward in validating an instrument that will help inform managers and policy makers to identify target areas for improvement to create a culture of appropriate psychotropic prescribing in nursing homes.


Streptomyces sp. strain TOR3209: a rhizosphere bacterium promoting growth of tomato by affecting the rhizosphere microbial community.
Aiming at revealing the possible mechanism of its growth promoting effect on tomato, the correlations among Streptomyces sp. TOR3209 inoculation, rhizobacteriome, and tomato growth/production traits were investigated in this study. By analyses of Illumina sequencing and plate coating, differences in rhizosphere microbial communities were found in different growth stages and distinct inoculation treatments. The plant biomass/fruit yields and relative abundances of families Flavobacteriaceae, Sphingobacteriaceae, Polyangiaceae and Enterobacteriaceae in treatments T (tomato inoculated with TOR3209) and TF (tomato inoculated with TOR3209 + organic fertilizer) were higher than that in the controls (CK and CK+ organic fertilizer), respectively. The analysis of Metastats and LEfSe revealed that the genera Flavobacterium and Sorangium in seedling stage, Klebsiella in flowering stage, Collimonas in early fruit setting stage, and genera Micrococcaceae, Pontibacte and Adhaeribacter in late fruit setting stage were the most representative rhizobacteria that positively responded to TOR3209 inoculation. By cultivation method, five bacterial strains positively correlated to TOR3209 inoculation were isolated from rhizosphere and root endosphere, which were identified as tomato growth promoters affiliated to Enterobacter sp., Arthrobacter sp., Bacillus subtilis, Rhizobium sp. and Bacillus velezensis. In pot experiment, TOR3209 and B. velezensis WSW007 showed joint promotion to tomato production, while the abundance of inoculated TOR3209 was dramatically decreased in rhizosphere along the growth of tomato. Conclusively, TOR3209 might promote the tomato production via changing of microbial community in rhizosphere. These findings provide a better understanding of the interactions among PGPR in plant promotion.


Diagnostic and classification systems with special emphasis on the Minicompendium.
With the introduction of major tranquillizers more than three decades ago symptom rating scales were soon accepted as the method of evaluating their clinical effects. The Mini-compendium is a collection of rating scales for measuring outcome of antianxiety drugs, antidepressants, antimanics, and anti-psychotics. The scales have been selected by their "cash values", i.e. the scales most frequently used for the respective dimensions. These scales have been further developed in terms of strict item definitions. The simple sum of the individual scale items has been considered as a sufficient statistic if they fulfilled latent structure analysis of shared phenomenology.


Inhibiting wild-type and C299S mutant AKR1B10; a homologue of aldose reductase upregulated in cancers.
AKR1B10 is an aldose reductase (AR) homologue overexpressed in liver cancer and various forms of that enzyme in carcinomas catalyze the reduction of anticancer drugs, potential cytostatic drug, and dl-glyceraldehyde but do not catalyze the reduction of glucose. Kinetic parameters for wild-type and C299S mutant AKR1B10 indicate that substitution of serine for cysteine at position 299 reduces the affinity of this protein for dl-glyceraldehyde and enhances its catalytic activity. Fibrates suppress peroxisome proliferation and the development of liver cancer in human. Here we report the potency of fibrate-mediated inhibition of the carbonyl reduction catalyzed by wild-type and C299S mutant AKR1B10 and compare it with known AR inhibitors. Wild-type AKR1B10-catalyzed carbonyl reduction follows pure non-competitive inhibition kinetics using zopolrestat, EBPC or sorbinil, whereas fenofibrate, Wy 14,643, ciprofibrate and fenofibric acid follow mixed non-competitive inhibition kinetics. In contrast, catalysis of reaction by the C299S AKR1B10 mutant is not inhibited by sorbinil and EBPC. Despite these differences, the C299S AKR1B10 mutant still manifests kinetics similar to the wild-type protein with other fibrates including zopolrestat, fenofibrate, Wy 14,346, gemfibrozil and ciprofibrate that show mixed non-competitive inhibition kinetics. The reaction of the mutant AKR1B10 is inhibited by fenofibric acid, but manifests pure non-competitive inhibition kinetics that are different from those demonstrated for the wild-type enzyme.


Listeria isolations from feces of patients with diarrhea and from healthy food handlers.
A study was undertaken on the presence and frequency of Listeria sp. in feces from 1,000 patients suffering from diarrheal diseases and from 2,000 healthy persons. Furthermore, the feces of patients were examined for other well-documented enteropathogens such as Campylobacter, Salmonella, Shigella, Staphylococcus aureus, Yersinia enterocolitica, protozoa and rotavirus as well as for organisms of questionable enteropathogenic potency such as fungi, i.e. Candida. Finally, in continuation of previously described investigations of the enteropathogenic role of Proteus mirabilis but not of Proteus vulgaris, both these species were studied too. Only Listeria innocua and Listeria monocytogenes could be detected in the investigated fecal specimens. There were no differences of the frequencies of L. innocua, and L. monocytogenes between patients and healthy persons. 17 strains (= 1.7%) of L. innocua and six strains (= 0.6%) of L. monocytogenes were isolated from 1,000 samples of patients. As a comparison 2,000 fecal samples from healthy people contained 40 strains (= 2.0%) of L. innocua and 16 strains (= 0.8%) of L. monocytogenes. A coincidence study showed that there were no statistically significant correlations between well-known enteropathogens and Listeria sp., Proteus sp. or any of the other isolates. Significant correlations were found only between harmless species such as L. innocua and P. vulgaris.


