The effects of platelet secretion inhibitors on protein phosphorylation.
Protein phosphorylation was investigated in human platelets after stimulation to secretion by thrombin. After stimulation by thrombin at 4 degrees C (in which secretion is inhibited), phosphorylations of the 80, 56, and 38 kDa polypeptides and dephosphorylation of the 67 kDa phosphopeptide eventually occurred. The phosphorylations of the 27 and 20 kDa polypeptides remained inhibited until the temperature was increased to 37 degree C, which also resulted in secretion. Various stimulants and inhibitors of platelet function were used to characterize individual protein phosphorylations. The divalent-cation ionophore, A23187, induced the phosphorylations (or dephosphorylation) of the same proteins as thrombin with the exception of the 80 kDa protein, which remained incompletely phosphorylated. The intracellular calcium antagonist, TMB-8, inhibited thrombin-stimulated secretion and phosphorylation of all the polypeptides except the 80 kDa protein. The dephosphorylation of the 67 kDa phosphoprotein was not affected by TMB-8. Incubation of platelets with prostaglandin E1 and isobutylmethylxanthine inhibited thrombin-stimulated secretion and the phosphorylation of the 38 and 20 kDa protein and increased the phosphorylation of the 67 and 27 kDa phosphoproteins. These observations may be used to correlate protein phosphorylation with secretion, suggesting a possible sequence of intracellular events that mediate thrombin-stimulated secretion.


Exercise attenuates oral intake of amphetamine in rats.
The effects of wheel running on oral intake of amphetamine were examined in six male Sprague-Dawley rats given a 0.075-mg/ml amphetamine sulfate solution as their sole source of liquid, six rats given a 0.15-mg/ml amphetamine solution, and four rats given water as their sole source of liquid. All animals were housed in Wahmann running wheels and adjoining cages, and had ad lib access to ground Purina Chow. For the first 7 days of the experiment, the doors to the running wheels were closed; the wheels were then opened for 6 days. This cycle was repeated a second time. Animals drinking the 0.15-mg/ml amphetamine solution consumed significantly less food and gained less weight than animals in the other two groups. Although there was no difference in food intake between rats drinking water and rats drinking the 0.075-mg/ml amphetamine solution, rats in the water group gained significantly more weight than rats in the 0.075-mg/ml amphetamine group. With respect to drug intake, rats consumed significantly less amphetamine when running in the wheels than when access to the wheels was prohibited. Access to running wheels did not alter water intake. These latter results suggest that drug intake can be reduced by the provision of an alternate behavior.


Vibrational spectroscopic study of the copper silicate mineral kinoite Ca2Cu2Si3O10(OH)4.
Kinoite Ca2Cu2Si3O10(OH)4 is a mineral named after a Jesuit missionary. Raman and infrared spectroscopy have been used to characterise the structure of the mineral. The Raman spectrum is characterised by an intense sharp band at 847 cm(-1) assigned to the ν1 (A1g) symmetric stretching vibration. Intense sharp bands at 951, 994 and 1000 cm(-1) are assigned to the ν3 (Eu, A2u, B1g) SiO4 antisymmetric stretching vibrations. Multiple ν2 SiO4 vibrational modes indicate strong distortion of the SiO4 tetrahedra. Multiple CaO and CuO stretching bands are observed. Raman spectroscopy confirmed by infrared spectroscopy clearly shows that hydroxyl units are involved in the kinoite structure. Based upon the infrared spectra, it is proposed that water is also involved in the kinoite structure. Based upon vibrational spectroscopy, the formula of kinoite is defined as Ca2Cu2Si3O10(OH)4·xH2O.


The effects of violet and blue light irradiation on ESKAPE pathogens and human cells in presence of cell culture media.
Bacteria belonging to the group of ESKAPE pathogens are responsible for the majority of nosocomial infections. Due to the increase of antibiotic resistance, alternative treatment strategies are of high clinical relevance. In this context visible light as disinfection technique represents an interesting option as microbial pathogens can be inactivated without adjuvants. However cytotoxic effects of visible light on host cells have also been reported. We compared the cytotoxicity of violet and blue light irradiation on monocytic THP-1 and alveolar epithelium A549 cells with the inactivation effect on ESKAPE pathogens. THP-1 cells displayed a higher susceptibility to irradiation than A549 cells with first cytotoxic effects occurring at 300 J cm-2 (405 nm) and 400 J cm-2 (450 nm) in comparison to 300 J cm-2 and 1000 J cm-2, respectively. We could define conditions in which a significant reduction of colony forming units for all ESKAPE pathogens, except Enterococcus faecium, was achieved at 405 nm while avoiding cytotoxicity. Irradiation at 450 nm demonstrated a more variable effect which was species and medium dependent. In summary a significant reduction of viable bacteria could be achieved at subtoxic irradiation doses, supporting a potential use of visible light as an antimicrobial agent in clinical settings.


Polarized distribution of binding sites for concanavalin A and wheat-germ agglutinin in the zona pellucida of goodeid oocytes (teleostei).
Zonae pellucidae of the viviparous goodeid teleosts Girardinichthys viviparus, Xenoophorus captivus, and Xenotoca eiseni were investigated ultrastructurally, and binding sites for ConA and WGA were localized on cross-sections using a colloidal gold technique. In late stages of development, the oocytes are surrounded by a three-zonated acellular matrix multiply perforated by pore canals allowing long microvilli of the oocyte to penetrate interstices of the follicle epithelium. Together, the surface of the microvilli and zona pellucida is coated by a thin layer of homogeneous slightly electron-dense material. In early oogenesis, the thin acellular layer is entirely packed with binding sites for WGA, whereas those for ConA occur only sparsely. Three-zonated zonae pellucidae amply contain both WGA and ConA receptors. The asymmetric labelling pattern obtained with both lectin protein gold preparations indicates a polarized organization of the different glycoconjugates. WGA receptors are concentrated within the outer region of the zona pellucida. Labelling with ConA-HRP-Au complexes produced heavy deposits of marker beads within the inner two thirds of the zona pellucida and weak labelling of the superficial coat. After prolonged digestion with neuraminidase, WGA binding sites were no longer detectable.


Spatial stochastic modelling of the Hes1 gene regulatory network: intrinsic noise can explain heterogeneity in embryonic stem cell differentiation.
Individual mouse embryonic stem cells have been found to exhibit highly variable differentiation responses under the same environmental conditions. The noisy cyclic expression of Hes1 and its downstream genes are known to be responsible for this, but the mechanism underlying this variability in expression is not well understood. In this paper, we show that the observed experimental data and diverse differentiation responses can be explained by a spatial stochastic model of the Hes1 gene regulatory network. We also propose experiments to control the precise differentiation response using drug treatment.


Psychosocial determinants of successful voice rehabilitation after laryngectomy.
This study gives an overview of publications on factors that are associated with the outcome of voice rehabilitation after laryngectomy. A systematic literature review was conducted. Fifty-six manuscripts were analyzed regarding the parameters investigated, the number of participants included, the study designs used, the assessment instruments, and the results. A broad range of factors were considered to contribute to successful voice rehabilitation, whereby psychosocial attributes related to success are mentioned as often as medical and treatment-related characteristics. The results of the studies are mostly inconsistent. It can be concluded, however, that active communication behavior, employment status, type of alaryngeal speech and the general physical condition are associated with rehabilitation outcomes, whereas alcohol consumption is not. More comprehensive prospective studies are needed which analyze the impact of psychosocial factors with validated and standardized instruments. A large sample size would be necessary to calculate all possibly relevant factors and their interaction. Clinicians should be careful about considering their patients to be "unmotivated" if the rehabilitation fails; instead, they should encourage them to communicate actively and take part in social activities.


Enhanced alveolar bone loss in a model of non-invasive periodontitis in rice rats.
The rice rat (Oryzomys palustris) develops periodontitis-like lesions when fed a diet rich in sucrose and casein (H-SC). We aimed to establish whether this model can accurately mimic the development of human periodontitis. For this purpose, 28-day-old rice rats (15/group) were assigned to standard (STD) or H-SC diets and sacrificed after 6, 12, and 18 weeks. Jaws were processed for morphometric, histometric, histologic, histomorphometric, and micro-CT analyses. We found a progressive increase in horizontal alveolar bone loss (ABL) with age in maxillae of rats fed the STD diet as determined by morphometry. The H-SC diet exacerbated horizontal ABL at the palatal surface at 12 and 18 weeks. Furthermore, increased vertical ABL was detected in mandibles and maxillae of rats fed the H-SC diet for 12 and/or 18 weeks by histometry and micro-CT. Remarkably, the H-SC diet significantly increased bone remodeling at the interproximal alveolar bone of mandibles from rats fed for 6 weeks, but not in those fed for longer periods. These findings indicate that the H-SC diet induced a transient increase in alveolar bone remodeling, which is followed by ABL characteristic of moderate periodontitis.


Validation of the English version of the KINDL generic children's health-related quality of life instrument for an Asian population--results from a pilot test.
To evaluate the psychometric properties of the KINDL questionnaire in an Asian population. Consecutive patients with diabetes mellitus (DM) and healthy subjects were recruited to complete the English KINDL questionnaire. The inclusion criteria for patients were age 8-16 years, English-speaking, diagnosed with DM and absence of co-morbid conditions. Thirty children with DM (mean age: 10.7 +/- 1.35 years; 11 M) and 39 healthy subjects (mean age: 10.6 +/- 1.23 years, 17M) completed the child version whereas 31 adolescents with DM (mean age: 14.5 +/- 1.48 years; 15M) and 32 healthy subjects (mean age: 14.3 +/- 0.87 years, 16M) completed the adolescent version. Overall, children with DM reported better HRQoL than healthy children. Although this appeared counter-intuitive, several explanations are possible: (1) the development of resilience to the disease over time, (2) our subjects are well-managed, (3) response shift, (4) the provision of high quality medical care, (5) compared to normal children, diabetic subjects and their family pay greater attention to health issues. The reliability coefficients were (overall, scales): KINDL-Kid DM (0.79, 0.44-0.65), KINDL-Kid Healthy (0.71,0.60-0.80), KINDL-Kiddo DM (0.77, 0.37-0.74) and KINDL-Kiddo Healthy (0.84, 0.21-0.79). The KINDL questionnaire appeared promising for use in Asian children. However, further validation in a sample more representative of the general population is required.


