Myricitrin as a substrate and inhibitor of myeloperoxidase: implications for the pharmacological effects of flavonoids.
Flavonoids are increasingly being ingested by the general population as chemotherapeutic and anti-inflammatory agents. They are potentially toxic because of their conversion to free radicals and reactive quinones by peroxidases. Little detailed information is available on how flavonoids interact with myeloperoxidase, which is the predominant peroxidase present at sites of inflammation. This enzyme uses hydrogen peroxide to oxidize chloride to hypochlorous acid, as well as to produce an array of reactive free radicals from organic substrates. We investigated how the flavonoid myricitrin is oxidized by myeloperoxidase and how it affects the activities of this enzyme. Myricitrin was readily oxidized by myeloperoxidase in the presence of hydrogen peroxide. Its main oxidation product was a dimer that underwent further oxidation. In the presence of glutathione, myricitrin was oxidized to a hydroquinone that was conjugated to glutathione. When myeloperoxidase oxidized myricitrin and related flavonoids it became irreversibly inactivated. The number of hydroxyl groups in the B ring of the flavonoids and the presence of a free hydroxyl m-phenol group in the A ring were important for the inhibitory effects. Less enzyme inactivation occurred in the presence of chloride. Neutrophils also oxidized myricitrin to dimers in a reaction that was partially dependent on myeloperoxidase. Myricitrin did not affect the production of hypochlorous acid by neutrophils. We conclude that myricitrin will be oxidized by neutrophils at sites of inflammation to produce reactive free radicals and quinones. It is unlikely to affect hypochlorous acid production by neutrophils.


Opiate-like excitatory effects of steroid sulfates and calcium-complexing agents given cerebroventricularly.
Intracerebroventricular administration of 10--20 microgram of steroid-O-sulfates induced hypermotility, agitation, salivation, EEG abnormalities, stereotypies, wet dog shakes and seizures. Equivalent effects resulted from 30--200 microgram morphine sulfate (H2SO4 salt), 50 microgram EGTA or 300--400 microgram of sodium sulfate or phosphate, but not chloride, nitrate or acetate. Non-steroid sulfates, steroid glucuronides and steroid phosphates were inactive. Naloxone, previously found to antagonize the excitatory effects of androsterone sulfate, failed to antagonize those of cortisol sulfate, sodium sulfate or EGTA. These findings suggest a role for extracellular calcium ions and for sulfate derived from circulating steroids in central responses to opiates.


Saccharomyces cerevisiae strains sensitive to inorganic mercury. III. Tyrosine uptake.
In Saccharomyces cerevisiae, the HGS2-1 allele confers sensitivities to inorganis mercury (Ono and Sakamoto 1985) and to excess fermentable sugars such as glucose (Sakamoto et al. 1985); exogenous tyrosine antagonizes both inorganic mercury and excess glucose. In this study, the inorganic mercury sensitive strain has been shown to have about twice more glucose-1,6-bisphosphate and slightly less pyruvate than the normal strains, suggesting that the inorganic mercury sensitive strain has the reduced aldolase activity. It has been also shown that the growth retarded cells accumulate trehalose, by which the lower level of glucose-6-phosphate in the inorganic mercury sensitive strain is accounted for, and that inorganic mercury, presumably excess glucose also, causes growth inhibition via depletion of cellular tyrosine. The mechanism how cellular tyrosine is depleted by inorganic mercury or excess glucose is accounted for by the facts that (1) the tyrosine uptake activity is decreased with increase of glucose concentration in growth medium, (2) HGS2-1 enhances the effect of glucose on the tyrosine uptake activity, and (3) inorganic mercury inhibits the tyrosine uptake system by binding to its SH-group(s). Thus, it is concluded that the role of tyrosine is not to detoxify inorganic mercury nor excess fermentable sugars but simply to counteract depletion of cellular tyrosine induced by them.


Calcium-calmodulin signaling induced by epithelial cell differentiation upregulates BRAK/CXCL14 expression via the binding of SP1 to the BRAK promoter region.
The chemokine BRAK/CXCL14 (BRAK) is expressed in normal squamous epithelium, but is not expressed or is expressed at negligible levels in head and neck squamous cell carcinoma. Malignant cells are known to be dedifferentiated compared with normal epithelial cells, suggesting a role for differentiation cues in the expression of BRAK. Thus, we examined the relationship between BRAK expression and stages of differentiation level in epithelial cells. Immunohistochemical analysis showed that BRAK protein was expressed in cells above the spinous cell layer in normal epithelia. In HSC-3 cells in culture, expression of BRAK mRNA was significantly upregulated by cell contact in a cell density-dependent manner, and mRNA expression of cell differentiation markers such as involucrin, cystatin-A, TGM1, TGM3, and TGM5 was concomitantly augmented. Furthermore, the upregulation of BRAK induced by cell contact was suppressed by chlorpromazine, a specific inhibitor of calmodulin. We previously reported that GC boxes and a TATA-like sequence in the BRAK promoter region are associated with the expression of BRAK. Using a promoter assay and ChIP, we demonstrated that binding of the stimulating protein-1 (SP1) transcription factor to a GC box upstream of the BRAK transcription start site was necessary for cell density-dependent upregulation of BRAK. These results indicated that upregulation of BRAK was accompanied by differentiation of epithelial cells induced by calcium/calmodulin signaling, and that SP1 binding to the BRAK promoter region played an important role in this signaling.


Results of intraoperative radiotherapy given as a boost after breast conserving-surgery.
Whole breast irradiation after breast-conserving surgery (BCS) with an external beam boost of 10-16 Gy is currently the standard treatment in breast cancer. Various modalities have been used for tumor bed boost irradiation. This study aimed to evaluate the local recurrence rate, overall survival rate (OSR), toxicity and cosmetic outcome of intraoperative radiotherapy (IORT) as a boost followed by whole breast irradiation in patients who received BCS. This is a retrospective study. Between December 2009 and March 2017, 81 patients who underwent BCS with IORT as a boost were enrolled in this study. For IORT, a single dose of 20 Gy was delivered using a 30-50 kV photon beam, intraoperatively. All patients received whole breast radiation therapy (WBRT) of 42.5-50 Gy over 4-5 weeks. The primary endpoint was a 3-year local recurrence rate. Secondary endpoints included the OSR, toxicity and cosmetic outcome at 6 months after radiation treatment. At a median follow-up of 43 months, ipsilateral local recurrence was observed in one of the 81 patients (1.2%) which occurred in the same quadrant of the breast index. The 3-year OSR was 89.8%. Treatment was well-tolerated with no grade 3-4 acute and late toxicity, and 87% of patients were recorded as excellent-good cosmesis. The use of BCS with IORT as a boost resulted in a low local recurrence rate and excellent cosmetic outcome in early breast cancer. Thus, IORT as a boost could be considered as an alternative to an external beam boost. Prospective studies are needed to confirm this data.


Nitrogen fixation by Spirillum sp. from rice roots.
Nitrogen fixation by Spirillum sp. obtained from the roots of rice plants grown at different levels of combined nitrogen was studied. The roots of rice plants exposed to low levels of combined nitrogen (20--40 kg N/ha) harboured Spirillum sp. possessing higher nitrogen-fixing efficiency as compared to the cultures from plants receiving 60--100 kg N/ha. Moreover, the nitrogen-fixing efficiency of these Spirillum spp. varied with age of the plant, irrespective of the dosage of combined nitrogen.


Uterine synechiae after bipolar hysteroscopic resection of submucosal myomas in patients with infertility.
To determine the rate of uterine synechiae after bipolar hysteroscopic myomectomy in patients suffering from infertility. Retrospective case series study. University obstetrics gynecologic and assisted reproduction center. A group of 53 patients with primary (n = 30) and secondary (n = 23) infertility. Patients underwent bipolar hysteroscopic resection of myomas between 2001 and 2006, and an outpatient hysteroscopy was performed 2 months after the fibroid resection. The formation of uterine synechiae and pregnancy rates were collected from the patients' clinical notes. The submucosal myomas were intracavitary class 0 (n = 12), intramural class 1 (n = 19), and intramural class 2 (n = 22). The mean age of the women was 35.0 +/- 4.8 years. The mean myoma size was 25 +/- 11 mm. Postoperative office hysteroscopies revealed synechiae in four (7.5%) of 53 patients. Sixteen (32.7%) of the 49 patients not lost to follow-up conceived, and 12 (24.5%) of them delivered at term. Myoma size >or=3.5 cm and age <35 years were associated with a significantly higher pregnancy rate in univariate and multivariate analysis. The incidence of uterine synechiae after bipolar hysteroscopic resection of fibroids was 7.5%. This appears to be lower than that reported in previous studies using monopolar energy. Bipolar hysteroscopic myomectomy may be a better option for infertile women.


Anisotropic silk fibroin/gelatin scaffolds from unidirectional freezing.
Recent studies have underlined the importance of matching scaffold properties to the biological milieu. Tissue, and thus scaffold, anisotropy is one such property that is important yet sometimes overlooked. Methods that have been used to achieve anisotropic scaffolds present challenges such as complicated fabrication steps, harsh processing conditions and toxic chemicals involved. In this study, unidirectional freezing was employed to fabricate anisotropic silk fibroin/gelatin scaffolds in a simple and mild manner. Morphological, mechanical, chemical and cellular compatibility properties were investigated, as well as the effect of the addition of gelatin to certain properties of the scaffold. It was shown that scaffold properties were suitable for cell proliferation and that mesenchymal stem cells were able to align themselves along the directed fibers. The fabricated scaffolds present a platform that can be used for anisotropic tissue engineering applications such as cardiac patches.


Congenital goitre and hypothyroidism with impaired iodide organification and high thyroid peroxidase concentration.
A sibship of thirteen subjects whose parents were first cousins was studied for a defect in thyroid hormone synthesis. Five sibs were goitrous and had congenital hypothyroidism. All but one showed a positive perchlorate discharge test (PDT). Three other subjects were goitrous and euthyroid (one with a positive PDT), and the remaining five sibs were euthyroid with a presumably normal thyroid. However, an abnormally exaggerated TSH response to TRH was observed not only in the hypothyroid patients but also in six of the other subjects, indicating a decreased thyroid feedback at the pituitary level in the presence of a normal serum concentration of thyroid hormones. In two hypothyroid patients a normal serum T3, low serum T4 and a low reverse T3 were observed. Microscopic studies of thyroid tissue from three of the sibs disclosed marked cellular hyperplasia with no lymphocytic infiltration anywhere in the tissue. Peroxidase activity was determined on tissue from three sibs by three different assay procedures. It was within the normal range in one patient and was significantly elevated in the other two. There was no evidence for a qualitatively defective peroxidase. The defect in thyroid function in this family does not appear to involve a peroxidase deficiency. Thyroglobulin isolated from the thyroid glands of two of the goitrous, hypothyroid subjects was poorly iodinated but was judged to be normal by immunoreactive and ultracentrifugation procedures. Although the nature of the thyroid metabolic defect in this family was not elucidated, the evidence suggests a genetic defect, probably involving a recessive gene.