Analysis of self-assembly of S-layer protein slp-B53 from Lysinibacillus sphaericus.
The formation of stable and functional surface layers (S-layers) via self-assembly of surface-layer proteins on the cell surface is a dynamic and complex process. S-layers facilitate a number of important biological functions, e.g., providing protection and mediating selective exchange of molecules and thereby functioning as molecular sieves. Furthermore, S-layers selectively bind several metal ions including uranium, palladium, gold, and europium, some of them with high affinity. Most current research on surface layers focuses on investigating crystalline arrays of protein subunits in Archaea and bacteria. In this work, several complementary analytical techniques and methods have been applied to examine structure-function relationships and dynamics for assembly of S-layer protein slp-B53 from Lysinibacillus sphaericus: (1) The secondary structure of the S-layer protein was analyzed by circular dichroism spectroscopy; (2) Small-angle X-ray scattering was applied to gain insights into the three-dimensional structure in solution; (3) The interaction with bivalent cations was followed by differential scanning calorimetry; (4) The dynamics and time-dependent assembly of S-layers were followed by applying dynamic light scattering; (5) The two-dimensional structure of the paracrystalline S-layer lattice was examined by atomic force microscopy. The data obtained provide essential structural insights into the mechanism of S-layer self-assembly, particularly with respect to binding of bivalent cations, i.e., Mg2+ and Ca2+. Furthermore, the results obtained highlight potential applications of S-layers in the fields of micromaterials and nanobiotechnology by providing engineered or individual symmetric thin protein layers, e.g., for protective, antimicrobial, or otherwise functionalized surfaces.


Hormonal modulation of cytoplasmic calcium concentration in renal tubular epithelium.
Recent advent in techniques to measure cytosolic calcium concentration significantly stimulated research of signal transduction. The results of the studies of a messenger role of calcium in renal tubular epithelial cells as well as some difficulties encountered in these efforts are briefly summarized below.


Obesity-Induced Hypertension: Brain Signaling Pathways.
Obesity greatly increases the risk for cardiovascular, metabolic, and renal diseases and is one of the most significant and preventable causes of increased blood pressure (BP) in patients with essential hypertension. This review highlights recent advances in our understanding of central nervous system (CNS) signaling pathways that contribute to the etiology and pathogenesis of obesity-induced hypertension. We discuss the role of excess adiposity and activation of the brain leptin-melanocortin system in causing increased sympathetic activity in obesity. In addition, we highlight other potential brain mechanisms by which increased weight gain modulates metabolic and cardiovascular functions. Unraveling the CNS mechanisms responsible for increased sympathetic activation and hypertension and how circulating hormones activate brain signaling pathways to control BP offer potentially important therapeutic targets for obesity and hypertension.


Substrate and procedural predictors of outcomes after catheter ablation for atrial fibrillation in patients with hypertrophic cardiomyopathy.
Hypertrophic cardiomyopathy (HCM) is often accompanied by atrial fibrillation (AF) due to diastolic dysfunction, elevated left atrial pressure, and enlargement. Although catheter ablation for drug-refractory AF is an effective treatment, the efficacy in HCM remains to be established. Thirty-three consecutive patients (25 male, age 51 +/- 11 years) with HCM underwent pulmonary vein (PV) isolation (n = 8) or wide area circumferential ablation with additional linear ablation (n = 25) for drug-refractory AF. Twelve-lead and 24-hour ambulating ECGs, echocardiograms, event monitor strips, and SF 36 quality of life (QOL) surveys were obtained before ablation and for routine follow-up. Twenty-one (64%) patients had paroxysmal AF and 12 (36%) had persistent/permanent AF for 6.2 +/- 5.2 years. The average ejection fraction was 0.63 +/- 0.12. The average left atrial volume index was 70 +/- 24 mL/m(2). Over a follow-up of 1.5 +/- 1.2 years, 1-year survival with AF elimination was 62%(Confidence Interval [CI]: 66-84) and with AF control was 75%(CI: 66-84). AF control was less likely in patients with a persistent/chronic AF, larger left atrial volumes, and more advanced diastolic disease. Additional linear ablation may improve outcomes in patient with severe left atrial enlargement and more advanced diastolic dysfunction. Two patients had a periprocedureal TIA, one PV stenosis, and one died after mitral valve replacement from prosthetic valve thrombosis. QOL scores improved from baseline at 3 and 12 months. Outcomes after AF ablation in patients with HCM are favorable. Diastolic dysfunction, left atrial enlargement, and AF subtype influence outcomes. Future studies of rhythm management approaches in HCM patients are required to clarify the optimal clinical approach.


A case report of effective treatment of diabetic foot with the integration of traditional Chinese medicine and western medicine.
Diabetic foot has become one of the leading causes of disability and death in diabetic patients. Restoring blood supply to the lower limbs, especially by increasing collateral vessels, is currently the most effective strategy. We report a 70-year-old female patient diagnosed with diabetic foot who was treated with integrated traditional Chinese and Western medicine. Western medicine treatment includes blood glucose control, lipid regulation, plaque stabilization, antiplatelet coagulation and anti-inflammation. Traditional Chinese medicine (TCM) treatment is based on the principles of promoting blood circulation and relieving pain, benefiting Qi and activating blood circulation, including oral Chinese medicine Tongxinluo and electro-acupuncture treatment. The vascular morphology of the patient's lower limbs and the levels of glucolipid metabolism were evaluated before and after treatment. The results showed that after treatment, the patient had increased blood flow in the lower limbs, reduced plaque in the femoral arteries, and improved levels of glucolipid metabolism.


A phase II study of thioTEPA in children with recurrent solid tumor malignancies: a Children's Cancer Group study.
A Phase II study of thioTEPA was performed by the Children's Cancer Group. ThioTEPA was administered intravenously every three weeks, at a dose of 65 mg/m2. Pediatric patients with recurrent sarcomas were targeted, but patients with other tumor diagnoses were also eligible. Toxicity was primarily hematopoietic, with thrombocytopenia being predominant. ThioTEPA did not demonstrate significant activity in the target tumor groups evaluated.


