Comparison of Three Total Ankle Replacement Systems Done at a Single Facility.
Ankle replacement surgery is an established and accepted way to treat end stage ankle arthritis. Though there are multiple publications looking at results with various ankle replacement systems, most of them are single implant longitudinal studies from a single institution. There are, however, no prospective randomized studies evaluating the outcomes of different total ankle arthroplasty (TAA) systems; in fact, there are no comparative studies at all. The comparative results of 3 different total ankle systems (INBONE, STAR, and Salto Talaris) were evaluated. All the TAA system implants were performed at a single institution from 2007 to 2011. The data were evaluated by authors completely independent from the study institution. The goal was to look at the results in an objective, noninstitution perspective. At minimum 2-year follow-up there is no statistical difference in outcomes scores or functional tests between the INBONE, STAR, or Salto Talaris, with all 3 TAA systems resulting in statistically significant improvement of all parameters since baseline. This is the first study that compares the results of 3 different total ankle replacement systems done at a single institution over the same period of time. Even though it is not a randomized study, it gives a valuable perspective of the short-term results. Therapeutic, Level IV: Case series.


[Effects of Cd on rape growth and antioxidant enzyme system].
The study with pot experiment showed that the fresh weights of rape plant and leaf decreased with increasing Cd concentration, and the decrease of leaf fresh weight resulted in the decrease of whole plant fresh weight. The permeability of cell membrane and the content of MDA increased with increasing Cd concentration. When the concentration of Cd was 20 mg x kg(-1), compared with the control, cell membrane permeability and MDA content were increased by 29.68% and 15.19% respectively, and there was a significant correlation between these two indices. When the Cd concentration was 5 mg x kg(-1), the contents of chlorophyll a, b and a + b reached their peaks, and were 23.97%, 33.63% and 26.45% higher than the control, respectively. Cd stress had no significant effect on carotenoid content. The sensibility of the pigments to Cd stress was chlorophyll b> chlorophyll a> chlorophyll a + b> carotenoid, and that of protective enzymes was POD>CAT>SOD. The IC50 of test physiological indices suggested that rape could only grow well on the soil with < 5 mg x kg(-1) Cd.


Synthesis, properties, crystal structures, and semiconductor characteristics of naphtho[1,2-b:5,6-b']dithiophene and -diselenophene derivatives.
In this paper we present the synthesis, structures, characterization, and applications to field-effect transistors (FETs) of naphtho[1,2-b:5,6-b']dithiophene (NDT) and -diselenophene (NDS) derivatives. Treatment of 1,5-dichloro-2,6-diethynylnaphthalenes, easily derived from commercially available 2,6-dihydroxynaphthalene, with sodium chalcogenide afforded a straightforward access to NDTs and NDSs including the parent and dioctyl and diphenyl derivatives. Physicochemical evaluations of NDT and NDS derivatives showed that these heteroarenes have a similar electronic structure with isomeric [1]benzothieno[2,3-b][1]benzothiophene (BTBT) and [1]benzoselenopheneno[2,3-b][1]benzoselenophene (BSBS) derivatives, respectively. Although attempts to fabricate solution-processed field-effect transistors (FETs) with soluble dioctyl-NDT (C(8)-NDT) and -NDS (C(8)-NDS) failed, diphenyl derivatives (DPh-NDT and DPh-NDS) afforded vapor-processed FETs showing field-effect mobility as high as 0.7 cm(2) V(-1) s(-1). These results indicated that NDT and NDS are new potential heteroarene core structures for organic semiconducting materials.


Exercise oxygen pulse kinetics in patients with hypertrophic cardiomyopathy.
Reduced cardiac output (CO) has been considered crucial in symptoms' genesis in hypertrophic cardiomyopathy (HCM). Absolute value and temporal behaviour of O2-pulse (oxygen uptake/heart rate (VO2/HR)), and the VO2/work relationship during exercise reflect closely stroke volume (SV) and CO changes, respectively. We hypothesise that adding O2-pulse absolute value and kinetics, and VO2/work relationship to standard cardiopulmonary exercise testing (CPET) could help identify more exercise-limited patients with HCM. CPETs were performed in 3 HCM dedicated clinical units. We retrospectively enrolled non-end-stage consecutive patients with HCM, grouped according to left ventricle outflow tract obstruction (LVOTO) at rest or during Valsalva manoeuvre (72% of patients with LVOTO <30; 10% between 30 and 49 and 18% ≥50 mm Hg). We evaluated the CPET response in HCM focusing on parameters strongly associated with SV and CO, such as O2-pulse and VO2, respectively, considering their absolute values and temporal behaviour during exercise. We included 312 patients (70% males, age 49±18 years). Peak VO2 (percentage of predicted), O2-pulse and ventilation to carbon dioxide production (VE/VCO2) slope did not change across LVOTO groups. Ninety-six (31%) patients with HCM presented an abnormal O2-pulse temporal behaviour, irrespective of LVOTO values. These patients showed lower peak systolic pressure, workload (106±45 vs 130±49 W), VO2 (21.3±6.6 vs 24.1±7.7 mL/min/kg; 74%±17% vs 80%±20%) and O2-pulse (12 (9-14) vs 14 (11-17) mL/beat), with higher VE/VCO2 slope (28 (25-31) vs 27 (24-31)) (p<0.005 for all). Only 2 patients had an abnormal VO2/work slope. None of the frequently used CPET parameters, either as absolute values or dynamic relationships, were associated with LVOTO. Differently, an abnormal temporal behaviour of O2-pulse during exercise, which is strongly related to inadequate SV increase, correlates with reduced functional capacity (peak and anaerobic threshold VO2 and workload) and increased VE/VCO2 slope, identifying more advanced disease irrespectively of LVOTO.


HGF synthesis in human lung fibroblasts is regulated by oncostatin M.
Oncostatin M (OSM) is a IL-6 family cytokine locally produced in acute lung injury. Its profibrotic properties suggest a role in lung wound repair. Hepatocyte growth factor (HGF), produced by fibroblasts, is involved in pulmonary epithelial repair. We investigated the role of OSM in HGF synthesis by human lung fibroblasts. We showed that OSM upregulated HGF mRNA in MRC5 cells and in human lung fibroblasts, whereas IL-6 and leukemia inhibitory factor did not. OSM induced HGF secretion to a similar extent as IL-1beta in both a time- and dose-dependent manner. HGF was released in its cleaved mature form, and its secretion was completely inhibited in the presence of cycloheximide, indicating a de novo protein synthesis. OSM in combination with prostaglandin E(2), a powerful HGF inductor, led to an additive effect. OSM and indomethacin in combination further increased HGF secretion. This could be explained, at least in part, by a moderate upregulation of specific OSM receptor beta mRNA expression through cyclooxygenase inhibition. These results demonstrate that OSM-induced HGF synthesis did not involve a PGE(2) pathway. OSM-induced HGF secretion was inhibited by PD-98059 (a specific pharmacological inhibitor of ERK1/2), SB-203580 (a p38 MAPK inhibitor), and SP-600125 (a JNK inhibitor) by 70, 82, and 100%, respectively, whereas basal HGF secretion was only inhibited by SP-600125 by 30%. Our results demonstrate a specific upregulation of HGF synthesis by OSM, most likely through a MAPK pathway, and support the suggestion that OSM may participate in lung repair through HGF production.


Germline breast cancer susceptibility gene mutations and breast cancer outcomes.
It is unclear whether germline breast cancer susceptibility gene mutations affect breast cancer related outcomes. We wanted to evaluate mutation patterns in 20 breast cancer susceptibility genes and correlate the mutations with clinical characteristics to determine the effects of these germline mutations on breast cancer prognosis. The study cohort included 480 ethnic Chinese individuals in Taiwan with at least one of the six clinical risk factors for hereditary breast cancer: family history of breast or ovarian cancer, young age of onset for breast cancer, bilateral breast cancer, triple negative breast cancer, both breast and ovarian cancer, and male breast cancer. PCR-enriched amplicon-sequencing on a next generation sequencing platform was used to determine the germline DNA sequences of all exons and exon-flanking regions of the 20 genes. Protein-truncating variants were identified as pathogenic. We detected a 13.5% carrier rate of pathogenic germline mutations, with BRCA2 being the most prevalent and the non-BRCA genes accounting for 38.5% of the mutation carriers. BRCA mutation carriers were more likely to be diagnosed of breast cancer with lymph node involvement (66.7% vs 42.6%; P = 0.011), and had significantly worse breast cancer specific outcomes. The 5-year disease-free survival was 73.3% for BRCA mutation carriers and 91.1% for non-carriers (hazard ratio for recurrence or death 2.42, 95% CI 1.29-4.53; P = 0.013). After adjusting for clinical prognostic factors, BRCA mutation remained an independent poor prognostic factor for cancer recurrence or death (adjusted hazard ratio 3.04, 95% CI 1.40-6.58; P = 0.005). Non-BRCA gene mutation carriers did not exhibit any significant difference in cancer characteristics or outcomes compared to those without detected mutations. Among the risk factors for hereditary breast cancer, the odds of detecting a germline mutation increased significantly with having bilateral breast cancer (adjusted odds ratio 3.27, 95% CI 1.64-6.51; P = 0.0008) or having more than one risk factor (odds ratio 2.07, 95% CI 1.22-3.51; P = 0.007). Without prior knowledge of the mutation status, BRCA mutation carriers had more advanced breast cancer on initial diagnosis and worse cancer-related outcomes. Optimal approach to breast cancer treatment for BRCA mutation carriers warrants further investigation.


Comparative evaluation of single and bilayered lamotrigine floating tablets.
The purpose of this study was to prepare lamotrigine (LM) bilayered and single layered floating tablets and to compare their release profiles. LM floating tablets were prepared by direct compression method. Drug, hydroxy propyl methyl cellulose K4M, lactose monohydrate and polyvinylpyrrolidone K30 constitute controlled release layer components and floating layer components includes polymers and sodium bicarbonate. The prepared tablets were evaluated for physicochemical parameters such as hardness, friability, weight variation, thickness, floating lag time (FLT), floating time, in vitro buoyancy study, in vitro release studies. The drug-polymer interaction was studied by fourier transform infrared and differential scanning calorimetry. The FLT of all the formulations were within the prescribed limits (<3 min). When ethyl cellulose was used as floating layer component, tablets showed good buoyancy effect but eroded within 6-8 h. Hence it was replaced with hydroxypropyl cellulose -M hydrophilic polymer, which showed good FLT and floating duration for 16 h. Formulation LFC4 was found to be optimized with dissolution profile of zero order kinetics showing fickian diffusion. A comparative study of bilayered and single layered tablets of LM showed a highest similarity factor of 83.03, difference factor of 2.74 and t-test (P < 0.05) indicates that there is no significant difference between them. Though bilayered tablet possess many advantages, single layered tablet would be economical, cost-effective and reproducible for large scale production in the industry. However, the results of present study demonstrated that the in vitro development of bilayered gastro retentive floating tablets with controlled drug release profile for LM is feasible.


