Identification and characterization of an insulin receptor substrate 4-interacting protein in rat brain: implications for longevity.
The hypothalamus is organized as a collection of distinct, autonomously active nuclei that regulate discrete functions, such as feeding activity and metabolism. We used suppression subtractive hybridization (SSH) to identify genes that are enriched in the hypothalamus of the rat brain. We screened a subtractive library of 160 clones, and 4 genes that were predominantly expressed in the hypothalamus, compared to other brain regions. The mRNA for a member of the WD-repeat family of proteins, WDR6, was abundantly expressed in the hypothalamus, and we found that WDR6 interacted with insulin receptor substrate 4 (IRS-4) in the rat brain. Interestingly, WDR6 gene expression in the hypothalamic arcuate nucleus was decreased by caloric restriction, and in growth hormone (GH)-antisense transgenic rats, both of which are associated with an increased life span. Insulin-like growth factor (IGF)-I and insulin treatment increased WDR6 gene expression in mouse hypothalamus-derived GT1-7 cells. Our results might suggest that WDR6 participates in insulin/IGF-I signaling and the regulation of feeding behavior and longevity in the brain.


Mineralization of citric acid wastewater by photo-electrochemical chlorine oxidation.
This work demonstrates a novel chloride photo-electrochemical method for mineralizing citric acid. The electrolytic reactor with a length of 12 cm, a width of 12 cm and a height of 30 cm held 2.5 L of solution, which was involved in the batch reaction. Both anode and cathode were made of titanium coated with RuO2/IrO2. The results revealed that the solution pH dominated the production of hypochlorous acid (HOCl) oxidant in the presence of NaCl as direct current electricity was used. The chloride electrochemical process at pH 5.5 removed 59% of total organic carbon (TOC) in 4 h (NaCl = 200 mM, current = 5 A). UV irradiation (254 nm) in the reactor induced the photo-electrochemical reaction, increasing the TOC removal from 59% to 99.4%. Finally, the reaction pathway for citric acid mineralization was discussed with reference to the detection of intermediates using a liquid chromatography-mass spectrometry (LC-MS).


Prognostic utility of cardiovascular magnetic resonance upright maximal treadmill exercise testing.
Left ventricular wall motion abnormalities (LVWMA) observed during cardiovascular magnetic resonance (CMR) pharmacologic stress testing can be used to determine cardiac prognosis, but currently, information regarding the prognostic utility of upright maximal treadmill induced LVWMA is unknown. Our objective was to determine the prognostic utility of upright maximal treadmill exercise stress CMR. One hundred and fifteen (115) men and women with known or suspected coronary arteriosclerosis and an appropriate indication for cardiovascular (CV) imaging to supplement ST segment stress testing underwent an upright treadmill exercise CMR stress test in which LVWMA were identified before and immediately after exercise. Personnel blinded to results determined the post-test incidence of cardiac events (cardiac death, myocardial infarctions [MI], and unstable angina warranting hospital admission or coronary arterial revascularization). All participants completed the testing protocol, with 90% completing image acquisition within 60 s of exercise cessation. MI or cardiac death occurred in 3% of individuals without and 17% of individuals with inducible LVWMA (p = 0.024). The combination of MI, cardiac death, and unstable angina warranting hospitalization occurred in 14% of individuals without and 47% of individuals with inducible LVWMA (p = 0.002). The addition of CMR imaging identified those at risk for future events (p = 0.002), as opposed to the electrocardiogram stress test alone (p = 0.63). In patients with or suspected of coronary arteriosclerosis and appropriate indication for imaging to supplement ST segment analysis during upright treadmill exercise, the presence of inducible LVWMA during treadmill exercise stress CMR supplements ST segment monitoring and helps identify those at risk of the future combined endpoints of myocardial infarction, cardiac death, and unstable angina warranting hospitalization.


Haemorheology in exercise and training.
Disruption of the normal rheological properties of blood is considered an independent risk factor for cardiovascular disease and plays a significant role in the aetiology of atherothrombogenesis. The acute increase in whole blood viscosity may unfavourably affect the microcirculatory blood flow and oxygen delivery to the tissues. It is universally accepted that exercise and physical activity performed on a regular basis has health benefits. However, the effects of exercise on the rheological properties of blood have not received much research attention. Recent, limited evidence indicates that the viscosities of whole blood and plasma increase in response to a variety of exercise protocols. The increase in whole blood viscosity is mainly attributed to an increase in haematocrit and plasma viscosity, whereas the deformability and aggregability of red blood cells remain unaltered. The increases in plasma viscosity and haematocrit have been ascribed to exercise-induced haemoconcentration as a result of fluid transfer from the blood to the interstitial spaces. The haemorheological changes associated with strenuous exercise appear to be linked with enhanced oxidative stress and depletion of antioxidant capacity, and that may affect oxygen delivery and availability to the tissues. Although significant advances have been made in many areas of exercise haematology, the long-term effects of endurance training on blood rheology have been very briefly examined and the exact effect of training has not as yet been determined. Available cross-sectional and longitudinal studies indicate that the blood of endurance athletes is more dilute and this has been attributed to an expansion of blood volume, particularly plasma volume as a result of training. The low haematocrit values in trained athletes represent a hydration condition rather than iron stores deficiency. It has been suggested that this hypervolaemia and blood dilutional effect of endurance training may be advantageous for heat dissipation and greater cardiac stroke volume and lower heart rates during exercise. Enhanced blood fluidity also facilitates oxygen delivery to the exercising muscles because of a reduced resistance to blood flow within the microcirculation. Furthermore, the increase in plasma volume may contribute to the body water pool and help offset dehydration. The influence of strength and power training on blood rheology is not known. The physiological mechanisms responsible for and the functional consequences of the haemorheological changes associated with exercise to a large extent remain speculative. The paradox of haematocrit and blood rheology in exercise and training warrants additional studies. Likewise, further investigations are necessary to determine the possible link between overtraining and blood rheological profiles.


[Patient blood management: Current state of the literature].
Preoperative anemia has a prevalence of approximately 30% and is one of the strongest predictors of perioperative red blood cell (RBC) transfusion. It is rarely treated although it is an independent risk factor for the occurrence of postoperative complications. Additionally, the high variability in the worldwide usage of RBC transfusions is alarming. Due to these serious deficits in patient care, in 2011 the World Health Organization recommended the implementation of a patient blood management (PBM). This article provides information about PBM as a multidimensional and interdisciplinary approach. A selective literature search was carried out in the Medline and Cochrane library databases including consideration of national and international guidelines. A PBM promotes the medically and ethically appropriate use of all available resources, techniques and materials in favor of an optimized perioperative patient care. Patients' own resources should be specifically protected, strengthened and used and include (i) diagnosis and therapy of preoperative anemia, (ii) minimizing perioperative blood loss, (iii) blood-conserving surgical techniques, (iv) restriction of diagnostic blood sampling, (v) utilization of individual anemia tolerance, (vi) optimal coagulation and hemotherapy concepts and (vii) guideline-based, rational indications for the use of RBC transfusions. A PBM should be advocated as an incentive to evaluate and critically optimize local conditions. An individual, interdisciplinarily structured bundle of different PBM measures has great potential to optimize the quality of patient care and to make it safer.


[The role of podocyte autophagy and endoplasmic reticulum stress in diabetic kidney disease].
Diabetic kidney disease (DKD) is one of the serious complications of diabetes mellitus, and it has become the leading cause of chronic renal failure in China. Podocytes are highly differentiated epithelial cells and are the important part of the glomerular filtration barrier. Apoptosis and shedding of podocytes, foot process fusion and decreased expression of slit membrane proteins can lead to proteinuria, which in turn affects the progression of DKD. Autophagy is an important process for eukaryotic cells to degrade cytoplasmic proteins and organelles,the increase of autophagy level helps to reduce podocytes damage. Endoplasmic reticulum stress (ERS) is the accumulation of misfolded proteins in cells. It allows the cells into stress state, and may be able to regulate cell damage in both directions. Autophagy and ERS are regulated by multiple signaling pathways and are considered to be closely related to the occurrence and development of DKD. This article explained some pathways and the role of podocyte autophagy and ERS in DKD, and the interaction between podocyte autophagy and ERS, which providing some potential targets for the treatment of DKD by interfering with podocyte autophagy and ERS.


Dynorphin inhibits NEP activity in R1.1 mouse thymoma cells.
NEP/CALLA or CD10 is an endopeptidase (E.C. 126.96.36.199) that inactivates numerous neuropeptides, including dynorphin. Dynorphin is an endogenous opioid polypeptide that binds to kappa-opioid receptors with greatest affinity. R1.1 mouse thymoma cells highly express kappa-opioid receptors. In this study, on R1.1 cells, NEP activity was inhibited by kappa-opioid polypeptide dynorphin (10(-8)-10(-6) M) and by thiorphan (2 x 10(-4) M), a known inhibitor of NEP (30 min treatment). NEP inhibition by dynorphin was stronger than by thiorphan. A non-opioid opioid mechanism of action was mostly involved in this inhibition.


Incidence of endodontic implantitis and implant endodontitis occurring with single-tooth implants: a retrospective study.
The purposes of this study were to determine success and survival rates for implants and teeth adjacent to implants and the incidence of endodontic implantitis (E-I) (endodontic involvement in adjacent teeth causing implant failure) and implant endodontitis (I-E) (implant placement causing endodontic failure). The data were from 233 single-tooth implants placed in 116 subjects by postgraduate periodontal students with recall radiographs taken >or=9 months after implant placement. Three groups were analyzed: group A, implants with no adjacent teeth (n = 90); group B, implants with nonendodontically treated adjacent teeth (n = 123); and group C, implants with endodontically treated adjacent teeth (n = 20). The success and survival rates for implants were both 92.2% in group A, 98.4% and 99.2% for group B, and 85% and 95% for group C, respectively. For adjacent teeth, they were both 99.4% in group B compared with 75% and 90% in group C. However, after case review, none of the implants or adjacent teeth in group B were considered to have E-I or I-E, and one (5%) of the implants in group C had E-I and two (10%) of the adjacent teeth may have had I-E. The results of the present study agree with previous research, which suggests that endodontically treated teeth adjacent to single-tooth implants are usually successful and should be maintained.


110 GHz, 110 mW hybrid silicon-lithium niobate Mach-Zehnder modulator.
High bandwidth, low voltage electro-optic modulators with high optical power handling capability are important for improving the performance of analog optical communications and RF photonic links. Here we designed and fabricated a thin-film lithium niobate (LN) Mach-Zehnder modulator (MZM) which can handle high optical power of 110 mW, while having 3-dB bandwidth greater than 110 GHz at 1550 nm. The design does not require etching of thin-film LN, and uses hybrid optical modes formed by bonding LN to planarized silicon photonic waveguide circuits. A high optical power handling capability in the MZM was achieved by carefully tapering the underlying Si waveguide to reduce the impact of optically-generated carriers, while retaining a high modulation efficiency. The MZM has a [Formula: see text] product of 3.1 V.cm and an on-chip optical insertion loss of 1.8 dB.