Parametric uncertainty and global sensitivity analysis in a model of the carotid bifurcation: Identification and ranking of most sensitive model parameters.
In computational cardiovascular models, parameters are one of major sources of uncertainty, which make the models unreliable and less predictive. In order to achieve predictive models that allow the investigation of the cardiovascular diseases, sensitivity analysis (SA) can be used to quantify and reduce the uncertainty in outputs (pressure and flow) caused by input (electrical and structural) model parameters. In the current study, three variance based global sensitivity analysis (GSA) methods; Sobol, FAST and a sparse grid stochastic collocation technique based on the Smolyak algorithm were applied on a lumped parameter model of carotid bifurcation. Sensitivity analysis was carried out to identify and rank most sensitive parameters as well as to fix less sensitive parameters at their nominal values (factor fixing). In this context, network location and temporal dependent sensitivities were also discussed to identify optimal measurement locations in carotid bifurcation and optimal temporal regions for each parameter in the pressure and flow waves, respectively. Results show that, for both pressure and flow, flow resistance (R), diameter (d) and length of the vessel (l) are sensitive within right common carotid (RCC), right internal carotid (RIC) and right external carotid (REC) arteries, while compliance of the vessels (C) and blood inertia (L) are sensitive only at RCC. Moreover, Young's modulus (E) and wall thickness (h) exhibit less sensitivities on pressure and flow at all locations of carotid bifurcation. Results of network location and temporal variabilities revealed that most of sensitivity was found in common time regions i.e. early systole, peak systole and end systole.


Akirin2 regulates proliferation and differentiation of porcine skeletal muscle satellite cells via ERK1/2 and NFATc1 signaling pathways.
Akirin2, a novel nuclear factor, plays an important role in myogenesis. To investigate the role of Akirin2 in proliferation and differentiation of porcine skeletal muscle satellite cells, Akirin2 overexpression and Akirin2 silence technologies were employed. Our results showed that overexpression of Akirin2 markedly enhanced the proliferation and differentiation of porcine skeletal muscle satellite cells, whereas silencing of Akirin2 got the opposite results. Furthermore, our results showed that Akirin2 affected proliferation and differentiation of porcine skeletal muscle satellite cells through extracellular-signal regulated kinase-1/2 (ERK1/2) and NFATc1 signaling pathways. These results indicate that Akirin2 can effectively promote skeletal muscle satellite cells proliferation and differentiation, acting through ERK1/2- and NFATc1-dependent mechanisms.


A fractionated reticulocyte lysate retains high efficiency for protein synthesis.
The rabbit reticulocyte lysate is a highly efficient system for protein synthesis in vitro, and therefore has been used frequently in studies of translational control. However, when the lysate is fractionated into ribosomes and soluble proteins by centrifugation, there is a severe loss of activity, thereby making the system less suitable for identifying components involved in translational control. We have devised a new method of cell fractionation which employs rapid (20-min) centrifugation to pellet ribosomes. The post-ribosomal supernatant (S-100), high salt-washed ribosomes, and the high salt wash are all required in the reconstituted protein synthesis assay, and greater than 70% of the activity of the unfractionated lysate is attained. Proteins in the high salt wash have been further fractionated by ammonium sulfate precipitation, and the assay system has been used to measure the activities of eIF-4B and eIF-4F. This highly active fractionated lysate system should be useful in measuring the specific activities of translational components and may be appropriate for detecting changes due to covalent modifications such as phosphorylation.


Conference report: an agenda for medical rehabilitation outcomes research.
In August 1994, a conference was organized by the National Center for Medical Rehabilitation Research (National Institute of Child Health and Human Development, National Institutes of Health) and cosponsored by the Agency for Health Care Policy and Research to formulate recommendations for outcomes research in medical rehabilitation. Recommendations are presented in the areas of philosophical issues, strategy and design issues, measurement of disability and handicap, and measurement of quality of life and health status.


Pharmacological prophylaxis with pyridostigmine bromide against nerve agents adversely impact on airway function in an ex vivo rat precision-cut lung slice model.
The carbamate pyridostigmine bromide (PB) is the only fielded pharmacological prophylaxis for military use against nerve agents. Previous studies have shown differences in the PB-pretreatment efficacy for various nerve agents and in the influence of post-exposure treatment with common antidotes. In the present study, the aim was to evaluate the possibility of using an ex vivo rat precision-cut lung slice model to determine the impact of PB pretreatment on VX-induced bronchoconstriction. In addition, the efficacy of post-exposure treatment with atropine sulfate following PB-prophylaxis was investigated.Bronchoconstriction was induced by electric-field stimulation and was significantly aggravated by 10 µM PB. Airway recovery was decreased by both 1 and 10 µM PB. Evaluation of acetylcholineesterese inhibition by PB showed that the lower concentration met the clinical criteria of residual enzyme activity while the higher concentration completely inhibited the activity. Exposure to VX with or without pretreatment demonstrated similar contractions. However, VX-incubation following pretreatment caused decreased airway relaxation compared to pretreatment alone. Atropine treatment following PB- and VX-exposure significantly decreased the maximum airway contraction and increased the relaxation.In conclusion, no beneficial effect of PB-prophylaxis on VX-induced contractions was observed. The atropine efficacy to relax airways was significant demonstrating the importance of efficient post-exposure therapeutics to protect against the life-threatening respiratory contractions.


Weekly cisplatin and oral etoposide as treatment for relapsed epithelial ovarian cancer.
Response rates to chemotherapy in relapsed, platinum resistant epithelial ovarian cancer remain poor. We have explored the effectiveness of weekly cisplatin combined with prolonged oral etoposide in this patient group. Forty-two women with relapsed, advanced ovarian cancer were treated with cisplatin 60 mg/m2 on days 1, 8, 15, 29, 36 and 43 and oral etoposide 50 mg given from day 1-14 and day 29-43. In those who were responding and tolerating treatment (n = 13) oral etoposide 50 mg was continued for two further cycles (days 1-21 repeated every 28 days). The interval since last platinum containing chemotherapy was > 6 months in 28 patients and < 6 months in 16 patients. Thirty-six patients were evaluable for response according to CA 125 criteria giving an overall response rate of 44%. The response rate in evaluable patients declined with increasing numbers of previous treatments: 57% with one prior treatment, 42% with two, 40% with three or more. The response rate in patients who had received platinum chemotherapy within six months prior to treatment was 46%. The only significant non-haematological toxicity was nausea and vomiting in 4 patients who experienced greater than grade 2 toxicity. The number of patients experiencing haematological toxicity more than grade 2 was as follows: haemoglobin 3, white blood count 12, platelets 6. Sixteen patients had dose delays and two had dose reductions. We conclude that this short but intensive regimen provides worthwhile response rates, even in those patients who would ordinarily be considered refractory to platinum, and has an acceptable toxicity profile.


Ubiquitin expression in globose tangles in the locus coeruleus in brains of patients with Alzheimer's and Parkinson's diseases.
The locus coeruleus belongs to brain areas exhibiting remarkable neuronal loss already during physiological aging and very early neurofibrillary tangles. We performed a semiquantitative, immunocytochemical study focused on the expression of ubiquitin in neurofibrillary tangles in the locus coeruleus as compared with the central superior nucleus. The locus coeruleus exhibited later ubiquitin expression in the neurofibrillary tangles, a lower percentage of ubiquitinated tangles and more frequently granular cytoplasmic staining with Tau-1 than the central superior nucleus. These results suggesting different, probably delayed, processing of Tau protein in the locus coeruleus might contribute additionally to cell injury in this area.


Host-Guest Recognition and Fluorescence of a Tetraphenylethene-Based Octacationic Cage.
We report the synthesis and characterization of a three-dimensional tetraphenylethene-based octacationic cage that shows host-guest recognition of polycyclic aromatic hydrocarbons (e.g. coronene) in organic media and water-soluble dyes (e.g. sulforhodamine 101) in aqueous media through CH⋅⋅⋅π, π-π, and/or electrostatic interactions. The cage⊃coronene exhibits a cuboid internal cavity with a size of approximately 17.2×11.0×6.96 Å3 and a "hamburger"-type host-guest complex, which is hierarchically stacked into 1D nanotubes and a 3D supramolecular framework. The free cage possesses a similar cavity in the crystalline state. Furthermore, a host-guest complex formed between the octacationic cage and sulforhodamine 101 had a higher absolute quantum yield (ΦF =28.5 %), larger excitation-emission gap (Δλex-em =211 nm), and longer emission lifetime (τ=7.0 ns) as compared to the guest (ΦF =10.5 %; Δλex-em =11 nm; τ=4.9 ns), and purer emission (ΔλFWHM =38 nm) as compared to the host (ΔλFWHM =111 nm).


Efficacy of teicoplanin monotherapy following initial standard therapy in Enterococcus faecalis infective endocarditis: a retrospective cohort study.
Teicoplanin is often used in Enterococcus faecalis infective endocarditis as a relay in case of penicillin side effects, or in outpatients. We assessed the efficacy of teicoplanin used as continuation therapy after initial standard treatment of E. faecalis endocarditis. All adult patients consecutively diagnosed between 1997 and 2016 for E. faecalis endocarditis were retrospectively reviewed. Patients who received standard therapy (ST) were compared to those switched to teicoplanin to complete the treatment (teicoplanin therapy, TT). Seventy-one patients were enrolled: 34 in the ST group and 37 in the TT group. Amoxicillin was replaced by teicoplanin after a median duration of 18 days (IQ25 - 75 12-21). Teicoplanin (5.8 ± 2.3 mg/kg) was administered for a median duration of 29 days (IQ25 - 75 25-34). Gentamicin therapy was similar. Overall duration of antimicrobial therapy was 42 days (IQ25 - 75 35-43) in the ST group, and 46 days (IQ25 - 75 43-49) in the TT group (p = 0.001). Global and endocarditis-related mortality rates were 22/34 (65%) and 13/34 (38%) in the ST group, and 14/37 (38%) and 3/37 (8%) in the TT group (p ≤ 0.05). Relapses occurred in 2/26 patients who survived the treatment phase in the ST group (8%) and in 3/37 in the TT group (8%, p = 0.68). All relapses in the TT group occurred in patients presenting prosthetic valve endocarditis. Finally, 20 patients were cured in the ST group (59%), and 33 patients in the TT group (89%, p = 0.003). In E. faecalis endocarditis, the switch to teicoplanin in selected patients following an initial phase of standard treatment represents an alternative, particularly for outpatient therapy. Caution should be exercised in cases of prosthetic valve endocarditis.