Coronary artery spasm as a frequent cause of acute coronary syndrome: The CASPAR (Coronary Artery Spasm in Patients With Acute Coronary Syndrome) Study.
This study was conducted to clarify the incidence of coronary spasm in emergency patients with suspected acute coronary syndrome (ACS) and acute chest pain at rest. Chest pain at rest is a frequent symptom in the emergency room. Acute coronary syndrome is suspected in patients with elevation of cardiac markers, ischemic electrocardiographic changes, or simply typical clinical symptoms of unstable (usually resting) angina. However, of all patients with suspected ACS who undergo coronary angiography, up to 30% have nonobstructed coronary arteries. We sought to clarify how many of these patients suffer from coronary spasm as a possible cause of their chest pain. In a prospective study from June to December 2006, all patients with suspected ACS who underwent coronary angiography and had no culprit lesion underwent intracoronary provocation with acetylcholine. The ACH testing was considered positive at a vasoconstriction of >/=75% relative to the diameter after intracoronary nitroglycerine when the initially reported symptoms could be reproduced. Of 488 consecutive patients, 138 had no culprit lesion (28%). Twenty-two were found to have another diagnosis. The ACH testing was performed in 86 of the remaining 116 patients. In 42 patients, coronary spasm was verified (49%). Every fourth patient with ACS had no culprit lesion. Coronary spasm could be documented in nearly 50% of the patients tested by ACH. Coronary spasm is a frequent cause of ACS and should regularly be considered as a differential diagnosis.


Gestational diabetes mellitus among Norwegian women with polycystic ovary syndrome: prevalence and risk factors according to the WHO and the modified IADPSG criteria.
The consequences of the recently proposed International Association of Diabetes in Pregnancy Study Group (IADPSG) criteria for gestational diabetes mellitus (GDM) in women with polycystic ovary syndrome (PCOS) are not known. We compared the prevalence rates and risk factors for GDM in PCOS women according to both the WHO and the modified IADPSG criteria. Post hoc analyses from a randomized, multicenter study were used. Fasting and 2-h plasma glucose levels were measured using a 75 g oral glucose tolerance test. GDM was diagnosed according to both the WHO and the modified IADPSG criteria. The prevalence rates of GDM according to the WHO and the modified IADPSG criteria were 9.2 and 15.0% at week 12, 18.7 and 18.7% at week 19, and 25.6 and 24.2% at week 32. Shorter stature and increased insulin levels were correlated with WHO-GDM, but not with modified IADPSG-GDM at weeks 12 and 19. Less weight gain in pregnancy predicted GDM according to both sets of criteria. GDM diagnosis was correlated with less maternal weight loss the first year post-partum. No difference was found in the prevalence of GDM between the two sets of criteria used. Less weight gain in pregnancy was associated with GDM, independent of the diagnostic criteria used. Reduced weight loss the first year post-partum in women with GDM raises the question of whether GDM diagnosis per se or the fact that these women lose less weight after pregnancy predicts later diabetes mellitus.


[Biologically active helevin-based compositions in the treatment of pleural empyema].
The article analyses the method of topical open treatment of postoperative pyothorax in 17 patients with the use of biologically active helevin-based compositions. The control group was made up of 11 patients with a similar suppurative process who received topical treatment by the same method but with the use of ointments with antibiotics and antiseptics on a fat base. With the use of biologically active compositions (BAC) on a helevin-base, the empyema cavity was completely freed from the pyonecrotic masses and its walls filled with granulation tissue on day 7 of treatment. In the control group the cavity was completely cleansed only on day 19 of treatment. It is shown that BAC possesses a high antibacterial effect not only due to the antibacterial components but because it is based on the laws of physical antiseptics.


[The extracorporeal immunostimulating effect of terrilytin in staphylococcal infection].
The intravenous injection of terrilytin-treated lymphocytes into rats infected with staphylococci enhances the formation of staphylococcal alpha antitoxin in the animals and the development of immune response to T-dependent antigen, such as sheep red blood cells (SRBC), but produces no effect on the development of immune response induced by T-independent antigen (lipopolysaccharide). Terrilytin-treated lymphocytes induce the release of the factor promoting the development of immune response to staphylococcal antigens and SRBC by spleen cells, incapable of adherence to plastic, but have no influence on the development of immune response to lipopolysaccharide in rats infected with staphylococci. At the same time in such rats spleen cells adhering to plastic take part in the transfer of signals from terrilytin-treated lymphocytes to nonadhering spleen cells of recipients.


Cervical Facet Joint Infection and Associated Epidural Abscess with Streptococcus intermedius from a Dental Infection Origin A Case Report and Review.
Pyogenic cervical facet joint infections are rare and such infections from a dental origin are even less common. Of these few cases, none have described infection with Streptococcus intermedius as the pathogen. A 65-year-old orthopaedic surgeon complained of fevers, right-sided radiating neck pain, stiffness, swelling, erythema, and right upper extremity weakness one month after he had broken a crown over his right mandibular premolar, a continued source of pain. Imaging of the cervical spine showed a right C4-C5 facet inflammatory arthropathy and a small epidural abscess that was cultured and initially treated with intravenous antibiotics. The oral maxillofacial surgery team performed an extraction of the infected, symptomatic tooth. For continued right upper extremity weakness, the patient underwent C4-C5 laminoforaminotomy and irrigation and debridement of the right C4-C5 facet joint. After 6 weeks of intravenous antibiotics, the patient's infectious and inflammatory markers had normalized. By 4 months, he had regained full strength at his upper extremity and a painless and full range of motion of his cervical spine.Pyogenic cervical facet joint infection is very rare and potentially dangerous. A high clinical suspicion and appropriate imaging, including magnetic resonance imaging, are important for correct diagnosis. Prompt medical and surgical treatment may avert complications, and although the patient presented made a complete recovery, patients may be left with neurological compromise.


Postanalytical external quality assessment of urine albumin in primary health care: an international survey.
Microalbuminuria (MA) is recognized as an important risk factor for cardiovascular and renal complications in diabetes. We sought to evaluate how screening for MA is conducted and how urine albumin (UA) results are interpreted in primary care internationally. General practitioners (GPs) received a case history-based questionnaire depicting a male type 2 diabetes patient in whom UA testing had not been performed. Questions were related to type of urine sample used for UA testing, need for a repeat test, whether UA testing was performed in the office laboratory, and what changes in UA results were considered clinically important [critical difference (CD)]. Participants received national benchmarking feedback reports. We included 2078 GPs from 9 European countries. Spot urine samples were used most commonly for first time office-based testing, whereas timed collections were used to a larger extent for hospital-based repeat tests. Repeat tests were requested by 45%-77% of GPs if the first test was positive. Four different measurement units were used by 70% of participants in estimating clinically important changes in albumin values. Stated CDs varied considerably among GPs, with similar variations in each country. A median CD of 33% was considered clinically important for both improvement and deterioration in MA, corresponding to an achievable analytical imprecision of 14%, when UA is reported as an albumin/creatinine ratio. Guidelines on diagnosing MA are followed only partially, and should be made more practicable, addressing issues such as type of samples, measurement units, and repeat tests.


Molecular model for hydrated biological tissues.
A density-functional microscopic model for soft tissues (STmod) is presented. The model was based on a prototype molecular structure from experimentally resolved type I collagen peptide residues and water clusters treated in periodic boundary conditions. We obtained the optimized geometry, binding and coupling energies, dipole moments, and vibrational frequencies. The results concerning the stability of the confined water clusters, the water-water, and water-collagen interactions were successfully correlated to some important experimental trends of normal and inflammatory tissues.


Fabrication of silica nano/micro-fibers doped with one-dimensional assembly of silver nanoparticles.
Nano/micro fibers doped with metal nanocrystals are of great interest both theorectically and practically. Nevertheless, the ordered assembly of metal nanocrystals with desired patterns in nano/micro fibers still remains a big challenge, which constrains the further development of the performance of the material. In this investigation, we propose a facile strategy based on the sol-gel and coaxial electrospinning technique to fabricate silica submicron fibers incorporating ordered 1D array of silver nanoparticles. The silver nanoparticles align strictly in a head-to-tail manner in silica fibers, and their size, shape and population are conveniently controlled through tailoring the properties of the precursor solutions and the electrospinning parameters. Therefore, the plasmon property of the obtained fibers is tuned with great freedom. The fabrication method applied here holds great potential for low-cost preparation of metal/glass composite fibers for nano/micro optical applications in general.


The efficacy of chloroquine, sulfadoxine-pyrimethamine and a combination of both for the treatment of uncomplicated Plasmodium falciparum malaria in an area of low transmission in western Uganda.
We conducted an efficacy study of chloroquine (CQ), sulfadoxine-pyrimethamine (SP) and a combination of both (SP+CQ) for the treatment of uncomplicated malaria in an area of low transmission with low drug pressure. On day 3, fever clearance was 97.4% (95% CI, 86.8-99.9), 100% (95% CI, 87.2-100) and 96.6% (95% CI, 82.2-99.9) in the CQ, SP and SP+CQ groups, respectively, (P=0.65). On day 14, clinical success was 92.5% (95% CI, 79.6-98.4), 100% (95% CI, 87.2-100) and 100% (95% CI, 88.1-100) in the CQ, SP and CQ+SP groups, respectively. Clinical failure was seen in 7.5% with 5% (95% CI, 0.61-16.9) early treatment failure and 2.5% (95% CI, 0.06-13.2) late treatment failure of cases in the CQ group and 0% in the SP and SP+CQ groups. Parasitological resistance was observed at RI level in 10% (95% CI, 2.8-23.7), 18.5% (95% CI, 6.3-38.1) and 6.9% (95% CI, 0.85-22.8) for the CQ, SP and SP+CQ, respectively (P=0.37). There was no age-dependent difference in clinical failure or parasitological resistance in any of the treatment groups and prior CQ use within the last 2 weeks did not affect CQ treatment outcome. The findings of this study suggest that CQ is still effective for the treatment of uncomplicated malaria in this area of low transmission and SP. However, combination therapy of SP+CQ is recommended to delay the development SP resistance, and regular surveillance for emerging CQ and SP resistance is needed to plan for alternative antimalarial drug regimens.