Depression, post-traumatic stress disorder, and dry eye syndrome: a study utilizing the national United States Veterans Affairs administrative database.
To study the scope of dry eye syndrome (DES) in veterans on a national level and to evaluate the relationship between psychiatric diagnoses and DES. Case-control study. Patients were seen in a Veterans Affairs (VA) eye clinic between 2006 and 2011. Patients were divided into cases and controls with regard to their dry eye status (cases = ICD-9 code for DES plus dry eye therapy; controls = patients without ICD-9 code plus no therapy). The prevalence of DES and the influence of psychiatric diagnoses on the risk of DES. A total of 2 454 458 patients were identified as either a dry eye case (n = 462 641) or control (n = 1 991 817). Overall, 19% of male patients and 22% of female patients had a diagnosis of DES, with female sex imparting an increased risk of DES at each decade compared to male sex (odds ratio [OR] 1.22-2.09). Several conditions were found to increase DES risk, including post-traumatic stress disorder (OR 1.92, 95% CI 1.91-1.94) and depression (OR 1.92, 95% CI 1.91-1.94) (analyses adjusted for sex and age). The use of several systemic medications was likewise associated with an increased risk of DES, including antidepressant medications (OR 1.97, 95% CI 1.79-2.17) and antianxiety medication (OR 1.74, 95% CI 1.58-1.91). Multivariate analysis (adjusted for age and sex) revealed that for psychiatric diagnoses, both the use of medication and the diagnosis remained significant risk factors when considered concomitantly, although the magnitude of each association decreased. DES is a disease associated with depression and post-traumatic stress disorder, and is prevalent among male and female veterans receiving eye care services. The association could be driven by underlying disease physiology or medications used to treat psychiatric conditions. Regardless of the causal link, this suggests that individuals with a known psychiatric diagnosis should be questioned about dry eye symptoms and, if applicable, referred to an eye care physician.


Iron: how much is too much?
Gross iron overload has long been known to result in diabetes mellitus. However, it is now thought that milder levels of iron overload, possibly within the normal range, also increase the risk of diabetes mellitus. The article by Rawal et al in this issue (Diabetologia doi: 10.1007/s00125-016-4149-3 ) provides further support for the relationship between mild degrees of iron overload and the risk of gestational diabetes. The purpose of this commentary is to briefly discuss the background of this relationship and the implications it may have for routine pregnancy care.


Distinct behavior of the little finger during the vertical translation of an unsteady thumb platform while grasping.
Object stabilization while grasping is a common topic of research in motor control and robotics. Forces produced by the peripheral fingers (index and little) play a crucial role in sustaining the rotational equilibrium of a handheld object. In this study, we examined the contribution of the peripheral fingers towards object stabilization when the rotational equilibrium is disturbed. For this purpose, the thumb was placed over an unsteady platform and vertically translated. The task was to trace a trapezoid or an inverted trapezoid pattern by moving the thumb platform in the vertical direction. The thumb displacement data served as visual feedback to trace the pattern displayed. Participants were instructed to maintain the handle in static equilibrium at all times. We observed that the change in the normal force of the little finger due to the downward translation of the thumb was significantly greater than the change in the normal force of the index finger due to the upward translation. We speculate that morphological correlations (between thumb and little finger) during the displacement of the thumb might be a reason for such large increases in the little finger forces.


[Utility of mouth rinses with povidone-iodine and hydrogen peroxide in patients with COVID-19].
Povidone-iodine and hydrogen peroxide could be effective in against SARS-CoV-2. A "non-interventional trial" in 88 patients (43 ± 17 yrs, 55% men) with SARS-CoV-2 in nasopharyngeal swabs (RT-PCR). 31 received mouth rinses/gargling with povidone-iodine (every 8 h, two consecutive days), 17 with mouth rinses/gargling of hydrogen peroxide, and 40 controls. PCR were repeated at 3, 11 and 17 days. After intervention the viral load (Log 10 copies/ml) remained similar in povidone-iodine (4.3 ± 2.7 copies/ml), hydrogen peroxide (4.6 ± 2.9 copies/ml; p = 0.40) and controls (4.4 ± 3.0 copies/ml). The percentage of patients with a negative result in the second PCR was 27% in povidone-iodine group, 23% in hydrogen peroxide and 32% in controls; in the third PCR, 62%, 54% and 58% respectively; and in the fourth PCR, 81%, 75% and 81%. Our results do not support the clinical usefulness of mouth rinses/gargling with povidone-iodine or hydrogen peroxide in patients with COVID-19.


Preparation and characterization of aqueous dispersions of high amylose starch and conjugated linoleic acid complex.
Crystalline starch-CLA complexes were prepared by blending an alcoholic solution of conjugated linoleic acid (CLA) in an aqueous high-amylose maize starch dispersion. Recovery yield of CLA in the precipitates obtained by centrifuging the dispersion was dependent on reaction conditions such as temperature, time and pH. The CLA recovery reached a maximum when the reaction was performed at 90°C for 6h at neutral pH, with 67.7% of the initial CLA being co-precipitated with starch. The precipitates contained amylose-CLA complex exhibiting a V6I-type crystalline structure under X-ray diffraction analysis and a type II polymorph under DSC analysis. Ultrasonic treatment for the re-dispersed starch-CLA complex in water resulted in the reduction of hydrodynamic diameter of the complex particles to 201.5nm. The dispersion exhibited a zeta potential of -27.0mV and remained stable in an ambient storage without forming precipitates for more than 4weeks.


Detection of circulating stromal stem cells with osteogenic potential in the blood of coronary patients by laser flow cytometry.
The number of cells expressing antigen to osteonectin was appreciably increased in the blood of coronary patients, but no cells of this kind were detected in donors. The number of CD34+ stem cells in these patients virtually did not differ from that in normal subjects. A close relationship between atherosclerosis development and presence of stromal stem cells with osteogenic potential in the blood is hypothesized.


Concept analysis: sexual decision-making in adolescence.
This papers aims to clarify and explore the topic of adolescent decision-making regarding sexual activity. Published literature. Adolescent decision-making regarding the initiation or continuation of sexual activity is influenced by desire for intimacy, perceived relationship safety, problem-solving ability, cognitive ability, family and peer relationships, and concern regarding pregnancy or sexually transmitted infection.


Assessment of the trackability, flexibility, and conformability of coronary stents: a comparative analysis.
The efficacy and safety of coronary stent implantation depend on the mechanical features of these devices when deployed in atheromatous lesions of various morphologies. We evaluated the trackability, flexibility, and conformability of 17 coronary stents using specific mechanical bench tests. The quantifications used a dynamometer for assessment of trackability (maximal strength) and flexibility (stiffness) and a 3D optical gauging machine for assessment of conformability (distance between stent and arterial wall in a curvature). The maximal strength (measuring the trackability) ranged respectively from 0.24 +/- 0.06 and 0.38 +/- 0.03 N (Seaquest) to 1.31 +/- 0.42 and 1.34 +/- 0.35 N (Carbostent), concerning respectively curvatures of 90 degrees (P < 0.0001) and 135 degrees (P < 0.0001). The stiffness (measuring the flexibility) ranged from 0.53 +/- 0.16 (Seaquest) to 1.28 +/- 0.10 N/mm (NIR Royal; P < 0.0001). The mean distance between stent and external curvature (external conformability) ranged from 0.15 +/- 0.06 mm (S7) to 0.57 +/- 0.4 mm (NIR Royal; P < 0.0001). The mean distance between stent and internal curve (internal conformability) ranged from 0.26 +/- 0.13 (S7) to 0.44 +/- 0.12 mm (S670; P < 0.0001). These results may influence the choice of a particular stent adapted to a specific coronary anatomy.


Radiosensitivity of normal tissues in ataxia-telangiectasia heterozygotes.
Approximately 5% of cancer patients given radiation therapy exhibit severe injuries to the noncancerous tissue in the radiation field. Striking clinical sensitivity to ionizing radiation has been observed frequently in ataxia-telangiectasia (A-T) homozygotes. This study was undertaken to test the hypothesis that heterozygous carriers of a mutated gene for A-T may represent a substantial proportion of all patients who suffer severe radiation toxicity. The medical records of all A-T heterozygotes treated with radiation therapy for breast or prostate cancer were compiled from an ongoing study of mortality and cancer incidence in A-T families. Diagnostic, treatment, and follow-up records were reviewed. Acute and long-term radiation complications were scored according to Radiation Therapy and Oncology Group criteria. There were no instances of soft tissue necrosis or other apparent serious injuries to normal tissues of two A-T heterozygotes with prostate carcinoma and 11 with breast carcinoma who received moderate-to-high doses of conventionally fractionated radiation therapy by megavoltage techniques. There is no evidence that abnormal clinical radiosensitivity occurs in A-T heterozygotes receiving conventionally fractionated radiation therapy for breast or prostate cancer.


Reliability and repeatability of swept-source Fourier-domain optical coherence tomography and Scheimpflug imaging in keratoconus.
To evaluate the repeatability and reliability of a recently introduced swept-source Fourier-domain anterior segment optical coherence tomography (AS-OCT) system and a high-resolution Scheimpflug camera and to assess the agreement between the 2 instruments when measuring healthy eyes and eyes with keratoconus. Department of Ophthalmology, Medical and Health Science Center, University of Debrecen, Debrecen, Hungary. Evaluation of diagnostic test or technology. Three consecutive series of anterior segment images were taken with AS-OCT (Casia SS-1000) followed by rotating Scheimpflug imaging (Pentacam high resolution). Axial keratometry in the steep and flat meridians and astigmatism values were recorded. Pachymetry in the apex, center, and the thinnest position and anterior chamber depth (ACD) measurements were also taken. This study enrolled 57 healthy volunteers (57 eyes) and 56 patients (84 eyes) with keratoconus. Significant difference was found in all measured anterior segment parameters between normal eyes and keratoconic eyes (P<.05). In keratoconic eyes, the difference between repeated measurements was less with AS-OCT than with Scheimpflug imaging in every keratometry and astigmatism value, in apical thickness, and in ACD. For keratometry, the thinnest and central pachymetry measurement repeatability was better in healthy eyes than in keratoconic eyes with both instruments. In general, the mean difference between AS-OCT and Scheimpflug imaging was higher in cases of keratoconus. Significant differences in keratometry, pachymetry, and ACD results were found between AS-OCT and Scheimpflug imaging. However, the repeatability of the measurements was comparable. No author has a financial or proprietary interest in any material or method mentioned.


