[Centrally and peripherally induced anorectic actions of salmon calcitonin (sCT) in rats: separation of its novel derivative [Gly8]-sCT].
It has been reported based on animal studies that salmon calcitonin (sCT), besides hypocalcemic action, exhibits a variety of pharmacological actions. The anorectic action has been observed to ensue not only by central administration but also by peripheral injection, indicating that in clinical use to induce hypocalcemia or for other therapeutic purposes, the anorectic action may develop as a side effect. While studying the anorectic effect of [Gly8]-sCT in rats, a derivative of sCT having rather stronger hypocalcemic potency than the mother molecule, it was found that on peripheral injection, the derivative practically lacks the anorectic effect. Thus, a pharmacological evaluation of the novel peptide was made. When injected subcutaneously in rats at a dose level of 1 U/kg, sCT and the derivative induced similar patterns of hypocalcemia in either of which hypocalcemia reached a peak between 1 and 3 hr after injection. No notable difference existed between the action of the two peptides. In rats which were trained to take the daily food need within 2 hr (17:00 approximately 19:00), an intracerebroventricular injection of 1 U/rat of either peptide 30 min before food presentation significantly reduced both food and water intake, causing a loss of body weight as compared with the control which received the injection of saline alone. By subcutaneous injection of 100 U/kg, sCT was also active to decrease food and water intake. The effect was found to last longer than 24 hr and to cause a marked loss in body weight. In contrast, such effects did not develop in rats treated with the derivative. Both peptides were able to suppress the specific binding of 125I-sCT to the membrane fraction of rat brain and kidney.(ABSTRACT TRUNCATED AT 250 WORDS)


Gender-Based Violence and Armed Conflict: A Community-Informed Socioecological Conceptual Model From Northeastern Uganda.
The high prevalence of gender-based violence (GBV) in armed conflict has been documented in various national contexts, but less is known about the complex pathways that constitute the relation between the two. Employing a community-based collaborative approach, we constructed a community-informed socioecological conceptual model from a feminist perspective, detailing how armed conflict relates to GBV in a conflict-affected rural community in Northeastern Uganda. The research questions were as follows: (1) How does the community conceptualize GBV? and (2) How does armed conflict relate to GBV? Nine focus group discussions divided by gender, age, and profession and six key informant interviews were conducted. Participants' ages ranged from 9 to 80 years (n =34 girls/women, n = 43 boys/men). Grounded theory was used in analysis. Participants conceptualized eight forms of and 22 interactive variables that contributed to GBV. Armed conflict affected physical violence/quarreling, sexual violence, early marriage, and land grabbing via a direct pathway and four indirect pathways initiated through looting of resources, militarization of the community, death of a parent(s) or husband, and sexual violence. The findings suggest that community, organizational, and policy-level interventions, which include attention to intersecting vulnerabilities for exposure to GBV in conflict-affected settings, should be prioritized. While tertiary psychological interventions with women and girls affected by GBV in these areas should not be eliminated, we suggest that policy makers and members of community and organizational efforts make systemic and structural changes. Online slides for instructors who want to use this article for teaching are available on PWQ's website at http://journals.sagepub.com/page/pwq/suppl/index.


Coverage List: a provider-patient database supporting advanced hospital information services.
We have developed a provider-patient database system, known as Coverage List, which maintains the associations between house staff and inpatients in a teaching hospital. Coverage List automatically links each patient to the proper resident when the patient is admitted, and updates the linkage whenever the resident coverage changes due to night or weekend coverage, physician illness, changes in clinical rotations, and other factors. Using this association, decision-support applications that detect significant clinical events can transmit them directly to the responsible resident. Sign-out and patient-review systems, which collect information on all of a physician's patients, always know the patients for whom that physician is responsible. Nurses who need to contact a physician about a patient issue always know which physician is covering that patient. Coverage List also manages schedule entry and display for physicians, or for any other staff members. A physician can enter individual schedule changes, sign out her service and her pager for the day, and page consultants automatically without going through an operator. These functions support clinical practice directly and enhance the value of other clinical programs.


Homologous Gold Nanoparticles and Nanoclusters Composites with Enhanced Surface Raman Scattering and Metal Fluorescence for Cancer Imaging.
A large number of deaths from cancer can be attributed to the lack of effective early-stage diagnostic techniques. Thus, accurate and effective early diagnosis is a major research goal worldwide. With the unique phenomenon of localized surface plasmon resonance (LSPR), plasmonic nanomaterials have attracted considerable attention for applications in surface-enhanced Raman scattering (SERS) and metal-enhanced fluorescence (MEF). Both SERS and MEF are ultra-sensitive methods for the detection and identification of early tumor at molecular level. To combine the merits of the fast and accurate imaging of MEF and the stable and clear imaging of SERS, we propose a novel dual functional imaging nanoprobe based on gold nanoparticles and gold nanocluster composites (denoted AuNPC-RGD). The gold nanoparticles are used as LSPR substrates to realized enhancement of Raman or fluorescence signal, while the gold nanoclusters serve as a fluorophore for MEF imaging, and exhibit better biocompatibility and stability. Furthermore, target molecule of cyclic Arg-Gly-Asp (cRGD) is incorporated into the composite to improve delivery efficiency, selectivity and imaging accuracy. These integrated properties endow AuNPC-RGD composites with outstanding biocompatibility and excellent imaging abilities, which could be used to achieve accurate and effective diagnosis for early cancer.


Effect of the contents and form of rabies glycoprotein on the potency of rabies vaccination in cattle.
One of the methods used for controlling cattle rabies in Brazil consists of vaccination. Sometimes, however, rabies occurs in cattle supposedly protected. Since rabies vaccine batches are officially controlled by tests performed on laboratory animals, it is questionable whether the minimal mandatory requirements really correspond to immunogenicity in the target species. We have analyzed the association among potencies of rabies vaccines tested by the NIH test, the contents and form (free-soluble or virus-attached) of rabies glycoprotein (G) in the vaccine batches, and the virus-neutralizing antibodies (VNA) titers elicited in cattle. No correlation was found between G contents in the vaccine batches and the NIH values, whatever the presentation of G. There was no correlation either between NIH values and VNA titers elicited in cattle. There was, however, a positive correlation (r = 0.8681; p = 0.0001) between the amounts of virion-attached G present in the vaccine batches and VNA elicited in cattle. This was not observed when the same analysis was performed with total-glycoprotein or free-soluble glycoprotein. The study demonstrated that NIH values can not predict the effect of the immunogen in cattle. On the other hand, the quantification of virus-attached rabies glycoprotein has a strong correlation with VNA elicited in cattle.