Comparative Study on Bioactivities from Lingzhi or Reishi Medicinal Mushroom, Ganoderma lucidum (Agaricomycetes), Gives an Insight into the Fermentation Broth Showing Greater Antioxidative Activities.
Ganoderma lucidum is one of the most famous mushrooms in traditional Chinese medicine. At present, the fully utilized parts of G. lucidum are mainly fruiting body and spore powder. The wild and artificially cultivated G. lucidum fruiting body is costly and rare. Therefore, how to improve the utilization of G. lucidum by means of fermentation is worth investigating. The present study was to perform submerged fermentation of G. lucidum and compare the bioactivities of G. lucidum submerged fermentation broth and fruiting body extract. After the extraction and submerged fermentation methods were optimized, the optimum conditions for extraction were determined as ethanol extraction at 80°C with a solid-to-liquid ratio of 1:30, and those for submerged fermentation were cultivation on malt extract medium for 6 days at 30°C. Under the optimum conditions, the antioxidative activity and tyrosinase inhibition rate of the fermentation broth were 1.2-4.1 fold higher than those of the ethanol extract. Cytotoxicity analysis showed that the ethanol and water extracts and the fermentation broth effectively inhibited pancreatic cancer cells and prostate cancer cells, with much smaller effect on nontumor human embryonic kidney (HEK293T). These results demonstrate that the submerged fermentation could improve the utilization value of G. lucidum and the fermentation broth can be used as an antioxidant additive applied in food, drugs, and cosmetics.


Multiple Polyploidization Events across Asteraceae with Two Nested Events in the Early History Revealed by Nuclear Phylogenomics.
Biodiversity results from multiple evolutionary mechanisms, including genetic variation and natural selection. Whole-genome duplications (WGDs), or polyploidizations, provide opportunities for large-scale genetic modifications. Many evolutionarily successful lineages, including angiosperms and vertebrates, are ancient polyploids, suggesting that WGDs are a driving force in evolution. However, this hypothesis is challenged by the observed lower speciation and higher extinction rates of recently formed polyploids than diploids. Asteraceae includes about 10% of angiosperm species, is thus undoubtedly one of the most successful lineages and paleopolyploidization was suggested early in this family using a small number of datasets. Here, we used genes from 64 new transcriptome datasets and others to reconstruct a robust Asteraceae phylogeny, covering 73 species from 18 tribes in six subfamilies. We estimated their divergence times and further identified multiple potential ancient WGDs within several tribes and shared by the Heliantheae alliance, core Asteraceae (Asteroideae-Mutisioideae), and also with the sister family Calyceraceae. For two of the WGD events, there were subsequent great increases in biodiversity; the older one proceeded the divergence of at least 10 subfamilies within 10 My, with great variation in morphology and physiology, whereas the other was followed by extremely high species richness in the Heliantheae alliance clade. Our results provide different evidence for several WGDs in Asteraceae and reveal distinct association among WGD events, dramatic changes in environment and species radiations, providing a possible scenario for polyploids to overcome the disadvantages of WGDs and to evolve into lineages with high biodiversity.


Phototherapy achieves significant cost savings by the delay of drug-based treatment in psoriasis.
Although used for decades in psoriasis, access to phototherapy is becoming increasingly restricted. Besides patient inconvenience, this is in large part to do with a perception of "high cost." We previously reported a comprehensive analysis of direct and indirect phototherapy treatment cost. However, no robust data exist on the actual savings associated with providing phototherapy in the treatment pathway. To quantify the cost savings achieved by phototherapy by delaying alternative treatments. Costs accruing through the UK-wide established treatment pathway with and without phototherapy were analysed. Direct and indirectly incurred drug treatment costs were calculated using drug tariff, laboratory cost, estate rates and clinic review costs. To enhance reliability, ranges of cost scenarios were calculated by varying parameters such as drug dosing. Medium annual cost savings per patient were £2200 [range: £1800-£2900] for NB-UVB, and £3700 [range: £2500-£5300] if both NB-UVB and PUVA courses were administered, respectively. As the provider treated 656 ± 76 patients per year during the 6-year observational window, this amounted to savings of £Mio 2.4 [range: £Mio 1.6-£Mio 3.4], even excluding additional non-modelled drug-associated costs (eg diagnostics, adverse event management). Since we only consider cost savings by delay of drug treatment for the duration of phototherapy, drug price reductions through biosimilar introduction only have a small effect. We provide spreadsheets allowing adaptation cost savings projections by varying input variables. Healthcare providers may achieve significant cost savings by implementing and/or widening access to phototherapy.


Designing multifunctional polymers for cardiovascular implants.
Polymer-based biomaterials are extensively used in all disciplines of clinical medicine and innovations in biomaterial science are building a product pipeline, e.g., of future cardiovascular implants. Still, cardiovascular applications demand a number of extensive requirements of properties and functions to be fulfilled by the polymer matrix. This report provides an overview on some of these issues and how they can be addressed by a tailored design of novel polymer-based biomaterials. Multifunctional shape-memory polymers are highlighted as a class of materials that combine biocompatibility and the capability for stimuli-induced active movements for anchoring of implants with a controlled degradation and drug release profile to enable a functional regeneration of the tissue at the application site.


The integration of bio-medicine and culturally based alternative medicine: implications for health care providers and patients.
Complementary and alternative medicine (CAM) are therapies used along with or in place of bio-medicine. Many forms of CAM originate in culture, referred to as culturally based alternative medicines. Usage of CAM is high with large numbers of patients using CAM for mental health, pain and musculoskeletal problems. Their desire for holistic care may be the impetus for this interest, as alternative care practitioners spend more time analyzing illness symptoms. These factors along with the global migration of immigrants accustomed to traditional medicine but now immersed in biomedical health care systems, has created potential for misunderstanding. Drug interactions for some forms of CAM taken with bio-medicine can occur. Insufficient scientific studies about CAM has reduced acceptance and educational opportunities to learn about CAM are limited. Ideas for policy and research are forming.


Impact of late conversion from C0 to C2 monitoring of microemulsified cyclosporine in pediatric living donor liver transplant recipients.
The efficacy and feasibility of 2-h post-dose level (C2) monitoring of cyclosporine in long-term living donor liver transplantation (LDLT) is not clear. The aim of this study was to investigate the impact of late conversion from conventional trough-level (C0) monitoring to C2 monitoring of a microemulsion form of cyclosporine (Neoral) in pediatric LDLT recipients. From June 1994 to August 2002, we performed 116 LDLTs in 115 patients. Initially, we adapted conventional C0 monitoring of Neoral, which was converted to C2 monitoring starting in January 2002. The 60 patients who were enrolled in the study had the following characteristics: they were younger than or equal to 15 yr at transplantation, and they had survived LDLT, and they had received a Neoral-based immunosuppression regimen, and they underwent conversion to C2 more than 1 month after transplantation. We evaluated the impact of conversion on doses, blood levels, rejection, adverse effects, and patient/graft outcome. In the long-term patients, the mean C2 levels immediately after conversion were higher than the target levels at any time point selected after transplantation; thus, 34 patients (57%) finally required a dose reduction of Neoral. The current mean C2 level was significantly lower than that observed immediately after conversion (584.6 +/- 262.8 ng/ml vs. 893.1 +/- 260.2 ng/ml, mean +/- SD, p < 0.0001) with a mean follow-up period of 7.4 +/- 0.6 months (range: 5-8 months) after conversion. Only one patient encountered rejection after conversion (1.7%), and no de novo infection or adverse effects were observed. Traditional C0 monitoring of Neoral was safely replaced by C2 monitoring without an increase in the rejection rate or any adverse effects in pediatric LDLT patients. C2 monitoring contributed to the dose reduction of Neoral, which may lead to the avoidance of long-term complications due to immunosuppression.


Impact of Vitamin D3 Deficiency on Phosphatidylcholine-/Ethanolamine, Plasmalogen-, Lyso-Phosphatidylcholine-/Ethanolamine, Carnitine- and Triacyl Glyceride-Homeostasis in Neuroblastoma Cells and Murine Brain.
Vitamin D3 hypovitaminosis is associated with several neurological diseases such as Alzheimer's disease, Parkinson's disease or multiple sclerosis but also with other diseases such as cancer, diabetes or diseases linked to inflammatory processes. Importantly, in all of these diseases lipids have at least a disease modifying effect. Besides its well-known property to modulate gene-expression via the VDR-receptor, less is known if vitamin D hypovitaminosis influences lipid homeostasis and if these potential changes contribute to the pathology of the diseases themselves. Therefore, we analyzed mouse brain with a mild vitamin D hypovitaminosis via a targeted shotgun lipidomic approach, including phosphatidylcholine, plasmalogens, lyso-phosphatidylcholine, (acyl-/acetyl-) carnitines and triglycerides. Alterations were compared with neuroblastoma cells cultivated in the presence and with decreased levels of vitamin D. Both in cell culture and in vivo, decreased vitamin D level resulted in changed lipid levels. While triglycerides were decreased, carnitines were increased under vitamin D hypovitaminosis suggesting an impact of vitamin D on energy metabolism. Additionally, lyso-phosphatidylcholines in particular saturated phosphatidylcholine (e.g., PC aa 48:0) and plasmalogen species (e.g., PC ae 42:0) tended to be increased. Our results suggest that vitamin D hypovitaminosis not only may affect gene expression but also may directly influence cellular lipid homeostasis and affect lipid turnover in disease states that are known for vitamin D hypovitaminosis.


Short-Term Outcome of Early Primary Total Knee Arthroplasty for Fractures Around the Knee in the Elderly Population: The Experience of a Secondary Healthcare Centre in Malaysia.
The management of fractures around the knee in the elderly population can be challenging due to the complexity of the patients and the fracture characteristics. In this study, we aimed to investigate the short-term outcome of elderly patients who had fractures around the knee and who were treated with primary total knee arthroplasty. The study included patients who were at least 70 years old with poor bone quality and who presented with a fracture around the knee that would be difficult to treat with open reduction and internal fixation (ORIF) as well as patients who were at least 55 years old presenting with severe concomitant knee osteoarthritis. This is a cross-sectional study in which all the elderly patients who underwent early primary total knee replacement due to trauma around the knee at the Segamat Hospital between January 2015 and June 2019 were identified. Data were collected from clinical and operative notes. The clinical outcomes of these patients were evaluated by the range of motion of the knee and the Knee Society Score (KSS). Ten patients were identified to have undergone this procedure. Six patients sustained supracondylar femur fractures, two patients had tibial plateau fractures and two patients had concurrent supracondylar femur and tibial plateau fractures. The mean follow-up duration was 22.3 ± 13.9 months, the mean knee score was 87.7 ± 10.0 and the mean functional knee score was 56 ± 41.9. In this cohort, good short-term outcomes close to pre-fracture condition was noted in patients who did not suffer from any complications during the post-operative period. Two patients who had surgical site infection had lower functional knee scores. Another two patients with lower knee scores experienced surgical site infection of the distal tibia and contralateral fixed flexion deformity of the knee. Early primary total knee replacement remains a viable option in treating fractures around the knee in the elderly. Infection, which in this study affected 20% of the patients, is the main deterring factor in performing this procedure.