Sex related fibrinolytic activity in rat tissues.
Histochemical study of many organs of male and female adult Wistar rats of the same age showed no difference in fibrinolytic activity (plasminogen activator activity) between the sexes.


Screening and structure-based modeling of T-cell epitopes of Nipah virus proteome: an immunoinformatic approach for designing peptide-based vaccine.
Identification of Nipah virus (NiV) T-cell-specific antigen is urgently needed for appropriate diagnostic and vaccination. In the present study, prediction and modeling of T-cell epitopes of Nipah virus antigenic proteins nucleocapsid, phosphoprotein, matrix, fusion, glycoprotein, L protein, W protein, V protein and C protein followed by the binding simulation studies of predicted highest binding scorers with their corresponding MHC class I alleles were done. Immunoinformatic tool ProPred1 was used to predict the promiscuous MHC class I epitopes of viral antigenic proteins. The molecular modelings of the epitopes were done by PEPstr server. And alleles structure were predicted by MODELLER 9.10. Molecular dynamics (MD) simulation studies were performed through the NAMD graphical user interface embedded in visual molecular dynamics. Epitopes VPATNSPEL, NPTAVPFTL and LLFVFGPNL of Nucleocapsid, V protein and Fusion protein have considerable binding energy and score with HLA-B7, HLA-B*2705 and HLA-A2MHC class I allele, respectively. These three predicted peptides are highly potential to induce T-cell-mediated immune response and are expected to be useful in designing epitope-based vaccines against Nipah virus after further testing by wet laboratory studies.


MicroRNA-200 family expression analysis in metastatic clear cell renal cell carcinoma patients.
The aim of this study is to analyse the of expression levels of microRNA-200 family members in patients with metastatic clear cell renal cell carcinoma (ccRCC). Analysis of microRNA expression was performed on 23 paired DNA samples extracted from kidney tumour tissue and the surrounding normal renal parenchyma. MicroRna-200c was found to have significantly lower expression (in kidney tumour tissue compared to normal renal parenchyma. No other microRna-200 family members showed statistically significant differences in expression levels between tumour and normal kidney tissue. Recent data suggest that the role of microRNA-200c in tumour pathogenesis is rather contradictory, and the underlying mechanisms by which microRNA-200c affects the carcinogenic potential of malignant cells remains unclear and requires further investigation at the molecular level.


The impact of lipids on the cancer-immunity cycle and strategies for modulating lipid metabolism to improve cancer immunotherapy.
Lipids have been found to modulate tumor biology, including proliferation, survival, and metastasis. With the new understanding of tumor immune escape that has developed in recent years, the influence of lipids on the cancer-immunity cycle has also been gradually discovered. First, regarding antigen presentation, cholesterol prevents tumor antigens from being identified by antigen presenting cells. Fatty acids reduce the expression of major histocompatibility complex class I and costimulatory factors in dendritic cells, impairing antigen presentation to T cells. Prostaglandin E2 (PGE2) reduce the accumulation of tumor-infiltrating dendritic cells. Regarding T-cell priming and activation, cholesterol destroys the structure of the T-cell receptor and reduces immunodetection. In contrast, cholesterol also promotes T-cell receptor clustering and relative signal transduction. PGE2 represses T-cell proliferation. Finally, regarding T-cell killing of cancer cells, PGE2 and cholesterol weaken granule-dependent cytotoxicity. Moreover, fatty acids, cholesterol, and PGE2 can improve the activity of immunosuppressive cells, increase the expression of immune checkpoints and promote the secretion of immunosuppressive cytokines. Given the regulatory role of lipids in the cancer-immunity cycle, drugs that modulate fatty acids, cholesterol and PGE2 have been envisioned as effective way in restoring antitumor immunity and synergizing with immunotherapy. These strategies have been studied in both preclinical and clinical studies.


Ageing of the spinal ganglion neurons in the rat: a radioautographic study following injection of [3H]lysine.
After administration of [3H]lysine to 3- and 24-month-old rats, radioautography demonstrates a significantly less important uptake in the A-type spinal ganglion neurons and in the old animals. This is in agreement with the existence of at least two functional categories of neurons in the spinal ganglion and suggests that protein synthesis is diminished in the old animals. The very fact that incorporation varies between animals of the same age sustains the hypothesis according to which amplitude of ageing is essentially an individual physiological-dependent process.


Ceftazidime treatment in severe burns. Serious infections in patients with severe burns treated with ceftazidime.
In combination with active surgical and general management, ceftazidime is a useful antibiotic for the treatment of Gram negative septic complications in patients with severe burn wounds. Against S. aureus, however, ceftazidime is not the therapy of choice.


Retracted: Sustainable Development Research of Green Smart Park in High-End Manufacturing Based on Internet of Things.
[This retracts the article DOI: 10.1155/2022/3961647.].


Neodymium:YAG laser interaction with Alcon IOGEL hydrogel intraocular lenses: an in vitro toxicity assay.
The objective of this study was to determine the potential toxicity generated by the interaction of the Nd:YAG laser and Alcon IOGEL intraocular hydrogel lens material. The IOGEL lens is composed of poly 2-hydroxyethylmethacrylate, containing 38% water, previously shown to be highly biocompatible in a wide range of tissue culture and implantation experiments. In this study, intraocular lenses (IOLs) immersed in serum-free cell culture medium were purposely exposed to exaggerated doses of laser energy to cause extensive damage. An IOLAB polymethylmethacrylate (PMMA) lens served as a control lens material. The resultant solutions were assayed for cytotoxicity in a bioassay system using fourth passage human corneal endothelial cells. No cytotoxicity was seen in the bioassay for the IOGEL hydrogel IOLs or the PMMA control IOL at any laser range/dosage tested over a 72-hour incubation period. Hydrogel lenses exhibited decreasing yellowing with decreasing energy levels, and no lens discoloration was apparent at the lowest level of irradiation, 5 mJ/50 laser bursts; the PMMA control lens exhibited moderate yellowing at 15 mJ/50 bursts. Lens marking was moderate for all IOGEL IOLs; the PMMA lens marking was severe at the power level tested.


Black-blood imaging of the human heart using rapid stimulated echo acquisition mode (STEAM) MRI.
To develop a rapid stimulated echo acquisition mode (STEAM) MRI technique for "black-blood" imaging of the human heart that overcomes the single-slice limitation and partially compromised blood suppression associated with double inversion-recovery techniques. Black-blood multislice images of the heart along anatomic orientations and triggered to end diastole were obtained from healthy human subjects at 3T using rapid STEAM MRI sequences with five-eighths partial Fourier encoding and variable flip angles. Single-shot STEAM images at 2.5 x 2.5 mm2 in-plane resolution and 6-mm section thickness were recorded in 230 msec from individual heartbeats. Improved signal-to-noise ratio (SNR) and higher spatial resolution of 2.0 x 2.0 mm2 and 1.5 x 1.5 mm2 were achieved by segmented multishot STEAM MRI with interleaved k-space acquisitions (160 msec each) from several heartbeats. In a single breathhold covering 18 heartbeats selected applications employed either three segments with six sections or six segments with three sections. Because stimulated echoes (STEs) dephase signals from moving spins, rapid STEAM images are free from blood signal contamination. The method offers a flexible tradeoff between spatial resolution, imaging speed (i.e., number of segments), and volume coverage (i.e., number of sections). Rapid STEAM MRI of the heart emerges as a simple technique for multislice imaging of the myocardial wall with efficient flow suppression.


Prolonging islet allograft survival using in vivo bioluminescence imaging to guide timing of antilymphocyte serum treatment of rejection.
Bioluminescence imaging (BLI) is a sensitive and noninvasive method for tracking the fate of transplanted islets. The aim of this study was to investigate whether early detection of rejection by BLI can aid in the timing of antilymphocyte serum (ALS) treatment for prolonging islet graft survival. Transgenic islets (200 per recipient) expressing the firefly luciferase from FVB/NJ strain (H-2q) mice were transplanted under the kidney capsule of streptozotocin-induced diabetic allogeneic Balb/c strain (H-2q) mice. BLI signals and serum glucose levels were measured daily after transplant. Four groups of mice were transplanted: group 1 recipients were untreated controls (n=12), group 2 (n=8) received ALS before transplant, group 3 (n=10) received ALS at a time after transplant when normoglycemic but prompted by a reduction (approximately 30%) in BLI signal intensity for 2 consecutive days, and group 4 (n=5) received ALS after transplant when prompted by blood glucose levels increasing approximately 20% from the normoglycemic baseline (BLI reduction approximately 70%). The incidence of graft loss from rejection in groups 1, 2, 3, and 4 was 92.3%, 88%, 40%, and 100%, respectively. The mean (+/-SE) time to graft loss in groups 1, 2, 3 and 4 was 22.5+/-4.8, 29.2+/-9.9, 53.5+/-17.9, and 22.1+/-2.4 days, respectively. Noninvasive imaging modalities of functional islet mass, such as BLI (but not blood glucose levels), can prompt the appropriate timing of ALS treatment of islet allograft rejection and significantly prolong graft survival or protect the grafts from permanent loss.


Changes in pediatric waist circumference percentiles despite reported pediatric weight stabilization in the United States.
Obesity is a global health concern but the United States has reported a leveling in obesity rates in the pediatric population. To provide updated waist circumference (WC) percentile values, identify differences across time and discuss differences within the context of reported weight stabilization in a nationally representative sample of American children. Percentiles for WC in self-identified African Americans (AA), European Americans (EA) and Mexican Americans (MA) were obtained from 2009-2014 National Health and Nutrition Examination Survey data (NHANES2014). Descriptive trends across time in 10th, 25th, 50th, 75th and 90th percentile WC distributions were identified by comparing NHANES2012 with previously reported NHANESIII (1988-1994). WC increased in a monotonic fashion in AA, EA and MA boys and girls. When compared with NHANESIII data, a clear left shift of percentile categories was observed such that values that used to be in the 90th percentile are now in the 85th percentile. Differences in WC were observed in EA and MA boys during a reported period of weight stabilization. WC has changed in the US pediatric population across time, even during times of reported weight stabilization, particularly among children of diverse racial/ethnic backgrounds.