Normal autonomic neurophysiology of postural orthostatic tachycardia and recommended physiological assessments in postural orthostatic tachycardia syndrome.
The current surge of interest in postural orthostatic tachycardia syndrome commonly known as POTS requires good knowledge of the very complex physiology involved, but this is currently lacking. The often overlooked normal physiology of orthostasis is reviewed including the definition of normal postural orthostatic tachycardia. An illustrated functional anatomy that embeds orthostatic tachycardia within the learned and skilful motor functions in the human population is presented. The four physiological phases of orthostasis and the role of tachycardia are described in a laboratory-controlled and progressive orthostatic stress in normal human volunteers. Standardized surrogate measures of autonomic control were used to quantify the trigger level for excessive tachycardia and the minimum autonomic control required to sustain viable arterial blood pressure during severe orthostatic stress in normal human volunteers. Tachycardia during orthostasis is part of a "democratic" contribution by four cardiovascular parameters of which the chronotropic function of the heart is just one of the parameters contributing toward cardiovascular compensation. It is adjusted during orthostasis in proportion to contributions from the other three parameters, namely inotropic function of the heart, windkessel vascular resistance and venous vascular capacitance. The physiological effects of the two stressors during orthostasis, gravity and isometric contraction of skeletal muscles are reviewed. A model of how the four cardiovascular parameters are regulated during orthostasis to achieve proportionate contributions is proposed emphasizing the necessity to quantify individual contributions from all these four parameters. Any one or more of these parameters may be compromised due to disease requiring disproportionate contribution of the prevailing magnitude of orthostatic tachycardia in an individual. It therefore requires neurophysiological assessment of the autonomic regulation of all the four cardiovascular parameters to assess the condition fully. We recommend here some current and novel neurophysiological methods that use modern medical technology to quantify laboratory standardized surrogate measures of some of these cardiovascular parameters including central parasympathetic regulation in postural orthostatic tachycardia syndrome.


Anatomic Reconstruction of the Anterior Cruciate Ligament of the Knee With or Without Reconstruction of the Anterolateral Ligament: A Randomized Clinical Trial.
Rotational instability of the knee remains an issue after anterior cruciate ligament (ACL) reconstruction. Hypothesis/Purpose: The purpose was to evaluate the subjective and objective outcomes of combined reconstruction of the ACL and anterolateral ligament (ALL) of the knee. The hypothesis was that favorable outcomes can be achieved with this surgical procedure compared with isolated anatomic reconstruction of the ACL. Randomized controlled trial; Level of evidence, 2. One hundred ten patients with a unilateral ACL injury and high-grade pivot shift were randomly assigned to undergo either combined ACL and ALL reconstruction (group A) or isolated ACL reconstruction (group B). Preoperative and postoperative evaluations of the patients were conducted by obtaining history details, recording physical examination findings, measuring knee laxity using the KT-1000 arthrometer, and using validated outcome scores for the knee. P < .05 was considered as the cut-off level of statistical significance. The Fisher exact and Mann-Whitney U tests were used to assess statistical significance. At a mean follow-up of 27 months, 53 and 50 patients in groups A and B, respectively, were available for analysis. No statistically different outcomes were found between the 2 groups except for the KT-1000 arthrometer values. The median KT-1000 arthrometer result for combined ACL and ALL reconstruction was 1.3 mm, while the median result for isolated ACL reconstruction was 1.8 mm ( P < .001). None of the patients (n = 0; 0.0%) who underwent combined ACL and ALL reconstruction had anterior translation of greater than 5 mm at maximum pulling strength compared with their normal knees at final follow-up. On the other hand, 3 (6.0%) patients who underwent isolated ACL reconstruction had anterior translation of more than 5 mm. No serious complications were found in both groups. Combined ACL and ALL reconstruction was found to be effective in improving subjective and objective outcomes. Nevertheless, these findings were not significantly superior to isolated ACL reconstruction except for the instrumented knee laxity testing results. This might indicate that ALL reconstruction should not be performed routinely for patients undergoing ACL reconstruction.


Long-Acting Diclofenac Ester Prodrugs for Joint Injection: Kinetics, Mechanism of Degradation, and In Vitro Release From Prodrug Suspension.
A prodrug approach for local and sustained diclofenac action after injection into joints based on ester prodrugs having a pH-dependent solubility is presented. Inherent ester prodrug properties influencing the duration of action include their pH-dependent solubility and charge state, as well as susceptibility to undergo esterase facilitated hydrolysis. In this study, physicochemical properties and pH rate profiles of 3 diclofenac ester prodrugs differing with respect to the spacer carbon chain length between the drug and the imidazole-based promoiety were determined and a rate equation for prodrug degradation in aqueous solution in the pH range 1-10 was derived. In the pH range 6-10, the prodrugs were subject to parallel degradation to yield diclofenac and an indolinone derivative. The prodrug degradation was found to be about 6-fold faster in 80% (vol/vol) human plasma as compared to 80% (vol/vol) human synovial fluid with 2-(1-methyl-1H-imidazol-2-yl)ethyl 2-(2-(2,6 dichlorophenyl)amino)phenylacetate being the poorest substrate toward enzymatic cleavage. The conversion and release of parent diclofenac from prodrug suspensions in vitro were studied using the rotating dialysis model. The results suggest that it is possible to alter and control dissolution and reconversion behavior of the diclofenac prodrugs, thus making the prodrug approach feasible for local and sustained diclofenac action after joint injection.


Identification and characterization of a mitochondrial unfolded protein response transcription factor ATFS-1 in Litopenaeus vannamei.
A mitochondrial specific stress response termed mitochondrial unfolded protein response (UPR(mt)) is activated in responding to disturbance of protein homeostasis in mitochondria. The activating transcription factor associated with stress-1 (designated as ATFS-1) is the key regulator of UPR(mt). To investigating the roles of ATFS-1 (LvATFS-1) in Litopenaeus vannamei mitochondrial stress remission and immunity, it's full length cDNA was cloned. The open reading frame of LvATFS-1 was 1, 557 bp in length, deducing to a 268 amino acids protein. LvATFS-1 was highly expressed in muscle, hemocytes and eyestalk. Subcellular location assays showed that N-terminal of LvATFS-1 contained a mitochondrial targeting sequence, which could directed the fused EGFP located to mitochondria. And the C-terminal of LvATFS-1, which had a nuclear localization signal, expressed in nucleus. The in vitro experiments verified that LvATFS-1 could reduced the level of intracellular reactive oxygen species (ROS). And results of real-time RT-PCR indicated that LvATFS-1 might scavenge excess ROS via ROS-eliminating genes regulation. Reporter gene assays showed that LvATFS-1 could upregulated the expression of the antimicrobial peptide genes in Drosophila Schneider 2 cells. Results of real-time RT-PCR showed that Vibrio alginolyticus or white spot syndrome virus (WSSV) infection induced the expression of LvATFS-1. And knocked-down LvATFS-1 by RNAi resulted in a higher cumulative mortality of L. vannamei upon V. alginolyticus or WSSV infection. These results suggested that LvATFS-1 not only rolled in mitochondrial specific stress responding, but also important for L. vannamei immunologic defence.