Data on the model of loneliness and smartphone use intensity as a mediator of self-control, emotion regulation, and spiritual meaningfulness in nomophobia.
The study was conducted in three locations: Yogyakarta, Palembang, and Jambi. A total of 355 psychology students from three different universities were recruited using purposive sampling. Among the participants, there were 313 females (88.03%) and 42 males (11.83%). The participants completed several questionnaires in the Indonesian version, including the nomophobia NMP-Q scale (Yildirim & Correia, 2015), the R-UCLA Loneliness Scale (Russell et al., 1980), the self-control scale (Tangney, Baumeister & Boone, 2004), the Difficulties in Emotion Regulation Scale (DERS; Gratz & Roemer, 2004), and the Spiritual Meaningfulness scale developed based on the theory of Pargament (2007). Before commencing the analysis, the research team ensured the accuracy and reliability of the collected data sets. Participants who did not fully complete the questionnaire were removed from the sample. Ethical clearance for this study was obtained from the research ethics committee, and the researchers obtained permission from the respective university administrations for data collection. Prior to participation, all individuals agreed to take part in the study, provided voluntary informed consent, and were assured of the confidentiality and anonymity of their responses.


Production of Properly Folded NS1 Protein in Bacterial Cells.
Dengue virus (DENV) NS1 protein is a multifunctional protein involved in several pathogenic processes but also has been described as a protective antigen suitable for eliciting humoral response against DENV. NS1 is essential for virus replication and can be found in different cell compartments and at different oligomeric states. It is secreted to the extracellular medium and can also be found circulating in the blood of infected patients, being routinely used as the serum biomarker for early dengue diagnosis. High-yield production of the recombinant NS1 protein in a native-like conformation is essential for studies regarding its function during DENV infection as well as to those interested in the development of new diagnostic approaches based on this protein. In this chapter, we describe an optimized protocol for high-yield expression of native-like NS1 in Escherichia coli bacterial cells.


Ileo-uterine fistula as a complication of myomectomy. Case report.
A patient is described who developed an ileo-uterine fistula after myomectomy. The fistula caused no symptoms and was discovered at hysterosalpingography for infertility.


Heme Iron Release from Alginate Beads at In Vitro Simulated Gastrointestinal Conditions.
Heme iron (Fe) release from alginate beads at in vitro simulated gastrointestinal conditions for potential use as oral heme Fe supplement was studied. Five beads at different ratios of sodium alginate (SA)-to-spray-dried bovine blood cells (SDBC) with weight ratios of 1:1.25, 1:2.5, 1:5, 1:10, and 1:15 (w/w) were prepared. Release characteristics of these beads were investigated at in vitro simulated gastrointestinal conditions. Release media pH strongly influenced the controlled Fe release from the beads. The heme Fe-beads in simulated gastric fluid (pH 2) remained in a shrinkage state and Fe release was low: 25.8, 21.1, 11.6, 12.1, and 12.0 % for 1:1.25, 1:2.5, 1:5, 1:10, and 1:15 ratios, respectively. Proportion and amount of Fe released by 1:1.25 and 1:2.5 ratios was higher than the other ratios. The heme Fe-beads swelled and dissociated in simulated intestinal fluid (pH 6), releasing three-fourths of the Fe in 200 min. The morphology studies showed that Fe release followed formation of pores in the alginate matrix, generating erosion of the beads and complete disintegration after 75 and 200 min of gastric and intestinal incubation, respectively. These results indicate that heme Fe-beads may be useful for oral delivery of heme Fe supplement.


Simultaneous development of autoimmune disease and malignancy in two elderly patients.
Two elderly patients who presented with symptoms of "systemic rheumatic or autoimmune disease" had high serum titers of fluorescent antinuclear antibody (ANA). Signs of malignancy were evident at the time of the first examination. T-cell dysfunction in the aged may permit the simultaneous development of autoimmunity and neoplasia. When rheumatic symptoms with a high titer of fluorescent ANA develop in elderly patients, an exhaustive search for malignancy should be considered.


Label Free Poly(2,5-dimethoxyaniline)-Multi-Walled Carbon Nanotubes Impedimetric Immunosensor for Fumonisin B₁ Detection.
An impedimetric immunosensor for fumonisin B₁ (FB₁) was developed from a poly(2,5-dimethoxyaniline)-multi-walled carbon nanotube (PDMA-MWCNT) composite on the surface of glassy carbon electrode (GCE). The composite was prepared electrochemically and characterized using cyclic voltammetry. The preparation of the FB₁ immunosensor involved the drop-coating of a bovine serum albumin mixture of the anti-fumonisin antibody (anti-Fms) onto the composite polymer-modified GCE. The electrochemical impedance spectroscopy (EIS) responses of the FB₁ immunosensor (GCE/PDMA-MWCNT/anti-Fms) have a linear range of 7 to 49 ng·L-1, and the corresponding sensitivity and detection limits are 0.272 kΩ L·ng-1 and 3.8 pg·L-1, respectively. The limit of detection of the immunosensor for certified corn sample (i.e., certified reference material) is 0.014 ppm FB₁, which is in excellent agreement with the value published by the vendors and significantly more accurate than that obtained with enzyme-linked immunosorbent assay (ELISA).


Temporal masking curves for hearing-impaired listeners.
The decay of forward masking was investigated for three subjects with moderate sensorineural hearing loss. For such subjects, compression on the basilar membrane (BM) is thought to be largely absent, enabling one to determine the decay of masking without the influence of compression. Temporal masking curves (TMCs), plots of the masker level at threshold against delay between masker offset and signal onset, were measured for delays of 0, 15, 30, 45, 60, and 75 ms, for signal frequencies, fs, of 500, 1000, 2000, 4000, and 6000 Hz. Masker frequencies were 0.5, 0.8, 1.0, 1.15, and 1.3 times fs. Most of the TMCs were well fitted with single-segment straight lines, which, except for high masker levels, were roughly parallel for each fs, supporting the belief that BM compression was largely absent in these subjects. However, the slopes of the TMCs were greater for fs = 500 and 1000 Hz than for higher frequencies, which may indicate that the decay of forward masking is not the same for all signal frequencies. The results suggest that it may not be valid to infer BM compression at low signal frequencies by using a reference TMC for a high fs.


Comparative study of percutaneous vertebroplasty and kyphoplasty in the treatment of osteoporotic vertebral compression fractures.
To compare the therapeutic effect of percutaneous vertebroplasty (PVP) and percutaneous kyphoplasty (PKP) in the treatment of osteoporotic vertebral compression fractures (VCFs). A total of 244 patients with VCFs were treated by PVP or PKP and 192 had follow-up for at least 1 year. Clinical outcomes were determined by pain Visual Analog Scale (VAS) and Short Form 36 Health Survey (SF-36). Preoperative and postoperative radiographic assessment included measurement of posterior and anterior vertebral body height (AH and PH), as well as the kyphotic angle by the Cobb method. A total of 192 cases had follow-up for at least 1 year and 52 cases lost. The average amount of polymethylmethacrylate (PMMA) cement introduced per vertebra was 3.4 ± 1.5 ml in PVP and 4.5 ± 0.8 ml in PKP (P < 0.05). All patients subjectively reported immediate relief of their typical fracture pain, and the mean VAS decreased significantly from presurgery to postsurgery during the 1-year of follow-up. The RP, BP and GH dimensionality values of SF-36 in PKP were higher than PVP (P < 0.05). The improvement on AH was 11.13 ± 5.68% in PVP and 21.46 ± 9.87% in PKP (P < 0.01); on PH was 2.25 ± 1.36% in PVP and 7.57 ± 2.49% in PKP (P < 0.01). The average improvement in the kyphotic angle after the procedure was 5.21 ± 2.33° in PVP and 11.69 ± 5.18° in PKP (P < 0.01). PVP and PKP have the ability of reducing pain in osteoporotic VCF patients. The correction of kyphotic deformity and restoration of the anterior vertebral body heights associated with osteoporotic VCFs was better in PKP.


Inhalation carcinogenesis of N-nitrosomorpholine (NMOR) in rats and hamsters.
N-Nitrosomorpholine (NMOR) is a potent liver carcinogen in rats when administered orally. NMOR was found in the atmosphere at working places in the rubber industry in concentrations up to several hundred micrograms/m3. It can be assumed that NMOR inhalation may play a role in human carcinogenesis. Therefore an inhalation study was carried out to evaluate the carcinogenic potency of NMOR vapors in rats and hamsters. The concentration of volatile NMOR in the inhalation chamber was continuously determined with a Thermal Energy Analyzer. The rats received 29 administrations (4th/day, 5 days/week; mean inhaled daily dose: 130 micrograms/animal; total dose: 15 mg/kg bodyweight). The hamsters inhaled a total of 38 mg/kg of NMOR (21 applications, daily dose 260 micrograms/animal). In rats 4 carcinomas and 5 neoplastic nodules of the liver, 1 neuroblastoma and 1 mucoepidermoidal carcinoma of the nose, and 1 carcinoma of the thyroid gland were induced. In treated hamsters 4 carcinomas of the liver, 2 neurogenic sarcomas of the nasal region, and 5 papillomas of the trachea were found. None of these tumors were observed in control rats and control hamsters.


[Sanitary service of West Special Military District on the eve and in the first days of the Great Patriotic War of 1941-1945].
This article evaluates military and political situation in the world and operational-strategic environment on the West Theater of operations on the eve of the Great Patriotic War (1941-1945). We analyze structure and overall condition of sanitary service of West Special Military District of the Workers and Peasants Red Army and causes of failure of mobilization, organization and deployment of military units and establishments from the beginning of aggression of Fascist Germany to the Soviet Union.


Partial trisomy of the long arm of human chromosome 1 as demostrated by in situ hybridization with 5S ribosomal RNA.
In a newborn boy with multiple malformations, a tandem duplication was detected at the distal end of the long arm of one human chromosome 1. The Giemsa bands, 1q31 to 1q43--44, were repeated serially. Since 5S rRNA genes are located at 1q42--43, in situ hybridization of 125I 5S rRNA with fixed chromosome preparations was used to confirm the chromosomal duplication. The infant exhibited numerous developmental and clinical abnormalities as might be expected with an abnormality of chromosome structure relating to a ribosome component.