Botulinum toxin in hemifacial spasm: the challenge to assess the effect of treatment.
Hemifacial spasm is characterized by intermittent tonic or clonic contractions of the muscles supplied by the facial nerve. Although vision is less impaired than in patients with blepharospasm, the disease can impose significant psychosocial burden on patient's life. Botulinum toxin (BoNT) is the well-established pharmacotherapy of choice, but evidence from controlled clinical trials is sparse. There is a broad variety of rating scales used in clinical studies with BoNT and obviously no consensus has been reached how to assess treatment outcome in hemifacial spasm. Clinical rating scales focusing on objective function were used in a couple of controlled studies with BoNT and were appropriate to discriminate between BoNTA and placebo. But it has not been shown that they would be sensitive enough to detect minor differences between several BoNT formulations. Although most of the clinical scales consist of a five-point rating, the descriptors for the ordinal numbers are not necessarily the same so that the results of different clinical studies are not comparable to each other. The main disadvantage of clinical scales is that they do not take into account patient's perspective of disability and impact on daily life. For this reason some clinical studies applied health-related quality of life (HRQoL) questionnaires to assess efficacy, and one research group worked on the development of disease-specific tools. Although these HRQoL questionnaires have been validated and a good correlation to disease severity could be demonstrated, they are far from having become an established variable for efficacy assessment in hemifacial spasm trials. The challenge remains to establish tools which are appropriate to rate BoNT treatment effects in hemifacial spasm. Currently, it is virtually impossible to identify one rating scale which can cover all relevant aspects of the disorder. In consequence we recommend the implementation of a combination of different rating scales which address functional impairment as well as those issues which are most important to patients. Further research is needed to standardize and validate rating scales for hemifacial spasm in clinical studies.


"Fast Track" nasogastric decompression of rectal cancer surgery.
This study evaluates the application of fast track (FT) nasogastric decompression in patients who underwent anterior resection of rectal cancer. A randomized control trial was performed comparing the group with the fast track treatment (n = 57) and the group with traditional nasogastric decompression (n = 84). Preoperative characteristics and postoperative recovery indices were recorded and analyzed. The results indicate no significant differences in gender (P = 0.614), age (P = 0.653), tumor location (P = 0.113), and TNM stages (P = 0.054) were observed between the 2 groups. The differences in the type of resection, anastomosis, and adoption of protective colostomy were all not significant between the FT and the traditional group. During the first 24 hours after surgery, the volume of nasogastric drainage averaged 197 ml in the FT group and 155 ml in the traditional group (P = 0.197). The initiation of test-meal (P = 0.000), semiliquid diet (P = 0.002), and ordinary diet (P = 0.008) were all significantly shorter in the FT group. Furthermore, compared with the other group, the patients in the FT group enjoyed earlier removal of the abdominal drainage, urinary catheter, and shorter hospital stays (P = 0.000). Based on a correlation test, the duration of nasogastric decompression is related to the time of test-meal and semiliquid diet. The routine usage of nasogastric decompression in rectal surgery is unnecessary. The fast track procedure might help in facilitating postoperative functional and diet recovery, reducing the time of catheterization, and shortening hospital stay.


Impact of the fungal pathogen Fusarium oxysporum on the taxonomic and functional diversity of the common bean root microbiome.
Plants rely on their root microbiome as the first line of defense against soil-borne fungal pathogens. The abundance and activities of beneficial root microbial taxa at the time prior to and during fungal infection are key to their protective success. If and how invading fungal root pathogens can disrupt microbiome assembly and gene expression is still largely unknown. Here, we investigated the impact of the fungal pathogen Fusarium oxysporum (fox) on the assembly of rhizosphere and endosphere microbiomes of a fox-susceptible and fox-resistant common bean cultivar. Integration of 16S-amplicon, shotgun metagenome as well as metatranscriptome sequencing with community ecology analysis showed that fox infections significantly changed the composition and gene expression of the root microbiome in a cultivar-dependent manner. More specifically, fox infection led to increased microbial diversity, network complexity, and a higher proportion of the genera Flavobacterium, Bacillus, and Dyadobacter in the rhizosphere of the fox-resistant cultivar compared to the fox-susceptible cultivar. In the endosphere, root infection also led to changes in community assembly, with a higher abundance of the genera Sinorhizobium and Ensifer in the fox-resistant cultivar. Metagenome and metatranscriptome analyses further revealed the enrichment of terpene biosynthesis genes with a potential role in pathogen suppression in the fox-resistant cultivar upon fungal pathogen invasion. Collectively, these results revealed a cultivar-dependent enrichment of specific bacterial genera and the activation of putative disease-suppressive functions in the rhizosphere and endosphere microbiome of common bean under siege.


[Structural basis of frontal cortex control of thalamic and basal nuclei in dogs].
Fibrillar degeneration after extirpation of the frontal cortical field F2, central part, was observed in dogs by Nauta--Gygax and Fink--Heimer's methods. Degenerated fibrillae were stated to form two bundles and terminate near the neurons of nonspecific thalamic nuclei: n. ret, MD, pf, sprf, as well as in the neurons of specific thalamic nuclei: n. Vna, cgl, cgm, pul. Degenerated processes of the frontal cortex cells projected to the neurons of basal nuclei: the head of nucleus caudatus, putamen, globus pallidus. In the claustrum degenerative changes were not observed.


Effect of disopyramide on left ventricular performance: the relationship of free and total concentrations of the drug and of its mono-N-dealkylated metabolite to noninvasive indices of function.
We used M-mode echocardiography and recordings of systolic time intervals to follow changes in left ventricular systolic function of 10 normal subjects during administration of 200 mg oral disopyramide every 8 h. Left ventricular function was significantly depressed (peak rate of change of dimension - 17%, p less than 0.001; mean velocity of circumferential fiber shortening - 15%, p less than 0.01; percent fractional shortening - 16%, p less than 0.05) for as long as 7 h after a dose. These changes could be correlated with those in plasma concentrations of free and total disopyramide, and of its mono-N-dealkylated metabolite (change in peak rate of change of dimension versus levels of disopyramide plus metabolite, r = -0.41, p less than 0.03; changes in ratio preejection time/ejection time versus levels of disopyramide and metabolite, r = 0.62, p less than 0.002).