Setting your practice goals.
Goal setting is a powerful business technique. Far more than just a motivational concept, it is an outcome of strategic planning. Doctors who set goals are usually more clearly focused on where they want the practice to go and when they want to get there.


Attitudes towards health-care robots in a retirement village.
This study investigated the attitudes and preferences of staff, residents and relatives of residents in a retirement village towards a health-care robot. Focus groups were conducted with residents, managers and caregivers, and questionnaires were collected from 32 residents, 30 staff and 27 relatives of residents. The most popular robot tasks were detection of falls and calling for help, lifting, and monitoring location. Robot functionality was more important than appearance. Concerns included the loss of jobs and personal care, while perceived benefits included allowing staff to spend quality time with residents, and helping residents with self-care. Residents showed a more positive attitude towards robots than both staff and relatives. These results provide an initial guide for the tasks and appearance appropriate for a robot to provide assistance in aged care facilities and highlight concerns.


Characterization of Sepik and Entebbe bat viruses closely related to yellow fever virus.
Yellow fever virus has a special place in medical history as the first animal virus isolated and as the prototype virus in the genus Flavivirus, which contains many serious human pathogens. Only recently, its closely related viruses within the group were identified phylogenetically. In this study, we obtained complete or near complete genome sequences of two viruses most closely related to yellow fever virus: Sepik virus of Papua New Guinea and Entebbe bat virus of Africa. Based on full-genomic characterization and genomic traits among related viruses, we identified Sepik virus to be most closely related to yellow fever virus and analyzed the pattern of repeat and conserved sequence motifs in the 3'-noncoding region among the members of yellow fever virus cluster. We also discuss the geographic dispersal as a part of ecological traits of this lineage of flaviviruses.


Work factors and stress: a critical review.
Occupational stress research encompasses a very large and diversified field, yet the areas sometimes remain relatively distinct. In this review of the literature the authors shows that there have been numerous studies and conceptualizations of the effects of negative work factors on stress, but very few have placed the experience of stress in a comprehensive framework. Psychological approaches are presented and critically appraised as having several drawbacks, while it is argued that sociological approaches are essential to explaining the context of occupational stress. Labor process studies are closest to providing a comprehensive framework for understanding the causes and consequences of stress at work. The author develops an approach for extending labor process analysis to incorporate the effects on stress of management's control over work at a number of different levels of analysis, not only point of production activities.


Analysis of the relationship between treatment networks and the evolution of patients with Type 2 Diabetes Mellitus.
Type 2 Diabetes Mellitus (T2DM) is a chronic disease that has been increasing in prevalence in recent years and that can cause severe complications. To ensure patient care is administered correctly, it is necessary for medical treatment teams to be both multidisciplinary and cohesive. The analysis of health processes is a constant challenge due to their high variability and complexity. This paper proposes a method based on the analysis of social networks to detect treatment networks, and to identify a relationship between these networks and patient evolution, as measured by glycated hemoglobin (HbA1c) levels. The networks were segmented based on patient adherence to their medical appointments and their mean time of delay. We applied this method on a sample of 1574 patients diagnosed with T2DM. Results show that participatory treatment -in which a patient sees a particular group of professionals on a recurrent basis - together with high levels of adherence are associated to those patients who improve their HbA1c levels in the case of high levels of adherence, while those who continually experience referrals to different professionals, remain unstable and, in some cases, get worse. On the other hand, in order to maintain a patient as stable, continuous control of the patient is enough, regardless of the recurrence to the same professionals.


Endothelial cell plasticity in kidney fibrosis and disease.
Renal endothelial cells demonstrate an impressive remodeling potential during angiogenic sprouting, vessel repair or while transitioning into mesenchymal cells. These different processes may play important roles in both renal disease progression or regeneration while underlying signaling pathways of different endothelial cell plasticity routes partly overlap. Angiogenesis contributes to wound healing after kidney injury and pharmaceutical modulation of angiogenesis may home a great therapeutic potential. Yet, it is not clear whether any differentiated endothelial cell can proliferate or whether regenerative processes are largely controlled by resident or circulating endothelial progenitor cells. In the glomerular compartment for example, a distinct endothelial progenitor cell population may remodel the glomerular endothelium after injury. Endothelial-to-mesenchymal transition (EndoMT) in the kidney is vastly documented and often associated with endothelial dysfunction, fibrosis, and kidney disease progression. Especially the role of EndoMT in renal fibrosis is controversial. Studies on EndoMT in vivo determined possible conclusions on the pathophysiological role of EndoMT in the kidney, but whether endothelial cells really contribute to kidney fibrosis and if not what other cellular and functional outcomes derive from EndoMT in kidney disease is unclear. Sequencing data, however, suggest no participation of endothelial cells in extracellular matrix deposition. Thus, more in-depth classification of cellular markers and the fate of EndoMT cells in the kidney is needed. In this review, we describe different signaling pathways of endothelial plasticity, outline methodological approaches and evidence for functional and structural implications of angiogenesis and EndoMT in the kidney, and eventually discuss controversial aspects in the literature.


Laparoscopic appendectomy during pregnancy is safe for both the mother and the fetus.
The diagnosis and treatment of acute appendicitis during pregnancy is still debated. While laparoscopic appendectomy in general has become the gold standard, this procedure has not generally been implemented for pregnant women. We retrospectively reviewed the patient charts of all patients who underwent appendectomy during pregnancy in the period from 2000 to 2012. Open appendectomy (OA) was performed in 25 cases and laparoscopic (LA) in 19. We observed a significantly longer operation time (69 versus 49 min., p = 0.002), but fewer complications, a shorter hospital stay (2.6 versus 5.5 days, p = 0.004) and a lower rate of negative appendectomies (16% versus 52%, p = 0.02) in the LA group compared with the OA group. The mean gestation age at appendectomy was significantly lower in the LA group. There were no significant differences in gestational age at birth, Apgar score, birth weight or height between the two groups. Five births (11%) were categorised as mildly to moderately preterm. There were no cases of fetal loss. Laparoscopic appendectomy is safe for both the mother and the fetus during pregnancy irrespective of gestational age, and the procedure is associated with a low risk of post-operative complications. none. not relevant.


Nasotracheal intubation.
Blind nasotracheal intubation presumes a spontaneously breathing patient but offers a very useful alternative method to instrumented access to the airway and is used primarily in traumatized patients whose cervical spines are suspect. It has a high success rate (90-92 per cent), even when the operator is relatively inexperienced, and is associated with few complications (10 per cent or fewer); a rate that is lower when there is adequate time to prepare the patient with vasoconstrictor and topical anesthesia. The most common complication is epistaxis. Surgical methods of intubation also are discussed of which cricothyroidostomy currently enjoys prominence.