Anti-metatype antibodies stabilize the fluorescein single-chain antibody 4-4-20 complex against dissociation by hydrostatic pressure.
Hydrostatic pressure was used to promote dissociation of fluorescein (Fl) from single-chain antibody 4-4-20 (SCA 4-4-20). Fl fluorescence intensity was quenched by 97% upon binding to SCA 4-4-20. Increasing pressure to 2.4 kbar enhanced Fl fluorescence from the remaining 3% to 14-17%. The capacity of anti-metatype antibodies (anti-Met), which specifically recognize liganded anti-Fl antibodies, to protect against pressure-induced Fl dissociation was tested. Both polyclonal and monoclonal anti-Met antibodies protected against Fl dissociation, reducing the fluorescence intensity at 2.4 kbar from 14-17% to 6-8%. Additive effects of anti-Met antibodies in protection against pressure-induced Fl dissociation were suggested by the fact that a 2-fold molar excess polyclonal anti-Met reagent promoted additional protection relative to an equimolar amount. On the other hand, combination of different monoclonal anti-Met antibodies did not promote additive protection, suggesting recognition of overlapping metatopes by these monoclonals. The complex formed by SCA 4-4-20 and the Fl analog HPF was more sensitive to pressure than the Fl-SCA 4-4-20 complex. Addition of both polyclonal and monoclonal anti-Met antibodies reduced the Fl fluorescence recovery at 2.4 kbar from 75% to 40-55%. In order to directly study binding of anti-Met antibodies to mAb 4-4-20, monoclonal anti-Met antibody 3A5-1 was labeled with 2-dimethylaminonaphthalene-5-sulfonyl chloride (2,5-Dns-Cl) and Dns fluorescence anisotropy measured. Unliganded mAb 4-4-20 did not bind to 2,5-Dns-3A5-1 as indicated by the absence of measurable changes in Dns fluorescence anisotropy upon increasing mAb concentration. Addition of mAb 4-4-20 bound to Fl produced a sigmoidal increase in Dns anisotropy, compatible with association of the primary immune complex and 3A5-1. An affinity constant, K0.5, of 1.5 x 10(-7) M and a cooperativity coefficient (n) of 3.1 were calculated for formation of the Fl-mAb 4-4-20 complex. The HPF-mAb 4-4-20 complex was also recognized by 2,5-Dns-3A5-1 but with lower affinity, indicating that the monoclonal anti-Met 3A5-1 distinguished between mAb 4-4-20 liganded to different haptens.


Quantum pBac: An effective, high-capacity piggyBac-based gene integration vector system for unlocking gene therapy potential.
Recent advances in gene therapy have brought novel treatment options for cancer. However, the full potential of this approach has yet to be unlocked due to the limited payload capacity of commonly utilized viral vectors. Virus-free DNA transposons, including piggyBac, have the potential to obviate these shortcomings. In this study, we improved a previously modified piggyBac system with superior transposition efficiency. We demonstrated that the internal domain sequences (IDS) within the 3' terminal repeat domain of hyperactive piggyBac (hyPB) donor vector contain dominant enhancer elements. Plasmid-free donor vector devoid of IDS was used in conjunction with a helper plasmid expressing Quantum PBase™ v2 to generate an optimal piggyBac system, Quantum pBac™ (qPB), for use in T cells. qPB outperformed hyPB in CD20/CD19 CAR-T production in terms of performance as well as yield of the CAR-T cells produced. Furthermore, qPB also produced CAR-T cells with lower donor-associated variabilities compared to lentiviral vector. Importantly, qPB yielded mainly CD8+ CAR-TSCM cells, and the qPB-produced CAR-T cells effectively eliminated CD20/CD19-expressing tumor cells both in vitro and in vivo. Our findings confirm qPB as a promising virus-free vector system with an enhanced payload capacity to incorporate multiple genes. This highly efficient and potentially safe system will be expected to further advance gene therapy applications.


Outcomes of 43 small breed dogs treated for splenic hemangiosarcoma.
To determine outcome and prognostic factors in small breed dogs in which hemangiosarcoma was diagnosed and whether outcomes differed between small and large breed dogs with splenic hemangiosarcoma. Bi-institutional retrospective study. Forty-three small breed (<20 kg) and 94 large breed client-owned dogs. Medical records were reviewed to identify dogs treated with splenectomy for splenic hemangiosarcoma. Data acquired included signalment, preoperative staging, bloodwork results, surgical findings, histopathologic findings, administration of chemotherapy, presence/absence of metastatic disease, and survival time (ST). Cox proportional hazards regression analysis was performed to assess prognostic factors associated with survival. The overall median ST was 116 days and 97 days for small and large breed dogs, respectively. The ST for dogs treated with surgery and chemotherapy was 207 and 139 days for small and large breed dogs, respectively. The disease-free interval (DFI) was 446 and 80 days for small and large breed dogs, respectively. Dog size was associated with DFI (P = .02) but not with ST (P = .09). The presence of metastasis at diagnosis was associated with decreased ST in small (P = .03) and large (P = .0009) breed dogs. Administration of chemotherapy (P = .02) was associated with increased ST (P = .02) in small breed dogs. The ST was not different in small and large breed dogs with splenic hemangiosarcoma treated with splenectomy and chemotherapy. Prognosis remains poor despite aggressive therapies in small and large breed dogs.


Hypothalamic-pituitary responses to high concentrations of gonadal steroids in a three-month-old infant with a feminizing gonadal stromal tumor.
A 3-month-old female infant feminized by an ovarian stromal tumor is presented. Clinicopathologic aspects of such tumors occurring in infancy are discussed. In addition, the evaluation of hypothalamic-pituitary function preoperatively and postoperatively are presented. In the preoperative, high-steroid environment, both basal and stimulated secretion of follicle-stimulating hormone (FSH) was suppressed. Secretion of luteinizing hormone (LH) was normal. Following surgical castration, stimulated secretion of both gonadotropins clearly increased. These findings suggest an active but less sensitive negative feedback mechanism for FSH than for LH during infancy, i.e., high concentrations of gonadal steroids are necessary to maximally suppress FSH secretion while normal steroid concentrations appear to maximally suppress LH secretion. Developmental changes in hypothalamic-pituitary sensitivity to negative feedback controls are discussed in light of these findings.


Induction of a chemoattractive proinflammatory cytokine response after stimulation of keratinocytes with Propionibacterium acnes and coproporphyrin III.
The inflammation in acne vulgaris is widely thought to be induced by an immunological reaction, but the role of Propionibacterium acnes is unclear. To examine the local host response mechanism of a keratinocyte cell line 3 h and 6 h after stimulation with viable and heat-killed P. acnes. The quantitative expression of cytokines was measured at the mRNA level by real-time reverse transcription-polymerase chain reaction. The coincubation of a keratinocyte cell line with viable, but not heat-killed, P. acnes modulated an adequate cytokine response for interleukin (IL)-1beta, granulocyte/macrophage colony-stimulating factor and IL-8. High-performance liquid chromatographic analysis of the in vivo porphyrin pattern secreted by P. acnes revealed a predominance of coproporphyrin III in acne lesions. This same porphyrin fraction also modestly induced IL-8 expression by keratinocytes. This cytokine pattern may favour a chemotactic response and implicates P. acnes and coproporphyrin III in the recruitment of inflammatory cells to the site of infection and in the development of acne lesions.


The involvement of neuropeptide Y in the antimuricide action of noradrenaline injected into the medial amygdala of olfactory bulbectomized rats.
The present study was designed to clarify the functional role of neuropeptide Y (NPY) in the regulation of muricide induced by olfactory bulbectomy (OB) in relation to that of noradrenaline (NA) in the medial amygdala (AME). NA injected into AME inhibited muricide dose-dependently in OB rats. NPY at doses of 5 and 10 micrograms/microliter injected alone into AME failed to suppress muricide. When NPY 10 micrograms was injected into AME in combination with the maximal non-effective dose of NA, which was determined in each rat, muricide was suppressed in 80% of OB rats. The present study has provided the first evidence suggesting that NPY may be involved in the regulation of OB-induced muricide.


Facilitated sexual behavior reversed and serotonin restored by raphe nuclei transplanted into denervated hypothalamus.
Fetal raphe cells transplanted into the hypothalamus reversed facilitation of feminine sexual behavior in rats with brain lesions induced by 5,7-dihydroxytryptamine. Immunocytochemical and chemical analyses of serotonin indicate that reinnervation of the ventromedial nucleus of the hypothalamus by the transplants is associated with behavioral recovery. The findings suggest that transplanted fetal tissue can exert functional regulation over an innate, complex, hormone-dependent behavior in adult rats.


Protein kinase C inhibitors block generation of anoxia-induced long-term potentiation.
The aim of this study was to study the possible intracellular mechanisms underlying the anoxia-induced long-term potentiation (anoxic LTP) in the CA1 neurons of rat hippocampal slices using extra- and intracellular recording techniques. Superfusion of the hippocampal slices with the protein kinase C (PKC) inhibitors NPC-15437 (20 microM) or H-7 (20 microM) specifically prevented the induction of anoxic LTP. Moreover, the anoxic LTP was completely abolished in neurons intracellularly recorded with the selective PKC inhibitor PKCI 19-36 (50 microM). The specific cAMP-dependent protein kinase (PKA) inhibitor Rp-cyclic adenosine 3',5'-monophosphate (Rp-cAMPS, 25 microM) had no effect on the anoxic LTP. It is concluded that induction of anoxic LTP requires the activation of postsynaptic PKC.


Deterioration of chest wall depression causing congestive hepatopathy after an open thoracostomy window in a patient with pectus excavatum and tuberculosis empyema.
A 27-year-old man with severe pectus excavatum, dextrocardia and spinal scoliosis underwent thoracoscopic pleural decortication due to failure of 1-month medical treatment for tuberculous empyema. One month after the pleural decortication, he again underwent open thoracostomy window for repetitive pleuro-cutaneous fistula with tuberculosis empyema. He was subsequently referred to our clinic for progressive dyspnea and bilateral leg edema 4 months after the open thoracostomy window. Evaluations revealed deterioration of the chest wall depression and further compression of the inferior vena cava, which were considered an aggravation of the pectus excavatum after the open thoracostomy window. Herein, we present an extremely rare case of deterioration of chest wall depression causing congestive hepatopathy after an open thoracostomy window in a patient with pectus excavatum and tuberculosis empyema.


Haemoptysis as a prognostic factor in lung adenocarcinoma after curative resection.
Haemoptysis is a common symptom of lung cancer. Its prognostic role and mechanisms are still poorly understood. We retrospectively reviewed 666 consecutive patients with primary lung adenocarcinoma who underwent complete resection. The prognostic value of haemoptysis with respect to overall survival (OS), disease-specific survival (DSS) and disease-free survival (DFS) was analysed. To further explore the possible mechanisms of haemoptysis, we evaluated vascular endothelial growth factor (VEGF) expression, tumour necrosis, vascular invasion and extratumoural microvessel density (MVD) in 112 randomly selected patients. Haemoptysis predicted poor OS, DSS and DFS in operable lung adenocarcinoma (all P<0.001). In addition, haemoptysis was associated with high white blood cell (WBC) count (P=0.032), high fibrinogen (Fib; P<0.001), high tumour greatest dimension (P<0.001), severe vascular invasion (P=0.002) and central tumour location (P<0.001). We obtained no statistically significant differences of VEGF expression, tumour necrosis and extratumoural MVD in haemoptysis and non-haemoptysis groups. Our study demonstrates that haemoptysis predicts poor OS, DSS and DFS in lung adenocarcinoma after curative resection. Vascular invasion rather than angiogenesis or tumour necrosis could be the most important mechanism of haemoptysis in lung adenocarcinoma.