Mechanical activation of lung epithelial cells through the ion channel Piezo1 activates the metalloproteinases ADAM10 and ADAM17 and promotes growth factor and adhesion molecule release.
In the lung, pulmonary epithelial cells undergo mechanical stretching during ventilation. The associated cellular mechanoresponse is still poorly understood at the molecular level. Here, we demonstrate that activation of the mechanosensitive cation channel Piezo1 in a human epithelial cell line (H441) and in primary human lung epithelial cells induces the proteolytic activity of the metalloproteinases ADAM10 and ADAM17 at the plasma membrane. These ADAMs are known to convert cell surface expressed proteins into soluble and thereby play major roles in proliferation, barrier regulation and inflammation. We observed that chemical activation of Piezo1 promotes cleavage of substrates that are specific for either ADAM10 or ADAM17. Activation of Piezo1 also induced the synthesis and ADAM10/17-dependent release of the growth factor amphiregulin (AREG). In addition, junctional adhesion molecule A (JAM-A) was shed in an ADAM10/17-dependent manner resulting in a reduction of cell contacts. Stretching experiments combined with Piezo1 knockdown further demonstrated that mechanical activation promotes shedding via Piezo1. Most importantly, high pressure ventilation of murine lungs increased AREG and JAM-A release into the alveolar space, which was reduced by a Piezo1 inhibitor. Our study provides a novel link between stretch-induced Piezo1 activation and the activation of ADAM10 and ADAM17 in lung epithelium. This may help to understand acute respiratory distress syndrome (ARDS) which is induced by ventilation stress and goes along with perturbed epithelial permeability and release of growth factors.


miR-137 downregulates c-kit expression in acute myeloid leukemia.
The oncogene c-kit plays a vital role in the pathogenesis of acute myeloid leukemia (AML). However, the mechanism of microRNAs targeting c-kit in AML has not been determined in detail. Moreover, the role miR-137 in tumor cell proliferation remains controversial. The aim of this work was to verify whether miR-137 targets c-kit and to research the biological effects of restoring miR-137 expression in leukemia cells. We found that miR-137 binds specifically to the 3'-UTR of c-kit and suppresses the expression and activities of c-kit. There is a negative correlation between miR-137 and c-kit expression in both patients and cell lines determined by screening large clinical samples. We found that miR-137 can inhibit proliferation, promote apoptosis, and induce differentiation of c-kit+ AML cells. We determined that miR-137 can participate in the leukemogenesis by regulating c-kit, which could be used as a therapeutic target for acute myeloid leukemia.


To infer the probability of cervical ossification of the posterior longitudinal ligament and explore its impact on cervical surgery.
The ossification of the posterior longitudinal ligament (OPLL) in the cervical spine is commonly observed in degenerative changes of the cervical spine. Early detection of cervical OPLL and prevention of postoperative complications are of utmost importance. We gathered data from 775 patients who underwent cervical spine surgery at the First Affiliated Hospital of Guangxi Medical University, collecting a total of 84 variables. Among these patients, 144 had cervical OPLL, while 631 did not. They were randomly divided into a training cohort and a validation cohort. Multiple machine learning (ML) methods were employed to screen the variables and ultimately develop a diagnostic model. Subsequently, we compared the postoperative outcomes of patients with positive and negative cervical OPLL. Initially, we compared the advantages and disadvantages of various ML methods. Seven variables, namely Age, Gender, OPLL, AST, UA, BMI, and CHD, exhibited significant differences and were used to construct a diagnostic nomogram model. The area under the curve (AUC) values of this model in the training and validation groups were 0.76 and 0.728, respectively. Our findings revealed that 69.2% of patients who underwent cervical OPLL surgery eventually required elective anterior surgery, in contrast to 86.8% of patients who did not have cervical OPLL. Patients with cervical OPLL had significantly longer operation times and higher postoperative drainage volumes compared to those without cervical OPLL. Interestingly, preoperative cervical OPLL patients demonstrated significant increases in mean UA, age, and BMI. Furthermore, 27.1% of patients with cervical anterior longitudinal ligament ossification (OALL) also exhibited cervical OPLL, whereas this occurrence was only observed in 6.9% of patients without cervical OALL. We developed a diagnostic model for cervical OPLL using the ML method. Our findings indicate that patients with cervical OPLL are more likely to undergo posterior cervical surgery, and they exhibit elevated UA levels, higher BMI, and increased age. The prevalence of cervical anterior longitudinal ligament ossification was also significantly higher among patients with cervical OPLL.


One-way Acoustic Beam Splitter.
As a key component of various acoustic systems, acoustic beam splitter (BS) finds important application in many scenarios, yet are conventionally based on the assumption that the acoustic waves propagate as easily when incident from either input or output side. It would therefore be intriguing, from the viewpoints of both science and technology, to break through this limit by realizing acoustic BSs supporting asymmetric transmission. Here we propose the concept of one-way acoustic BS capable of splitting acoustic beam incident from the input port into multiple beams while effectively reducing the backward transmission from any of the output ports. Furthermore, our design enables flexibly adjusting the number and angle of output beams by blocking the unused line defects. The numerical results verify the theoretical predictions and demonstrate the phenomenon of one-way acoustic BS at the predesigned frequency. Our design with functionality and flexibility bridges the gap between acoustic diodes and BSs and may enable novel multi-functional devices with great application prospects in diverse fields such as acoustic integrated circuits and acoustic communication.


Enzymatic oxidation of mercury vapor by erythrocytes.
The formation of glutathione radicals, the evolution of nascent oxygen or the peroxidatic reaction with catalase complex I are considered as possible mechanisms for the oxidation of mercury vapor by red blood cells. To select among these, the uptake of atomic mercury by erythrocytes from different species was studied and related to their various activities of catalase (hydrogenperoxide : hydrogen-peroxide oxidoreductase, EC 184.108.40.206) and glutathione peroxidase (glutathione : hydrogen-peroxide oxidoreductase, EC 22.214.171.124). A slow and continuous infusion of diluted H2O2 was used to maintain steady concentrations of complex I. 1% red cell supsensions were found most suitable showing high rates of Hg uptake and yielding still enough cells for subsequent determinations. The results indicate that the oxidation of mercury depends upon the H2O2-generation rate and upon the specific acticity of red-cell catalase. The oxidation occurred in a range of the catalase-H2O2 reaction where the evolution of oxygen could be excluded. Compounds reacting with complex I were shown to be effective inhibitors of the mercury uptake. GSH-peroxidase did not participate in the oxidation but rather, was found to inhibit it by competing with catalase for hydrogen peroxide. These findings support the view that elemental mercury is oxidized in erythrocytes by a peroxidatic reaction with complex I only.