The development of cancer vaccines.
Extract: In the late 19th century, William Coley of the Memorial Sloan-Kettering Cancer Center in New York noticed the rare occurrence of tumors appearing to improve spontaneously, usually following an infection. This led him to propose that the human immune system could respond to tumors. However, his experiments to prove this fact met with limited success. Studies building from these observations conducted in the 1960's, led to the proposal of a theory of "the immune surveillance of cancer" by Burnet. They suggested that vaccines could be produced to promote the immune system's ability to protect against tumors. Unfortunately, subsequent clinical trials and animal models (comparing cancer rates in normal and immuno-compromised subjects) did not show any differences, which was explained by the suggestion that tumors are too similar to normal tissue to be distinguished by the immune system.


MRI of ossification of ligamentum flavum.
Magnetic resonance imaging of 28 patients with radiological and/or histopathologically proved ossification of the ligamentum flavum (OLF) was reviewed. The locations of OLF were cervical (n = 4), thoracic (n = 22), and lumbar (n = 2). On T1- and T2-weighted images, OLF demonstrated low signal intensity. Areas of high or intermediate signal intensity within the OLF on T1-weighted images were observed in three cases and were interpreted to be due to fat infiltration. In six cases, high intensity areas in the spinal cord caused by compressing OLF were demonstrated on T2-weighted images. Gadolinium-diethylenetriamine pentaacetic acid, which was used in four cases, showed cord enhancement at the level of compression by OLF in three cases.


Protective effect of Thymus munbyanus aqueous extract against 2,4-dichlorophenoxyacetic acid-induced nephrotoxicity in Wistar rats.
The aim of the present study was to examine the possible protective effects of the aqueous extract of Thymus munbyanus (TMAE) against 2,4-dichlorophenoxyacetic acid (2,4-D)-induced oxidative stress and renal injury in the kidney of male albino rats. Furthermore, TMAE was assessed to determine the phenolic content. In vitro, antioxidant activities were evaluated by DPPH radical scavenging, inhibition of β-carotene bleaching, and reducing power. The results showed that TMAE contained high amounts of phenolics, flavonoids, and tannins. Additionally, 24 rats were randomly divided into four groups: a control group, and three groups treated with TMAE (10 mL/kg body weight), 2,4-D (5 mg/kg body weight), and 2,4-D/combined with the TMAE for 4 weeks. Treatment with 2,4-D induced kidney dysfunctions demonstrated as an increase in the potential markers of renal filtration, namely urea and creatinine, associated with a decrease in uric acid. Moreover, 2,4-D increased malondialdehyde and carbonyl protein levels. Additionally, reduced glutathione (GSH) content, as well as superoxide dismutase (SOD), glutathione peroxidase (GPx), and glutathione S-transferase (GST) activities were significantly decreased. Our results demonstrated that oral TMAE supplementation in 2,4-D-treated rats improved and restored some blood parameters and alleviated the adverse cytotoxic effects of 2,4-D by increasing certain antioxidants, consequently attenuating the intensity of oxidative stress induced by 2,4-D; this was confirmed by the histological improvements observed in the kidneys. In conclusion, TMAE demonstrated potential as a natural antioxidant, effectively alleviating 2,4-D induced kidney oxidative injury.


Clinical profiles and trend analysis of newly diagnosed lung cancer in a tertiary care hospital of East China during 2011-2015.
More than one-third of lung cancer worldwide occurring in China. However, the clinical profiles of lung cancer patients in the mainland of China are rarely reported and largely unknown. The objective of this study is to analyze the characteristics and time trends of newly diagnosed lung cancer cases during the past 5 years in East China. The data came from an academic tertiary care hospital of East China. Patients who were newly diagnosed as lung cancer from 2011 to 2015 were enrolled. All new cases got pathological supports by lung biopsy or surgery. Tumor staging was performed according to the seventh edition of the tumor node metastasis (TNM) classification of malignant tumors. The patients' disease information was collected from the database of the hospital information system (HIS). From 2011 to 2015, aggregately 5,779 patients, including 3,719 males and 2,060 females, were diagnosed as lung cancer. The major histologic subtypes of lung cancer were adenocarcinoma (ADC, 60.0%), squamous cell carcinoma (SCC, 25.6%), small cell lung cancer (SCLC, 8.5%), large cell carcinoma (0.6%), adenosquamous carcinoma (1%), other non-small cell carcinoma (1.6%) and unclassified or rare carcinoma (2.8%). ADC proportion of female was much higher than that of male. A higher proportion of advanced stage (stage IIIB, IV) of lung cancer existed in patients who were admitted to hospital due to respiratory or cancer related symptoms (RCRS) than those without RCRS. Smoking rate in male patients reached 80.2%, while it was only 2.7% in females. EGFR mutation existed in 66% of female and 37% of male patients with ADC. This study demonstrates the clinicopathologic characteristics of lung cancer patients from East China, including histologic composition, staging proportion, smoking prevalence and gene mutation status. During the past 5 years, the proportion of ADC has increased gradually whereas SCC decreased.


Challenging the understanding of significant improvement and outcome in schizophrenia - the concept of reliable and clinically significant change methods.
Significant changes of schizophrenia patients during inpatient treatment were evalutaed and compared to established outcome criteria. The concept of reliable and clinically significant change methods was applied to three hundred and ninety-six patients suffering from a schizophrenia spectrum disorder. First, information on whether or not the change of the patient's condition is sufficient in order to declare that it is beyond a measurement error or random effect (= reliable change) was evaluated and in a second step it was observed if the reliable change was clinically meaningful (= clinically significant change). Different Positive and Negative Syndrome Scale for Schizophrenia (PANSS) thresholds were applied to define the clinically significant change (40, 45 and 50 points). These changes were then compared to established outcome criteria such as response and remission. Seventy-nine of the 396 patients (20%) showed a reliable improvement of symptoms, whereas 70% improved without achieving a reliable change of their condition. Of the 79 patients achieving a reliable change during treatment 8-15% concurrently showed a clinically significant change depending on the respective PANSS threshold. In contrast, 56% of the patients achieved response and 60% were in remission at discharge when applying established outcome criteria. Our results showed that a rather small number of schizophrenia patients were found to reliably change during inpatient treatment, with even less patients achieving a clinically significant change. The concept of reliable and clinically significant changes revealed to be a lot more stringent than today's established outcome criteria and should be critically evaluated regarding its use in schizophrenia patients.


A phase I study of amrubicin and carboplatin for previously untreated patients with extensive-disease small cell lung cancer.
Amrubicin and cisplatin are active in the treatment of small cell lung cancer (SCLC), and carboplatin is an analogue of cisplatin with less nonhematological toxicity. The appropriate dose of amrubicin and carboplatin combination chemotherapy for previously untreated patients with extensive-disease (ED) SCLC has not been established. To determine the maximum-tolerated dose and dose-limiting toxicity (DLT) of amrubicin and carboplatin in ED-SCLC. Eligibility criteria were chemotherapy-naive ED-SCLC patients, performance status 0-1, age < or =75, and adequate hematological, hepatic, and renal function. Patients received escalating amrubicin doses under a fixed target area under the curve (AUC) 5 of carboplatin (Chatelut formula). Amrubicin and carboplatin were administered by intravenous (IV) infusion on days 1, 2, and 3, and day 1, respectively. The initial dose of amrubicin was 30 mg/m(2), and the dose was escalated to 35 and 40 mg/m(2). Sixteen patients were enrolled and 15 eligible patients were evaluated. One of six patients in level 1, one of six in level 2, and three of three in level 3 experienced DLTs. The presentation of DLTs included neutropenia, leukopenia, thrombocytopenia, febrile neutropenia, and liver dysfunction. Evaluation of responses were two complete response, nine partial response, three stable disease, and one progressive disease (response rate 73%), and the median survival time was 13.6 months. The maximum-tolerated doses of amrubicin and carboplatin were determined as 40 mg/m(2) and AUC 5. A dose of 35 mg/m(2) amrubicin and carboplatin AUC 5 was recommended in this regimen. This regimen is associated with an acceptable tolerability profile, and warrants evaluation in the phase II setting.


Outcome Findings from a Parent Training Programme for Young People with Conduct Problems.
Group-based parent training programmes are a common intervention for tackling conduct problems in young people. The objective of this study was to evaluate the impact of a parent training programme on young people presenting with conduct problems. 123 parents of young people aged 10 to 17 with conduct problems participated in the study. A one-group, pre-post design was adopted. Participants completed the Child Behaviour Check List (CBCL) at the beginning and end of the parenting programme. The degree of change was indexed by: a) Mean change; b) change from clinical to non-clinical status; and c) Reliable change. Logistic regression was used to identify predictors of reliable positive change in CBCL problems. Analyses from all three sources suggest that there was a significant reduction in CBCL internalising, externalising and total scores. Withdrawn score pre-treatment was the only independent predictor of reliable change in internalising and total scores: the higher the score pre-treatment, the greater the chances of reliable improvement in post-treatment scores. The study provides evidence in support of the therapeutic improvement achieved by some young people whose parents attended the group parent training programme. The programme had a significant impact on internalising as well as externalising problems. Further studies of the programme would benefit from being run as a randomised clinical trial.


The influence of body composition on quality of life of patients with breast cancer.
Unwanted changes in body composition, as well as their impact on these people's quality of life, have been little investigated in patients with breast cancer. [corrected] To assess the role of body composition on quality of life and the impact of chemotherapy on both, in women with breast cancer. It was assessed prospectively women with breast cancer in a cohort of patients undergoing chemotherapy. Body composition was estimated through bioelectrical impedance. The quality of life was evaluated using the World Health Organization quality of life questionnaire. This study assessed 70 women, 77 and 73% of those were initially overweight and had excess of body fat, respectively. There was a significant increase in fat-free mass (p > 0.001), body mass index (p = 0.03) and weight (p = 0.02) while quality of life stayed the same during the study. Moreover, women with excess of body fat showed a significantly lower initial general health score, compared to those with normal body fat (p = 0.02). Chemotherapy proved to be a potential inducer in the weight gain in this population. We highlight the importance of further investigation about the impact of body fat accumulation on those women's quality of life.