Carotid Artery Stenting With Proximal Embolic Protection via a Transradial or Transbrachial Approach: Pushing the Boundaries of the Technique While Maintaining Safety and Efficacy.
To compare the feasibility and safety of proximal cerebral protection to a distal filter during carotid artery stenting (CAS) via a transbrachial (TB) or transradial (TR) approach. Among 856 patients who underwent CAS between January 2007 and July 2015, 214 (25%) patients (mean age 72±8 years; 154 men) had the procedure via a TR (n=154) or TB (n=60) approach with either Mo.MA proximal protection (n=61) or distal filter protection (n=153). The Mo.MA group (mean age 73±7 years; 54 men) had significantly more men and more severe stenosis than the filter group (mean age 71±8 years; 100 men). Stent type and CAS technique were left to operator discretion. Heparin and a dedicated closure device or bivalirudin and manual compression were used in TR and TB accesses, respectively. Technical and procedure success, crossover to femoral artery, 30-day major adverse cardiovascular/cerebrovascular events (MACCE; death, all strokes, and myocardial infarction), vascular complications, and radiation exposure were compared between groups. Crossover to a femoral approach was required in 1/61 (1.6%) Mo.MA patient vs 11/153 (7.1%) filter patients mainly due to technical difficulty in engaging the target vessel. Five Mo.MA patients developed acute intolerance to proximal occlusion; 4 were successfully shifted to filter protection. A TR patient was shifted to filter because the Mo.MA system was too short. CAS was technically successful in the remaining 55 (90%) Mo.MA patients and 142 (93%) filter patients. The MACCE rate was 0% in the Mo.MA patients and 2.8% in the filter group (p=0.18). Radiation exposure was similar between groups. Major vascular complications occurred in 1/61 (1.6%) and in 3/153 (1.96%) patients in the Mo.MA and filter groups (p=0.18), respectively, and were confined to the TB approach in the early part of the learning curve. Chronic radial artery occlusion was detected by Doppler ultrasound in 2/30 (6.6%) Mo.MA patients and in 4/124 (3.2%) filter patients by clinical assessment (p=0.25) at 8.1±7.5-month follow-up. CAS with proximal protection via a TR or TB approach is a feasible, safe, and effective technique with a low rate of vascular complications.


Myosin components of the latissimus dorsi and the pectoralis major muscles in the dystrophic chicken.
The myosin composition of the anterior latissimus dorsi, the posterior latissimus dorsi, and the pectoralis major muscles was examined in the inbred White Leghorn dystrophic chicken and its isogenic normal line at different ages during development and maturation. Using the biochemical methods of native gel electrophoresis, one- and two-dimensional sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS PAGE), and peptide mapping, it was found that myosin isozyme changes occurred normally in the anterior latissimus dorsi muscle. However, in the posterior latissimus dorsi muscle, slow myosin components which were not present in the adult normal muscle were present in the adult dystrophic muscle. In addition, the pectoralis major muscle of the dystrophic chicken failed to undergo the neonatal to adult fast myosin isozyme transition. Our data also showed that muscle cell cultures derived from the pectoralis major muscle of dystrophic chickens expressed identical myosin components to cultures derived from normal embryos. However, since these cultures only produced embryonic myosins even after 1 month in culture, it implied that cells in tissue culture were phenotypically normal because present cell culture conditions were insufficient to induce the fetal to adult isozyme changes.


Collection, processing and storage of peripheral blood stem cells (PBSC).
Eight patients with hematological malignancies were treated with autologous blood stem cell transplantation (ABSCT). Hemopoietic precursor cells were mobilized into the peripheral blood (PB) by chemotherapeutic induction of transient myelosuppression followed by an overshooting of blood stem cell concentration. PB CFU-GM showed a 15-20 fold increase on days 15-20 after chemotherapy. Peripheral blood stem cells were collected by 5-8 continuous flow leukaphereses using a Fenwall CS 3000 blood cell separator when platelet and WBC count was rising rapidly (platelet greater than 50 x 10e9/L and WBC greater than 1 x 10e9/L). Mean CFU-GM collected per run by leukapheresis were 10.85 x 10e4/Kg (procedure 3), 10.03 x 10e4/Kg (modified procedure 1). Mononuclear cell suspension in 10% DMSO was frozen at controlled rate freezer (-1 degree C to -4 degrees C) and stored in the liquid phase of nitrogen. After thawing CFU-GM recoveries ranged from 13.8% to 81.5%; 55-70% of recovered cells excluded trypan blue dye.


Electrokinetic translocation of a deformable nanoparticle controlled by field effect in nanopores.
Nanopores have become a popular single-molecule manipulation and detection technology. In this paper, we have constructed a continuum model of the nanopore; the arbitrary Lagrangian-Eulerian (ALE) method is used to describe the motion of particles and fluid. The mathematical model couples the stress-strain equation for the dynamics of a deformable particle, the Poisson equation for the electric field, the Navier-Stokes equations for the flow field, and the Nernst-Planck equations for ionic transport. Based on the model, the mechanism of field-effect regulation of particles passing through a nanopore is investigated. The results show that the transport of particles which is controlled by the field effect depends on the electroosmotic flow (EOF) generated by the gate electrode in the nanopore and the electrostatic interaction between the nanopore and particles. That also explains the asymmetry of particle transport velocity in the nanopore with a gate electrode. When the gate potential is negative, or the gate electrode length is small, the maximum deformation of the particles is increased. The field-effect regulation in the nanopore provides an active and compatible method for nanopore detection, and provides a convenient method for the active control of the particle deformation in the nanopore.


Quantification of the ratio of positional isomer dilinoleoyl-oleoyl glycerols in vegetable oils.
The distribution of fatty acids in a triacylglycerol is of great importance from nutritional, biochemical, quality and technological points of view. The ratio of triacylglycerol positional isomers containing two linoleic acid (18:2) and one oleic acid (18:1) moieties--namely, 1(3),2-dilinoleoyl-3(1)-oleoyl glycerol (LLO) and 1,3-dilinoleoyl-2-oleoyl glycerol (LOL)--were quantified in grape seed, olive, pumpkin seed, soybean, sunflower and wheat germ oils by high-performance liquid chromatography/atmospheric pressure chemical ionization mass spectrometry (HPLC/APCI-MS) in selected ion monitoring (SIM) mode. Relative LOL contents (LOL/(LLO+LOL)) of the oils were calculated from the mass abundances of the [LL]+ and [LO]+ diacylglycerol fragment ions ([M+H-RCOOH]+) using a calibration curve. The calibration curve of the relative diacylglycerol mass abundances was measured in SIM mode. The relative LOL contents were found to be relatively consistent for each oil variety. The relative LOL content in grape seed, sunflower, pumpkin seed, soybean and wheat germ oils accounted for 44.2 +/- 2.6, 26.8 +/- 3.2, 16.7 +/- 4.6, 15.9 +/- 2.9 and 13.9 +/- 4.3%, respectively. Only olive oils contained practically 100% of the LLO isomer. These results indicate that the unsaturated fatty acids such as linoleic and oleic acids have 'non-random' distribution patterns in various oils.