Perioperative management of P2Y12 inhibitors in patients undergoing cardiac surgery within 1 year of PCI.
To evaluate the impact of perioperative P2Y12 receptor inhibitor therapy among patients undergoing cardiac surgery within 1 year of percutaneous coronary intervention (PCI). Patients undergoing cardiac surgery in the year post-PCI at three tertiary care centres between 2011 and 2018 were stratified into those who had received at least one dose of P2Y12 inhibitor prior to surgery (within 5 days for clopidogrel or prasugrel, or within 3 days for ticagrelor) and those who had not. The outcomes of interest were major adverse cardiac and cerebrovascular events (MACCEs) and bleeding. Among 20 279 PCI patients, 359 (1.8%) underwent cardiac surgery in the ensuing year, 76.3% of whom received coronary artery bypass grafts. Overall, 33 (9.2%) MACCEs and 85 (23.7%) bleeding events occurred within 30 days post-cardiac surgery. Perioperative P2Y12 inhibition (N = 133, 37%) was not associated with the risk of MACCEs or bleeding, despite numerically lower rates of myocardial infarction or stent thrombosis (0.0% vs. 2.6%; P = 0.089). Patients who continued the P2Y12 inhibitor until the day of surgery (N = 60, 17%) had significantly higher bleeding risk [adjusted odds ratio 2.93, 95% confidence interval 1.53-5.59)]. Predictors of MACCEs included a time interval from PCI to cardiac surgery of ≤30 days and reduced ejection fraction, whereas urgent/emergent surgery predicted bleeding. Chronic kidney disease and myocardial infarction as indication for PCI predicted both MACCEs and bleeding. Among patients undergoing cardiac surgery in the year after PCI, the perioperative risk of ischaemic and bleeding events might be influenced by P2Y12 inhibitor therapy in addition to other risk parameters, including the timing and urgency of the procedure.


miR-290 cluster modulates pluripotency by repressing canonical NF-κB signaling.
Embryonic stem cell (ESC)-specific microRNAs (miRNAs) play a critical role in the maintenance of pluripotency and self-renewal but the complete network between these miRNAs and their broad range of target genes still remains elusive. Here we demonstrate that miR-290 cluster, the most abundant miRNA family in ESCs, targets the NF-κB subunit p65 (also known as RelA) by repressing its translation. Forced expression of p65 causes loss of pluripotency, promotes differentiation of ESCs, and leads to an epithelial to mesenchymal transition. These data define p65 as a novel target gene of miR-290 cluster and provide new insight into the function of ESC-specific miRNAs.


A Novel Approach to Penile Augmentation Urethroplasty Using Buccal Mucosa and Amniotic Membrane: A Pilot Study in a Rabbit Model.
To evaluate and compare the success of amniotic membrane (AM) and buccal mucosa (BM) grafts and simultaneous use of both in penile augmentation urethroplasty in rabbits. A total of 12 New Zealand rabbits were divided into 3 groups by grafting style: Group 1 (AM), Group 2 (BM), and Group 3 (simultaneous use of BM and AM). In all animals, a standardized urethral defect was created. BM and AM were obtained from the rabbits. Solely AM grafts were affixed to the defects in Group 1, solely BM grafts were affixed to the urethral defects in Group 2, and simultaneous AM + BM grafts were affixed in Group 3. At 4 and 8 weeks, the penises were subject to histological assessment of subepithelial fibrosis, epithelial transformation, and inflammatory reaction. Stenosis was detected in none of the groups. A dehiscence was developed in one rabbit in Group 1 and a fistula was developed in one rabbit in Group 2. After 4 weeks, minimal subepithelial fibrosis and inflammatory reaction were observed in Group 2, while subepithelial fibrosis was not in Groups 3. After 8 weeks, subepithelial connective tissue proliferation was moderate in Group 2, at both 4th and 8th weeks in Group 2. After 8 weeks, the best epithelial transformations were observed in Group 3. In an animal model, the simultaneous use of AM and BM grafts following acute urethral injury may be feasible for penile augmentation urethroplasty. Further study is needed.


Radiofrequency catheter ablation of atrioventricular nodal reciprocating tachycardia using intracardiac echocardiography in pregnancy.
We describe a case report of a 32-year-old woman during the 10th week of pregnancy with symptomatic and recurrent atrioventricular nodal reciprocating tachycardia successfully treated by conventional radiofrequency ablation, under intracardiac echocardiography surveillance.


Cutaneous sensory outcomes from three transhumeral targeted reinnervation cases.
Although targeted muscle reinnervation has been shown to be effective in enhancing prosthetic control for upper limb amputees, restored hand sensations have been variable. An understanding of possible sensory feedback channels is crucial in working toward more effective closed-loop prosthetic control. To compare sensory outcomes of different targeted sensory reinnervation approaches. Case series, cross-sectional, and retrospective. Three transhumeral amputees that had undergone different sensory reinnervation approaches were recruited. Skin pressure sensitivity thresholds and anatomic sensory mapping were performed using Semmes-Weinstein monofilaments. The clinical charts of the subjects were reviewed to compare the sensory maps performed during the earlier post-reinnervation period. While the first two subjects achieved return of hand sensations on the stump skin in early follow-up, the maps showed attenuation over time. The last subject developed discrete sensations of all digits in the recipient cutaneous nerve territories away from the reinnervated muscles. These findings confirm that it is feasible to restore hand sensation after transhumeral targeted reinnervation, but there is a significant intersubject variability. The intrafascicular approach may be particularly effective in restoring digit sensation and deserves further exploration, as do factors affecting stability of the hand maps over time. In addition to enabling intuitive motor control of myoelectric prosthesis, targeted reinnervation can also result in sensory restoration of the hand. Documentation of sensory mapping present after reinnervation may assist with exploring future techniques for sensory enhancement, with the goal of working toward closed-loop prosthetic control.


Prevalence, awareness and control of hypertension in Uganda.
Prevention and control of hypertension are critical in reducing morbidity and mortality attributable to cardiovascular diseases. Awareness of hypertension is a pre-condition for control and prevention. This study estimated the proportion of adults who were hypertensive, were aware of their hypertension and those that achieved adequate control. We conducted a community based cross sectional survey among people ≥ 15 years in Buikwe and Mukono districts of Uganda. People had their blood pressure measured and were interviewed about their social-demographic characteristics. Hypertension was defined as systolic blood pressure ≥ 140 mmHg, or diastolic blood pressure ≥ 90 mmHg, or previous diagnosis of hypertension. Participants were classified as hypertensive aware if they reported that they had previously been informed by a health professional that they had hypertension. Control of hypertension among those aware was if systolic blood pressure was <140 mmHg and diastolic blood pressure was <90 mmHg. The age standardized prevalence of hypertension was 27.2% (95% CI 25.9-28.5) similar among females (27.7%) and males (26.4%). Prevalence increased linearly with age, and age effect was more marked among females. Among the hypertensive participants, awareness was 28.2% (95% CI 25.4-31.0) higher among females (37.0%) compared to males (12.4%). Only 9.4% (95% CI 7.5-11.1) of all hypertensive participants were controlled. Control was higher among females (13.2%) compared to males (2.5%). More than a quarter of the adult population had hypertension but awareness and control was very low. Measures are needed to enhance control, awareness and prevention of hypertension.


Outcomes and factors influencing prognosis in patients with vascular pythiosis.
Vascular pythiosis, caused by Pythium insidiosum, is associated with a high mortality rate. We reviewed the outcomes and established the factors predicting prognosis of patients treated in our institution with surgery, antifungal therapy, or immunotherapy. We undertook a retrospective record review of patients with vascular pythiosis treated in Siriraj Hospital, Bangkok, Thailand, between January 2005 and January 2015. Patient characteristics, type of surgery, adjunctive antifungal treatment, adjunctive immunotherapy, and disease status of surgical arterial and surrounding soft tissue margins were recorded. We calculated the mortality rate and established factors predicting prognosis. The records of 11 patients were reviewed. All patients had thalassemia. Nine patients (81.8%) had a history of contact with contaminated water. The clinical presentations were chronic ulcers (45.5%), toe gangrene (27.3%), pulsatile mass (27.3%), and acute limb ischemia (27.3%). Above-knee amputation was required in 10 patients (90.9%). The mortality rate was 36.4%. Independent variables between survivors and nonsurvivors were lack of an arterial disease-free surgical margin (P = .003), lack of a surrounding soft tissue disease-free surgical margin (P < .05), a suprainguinal lesion (P < .05) and duration of symptoms (P < .05). Adjuvant itraconazole, terbinafine, and Pythium vaccine have a role to play in patients with a disease-free arterial surgical margin but in whom infected surrounding soft tissue could not be completely excised. Achieving adequate disease-free surgical margins-especially the arterial margin-at amputation or débridement is the most important prognostic factor in patients with vascular pythiosis. Early detection combined with a multidisciplinary approach to treatment, including surgery, antifungal agents, and immunotherapy, allows the best possible outcome to be obtained.


Characterization of Mycobacterium tuberculosis isolates from Hebei, China: genotypes and drug susceptibility phenotypes.
Tuberculosis remains a major public health problem in China. The Hebei province is located in the Beijing-Tianjin-Hebei integration region; however little information about the genetic diversity of Mycobacterium tuberculosis was available in this area. This study describes the first attempt to map the molecular epidemiology of MTB strains isolated from Hebei. Spoligotyping and 15-locus MIRU-VNTR were performed in combination to yield specific genetic profiles of 1017 MTB strains isolated from ten cities in the Hebei province in China during 2014. Susceptibility testing to first line anti-TB drugs was also conducted for all strains using the L-J proportion method. Based on the SpolDB4.0 database, the predominant spoligotype belonged to the Beijing family (90.5%), followed by T family (6.3%). Using 15-locus MIRU-VNTR clustering analysis, 846 different patterns were identified, including 84 clusters (2-17 strains per cluster) and 764 individual types. Drug susceptibility pattern showed that 347 strains (34.1%) were resistant to at least one of the first line drugs, including 134 (13.2%) multi-drug resistance strains. Statistical analysis indicated that drug resistance was associated with treatment history. The Beijing family was associated with genetic clustering. However, no significant difference was observed between the Beijing and non-Beijing family in gender, age, treatment history and drug resistance. The Mycobacterium tuberculosis strains in Hebei exhibit high genetic diversity. The Beijing family is the most prevalent lineage in this area. Spoligotyping in combination with 15-locus MIRU-VNTR is a useful tool to study the molecular epidemiology of the MTB strains in Hebei.