[Evaluation of the speech outcomes in patients with unilateral maxillary defect rehabilitated with maxillary obturator prosthesis].
Evaluation of the outcomes in 15 patients with unilateral maxillary defect before and after maxillofacial obturator prosthesis. 15 patients with unilateral maxillary defect were included in this study, who received obturator prosthesis for maxillary rehabilitation. The pronunciation of the examined phonetics such as /a/, /o/, /e/, /i/, /u/ were transferred into CSL4400 before and after treatment. The mean value of the first, second, third formant were measured. Paired t test of SPSS11.0 was used for statistical analysis. There was statistically significant difference on F2 and F3 before and after treatment (P<0.05). After treatment the value of F3 was increased significantly. The soft palate was reconstructed after obturator treatment. The space between the nasal and oral cavity was sealed,through which a similar normal oral cavity was obtained. Except F1, F2 and F3 of all the vowels changed after treatment. Maxillofacial prosthesis can improve the speech function of patients with unilateral maxillary defect effectively.


Astrocyte-conditioned saline supports embryonic rat hippocampal neuron differentiation in short-term cultures.
Embryonic rat hippocampal neurons were cultured for 1-2 days in serum-free, HEPES-buffered Tyrode's solution. The effects of cortical astrocytes and astrocyte-conditioned saline on neuron survival, membrane surface area and the expression of functional amino acid neurotransmitter receptors were studied. Neurons grown in Tyrode's solution alone survived well for 1 day but deteriorated thereafter both in terms of percent neurons surviving and the amplitudes and densities of GABA-, glycine-, kainate-and NMDA-induced currents. Neurons grown in Tyrode's previously conditioned by astrocytes for 24 h had significantly larger apparent plasma membrane surface area, as indexed by whole-cell membrane capacitance, and larger amplitudes and densities of the amino acid-induced currents after both 1 and 2 days. The survival rate and neurite outgrowth were also greater in the astrocyte-conditioned saline group after 2 days in culture. Similarly, neurons cultured on glass cover-slips facing a confluent monolayer of astrocyte were larger in apparent plasma membrane area and amino acid-induced currents than neurons cultured in Tyrode's alone. Neurons cultured in saline conditioned by astrocytes provide a strategy to study the physiological basis of astrocyte-directed neuronal differentiation in the absence of ambiguities arising from the inclusion of sera and other additives often used in vitro.


Viral vectors engineered for gene therapy.
Gene therapy has seen major progress in recent years. Viral vectors have made a significant contribution through efficient engineering for improved delivery and safety. A large variety of indications such as cancer, cardiovascular, metabolic, hematological, neurological, muscular, ophthalmological, infectious diseases, and immunodeficiency have been targeted. Viral vectors based on adenoviruses, adeno-associated viruses, herpes simplex viruses, retroviruses including lentiviruses, alphaviruses, flaviviruses, measles viruses, rhabdoviruses, Newcastle disease virus, poxviruses, picornaviruses, reoviruses, and polyomaviruses have been used. Proof-of-concept has been demonstrated for different indications in animal models. Therapeutic efficacy has also been achieved in clinical trials. Several viral vector-based drugs have been approved for the treatment of cancer, and hematological, metabolic, and neurological diseases. Moreover, viral vector-based vaccines have been approved against COVID-19 and Ebola virus disease.


Effect of nephrotoxicants and hepatotoxicants on gene expression profile in human peripheral blood mononuclear cells.
Studying peripheral blood transcriptome in the quest for translational markers of toxicity is considered to be an attractive offshoot in the field of toxicogenomics. Moreover, it is acknowledged that, xenobiotics which cause a toxic response through similar mechanisms lead to distinctive gene expression patterns. The current study was undertaken to gauge the response of an accessible surrogate tissue, such as blood, to drug-induced perturbations aimed at deriving gene expression patterns. Human peripheral blood mononuclear cells (hPBMC) were exposed to conventional drugs, with reported kidney and/or liver injury, in order to determine their transcriptomic response. Test drugs were divided into two classes viz., drugs affecting kidney (cyclophosphamide, amphotericin B, gentamicin and cisplatin) and liver (acetaminophen, rosiglitazone, fluconazole and isoniazid). After performing gene expression analysis and hierarchical clustering, signature patterns for the two classes were obtained, with a set of 365 genes that can discriminate the two classes of drugs. Our results imply that transcriptional profile of hPBMC get altered as a consequence of drug exposure and unique patterns indicative of specific organ toxicity can hence be deduced. These signature patterns obtained for drugs could be studied for their qualification to identify drug-induced toxicity.


Author Correction: Binding of the protein ICln to α-integrin contributes to the activation of IClswell current.
An amendment to this paper has been published and can be accessed via a link at the top of the paper.


Exploration of patient-centered success criteria and clinically measured improvement during falls rehabilitation.
One method for defining successful rehabilitation outcomes is to use a threshold of performance on a clinical measure. Patients also have their own criteria for success. The aim of this study was to examine the association between clinical measures and patient criteria for determining successful intervention. Twenty-two participants participated in a 12-week intervention program for balance disorders. Participants were tested using the Berg balance scale (BBS) and dynamic gait index (DGI) at the first and final visits. They also used the patient's perspective outcomes questionnaire (PPOQ) at the first visit to rate impairments in the core domains from the international classification of Function. Participants rated their usual levels of impairment across domains, their desired levels of impairment after intervention (success criteria), and how important it was to change in each domain. At the final visit, all participants used the PPOQ to rate their current impairment across domains and completed a 15-point global rating of change (GRC). The intervention was defined as a success if the participant rated himself or herself as "a great deal" or "a very great deal" better using the GRC. Changes in the BBS and the DGI were dichotomized on the basis of whether the change exceeded the minimal detectable change (MDC) of the instrument. Participants' ratings of impairment at 12 weeks were compared with their success criteria and dichotomized on the basis of whether the success criteria had been met. The Freidman test was used to test differences across domains at baseline with Wilcoxon tests for follow-up. Wilcoxon tests were also used to examine the importance of change across domains. Chi-square tests were used to explore the association among the GRC, performance on clinical tests, and whether success criteria were met. Significant changes were noted for the group for both BBS (P < .001) and DGI (P = .006). Only 40% of participants exceeded or met their desired or expected change in impairment for mobility. No significant associations were noted between exceeding MDC on the BBS or DGI and any of the domains on the PPOQ (all Ps = .263). Bivariate associations were noted between baseline measures of psychological factors and many of the participant ratings of impairment. Fifty-five percent of participants indicated that they were a great deal better or a very great deal better. Significant association was identified between success and exceeding MDC on the BBS (χ = 5.84, P = .016) but not the DGI. When considering participants' desired change in impairment, only meeting desired changes in mental function was associated with considering the intervention a success (χ = 4.55, P = .033). Treatment success from the perspective of this group of older adults was related to improvement on a clinic-based performance measure and not the participants' intrinsic success criteria assessed at the beginning of the intervention. Making measurable change in gait and balance translates into perceived success for the patient with a balance disorder.


Characterization of MgO nanocatalyst to produce biodiesel from goat fat using transesterification process.
In this study, biodiesel was produced from goat fat in the presence of magnesium oxide (MgO) nano-catalyst using transesterification process. The characteristics of the catalyst were studied using field emission scanning electron microscope (FE-SEM), transmission electron microscope (TEM), Brunauer-Emmett-Teller (BET), energy dispersive X-ray/mapping (EDX/Map), Fourier-transform infrared spectroscopy (FTIR), thermal gravimetric analysis (TGA), and dynamic light scattering (DLS). The result showed that the specific surface area and the average pore diameter of the nanocatalyst were 40.44 m2/g and 36.7 nm, respectively, which showed that the catalyst is mesoporous. According to the results of the DLS analysis, the average particle size of the catalyst was determined to be 5.5 nm. Also, the maximum biodiesel yield of 93.12% was obtained at temperature of 70 °C, methanol/oil molar ratio of 12:1, the catalyst content of 1 wt.%, and reaction time of 3 h. In addition, biodiesel was mixed with diesel at different ratios (B25, B50, B75, and B100) to improve fuel properties of the produced biodiesel. The results indicated that the mixtures of B75 and B100 had better density, viscosity, and flash point in comparison to the other mixtures and their properties were within the range of international standards.


Cystic meningiomas.
Twenty-two cases of unusual intracranial meningioma associated with a cyst are reported and 144 published cases reviewed. The complex mechanisms leading to the formation of the cyst within the meningioma are analyzed on the basis of the surgical and histopathological evidence. The neuroradiological features (Computed Tomography and Angiography) which supply a correct preoperative diagnosis are discussed. It is clear from the literature how difficult preoperative diagnosis is, being possible only in 38% of cases with CT scanning and in 13% with angiography. It is necessary to remove not only the solid portion of the meningioma but also the cyst wall in order to prevent a recurrence. This is technically difficult for the type II intratumoural variety of Nauta's classification.


circCAPRIN1 interacts with STAT2 to promote tumor progression and lipid synthesis via upregulating ACC1 expression in colorectal cancer.
Circular RNAs (circRNAs) generated by back-splicing of precursor mRNAs (pre-mRNAs) are often aberrantly expressed in cancer cells. Accumulating evidence has revealed that circRNAs play a critical role in the progression of several cancers, including colorectal cancer (CRC). However, the current understandings of the emerging functions of circRNAs in CRC lipid metabolism and the underlying molecular mechanisms are still limited. Here, we aimed to explore the role of circCAPRIN1 in regulating CRC lipid metabolism and tumorigenesis. circRNA microarray was performed with three pairs of tumor and non-tumor tissues from CRC patients. The expression of circRNAs were determined by quantitative PCR (qPCR) and in situ hybridization (ISH). The endogenous levels of circRNAs in CRC cells were manipulated by transfection with lentiviruses overexpressing or silencing circRNAs. The regulatory roles of circRNAs in the occurrence of CRC were investigated both in vitro and in vivo using gene expression array, RNA pull-down/mass spectrometry, RNA immunoprecipitation assay, luciferase reporter assay, chromatin immunoprecipitation analysis, and fluorescence in situ hybridization (FISH). Among circRNAs, circCAPRIN1 was most significantly upregulated in CRC tissue specimens. circCAPRIN1 expression was positively correlated with the clinical stage and unfavorable prognosis of CRC patients. Downregulation of circCAPRIN1 suppressed proliferation, migration, and epithelial-mesenchymal transition of CRC cells, while circCAPRIN1 overexpression had opposite effects. RNA sequencing and gene ontology analysis indicated that circCAPRIN1 upregulated the expressions of genes involved in CRC lipid metabolism. Moreover, circCAPRIN1 promoted lipid synthesis by enhancing Acetyl-CoA carboxylase 1 (ACC1) expression. Further mechanistic assays demonstrated that circCAPRIN1 directly bound signal transducer and activator of transcription 2 (STAT2) to activate ACC1 transcription, thus regulating lipid metabolism and facilitating CRC tumorigenesis. These findings revealed the oncogenic role and mechanism of circCAPRIN1 in CRC. circCAPRIN1 interacted with STAT2 to promote CRC tumor progression and lipid synthesis by enhancing the expression of ACC1. circCAPRIN1 may be considered as a novel potential diagnostic and therapeutic target for CRC patients.