Contributions of musculoskeletal rehabilitation in patients after chikungunya fever: a systematic review.
Chikungunya fever is an infection transmitted by the Chikungunya virus (CHIKV), which is an arbovirus that is transmitted by the mosquitoes Aedes aegypti and Aedes albopictus. The most common sequelae caused by CHIKV are chronic musculoskeletal pain, nerve damage, joint deformation and functional impairment. To systematically identify the literature on the contributions of physiotherapy in the treatment of patients with CHIKV sequelae. Systematic review of the literature, guided by the recommendations of the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA). The databases used were PUBMED, LILACS, Scielo and PEDro. Experimental studies and/or full case studies published without language restriction or publication data were included, in which they stood out as contributions of musculoskeletal functional rehabilitation in the treatment of patients with the condition in question. Analytical observational studies, editorial letters, review protocols, reflective studies, literature reviews and articles that do not have an abstract and/or full text available online were excluded. The search in the databases was carried out between July and August 2022. A total of 4,782 articles were found on the platforms used and 10 articles from the gray literature search. After the duplicate analysis, 2,027 studies were excluded, leaving 2,755 articles that had their titles and abstracts read, of which 600 articles were selected for full reading. After this step, a final sample of 13 articles was eligible for this review. The most consolidated approaches used in the literature demonstrate that kinesiotherapy, associated or not with electrothermophototherapy, the pilates method and auriculotherapy are useful resources in the treatment of these individuals, significantly inspired by pain relief, improved quality of life and of functionality.


Cardiac MRI measurements of pericardial adipose tissue volumes in patients on in-centre nocturnal hemodialysis.
Conversion from conventional hemodialysis (CHD) to in-centre nocturnal hemodialysis (INHD) is associated with left ventricular (LV) mass regression, but the underlying mechanisms are not fully understood. Using cardiac MRI (CMR), we examined the effects of INHD on epicardial adipose tissue (EAT) and paracardial adipose tissue (PAT), and the relationships between EAT, PAT and LV remodeling, biomarkers of nutrition, myocardial injury, fibrosis and volume. We conducted a prospective multicenter cohort study of 37 patients transitioned from CHD to INHD and 30 patients on CHD (control). Biochemical markers and CMR were performed at baseline and 52 weeks. CMR images were analyzed by independent readers, blinded to order and treatment group. Among 64 participants with complete CMR studies at baseline (mean age 54; 43% women), there were no significant differences in EAT index (60.6 ± 4.3 mL/m2 vs 64.2 ± 5.1 mL/m2, p = 0.99) or PAT index (60.0 ± 5.4 mL/m2 vs 53.2 ± 5.9 mL/m2, p = 0.42) between INHD and CHD groups. Over 52 weeks, EAT index and PAT index did not change significantly in INHD and CHD groups (p = 0.21 and 0.14, respectively), and the changes in EAT index and PAT index did not differ significantly between INHD and CHD groups (p = 0.30 and 0.16, respectively). Overall, changes in EAT index inversely correlated with changes in LV end-systolic volume index (LVESVI) but not LV end-diastolic volume index (LVEDVI), LV mass index (LVMI), and LV ejection fraction (LVEF). Changes in PAT index inversely correlated with changes in LVESVI, LVMI and positively correlated with changes in LVEF. There were no correlations between changes in EAT index or PAT index with changes in albumin, LDL, triglycerides, troponin-I, FGF-23, or NT-proBNP levels over 52 weeks (all p > 0.30). INHD was not associated with any changes in EAT index and PAT index over 12 months. Changes in EAT index were not significantly associated with changes in markers of LV remodeling, nutrition, myocardial injury, fibrosis, volume status. In contrast, changes in PAT index, which paradoxically is expected to exert less paracrine effect on the myocardium, were correlated with changes in LVESVI, LVMI and LVEF. Larger and longer-term studies may clarify the role of PAT in cardiac remodeling with intensified hemodialysis. CLINICALTRIALS. NCT00718848.


[Refractory psoriasis treatment with etanercept].
Etanercept is a dimeric fusion protein that binds to tumor necrosis factor and blocks inflammatory response. The purpose of this study was to assess the effects of etanercept and its maintenance in patients with severe and refractory psoriasis. Twenty two patients with severe and refractory psoriasis in an open-label clinical trial were studied. Patients received etanercept 50 mg/week subcutaneously during 6 months. PASI (Psoriasis Assessment and Severity Index) was used to monitor disease activity in each month of treatment and in the follow up. Results at weeks 12 and 24 are shown. 96% of patients improved their PASI basal score early at week 12. This improvement was maintained until week 24. Etanercept was well tolerated without any significant adverse reaction. Time until relapse was 2.27 +/- 0.59 months (CI 95%: 1.94-2.60). Etanercept seems an effective therapy for severe and refractory psoriasis yet long-term dosing and safety studies of etanercept in psoriasic patients are needed.


Synthesis and antitumor activity of ring A modified glycyrrhetinic acid derivatives.
Triterpenoic acids show many pharmacological effects, among them an antiinflammatory or an antitumor activity. One of these, glycyrrhetinic acid (1) is of interest because of its antitumor profile. Glycyrrhetinic acid is not only cytotoxic but also triggers apoptosis in various human tumor cell lines. To improve the cytotoxicity of parent 1 we set out to synthesize new derivatives of it--differing in structure and lipophilicity. These compounds were tested in a sulforhodamine B assay for cytotoxicity, and screened for their ability to induce apoptosis using an acridine orange/ethidium bromide assay and trypan blue staining. The most active compound, 34, a benzyl glycyrrhetinate holding an extra 3-N-(3-aminopropyl)glycyl substituent showed IC(50) between 1.96 and 5.14 μm for five human cancer cell lines and triggers apoptosis in 80% of the cells.


Comparison of Reconstruction Algorithms for Decreasing the Exposure Dose During Digital Tomosynthesis for Arthroplasty: a Phantom Study.
To explore the possibility of decreasing the radiation dose during digital tomosynthesis (DT) for arthroplasty, we compared the image qualities of several reconstruction algorithms, such as filtered back projection (FBP) and two iterative reconstruction (IR), methods maximum likelihood expectation maximization (MLEM) and the simultaneous iterative reconstruction technique (SIRT) under different radiation doses. The three algorithms were implemented using a DT system and experimentally evaluated by contrast-to-noise ratio (CNR), artifact spread function (ASF), and power spectrum measurements on a prosthesis phantom. The CNR and ASF data were statistically analyzed by a one-way analysis of variance. The effectiveness of each technique for enhancing the visibility of the prosthesis phantom was quantified by the CNR (reference dose vs. 20 % reduced dose in FBP, P = 0.62; reference vs. 37 % reduced dose in FBP, P = 0.16; reference vs. 55 % reduced dose in FBP, P < 0.05; reference vs. 20 % reduced dose in IR, P = 0.92; reference vs. 37 % reduced dose in IR, P = 0.40; reference vs. 55 % reduced dose in IR, P < 0.05) and ASF (reference dose vs. 20 % reduced dose in FBP, P = 0.25; reference vs. 37 and 55 % reduced dose in FBP, P < 0.05; reference vs. 20 % reduced dose in IR, P = 0.16; reference vs. 37 and 55 % reduced dose in IR, P < 0.05). The power spectra under the reference and reduced doses are equivalent. In this phantom study, the radiation dose of the reference dose could be decreased by 20 % with FBP and IR for consideration of common factors.


[Selective dry cow therapy on dairy farms in Southern Germany - a case series].
The aim of this case series was to describe how the selective dry-off therapy affected the udder health of Bavarian dairy farms under field conditions as well as to record whether a long-term reduction in antibiotic dry-off therapy was feasible. Between 2016 and 2021, 90 herds participated. A subset of dairy herds participated over a period of several years. Quarter milking samples were taken annually from all lactating cows in the herds, and treatment and test day results were evaluated. Major pathogens were detected during the initial whole herd testing (e. g., Streptococcus agalactiae, Streptococcus canis) and the treatment regimen needed to be adjusted. Even though the median treatment risk decreased, at least numerically, from 63% to 50%, the treatment rate in individual herds could vary greatly between years (-60% to+40%). Selective dry-off therapy can be implemented without endangering the udder health of the herd.


Lysosomal glucose sensing and glycophagy in metabolism.
Lysosomes are cellular organelles that function to catabolize both extra- and intracellular cargo, act as a platform for nutrient sensing, and represent a core signaling node integrating bioenergetic cues to changes in cellular metabolism. Although lysosomal amino acid and lipid sensing in metabolism has been well characterized, lysosomal glucose sensing and the role of lysosomes in glucose metabolism is unrefined. This review will highlight the role of the lysosome in glucose metabolism with a focus on lysosomal glucose and glycogen sensing, glycophagy, and lysosomal glucose transport and how these processes impact autophagy and energy metabolism. Additionally, the role of lysosomal glucose metabolism in genetic and metabolic diseases will be briefly discussed.


An antifungal peptide from Coffea canephora seeds with sequence homology to glycine-rich proteins exerts membrane permeabilization and nuclear localization in fungi.
The superfamily of glycine-rich proteins (GRPs) corresponds to a large and complex group of plant proteins that may be involved in many developmental and physiological processes such as RNA biogenesis, stress tolerance, pollen hydration and plant-pathogen interactions, showing defensive activity against fungi, bacteria and viruses. In this study, the peptides from Coffea canephora seeds were extracted according to the methods of Egorov et al. (2005). The purified peptide was submitted for amino acid sequencing and antimicrobial activity measurement. The purified peptide with a molecular weight of 7kDa, named Cc-GRP, was observed to display homology to GRPs. The Cc-GRP-fungi interaction led to morphological changes and membrane permeability, including the formation of pseudohyphae, which were visualized with the aid of SYTOX green dye. Additionally, Cc-GRP also prevented colony formation by yeasts. Antifungal assays of Fusarium oxysporum and Colletotrichum lindemuthianum, observed by light microscopy, showed that the two molds exhibited morphological changes after the growth assay. Cc-GRP coupled to FITC and its subsequent treatment with DAPI revealed the presence of the peptide in the cell wall, cell surface and nucleus of F. oxysporum. In this work we purified, characterized and evaluated the in vitro effect on fungi of a new peptide from coffee, named Cc-GRP, which is involved in the plant defense system against pathogens by acting through a membrane permeabilization mechanism and localized in the nuclei of fungal cells. We also showed, for the first time, the intracellular localization of Cc-GRP during antimicrobial assay.