Oncological superiority of hilar en bloc resection for the treatment of hilar cholangiocarcinoma.
Long-term results after liver resection for hilar cholangiocarcinoma are still not satisfactory. Previously, we described a survival advantage of patients who undergo combined right trisectionectomy and portal vein resection, a procedure termed "hilar en bloc resection." The present study was conducted to analyze its oncological effectiveness compared to conventional hepatectomy. During hilar en bloc resection, the extrahepatic bile ducts were resected en bloc with the portal vein bifurcation, the right hepatic artery, and liver segments 1 and 4 to 8. With this "no-touch" technique, preparation of the hilar vessels in the vicinity of the tumor was avoided. The long-term outcome of 50 consecutive patients who underwent curative (R0) hilar en bloc resection between 1990 and 2004 was compared to that of 50 consecutive patients who received curative conventional major hepatectomy for hilar cholangiocarcinoma (perioperative deaths excluded). The 1-, 3-, and 5-year survival rates after hilar en bloc resection were 87%, 70%, and 58%, respectively, which was significantly higher than after conventional major hepatectomy. In the latter group, 1-, 3-, and 5-year survival rates were 79%, 40%, and 29%, respectively (P = 0.021). Tumor characteristics were comparable in both groups. A high number of pT3 and pT4 tumors and patients with positive regional lymph nodes were present in both groups. Multivariate analysis identified hilar en bloc resection as an independent prognostic factor for long-term survival (P = 0.036). In patients with central bile duct carcinomas, hilar en bloc resection is oncologically superior to conventional major hepatectomy, providing a chance of long-term survival even in advanced tumors.


About the age and depositional depth of the sediments with reported bipedal footprints at Trachilos (NW Crete, Greece).
New data on the foraminifers and the regional geological setting of the Trachilos sediments (NW Crete, Greece) from which Gierlinski et al. (Proc Geol Assoc 128: 697-710, 2017) described hominin-like footprints show that the published 6.05 Ma-shallow marine interpretation is incorrect. In our new interpretation, the Trachilos succession is Late Pliocene and part of a shallowing marine series that became subaerially exposed some 3 millions of years ago. Placed in a larger geological context, Crete was an island during the Late Pliocene and separated by ~ 100 km of open sea from the nearest European mainland, and therefore out of reach of Late Pliocene hominins.


Direct chromosomal preparation for studying hydatidiform moles.
This report describes a simple direct method to obtain chromosomes from hydatidiform moles. Of 24 moles, 20 have been successfully karyotyped by this method. Of the 20 cases, 14 were complete and six were partial. The karyotype of complete moles was invariably diploid. Three of the partial moles were triploid (69,XXX), but three showed diploid/tetraploid mosaicism.


Conversion of bilateral hip and knee ankylosis to total joint replacements.
We present a 25-year-old patient with juvenile rheumatoid arthritis and ankylosis of both hips and both knees treated by staged bilateral hip and knee arthroplasty. She was followed up for 18 months. We discuss the pre-operative planning, surgical details and post-operative rehabilitation.


Observation of the effect of tetrandrine on experimental silicosis of rats.
It was proved in this experiment that tetrandrine, one of the bisbenzylisoquinoline alkaloids, may inhibit the development of experimental silicosis on rats whether the drug was given to the animal right after dusting or after the formation of silicotic nodules. As compared to the silicotic control rats, lowering of total weight and collagen content of the lungs were shown and some degradation of collagen fibers was also indicated from the histopathological examination.


A Gradient of Sharpening Effects by Perceptual Prior across the Human Cortical Hierarchy.
Prior knowledge profoundly influences perceptual processing. Previous studies have revealed consistent suppression of predicted stimulus information in sensory areas, but how prior knowledge modulates processing higher up in the cortical hierarchy remains poorly understood. In addition, the mechanism leading to suppression of predicted sensory information remains unclear, and studies thus far have revealed a mixed pattern of results in support of either the "sharpening" or "dampening" model. Here, using 7T fMRI in humans (both sexes), we observed that prior knowledge acquired from fast, one-shot perceptual learning sharpens neural representation throughout the ventral visual stream, generating suppressed sensory responses. In contrast, the frontoparietal and default mode networks exhibit similar sharpening of content-specific neural representation, but in the context of unchanged and enhanced activity magnitudes, respectively: a pattern we refer to as "selective enhancement." Together, these results reveal a heretofore unknown macroscopic gradient of prior knowledge's sharpening effect on neural representations across the cortical hierarchy.SIGNIFICANCE STATEMENT A fundamental question in neuroscience is how prior knowledge shapes perceptual processing. Perception is constantly informed by internal priors in the brain acquired from past experiences, but the neural mechanisms underlying this process are poorly understood. To date, research on this question has focused on early visual regions, reporting a consistent downregulation when predicted stimuli are encountered. Here, using a dramatic one-shot perceptual learning paradigm, we observed that prior knowledge results in sharper neural representations across the cortical hierarchy of the human brain through a gradient of mechanisms. In visual regions, neural responses tuned away from internal predictions are suppressed. In frontoparietal regions, neural activity consistent with priors is selectively enhanced. These results deepen our understanding of how prior knowledge informs perception.


The Viscum album extract Iscador P does not cause an autocrine interleukin-6 loop in B-Non-Hodgkin's Lymphoma cell lines.
Single cases of clinical observations suggest the efficacy of the Viscum album (VA) extract Iscador P in the treatment of follicular B-Non-Hodgkin's Lymphoma (B-NHL). A previously published study aroused a controversial dispute as it indicated that IL-6 serum levels are elevated following i.v. VA treatment. Increased IL-6 levels have been shown to promote the progression of B-cell neoplasia such as B-NHL. Objective of this study was to investigate whether the VA extract influences the expression of IL-6 and its receptor components in follicular B-NHL cell lines. Follicular B-NHL cell lines (WSU-NHL, DoHH-2) were incubated with clinically relevant doses of VA extract for up to 3 days. At specified time points (6, 24, 48, 72 h) samples were taken and the expression of IL-6 and its receptor components were analysed by real-time-RT-PCR, flow cytometry and ELISA. Treatment of follicular B-NHL cell lines with VA extract did not alter the expression level of IL-6 and its' receptor components at any time and with any of the applied VA extract concentrations. Clinically relevant doses of the VA extract do not trigger an autocrine or paracrine IL-6 loop nor do they initiate IL-6 trans-signalling in follicular B-NHL cell lines.


A model for agonists acting directly as well as indirectly.
A theoretical model is presented to describe the receptor interaction of a drug which possesses indirect as well as direct pharmacological action. Sets of theoretical log concentration-effect curves predicted by this model are presented. The model predicts that the shape of the log concentration-effect curves may be sigmoid (S-shaped), biphasic (bell-shaped) or composed of a combination of two sigmoid curves, joined together by a plateau. The theoretical predictions are comparable with the results obtained from an experimental study.


Fitting and using growth curves.
A technique is presented for fitting and analyzing growth patterns using Gompertz, power, and exponential curves. Data collection involves measuring growth rate as a function of size. This is useful because growth rates at many different sizes can be measured at the same time, which removes the effect of environmental change from the observed growth pattern. Using size instead of age as the independent variable is important because size is usually more closely related to growth rate than is age. The particular technique presented here yields estimates of the variance of the curve parameters so that growth curves for different populations can be compared.


Human Urinary Kallidinogenase Pretreatment Inhibits Myocardial Inflammation and Apoptosis after Coronary Microembolization by Activating PI3K/Akt/FoxO1 Axis.
As a fatal cardiovascular complication, coronary microembolization (CME) results in severe cardiac dysfunction and arrhythmia associated with myocardial inflammation and apoptosis. Human urinary kallidinogenase (HUK) can provide a protective function for cardiomyocytes by improving microcirculation. However, the therapeutic effects and underlying mechanisms of HUK in CME-induced myocardial injury remain unclear. We evaluated the effect of HUK on cardiac protection in a rat model of CME and whether it could restrain myocardial inflammation and apoptosis, and alleviate CME-induced myocardial injury. We established the CME model by injecting 42 μm inert plastic microspheres into the left ventricle of rats in advance, then the rats were randomly and equally divided into CME, CME + HUK (the dose of HUK at 0.016 PNA/kg/day), CME + HUK + LY (the dose of LY294002 at 10 mg/kg, 30 minutes before modeling), and Sham operation groups. Cardiac function, the serum levels of myocardial injury biomarkers, myocardial inflammation and apoptosis-related genes were measured; and the myocardial histopathological examination was performed at 12 h after the operation. The results revealed that HUK effectively reducing myocardial inflammation, apoptosis, and myocardial infarction area; and improving CME-induced cardiac injury by activating the PI3K/Akt/FoxO1 axis. In addition, these cardioprotective effects can be reduced by the PI3K specific inhibitor LY294002, suggesting that the aforementioned protective effects may be related to activation of the PI3K/Akt/FoxO1 axis. HUK seems to control inflammatory infiltration and cardiomyocyte apoptosis significantly to improve CME-induced cardiac injury via regulating the PI3K/Akt/FoxO1 axis.


Discovery of target genes and pathways at GWAS loci by pooled single-cell CRISPR screens.
Most variants associated with complex traits and diseases identified by genome-wide association studies (GWAS) map to noncoding regions of the genome with unknown effects. Using ancestrally diverse, biobank-scale GWAS data, massively parallel CRISPR screens, and single-cell transcriptomic and proteomic sequencing, we discovered 124 cis-target genes of 91 noncoding blood trait GWAS loci. Using precise variant insertion through base editing, we connected specific variants with gene expression changes. We also identified trans-effect networks of noncoding loci when cis target genes encoded transcription factors or microRNAs. Networks were themselves enriched for GWAS variants and demonstrated polygenic contributions to complex traits. This platform enables massively parallel characterization of the target genes and mechanisms of human noncoding variants in both cis and trans.


Effects of cardiac myosin binding protein-C on the regulation of interaction of cardiac myosin with thin filament in an in vitro motility assay.
Modulatory role of whole cardiac myosin binding protein-C (сMyBP-C) in regulation of cardiac muscle contractility was studied in the in vitro motility assay with rabbit cardiac myosin as a motor protein. The effects of cMyBP-C on the interaction of cardiac myosin with regulated thin filament were tested in both in vitro motility and ATPase assays. We demonstrate that the addition of cMyBP-C increases calcium regulated Mg-ATPase activity of cardiac myosin at submaximal calcium. The Hill coefficient for 'pCa-velocity' relation in the in vitro motility assay decreased and the calcium sensitivity increased when сMyBP-C was added. Results of our experiments testifies in favor of the hypothesis that сMyBP-C slows down cross-bridge kinetics when binding to actin.