[Relationship between indicators of equilibrium function and spatial-form perception in children with posture disorders].
The balance function and spatial-figurative thinking (SFT) of children aged 7 to 9 with and without disturbances of bearing were studied. A negative correlation was revealed between balance function and SFT in children with disordered bearing. The results of this study should be taken into account when carrying out hygienic measures for the prevention of bearing disorders in children.


Increase in vascular permeability and vasodilation are critical for proangiogenic effects of stem cell therapy.
Proangiogenic cell therapy based on administration of bone marrow-derived mononuclear cells (BMCs) or endothelial progenitor cells (EPCs) is now under investigation in humans for the treatment of ischemic diseases. However, mechanisms leading to the beneficial effects of BMCs and EPCs remain unclear. BMC- and CD34+-derived progenitor cells interacted with ischemic femoral arteries through SDF-1 and CXCR4 signaling and released nitric oxide (NO) via an endothelial nitric oxide synthase (eNOS)-dependent pathway. BMC-induced NO production promoted a marked vasodilation and disrupted vascular endothelial-cadherin/beta-catenin complexes, leading to increased vascular permeability. NO-dependent vasodilation and hyperpermeability were critical for BMC infiltration in ischemic tissues and their proangiogenic potential in a model of hindlimb ischemia in mice. Our results propose a new concept that proangiogenic progenitor cell activity does not rely only on their ability to differentiate into endothelial cells but rather on their capacity to modulate the function of preexisting vessels.


PROX1 Inhibits PDGF-B Expression to Prevent Myxomatous Degeneration of Heart Valves.
Cardiac valve disease is observed in 2.5% of the general population and 10% of the elderly people. Effective pharmacological treatments are currently not available, and patients with severe cardiac valve disease require surgery. PROX1 (prospero-related homeobox transcription factor 1) and FOXC2 (Forkhead box C2 transcription factor) are transcription factors that are required for the development of lymphatic and venous valves. We found that PROX1 and FOXC2 are expressed in a subset of valvular endothelial cells (VECs) that are located on the downstream (fibrosa) side of cardiac valves. Whether PROX1 and FOXC2 regulate cardiac valve development and disease is not known. We used histology, electron microscopy, and echocardiography to investigate the structure and functioning of heart valves from Prox1ΔVEC mice in which Prox1 was conditionally deleted from VECs. Isolated valve endothelial cells and valve interstitial cells were used to identify the molecular mechanisms in vitro, which were tested in vivo by RNAScope, additional mouse models, and pharmacological approaches. The significance of our findings was tested by evaluation of human samples of mitral valve prolapse and aortic valve insufficiency. Histological analysis revealed that the aortic and mitral valves of Prox1ΔVEC mice become progressively thick and myxomatous. Echocardiography revealed that the aortic valves of Prox1ΔVEC mice are stenotic. FOXC2 was downregulated and PDGF-B (platelet-derived growth factor-B) was upregulated in the VECs of Prox1ΔVEC mice. Conditional knockdown of FOXC2 and conditional overexpression of PDGF-B in VECs recapitulated the phenotype of Prox1ΔVEC mice. PDGF-B was also increased in mice lacking FOXC2 and in human mitral valve prolapse and insufficient aortic valve samples. Pharmacological inhibition of PDGF-B signaling with imatinib partially ameliorated the valve defects of Prox1ΔVEC mice. PROX1 antagonizes PDGF-B signaling partially via FOXC2 to maintain the extracellular matrix composition and prevent myxomatous degeneration of cardiac valves.


Isolated granulomatous gastritis. Treatment with corticosteroids.
Granulomatous disease of the stomach is a rare disorder with multiple causes. We successfully treated a patient who had granulomatous disease that was confined to the gastric antrum with corticosteroids. We believe this is the first such report.


The Escherichia coli SeqA protein destabilizes mutant DnaA204 protein.
In wild-type Escherichia coli cells, initiation of DNA replication is tightly coupled to cell growth. In slowly growing dnaA204 (Ts) mutant cells, the cell mass at initiation and its variability is increased two- to threefold relative to wild type. Here, we show that the DnaA protein concentration was two- to threefold lower in the dnaA204 mutant compared with the wild-type strain. The reason for the DnaA protein deficiency was found to be a rapid degradation of the mutant protein. Absence of SeqA protein stabilized the DnaA204 protein, increased the DnaA protein concentration and normalized the initiation mass in the dnaA204 mutant cells. During rapid growth, the dnaA204 mutant displayed cell cycle parameters similar to wild-type cells as well as a normal DnaA protein concentration, even though the DnaA204 protein was highly unstable. Apparently, the increased DnaA protein synthesis compensated for the protein degradation under these growth conditions, in which the doubling time was of the same order of magnitude as the half-life of the protein. Our results suggest that the DnaA204 protein has essentially wild-type activity at permissive temperature but, as a result of instability, the protein is present at lower concentration under certain growth conditions. The basis for the stabilization in the absence of SeqA is not known. We suggest that the formation of stable DnaA-DNA complexes is enhanced in the absence of SeqA, thereby protecting the DnaA protein from degradation.


Ag-doped Cu nanosheet arrays for efficient hydrogen evolution reaction.
A zinc-infiltration process was adopted to prepare silver-doped copper nanosheet arrays. The larger atomic radius of Ag introduces tensile stress, which lowers the electron density at the s-orbitals of Cu atoms and improves the adsorption capability for hydrogen atoms. As a catalyst for hydrogen evolution, these silver doped copper nanosheet arrays achieved a low overpotential of 103 mV at 10 mA cm-2 in 1 M KOH, which is 604 mV lower than that of pure copper foil.


Construction and analysis of genomic, full-length infectious foamy virus DNA clones.
The molecular engineering of recombinant plasmid DNA clones containing the full-length and replication-competent feline foamy (retro)virus (FFV) proviral genome is described. The methods used to combine subgenomic FFV DNA fragments can be applied to other retrovirus genomes, resulting in full-length, bacterially cloned retroviruses. In addition, techniques used to determine the replication competence of the cloned viral genomes are described. Alternative technologies (not described here) are also discussed, together with the application of cloned genomes in modern molecular virology; for example, in functional genetic studies or as starting material for retrovirus vector development.


Biotechnology of Rhodococcus for the production of valuable compounds.
Bacteria belonging to Rhodococcus genus represent ideal candidates for microbial biotechnology applications because of their metabolic versatility, ability to degrade a wide range of organic compounds, and resistance to various stress conditions, such as metal toxicity, desiccation, and high concentration of organic solvents. Rhodococcus spp. strains have also peculiar biosynthetic activities that contribute to their strong persistence in harsh and contaminated environments and provide them a competitive advantage over other microorganisms. This review is focused on the metabolic features of Rhodococcus genus and their potential use in biotechnology strategies for the production of compounds with environmental, industrial, and medical relevance such as biosurfactants, bioflocculants, carotenoids, triacylglycerols, polyhydroxyalkanoate, siderophores, antimicrobials, and metal-based nanostructures. These biosynthetic capacities can also be exploited to obtain high value-added products from low-cost substrates (industrial wastes and contaminants), offering the possibility to efficiently recover valuable resources and providing possible waste disposal solutions. Rhodococcus spp. strains have also recently been pointed out as a source of novel bioactive molecules highlighting the need to extend the knowledge on biosynthetic capacities of members of this genus and their potential utilization in the framework of bioeconomy. KEY POINTS: • Rhodococcus possesses promising biosynthetic and bioconversion capacities. • Rhodococcus bioconversion capacities can provide waste disposal solutions. • Rhodococcus bioproducts have environmental, industrial, and medical relevance. Graphical abstract.


Changes in the pattern of SDH and PhR staining in fibres of rat masseter muscle following long-term functional stretch.
Histochemical changes in the three basic fibre types of the deep masseter muscle of the rat were studied following functional stretch due to increased vertical dimension of the occlusion. A large number of muscle fibres showed changing histochemical profiles for succinic dehydrogenase (SDH) and phosphorylase (PhR) during degeneration and subsequent regeneration of muscle fibres. On the other hand, a small number of muscle fibres with well defined sarcolemmas presented a normal pattern (i.e. low SDH and high or intermediate PhR activities) during this experiment. The ratio between the three basic fibre types remained unchanged after recovery of the muscle fibres. These results suggest that fast-twitch-oxidative-glycolytic and slow-twitch-oxidative fibres underwent degeneration and regeneration, while almost all the fast-twitch-glycolytic fibres retained normal SDH and PhR staining following functional stretch.


Low tidal volume ventilation induces proinflammatory and profibrogenic response in lungs of rats.
We examined whether mechanical ventilation with low tidal volume induces polymorphonuclear infiltration and proinflammatory and profibrogenic responses in rat lungs compared dependent and nondependent lung region to expression of interleukin-1beta (IL-1beta) and alpha-1 procollagen III (PC III) mRNA. An experimental, randomized and controlled protocol with previously normal rats. Three groups of ten animals were studied. Two groups were ventilated (FIO2=0.3) in supine position for 1 h without positive end expiratory pressure, one group with a low tidal volume (6 ml/kg), and the other with a high tidal volume (24 ml/kg). In the third group animals were kept in spontaneous ventilation for 1 h. After ventilation the right lung was used to quantify polymorphonuclear infiltration. The left lung was divided into dependent and nondependent regions, and expression of IL-1beta and PC III mRNA was quantified by northern blot analysis. The group ventilated with low tidal volume had greater polymorphonuclear infiltration IL-1beta and PC III mRNA expression than the nonventilated group. Similar results were observed with high tidal volumes. There was no difference between low and high tidal volume ventilation. Expression levels of IL-1beta and PC III mRNA were higher in the nondependent region of ventilated groups and equal in the nonventilated group. Even a low tidal volume mode of mechanical ventilation induces proinflammatory and profibrogenic response, with a nondependent predominance for IL-1beta and PC III mRNA expression in supine, ventilated, previously normal rats.