Tislelizumab Plus Chemotherapy Versus Placebo Plus Chemotherapy as First-Line Treatment for Chinese Patients with Advanced Esophageal Squamous Cell Carcinoma: A Cost-Effectiveness Analysis.
Advanced esophageal squamous cell carcinoma (ESCC) is a prevalent and highly malignant tumor with a poor prognosis. Recently, the RATIONALE-306 trial demonstrated that tislelizumab combined with chemotherapy provided overall survival benefits for these patients. This study aimed to assess the cost-effectiveness of this treatment approach in Chinese patients with advanced ESCC from the perspective of healthcare system. A Markov model was constructed to assess the economic and health benefits associated with tislelizumab plus chemotherapy over a 10-year lifetime horizon, utilizing data from the RATIONALE-306 trial. The analysis encompassed the calculation of several key parameters, including the incremental cost-effectiveness ratio (ICER), total cost, incremental cost, total effectiveness, and incremental effectiveness. Tislelizumab was considered cost-effective if the ICER obtained was below the willingness-to-pay (WTP) threshold of US$38,223 per quality-adjusted life-year (QALY); otherwise, it would be deemed not cost-effective. To ensure the robustness of the findings, the results were subjected to one-way sensitivity analysis and probabilistic sensitivity analysis (PSA). In the base-case analysis, the incremental effectiveness and cost associated with tislelizumab plus chemotherapy, compared to chemotherapy alone, were determined to be 0.40 QALY and US$7604, respectively. This resulted in an ICER of US$18,846 per QALY, which is below the WTP threshold of US$38,223 per QALY. Furthermore, the results from the one-way sensitivity analysis and PSA indicated robustness of the findings. Our lifetime simulation study demonstrated that, in the case of advanced ESCC, the combination of tislelizumab and chemotherapy offers increased effectiveness compared to chemotherapy alone, albeit at a higher cost. Moreover, considering the current WTP threshold in China, the addition of tislelizumab to chemotherapy is considered a cost-effective approach.


Highly Efficient Alkaline Water Splitting with Ru-Doped Co-V Layered Double Hydroxide Nanosheets as a Bifunctional Electrocatalyst.
Active electrocatalysts for the hydrogen evolution reaction (HER) and oxygen evolution reaction (OER) are decisive for achieving efficient energy conversion from electricity to hydrogen fuel through water electrolysis. In this study, tremella-like Ru-doped Co-V layered double hydroxide nanosheets on Ni Foam (Ru-CoV-LDH@NF) was fabricated by a one-pot solvothermal reaction. As-prepared Ru-CoV-LDH@NF, with a nominal Ru loading of around 51.6 μg cm-2 exhibits excellent bifunctional catalytic activity towards HER and OER in alkaline media. To accomplish a current density of 10 mA cm-2 , it demands 32 mV and 230 mV overpotentials for HER and OER, respectively. The alkali electrolyzer utilizing Ru-CoV-LDH/NF as bifunctional electrocatalyst affords 10 mA cm-2 electrolytic current density at an extremely low cell voltage of 1.50 V, showing excellent performance compared to a Pt/C-RuO2 -based electrolyzer and many other bifunctional electrocatalyst-based ones. The incorporation of Ru changes the morphology of the resultant nanosheets to offer high electrochemical surface areas for electrocatalysis; at the same time, it significantly boosts the intrinsic HER/OER electrocatalytic activity. For HER, the energy barrier of the Volmer step is efficiently reduced upon Ru doping, whereas the Ru dopants optimize the absorption strength of *O intermediates to facilitate the OER process. This work offers a feasible means to optimize the Co-based hydroxide materials for improved electrocatalysis in overall water splitting.


Maintaining a physiological blood glucose level with 'glucolevel', a combination of four anti-diabetes plants used in the traditional arab herbal medicine.
Safety and anti-diabetic effects of Glucolevel, a mixture of dry extract of leaves of the Juglans regia L, Olea europea L, Urtica dioica L and Atriplex halimus L were evaluated using in vivo and in vitro test systems. No sign of toxic effects (using LDH assay) were seen in cultured human fibroblasts treated with increasing concentrations of Glucolevel. Similar observations were seen in vivo studies using rats (LD50: 25 g/kg). Anti-diabetic effects were evidenced by the augmentation of glucose uptake by yeast cells (2-folds higher) and by inhibition of glucose intestinal absorption ( approximately 49%) in a rat gut-segment. Furthermore, treatment with Glucolevel of Streptozotocin-induced diabetic rats for 2-3 weeks showed a significant reduction in glucose levels [above 400 +/- 50 mg/dl to 210 +/- 22 mg/dl (P < 0.001)] and significantly improved sugar uptake during the glucose tolerance test, compared with positive control. In addition, glucose levels were tested in sixteen human volunteers, with the recent onset of type 2 diabetes mellitus, who received Glucolevel tablets 1 x 3 daily for a period of 4 weeks. Within the first week of Glucolevel consumption, baseline glucose levels were significantly reduced from 290 +/- 40 to 210 +/- 20 mg/dl. At baseline, a subgroup of eleven of these subjects had glucose levels below 300 mg% and the other subgroup had levels >/= 300 mg%. Clinically acceptable glucose levels were achieved during the 2-3 weeks of therapy in the former subgroup and during the 4th week of therapy in the latter subgroup. No side effect was reported. In addition, a significant reduction in hemoglobin A1C values (8.2 +/- 1.03 to 6.9 +/- 0.94) was found in six patients treated with Glucolevel. Results demonstrate safety, tolerability and efficacy of herbal combinations of four plants that seem to act differently but synergistically to regulate glucose-homeostasis.