Effects of adenine nucleotide translocase inhibitors on dinitrophenol-induced Ca2+ efflux from pig heart mitochondria.
Bongkrekic acid and atractyloside, inhibitors of adenine nucleotide translocase, do not inhibit Ca2+ uptake and H+ production by pig heart mitochondria. However, bongkrekic acid, but not atractyloside, inhibits dinitrophenol-induced Ca2+ efflux and H+ uptake. Conversely, ruthenium red blocks Ca2+ uptake and H+ production but does not prevent dinitrophenol-induced Ca2+ efflux and H+ uptake by mitochondria. These results suggest that mitochondrial Ca2+ uptake and release exist as two independent pathways. The efflux of Ca2+ from mitochondria is mediated by a bongkrekic acid sensitive component which is apparently not identical to the ruthenium red sensitive Ca2+ uptake carrier.


Depression, somatization and steroid use in chronic obstructive pulmonary disease.
Steroid therapy has become part of the adjunctive treatment for COPD patients in some settings. Emotional changes have been reported in some patients while on these medications, but whether these changes are associated with the pathophysiological state or a side effect of the medication is not known. In this study self-reports of depression and somatic complaints were compared between two groups of COPD patients, 20 not receiving steroids and 20 receiving steroids. Both groups demonstrated comparable levels of disease and somatic complaints. Mean FEV1 value for those not receiving steroids was 34% of predicted while the mean for those receiving steroids was 30% of predicted. Depression was found to be significantly higher (t = 11.21, df = 38, p less than 0.01) in the group receiving steroids when compared to those not receiving steroids using a Student's t test. The higher degree of depression among steroid treated COPD patients has implications for clinical practice. The emotional status of this group of patients needs to be monitored and interventions initiated when necessary.


Detection of Legionella pneumophila in biofilms containing a complex microbial consortium by gas chromatography-mass spectrometry analysis of genus-specific hydroxy fatty acids.
A gas chromatographic-mass spectrometric method was used to detect Legionella pneumophila in biofilms in potable water containing a complex microbial consortium. The unique 3-hydroxy and 2,3-dihydroxy fatty acids of the L. pneumophila lipopolysaccharides (LPS) were detected in both the planktonic phase of the continuous culture model and in the biofilms forming on both copper and polyethylene substrata. The technique confirmed that lower numbers of Legionella colonised and grew on copper in comparison to polyethylene and offers promise for routine detection of Legionella in biofilms in the environment.


Seasonal variation of human semen parameters: A retrospective study in Italy.
Human infertility is a common condition secondary to many primary or secondary causes. As for these latter, different seasonal and climatic patterns have been hypothesized to play a role. The aim of this study was to assess the presence of a possible seasonal pattern in the functional parameters of semen samples maintained in a large tertiary center database. The reports of spermograms of 5188 consecutive subjects, collected at the Center for Reproductive Incapacity of the University Hospital of Parma during a 11-year period (2003-2014), were retrospectively analyzed. The reports included sperm motility, volume, and number, as well as pH, swelling and eosin tests. Data of different parameters were analyzed by season of sample collection. The ANOVA test was used for the evaluation of continuous variables, after Log transformation in case of a non-normal distribution, while χ(2) test was used for categorical variables. Moreover, logistic regression analysis was performed, to identify factors independently associated with normal sperm motility. Compared with the other seasons of the year, a higher sperm motility was found during the summer. Moreover, the prevalence of samples with a normal sperm pH (7.2-8) was higher during the spring, whilst the volume of sperm was higher in winter. Logistic regression analysis showed that normal sperm motility (>40%) was independently associated with spring (1.227; 95% CI 1.077-1.507, p = 0.005), summer (2.031; 95% CI 1.689-2.442, p < 0.001), swelling test (1.953; 95% CI 1.670-2.284, p < 0.001), eosin test (2.804; 95% CI 2.477-3.174, p < 0.001), pH (0.507; 95% CI 0.346-0.743, p < 0.001), LOG-number (2.949; 95% CI 2.470-3.522, p < 0.001) and LOG-volume (2.216; 95% CI 1.696-2.894, p < 0.001) of semen. This study suggests the existence of a positive relationship between some semen parameters and seasons.


Separation of steroidal drugs on porous graphitized carbon column.
The retention time of 11 steroidal drugs was determined on a porous graphitized carbon (PGC) column using water tetrahydrofuran mixtures as eluents. Linear correlations were calculated between the logarithm of the capacity factor (k') and the tetrahydrofuran concentration in the eluent. To find the molecular parameters significantly influencing the retention the intercept and slope values of the above relationship were correlated with the physicochemical characteristics of steroidal drugs using principal component analysis (PCA). Both the slope and intercept values show high differences proving that steroidal drugs can be successfully separated on a PGC column. Five principal components explained > 90% of the total variance. Calculations indicated that both electrostatic interactions and sterical conditions can influence the retention of steroidal drugs on PGC column.


Murine hoxd4 expression in the CNS requires multiple elements including a retinoic acid response element.
We have identified a retinoic acid response element (RARE) within a neural enhancer located 3' to the Hoxd4 gene. This RARE is required for the initiation and maintenance of Hoxd4 transgene expression in neurectoderm, and for full anteriorized expression upon retinoic acid (RA) treatment. Mutations within the sequence TTTTCTG, located 2 bp downstream of the RARE, posteriorized transgene activity. However, the onset of transgene expression and its response to RA were indistinguishable from wild type. While the TTTTCTG motif resembles a CDX binding site, human CDX1 protein did not interact with this element in vitro. Three additional regions were also shown to control transgene expression in neurectoderm, establishing that multiple elements constitute the Hoxd4 neural enhancer.


Synthesis of artificial humic acid-urea complex improves nitrogen utilization.
The inefficient use of conventional nitrogen (N) fertilizers leads to N enrichment in the soil, resulting in N loss via runoff, volatilization and leaching. While using artificial humic acid to prepare novel N fertilizer is a good choice to improve its efficiency, the high heterogeneity of artificial humic acid limits its structural analysis and utilization efficiency. To solve above problems, this work mainly carried out the fractionation experiments, melt penetration experiments and soil incubation experiments. The results revealed that four fractions with different aromatization degree and molecular weights were obtained by the newly proposed continuous dissolution method, particular in the extraction solution of pH = 3-4, which were extracted with the highest aromatization degree. Furthermore, artificial humic acid urea complex fertilizers prepared at pH = 3-4 significantly improved the release of NH4+-N by 38.32% on days 7 and NO3--N by 10.30% on days 14, compared to urea application. The highly aromatic complex fertilizer with loading of urea-N was able to supply more inorganic N to the soil on days 3-14 (low molecular weight N) and to maintain a higher N content on days 70 (highly aromatized N). This can partially offset the mineralization of readily available organic N, buffering the immobilization of inorganic N from the soil when unstable organic compounds (e.g. conventional urea) were incorporated. A-HAU3-4 addition on days 70, Proteobacteria and Actinobacteriota were found to be the dominant phylum in the soil and the relative abundance of Endophytic bacteria was increased, which was conducive to the improvement of soil N utilization efficiency and soil N sequestration. Therefore, the preparation of artificial humic urea fertilizer with high aromatization degree or low molecular weight were an effective way to improve N utilization efficiency in the initial stages of soil incubation and maintain N fixation in the later stages of soil incubation. The future application of the strategy presented by this study would have an important ecological significance for alleviating agricultural N pollution.


Acceleration of cellodextrin phosphorolysis for bioelectricity generation from cellulosic biomass by integrating a synthetic two-enzyme complex into an in vitro synthetic enzymatic biosystem.
Cellulosic biomass, the earth's most abundant renewable resource, can be used as substrates for biomanufacturing biofuels or biochemicals via in vitro synthetic enzymatic biosystems in which the first step is the enzymatic phosphorolysis of cellodextrin to glucose 1-phosphate (G1P) by cellodextrin phosphorylase (CDP). However, almost all the CDPs prefer cellodextrin synthesis to phosphorolysis, resulting in the low reaction rate of cellodextrin phosphorolysis for biomanufacturing. To increase the reaction rate of cellodextrin phosphorolysis, synthetic enzyme complexes containing CDP and phosphoglucomutase (PGM) were constructed to convert G1P to glucose 6-phosphate (G6P) rapidly, which is an important intermediate for biomanufacturing. Four self-assembled synthetic enzyme complexes were constructed with different spatial organizations based on the high-affinity and high-specific interaction between cohesins and dockerins from natural cellulosomes. Thus, the CDP-PGM enzyme complex with the highest enhancement of initial reaction rate was integrated into an in vitro synthetic enzymatic biosystem for generating bioelectricity from cellodextrin. The in vitro biosystem containing the best CDP-PGM enzyme complex exhibited a much higher current density (3.35-fold) and power density (2.14-fold) than its counterpart biosystem containing free CDP and PGM mixture. Hereby, we first reported bioelectricity generation from cellulosic biomass via in vitro synthetic enzymatic biosystems. This work provided a strategy of how to link non-energetically favorable reaction (cellodextrin phosphorolysis) and energetically favorable reaction (G1P to G6P) together to circumvent unfavorable reaction equilibrium and shed light on improving the reaction efficiency of in vitro synthetic enzymatic biosystems through the construction of synthetic enzyme complexes.


Peripheral neuroectodermal tumour (neuroepithelioma) of the thoracopulmonary region: light and electron microscopic cytology.
We describe a case of peripheral neuroectodermal tumour of the thoracopulmonary region diagnosed by fine needle aspiration cytology. Light microscope examination revealed numerous small tumour cells arranged in large irregular aggregates occasionally delimiting empty vascular-type spaces or forming rosette-like structures. Cytologically the tumour cells showed a marked degree of nuclear anaplasia, scanty cytoplasm and long thin cytoplasmic processes. Electron microscopy revealed cells with characteristics of neuroectodermal differentiation.


Reducing commercial fishing deck hazards with engineering solutions for winch design.
The majority (67%) of hospitalized injuries among Alaska commercial fishermen are associated with deck machinery. This paper describes the "Prevention Through Design" process to mitigate one serious machinery entanglement hazard posed by a capstan deck winch. After observing that the capstan winch provides no entanglement protection and the hydraulic controls are usually out of reach of the entangled person, NIOSH personnel met with fishermen and winch manufacturers to discuss various design solutions to mitigate these hazards. An emergency-stop ("e-stop") system was developed that incorporated a momentary contact button that when pushed, switches a safety-relay that de-energizes the solenoid of an electro-hydraulic valve stopping the rotating winch. The vessel owners that had the e-stop installed enthusiastically recommend it to other fishermen. NIOSH entered into a Proprietary Technology Licensing Agreement with a company to develop the system for commercial use. This is an example of a practical engineering control that effectively protects workers from a hazardous piece of equipment by preventing injuries due to entanglement. This solution could reduce these types of debilitating injuries and fatalities in this industry.