Responses of ajowan (Trachyspermum ammi L.) to exogenous salicylic acid and iron oxide nanoparticles under salt stress.
This research with a factorial arrangement was undertaken to investigate physiological responses of ajowan plants to foliar treatment of salicylic acid (1 mM) and nano-Fe2O3 (3 mM) under various salinity levels (0, 4, 8, 12 dS m-1 NaCl, respectively). Rising salinity enhanced sodium and endogenous SA contents, soluble sugars, protein, glycine betaine, proline, antioxidant enzymes activities, ROS generation, and lipid peroxidation, while reduced potassium and iron contents, membrane stability index, leaf water content, leaf pigments, root and shoot biomasses, and seed yield. Application of particularly SA and SA+nano-Fe2O3 alleviated salt toxicity via enhancing K+ uptake, K+/Na+ ratio, Fe content, endogenous level of SA, the activities of antioxidant enzymes (superoxide dismutase, catalase, peroxidase, and polyphenol oxidase), and most of the osmolytes. These changes were resulted in improving membrane stability index, leaf water content, leaf pigments, root and shoot growth, and finally seed yield of plants under moderate and severe salinities. Therefore, these treatments can additively enhance salt tolerance and physiological performance of ajowan through increasing antioxidant capacity, osmolytes, and photosynthetic pigments. Graphical Abstract .


Effectiveness and Safety of Combination Therapy with Herbal Medicine and Growth Hormone Compared to Growth Hormone Monotherapy for Short Stature Children: A Systematic Review and Meta-Analysis.
Herbal medicines (HM) and growth hormones (GH) are widely used to treat short stature (SS) in children. This systematic review aimed to evaluate the effectiveness and safety of combination therapy with HM and GH (CHG) compared to those of GH monotherapy (GHM) in children with SS. We searched 17 electronic databases from inception to 1 April 2021. Only randomized controlled trials (RCTs) were included. Two authors independently performed the selection and quality assessment of the included studies using Cochrane Handbook criteria. Relative risk (RR) was used to measure dichotomous outcomes with a 95% confidence interval (CI). Mean difference (MD) or standard MD (SMD) was used to measure continuous outcomes with a 95% CI. Seven RCTs involving 455 participants with SS were included. Standard deviations in height (MD = 0.31, 95% CI: 0.24-0.38, p < 0.00001), and insulin-like growth factor binding protein-3 (MD = 1.39, 95% CI: 0.93-1.85, p < 0.00001) were significantly higher in the CHG group than in the GHM group. Growth velocity (MD = 1.82, 95% CI: 1.34-2.31, p < 0.00001) and insulin-like growth factor-1 (MD = 61.85, 95% CI: 55.80-67.90, p < 0.00001) were significantly higher in the CHG group. Adverse events were significantly lower in the CHG group (risk ratio: 0.10, 95% CI: 0.02-0.54, p = 0.007). However, the level of evidence was low. CHG demonstrated significantly better efficacy than GHM for treating SS, with a low incidence of adverse events. However, since the level of evidence is low, methodologically standardized RCTs are required to verify these results.


Mini-interfacial fracture toughness as a new validated enamel-bonding effectiveness test.
Today׳s most commonly applied bonding effectiveness tests are criticized for their high variability and low reliability, the latter in particular with regard to measuring the actual strength of the adhesive interface. in continuation of previous research conducted at dentin, we hereby aimed to validate the novel mini-interfacial fracture toughness (mini-iFT) test on its applicability to assess bonding effectiveness of contemporary adhesives when bonded to enamel. The 3-step etch&rinse (E&R) adhesive OptiBond FL (Kerr), the 2-step self-etch (SE) adhesive Clearfil SE Bond (Kuraray Noritake) and the two multi-mode adhesives Clearfil S(3) Bond Plus (Kuraray Noritake) and Scotchbond Universal (3M ESPE), both used following a 2-step E&R and 1-step SE mode, were applied to clinically relevant, flattened enamel surfaces. A composite (Filtek Z100; 3M ESPE) build-up was made in layers. After 1-week water storage at 37°C, all specimens were sectioned perpendicular to the interface to obtain rectangular sticks. A mini-iFT notch was prepared at the adhesive-enamel interface using a thin diamond blade under water cooling. Finally, the specimens were loaded in a 4-point bending test until failure. the mini-iFT onto human enamel was significantly higher for the adhesives applied in E&R mode versus those applied in SE mode. The lowest mini-iFT was found for the adhesives applied following a 1-step SE approach. SEM fracture analysis revealed that all fractures originated at the adhesive-enamel interface and that the induced crack propagated preferentially along this interface. mini-iFT appeared a valid alternative method to assess the mechanical properties of adhesive-enamel interfaces.


Scleraxis is required for maturation of tissue domains for proper integration of the musculoskeletal system.
Scleraxis (Scx) is a basic helix-loop-helix transcription factor that is expressed persistently in tendons/ligaments, but transiently in entheseal cartilage. In this study, we generated a novel ScxCre knock-in (KI) allele, by in-frame replacement of most of Scx exon 1 with Cre recombinase (Cre), to drive Cre expression using Scx promoter and to inactivate the endogenous Scx. Reflecting the intensity and duration of endogenous expression, Cre-mediated excision occurs in tendinous and ligamentous tissues persistently expressing Scx. Expression of tenomodulin, a marker of mature tenocytes and ligamentocytes, was almost absent in tendons and ligaments of ScxCre/Cre KI mice lacking Scx to indicate defective maturation. In homozygotes, the transiently Scx-expressing entheseal regions such as the rib cage, patella cartilage, and calcaneus were small and defective and cartilaginous tuberosity was missing. Decreased Sox9 expression and phosphorylation of Smad1/5 and Smad3 were also observed in the developing entheseal cartilage, patella, and deltoid tuberosity of ScxCre/Cre KI mice. These results highlighted the functional importance of both transient and persistent expression domains of Scx for proper integration of the musculoskeletal components.


Comparison of the Results of a Parkinson's Holter Monitor With Patient Diaries, in Real Conditions of Use: A Sub-analysis of the MoMoPa-EC Clinical Trial.
For specialists in charge of Parkinson's disease (PD), one of the most time-consuming tasks of the consultations is the assessment of symptoms and motor fluctuations. This task is complex and is usually based on the information provided by the patients themselves, which in most cases is complex and biased. In recent times, different tools have appeared on the market that allow automatic ambulatory monitoring. The MoMoPa-EC clinical trial (NCT04176302) investigates the effect of one of these tools-Sense4Care's STAT-ON-can have on routine clinical practice. In this sub-analysis the agreement between the Hauser diaries and the STAT-ON sensor is analyzed. Eighty four patients from MoMoPa-EC cohort were included in this sub-analysis. The intraclass correlation coefficient was calculated between the patient diary entries and the sensor data. The intraclass correlation coefficient of both methods was 0.57 (95% CI: 0.3-0.73) for the OFF time (%), 0.48 (95% CI: 0.17-0.68) for the time in ON (%), and 0.65 (95% CI%: 0.44-0.78) for the time with dyskinesias (%). Furthermore, the Spearman correlations with the UPDRS scale have been analyzed for different parameters of the two methods. The maximum correlation found was -0.63 (p < 0.001) between Mean Fluidity (one of the variables offered by the STAT-dON) and factor 1 of the UPDRS. This sub-analysis shows a moderate concordance between the two tools, it is clearly appreciated that the correlation between the different UPDRS indices is better with the STAT-ON than with the Hauser diary. https://clinicaltrials.gov/show/NCT04176302 (NCT04176302).


CVD Prevention Through Policy: a Review of Mass Media, Food/Menu Labeling, Taxation/Subsidies, Built Environment, School Procurement, Worksite Wellness, and Marketing Standards to Improve Diet.
Poor diet is the leading cause of cardiovascular disease in the USA and globally. Evidence-based policies are crucial to improve diet and population health. We reviewed the effectiveness for a range of policy levers to alter diet and diet-related risk factors. We identified evidence to support benefits of focused mass media campaigns (especially for fruits, vegetables, salt), food pricing strategies (both subsidies and taxation, with stronger effects at lower income levels), school procurement policies (for increasing healthful or reducing unhealthful choices), and worksite wellness programs (especially when comprehensive and multicomponent). Evidence was inconclusive for food and menu labeling (for consumer or industry behavior) and changes in local built environment (e.g., availability or accessibility of supermarkets, fast food outlets). We found little empiric evidence evaluating marketing restrictions, although broad principles and large resources spent on marketing suggest utility. Widespread implementation and evaluation of evidence-based policy strategies, with further research on other strategies with mixed/limited evidence, are essential "population medicine" to reduce health and economic burdens and inequities of diet-related illness worldwide.


Does radiation exposure during pediatric supracondylar humeral fracture surgery change according to the C-arm position? A comparison of two different techniques.
In the surgical treatment of supracondylar humeral fractures (SHF), the surgeon has to stand right next to the fluoroscopy device, so it is very important to know how to use it in the most appropriate way to reduce radiation exposure. The aim of this study was to investigate the effect of using C-arm in uniplanar (inverted) and biplanar (standard-horizontal) configurations on (1) the radiation exposure to the surgeon, and (2) surgical time and fluoroscopy exposure time. This prospective randomised study was conducted on 20 patients who underwent fluoroscopy during closed reduction and percutaneous pinning for a SHF. In the first configuration, the C-arm was inverted and the image intensifier was used as a surgical table. In the second configuration, the C-arm was used biplanar. The operations were performed by 5 surgeons, with each surgeon using each method only twice. During the operation, to find a value closed to direct radiation exposure measurement was made by attaching a dosimeter to the wrist and scatter radiation exposure was measured by attaching a dosimeter to the neck and waist of the surgeons. The operation time and fluoroscopy exposure time were determined. The duration of operations performed with the biplanar C-arm position and the fluoroscopy exposure time in operations performed with the uniplanar method were found to be statistically significantly longer (p = 0.001). The measurements on the dosimeter worn on the neck of surgeons were found to be statistically significantly higher while using the uniplanar C-arm configuration (p = 0.001). There was no statistically significant difference between the dosimeter measurements on the wrists and waists of the surgeons and the C-arm configurations (p = 0.820; p = 0.185). Although the use of biplanar C-arm has no effect on radiation exposure to the surgeon's wrist, the most important advantages are that the neck area is exposed to less radiation and it shortens the fluoroscopy time so the use of a biplanar C-arm can be recommended. Level II.


Apoptotic and proliferative activity in ovarian benign, borderline and malignant tumors.
To determine the apoptotic and proliferative activities in various ovarian epithelial tumors. Formalin-fixed, paraffin-embedded tissues of 86 ovarian epithelial tumors, including 52 adenocarcinomas, 23 borderline tumors and 11 cystadenoma, were retrieved. Apoptotic (AI) and proliferative (PI) index were estimated using the monoclonal antibodies: M30, Ki-67 and Ki-S1 in these tumors. Quantitative assessment of AI and PI was estimated by calculating the percentage of positive cells among no less than 1000 tumor cells. Statistically significant difference in AI was found between benign and borderline tumors or carcinomas (P = 0.028, 0.001, respectively). Significant differences in PI, as assessed by both Ki-67 and topo IIalpha, were demonstrated between carcinomas and benign or borderline tumors (both P < 0.001). Benign tumors had both low PI and AI; borderline tumors had lower PI but higher AI, while adenocarcinomas had both high proliferative and high apoptotic rates. Among borderline tumors, serious tumors had significantly lower AI and higher PI than mucinous ones. The results suggest that apoptotic and proliferative activities play important roles in the pathogenesis and development of ovarian borderline and malignant tumors. The high apoptotic rate in borderline tumor may explain its relatively indolent behavior while the high proliferative rate in carcinomas tends to explain its aggressive behavior.