Natural Short-term Course of Recurrent Macular Edema Following Intravitreal Bevacizumab Therapy in Branch Retinal Vein Occlusion.
To evaluate the 3-month natural course of recurrent macular edema secondary to branch retinal vein occlusion (BRVO) treated with intravitreal bevacizumab. This retrospective, observational study included 36 eyes with macular edema secondary to BRVO. All patients were initially treated with intravitreal bevacizumab for macular edema. Recurrence of macular edema was either not treated (untreated group) or treated with a single intravitreal bevacizumab injection (treated group). Central foveal thickness (CFT) and best-corrected visual acuity (BCVA) were compared at the time of recurrence and 3 months later. At the time of recurrence, the mean CFT and logarithm of the minimum angle of resolution BCVA were 484.9 ± 124.1 µm and 0.58 ± 0.26 in the untreated group (n = 19) and 456.3 ± 126.8 µm and 0.51 ± 0.21 in the treated group (n = 17), respectively. Three months later, the mean CFT and BCVA had changed to 493.7 ± 123.9 µm and 0.62 ± 0.29 in the untreated group and 294.7 ± 104.4 µm and 0.40 ± 0.24 in the treated group, respectively. The differences in CFT and BCVA between the two time points were not significant in the untreated group (p = 0.106 and p = 0.687, respectively), whereas statistically significant differences were noted in the treated group (p = 0.002 and p < 0.001, respectively). Unlike the first episode of macular edema following BRVO, recurrent macular edema following intravitreal bevacizumab therapy did not spontaneously resolve, suggesting the potential benefit of prompt treatment.


Exploring the potential of ChatGPT as a supplementary tool for providing orthopaedic information.
To investigate the potential use of large language models (LLMs) in orthopaedics by presenting queries pertinent to anterior cruciate ligament (ACL) surgery to generative pre-trained transformer (ChatGPT, specifically using its GPT-4 model of March 14th 2023). Additionally, this study aimed to evaluate the depth of the LLM's knowledge and investigate its adaptability to different user groups. It was hypothesized that the ChatGPT would be able to adapt to different target groups due to its strong language understanding and processing capabilities. ChatGPT was presented with 20 questions and response was requested for two distinct target audiences: patients and non-orthopaedic medical doctors. Two board-certified orthopaedic sports medicine surgeons and two expert orthopaedic sports medicine surgeons independently evaluated the responses generated by ChatGPT. Mean correctness, completeness, and adaptability to the target audiences (patients and non-orthopaedic medical doctors) were determined. A three-point response scale facilitated nuanced assessment. ChatGPT exhibited fair accuracy, with average correctness scores of 1.69 and 1.66 (on a scale from 0, incorrect, 1, partially correct, to 2, correct) for patients and medical doctors, respectively. Three of the 20 questions (15.0%) were deemed incorrect by any of the four orthopaedic sports medicine surgeon assessors. Moreover, overall completeness was calculated to be 1.51 and 1.64 for patients and medical doctors, respectively, while overall adaptiveness was determined to be 1.75 and 1.73 for patients and doctors, respectively. Overall, ChatGPT was successful in generating correct responses in approximately 65% of the cases related to ACL surgery. The findings of this study imply that LLMs offer potential as a supplementary tool for acquiring orthopaedic knowledge. However, although ChatGPT can provide guidance and effectively adapt to diverse target audiences, it cannot supplant the expertise of orthopaedic sports medicine surgeons in diagnostic and treatment planning endeavours due to its limited understanding of orthopaedic domains and its potential for erroneous responses. V.


One-Third Tubular Plate Remains a Clinically Good Option in Danis-Weber Type B Distal Fibular Fracture Fixation.
To compare the clinical outcomes of locking plate (LP) and non-locking one-third tubular plate (TP) fixation, and to provide guidance on plate selection for Danis-Weber type B distal fibular fracture treatment. In total, 83 patients who underwent plate fixation for Danis-Weber type B distal fibular fractures between March 2013 and July 2018 were retrospectively reviewed: 41 (49.0%) received LPs and 42 (51.0%) received TPs. Patients' demographic data, follow-up durations, the proportion of comminuted fractures, and ankle range of motion were investigated. The American Orthopaedic Foot and Ankle Society (AOFAS) ankle-hindfoot scale, Karlsson scale, Foot and Ankle Ability Measure (FAAM), and Lower Extremity Functional Scale (LEFS) scores were assessed. The radiographic union progression and implant removal time were evaluated, along with postoperative complications. Data from the LP and TP groups were compared statistically. The mean patient ages were 53.3 ± 17.5 years (range, 16-80 years) and 47.6 ± 17.0 years (range, 14-68 years) in the LP and TP groups, respectively (P > 0.05). The gender distribution did not differ significantly between groups (P > 0.05). Other demographic data also did not differ significantly between groups (P > 0.05). The mean follow-up durations were 16.8 ± 7.7 months (range, 13.0-19.0 months) in the LP group and 16.1 ± 6.2 months (range, 12.0-20.0 months) in the TP group (P > 0.05). Comminuted fractures were observed in 18 of 41 (43.9%) patients with LP and 10 of 42 (23.8%) patients with TP (P > 0.05). Forward bending ankle dorsiflexion was possible at the final follow-up in 82.9% and 85.7% of LP and TP patients, respectively (P > 0.05). The AOFAS ankle-hindfoot scale, Karlsson scale, FAAM, and LEFS scores did not differ significantly between groups at the final follow-up (P > 0.05). The pre-fracture and final postoperative scores on these four instruments did not differ significantly in the LP or TP group (P > 0.05). The mean times to radiographic union progression were 13.5 ± 7.1 weeks and 15.1 ± 10.2 weeks in the LP and TP groups, respectively (P > 0.05). The mean times to implant removal surgery reaffirming solid union were 15.6 ± 5.5 months and 14.8 ± 4.9 months in the LP and TP groups, respectively (P > 0.05). Hardware irritation was detected in five patients in the LP group (12.2%) and three in the TP group (7.1%) (P > 0.05). One patient in the LP group and two in the TP group developed superficial wound infections, which resolved without further surgical intervention. Conventional TP remains a good option for the fixation of Danis-Weber type B distal fibular fractures, regardless of the biomechanical properties.