Thermal and light-induced spin-crossover in salts of the heptadentate complex [tris(4-{pyrazol-3-yl}-3-aza-3-butenyl)amine]iron(ii).
The syntheses of [FeL][BF(4)](2).H(2)O, [FeL][ClO(4)](2).H(2)O, [FeL][NO(3)](2).CH(3)NO(2) and [FeL][CF(3)SO(3)](2) (L = tris(4-{pyrazol-3-yl}-3-aza-3-butenyl)amine) are described. The isostructural BF(4)(-) and ClO(4)(-) salts are high-spin between 5-300 K, while the other two compounds are high-spin at room temperature but undergo gradual high-->low spin transitions upon cooling. For [FeL][NO(3)](2) this transition is centred at 139 K and proceeds to near-completeness, while for [FeL][CF(3)SO(3)](2) it is centred at 144 K and only proceeds to 50% conversion. The CF(3)SO(3)(-) salt also undergoes spin-crossover centred at 200 K in (CD(3))(2)CO solution, and exhibits dynamic inversion of its helical ligand conformation. All these compounds except the triflate salt have been crystallographically characterised, and show capped trigonal antiprismatic [6 + 1] coordination geometries. The NO(3)(-) and CF(3)SO(3)(-) salts undergo quantitative conversion to trapped, high-spin excited states upon irradiation with a green laser at 10 K (the LIESST effect; LIESST = Light-Induced Excited Spin State Trapping). The thermal stabilities of their LIESST excited states (T(LIESST) = 80-82 K) resemble those found for iron(ii) complexes of bidentate N-heterocyclic ligands. Hence, the LIESST properties of [FeL](2+) are those of a complex of three rigid bidentate domains linked by a flexible spacer, rather than of a single encapsulating podand.


Selection of starter cultures for the production of sour cassava starch in a pilot-scale fermentation process.
Sour cassava starch (Polvilho azedo) is obtained from a spontaneous fermentation conducted by microorganisms from raw materials and fermentation tanks. This product is traditionally used in the baking industry for the manufacture of biscuits and Brazilian cheese breads. However, the end of fermentation is evaluated empirically, and the process occurs without standardization, which results in products of inconsistent quality. Predominant microbiota from a cassava flour manufacturer was isolated in order to select starter cultures for the production of sour cassava starch in a pilot-scale fermentation process. Lactic acid bacteria and yeasts were isolated, enumerated and grouped by Restriction Fragment Length Polymorphism, and PCR fingerprinting, respectively. One isolate of each molecular profile was identified by sequencing of the rRNA gene. LAB were prevalent throughout the entire process. Lactobacillus brevis (21.5%), which produced the highest values of acidity, and Lactobacillus plantarum (13.9%) were among the most frequent species. Pichia scutulata (52.2%) was the prevalent yeast and showed amylolytic activity. The aforementioned species were tested as single and mixed starter cultures in a pilot-scale fermentation process for 28 days. L. plantarum exhibited better performance as a starter culture, which suggests its potential for the production of sour cassava starch.


Computational fluid dynamics in abdominal aorta bifurcation: non-Newtonian versus Newtonian blood flow in a real case study.
Hemodynamic in abdominal aorta bifurcation was investigated in a real case using computational fluid dynamics. A Newtonian and non-Newtonian (Walburn-Schneck) viscosity models were compared. The geometrical model was obtained by 3D reconstruction from CT-scan and hemodynamic parameters obtained by laser-Doppler. Blood was assumed incompressible fluid, laminar flow in transient regime and rigid vessel wall. Finite volume-based was used to study the velocity, pressure, wall shear stress (WSS) and viscosity throughout cardiac cycle. Results obtained with Walburn-Schneck's model, during systole, present lower viscosity due to shear thinning behavior. Furthermore, there is a significant difference between the results obtained by the two models for a specific patient. During the systole, differences are more pronounced and are preferably located in the tortuous regions of the artery. Throughout the cardiac cycle, the WSS amplitude between the systole and diastole is greater for the Walburn-Schneck's model than for the Newtonian model. However, the average viscosity along the artery is always greater for the non-Newtonian model, except in the systolic peak. The hemodynamic model is crucial to validate results obtained with CFD and to explore clinical potential.


Nutritional status of tribal and non-tribal adults in rural Bangladesh: A comparative study.
Nutritional status is an important indicator of health status among adults. However, to date, there exists scanty information on the nutritional status of tribal populations of Bangladesh. The aim of the study was to investigate the nutritional status of tribal (T) and non-tribal (NT) adult people living in the rural area of Rajshahi district, Bangladesh. A total of 420 (72 T and 348 NT) households were studied. The samples were selected using multistage stratified sampling with proportional allocation. The nutritional status of adults was measured using body mass index (BMI). Descriptive statistics, t-test, ANOVA and Z-proportional test were utilized for data analysis. The study revealed that 8.3% and 9.2% of T and NT men were suffering from under nutrition respectively, while the corresponding figures in women were 12.5% and 10.1% respectively. Overall, 11.1% and 27.0% men, and 13.9% and 29.3% women T and NT were over-nourished respectively. The rate of over nutrition among T was significantly (p<0.05) higher than NT for both sexes. The mean weight and BMI of the NT men were significantly (p<0.01) higher than T men. The mean weight, height and BMI of NT women were higher (p<0.05) than T women. ANOVA demonstrated that the variation in BMI among education levels of NT men and the variation among occupation for both ethnicities were significant (p<0.01). The variation in BMI among education levels and occupation of T and NT women were significant (p<0.05), moreover ordinal logistic regression model demonstrated that hygienic toilet facilities and father's occupation were predictors of nutritional status. The interaction effects of education and occupation, and education and household monthly income on BMI were significant (p<0.01) for T men and both T and NT women (p<0.05). The prevalence of over-nutrition among NT is higher than T for both sexes. Some socio-economic and demographic factors were found as predictors of malnutrition. At least 12 of the 17 Sustainable Development Goals (SDGs) contain indicators that are highly related to nutrition, our findings can help Bangladesh Government for achieving SDGs by 2030. Appropriate nutritional intervention and awareness programmes can be initiated by the Government to ameliorate the burden of malnutrition among adults in the country.