Ovulation and luteal characteristics following removal of the ovine corpus luteum (lutectomy) at four times during the oestrous cycle.
The life span of the corpus luteum (CL) may depend on follicular development. To provide evidence relating to this hypothesis, each of 32 ewes was randomly assigned to have its CL removed on day 2, 3, 4 or 10 after oestrus. Twenty ewes were treated with 1000 IU of human chorionic gonadotrophin (hCG) 36 h after CL removal to induce ovulation; the other 12 ewes were not treated with hCG. Blood samples were collected daily to monitor the ovulatory response and the characteristics of the next cycle at the first sign of oestrus and up to day 21 after surgery or hCG administration. Every animal ovulated within 7 days of hCG administration, regardless of when its CL had been removed. It was concluded that the follicles found in the ovary as early as the second day after oestrus respond to endogenous or exogenous ovulatory stimuli affecting the life span of resulting CL.


Sexual anxiety and female sexual arousal: a comparison of arousal during sexual anxiety stimuli and sexual pleasure stimuli.
Sexual arousal occurring during sexual anxiety stimuli was compared to sexual arousal occurring during sexual pleasure stimuli in 19 sexually functional women. Stimuli were individualized narratives based on descriptions given by each subject. Sexual arousal was measured by monitoring vaginal blood flow with a vaginal photoplethysmograph. Results showed significant increases in vaginal blood flow in response to both sexual anxiety and sexual pleasure. However, increases in the pleasure condition were significantly greater than those in the anxiety condition. Analysis of the blood flow across time showed a significant linear increasing trend in the pleasure condition and a lack of such a trend in the anxiety condition.


Incorporation of Storytelling as a Method of Oral Health Education among 3-6-year-old Preschool Children.
To find the effectiveness of storytelling as a method of oral health education among 3-6-year-old preschool children. A non-randomized experimental pre-post study design. Preschools located in urban Bengaluru. Two hundred, 3-6 years, preschool children. An age-appropriate story with oral health messages was delivered using hand puppets during the storytelling session in preschool. A self-administered 11-item picture-based, closed-ended questionnaire assessed children's knowledge and attitude at baseline and post-intervention. A 1-week audit sheet to monitor the brushing, eating, and mouth rinsing pattern was administered for the parents to measure the change in behavior post-intervention. Change in KAP mean scores was assessed using the "Wilcoxon Sign Rank test" at p < 0.05. "Cohen's d" was used to calculate the "Effect size". Significant improvement was observed in mean KAP score (pre 7.52 ± 1.95 post 8.60 ± 1.55, p = 0.0001) with effect size 0.2. There was a significant increase in the knowledge and attitude and practice score, knowledge (pre 2.97 ± 1.02, post 3.63 ± 0.78, p = 0.0001, effect size: 0.3), attitude (2.27 ± 0.81, 2.77 ± 0.60, p = 0.000, effect size: 0.3), and practice (2.04 ± 1.07, 2.28 ± 0.60, p = 0.0001, effect size: 0.1). The storytelling method was effective in improving the oral health-related KAP of children aged 3-6 years. This study attempts to inculcate good oral hygiene practices at a very early stage by targeting 3-6-year-old preschool children. Storytelling being humankind's oldest form of teaching and motivating change, can not only address the prevailing oral disease burden but also the oral health inequality by reaching out to every community. Shruti T, Govindraju HA, Sriranga J. Incorporation of Storytelling as a Method of Oral Health Education among 3-6-year-old Preschool Children. Int J Clin Pediatr Dent 2021;14(3):349-352.


Nonmelanoma skin cancer visits and procedure patterns in a nationally representative sample: national ambulatory medical care survey 1995-2007.
The rising incidence of nonmelanoma skin cancer (NMSC) is well documented, but data are limited on the number of visits and treatment patterns of NMSC in the outpatient setting. To evaluate practice and treatment patterns of NMSC in the United States over the last decade and to characterize differences according to sex, age, race, insurance type, and physician specialty. Adults with an International Classification of Diseases, Ninth Revision, diagnosis of NMSC were included in this cross-sectional survey study of the National Ambulatory Medical Care Survey between 1995 and 2007. Primary outcomes included population-adjusted NMSC visit rates and odds ratios of receiving a procedure for NMSC using logistic regression. Rates of NMSC visits increased between 1995 and 2007. The number of visits was significantly higher in men, particularly those aged 65 and older. Fifty-nine percent of NMSC visits were associated with a procedure, and the individuals associated with that visit were more likely to be male, to be seen by a dermatologist, and to have private-pay insurance. Nonmelanoma skin cancer visit rates increased from 1995 to 2007 and were higher in men than women. Visits to a dermatologist are more likely to be associated with a procedure for NMSC, and there may be discrepancies in treatment patterns based on insurance type and sex.


Surgical and endovascular treatment of severe complications secondary to noncirrhotic portal hypertension: experience of 56 cases.
Major complications of noncirrhotic portal hypertension (NCPH) include bleeding esophagogastric varices, hypersplenism, ascites, and bowel ischemia under acute circumstances. The aim of this article is to determine the outcomes of surgical and endovascular treatments for severe complications from NCPH. From January 2000 to June 2011, 56 patients with symptomatic NCPH underwent open surgery or endovascular thrombolysis. The medical records were retrospectively reviewed. Of the 56 patients, there were 39 males and 17 females. The mean age was 21 years, ranging from 2 to 54 years. Forty-one of them were diagnosed to have prehepatic portal vein obstruction (PHPVO), 9 had Budd-Chiari syndrome (BCS), and 6 had noncirrhotic portal fibrosis (NCPF). All patients were symptomatic from 5 days to 14 years (mean 25 months). Portosystemic shunt (PSS) was primarily performed in 49 patients. Shunts were as follows: 35 mesocaval; 7 splenorenal; 4 portocaval; 2 paraumbilical-jugular; and 1 portal to right atrial. Esophagogastric devascularization was performed in 3 patients, but was converted to mesocaval shunt later in 2. The remaining 4 patients with acute superior mesenteric vein (SMV) and portal vein thrombosis were treated with endovascular catheter-directed thrombolysis. Warfarin was prescribed to all the patients for at least 6 months. Mean follow-up was 57 months, ranging from 2 to 125 months. The outcomes, focusing on 30-day mortality, recurrent bleeding, and hypersplenism, were recorded. In the 49 patients undergoing primary PSS, the shunts remained patent and there was no recurrent variceal bleeding during the follow-up. All 3 patients with esophagogastric devascularization had recurrent variceal bleeding at 8, 13, and 24 months postoperatively. Two of them were converted to mesocaval shunt, and 1 died before redo operation. Thrombolysis in all 4 patients with acute SMV and portal thrombosis was technically successful. Three of the 4 survived without complications and 1 died from small bowel infarction due to recurrent thrombosis 40 days later. In the 47 patients with hypersplenism, mean platelet counts increased from 43×10(9)/L to 239×10(9)/L 2 weeks after surgery. Ascites in 30 of the 31 patients disappeared within 2 months after PSS. There was no postoperative encephalopathy, and perioperative 30-day mortality was 0%. PSS can be employed to treat bleeding esophagogastric varices and severe hypersplenism secondary to NCPH. Post-PSS encephalopathy is less of a concern in NCPH patients with normal liver function. Endovascular catheter-directed thrombolysis via superior mesenteric artery is a useful alternative treatment for acute portal and/or mesenteric venous thrombosis.


Occurrence of Raphidiopsis raciborskii blooms in cool waters: Synergistic effects of nitrogen availability and ecotypes with adaptation to low temperature.
Raphidiopsis raciborskii is a diazotrophic and potentially toxic cyanobacterium. To date, this species has successfully invaded many regions from the tropics to sub-tropical and temperate regions, typically forming blooms at temperatures greater than 25 °C. However, there have been a few cases in which R. raciborskii blooms have occurred at low temperatures (below 15 °C), but its cause and mechanisms remain unclear. In this study, field investigations revealed that R. raciborskii blooms occurred at 10-15 °C in Lake Xihu, Yunnan, China. The biomass of R. raciborskii was found to be positively related to nitrate concentrations in this lake. Three strains of R. raciborskii, two isolated from Lake Xihu (CHAB 6611 and CHAB 6612) and one from Lushui Reservoir in central China (CHAB 3409), were used for growth experiments at 15 °C. The three strains exhibited genotypic (16S rRNA and ITS-L genes) and physiological differences in response to nitrogen concentrations at low temperature. The growth rates of strains CHAB 6611 and CHAB 6612 increased with nitrogen concentration while CHAB 3409 could not grow at 15 °C. Furthermore, the growth and phenotypic responses of CHAB 6611 and CHAB 6612 to nitrogen concentrations were different, despite the closer genetic relationship shared by these two strains. Thus, increased nitrogen concentration in water may enhance the biological availability and utilization of nitrogen by R. raciborskii, which is the external promoter, leading to improving the resistance of R. raciborskii to low temperature. The internal cause is the presence of ecotypes in R. raciborskii populations with adaptation to low temperature. With increasing global eutrophication, the distribution range of R. raciborskii as well as the scale of its blooms will increase. As such, the risk of exposure of aquatic biota and humans to cylindrospermopsin is also expected to increase.


Resources limit the fecundity of three woodland herbs.
Effects of supplemental hand pollination on fruit set, seed number, and seed weight were examined for 3 perennial, woodland herbs, Uvularia sessilifolia, Geranium maculatum, and Maianthemum canadense. We found no evidence for pollen limitation of any measure of fecundity. Low light probably limited fecundity in Geranium, while soil nitrogen limited the number of sseds/fruit in Maianthemum. For Geranium and Maianthemum the relationship between the number of flowers and fecundity varied in differeent years. Maianthemum ramets with greater than average flower numbers had a decreased chance of reproductive failure than did ramets with few flowers.