Time course of "escape" from calcitonin-induced inhibition of motility and resorption of disaggregated osteoclasts.
The reversible calcitonin (CT)-induced inhibition of osteoclastic activity has been studied to clarify the mechanisms responsible for the so-called "escape phenomenon." Osteoclasts disaggregated from neonatal rabbits were cultured on glass coverslips or thin bovine bone slices. Resorption activity was evaluated by using time-lapse recording and scanning electron microscopy. Addition of CT to the cultures caused most osteoclasts on glass surfaces to be immotile and contracted. From 1.5 h onward, in cultures with CT, osteoclasts started to escape from CT-induced quiescence independently of other cells. CT also prevented osteoclasts on bone slices from excavating bone while concomitant cell immobility occurred. Inhibited osteoclasts were able to regain apparent bone-resorbing potency only after resumption of cytoplasmic immobility. The resumption of bone resorption could begin as early as 9.7 h after CT addition. The observations indicate that CT-induced inhibition of osteoclastic bone resorption is associated with inhibition of cytoplasmic motility and that the "escape" phenomenon reflects resumption of activity of osteoclasts that were previously inhibited by CT action rather than the resportive activity of newly formed osteoclasts.


Minimally invasive approach for the management of the leaking tracheoesophageal puncture.
An enlarging tracheoesophageal puncture (TEP) site after total laryngectomy is associated with substantial functional, hygienic, and potentially life-threatening problems. The enlarged TEP is challenging to manage. TEP injection (TEP-I) for control of the enlarged puncture site may be beneficial in avoiding surgery. Our study reviewed the clinical outcomes of patients at a single institution with enlarged TEP treated by office-based TEP-I. Retrospective study. Chart review of eight patients who had an enlarged TEP with leakage around the prosthesis treated with TEP-I after attempted customization of voice prostheses. Patient demographics and treatments were reviewed, and injection efficacy was evaluated by the duration of leakage resolution. Eight patients underwent 20 TEP-I procedures. The average duration of leak resolution after each injection was 174.5 days. There were no complications. Six patients required custom modifications of the voice prosthesis to control TEP leakage after TEP-I, and all patients resumed their baseline speech and swallowing function. There was a trend toward an increase in number of injections among patients with N+ disease, disease recurrence, a history of irradiation and secondary TEP. No patients required surgical closure of the TEP. Office-based TEP-I is a safe and effective treatment option for patients with an enlarged TEP site who have failed more conservative measures. A history of irradiation, disease recurrence, secondary TEP, and high-volume neck disease were predictive of multiple injections. Further study is warranted to accurately identify patients who may benefit from TEP-I to control leakage around the TEP.


[Towards teaching eco-design of care in the initial training of future health professionals].
Our society is regularly faced with new dangers, linked to the evolution of living conditions, production, work, consumption and housing. Health systems are no stranger to this. On the contrary, they have a real impact on the environment, which needs to be mitigated. Professionals can contribute to this by changing their practices (prescribing certain examinations that consume less energy, using low-impact therapeutic methods, teaching patients not to over-consume, etc.). For this eco-design of care to work, it is essential to make students aware of it as early as their initial training.


Flash Ostial Balloon in Right Internal Mammary Artery Percutaneous Coronary Intervention: A Novel Approach.
Despite the widespread use of coronary stents and effective anticoagulation regimens, the treatment of ostial lesions is limited by high restenosis rates. Ostial stenosis is a technically difficult condition to treat but this novel technique shows the ability to enable the optimal coverage of the ostium with excellent stent flaring using a Flash ostial balloon (Cardinal Health Inc., Dublin, OH).


Insulin signaling pathways in time and space.
Despite remarkable progress in dissecting the signaling pathways that are crucial for the metabolic effects of insulin, the molecular basis for the specificity of its cellular actions is not fully understood. One clue might lie in the spatial and temporal aspects of signaling. Recent evidence suggests that signaling molecules and pathways are localized to discrete compartments in cells by specific protein interactions. Also, the rapid termination of tyrosine or lipid phosphorylation by phosphatases or serine kinases might tightly control the strength of a signaling pathway, thus determining its effect on growth, differentiation and metabolism.


SARS-CoV-2-associated haemorrhagic encephalitis mimicking Herpes encephalitis.
Although acute encephalopathy is quite commonly seen in patients of SARS-CoV-2 infection, encephalitis characterised by brain inflammation is relatively rare. Encephalitis caused by Herpes simplex type 1 is the most common cause of identified sporadic encephalitis, and early diagnosis and prompt treatment can prevent the devastating outcome. In this brief communication, we report a case of SARS-CoV-2 associated haemorrhagic encephalitis mimicking herpes encephalitis. In today's pandemic era, it is especially important to distinguish herpes encephalitis from SARS-CoV-2-associated encephalitis as treatment and prognosis of both the conditions differ greatly. This case highlights the importance of suspecting SARS-CoV-2 infection in a patient presenting with clinical symptoms and brain imaging suggestive of Herpes encephalitis.


Imaging of female infertility.
Normal reproduction requires healthy female anatomy. Cervical, uterine, tubal, ovarian, and peritoneal factors can coexist and cause female infertility. Ultrasound, hysterosalpingography, MR imaging, and fallopian tube catheterization are the radiologists' armamentarium for diagnosis. This article illustrates important findings in the infertile woman. An understanding of these entities helps i n accurateand sympathetic treatment.


In vitro and in vivo evaluation of cypermethrin, amitraz, and piperonyl butoxide mixtures for the control of resistant Rhipicephalus (Boophilus) microplus (Acari: Ixodidae) in the Mexican tropics.
A study was conducted to evaluate the efficacy of cypermethrin, amitraz, and piperonyl butoxide (PBO) mixtures, through in vitro laboratory bioassays and in vivo on-animal efficacy trials, for the control of resistant Rhipicephalus (Boophilus) microplus on cattle in the Mexican tropics. Also, to examine mechanisms of resistance to cypermethrin in this tick population, the frequency of a mutated sodium channel gene (F1550I) was determined using a PCR assay. Results of laboratory bioassays using modified larval packet tests revealed that cypermethrin toxicity was synergized by PBO (from 46.6-57.0% to 83.7-85.0% larval mortality; P<0.05). The cypermethrin and amitraz mixture showed an additive effect (from 46.6-57.0% to 56.0-74.3% larval mortality). Strong synergism was observed with the mixture of cypermethrin+amitraz+PBO and this mixture was the most effective killing resistant tick larvae in vitro (96.7-100% of larval mortality). Tick larvae surviving exposure to cypermethrin or mixtures either with amitraz and PBO in vitro showed 2.9-49.6 higher probability to present the mutated allele than those killed by acaricide treatment (P<0.05). In the in vivo trial, the mixtures containing cypermethrin+PBO (80.6-97.3%), and cypermethrin+amitraz (87.0-89.7%) were more efficacious than cypermethrin alone (76.3-80.5%). The highest level of efficacy was obtained with the mixture of cypermethrin+amitraz+PBO, which yielded >95% control that persisted for 28 days post-treatment against R. microplus infesting cattle when tested under field conditions in the Mexican tropics. Although this mixture is a potentially useful tool to combat pyrethroid resistance, a product based on an acaricide mixture like the one tested in this study has to be used rationally.


Atomically precise metal nanoclusters meet metal-organic frameworks.
Significant progress has been made in both fields of atomically precise metal nanoclusters (NCs) and metal-organic frameworks (MOFs) in recent years. A promising direction is to integrate these two classes of materials for creating unique composites with improved properties for catalysis and other applications. NCs incorporated with MOFs exhibit an optimized catalytic performance in many catalytic reactions, in which MOFs play a vital supporting role or as cocatalysts. In this Perspective, we first provide a brief summary of the methods that have been developed for the preparation of NCs/MOF composites and the characteristics of these strategies are analyzed. Following that, some recent works are highlighted to demonstrate the crucial role of MOF matrices in the enhancement of NCs catalytic properties. Finally, we outline some potentially important aspects for future work. This Perspective is in hopes of stimulating more interest in the research on the integration of NCs with MOFs toward functional materials.


Prevention of fat embolism syndrome in patients with femoral fractures--immediate or delayed operative fixation?
From January 1976 until August 1980, femoral fractures in our department were initially stabilized with tibial traction and fixed operatively after 4-7 days. From August 1980 the fractures were treated with immediate operative fixation. In this retrospective study, we compared the incidence of fat embolism syndrome in 106 patients treated with delayed operative fixation to the incidence in 114 patients treated with immediate operative fixation. Eleven patients (10.4%) developed fat embolism syndrome in the group treated with delayed fixation, compared with two patients (1.8%) in the immediate osteosynthesis group (p less than 0.02). We concluded that early operative fixation of femoral fractures seems beneficial for the prevention of fat embolism syndrome.


Neural correlates of implied motion.
Current views of the visual system assume that the primate brain analyses form and motion along largely independent pathways; they provide no insight into why form is sometimes interpreted as motion. In a series of psychophysical and electrophysiological experiments in humans and macaques, here we show that some form information is processed in the prototypical motion areas of the superior temporal sulcus (STS). First, we show that STS cells respond to dynamic Glass patterns, which contain no coherent motion but suggest a path of motion. Second, we show that when motion signals conflict with form signals suggesting a different path of motion, both humans and monkeys perceive motion in a compromised direction. This compromise also has a correlate in the responses of STS cells, which alter their direction preferences in the presence of conflicting implied motion information. We conclude that cells in the prototypical motion areas in the dorsal visual cortex process form that implies motion. Estimating motion by combining motion cues with form cues may be a strategy to deal with the complexities of motion perception in our natural environment.


Populations in environments with a soft carrying capacity are eventually extinct.
Consider a population whose size changes stepwise by its members reproducing or dying (disappearing), but is otherwise quite general. Denote the initial (non-random) size by [Formula: see text] and the size of the nth change by [Formula: see text], [Formula: see text]. Population sizes hence develop successively as [Formula: see text] and so on, indefinitely or until there are no further size changes, due to extinction. Extinction is thus assumed final, so that [Formula: see text] implies that [Formula: see text], without there being any other finite absorbing class of population sizes. We make no assumptions about the time durations between the successive changes. In the real world, or more specific models, those may be of varying length, depending upon individual life span distributions and their interdependencies, the age-distribution at hand and intervening circumstances. We could consider toy models of Galton-Watson type generation counting or of the birth-and-death type, with one individual acting per change, until extinction, or the most general multitype CMJ branching processes with, say, population size dependence of reproduction. Changes may have quite varying distributions. The basic assumption is that there is a carrying capacity, i.e. a non-negative number K such that the conditional expectation of the change, given the complete past history, is non-positive whenever the population exceeds the carrying capacity. Further, to avoid unnecessary technicalities, we assume that the change [Formula: see text] equals -1 (one individual dying) with a conditional (given the past) probability uniformly bounded away from 0. It is a simple and not very restrictive way to avoid parity phenomena, it is related to irreducibility in Markov settings. The straightforward, but in contents and implications far-reaching, consequence is that all such populations must die out. Mathematically, it follows by a supermartingale convergence property and positive probability of reaching the absorbing extinction state.