E74‑like ETS transcription factor 5 facilitates cell proliferation through regulating the expression of adenomatous polyposis coli 2 in non‑small cell lung cancer.
E74‑like ETS transcription factor 5 (ELF5) is known to regulate the specification and differentiation of epithelial cells in the embryonic lung. However, the pathological function of ELF5 in lung cancer has yet to be fully elucidated. In the present study, the expression of ELF5 was found to be significantly higher in lung adenocarcinoma compared with that in corresponding adjacent normal tissues. Subsequently, cell and animal experiments were performed to investigate the role of ELF5 in lung adenocarcinoma cells. The results indicated that the overexpression of ELF5 increased the proliferation of lung adenocarcinoma cells, whereas, by contrast, a reduction in the expression of ELF5 led to a decrease in their proliferation. Mechanistically, the hypothesis is advanced that ELF5 can promote lung cancer cell proliferation through inhibiting adenomatous polyposis coli 2 and increasing the expression of cyclin D1, which is a critical downstream target of the Wnt pathway. Taken together, these findings support the notion that ELF5 exerts an essential role in the proliferation of lung adenocarcinoma cells and may be a therapeutic target for the treatment of lung adenocarcinoma.


Decreased microRNA-224 and its clinical significance in non-small cell lung cancer patients.
MicroRNA-224 has been proven dysregulated in some human malignancies and correlated with tumor progression. However, its expression and clinical significance in non-small cell lung cancer (NSCLC) is still unclear. Thus, the aim of this study was to explore the effects of miR-224 in NSCLC tumorigenesis and development. Using real-time quantitative RT-PCR, we detected miR-224 expression in NSCLC cell lines and primary tumor tissues. The association of miR-224 expression with clinicopathological factors and prognosis was also statistically analyzed. MTT, flow cytometric, Transwell invasion and migration assays, and scratch migration assay were used to test the proliferation, apoptosis, invasion, and migration of NSCLC cells after miR-224 mimics transfection. MiR-224 expression levels were significantly down-regulated in NSCLC compared to the corresponding noncancerous lung tissues (P <0.001). In addition, decreased miR-224 expression was significantly associated with lymph node metastasis (P = 0.002), advanced TNM stage (P <0.001), and shorter overall survival (P <0.001). Multivariate regression analysis corroborated that down-regulation of miR-224 was an independent unfavourable prognostic factor for patients with NSCLC. Furthermore, transfection of miR-224 mimics in NSCLC A549 cells was able to reduce cell proliferation, invasion, and migration, and promote cell apoptosis. These findings indicate that miR-224 may act not only as a novel diagnostic and prognostic marker, but also as a potential target for miR-based therapy of NSCLC. The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/13000_2014_198.


Rare association of pulmonary artery sling with tracheo-oesophageal fistula and patent ductus arteriosus.
Congenital tracheo-oesophageal fistula (TEF) is a life-threatening complication caused by communication between the oesophagus and the tracheobronchial tree within the neck or the thorax. TEF without oesophageal atresia is commonly known as 'H'-type TEF, and it is extremely rare in infants, accounting for ∼2-4% of all congenital tracheo-oesophageal malformations. Here, we report a rare case of a pulmonary artery sling with TEF and patent ductus arteriosus.


Electrochemical probing of ground state electronic interactions in polynuclear complexes of a new heteroditopic ligand.
The synthesis and electronic properties of dinuclear ([(bipy)2Ru(I)M(terpy)][PF6]4(bipy = 2,2'-bipyridine, terpy = 2,2':6',2''-terpyridine; M = Ru, Os)) and trinuclear ([[(bipy)2Ru(I)]2M][PF6]6 M = Ru, Os, Fe, Co) complexes bridged by 4'-(2,2'-bipyridin-4-yl)-2,2':6',2''-terpyridine (I) have been investigated and are compared with those of mononuclear model complexes. The electrochemical analysis using cyclic voltammetry and differential pulse voltammetry reveals that there are no interactions in the ground state between adjacent metal centres. However, there is strong electronic communication between the 2,2'-bipyridine and 2,2':6',2''-terpyridine components of the bridging ligand. This conclusion is supported by a step-by-step reduction of the dinuclear and trinuclear complexes and the assignment of each electrochemical process to localised ligand sites within the didentate and terdentate domains. The investigation of the electronic absorption and emission spectra reveals an energy transfer in the excited state from the terminating bipy-bound metal centres to the central terpy-bound metal centre. This indicates that the bridge is able to facilitate energy transfer in the excited state between the metal centres despite the lack of interactions in the ground state.


Update on the management of upper gastrointestinal bleeding.
Upper gastrointestinal bleeding is a common emergency presentation requiring prompt resuscitation and management. Peptic ulcers are the most common cause of the condition. Thorough initial management with a structured approach is vital with appropriate intravenous fluid resuscitation and use of a restrictive transfusion threshold of 7-8 g/dL. Pre-endoscopic scoring tools enable identification of patients at high risk and at very low risk who might benefit from specific management. Endoscopy should be carried out within 24 h of presentation for patients admitted to hospital, although optimal timing for patients at a higher risk within this period is less clear. Endoscopic treatment of high risk lesions and use of subsequent high dose proton pump inhibitors is a cornerstone of non-variceal bleeding management. Variceal haemorrhage results in higher mortality than non-variceal haemorrhage and, if suspected, antibiotics and vasopressors should be administered urgently, before endoscopy. Oesophageal variceal bleeding requires endoscopic band ligation, whereas bleeding from gastric varices requires thrombin or tissue glue injection. Recurrent bleeding is managed by repeat endoscopic treatment. If uncontrolled bleeding occurs, interventional radiological embolisation or surgery is required for non-variceal bleeding or transjugular intrahepatic portosystemic shunt placement for variceal bleeding.


Effects of dipyrone on the digestive tract.
Dipyrone (metamizole), acting through its main metabolites 4-methyl-amino-antipyrine and 4-amino-antipyrine, has established analgesic, antipyretic, and spasmolytic pharmacological effects, which are mediated by poorly known mechanisms. In rats, intravenously administered dipyrone delays gastric emptying (GE) of liquids with the participation of capsaicin-sensitive afferent fibers. This effect seems to be mediated by norepinephrine originating from the sympathetic nervous system but not from the superior celiac-mesenteric ganglion complex, which activates β2-adrenoceptors. In rats, in contrast to nonselective non-hormonal anti-inflammatory drugs, dipyrone protects the gastric mucosa attenuating the development of gastric ulcers induced by a number of agents. Clinically, it has been demonstrated that dipyrone is effective in the control of colic-like abdominal pain originating from the biliary and intestinal tracts. Since studies in humans and animals have demonstrated the presence of β2-adrenoceptors in biliary tract smooth muscle and β2-adrenoceptor activation has been shown to occur in dipyrone-induced delayed GE, it is likely that this kind of receptors may participate in the reduction of smooth muscle spasm of the sphincter of Oddi induced by dipyrone. There is no evidence that dipyrone may interfere with small bowel and colon motility, and the clinical results of its therapeutic use in intestinal colic appear to be due to its analgesic effect.