AlkB reverses etheno DNA lesions caused by lipid oxidation in vitro and in vivo.
Oxidative stress converts lipids into DNA-damaging agents. The genomic lesions formed include 1,N(6)-ethenoadenine (epsilonA) and 3,N(4)-ethenocytosine (epsilonC), in which two carbons of the lipid alkyl chain form an exocyclic adduct with a DNA base. Here we show that the newly characterized enzyme AlkB repairs epsilonA and epsilonC. The potent toxicity and mutagenicity of epsilonA in Escherichia coli lacking AlkB was reversed in AlkB(+) cells; AlkB also mitigated the effects of epsilonC. In vitro, AlkB cleaved the lipid-derived alkyl chain from DNA, causing epsilonA and epsilonC to revert to adenine and cytosine, respectively. Biochemically, epsilonA is epoxidized at the etheno bond. The epoxide is putatively hydrolyzed to a glycol, and the glycol moiety is released as glyoxal. These reactions show a previously unrecognized chemical versatility of AlkB. In mammals, the corresponding AlkB homologs may defend against aging, cancer and oxidative stress.


A medium for the detection of yeasts using a conductimetric method.
A new medium is described for the detection of yeasts using a Malthus microbial growth analyser which measures conductivity. This medium is superior to previous media devised for use in the Malthus, and allows the detection of a wide range of yeasts including those important in food spoilage. The new medium was inferior to existing media used to detect yeasts in the Bactometer 32 instrument which measures impedance.


Truncated dopamine transporter's epigenetics: Heterozigosity of the grandmother rat temperates the vulnerable phenotype in second-generation offspring.
Behavioral phenotype differs among epigenotypes of dopamine-transporter heterozygous (DAT-HET) rats. Epigenetic regulations act through transgenerational effects, referring to phenotypic variations emerging at second or third generation. To investigate transgenerational influences exerted by maternal grandmothers, we developed breeding schemes where only the genotype of maternal grandmothers varied. HET females, to serve as MAT vs. MIX mothers, were generated, respectively, from WT × KO = MAT and MAT × KO = MIX breeding, with KO males acting as grandfather. The HET experimental groups, generated from either MAT or MIX mothers, were called MIX-by-MAT and MIX2 (male-fathers KO; asset-M: wild/healthy-allele from dam) or SOT and SIX (male-fathers WT; asset-P: mutated-allele from dam). Thus, sequelae of first encounter between wild/healthy and mutated DAT alleles (in maternal-lineage) were compared at first- (MAT-dam, WT-grandmother) vs. at second- (MIX-dam, HET-grandmother) generation. We characterized, within these epigenotypes, (1) circadian home-cage activity and (2) preference for social stimuli. Marked alterations of circadian activity appeared in MIX-by-MAT HETs, offspring of MAT-dams, compared with MIX2 HET (offspring of MIX-dams); The latter, in turn, were undistinguishable from WT-controls. A clear-cut social preference by WT rats was expressed towards SIX compared with SOT stimulus rats, confirming that the latter elicited reduced social motivations. In conclusion, significant epigenetic modulations took place in DAT-HET rats, as a function of maternal grandmother's genotype.


New Optical Imaging Reporter-labeled Anaplastic Thyroid Cancer-Derived Extracellular Vesicles as a Platform for In Vivo Tumor Targeting in a Mouse Model.
Extracellular vesicles (EVs), originating from multivesicular bodies by invagination of the endosomal membrane, are communication channels between distant cells. They are natural carriers of exogeneous cellular materials and have been exploited as drug delivery carriers in various diseases. Here, we found that tumor cell-derived EVs can be used as efficient targets in tumors by monitoring with an optical reporter system. Anaplastic thyroid cancer (CAL62) cell-derived EVs with Renilla luciferase (Rluc) were used to target CAL62 tumors in a mouse model. Optical imaging revealed that cancer cell-derived EVs (EV-CAL62/Rluc) targeted the original tumor (CAL62) in mice within 30 min after systemic injection. Furthermore, fluorescence imaging revealed that EV-CAL62/Rluc were internalized into CAL62 tumors in the mice. Ex vivo Optical imaging further confirmed the in vivo finding. Here, we successfully monitored the tumor targeting ability of tumor cell-derived EVs by optical imaging. Based on these results, tumor cell-derived EVs are highly effective natural carriers for drug delivery for cancer therapies.


Characterization of two point mutations in the androgen receptor gene of patients with perineoscrotal hypospadia.
Perineoscrotal hypospadia is a major sign of sexual ambiguity due to inadequate androgen action in genetic and gonadal males. In patients showing these symptoms we have detected two androgen receptor gene mutations. In consequence we characterized the properties of the mutant receptors with respect to hormone-binding, transactivation and DNA-binding. An amino acid substitution alanine-596-->threonine in the D-box of the androgen receptor was detected in 3 and 2 brothers, respectively. This mutant receptor, AR-thr596, bound ligand in a normal fashion. It showed a promoter-dependent defect of transactivation and was unable to induce transcription of a promoter containing one androgen responsive element but showed almost wild-type transactivation of a promoter containing two closely spaced androgen-responsive elements. The complex promoter of the human prostate-specific antigen gene was induced with intermediate efficiency. In electrophoretic mobility shift assays AR-thr596 was unable to form a complex with oligonucleotides containing 1 or 2 androgen responsive elements, however its DNA-binding activity was restored by an anti-androgen receptor antibody in the presence of ligand. A point mutation which caused substitution of serine-703 in the hormone-binding domain with glycine was detected in a new-born male with ambiguous genitalia. This mutant receptor, AR-gly703, showed a reduced ligand affinity. The total amount of specific androgen binding sites in genital fibroblasts of the patient was reduced. Transactivation activity of AR-gly703 was dependent on hormone concentration. It was inactive at low levels of androgens but was fully activated in the presence of high androgen concentrations. The nature of the promoter had no effect on transactivation properties of this mutant androgen receptor. Its DNA-binding activity in gel shift experiments was normal.


Canalplasty: the technique and the analysis of its results.
To describe the technique for canalplasty as performed in the Academic Medical Center, Amsterdam, the Netherlands and to present the results of this technique. Retrospective chart analysis. Charts of patients who underwent a canalplasty prodedure between 2001 and 2010 were reviewed for indication for surgery, side of surgery, age at the time of surgery, gender, smoking habits, surgical outcome, results of pure tone audiometry pre-and post-operatively and the occurrence of complications. 193 canalplasty procedures with or without more extensive otosurgery in 174 patients were performed for various indications in the Academic Medical Center, Amsterdam, the Netherlands between 2001 and 2010. Complete re-epithelialization took approximately 6.7 weeks and was influenced by smoking and the surface needed to re-epithelialize. Complications occurred in 28.0% of cases, of which most (98%) could be regarded as transient. No significant changes in pure tone bone conduction levels at 1, 2 and 4 kHz were observed. This retrospective study shows that technique for canalplasty as used in the Academic Medical Center, Amsterdam, the Netherlands can be used for a wide variety of indications, highlighting its added value in otosurgery.


Multi-antigen immunization using IgG binding domain ZZ as carrier.
This article describes a method in which multiple vaccine candidates can be tested in parallel for their immunogenicity. Antigens derived from the genome sequence of Neisseria meningitidis group B strain MC58 were cloned and expressed as recombinant proteins fused to the IgG-binding domain ZZ or to a His-tag. Immunization of mice with a mixture of 22 ZZ-fusion antigens applied with the adjuvant QuilA, induced an enhanced immune response as compared to the same antigen mixture without QuilA or a mixture containing the corresponding His-tagged antigens with QuilA. The enhanced immune response of the ZZ-fusion antigens/QuilA preparation was apparent from 1) the higher number of antigens in the mixture that elicited an antibody response and 2) the much lower antigen dose needed to get this response. Our approach using ZZ-fusion antigens/QuilA mixtures may serve as a high throughput discovery tool for new vaccine candidates.


Current overview of the role of Akt in cancer studies via applied immunohistochemistry.
The family of AKT kinases, AKT-1, 2, and 3, collectively play a crucial role in key processes, as well as pathologic processes such as oncogenesis. The numerous AKT phosphorylation targets include proteins essential to the regulation of cell cycling, protein translation, suppression of programmed cell death, all of which, upon activation via AKT-mediated phosphorylation, promote tumor growth, survival, and aggressiveness. Activation of the AKT pathway can be immunohistochemically detected with antibodies that specifically react with phosphorylated or nonphosphorylated forms of AKT. The following review summarizes the use of phospho-AKT immunohistochemistry as a potentially valuable tool in cancer prognostication in a wide spectrum of common and uncommon malignancies, including squamous carcinoma of cervix and of head and neck; adenocarcinoma of endometrium, ovarian, breast, prostate, kidney, colon, and pancreas; carcinomas of lung and thyroid; and hematopoietic, soft tissue, and central nervous system neoplasms. To date, the findings overall suggest that the major use of p-AKT immunohistochemical staining lies in prognostication and possibly in individualization of therapy rather than in differential diagnosis.


Cerebral microstructural changes in children suffering from hemolytic uremic syndrome.
To evaluate microstructural cerebral changes in children suffering from typical hemolytic uremic syndrome (HUS) based on apparent diffusion coefficient (ADC) maps. For 12 pediatric HUS patients (0.8 - 14.6 years of age) conventional magnetic resonance imaging (cMRI) at 1.5 T was retrospectively analyzed. ADC values were measured in 35 different brain regions and compared with age-related, previously published ADC reference values from a healthy pediatric control group. The HUS cohort was divided into 2 subgroups depending on clinical outcome. Subgroup A showed poor neurological outcome whereas subgroup B demonstrated improvement without lasting neurological deficits. Qualitative analysis revealed lesions by diffusion-weighted imaging (DWI) with hypointense correlate on the ADC map in basal ganglia and/or thalami and corresponding T2 hyperintensities in the majority of patients in Subgroup A (80%). Those in Subgroup B did not show qualitative DWI alterations with ADC correlate even when T2 hyperintense lesions were detected in basal ganglia and/or thalami. Quantitative analysis demonstrated abnormal ADC values in all HUS patients with a trend to a greater number of affected regions in Subgroup A compared to Subgroup B (16 versus 11 median number of regions respectively, p = 0.56). Conclusion: Using DWI qualitative and quantitative differences were found between HUS patients showing poor neurological outcome and those without neurological deficits at discharge. While ADC values indicated more extensive cerebral changes than conventional qualitative findings, both may provide early prognostic indicators for neurological outcome in pediatric HUS patients. What is Known: • In patients with STEC-HUS and neurological symptoms, MRI may show hyperintense signals on T2 and altered diffusivity mostly affecting basal ganglia, thalami and periventricular white matter. What is New: • In such patients, early MRI including quantitative ADC measurements over different brain regions may allow for detection of signal alterations possibly reflecting microstructural changes in such patients.