Wearing graduated compression stockings augments cutaneous vasodilation in heat-stressed resting humans.
We investigated whether graduated compression induced by stockings enhances cutaneous vasodilation in passively heated resting humans. Nine habitually active young men were heated at rest using water-perfusable suits, resulting in a 1.0 °C increase in body core temperature. Heating was repeated twice on separate occasions while wearing either (1) stockings that cause graduated compression (pressures of 26.4 ± 5.3, 17.5 ± 4.4, and 6.1 ± 2.0 mmHg at the ankle, calf, and thigh, respectively), or (2) loose-fitting stockings without causing compression (Control). Forearm vascular conductance during heating was evaluated by forearm blood flow (venous occlusion plethysmography) divided by mean arterial pressure to estimate heat-induced cutaneous vasodilation. Body core (esophageal), skin, and mean body temperatures were measured continuously. Compared to the Control, forearm vascular conductance during heating was higher with graduated compression stockings (e.g., 23.2 ± 5.5 vs. 28.6 ± 5.8 units at 45 min into heating, P = 0.001). In line with this, graduated compression stockings resulted in a greater sensitivity (27.5 ± 8.3 vs. 34.0 ± 9.4 units °C-1, P = 0.02) and peak level (25.5 ± 5.8 vs. 29.7 ± 5.8 units, P = 0.004) of cutaneous vasodilation as evaluated from the relationship between forearm vascular conductance with mean body temperature. In contrast, the mean body temperature threshold for increases in forearm vascular conductance did not differ between the Control and graduated compression stockings (36.5 ± 0.1 vs. 36.5 ± 0.2 °C, P = 0.85). Our results show that graduated compression associated with the use of stockings augments cutaneous vasodilation by modulating sensitivity and peak level of cutaneous vasodilation in relation to mean body temperature. However, the effect of these changes on whole-body heat loss remains unclear.


Translation and validation of the Chinese version of the Current Opioid Misuse Measure (COMM) for patients with chronic pain in Mainland China.
Management of prescription opioids misuse and abuse problems among chronic pain patients has been increasingly important worldwide and little literature concerning prescription opioids can be found in mainland China so far. The Current Opioid Misuse Measure (COMM) was translated into Chinese following Brislin's model of cross-culture translation and was completed by a convenience sample of 180 patients with chronic pain recruited from two major hospitals in Jinan, Shandong province. Data were analyzed using internal consistency, test-retest reliability, exploratory factor analysis and confirmatory factor analysis. The internal consistency coefficient for the total score of the COMM was 0.85 and item-total correlations of all items were above 0.20. Besides, the test-retest reliability was satisfactory with an ICC of 0.91 (95% CI = 0.65-0.98). Four principal components were extracted, accounting for 65.30% of the variance, and the factor loadings of all 17 items were above 0.40. The Chinese version of COMM showed satisfactory reliability and validity, and could be used as a screening tool to evaluate and monitor current aberrant drug-related behavior among Chinese patients with chronic pain.


Retracted: Histological Classification and Invasion Prediction of Thymoma by Machine Learning-Based Computed Tomography Imaging.
[This retracts the article DOI: 10.1155/2022/4594757.].


Relationship between controlled attenuated parameter and magnetic resonance imaging-proton density fat fraction for evaluating hepatic steatosis in patients with NAFLD.
We used cross-sectional and longitudinal studies to comprehensively compare hepatic steatosis measurements obtained with magnetic resonance imaging-proton density fat fraction (MRI-PDFF) and controlled attenuated parameter (CAP) in hepatic steatosis in adults with nonalcoholic fatty liver disease (NAFLD). A total of 185 participants with NAFLD and 12 non-NAFLD controls were recruited. CAP and MRI-PDFF data were collected at baseline from all participants and from 95 patients included in the longitudinal study after 24 weeks of drug or placebo intervention. Pearson correlation, linear regression, and piecewise linear regression analyses were used to evaluate the relationship between the two modalities. Linear analysis suggested a positive correlation between CAP and MRI-PDFF (r = 0.577, p < 0.0001); however, piecewise linear regression showed no correlation when CAP was ≥331 dB/m (p = 0.535). In the longitudinal study, both the absolute and relative change measurements were correlated between the two modalities; however, the correlation was stronger for the relative change (relative r = 0.598, absolute r = 0.492; p < 0.0001). Piecewise linear regression analysis revealed no correlation when CAP was reduced by more than 53 dB/m (p = 0.193). Conclusions: We found a correlation between CAP and MRI-PDFF measurements for grading hepatic steatosis when CAP was <331 dB/m. While the measured absolute change and relative change were correlated, it was stronger for the relative change. These findings have implications for the clinical utility of CAP or MRI-PDFF in the clinical diagnosis and assessment of NAFLD.


Predictive factors for treatment response and mortality in chronic pulmonary aspergillosis.
Chronic pulmonary aspergillosis (CPA) is associated with significant mortality, and suboptimal antifungal treatment response. We describe predictive factors for treatment response and survival. We retrospectively analysed clinical, serological and radiological parameters at baseline and following antifungal treatment in patients with CPA and correlated with clinical and radiological response and survival. Fifty-nine patients were included with a mean age of 61 years. Thirty (51%) had a diagnosis of COPD. On clinical assessment at 6 months, 21 (36%) had clinically improved, 20 (34%) were clinically stable and 15 (25%) had deteriorated. Radiological improvement was observed in 30 (53%), stability in 11 (19%) and deterioration in 16 (28%). Only a lower C-reactive protein (CRP) at baseline was associated with a favourable clinical-radiological response. On univariate analysis, lower CRP, higher albumin, lower Aspergillus IgG and use of inhaled steroids were associated with lower mortality. An overall favourable response at 6 months was associated with lower mortality. Inflammatory markers and Aspergillus IgG were predictors of mortality in CPA. This suggests that mortality in CPA is driven mainly by the chronic fungal infection itself rather than the underlying disease, therefore early optimised treatment of CPA may lead to improved outcomes.


Liver enzymes and stroke risk in middle-aged German adults.
To investigate the association between the liver enzymes γ-glutamyltransferase (GGT) and (alanine aminotransferase) ALT and risk of stroke, its subtypes including TIA as well as fatal and non-fatal events. A case-cohort study within the European Prospective Investigation into Cancer and Nutrition-Potsdam Study comprising 27548 middle-aged subjects was designed. GGT and ALT were measured in plasma of 353 individuals who developed a stroke and in 2110 individuals who remained free of cardiovascular events during a mean follow-up of 8.2 ± 2.2 years. Cox proportional-hazard models were applied to evaluate the association between liver enzymes and stroke risk. After adjustment for established clinical and lifestyle factors, a 1 unit change in naturally logged GGT was related to a 1.20 (95%CI: 1.03-1.40) increased stroke risk. Risk estimates did not significantly differ between fatal (Relative Risk (RR) = 1.35, 95%CI: 1.14-1.61) and non-fatal events (RR = 1.15; 95%CI: 0.97-1.36). ALT was not associated with overall stroke risk (RR = 0.95; 95%CI: 0.71-1.26). However, in subtype analyses we observed in multivariable adjusted models a significant increased risk of hemorrhagic stroke (RR = 2.00; 95% CI: 1.01-3.96), but decreased risk of ischemic stroke (RR = 0.66; 95%CI: 0.44-0.998). Our data provide further evidence for a link between GGT, but not ALT and overall stroke suggesting that these biomarkers are involved in different pathways of disease development. Further studies are needed to clarify the putative relationships between ALT and subtypes of stroke.


Embryonic periventricular endothelial cells demonstrate a unique pro-neurodevelopment and anti-inflammatory gene signature.
Brain embryonic periventricular endothelial cells (PVEC) crosstalk with neural progenitor cells (NPC) promoting mutual proliferation, formation of tubular-like structures in the former and maintenance of stemness in the latter. To better characterize this interaction, we conducted a comparative transcriptome analysis of mouse PVEC vs. adult brain endothelial cells (ABEC) in mono-culture or NPC co-culture. We identified > 6000 differentially expressed genes (DEG), regardless of culture condition. PVEC exhibited a 30-fold greater response to NPC than ABEC (411 vs. 13 DEG). Gene Ontology (GO) analysis of DEG that were higher or lower in PVEC vs. ABEC identified "Nervous system development" and "Response to Stress" as the top significantly different biological process, respectively. Enrichment in canonical pathways included HIF1A, FGF/stemness, WNT signaling, interferon signaling and complement. Solute carriers (SLC) and ABC transporters represented an important subset of DEG, underscoring PVEC's implication in blood-brain barrier formation and maintenance of nutrient-rich/non-toxic environment. Our work characterizes the gene signature of PVEC and their important partnership with NPC, underpinning their unique role in maintaining a healthy neurovascular niche, and in supporting brain development. This information may pave the way for additional studies to explore their therapeutic potential in neuro-degenerative diseases, such as Alzheimer's and Parkinson's disease.


Heterogeneity in the chemistry, structure and function of plant cell walls.
Higher plants resist the forces of gravity and powerful lateral forces through the cumulative strength of the walls that surround individual cells. These walls consist mainly of cellulose, noncellulosic polysaccharides and lignin, in proportions that depend upon the specific functions of the cell and its stage of development. Spatially and temporally controlled heterogeneity in the physicochemical properties of wall polysaccharides is observed at the tissue and individual cell levels, and emerging in situ technologies are providing evidence that this heterogeneity also occurs across a single cell wall. We consider the origins of cell wall heterogeneity and identify contributing factors that are inherent in the molecular mechanisms of polysaccharide biosynthesis and are crucial for the changing biological functions of the wall during growth and development. We propose several key questions to be addressed in cell wall biology, together with an alternative two-phase model for the assembly of noncellulosic polysaccharides in plants.


Associations Between Built Environment Characteristics and Walking in Older Adults in a High-Density City: A Study From a Chinese Megacity.
The built environment is an important factor affecting physical activity, especially walkability. Walkability is used to characterize the user friendliness of outdoor physical activity. However, studies on walkability and physical activity are mainly concentrated on low-density Western cities. Study on the walkability of high-density cities in Asia, especially with the elderly, is seriously lacking. And walkability is often used as a composite indicator. This study mainly re-examines the relationship between the common indicators of walkability (population density, street connectivity, land-use mix, and retail density), transport-related walking, and leisure-time walking with older adults in China's megacities. Twelve housing estates in Wuhan were selected for study areas. We explored the association between the walking activities of 1,161 elderly people (≥60 years old) and the indicators of walkability in their neighborhoods. Socio-demographic characteristics were controlled in the multilevel logistic regression models of the built environment walking associations. We found that there was no significant correlation between the four indicators of walkability and transport-related walking. Street connectivity is significantly positively correlated with the participants' leisure-time walking (OR = 1.499, 95% CI = 1.068~2.103), and there was no significant correlation between the other indicator of walkability and leisure-time walking. The results show that there was no statistical correlation between walkability and transport-related walking in the elderly, and only one indicator was related to leisure-time walking. It is extremely important to re-examine the characteristics of built environments and elderly walking activities in high-density cities. Only by implementing effective intervention strategies in different urban backgrounds can cities move toward a more active and healthier path.