Effect of supplementation with algae β-glucans on performance, health, and blood metabolites of Holstein dairy calves.
Studies have shown that β-glucans extracted from the cell wall of cereals, algae, and yeasts have been associated with improved immune function. However, it is unknown whether algae β-glucan supplementation affects the performance, blood metabolites, or cell counts of immune cells in dairy calves. The objective of this randomized clinical trial was to evaluate whether supplementation of β-glucans to milk replacer in dairy calves fed 6 L/d improved growth performance and fecal status and altered the blood metabolite profile. In this trial, we enrolled Holstein calves (n = 34) at birth (body weight 36.38 ± 1.33 kg; mean ± standard deviation) to receive, from 1 d of age, either 2 g/d algae β-glucans mixed into 6 L/d of milk replacer (22.4% crude protein and 16.2% fat) or an unsupplemented milk replacer (control). The calves were blocked in pairs according to birth weight, sex, and date of birth (up to 5 d difference). Calves were housed individually, and calf starter (24.7% crude protein and 13.9% neutral detergent fiber) was offered ad libitum based on orts of the previous day until 56 d of age (end of the trial). Body weight was measured weekly, and health checks and daily fecal consistency were evaluated daily in every calf by the same observer. Calves with 2 consecutive days of loose feces that sifted through bedding were considered diarrhea positive. We used a linear mixed effects model to evaluate the effects of β-glucan supplementation fed during the preweaning period on performance (average daily gain), final weight, feed efficiency (FE), white blood cell count, and selected blood metabolites, repeated by time. A generalized linear mixed effects model was also run to evaluate the likelihood of a diarrhea bout in the first 28 d of life, controlling for the calf as the subject with a logistic distribution. We included age, serum total protein at 48 h, and birth weight as covariates. At 56 d, β-glucan-supplemented calves weighed more than control calves (56.3 vs. 51.5 kg). Treatment had no effect on total starter intake, but there was a treatment by age interaction for FE, with greater FE for β-glucan-supplemented calves in wk 3 and 5 of age. There was only a tendency for average daily gain to be greater in supplemented calves than in control calves for the duration of the study. Furthermore, control calves had 14.66 [95% confidence interval (95% CI): 9.87-21.77] times greater odds of having a diarrheal bout than β-glucan-supplemented calves. Control calves had 12.70 (95% CI: 8.82-18.28) times greater odds of having an additional day with an abnormal fecal score compared with β-glucan-supplemented calves, suggesting that supplementation ameliorated diarrhea severity. We found no association of treatment with concentrations of serum total protein, albumin, creatinine, or glucose during the preweaning period. Our findings suggest that dietary supplementation of 2 g/d of algae β-glucans to milk replacer improved fecal status and may affect growth, as evidenced by a higher weaning weight, compared with control calves. Future studies should explore the effect of algae β-glucans on lower-gut physiology and digestibility in dairy calves.


[Salmonella enteritidis outbreak in a home for the aged].
An outbreak of gastroenteritis caused by Salmonella Enteritidis (SE), phagotype 1, reported at a senior citizen living facility in Burgos on November 15, 1999 is discussed. The objective of the research of this outbreak was that of ascertaining the source of infection, the mechanism by which it was transmitted and to propose the suitable measures for preventing any recurrence of this problem. An observational retrospective cohort study has been made by surveying 106 of a total of 119 residents and 9 employees at the center in question. The Relative Risk of being affected by this disorder has been estimated in terms of the intake of different foods. Logic Regression was employed for calculating the odds ratio adjusted by age, sex and by the intake of foods and wine. The concordance of the clinical diagnosis with the coproculture diagnosis was studied using the Cohen's Kappa index of agreement. A total of 42 individuals reported symptoms (37 residents and 5 employees). The clinical attack rate was 36.5%. Forty-five (45) of the 91 coprocultures performed (82 on residents and 9 on employees) were positive (41 in residents and 4 in employees). The attack rate for cases confirmed by coproculture was 49.5% among those investigated. Fried breaded milk and flour batter sweets was the food product implicated epidemiologically with the onset of the outbreak: RR 3.25 (C.I at 95% 1.10-9.59). The protective effect of the wine (Odds Ratio: 0.68) was not high enough to be statistically significant (p = 0.36). The Kappa index was 0.43 (p < 0.001), which reveals very little agreement between the clinical diagnosis and the coproculture diagnosis. Epidemiological evidence exists of the intake of fired breaded milk and flour batter sweets having been the mechanism for the transmission of the infection, and the food product in question having been stored at room temperature having been the determining contributing factor in the start of the outbreak. This reveals that the best way of preventing this type of outbreaks are clean habits and practices on the part of all those involved in the food-handling sector.


[Perazine-induced agranulocytosis--case report and discussion].
A 22-year-old female patient developed agranulocytosis 26 days after starting single agent treatment with perazine. In accordance with the clinical and hematological picture this agranulocytosis is classified as antibody mediated with destruction of peripheral neutrophils. After cessation of perazine treatment and proper therapy of infection the patient recovered within two weeks. The diagnosis of agranulocytosis should be suspected in anyone on neuroleptic treatment who develops fever, malaise or objective evidence of an infection and in neutropenic patients the adequate treatment should be started immediately.


Increased level of hemoglobin 1 enhances survival of hypoxic stress and promotes early growth in Arabidopsis thaliana.
Overexpression of a class 1 Hb (GLB1) protects Arabidopsis thaliana plants from the effects of severe hypoxia. Overexpression of the bifunctional symbiotic Hb (GLB1S) from Parasponia andersonii in A. thaliana also increases survival after hypoxia. Plants overexpressing the Hb 1 protein, mutated to have a low oxygen affinity, are as susceptible to hypoxia as WT plants, suggesting that the protection against hypoxia depends on the ability of the Hb to bind ligands, such as oxygen, with high affinity. A mild hypoxia pretreatment (5%) induces the Hb gene and increases the survival of plants after severe hypoxic treatment (0.1%). These results with Hb 1 show that plant Hbs have a role other than in nitrogen-fixing root nodules. Plants overexpressing the GLB1 protein show early vigorous growth in nonhypoxic conditions and are 50% larger in weight than the controls at 14 days. The constitutive expression of GLB1 also resulted in a reduced number of root hairs and increased number of laterals in the root system.


[Isolation of a novel candidate proto-oncogene involved in human lymphoid neoplasm].
The 14;19 translocation [t(14;19) (q32;q13)] is a recurring chromosomal translocation observed in leukemic cells of chronic lymphocytic leukemia showing prolymphocytic transformation. We have cloned the breakpoint junction of the translocation and identified a new gene, bcl-3, on the chromosome band 19q13 adjacent to the breakpoint. The translocation occurred at the switch region of the alpha constant locus of the immunoglobulin heavy chain gene and the upper stream of the bcl-3 gene, resulting in a head-to-head recombination between the two genes on the 14q+ chromosome. The bcl-3 gene was highly expressed in the leukemic cells carrying the 14;19 translocation. The bcl-3 gene product contained repeat structures found in proteins involved in cell cycle control and cell lineage determination. These results suggest that the bcl-3 is a proto-oncogene that may contribute to the development of leukemias carrying the 14;19 translocation.


Genetic variants associated with sepsis.
The variable presentations and different phenotypes of sepsis suggest that risk of sepsis comes from many genes each having a small effect. The cumulative effect can be used to create individual risk profile. The purpose of this study was to create a polygenic risk score and determine the genetic variants associated with sepsis. We sequenced ~14 million single nucleotide polymorphisms with a minimac imputation quality R2>0.3 and minor allele frequency >10-6 in patients with Sepsis-2 or Sepsis-3. Genome-wide association was performed using Firth bias-corrected logistic regression. Semi-parsimonious logistic regression was used to create polygenic risk scores and reduced regression to determine the genetic variants independently associated with sepsis. 2261 patients had sepsis and 13,068 control patients did not. The polygenic risk scores had good discrimination: c-statistic = 0.752 ± 0.005 for Sepsis-2 and 0.752 ± 0.007 for Sepsis-3. We found 772 genetic variants associated with Sepsis-2 and 442 with Sepsis-3, p<0.01. After multivariate adjustment, 100 variants on 85 genes were associated with Sepsis-2 and 69 variants in 54 genes with Sepsis-3. Twenty-five variants were present in both the Sepsis-2 and Sepsis-3 groups out of 32 genes that were present in both groups. The other 7 genes had different variants present. Most variants had small effect sizes. Sepsis-2 and Sepsis-3 have both separate and shared genetic variants. Most genetic variants have small effects sizes, but cumulatively, the polygenic risk scores have good discrimination.


MicroRNA in cardiovascular biology and disease.
MicroRNAs (miRNAs) are members of a non-coding RNA family. They act as negative regulators of protein translation by affecting messenger RNA (mRNA) stability; they modulate numerous signaling pathways and cellular processes, and are involved in cell-to-cell communication. Thus, studies on miRNAs offer an opportunity to improve our understanding of complex biological mechanisms. In the cardiovascular system, miRNAs control functions of various cells, such as cardiomyocytes, endothelial cells, smooth muscle cells and fibroblasts. The pivotal role of miRNAs in the cardiovascular system provides a new perspective on the pathophysiology of disorders like myocardial infarction, hypertrophy, fibrosis, heart failure, arrhythmia, inflammation and atherosclerosis. MiRNAs are differentially expressed in diseased tissue and can be released into circulation. Manipulation of miRNA activity may influence the course of a disease. Therefore, miRNAs have become an active field of research for developing new diagnostic and therapeutic tools. This review discusses emerging functions of miRNAs in cardiogenesis, heart regeneration and the pathophysiology of cardiovascular diseases.


Porcine serum amyloid A3 is expressed in extrahepatic tissues and facilitates viral replication during porcine respiratory and reproductive syndrome virus infection.
Serum amyloid A (SAA) is an acute phase protein that is expressed rapidly in response to infection and inflammation in vertebrates. Here, we detected the expression of porcine SAA3, an isoform of porcine SAA, during porcine respiratory and reproductive syndrome virus (PRRSV) infection, which is a major threat to the pig industry. In response to PRRSV infection, porcine SAA3 expression was upregulated significantly in porcine pulmonary alveolar macrophages and in extrahepatic tissues, including the lungs and inguinal, mandibular, and hilar lymph nodes, which were affected mainly by PRRSV infection, demonstrating that porcine SAA3 is a tissue-derived isoform that is induced in extrahepatic tissues during the acute phase response. Overexpression of porcine SAA3 increased PRRSV titers in cultured cells, and the exogenous administration of porcine SAA3 facilitated PRRSV adsorption to cells, suggesting that porcine SAA3 assists PRRSV replication. Our data provide insights into the role of porcine SAA3 during PRRSV infection.