Acute Kidney Injury and Extracorporeal Membrane Oxygenation: Review on Multiple Organ Support Options.
Extracorporeal membrane oxygenation (ECMO) is a temporary life support system used to assist patients with life-threatening severe cardiac and/or respiratory insufficiency. Patients requiring ECMO can be considered the sickest patients admitted to the intensive care unit (ICU). Acute kidney injury (AKI) represents a frequent complication during ECMO, affecting up to 70% of patients, with multifactorial pathophysiology and an independent risk factor for mortality. Severe AKI requiring Continuous Renal Replacement Therapy (CRRT) occurs in 20% of ECMO patients, but multiple indications and different timing may imply a significantly higher application rate in different centers. CRRT can be run in parallel to ECMO through different vascular access, or it can be conducted in series by connecting the circuits. Anticoagulation of ECMO is typically managed with systemic heparin, but several approaches can be applied for the CRRT circuit, from no anticoagulation to the addition of intra-filter heparin or regional citrate anticoagulation. The combination of CRRT and ECMO can be considered a form of multiple organ support therapy, but this approach still requires optimization in timing, set-up, anticoagulation, prescription and delivery. The aim of this report is to review the pathophysiology of AKI, the CRRT delivery, anticoagulation strategies and outcomes of patients with AKI treated with ECMO.


Activation of the metaphase checkpoint and an apoptosis programme in the early zebrafish embryo, by treatment with the spindle-destabilising agent nocodazole.
We have studied the developmental activation of the metaphase checkpoint, and the consequences of activating this checkpoint, in the zebrafish embryo. (1) Treatment with nocodazole (a microtubule destabiliser) before mid-blastula transition (MBT) produces complete destruction of all nuclei in the deep cell layer of the embryo. In contrast, nocodazole treatment after MBT efficiently produces metaphase arrest in this cell layer. Thus, the metaphase checkpoint becomes activated at MBT. (2) Although a metaphase arrest is induced by nocodazole, it is not induced by paclitaxel (a microtubule stabiliser). Thus the metaphase checkpoint appears to sense a destabilisation, but not a stabilisation, of spindle microtubules. (3) Metaphase-arrested cells (in nocodazole) can be driven into the next interphase by adding the Ca2+-specific ionophore A23187. Thus, a Ca2+-signalling pathway lies downstream of, or parallel to, the metaphase checkpoint. (4) After mid-gastrula stage, treatment with nocodazole produces DNA fragmentation in all three cell layers. In the enveloping epithelial monolayer (EVL), this is associated with a classical apoptotic phenotype. In the deep layer, it is associated with an unusual, highly condensed nuclear state that is entered directly from metaphase arrest. Thus, after the mid-gastrula stage, the embryo responds to nocodazle by undergoing apoptosis. (5) Nocodazole-induced apoptosis in the deep cell layer can be blocked by the caspase-1,4,5 inhibitors Ac-YVAD-CHO and Ac-YVAD-CMK. This suggests that a homologue of the C. elegans ced-9-ced-4-ced-3 pathway is involved in control over apoptosis in the early zebrafish embryo.


The thrombin-dependent enrichment of alkenylacyl ethanolamine phosphoglyceride with [14C]eicosapentaenoic and [3H]arachidonic acids in prelabelled human platelets.
The thrombin-dependent enrichment of alkenylacyl ethanolamine phosphoglyceride in [14C]eicosapentaenoic acid [( 14C]EPA) was demonstrated and compared with [3H]arachidonic acid [( 3H]AA) following the simultaneous prelabelling of individual human platelet phospholipids with these two fatty acids. The alkenylacyl, diacyl, and alkylacyl classes of ethanolamine phosphoglycerides (PE) were separated by thin-layer chromatography as their acetylated derivatives after hydrolysis of the parent phospholipid with phospholipase C. The ratios of [3H]/[14C] for the increased radioactivity appearing in alkenylacyl PE following 60 and 120 s of thrombin stimulation were the same as the corresponding ratio (2.0) found in the choline phosphoglycerides (PC) from control (unstimulated) platelets. These results suggest no significant selectivity between EPA and AA in the thrombin-stimulated transfer of these fatty acids from diacyl PC to alkenylacyl PE. The present findings may possibly bear some relevance to the altered platelet reactivity and (or) decreased thromboxane A2 formation observed in human subjects following the ingestion of marine lipid containing EPA.


Verification of the mediation effect of recovery resilience according to the relation between elderly users' participation in exercise rehabilitation program and their successful aging.
This study aims to verify the mediation effect of recovery resilience according to the relation between Senior Citizen Community Center (SCCC) elderly users' participation in exercise rehabilitation programs and their successful aging. Toward that end, 400 65-yr or older participants and non-participants in SCCCs' exercise rehabilitation programs, living in Incheon, were sampled. Of their answered questionnaires, 35 copies which were deemed low-reliability, duplicated, and inadequately specified were excluded from the analysis. And, the other data were coded through computers, and underwent a descriptive statistical analysis (DSA) and a standard multiple regression analysis (SMRA) using Windows SPSS/PC+21.0 Version statistical program. Thus it was firstly found that elderly people's participation or non-participation in exercise rehabilitation programs partially influenced their recovery resilience and successful aging. The participants group, compared with the non-participants group, had greater recovery resilience and experienced successful aging. Second, the relation between the degree of participation in exercise rehabilitation programs, recovery resilience and successful aging revealed that the longer and the more frequent the participation in exercise rehabilitation programs was, the greater the recovery resilience was and the more successful aging was. Third, the verification of the mediation effect of recovery resilience in the relation between the program participation degree and the successful aging revealed that, compared with those of the model of direct effects of independent variables and dependent variables, the recovery resilience-mediated model's verification power and explanation power were greater.


Elevated Serum Levels of Ischemia Modified Albumin and Malondialdehyde are Related to Atherogenic Index of Plasma in a Cohort of Prediabetes.
Prediabetes, defined as impaired glucose tolerance and/or impaired fasting glucose, is a risk factor for future type 2 diabetes, dyslipidemia, cardiovascular disease and all-cause mortality. High serum levels of ischemia modified albumin (IMA) and malondialdehyde (MDA) as oxidative stress markers were determined in diabetes, however, no studies have investigated these markers together in prediabetes. The aim of the present study was to investigate the circulating levels of both IMA and MDA in a cohort of prediabetic adults. The possible associations between both markers and the atherogenic index of plasma (AIP) were also evaluated. This study enrolled 100 adults with prediabetes and 50 healthy controls matched for age and sex. Anthropometric measurements, fasting and 2-hour post load glucose, glycosylated hemoglobin (A1c), lipids profile, fasting insulin, homeostasis model assessment of insulin resistance (HOMA-IR), high sensitivity C-reactive protein (hs-CRP), AIP, IMA and MDA were assessed. IMA, MDA, hs-CRP and AIP were significantly higher in adults with prediabetes than in healthy controls. Male gender, fasting and post load glucose, A1c, fasting insulin, TGs, HDL-C, hs- CRP, AIP and MDA were independent predictor variables of IMA, whereas male gender, WC, fasting and post load glucose, A1c, fasting insulin, TC, TGs, LDL-C, HDL-C, hs-CRP and AIP were independent predictor variables of MDA. The elevation of IMA concomitantly with MDA reflecting the antioxidant status in prediabetes, and their associations with hs-CRP and AIP should reinforce the idea of screening and treatment of prediabetes.