Clinical Trial Accrual at Initial Course of Therapy for Cancer and Its Impact on Survival.
This retrospective cohort study sought to characterize the accrual of patients with cancer into clinical trials at the time of diagnosis and analyze the impact of accrual on survival. The National Cancer Database (NCDB) was queried for patients enrolled in clinical trials at their initial course of treatment for 46 cancers from 2004 through 2015. Descriptive statistics were used to characterize the accrual of patients with cancer in clinical trials at diagnosis, and Kaplan-Meier graphical displays, log-rank tests, odds ratios, and stratified Cox proportional hazards models were used to analyze the impact of accrual on overall survival (OS). Strata were defined using 10 variables. Model-based adjusted survival curves of 2 groups were reverse-generated based on a Weibull distribution. Of 12,097,681 patients in the NCDB, 11,576 (0.1%) were enrolled in trials. Patients in clinical trials typically had metastatic disease (30.9% vs 16.4%; P<.0001), were white (88.0% vs 84.8%; P<.0001), had private/managed care insurance (56.4% vs 41.8%; P<.0001), had fewer comorbidities (Charlson-Deyo score 0: 81.9% vs 75.7%; P<.0001, and Charlson-Deyo scores 1-3: 18.1% vs 24.3%; P<.0001) compared with those not in trials. At a median follow-up of 64 months, enrollment in a clinical trial was associated with improved OS in univariate and stratified analyses, with a median survival of 60.0 versus 52.5 months (hazard ratio, 0.876; 95% CI, 0.845-0.907; P<.0001). Stratified analysis with matched baseline characteristics between patients enrolled and not enrolled in a clinical trial showed superior OS at 5 years (95.0% vs 90.2%; P<.0001). Enrollment in clinical trials at first line of therapy in the United States is exceedingly low and favors young, healthy, white patients with metastatic disease and private insurance who are treated at academic medical centers. Patients with cancer treated in clinical trials live longer than those not treated in trials.


Cutaneous side effects of hydroxychloroquine in health care workers in a COVID referral hospital - implications for clinical practice.
The utility of hydroxychloroquine for the prophylaxis and treatment of alarmingly rising COVID-19 infection has been widely explored in several studies. However, its cutaneous adverse effects among health care workers and COVID patients taking prophylactic doses has not been reported. We report cases of palmoplantar among health care workers who were on prophylactic doses of hydroxychloroquine and their management with cetirizine and methylprednisolone.


A study on the effects of interaction between naloxone and 2-Br-alpha-ergocryptine or clonidine on luteinizing hormone, follicle-stimulating hormone, prolactin and thyroid-stimulating hormone levels in normal man serum.
The effects of 2-Br-alpha-ergocryptine (2.5 mg/osM), clonidine (50 microgram, intramuscularly) and naloxone (0.4 mg, intramuscularly) as well as the interaction between naloxone and 2-Br-alpha-ergocryptine or clonidine on luteinizing hormone (LH) follicle-stimulating hormone (FSH), prolactin (PL) and thyroid-stimulating hormone (TSH) serum levels in normal man have been studied. 2-Br-alpha-ergocryptine and clonidine clearly reduce and naloxone tends to reduce PL serum levels. TSH levels are lowered by naloxone as well by clonidine plus naloxone. The results obtained point also to a possible different pattern of LH and FSH secretion after naloxone, that is after opiate receptor blockade. The clonidine effects on PL secretion are discussed in the frame of a possible adrenergic control of the release of this hormone.


Brachial-ankle pulse wave velocity is associated with intracranial artery calcification in acute stroke patients.
Intracranial artery calcification (IAC) is closely associated with cerebrovascular disease. Brachial-ankle pulse wave velocity (baPWV) is a noninvasive method for estimating arterial stiffness, which reflects the stiffness of peripheral arteries. This study aimed to examine the association of baPWV with the presence and degree of IAC in patients with acute ischemic stroke. A total of 143 ischemic stroke subjects were recruited. A head computed tomography (CT) scan was used to assess the presence and severity of IAC. The oscillometric method was used to simultaneously measure bilateral brachial and posterior tibial arterial pulse waveforms and arterial BP. Multiple logistic regression analysis was used to identify the independent relationship between baPWV and IAC. 143 subjects were included in this study. The demographic and clinical characteristics of the study population were classified according to the baPWV quartile. A higher prevalence of IAC was noted across increasing baPWV quartiles (Q1: 53 %, Q2: 69 %, Q3: 86 %, Q4: 94 %, P < 0.001). IAC scores were also increased with elevated ccPWV values (1.60 ± 1.71; 2.56 ± 1.99; 3.44 ± 1.91; 4.64 ± 1.58. P < 0.001). After an additional adjustment for age and hypertension, the odds ratio (95 % confidence interval) for the IAC scores was 1.61 (1.06-2.45; P = 0.025) in the top quartile of baPWV compared with those in the lowest quartile. Arterial stiffness as defined by baPWV was positively associated with the degree of IAC in patients with acute ischemic stroke, suggesting the severity of IAC may also be a marker of peripheral or systemic arterial stiffness.


Cryptosporidium and Giardia in urban wastewater: A challenge to overcome.
This study aimed to quantify Giardia and Cryptosporidium in disinfected water reuse samples from two Wastewater Treatment Plants (A and B), which were quantified by USEPA 1693/2014 Method. Giardia was found in 35.8% of the total samples (<0.03 to 16 cysts/L) while Cryptosporidium in 30.2% (<0.03 to 25.8 oocysts/L). This study highlights the presence of both parasites in water for reuse despite treatment processes for their removal, which means there is a challenge to overcome. Their presence is preoccupant even though in low concentrations because the infectivity dose is low coupled with high prevalence in the global population. The practice of water recycling is valuable for sustainable water management and it is in line with Sustainable Developments Goals but should not threaten human health. Tackling this issue is more critical in developing countries because treatment processes are often more limited, the monitoring data from water reuse are not always available, the lack of regulation for water reuse quality and the lack of planning for its sustainable usage.


Unusual regioselective intramolecular Diels-Alder reaction forming tricyclo[184.108.40.206(3,7)]decane system.
The intramoleculae Diels-Alder reaction of cyclohexenone having an unsaturated ester side chain afforded tricyclo[22.214.171.124(3,7)]decanone in both a regio- and stereoselective manner under TMSCl-NEt(3)-ZnBr(2) conditions. Unexpectedly, the regiochemical control was against the conventional orbital requirement.


Is it possible to shorten serum bactericidal testing?
Serum bactericidal test represents an alternative possibility for optimization of antibiotic treatment. The paper aimed to confirm non-inferiority of bactericidal testing using the broth dilution method according to the CLSI method (M21A) in comparison with turbidimetric and colorimetric modifications. We tested human blood sera (n = 76) of ten hematological patients, their blood was withdrawn prior to and during the course of antibiotic therapy. Testing employed the reference strain Escherichia coli ATCC 25922. The results of the modified turbidimetric method did not differ in a statistically significant way with the use of the wavelengths of 620 nm or 405 nm and the break-point <30% turbidity change after 24-hour incubation. The colorimetric method was also non-inferior from the CLSI method when resazurin was applied after 8-hour incubation and the results of subculture were read after 24-hour incubation. Both tested modifications can represent a shorter alternative to the CLSI reference method.


Clinical and magnetic resonance imaging features of canine compressive cervical myelopathy with suspected hydrated nucleus pulposus extrusion.
To describe clinical and magnetic resonance imaging features in dogs with compressive cervical myelopathy due to acute suspected hydrated nucleus pulposus extrusion. Retrospective case series. Ten dogs with compressive cervical myelopathy caused by acute suspected hydrated nucleus pulposus extrusion. Medical records and magnetic resonance images of dogs evaluated from 2005 through 2010 were reviewed. The inclusion criteria were clinical signs compatible with cervical myelopathy, magnetic resonance imaging of the spine performed within 48 hours after onset, magnetic resonance imaging findings consistent with compressive suspected hydrated nucleus pulposus extrusion, complete medical records and follow-up information. Six dogs were presented with acute onset tetraplegia and four dogs with acute onset of nonambulatory tetraparesis. Compromised respiratory function was present in three dogs. Compressive suspected hydrated nucleus pulposus extrusion was found on magnetic resonance imaging at the C4-C5 (n=6), C3-C4 (n=3) and C5-C6 (n=1) intervertebral disc spaces. Seven dogs underwent surgical treatment and three dogs were treated conservatively. All dogs except one regained ambulatory status within two weeks after the onset, and had a favourable outcome. Compressive myelopathy caused by acute suspected hydrated nucleus pulposus extrusion has not been reported previously and, even though neurological deficits can be severe on presentation, outcome is favourable.


New-onset diabetes after liver transplantation.
The impact of new-onset diabetes (NOD) posttransplantation has been underestimated in the past. The aim of this study was to evaluate the incidence of diabetes after liver transplantation. We retrospectively analyzed the incidence of NOD in 899 patients transplanted in our center. According to International Consensus 2003 Guidelines, criteria for diagnosis of diabetes were: fasting plasma glucose > or =126 mg/dL, symptoms of diabetes plus casual plasma glucose concentrations > or =200 mg/dL, and 2-hour plasma glucose levels > or =200 mg/dL during an oral glucose tolerance test. We considered only patients with follow-up over 10 months. We evaluated the risk factors correlated with NOD (age, hepatitis C virus [HCV] positivity, tacrolimus vs cyclosporine, steatosic graft), and the outcomes of diabetic patient and their grafts. The incidence of NOD was 10.8% (90/830 patients). Sixty nine patients were diabetic before transplantation. Recipient age >45 years (14.7% vs 6.8%, P = .002, OR = 2.4) and HCV positivity (15.5% vs 7.8%, P = .001, OR = 2.2) significantly correlated with NOD. Multivariate analysis confirmed these variables to be independently associated with diabetic risk. Tacrolimus was associated with an increased risk of NOD (16.2% in HCV-negative patients, 25% in HCV-positive patients), but this difference was not statistically significant. Steatotic grafts (>10%) were associated with an increased risk of NOD (28.6% vs 10%, P = .001, OR = 3.6). The outcome of patients and grafts in the group of diabetic patients was not significantly different from all other patients. The incidence of NOD was more relevant in patients older than 45 years and/or HCV-positive. A steatotic graft was an important risk factor, and the match with high-risk patients should be avoided.