Purification, cloning, and characterization of an acidic ectoprotein phosphatase differentially expressed in the infectious bloodstream form of Trypanosoma brucei.
We purified an ecto-phosphatase of 115 kDa (TryAcP115) specifically expressed by bloodstream forms of Trypanosoma brucei. The corresponding gene coded for a 45-kDa protein potentially including a signal peptide, a membrane-spanning domain and an N-terminal domain containing 8 N-glycosylation sites. There was no significant sequence homology with other phosphatases. Antiserum to the Escherichia coli recombinant N-terminal domain, Petase7, recognized a protein of 55 kDa in Western blots after deglycosylation of the TryAcP115 protein by N-glycosidase F. Immunofluorescence and trypsin treatment of living parasites showed that TryAcP115 was localized to the surface of the parasite and that its N-terminal domain was oriented extracellularly. The recombinant N-terminal domains, expressed in E. coli and Leishmania amazonensis, harbored phosphatase activity against Tyr(P)-Raytide, Ser(P)-neurogranin, and ATP. The enzymatic properties of native TryAcP115 and the recombinant proteins for the substrate Tyr(P)-Raytide were virtually identical and included: (i) K(m) and V(max) values of 15 nM and 200 pmol/min/mg, (ii) no requirement for divalent cations, and (iii) sensitivity to vanadate, sodium fluoride, and tartrate, but insensitivity to okadaic acid and tetramisole. Although the function of TryAcP115 remains unknown, a differentially expressed, unique ecto-phosphatase could regulate growth or influence parasite-host interactions and might provide a useful target for chemotherapy.


Gold(III)-catalyzed tandem reaction of O-arylhydroxylamines with 1,3-dicarbonyl compounds: highly selective synthesis of 3-carbonylated benzofuran derivatives.
A highly regioselective protocol for the synthesis of 3-carbonylated benzofuran derivatives has been developed involving the gold(III)-catalyzed tandem condensation/rearrangement/cyclization reaction of O-arylhydroxylamines with 1,3-dicarbonyl compounds.


Oculomotor corollary discharge in the cat pretectum.
Unit activity bursting after the onset of spontaneous eye movements made in total darkness has been recorded from the nucleus of the optic tract (NOT) of the cat pretectum. The present experiments are aimed at determining the functional significance of these neuronal reactions, namely whether the NOT discharge results from an afferent input arising from eye muscle proprioceptors or from a central signal (corollary discharge or efference copy). The results point to a central, rather than a peripheral, origin for NOT discharge. After both eyes have been paralysed, and therefore after eye-muscle proprioceptive input has been removed, NOT activity remained time-locked with increased activity in motoneurons of the III nerve nucleus.


Miniature scintillating detector for small field radiation therapy.
In planning stereotactic radiosurgery treatments, depth dose curves, profiles, and dose rate of treatment beams are difficult to obtain with conventional detectors because of loss of lateral electronic equilibrium and volume averaging. A scintillating detector with high spatial resolution and good reliability has been developed to overcome this problem. The miniature dosimeter consists of two identical radiation-resistant 10 m long silica optical fibers, each connected to an independent silicon photodiode. A small cylindrical polystyrene scintillator (3.9 mm3) is optically glued to the detection fiber. The light seen by the photodiode connected to this fiber arises from fluorescence of the scintillator and from the Cerenkov effect produced in silica. The reference signal produced by the fiber without scintillator is used to subtract the Cerenkov light contribution from the raw detector response. The sensitive volume of the scintillating detector is nearly water-equivalent and thus minimizes dose distribution perturbation in water. The miniature dosimeter has a spatial resolution comparable to the film-densitometer system. Profiles of 1 cm diam, 6 MV photon beam measured with both systems show very similar shapes. Furthermore, the use of photodiodes instead of photomultiplier tubes gives a better stability response and offers the possibility to perform absolute dosimetry.


Synthesis, characterization of acrylate polymer having chalcone moiety: evaluation of antimicrobial, anticancer and drug release study.
This article describes synthesis, characterization, antimicrobial, drug-releasing and anti-cancer activity of acrylate monomer and its polymer containing chalcone moiety. The synthesized polymers were characterized through IR, 1H NMR and UV-visible spectroscopy techniques. The molecular weight of the obtained polymer is found to be around 4000 g/mol. The synthesized polymers are thermally stable up to 260 °C. The monomer and its polymer show higher activity against gram-negative bacteria and these compounds show remarkable activity over breast cancer cells. The synthesized monomer and polymers showed higher anticancer activity. The inhibitory potential of monomers and polymers premeditated using optimized in vitro evaluation MTT assay and live cell images. The drug release potential was controlled through co-monomer, pH and temperature.


Effects of antibodies to intact cytochrome-c oxidase and its subunit V on the enzymatic activity.
Antibodies have been raised in rabbits against whole beef heart cytochrome-c oxidase and purified subunit V. Antioxidase recognizes nearly all the enzyme subunits but reacts very strongly with subunits II and IV. Antisubunit V is quite specific against subunit V. Inhibition of enzyme activity by antioxidase is typically biphasic in time, indicating populations of both rapidly and slowly reacting molecules. Variation of cytochrome c concentration shows partially competitive kinetics, but the antibody also affects "internal" enzymatic events, including the catalytic turnover induced by N,N,N',N'-tetramethyl-p-phenylenediamine alone and the spin-state change in cytochrome a3 that follows reduction of cytochrome a. No spectral effects can be seen however. Antioxidase also inhibits proteoliposomal respiration with external cytochrome c, but not that with internally trapped cytochrome c. No functionally significant epitopes are detectable on the N side of the membrane in proteoliposomes, although some small effects can be seen with submitochondrial particles. Antisubunit V inhibits the isolated enzyme by at least 60%. The inhibition at high ionic strength induces a biphasic pattern with respect to cytochrome c concentration. Antisubunit V may thus slow the dissociation of cytochrome c from its complex with the enzyme. Antisubunit V has only small effects on the activities of proteoliposomal and submitochondrial particle oxidase in either orientation. On subunit V, some sites, the binding of which can give rise to inhibition, are thus not accessible to antisubunit V when the enzyme is embedded in a functional membrane system.


Endothelial Function in Children and Adolescents Is Mainly Influenced by Age, Sex and Physical Activity - An Analysis of Reactive Hyperemic Peripheral Artery Tonometry.
As adolescents rarely experience cardiovascular events, surrogate markers of atherosclerosis are useful to justify and monitor effects of primary prevention and therapy of risk factors. Endothelial function assessed by reactive hyperemic peripheral arterial tonometry (RH-PAT) resulting in a reactive hyperemic index (RHI) is a noninvasive method with limited data for use in children and adolescents.Methods and Results:We performed a total of 931 RHI measurements in 445 high-school students, aged 10-17 years, over a time period of 5 years. Students were randomized by class to 60 min physical exercise (PE) at school daily (intervention group), or 2 units of 45-min PE weekly (control group). To characterize the factors influencing the RHI, anthropometry, cardiopulmonary exercise testing, blood cholesterol and quality of life were assessed and used to build mixed linear models. Main influential factors were age, with an increase of RHI from 1.53±0.42 in the youngest to 1.96±0.59 in the oldest students, sex, with higher values in girls, and physical activity. This increase adjusted by age and sex was estimated as 0.11 [0.08, 0.14] per year. RHI was higher in the intervention group by 0.09 [-0.05, 0.23] in comparison with the control group. If RH-PAT is used in research or as a clinical tool in adolescents, the shown age- and sex-dependence of RHI have to be taken in account.


Magnetic sphincter augmentation: Optimal patient selection and referral care pathways.
Outcomes associated with magnetic sphincter augmentation (MSA) in patients with gastroesophageal reflux disease (GERD) have been reported, however the optimal population for MSA and the related patient care pathways have not been summarized. This Minireview presents evidence that describes the optimal patient population for MSA, delineates diagnostics to identify these patients, and outlines opportunities for improving GERD patient care pathways. Relevant publications from MEDLINE/EMBASE and guidelines were identified from 2000-2018. Clinical experts contextualized the evidence based on clinical experience. The optimal MSA population may be the 2.2-2.4% of GERD patients who, despite optimal medical management, continue experiencing symptoms of heartburn and/or uncontrolled regurgitation, have abnormal pH, and have intact esophageal function as determined by high resolution manometry. Diagnostic work-ups include ambulatory pH monitoring, high-resolution manometry, barium swallow, and esophagogastroduodenoscopy. GERD patients may present with a range of typical or atypical symptoms. In addition to primary care providers (PCPs) and gastroenterologists (GIs), other specialties involved may include otolaryngologists, allergists, pulmonologists, among others. Objective diagnostic testing is required to ascertain surgical necessity for GERD. Current referral pathways for GERD management are suboptimal. Opportunities exist for enabling patients, PCPs, GIs, and surgeons to act as a team in developing evidence-based optimal care plans.


[Auditory thresholds in young Italians from 18-19 years of age].
The aim of the study was to assess the state of hearing levels in young Italian subjects via an epidemiological study, and also, by means of a questionnaire, to assess the attitude of young people to music, how they listen to music and how they perceive the risk of noise-induced hearing damage. The sample studied consisted of 391 youths undergoing their first medical examination for military service. The hearing threshold was assessed by means of a semiclinical tonal audiometry with sound-proof earphones calibrated to ISO Standard 389 following the method of ISO Standard 6189. At the end of the study 315 youths were judged eligible for the study, 81% of whom lived in the city of Milan. 63% said they went to a discotheque 1-4 times a week and 3% said they listened to music with earphones at maximum volume. These conditions are considered to be potentially dangerous for hearing since among youths leaving discotheques disorders have been observed that are indicative of hearing fatigue: lowering of the hearing level 7%, buzzing in the ears 37%, sense of muffled sound 12%. In the group studied, environmental noise was a factor of disturbance for sleep (13%), for study and reading (43%), listening to the radio, to music and watching TV (29%). Only 7 youths said their hearing was "not normal", but the thresholds were all higher than audiometric zero, which are clearly worse than the values observed in similar studies reported in the literature. This study reports the mean values, SD, minimum and maximum and centile values of the distribution of hearing thresholds, separately for right and left ears. A comparison was made between the hearing in the group least exposed: a significant difference was observed only for the right ear while for the left ear there was only a tendency. The authors conclude that hearing in young people to-day is worse than in the past, whatever be the causes, and that due account should be taken of this state of affairs, by encouraging prevention programmes for noise-induce hearing loss at all levels and on every possible occasion.