Colonization and performance of a pyrene-degrading bacterium Mycolicibacterium sp. Pyr9 on root surfaces of white clover.
Some rhizosphere bacteria could colonize on the root surface of plants, or even form biofilm to promote plant growth, enhance plant resistance to harsh external environments and block the soil contamination. In this study, to explore the effects of pyrene-degrading bacterium on root surface on plant uptake of pyrene, a pyrene-degrading bacterium Mycolicibacterium sp. Pyr9 was isolated from the root surface of Eleusine indica L. Gaertn. in PAH-contaminated fields; after antibiotic labeling, it was colonized onto the root surface of white clover (Trifolium repens L.), and its distribution and performance were monitored under different levels of pyrene contamination. Strain Pyr9 could degrade 98% of pyrene (with an initial concentration of 50 mg L-1) in culture solution within 8 d; it also owns a variety of plant growth promoting characteristics and appreciable tolerance to harsh environments. The transcription of pyrene catabolic genes in Pyr9 enhanced obviously when induced by pyrene. Pyr9 colonized and grew well on the root surface of white clover via root inoculation; some cells could even enter into the root tissues and move to the shoots. Compared with the Pyr9-free treatment, the pyrene contents in the roots and shoots of Pyr9-inoculated white clover decreased by 25%-30% and 33%-42%, respectively. Correspondingly, the pyrene accumulation and translocation factors in white clover decreased as well. These results indicate that Pyr9 would be a good potential to circumvent plant pyrene pollution. This research may provide a theoretical basis and technical support for the safety of agricultural products and human health in PAH-contaminated sites.


Improving the spectral resolution of wedged etalons and linear variable filters with incidence angle.
Compact spectrometers fabricated by placing a wedged etalon or a linear variable filter in front of a linear photodiode array typically do not exhibit the spectral resolution of a parallel filter of the same finesse. A theoretical analysis of the beam emerging from a wedged etalon is shown to predict a comalike aberration, explaining the loss in resolution. This analysis also predicts a focused beam waist whose axial position depends on the incidence angle, indicating that resolution can be improved by placing this waist on the detector. These results are experimentally confirmed in a multicavity linear variable filter to achieve 0.09 nm spectral resolution at 1550 nm.


Studies on proteins of animal ribosomes. XXVIII. Preparation and antigenic properties of 40 S subunit proteins of rat liver ribosomes.
By combination of ion exchange chromatography, gel filtration, preparative polyacrylamide gel electrophoresis and perchloric acid fractionation 21 proteins of the small ribosomal subunit of rat liver were isolated with a purity of more than 95%. It could be demonstrated by immunological studies that no extensive structural homologies exist between these proteins.


Enzymatic amplification of DNA by PCR: standard procedures and optimization.
This unit describes a method for amplifying DNA enzymatically by the polymerase chain reaction (PCR), including procedures to quickly determine conditions for successful amplification of the sequence and primer sets of interest, and to optimize for specificity, sensitivity, and yield. Hot-start methods are described which can greatly improve specificity, sensitivity, and yield. This protocol suggests some relatively inexpensive methods to achieve hot start, and lists several commercial hot-start options which may be more convenient, but of course more expensive. The unit has recently been updated to include new information on reagents to enhance the reaction, better cycling parameters, and innovations in robotics and high-performance thermocyclers.


Engineering of a tumor cell-specific, cytosol-penetrating antibody with high endosomal escape efficacy.
The main obstacles for practical uses of cytosol-penetrating peptides and proteins include their lack of cell- or tissue-specific targeting and limited cytosolic access owing to the poor endosomal escape ability. We have previously reported a cytosol-penetrating, human IgG1 antibody TMab4-WYW, generally referred to as a cytotransmab (CT), which reaches the cytosol of living cells but nonspecifically because it is endocytosed via a ubiquitously expressed receptor called heparan sulfate proteoglycan (HSPG). Here, our aim was to construct a next-generation CT with tumor cell specificity and improved endosomal escape efficiency. We first substantially reduced the HSPG-binding activity of TMab4-WYW and then fused a cyclic peptide specifically recognizing tumor-associated epithelial cell adhesion molecule (EpCAM) to the N terminus of the light chain for EpCAM-mediated endocytosis, while maintaining the endosomal escape ability in the light chain variable domain (VL), thus generating epCT05. Then, we separately engineered another CT, dubbed epCT65-AAA, with an endosomal escape ability only in the heavy chain variable domain (VH) but not in VL, by functional grafting of the endosomal escape motif of epCT05 VL to the VH. We finally combined the heavy chain of epCT65-AAA and the light chain of epCT05 to create epCT65 with endosomal escape capacity in both the VH and VL. epCT65 effectively localized to the cytosol of only EpCAM-expressing tumor cells and showed approximately twofold improved endosomal escape efficiency, as compared with CTs with endosomal escape motifs in either VH or VL. The full-IgG format CT, epCT65, with a tumor cell-specific cytosol-penetrating activity, has a great potential for practical medical applications, e.g., as a carrier for cytosolic delivery of payloads.


A review of physical phenomena associated with ultrasonic contrast agents and illustrative clinical applications.
Successful clinical applications of contrast agents involve an understanding of the physical interaction of ultrasound (US) with contrast agents. This paper reviews the physical phenomena involved in these interactions and discusses the relevant theoretical background for modeling US-contrast agent interactions. Measurement techniques using US to obtain information regarding contrast agents are summarized. Illustrative clinical applications are given in the second part of the paper. Recent developments in nonlinear imaging techniques and transient techniques are reviewed. New methods, such as depletion perfusion measurement, and high-frequency applications are included.


Propranolol and verapamil inhibit mRNA expression of RyR2 and SERCA in L-thyroxin-induced rat ventricular hypertrophy.
To study the alteration in the mRNA level of cardiac ryanodine receptor 2 (RyR2) and sarco-endoplasmic reticulum Ca2+-ATPase (SERCA) in L-thyroxin-induced hypertrophy. L-thyroxin (500 g/kg) daily was injected for 10 d. RT-PCR was used to determine mRNA expression. An increase in the relative amount of RyR2 (111 %) and SERCA mRNA (65 %) expression was observed in the hypertrophied rats (RyR2: 77+/-11; SERCA: 87+/-10, n=9) compared with the normal rats (RyR2: 36+/-10; SERCA: 53+/-10, n=9). Propranolol was effective to inhibit the increase in RyR2 (51+/-7) and SERCA (63+/-13) mRNA expression in hypertrophied rats, respectively. Verapamil also reduced RyR2 (62+/-5) and SERCA (75+/-8) mRNA expression. Both RyR2 and SERCA mRNA level in L-thyroxin-induced cardiac hypertrophy was over-expressed and propranolol or verapamil inhibited the alteration.