[Hereditary and non-hereditary syndromic gastointestinal stromal tumours].
The majority of gastrointestinal stromal tumours (GISTs) present as solitary gastrointestinal masses in adults aged 50-70 years. A small subset of GISTs (≤5%) occurs in the setting of familial or idiopathic multitumour syndrome. In decreasing order of frequency, neurofibromatosis Recklinghausen (NF-1), Carney triad (gastric GIST, pulmonary chondroma and extra-adrenal paraganglioma), familial GIST syndromes resulting from germline mutations in c-Kit/PDGFRA and the Carney-Stratakis syndrome (hereditary GIST paraganglioma syndrome caused by germline mutations in the mitochondrial tumour suppressor gene pathway involving the succinate dehydrogenase subunits SDHD, SDHC and SDHB) represent the four most important GIST syndromes characterized to date. Since affected patients and their family members require special treatment and/or counseling and follow-up, early diagnosis and precise classification of this likely still underdiagnosed diseases is of the utmost importance. This review summarizes the pertinent clinicopathological and molecular features of the main GIST syndromes to facilitate their diagnosis and distinction from their non-syndromic mimics.


Small-incision cholecystectomy (through a cylinder retractor) under local anaesthesia and sedation: a prospective observational study of five hundred consecutive cases.
Transcylindrical cholecystectomy (TC) can be performed under local anaesthesia and sedation (LAS) in ambulatory surgery (AS). The aim of this study was to assess the feasibility and results of TC under LAS. TC under LAS was proposed to 583 consecutive patients with cholelithiasis in an AS unit. For the TC procedure, a cylindrical retractor with a transparent plunger was inserted into the hepatocystic triangle, and cholecystectomy was performed through the retractor with reusable open instruments. Pre-, intra-, and post-operative variables were prospectively registered, including complications, reasons for conversion to general anaesthesia (GA), non-programmed admissions, readmissions, pain assessments, and satisfaction with the procedure. Five hundred patients were eligible for LAS, with GA being required in 128 (25.6%) of them. AS was programmed for 447 patients. The rates of non-programmed admissions, readmissions, and conversion to laparotomy were 8.7% (39), 0.8% (4), and 2.6% (13), respectively. There was no main bile duct injury. At 24 h, physical status was good or excellent in 80.4% of the patients. A history of acute cholecystitis, male sex, a body mass index (BMI) ≥ 39.5 kg/m2, and non-suspected acute cholecystitis were found to be independent variables associated with conversion to GA. TC under LAS is a safe procedure in AS and is feasible in 74% of cholelithiasis patients. Male sex, BMI, gallbladder wall thickness, and a history of acute cholecystitis are factors that increase the probability of conversion to GA. This prospective study was approved by the ethics committee of Badajoz for patient protection for biomedical research and has been retrospectively registered under the research registry UIN: researchregistry3979.


A critical evaluation of the use of filipin-permeabilized rat hepatocytes to study functions of the endoplasmic reticulum in situ.
We have used transmission (TEM) and scanning electron microscopy (SEM) and leakage of lactate dehydrogenase (LDH; EC 126.96.36.199) to evaluate two published procedures which use filipin to render isolated rat hepatocytes permeable to ionic substrates. Cells treated by the procedure of Jorgenson and Nordlie retained less than 10 per cent of their LDH. TEM revealed severe damage to the internal structure of these cells, which included swelling, disintegration and extensive vesicularization of the endoplasmic reticulum (ER). Hepatocytes treated with filipin by the procedure of Gankema et al. retained 65-75 per cent of their LDH and displayed incomplete but highly variable permeability to Trypan blue. SEM revealed the loss of microvilli, other signs of swelling, and the presence of large lesions in the plasma membrane. TEM revealed signs of cell swelling, but the nuclei and the mitochondria were only moderately altered. The rough ER was not swollen, but significant fragmentation was evident and characteristic stacks of lamellar ER were never seen. We conclude that useful information about the functions of the ER in situ cannot be obtained from studies of filipin-treated cells. Our results indicate that retention of LDH is not a sufficient criterion of preservation of cell morphology and that staining with Trypan blue may significantly underestimate the permeability of cells to small ionic metabolites.


Pediatric interventional radiology: current practice and innovations.
The purpose of this article is to provide an update of pediatric interventional procedures for the interventionalist, and especially for those who treat children infrequently. Most pediatric interventional procedures are modifications of techniques devised for adults, in that some are unique to pediatrics. These are stressed in the presentation.


The synthesis of fatty acids in mitochondria, microsomes and supernatant of rat adipose tissue was studied after administration of U-(14)C(-) glucose. The major site of fatty acids synthesis was the supernatant in controls and the microsomes in insulin-treated animals. The action of insulin cannot be explained only by an increase of the intra-cellular penetration of glucose. An action on enzyme synthesis is probable.


Crystal structure of the protein At3g01520, a eukaryotic universal stress protein-like protein from Arabidopsis thaliana in complex with AMP.
Members of the universal stress protein (USP) family are conserved in a phylogenetically diverse range of prokaryotes, fungi, protists, and plants and confer abilities to respond to a wide range of environmental stresses. Arabidopsis thaliana contains 44 USP domain-containing proteins, and USP domain is found either in a small protein with unknown physiological function or in an N-terminal portion of a multi-domain protein, usually a protein kinase. Here, we report the first crystal structure of a eukaryotic USP-like protein encoded from the gene At3g01520. The crystal structure of the protein At3g01520 was determined by the single-wavelength anomalous dispersion method and refined to an R factor of 21.8% (Rfree = 26.1%) at 2.5 Å resolution. The crystal structure includes three At3g01520 protein dimers with one AMP molecule bound to each protomer, comprising a Rossmann-like α/β overall fold. The bound AMP and conservation of residues in the ATP-binding loop suggest that the protein At3g01520 also belongs to the ATP-binding USP subfamily members.


Arousal has no effect on non-nutritive breathing-swallowing coordination during the first year of human life.
Although the brainstem plays an important role in breathing-swallowing coordination (BSC), the role of suprabulbar structures is ill defined. Given the known decrease in global cerebral activity during sleep, the sleep-wake paradigm was used to elucidate suprabulbar influences. Non-nutritive BSC of 10 healthy human infants was monitored longitudinally during wakefulness and sleep from birth to 1 year of age. Time-locked recordings of submental muscle activity, nasal airflow, and thyroid acoustics enabled the categorization of swallows depending on the preceding and following respiratory phase. In contrast to the change in the overall pattern of BSC with age, and despite well-known marked postnatal cortical development over this time, no arousal-related differences were seen during the first year of life. This most likely reflects complete brainstem control of non-nutritive BSC in infants.


Transfer of maternal immunity and programming of the newborn immune system.
As placental mammals, the pregnant women and the fetus have intense and prolonged interactions during gestation. There is increasing evidence that multiple molecular as well as cellular components originating in pregnant women are transferred to the fetus. The transfer of maternal antibodies has long been recognized as a central component of newborn immunity against pathogens. More recent studies indicate that inflammatory mediators, micronutrients, microbial products and maternal cells are transferred in utero and influence the fetal immune system. Together, these multiple signals are likely to form a complex network of interactions that program the neonatal immune system and tune its homeostatic regulation. Maternal disorders, in particular infectious diseases, modify these signals and may thereby alter immunity in early life. Understanding maternal programming of the newborn immune system could provide a basis for interventions promoting child health.


Transition of the Reaction from Three-Phase to Two-Phase by Using a Hybrid Conductor for High-Energy-Density High-Rate Solid-State Li-O2 Batteries.
Solid-state Li-O2 batteries possess the ability to deliver high energy density with enhanced safety. However, designing a highly functional solid-state air electrode is the main bottleneck for its further development. Herein, we adopt a hybrid electronic and ionic conductor to build solid-state air electrode that makes the transition of Li-O2 battery electrochemical mechanism from a three-phase process to a two-phase process. The solid-state Li-O2 battery with this hybrid conductor solid-state air electrode shows decreased interfacial resistance and enhanced reaction kinetics. The Coulombic efficiency of Li-O2 battery is also significantly improved, benefiting from the good contact between discharge products and electrode materials. In situ environmental transmission electron microscopy under oxygen was used to illustrate the reversible deposition and decomposition of discharge products on the surface of this hybrid conductor, visually verifying the two-phase reaction.


The Association Between Allergic Contact Dermatitis and Erythema Multiforme: A Systematic Review of the Literature.
The relationship between erythema multiforme (EM) and allergic contact dermatitis (ACD) remains unclear. There have been multiple reports of EM-like lesions occurring in conjunction with or presenting after ACD; however, various definitions and terminologies have been used to denote the patient's diagnosis in these cases. In this systematic review, we summarize the key presenting features of recent cases of EM-like eruptions associated with ACD, as well as diagnostic findings, responsible allergens, treatments, and outcomes. We propose that, whenever possible, these cases should be classified into 2 distinct categories: (1) EM-like ACD and (2) EM after ACD (ACD-induced EM). Because the clinical courses, potential complications, and treatment plans differ between the two, a critical need exists for further characterization and distinguishment of EM-like ACD and ACD-induced EM.


The cerebral mechanism of the specific and nonspecific effects of acupuncture based on knee osteoarthritis: study protocol for a randomized controlled trial.
Research on the effect of acupuncture has been limited. Whether the effect of acupuncture is equivalent to placebo has been the focus of debate in this field. This study will explore the specific and non-specific effects of acupuncture for knee osteoarthritis (KOA) by functional magnetic resonance imaging (fMRI). Ninety participants diagnosed with KOA will be randomly divided into the acupuncture group, sham acupuncture group, and waiting list group in a ratio of 1:1:1. Except for the waiting list group, the other participants will receive acupuncture or sham acupuncture three sessions per week for 4 weeks respectively. The primary outcome will be the response rate which is defined on an individual basis as at least a 2-point decrease in the numerical rating scale (NRS) of pain at the end of intervention period compared with the baseline. fMRI scans will be performed at baseline and the end of the intervention period to examine the response of various brain regions. The secondary outcomes will include the Western Ontario and McMaster Osteoarthritis Index (WOMAC), State-Trait Anxiety Scale-State Anxiety Subscale (STAI-S), and Stanford Expectations of Treatment Scale (SETS). Pearson's correlation coefficient will be performed to investigate the changes in brain activity and clinical variables. The results of our study will help to evaluate the specific and nonspecific effects of acupuncture combined with clinical and brain function changes based on KOA. Chinese Clinical Trial Registry ChiCTR1900025799. Registered on 9 September 2019.