Dentin bond strength of a new adhesive system containing calcium phosphate experimentally developed for direct pulp capping.
The purpose of this study was to evaluate the microtensile bond strength (microTBS) to human dentin of an experimental bonding agent containing calcium phosphates experimentally developed for direct pulp capping. Different concentrations of four types of calcium phosphates were added to an experimental bonding monomer, and six experimental bonding agents were thus prepared. Clearfil SE Bond/Bond was used as the control. Flat dentin surfaces of human molars were assigned to the experimental adhesive systems and the control. After Clearfil SE Bond/Primer was applied to the dentin surface, each experimental bonding agent was applied and photopolymerized, and then a resin composite paste was placed and photopolymerized. The specimens were subjected to microTBS testing. Results revealed that there were no significant differences among the microTBS values of the experimental bonding agents and the control. In other words, the calcium phosphate-containing experimental adhesives did not adversely affect the microTBS to dentin.


Changes in Chloroplast Membrane Lipids during Adaptation of Barley to Extreme Salinity.
During adaptation of barley (Hordeum vulgare L.) seedlings to extremely high concentrations of sodium chloride in the root space, the content of galactolipids of chloroplast membranes decreased considerably. Alterations in membrane lipids were due to the high concentration of ions rather than to the increase in the water potential. Sodium chloride was accumulated in the leaf cells and affected lipid-synthesizing enzymes such as galactosyl transferase and acylase which are attached to the chloroplast envelope. The return of salt-adapted barley seedlings to a nutrient solution with low salt concentration resulted in a reversal of the observed changes. It is suggested that the decrease in content of galactolipids in biomembranes is one of the factors causing increased salt resistance in barley plants which are adapted to extreme salinity.


Fear, Anxiety, Burnout, and Insomnia Levels of Healthcare Workers during COVID-19 Pandemic in Turkey.
This study aims to assess fear, anxiety, anxiety sensitivity, burnout, and insomnia of healthcare workers (HCWs) during novel coronavirus-2019 (COVID-19) outbreak and to identify their relation to sociodemographic and clinical characteristics. Totally 600 HCWs were included in this cross-sectional study. A Sociodemographic Data Form, Coronavirus Anxiety Scale (CAS), Fear of COVID-19 Scale (FCV-19S), Anxiety Sensitivity Index-3 (ASI-3), Maslach Burnout Inventory (MBI), and Insomnia Severity Index (ISI) were used. Of participants, 364 were females and 236 were males with a mean age of 33.49±7.29 years. About 95.3% of HCWs had a fear of infecting their loved ones. Mean MBI and ISI scores were significantly higher among HCWs working in COVID-19 clinics and intensive care units (p=0.000; p=0.039). Mean CAS, FCV-19S, MBI, and ISI scores were significantly higher in women than men (p=0.000; p=0.000; p=0.027; p=0.005). Mean CAS and ISI scores were significantly higher among nurses (p=0.008; p=0.004), while mean ASI-3 of the other HCWs and MBI scores of physicians were significantly higher (p=0.009; p=0.000). The COVID-19 pandemic is a major health issue associated with psychiatric illnesses in HCW subgroups with distinct sociodemographic characteristics. It is of utmost importance to develop individualized preventive and therapeutic psychiatric services for HCWs.


Seminal lipid profiling and antioxidant capacity: A species comparison.
On their way to the oocyte, sperm cells are subjected to oxidative stress, which may trigger the oxidation of phospholipids (PL). Applying MALDI-TOF MS, HPTLC and ESI-IT MS, we comparatively analyzed the PL compositions of semen and blood of species differing in their reproductive systems and types of nutrition (bull, boar, stallion, lion and man) with regard to the sensitivity to oxidation as well as the accumulation of harmful lyso-PL (LPL), transient products of lipid oxidation. In addition, the protective capacity of seminal fluid (SF) was also examined. The PL composition of erythrocytes and blood plasma is similar across the species, while pronounced differences exist for sperm and SF. Since the blood function is largely conserved across mammalian species, but the reproductive systems may vary in many aspects, the obtained results suggest that the PL composition is not determined by the type of nutrition, but by the relatedness of species and by functional requirements of cell membranes such as fluidity. Sperm motion and fertilization of oocytes require a rather flexible membrane, which is accomplished by significant moieties of unsaturated fatty acyl residues in sperm lipids of most species, but implies a higher risk of oxidation. Due to a high content of plasmalogens (alkenyl ether lipids), bull sperm are most susceptible to oxidation. Our data indicate that bull sperm possess the most effective protective power in SF. Obviously, a co-evolution of PL composition and protective mechanisms has occurred in semen and is related to the reproductive characteristics. Although the protective capacity in human SF seems well developed, we recorded the most pronounced individual contaminations with LPL in human semen. Probably, massive oxidative challenges related to lifestyle factors interfere with natural conditions.


Molecular mechanisms underlying inner ear patterning defects in kreisler mutants.
Prior studies have shown that kreisler mutants display early inner ear defects that are related to abnormal hindbrain development and signaling. These defects in kreisler mice have been linked to mutation of the kr/mafB gene. To investigate potential relevance of kr/mafB and abnormal hindbrain development in inner ear patterning, we analyzed the ear morphogenesis in kreisler mice using a paint-fill technique. We also examined the expression patterns of a battery of genes important for normal inner ear patterning and development. Our results indicate that the loss of dorsal otic structures such as the endolymphatic duct and sac is attributable to the downregulation of Gbx2, Dlx5 and Wnt2b in the dorsal region of the otocyst. In contrast, the expanded expression domain of Otx2 in the ventral otic region likely contributes to the cochlear phenotype seen in kreisler mutants. Sensory organ development is also markedly disrupted in kreisler mutants. This pattern of defects and gene expression changes is remarkably similar to that observed in Gbx2 mutants. Taken together, the data show an important role for hindbrain cues, and indirectly, kr/mafB, in guiding inner ear morphogenesis. The data also identify Gbx2, Dlx5, Wnt2b and Otx2 as key otic genes ultimately affected by perturbation of the kr/mafB-hindbrain pathway.


A two-phase partitioning airlift bioreactor for the treatment of BTEX contaminated gases.
This investigation characterizes a novel 11 L airlift two-phase partitioning bioreactor (TPPB) for the treatment of gases contaminated with a mixture of benzene, toluene, ethylbenzene, and o-xylene (BTEX). The application of the TPPB technology in an airlift bioreactor configuration provides a novel technology that reduces energy intensity relative to traditional stirred tank TPPB configurations. The addition of a solid second phase of silicone rubber beads (10%, v/v) or of a liquid second phase of silicone oil (10%, v/v) resulted in enhanced performance of the airlift bioreactor relative to the single phase case, with 20% more BTEX being removed from the gas phase during an imposed transient loading. During a 4 h loading step change of three times the nominal loading (60 g m(-3) h(-1)), overall removal efficiencies for the airlift TPPBs containing a liquid or solid phase remained above 75%, whereas the single phase airlift had an overall removal efficiency of 47.1%. The airlift TPPB containing a silicone rubber second phase was further characterized by testing performance during steady-state operation over a range of loadings and inlet gas flow rates in the form of a 3(2) factorial experimental design. Optimal operating conditions that avoid oxygen limitations and that still have a slow enough gas flow rate for sufficient BTEX transfer from the gas phase to the working volume are identified. The novel solid-liquid airlift TPPB reduces energy inputs relative to stirred tank designs while being able to eliminate large amounts of BTEX during both steady-state and fluctuating loading conditions.


Down-regulation of HLA-A expression correlates with a better prognosis in colorectal cancer patients.
To evaluate the prognostic impact of human leukocyte antigen class I (HLA-I) expression on immune surveillance in colorectal cancer, we studied 88 curatively resected tumors for HLA-A and HLA-B/C expression and correlated these data to clinical and histopathological parameters. HLA-A was normal (all tumor cells had HLA expression) in 32%, reduced (HLA-negative and -positive tumor cells coexisted) in 56%, or absent (no tumor cells expressed HLA) in 12% of evaluable cases. HLA-B/C was normal in 47%, reduced in 47%, and absent in 7% of the cases. Considering both markers, total HLA-I expression was normal in 27%, reduced in 63%, absent in 7%, and could not be evaluated in 3% of the cases due to absent HLA-A expression in tumor and normal cells. Down-regulation of HLA-A expression significantly correlated with a lower tumor stage (p = 0.005), mucinous tumors (p = 0.05), a lower incidence of recurrences (p = 0.03), and a longer disease-free survival (p = 0.02). Down-regulation of HLA-B/C expression correlated with a lower tumor stage (p < 0.001) and a longer disease-free survival (p = 0.04). In multivariate analysis, HLA-A down-regulation was the only prognostic factor correlated with a longer disease-free survival (p = 0.02). Six tumors were negative for HLA-A and -B/C and did not recur during follow-up. Therefore, we analyzed microsatellite instability (MSI) in these cases. Three of these six tumors indeed showed down-regulation of MLH-1, MSH-2, or MSH-6, indicating a MSI-high phenotype. Beta-2-microglobulin protein expression was lost in five of six of the HLA-I-negative cases, but frame shift mutations in three repetitive sequences in beta2-microglobulin were absent. In contrast, loss of MLH-1, MSH-2, and MSH-6-protein expression was only observed in two of nine matched controls with reduced or normal HLA-A and -B/C expression. Our data showed that HLA-I was down-regulated in 72% of colorectal cancers and provided independent prognostic information for a longer disease-free survival. The better prognosis may be caused by elimination of HLA-negative cells by natural killer cells or by an attenuated tumor aggressiveness, as is seen in tumors with a MSI-high phenotype.


Cytotoxicity of antimicrobial photodynamic inactivation on epithelial cells when co-cultured with Candida albicans.
This study assessed the cytotoxicity of antimicrobial Photodynamic Inactivation (aPDI), mediated by curcumin, using human keratinocytes co-cultured with Candida albicans. Cells and microorganisms were grown separately for 24 hours and then kept in contact for an additional 24 hours. After this period, aPDI was applied. The conditions tested were: P+L+ (experimental group aPDI); P-L+ (light emitting diode [LED] group); P+L- (curcumin group); and P-L- (cells in co-culture without curcumin nor LED). In addition, keratinocytes and C. albicans were grown separately, were not placed in the co-culture and did not receive aPDI (control group). Cell proliferation was assessed using Alamar Blue, MTT, XTT and CFU tests. Qualitative and quantitative analyses were performed. Analysis of variance (ANOVA) was applied to the survival percentages of cells compared to the control group (considered as 100% viability), complemented by multiple comparisons using Tukey's test. A 5% significance level was adopted. The results of this study showed no interference in the metabolism of the cells in co-culture, since no differences were observed between the control group (cultured cells by themselves) and the P-L- group (co-culture cells without aPDI). The aPDI group reached the highest reduction (p = 0.009), which was equivalent to 1.7 log10 when compared to the control group. The P+L-, P-L+, P-L- and control groups were not statistically different (ρ > 0.05). aPDI inhibited the growth of keratinocytes and C. albicans in all tests, so the therapy was considered slightly (inhibition between 25 and 50% compared to the control group) to moderately (inhibition between 50 and 75% compared to the control group) cytotoxic.