The in vitro invasiveness and interactions with laminin of K-1735 melanoma cells. Evidence for different laminin-binding affinities in high and low metastatic variants.
The invasive and metastatic characteristics of cloned cells derived from the K-1735 murine melanoma were investigated. Cell lines which are highly metastatic in mice were found to be invasive in vitro, and to show an enhanced attachment to, spreading on and migration toward laminin. As attachment, spreading and directional migration are thought to be receptor-mediated events, the binding of laminin to these cells was studied. Biotinylated laminin was used to evaluate receptor binding by fluorescence activated cell sorting (FACS) and this method was compared with that in which the binding of radioactive laminin is measured. Both studies revealed that metastatic K-1735 cells (a) have more receptors for laminin compared with non-metastatic cells and (b) exhibit a second population of low-affinity binding sites not present on the non-metastatic cells. The differences in receptor number and type may account for the greater interaction of metastatic cells with laminin and their invasive phenotype.


Clinical and histopathological features of progressive-type familial amyloidotic polyneuropathy with TTR Lys54.
The purpose of this study was to evaluate the clinical and pathological features in patients with progressive-type familial amyloidotic polyneuropathy (FAP) using autopsy and biopsy specimens. A proband is a 33-year-old man with FAP type I who developed motor, sensory and autonomic impairments with neuropathy, heart failure, and anorexia. Genetic findings of transthyretin (TTR) revealed G to A transition in codon 54 causing a rare mutation of TTR Lys54. He died of pneumonia and severe cardiac failure 4 years after onset. Autopsy showed heavy amyloid deposition in the heart, peripheral nerves, thyroid, skin, fat tissue, prostate and testis, moderate in the sympathetic nerve trunk, vagal nerve, celiac plexus, pelvic plexus, bladder, gastrointestinal tract, tongue, pancreas, lung, pituitary, blood vessel, gall bladder, adrenals and muscles, and free in the central nervous system, liver, kidney and spleen. Sural nerve biopsy in a sibling confirmed TTR amyloidosis immunohistochemically. Electronmicroscopic findings of amyloid fibrils were similar to that of FAP Met30. Immunoelectronmicroscopic findings indicated the relationship between amyloid fibrils or non-fibrillar structure and collagen fibers. The distribution of amyloid deposition, heavy in the heart and lacking in the kidney, is a characteristic feature and reflected severity of FAP with TTR Lys54.


The FeMoco-deficient MoFe protein produced by a nifH deletion strain of Azotobacter vinelandii shows unusual P-cluster features.
The His-tag MoFe protein expressed by the nifH deletion strain Azotobacter vinelandii DJ1165 (Delta(nifH) MoFe protein) was purified in large quantity. The alpha(2)beta(2) tetrameric Delta(nifH) MoFe protein is FeMoco-deficient based on metal analysis and the absence of the S = 3/2 EPR signal, which arises from the FeMo cofactor center in wild-type MoFe protein. The Delta(nifH) MoFe protein contains 18.6 mol Fe/mol and, upon reduction with dithionite, exhibits an unusually strong S = 1/2 EPR signal in the g approximately 2 region. The indigo disulfonate-oxidized Delta(nifH) MoFe protein does not show features of the P(2+) state of the P-cluster of the Delta(nifB) MoFe protein. The oxidized Delta(nifH) MoFe protein is able to form a specific complex with the Fe protein containing the [4Fe-4S](1+) cluster and facilitates the hydrolysis of MgATP within this complex. However, it is not able to accept electrons from the [4Fe-4S](1+) cluster of the Fe protein. Furthermore, the dithionite-reduced Delta(nifH) MoFe can be further reduced by Ti(III) citrate, which is quite unexpected. These unusual catalytic and spectroscopic properties might indicate the presence of a P-cluster precursor or a P-cluster trapped in an unusual conformation or oxidation state.


Recurrent hypersomnia following traumatic brain injury.
Recurrent hypersomnia (RH) following a traumatic brain injury (TBI) is a rare form of RH. According to the International Classification of sleep disorders, 2nd edition (ICSD-2), RH must be considered in the differential diagnosis as secondary to an organic insult of the central nervous system and not as the clinical subtype of RH, Kleine-Levin syndrome (KLS). The aim of our study was to investigate if cases of RH following TBI should be considered in the differential diagnosis of RH as indicated by the International classification of sleep disorders, 2nd edition or as genuine, or indicated by ICSD-2, RH must cases of KLS. Twelve cases of RH developed after TBI were collected and analyzed for circumstance at onset, severity of TBI, delay between TBI and occurrence of first episode of RH, symptoms of RH, duration and cycle length of episodes of hypersomnia, physical signs, and brain morphological imaging at the time of hypersomnia episodes. Factors such as the delay between TBI and the first episode of RH, the presence of other triggering factors and potential genetic factors, the degree of the severity of TBI, the presence or absence of any consistent brain imaging abnormality, provided the following results: (1) two of the cases could be considered as symptomatic of the underlying pathological brain process, (2) eight of the cases could be considered as simply triggered by TBI in patients at risk for KLS, and (3) two cases could be considered neither symptomatic nor triggered by TBI, due to the long delay between TBI and occurrence of symptoms. Cases of RH following TBI do not present under a single mechanism. Clinical assessment and laboratory tests are necessary to correctly classify them.


Effect of antibiotics for infectious diarrhea on the duration of hospitalization: A retrospective cohort study at a single center in Japan from 2012 to 2015.
Routine empirical antimicrobial therapy for patients with infectious diarrhea is not recommended in general practice. Conversely, prescription of empirical antibiotics for hospitalized patients remains controversial due to a lack of studies providing evidence for its benefits. Thus, this study aimed to examine whether empirical antimicrobial therapy would shorten the hospitalization duration for infectious diarrhea patients. This single-center, retrospective cohort study was performed at the Department of General Medicine and Emergency Care, Toho University Medical Center Omori Hospital, using medical records. Adult patients (aged ≥16 years) hospitalized for infectious diarrhea from 2012 to 2015 were enrolled. The primary outcome was the duration of hospitalization. Risk factors examined in parallel to antibiotic therapy included age, sex, relevant medical history, probiotics use, vital signs, leukocyte count, liver and renal functions, and microbiological data. We enrolled 138 and 50 patients treated with and without antimicrobial therapy, respectively. The median hospitalization periods were 6.0 days (interquartile range, 4.0-7.0 days) and 5.0 days (interquartile range, 3.25-6.0 days) for patients treated with and without antibiotics, respectively (p = 0.007). Multiple regression showed that empiric antimicrobial therapy (p = 0.017), advanced age (p = 0.003), hematochezia (p = 0.008), elevated serum creatinine (p < 0.001), and elevated serum C-reactive protein (p = 0.002) were significant risk factors of longer hospitalization duration. Empirical antimicrobial therapy was found to relate to a longer hospitalization duration for infectious diarrhea patients. Although its effects on the patients' symptoms were not evaluated, our results suggest that empirical antimicrobial therapy should be administered cautiously to not only outpatients, but also hospitalized patients.


[Studies on the chemical constituents of Lithocarpus polystachyus].
To study the chemical constituents from Lithocarpus polystachyus. Compounds were isolated and purified with silica gel, and there structures were identified by chemical property and spectral data. Nine compounds were isolated as phloridzin (I), phloretin (II), dihydrochalcone-2'-beta-D-glucopyranoside (III), daucossterol (IV), beta-sitosterol (V), quercetin (VI), luteolin (VII), quercitrin (VI), oleanolic acid (IX). Compounds II, IV - IX are isolated from this plant for the first time.


Socioeconomic factors impact colon cancer outcomes in diverse patient populations.
Cancer disparities among racial and ethnic groups are major public health concerns. Our objective was to examine the impact of socioeconomic status (SES) on survival of colon cancer patients within major racial and ethnic groups. Patients with colon adenocarcinoma from Los Angeles County (LAC) were assessed. SES was utilized as an indicator of healthcare access and categorized by tertiles (high, middle, and low). Patient characteristics were compared and survival analyses were performed. In our heterogeneous LAC cohort, we confirmed survival disparities. Asians had the best survival followed by Hispanics, whites, and blacks. For each stage of disease, Asians and Hispanics had better outcomes than whites and blacks. Then, we evaluated the impact of SES on survival within each racial and ethnic group. We observed significantly longer survival for high SES patients compared to middle and low SES patients for all racial/ethnic groups. While disparities across racial/ethnic groups are well-documented, our study is the first to identify socioeconomic disparities in survival for patients within the same group. These novel findings demonstrate the complex role of SES on race and ethnicity and identify the need to improve healthcare access even within select populations.


Influence of material choice on the force delivery of bimaxillary tooth positioners on canine malpositions.
Since their introduction in 1945, tooth positioners have been used to treat a range of malpositions. Although the original appliance was made of natural rubber, today's tooth positioners are fabricated from various elastic, transparent materials. It was the aim of this study to evaluate the forces and moments produced by current positioners on various upper canine malpositions. Seven positioners of different materials were tested on 11 upper canine malpositions: 0.25, 0.5, 1 mm supraposition; 0.25, 0.5, 1 mm infraposition; 5°, 10°, 20° mesiorotation; 5° mesioinclination, 5° buccal root torque. We measured forces and moments in vitro after bite closure by 0.5 mm, and opening by 1 mm using a three-dimensional robotic device. All measurements were taken in a temperature-controlled environment at 36 °C. The forces and moments measured at the canine varied greatly among the different positioners, with the thermoformed EVA positioner showing much greater forces and moments in almost all malpositions. At initial closure, we observed intrusive forces of 6-32 N for suprapositions, 0-11 N intrusive forces for infrapositions, 0-20 Nmm for mesiorotations, 6-12 Nmm for mesioinclinations, and - 23 Nmm to 5 Nmm for buccal root torque. All positioners were most effective on suprapositioned teeth. Very low or negligible correctional forces and moments in conjunction with all infrapositions and 5° with rotation were noted. Labial root torque led to unpredictable moments. Positioner material plays a major role in delivering forces to the teeth. However, tooth positioners did not induce corrective forces in all the malpositions tested. Clinically relevant correctional forces or moments in conjunction with all suprapositions, rotations of 10° and 20° as well as mesial tipping of the canine were observed.