Orange G is a potential inhibitor of human insulin amyloid fibrillation and can be used as a probe to study mechanism of amyloid fibrillation and its inhibition.
The extracellular insoluble deposits of highly ordered cross-β-structure-containing amyloid fibrils form the pathological basis for protein misfolding diseases. As amyloid fibrils are cytotoxic, inhibition of the process is a therapeutic strategy. Several small molecules have been identified and used as fibrillation inhibitors in the recent past. In this work, we investigate the effect of Orange G on insulin amyloid formation using fluorescence-based assays and negative-stain electron microscopy (EM). We show that Orange G effectively attenuates nucleation, thereby inhibiting amyloid fibrillation in a dose-dependent manner. Fluorescence quenching titrations of Orange G showed a reasonably strong binding affinity to native insulin. Binding isotherm measurements revealed the binding of Orange G to pre-formed insulin fibrils too, indicating that Orange G likely binds and stabilizes the mature fibrils and prevents the release of toxic oligomers which could be potential nuclei or templates for further fibrillation. Molecular docking of Orange G with native insulin and amyloid-like peptide structures were also carried out to analyse the contributing interactions and binding free energy. The findings of our study emphasize the use of Orange G as a molecular probe to identify and design inhibitors of amyloid fibrillation and to investigate the structural and toxic mechanisms underlying amyloid formation.


[Juvenile breast hypertrophy: analysis of long-term results of reductive mammoplasty].
Reduction mammaplasty has now become routine surgery with good results in middle-aged women. However the scars it leaves, its psychological and functional (breastfeeding) impact could limited its indications in teenage girls. The purpose of our study was to report the long-term results of reduction mammaplasty in teenage girls and to assess their consequences. We conducted a retrospective study of 65 reduction mammaplasty carried out between 1981 and 1997 in 15 to 17 years old girls. The study was based on data in their medical records and answers to a questionnaire which was sent to each patient. Average followup was 8.1 years. The reduction technique with superior pedicle were mainly used. Average breast tissue excised was 1050 g. Minor complications occurred in three cases. Eleven revisions had to be carried out with 1.6 years on average after primary surgery. The psychological and functional complaints observed preoperatively disappeared in more than 90% of the cases. In over 80% of the cases the patients were pleased or very pleased with the shape, the volume kept and the symmetry. Scars were well accepted in 83% of the cases. Seventeen women were given birth to 25 children. Five of whom breast-fed their babies, while six refused because of their breast surgery history. Although information about breast-feeding after such surgery is systematically given, 41 women claimed they had not received it. Reduction mammaplasty is reliable in teenage girls. Patients are generally satisfied and the remaining scar is well accepted. Breast-feeding is possible after this surgery and information on that point ought to be better developed.


Asymmetric division triggers cell-specific gene expression through coupled capture and stabilization of a phosphatase.
Formation of a division septum near a randomly chosen pole during sporulation in Bacillus subtilis creates unequal sized daughter cells with dissimilar programs of gene expression. An unanswered question is how polar septation activates a transcription factor (σ(F)) selectively in the small cell. We present evidence that the upstream regulator of σ(F), the phosphatase SpoIIE, is compartmentalized in the small cell by transfer from the polar septum to the adjacent cell pole where SpoIIE is protected from proteolysis and activated. Polar recognition, protection from proteolysis, and stimulation of phosphatase activity are linked to oligomerization of SpoIIE. This mechanism for initiating cell-specific gene expression is independent of additional sporulation proteins; vegetative cells engineered to divide near a pole sequester SpoIIE and activate σ(F) in small cells. Thus, a simple model explains how SpoIIE responds to a stochastically-generated cue to activate σ(F) at the right time and in the right place.


Fluoroscopically controlled transbronchial biopsy of solitary peripheral pulmonary lesions using the fibreoptic bronchoscope.
Experience of fluoroscopically controlled transbronchial biopsy using the fibreoptic bronchoscope in 30 patients with solitary lesions in the peripheral lung fields beyond bronchoscopic vision is described. At the time of submitting this paper for publication (30 January 1978) no account of the technique has been reported in the British literature. In 21 patients with a final diagnosis of bronchial carcinoma a positive biopsy diagnosis was obtained in 14 (67%). Five of seven patients (71%) with a final diagnosis of an inflammatory condition showed evidence of acute or chronic inflammation on biopsy. There were no complications. The procedure is indicated when a definitive diagnosis is required for management planning in clinically inoperable patients, or when a tissue diagnosis is particularly desired in an attempt to obviate the need for thoracotomy. The relative safety makes this the biopsy technique of choice for the evaluation of isolated peripheral pulmonary opacities.


Production of oxychemicals from precipitated hardwood lignin.
Lignin is a major byproduct in the biomass-to-ethanol process. The lignin produced from acid treatment of biomass has characteristics suitable for further conversion to organic chemicals. It is free of contaminants and has a relatively low molecular weight. In this study, catalytic oxidative conversion of the acid-soluble lignin precipitated from acid hydrolysates of hardwood was investigated. The process is based on aqueous alkaline oxidation of lignin with dissolved O2 in the presence of Fe3+ and Cu2+ catalysts at moderate reaction temperatures (160-180 degrees C). Aromatic aldehydes, ketones, and organic acids are found to be the primary products identifiable on extraction with ether. The combined weight yield of the total ether extractable products is about 20-25% of the initial lignin. The yield of the aldehydes (vanillin + syringaldehyde) is in the vicinity of 15% with an additional 3 to 4% of aromatic ketones. The yields of aldehydes plus ketones observed in this work far exceeded those obtainable from the conventional alkaline air oxidation of spent sulfite liquors. This article also provides comprehensive batch reaction data on conversion and product distribution.


5-HIAA in cerebrospinal fluid of patients with status epilepticus.
Cerebrospinal fluid concentration of 5-hydroxyindolacetic acid (5-HIAA) was determined in 15 patients soon after recovery from status epilepticus. Similarly, patients with generalised epilepsy and persons without epilepsy, serving as controls, were also studied. The level of 5-HIAA was significantly reduced in all epileptic patients with or without status epilepticus, as compared with the nonepileptic control group. However, there was no statistical difference between patients with status epilepticus and those with generalised epilepsy. Among patients with epilepsy, low 5-HIAA levels in CSF could not be correlated with frequency or severity of seizures, or with antiepileptic drugs. A link between CSF 5-HIAA and susceptibility of humans to epilepsy may indicate a possible future therapeutic approach.


Transformational deficits in cognition of schizophrenic children.
This study examined schizophrenic children for cognitive deficits in logical thinking, symbolic imagery, and conservation. Evaluation revealed persistent failure of the aberrant subjects to achieve at the level of age expectancy. Comparison with nonpsychotic, institutionalized children demonstrated no effect due to institutionalization. By mid-teens not one of the subjects had accomplished formal operations and very few were able to master concrete operations. Implications for development and treatment were discussed.


Prognostic impact of immunophenotypic aberrancies of blasts in lower risk myelodysplastic syndrome.
Low risk myelodysplastic syndrome (MDS) is a marrow failure state eventually leading to transfusion dependence. Flow cytometry has previously been demonstrated as prognostic tool in MDS, however not thoroughly studied in lower risk MDS. In this study, we assessed whether assessment for immunophenotypic blast aberrancies by flow in low risk MDS patients has a prognostic role in these patients. A total of 63 consecutive patients diagnosed with low/intermediate risk MDS were included. We recorded initial flow results, and collected time to transfusion dependence, and AML progression. On multivariate cox regression analysis, increasing IPSS-R score, an increase in the number of blast aberrancies on flow cytometry, and aberrant expression of CD7 on myeloid blasts increased likelihood of transfusion dependence. Low risk MDS patients with increasingly aberrant blast phenotypes by flow may be at risk for earlier transfusion dependence.


A caspase-dependent cleavage of CDC25A generates an active fragment activating cyclin-dependent kinase 2 during apoptosis.
The cellular level of the CDC25A phosphatase is tightly regulated during both the normal and genotoxic-perturbed cell cycle. Here, we describe a caspase-dependent cleavage of this protein at residue D223 in non-genotoxic apoptotic conditions. This specific proteolysis generates a catalytically active C-terminal fragment that localizes to the nuclear compartment. Accumulation of this active CDC25A fragment leads to reduced inhibitory phosphorylation of the CDC25A substrate cyclin-dependent kinase 2 (CDK2) on Tyr15. Moreover, CDK2 was found stably associated with this fragment, as well as with an ectopically expressed CDC25A224-525 truncation mutant that mimicks the cleavage product. Ectopic expression of this mutant induced CDK2 Tyr15 dephosphorylation, whereas its catalytically inactive version did not. Finally, this 224-525 mutant initiated apoptosis when transfected into HeLa cells, whereas its catalytic inactive form did not. Altogether, this study demonstrates for the first time that caspase-dependent cleavage of CDC25A is a central step linking CDK2 activation with non-genotoxic apoptotic induction.


Comparison of children with autism spectrum disorder with and without schizophrenia spectrum traits: gender, season of birth, and mental health risk factors.
Children with autism spectrum disorder (ASD) with and without co-occurring schizophrenia spectrum traits (SST) were examined for differences in co-occurring psychiatric symptoms, background characteristics, and mental health risk factors. Participating mothers and teachers completed a DSM-IV-referenced rating scale and a background questionnaire (mothers only) describing 147 children (6-12 years) with ASD. There was a clear pattern of group differences in co-occurring psychiatric symptom severity (+SST > SST-) and background characteristics. Children with impairing SST had more mental health risk factors. Girls were more likely to be classified SST according to mothers' ratings. Children born in spring-summer were more likely to be classified non-SST by teachers' ratings. Findings provide tentative evidence that SST may be a useful marker of behavioral heterogeneity within the ASD clinical phenotype.


[Differences in the measurement results of Goldmann applanation tonometry with and without fluorescein].
Goldmann applanation tonometry (GAT) is still the gold standard for measuring the intraocular pressure (IOP). Usually fluorescein eye drops are used additional to topical anesthesia to gain the best visualization results. The present study evaluated the differences in the results of GAT with and without fluorescein. A total of 400 eyes of 200 patients without known glaucoma were enrolled in this study and randomized to two groups: group A (first measurement without, second measurement with fluorescein) and group B (first measurement with fluorescein, second without). All measurements were performed by the same examiner with the same slit lamp. Results were analyzed by Bland-Altman plots and Spearman's correlation test. The examined groups showed no significant differences regarding patient age, astigmatism or reason for consulting. In both groups performing GAT without the application of fluorescein led to significantly lower measurement results. The differences were 1.5 ± 1.7 mmHg SD in group A, 1.2 ± 1.6 mmHg SD in group B and 1.4 ± 1.65 mmHg SD for all eyes. The intraocular pressure (IOP) and the differences between the groups were independent of patient age, astigmatism, reason of consulting or IOP level. Both groups showed outliers up to 10 mmHg difference because of corneal edema. Measurements from GAT without fluorescein differed significantly from measurements with fluorescein, independently of patient age, astigmatism, reason for consulting or IOP level. The mean difference of 1.4 mmHg may seem negligible in daily routine but can lead to serious consequences in borderline cases.