The effects of plant and tooth structure on intake and digestibility in two small mammalian herbivores.
We investigated the interaction between plant structure and animal tooth structure and how it can affect digestive performance in two small mammalian herbivores. Mastacomys fuscus, an exclusively herbivorous rodent, and Rattus lutreolus, a less herbivorous rodent, were fed diets varying in fibre structure and level (18%-45% neutral detergent fibre). On high-fibre whole wheat diets, R. lutreolus was not able to maintain body mass. M. fuscus was able to maintain body mass, and this was related to a much greater intake by M. fuscus on this diet. We attribute this result to more effective physical processing by M. fuscus as a consequence of a highly developed dentition. On a milled-wheat diet, intake by R. lutreolus increased significantly compared with the whole wheat diet, although intake was still not great enough to maintain body mass. On diets that were lower in fibre than the wheat diet, and with different fibre arrangements, R. lutreolus was able to achieve intakes great enough to maintain body mass. This suggests that, in addition to gut constraints, the physical form of the plant diet and dental structure can have a significant effect on digestive performance by animals in feeding trials.


Increased oxygen load in the prefrontal cortex from mouth breathing: a vector-based near-infrared spectroscopy study.
Individuals who habitually breathe through the mouth are more likely than nasal breathers to have sleep disorders and attention deficit hyperactive disorder. We hypothesized that brain hemodynamic responses in the prefrontal cortex might be different for mouth and nasal breathing. To test this hypothesis, we measured changes in oxyhemoglobin and deoxyhemoglobin in the prefrontal cortex during mouth breathing and nasal breathing in healthy adults (n=9) using vector-based near-infrared spectroscopy. The angle k, calculated from changes in oxyhemoglobin and deoxyhemoglobin and indicating the degree of oxygen exchange, was significantly higher during mouth breathing (P<0.05), indicating an increased oxygen load. Mouth breathing also caused a significant increase in deoxyhemoglobin, but oxyhemoglobin did not increase. This difference in oxygen load in the brain arising from different breathing routes can be evaluated quantitatively using vector-based near-infrared spectroscopy. Phase responses could help to provide an earlier and more reliable diagnosis of a patient's habitual breathing route than a patient interview.


Folate of pregnant women after a nationwide folic acid supplementation in China.
Folate insufficiency during the periconceptional period increases the risk of neural tube defects (NTDs) in offspring, and folic acid supplementation substantially reduces the risk. Widespread large-scale folic acid supplementation (0.4-mg folic acid tablet) has been adopted as a main strategy to prevent NTDs in China since 2009. We examined folate concentrations in plasma and red blood cells (RBCs) of pregnant women and the factors associated with blood folate concentrations in a population with a high prevalence of NTDs in northern China. A cross-sectional survey was conducted in 2014, and 1,107 pregnant women were recruited from 11 county or city maternal and child health centres across Shanxi province. Microbiological assays were used to determine folate concentrations. Factors associated with blood folate insufficiency were identified. The median (25th and 75th percentiles) folate concentrations were 28.4 (17.6, 45.2) nmol L-1 and 1,001.2 (658.7, 1,402.5) nmol L-1 in plasma and RBCs, respectively. According to the proposed RBC (906 nmol L-1 ) concentrations for optimal NTD prevention, 42.4% participants had RBC folate insufficiency. Rural women had a higher proportion of folate insufficiency than urban women. Folic acid supplementation was the only factor associated with RBC folate insufficiency. A large proportion of women had RBC folate concentrations that are not optimal for the prevention of NTDs despite free access to folic acid supplements. Actions that aim to improve folic acid supplementation compliance are needed to reach the full potential of the nationwide folic acid supplementation programme in terms of NTD prevention.


Magnetic resonance imaging in the diagnosis of breast disease.
Magnetic resonance imaging (MRI) of the breast was performed in 10 volunteers and 102 women with suspected breast disease, using a 0.35-T superconducting magnet. All patients had prior x-ray mammography. MRI was superior to mammography in differentiating solid from cystic lesions and equivalent to mammography in providing information regarding different parenchymal patterns. Of 21 surgically proven carcinomas of the breast, MRI correctly identified 18 and mammography identified 19. The major disadvantage of MRI is its inability to show calcifications, benign or malignant. Future studies will be needed to show the relative values of sonography and MRI in detecting small cysts. In addition, MRI in future should be able to demonstrate small, noncalcified masses in mammographically dense, fibrocystic breasts.


Novel functions of the alphavirus nonstructural protein nsP3 C-terminal region.
The functions of the alphavirus-encoded nonstructural protein nsP3 during infection are poorly understood. In contrast, nsP1, nsP2, and nsP4 have known enzymatic activities and functions. A functional analysis of the C-terminal region of nsP3 of Semliki Forest virus revealed the presence of a degradation signal that overlaps with a sequence element located between nsP3 and nsP4 that is required for proteolytic processing. This element was responsible for the short half-life (1 h) of individually expressed nsP3, and it also was functionally transferable to other proteins. Inducible cell lines were used to express native nsP3 or truncated mutants. The removal of 10 C-terminal amino acid (aa) residues from nsP3 increased the half-life of the protein approximately 8-fold. While the deletion of 30 C-terminal aa residues resulted in a similar stabilization, this deletion also changed the cellular localization of nsP3. This truncated mutant no longer exhibited a punctate localization in the cytoplasm, but instead filamentous stretches could be formed around the nuclei of induced cells, suggesting the existence of an additional functional element upstream of the degradation signal. C-terminally truncated uncleavable polyprotein P12(CA)3del30 was localized diffusely, which is in contrast to P12(CA)3, which is known to be associated with vesicle membranes. The induction of nsP3 or its truncated forms reduced the efficiency of virus multiplication in corresponding cells by affecting different steps of the infection cycle. The expression of nsP3 or a mutant lacking the 10 C-terminal aa residues repressed the establishment of infection, while the expression of nsP3 lacking 30 C-terminal aa residues led to the reduced synthesis of subgenomic RNA.


Predictors of Headache/Migraine and the Use of Complementary Medicine in U.S. Children: A Population-Based Analysis of 2017 National Health Interview Survey Data.
Background: This study set out to determine the prevalence and possible risk factors of headache and/or migraine in U.S. children, as well as the prevalence of complementary medicine use in this population. Methods: This is a secondary analysis of data from the 2017 U.S. National Health Interview Survey. Sociodemographic and clinical characteristics were compared between individuals with and without headaches. A backward stepwise procedure with a logistic regression statistic was used to test for potential predictors. Results: Six percent of children reported headaches and/or migraine within the past 12 months. Headaches were predicted by older age, female sex, non-Hispanic white ethnicity, and living in the southern United States. Inability to afford balanced meals and feeling sad or depressed in the past 6 months were also associated with higher odds of headache. A total of 19.2% of children with headaches reported using mind-body medicine, compared with 12.2% of children without headaches. Most frequently used therapy was yoga (57.2%), followed by spiritual meditation (31.1%) and mindfulness meditation (24.0%). The prevalence of visits to a complementary medicine practitioner or healer was 12.5%. Most frequently seen practitioners were chiropractors (62.1%), followed by naturopaths (21.2%), homeopaths (14.1%), and traditional healers (2.5%). Conclusions: The common use of complementary medicine among children suffering from headaches is worth noting. Understanding the motivation for using complementary medicine, as well as the choice of different forms of such therapy, may shed further light on the health-seeking behavior of this population.


[Operant and cognitive behavioural treatments in chronic pain].
In the present review learning procedures as operant and classical conditioning on the development of chronic pain as well as the influence of cognitive and affective factors will be reported. Characteristics of extinction and its applications in operant and cognitive behavioural treatment as well as its combination with pharmacological agents will be discussed. Operant and cognitive behavioural treatments were shown effective in treating chronic pain. Combinations with pharmacological agents have to be examined in future research.


Effects on angina pectoris and exercise tests of a 2% nitroglycerin gel adhesive in patients on chronic beta-blockade. A placebo-controlled study.
Twenty patients on chronic beta-blockade for angina pectoris were included in a double-blind randomized cross-over placebo-controlled study on a 2% nitroglycerin gel administered transdermally by an adhesive. Topinitro. The dose, 2.5-10 mg/day, was individually titrated and each treatment period was 28 days. The effect was evaluated by exercise tests and diary cards for anginal attacks and nitroglycerin tablets consumed. Results. In the 17 patients who completed the trial, active treatment did not influence systolic and diastolic blood pressure or resting and maximal heart rate. Maximal performance increased insignificantly from 92 +/- 23 to 96 +/- 20 W. The level at which 1 mm of ST depression appeared increased from 62 +/- 26 to 73 +/- 28 W (p less than 0.05). The number of attacks decreased significantly, from 92 +/- 30 to 14 +/- 28/4 weeks. The reduction in the number of sublingual nitroglycerin tablets consumed was insignificant. Conclusion. Nitroglycerin adhesive, in individual dosages, may improve signs and symptoms of ischemia.


Desmoid-type fibromatosis of the breast: A case report.
Desmoid-type fibromatosis of the breast (also referred to as desmoid tumor or aggressive fibromatosis) is exceedingly rare. Although it does not metastasize, desmoid-type fibromatosisis is frequently locally aggressive. Recurrence is common (up to 35%), even after presumed total excision of the primary tumor [1]. The breast is an unusual location for the development of this tumor, with relatively few cases reported in the literature. We report a case of desmoid-type fibromatosis in the breast in a 31-year-old female who presented with a four-month history of a palpable left breast mass. Her imaging was discordant, so she underwent surgical excision of the mass. Multiple positive margins were present. She underwent re-excision to the level of the sternum medially. Final pathology showed a focally positive posterior margin, without muscle or fascial involvement. The patient's case was discussed at the multidisciplinary tumor board conference and no further intervention was recommended. To our knowledge, this is the first case report in the literature in which negative margins were unable to be achieved for desmoid tumors of the breast operatively.