Salivary microbiome composition changes after bariatric surgery.
Recent studies show that the salivary microbiome in subjects with obesity differ from those without obesity, but the mechanism of interaction between the salivary microbiome composition and body weight is unclear. Herein we investigate this relation by analyzing saliva samples from 35 adult patients with obesity undergoing bariatric surgery. Our aim was to describe salivary microbiome changes during body weight loss on an individual-specific level, and to elucidate the effect of bariatric surgery on the salivary microbiome which has not been studied before. Analysis of samples collected before and 1 day after surgery, as well as 3 and 12 months after surgery, showed that the salivary microbiome changed in all study participants, but these changes were heterogeneous. In the majority of participants proportions of Gemella species, Granulicatella elegans, Porphyromonas pasteri, Prevotella nanceiensis and Streptococcus oralis decreased, while Veillonella species, Megasphaera micronuciformis and Prevotella saliva increased. Nevertheless, we found participants deviating from this general trend which suggests that a variety of individual-specific factors influence the salivary microbiome composition more effectively than the body weight dynamics alone. The observed microbiome alternations could be related to dietary changes. Therefore, further studies should focus on association with altered taste preferences and potential oral health consequences.


The pre-nervous serotonergic system of developing sea urchin embryos and larvae: pharmacologic and immunocytochemical evidence.
Forty serotonin-related neurochemicals were tested on embryos and larvae of Lytechinus variegatus and other sea urchin species. Some of these substances (agonists of 5-HT1 receptors, antagonists of 5-HT2, 5-HT3 or 5-HT4 receptors, and inhibitors of the serotonin transporter, SERT) perturbed post-blastulation development, eliciting changes in embryonic/larval phenotypes typical for each class of receptor ligand. These developmental malformations were prevented completely or partially by serotonin (5-HT) or 5-HT analogs (5-HTQ, AA-5-HT), providing evidence for the putative localization of cellular targets. Immunoreactive 5-HT, 5-HT receptors and SERT were found in pre-nervous embryos and larvae of both L. variegatus and Strongylocentrotus droebachiensis. During gastrulation, these components of the serotonergic system were localized to the archenteron (primary gut), mesenchyme-like cells, and often the apical ectoderm. These results provide evidence that pre-nervous 5-HT may regulate early events of sea urchin embryogenesis, mediated by 5-HT receptors or the 5-HT transporter.


In vivo evaluation of hemerythrin-based oxygen carriers: Similarities with hemoglobin-based counterparts.
We have previously proposed the annelid-derived protein, hemerythrin, as a viable replacement for hemoglobin in the synthesis of semi-synthetic oxygen carriers ("blood substitutes"). Here, we report the first in vivo tests for potential hemerythrin-based oxygen carriers (HrBOC), using a battery of experiments involving Wistar rats and previously tested on a series of hemoglobin-based oxygen carrier candidates (HBOC). At the concentrations tested, hemerythrin appears to behave similarly to hemoglobin - including, importantly, immunological effects. The antioxidant strategies based on albumin as well as based on rubrerythrin appear to offer observable physiological advantages.


Eyelid hypertrichosis associated with latanoprost is reversible.
A 56-year-old woman with primary open-angle glaucoma in an only eye presented with hypertrichosis after using Latanoprost to lower IOP. After trabeculectomy with adjunctive Mitomycin C, IOP was well controlled and antiglaucoma medications could be discontinued. At eight-month follow-up the abnormal eyelashes had disappeared.


A comparison of faculty-led small group learning in combination with computer-based instruction versus computer-based instruction alone on identifying simulated pulmonary sounds.
Computer-based learning has gained widespread acceptance in medical curricula, but can it replace faculty-led teaching. To investigate the effectiveness of independent computer-based learning of pulmonary auscultation alone and in combination with faculty-led teaching. The first method involved independent computer-based instruction (CBI; Group 1) of 113 second-year medical students. The second method involved a combination of faculty-led instruction and independent CBI (Group 2) of 79 second-year medical students. A pretest-posttest method of assessment was used. The pretest showed recognition rates of 48% for Group 1 and 46% for Group 2, whereas the posttest showed recognition rates of 81% for Group 1 and 88% for Group 2. The posttest clinical correlation scores were identical with both groups scoring 93 percent. The study demonstrates that student learning of pulmonary auscultation is similar whether a computer-based independent instructional approach is used alone or in combination with faculty-led sessions.


A strict-late viral promoter is a strong tumor-specific promoter in the context of an oncolytic herpes simplex virus.
Confinement of transgene expression to target cells is highly desirable in gene therapy. Current strategies of transcriptional targeting to tumors usually rely on tissue-specific promoters to control gene expression. However, such promoters generally have much lower activity than the constitutive viral promoters. We have explored an alternative approach, using a strict-late viral promoter (UL38p) in the context of an oncolytic herpes simplex virus (HSV) for tumor-selective gene expression. As with many DNA viruses, the genomic transcription of HSV is a tightly regulated molecular cascade in which early and late phases of gene expression are separated by viral DNA replication. In particular, some of the late transcripts are categorized as strict-late, whose expression depends rigorously on the initiation of viral DNA replication. Our in vitro and in vivo characterization showed that in normal nondividing cells, where the oncolytic HSV has limited ability to replicate, the UL38p has minimal activity. However, in tumor or cycling cells where the virus can fully replicate, transgene expression from UL38p was almost as high as from the cytomegalovirus immediate-early promoter. These results suggest that delivery of therapeutic genes driven by UL38p through an oncolytic HSV may be an effective approach to gene therapy for malignant diseases.