Do low levels of labour pain reflect low sensitivity to noxious stimulation?
In a study investigating factors affecting labour pain, 10 out of 97 subjects reported that they had never experienced any pain outwit childbirth. These subjects experienced comparatively low levels of pain within childbirth. They did not differ significantly from the majority of subjects on a large number of obstetric and psychological factors which normally affect pain in labour. It was suggested that these subjects were relatively insensitive to noxious stimulation, in that they do not experience pain when noxious stimulation is mild or moderate (as for example a consequence of menstruation, common accidents or ailments) and experience lower than average levels of pain when noxious stimulation is intense as in labour. Further investigation of such subjects is of theoretical interest and practical importance since it might allow for accurate prediction of pain levels in a proportion of parturants.


Genome-wide AP2/ERF gene family analysis reveals the classification, structure, expression profiles and potential function in orchardgrass (Dactylis glomerata).
The AP2/ERF transcription factor (TF) family is of great importance in developmental regulation and responses to stress and pathogenic stimuli. Orchardgrass (Dactylis glomerata), a perennial cold-season forage of high quality in the world's temperate zones, contributes to grazing land through mixed sowing with alfalfa (Medicago sativa) and white clover (Trifolium repens). However, little is known about AP2/ERF TFs in orchardgrass. In this study, 193 AP2/ERF genes were classified into five subfamilies and 13 subgroups through phylogenetic analysis. Chromosome structure analysis showed that AP2/ERF family genes in orchardgrass were distributed on seven chromosomes and specific conservative sequences were found in each subgroup. Exon-intron structure and motifs in the same subgroup were almost identical, and the unique motifs contributed to the classification and functional annotation of DgERFs. Expression analysis showed tissue-specific expression of DgERFs in roots and flowers, with most DgERFs widely expressed in roots. The expression levels of each subgroup (subgroups Vc, VIIa, VIIIb, IXa, and XIa) were high at the before-heading and heading stages (BH_DON and H_DON). In addition, 12 DgERFs in various tissues and five DgERFs associated with abiotic stresses were selected for qRT-PCR analysis showed that four dehydration-responsive element binding (DREB) genes and one ERF subfamily gene in orchardgrass were regulated with PEG, heat and salt stresses. DgERF056 belonged to ERF subfamily was involved in the processes of flowering and development stage. This study systematic explored the DgERFs at the genome level for the first time, which lays a foundation for a better understanding of AP2/ERF gene function in Dactylis glomerata and other types of forage.


Angiotensin II and interleukin-1 interact to increase generation of dopaminergic neurons from neurospheres of mesencephalic precursors.
Cultures of rat mesencephalic precursors treated with interleukin-1beta or angiotensin II contained significantly more dopaminergic neurons than controls. However, simultaneous treatment with angiotensin II and interleukin-1beta did not induce any further increase. Treatment with the angiotensin type-2 receptor antagonist PD 123319 precluded both the angiotensin- and the interleukin-induced increase. The present results indicate that angiotensin type-2 receptors and interleukin-1 cooperate to induce the dopaminergic phenotype.


A natural occurring bifunctional CPD/(6-4)-photolyase from the Antarctic bacterium Sphingomonas sp. UV9.
Photolyases are flavoproteins that repair ultraviolet-induced DNA lesions (cyclobutane pyrimidine dimer or CPD, and pyrimidine (6-4) pyrimidone photoproducts or (6-4)-PPs), using blue light as an energy source. These enzymes are substrate specific, meaning that a specific photolyase repairs either a CPD or a (6-4)-PP. In this work, we produced a class II CPD-photolyase (called as PhrSph98) from the Antarctic bacterium Sphingomonas sp. UV9 by recombinant DNA technology and we purified the enzyme using immobilized metal affinity chromatography. By using an immunochemistry assay, with monoclonal antibodies against CPD and (6-4)-PP, we found that PhrSph98 repairs both DNA lesions. The result was confirmed by immunocytochemistry using immortalized non-tumorigenic human keratinocytes. Results from structure prediction, pocket computation, and molecular docking analyses showed that PhrSph98 has the two expected protein domains (light-harvesting antenna and a catalytic domain), a larger catalytic site as compared with photolyases produced by mesophilic organisms, and that both substrates fit the catalytic domain. The results obtained from predicted homology modeling suggest that the electron transfer pathway may occur following this pathway: Y389-W369-W390-F376-W381/FAD. The evolutionary reconstruction of PhrSph98 suggests that this is a missing link that reflects the transition of (6-4)-PP repair into the CPD repair ability for the class II CPD-photolyases. To the best of our knowledge, this is the first report of a naturally occurring bifunctional, CPD and (6-4)-PP, repairing enzyme. KEY POINTS: • We report the first described bifunctional CPD/(6-4)-photoproducts repairing enzyme. The bifunctional enzyme reaches the nuclei of keratinocyte and repairs the UV-induced DNA damage. The enzyme should be a missing link from an evolutionary point of view. The enzyme may have potential uses in the pharmaceutical and cosmetic industries.


Age, cellular immunity and the HP axis in major depression.
1. To assess the effect of age on cellular immune status and the HP axis in patients with major depression, we examined peripheral blood mononuclear cells (PBMC) and measured the plasma level of four neurohormones. 2. In 36 subjects, decreasing T lymphocyte response to con A covaried with age. Percent of lymphocytes labeled as T8 lymphocytes tended to decrease and T4/T8 ratio tended to increase with increasing age. 3. Hamilton and Beck scores were significantly different between the two sex and race matched groups of 18 depressed patients and 18 control subjects, and plasma prolactin was significantly higher in depressed subjects. 4. Increasing age correlated with decreasing T lymphocyte response to con A in the combined group of all subjects, and in the control group, but not in the patient group. 5. Hamilton and Beck scores correlated inversely with T lymphocytes response in the combined group of all subjects. 6. Differences in mitogen responsiveness between patient and control groups were not found, having been obscured by the effect of age. 7. These findings indicate the need to age match subjects when studying the interaction between depression and immune cell function.


Hamstring muscle-tendon unit lengthening and activation in instep and cut-off kicking.
Hamstring muscle strain injury is one of the most common injuries in sports involving sprinting and kicking. Studies examining hamstring kinematics and activations are rich for sprinting but lacking for kicking. The purpose of this study was to examine kinematics and activations of hamstring muscles in instep and cut-off kicking tasks frequently performed in soccer. Videographic and electromyographic (EMG) data were collected for 11 male soccer-majored college students performing the two kicking tasks. Peak hamstring muscle-tendon unit lengths, elongation velocities, and maximum linear envelop EMG data were identified and compared among hamstring muscles and between kicking tasks. Hamstring muscles exhibited activated elongations before and after the contact of the kicking foot with the ball. The muscle-tendon unit lengths peaked in the follow-through phase. The peak elongation velocity of the semimembranosus was significantly greater than that of the semitendinosus and biceps femoris (p = 0.001). The maximum linear envelop EMG of the biceps femoris was significantly greater than that of the semimembranosus (p = 0.026). The potential for hamstring injury exists in the follow-through phase of each kicking task. The increased hamstring muscle-tendon unit elongation velocities in kicking tasks may explain the more severe hamstring injuries in kicking compared to sprinting.


[Surgical treatment of chronic ligament injuries of the knee joint].
Treatment for median knee-joint instability with a case history long time back may occasionally be time-consuming and dissatisfactory to patient and doctor. Several synthetic materials and autologous grafts are used in surgical therapy. Some of the methods are described in this paper. In one of them use of autologous tissue is combined with its "dynamisation".


A serum-free medium for clonal growth and serial subculture of diploid rat liver epithelial cells.
Clonal growth and serial subculture of diploid liver epithelial cells from neonatal rats were achieved in a serum-free medium (SFM) supplemented with linoleic and oleic acid linked to fatty acid-free bovine serum albumin (fafBSA), epidermal growth factor (EGF), transferrin, insulin, selenous acid, and fetuin. Because it is not known whether factors added to defined media facilitate attachment, support proliferation, or both, a serum-free "attachment medium" was first devised in which cells would attach to the substratum without loss of viability. Then a growth medium that would support cell proliferation was developed. Fetuin enhanced the degree of attachment, and the lipid supplements and EGF induced a marked proliferative response. Serum-free medium supported the formation of colonies equivalent in size, number, and morphology to those obtained in serum-supplemented medium. Cells plated at a higher inoculum density and subcultured regularly for up to 25 wk underwent two to three doublings per week and acquired a flattened epithelial cell morphology. Early passages of rat liver epithelial cells, cultured in SFM may be useful in studies of the regulation of cell proliferation and differentiation.


Verbal and visuospatial short-term memory in children: evidence for common and distinct mechanisms.
This study was designed to identify whether verbal and visuospatial short-term memory performance in children is served by common or distinct mechanisms. Five- and 8-year-old children were tested on their verbal recall of spoken letter names and digits, and on their recall of tapped sequences of blocks. The performance of the children on the verbal and visuospatial serial recall tasks was largely unrelated, extending evidence for dissociable memory systems found in adults. Detailed characteristics of recall, such as serial position functions, migration patterns, and distribution of error types, were similar in the tasks requiring recall of letters and of blocks, although order errors predominated in the block but not the letter recall task for the older children. These results appear to reflect the application of common processes specialized for the extraction of serial order information from the phonological and visuospatial components of short-term memory.


Activation of the ERK1/2 pathway mediates the neuroprotective effect provided by calycosin treatment.
Calycosin is a natural product extracted from some plant families and exhibits various biological properties. But the effect of calycosin on cerebral ischemia-reperfusion injury has not been fully elucidated. In this study, the neuroprotective effect of calycosin treatment on the differentiated SH-SY5Y cells exposed to OGD was evaluated using MTT and flow cytometry. Rats that were pretreatment with calycosin were subjected to MCAO, neurological behavior scores and brain infarct volume were evaluated. The protein expression of pERK/ERK were assessed using Western blot. siRNA-pERK and U0126 were administered to investigate the impact of the ERK pathway on calycosin preconditioning. The results demonstrated the neuronal viability in the calycosin-treated SH-SY5Y cells increased significantly, and the rate of apoptosis decreased compared with the Oxygen-glucose deprivation only SH-SY5Y cells. Calycosin pretreatment reduced infarct volume and improved neurological outcome in rats subjected to MCAO. Administration of calycosin increased the ratio of pERK/ERK expression, which was down-regulated in ischemia-reperfusion group. Down-regulation of pERK/ERK significantly attenuated the neuroprotective effect induced by calycosin pretreatment in vitro and in vivo. We concluded calycosin treatment could induce a neuroprotective effect against ischemia, which was related to the regulation of the ERK1/2 pathway.