[Colo-rectal spirochetosis: is it an anatomo-pathologic entity?].
Nineteen colorectal biopsy specimens, stained by Hematein-Eosin-Safran (HES), were examined by light microscopy and showed a thick, blue and fuzzy brush border. Without any further microbiologic investigation, this histologic feature is considered strongly suggestive of colorectal spirochetosis. Our study concerned 19 male patients aged between 35 and 68 years, who had no risk factor for HIV infection, but who belonged to these three groups: (a) those suffering from chronic diarrhea; (b) those without intestinal symptoms; (c) those who had a colonic tumor removed. Rectal biopsy specimens were also taken from a control group of 35 patients seropositive for HIV-1. This thickening, which measured 3-7 microns, showed some variation within the same patient but did not depend on the site of the biopsy. It appeared as a blue fuzzy band on HES stain, was purple on Periodic-Acid-Schiff stain and basophilic after Giemsa stain. Silver stain by Warthin-Starry method confirmed the presence in three cases of numerous spirochetes attached to the epithelial surface. Two of the three patients had no symptom. In the control group, a thickening of the brush border, was observed in only one case, but no spirochete by silver stain was seen. The thickened blue, fuzzy brush border of the colonic mucosa is not a specific criterion. The pathologist must be aware of the possible presence of spirochetes that can only be confirmed by a silver stain. The pathogenicity of spirochetosis remains to be defined.


[Relationship between radiotherapy enhancing effect of arsenic trioxide and the proliferation and apoptosis of related protein in nasopharyngeal carcinoma patients].
To explore the mechanism of arsenic trioxide (ATO) in enhancing radiotherapy in nasopharyngeal carcinoma (NPC) patients. Seventy-four patients with NPC of T(1-4) N(0-1)M0 were randomized into two groups: 35 patients in Group A were treated with conventional radiotherapy alone, and the 39 in Group B received radiotherapy and additional administering of ATO. The regressions of nasopharyngeal lesions and cervical lymph nodes were compared between the two groups at 40 Gy of radiation was given. And biopsy of the tissue from NPC was taken before treatment and 24 h after radiation of 20 Gy to determine the-expressions of proliferating cell nuclear antigen (PCNA), Bcl-2, Bax and p53 protein by immunohistochemistry. When irradiation for 40 Gy, the completely regression rates of nasopharyngeal lesion were 20.0% (7/35) in Group A and 43.6% (17/39) in Group B, showing significant difference between them (chi2 = 4.684, P = 0.003), but no significant difference was shown between the two groups in regression rate of cervical lymph node. Expression of PCNA, Bax, Bcl-2 and p53 protein was reduced in both groups, but significant difference only showed between pre- and post-treatment in PCNA (Z = -2.449, P = 0.014) and Bax protein (Z = -3.031, P = 0.002) in Group B. Significantly reduction of PCNA (Z = -2.656, P = 0.008), Bax (Z = -2.359, P = 0.018) and p53 protein (Z = -1.999, P = 0.046) in patients with complete tumor regression at radiation for 20 Gy, while in those with no complete tumor regression only PCNA showed significant reduction (Z = -32.815, P = 0.015). ATO shows effect in enhancing radiotherapy on NPC patients, its mechanism might be associated with the down-regulation of PCNA and apoptosis related protein and the inhibition on tumor proliferation and apoptosis inducing.


A new approach for hydroxyapatite coating on polymeric materials using laser-induced precursor formation and subsequent aging.
A new process, laser-induced precursor formation and subsequent aging in a supersaturated calcium phosphate aqueous solution (CP solution), was applied for coating a hydroxyapatite (HAP) film on a polymeric material, ethylene-vinyl alcohol copolymer (EVOH). Laser irradiation onto EVOH immersed in the CP solution induced the formation of CP precursors, and an HAP film composed of a submicrometer-scale cavernous structure was formed by subsequent aging in a CP solution without laser irradiation. The resulting HAP film coated on EVOH demonstrated excellent structural and chemical uniformity and cell adhesion with the CHO-K1 and BHK-21 cells. This process provides a practical technique for coating HAP onto polymeric materials.


The Effects of Ionizing Radiation on the Oral Cavity.
The aim of this study is to present a literature review on the effects of the ionizing radiation from radiotherapy treatment on dental tissues. Among the effects of increasing global life expectancy and longevity of the teeth in the oral cavity, increasing rates of neoplastic diseases have been observed. One of the important treatment modalities for head and neck neoplastic diseases is radiotherapy, which uses ionizing radiation as the main mechanism of action. Therefore, it is essential for dentists to be aware of the changes in oral and dental tissues caused by ionizing radiation, and to develop treatment and prevention strategies. In general, there is still controversy about the effects of ionizing radiation on dental structures. However, qualitative and quantitative changes in saliva and oral microbiota, presence of oral mucositis and radiation-related caries are expected, as they represent the well-known side effects of treatment with ionizing radiation. Points that still remain unclear are the effects of radiotherapy on enamel and dentin, and on their mechanisms of bonding to contemporary adhesive materials. Ionizing radiation has shown important interaction with organic tissues, since more deleterious effects have been shown on the oral mucosa, salivary glands and dentin, than on enamel. With the increasing number of patients with cancer seeking dental treatment before and after head and neck radiotherapy, it is important for dentists to be aware of the effects of ionizing radiation on the oral cavity.


[Changes in prostatic acid phosphatase, gamma-seminoprotein and prostate specific antigen after endocrine therapy for stage D2 prostate cancer].
Prostatic acid phosphatase (PAP), gamma-seminoprotein (gamma-Sm) and prostate specific antigen (PSA) were examined on 120 cases of stage D2 prostate cancer between 1979 and 1989. All patients received endocrine therapy as the first treatment; castration and immediate administration of estrogen or antiandrogen (101), LH-RH analogs (13), estrogen (3) and antiandrogen (3). The actuarial survival rates were calculated by the cause-specific survival method. Pretreatment levels of PAP, gamma-Sm and PSA did not influence prognosis. After start of treatment, the relationship between the changes of the markers and prognosis were examined. At 1 month after the start of the treatment, normalization of PAP or gamma-Sm was not reflected in the following course. On the contrary, at 3 and 6 months, groups with normalization of PAP or gamma-Sm showed better prognosis than those with elevated levels. The same tendency of PSA was obtained at 6 months after start of treatment. In patients with normalized PAP at 3 months, abnormal gamma-Sm showed worse prognosis than normalized gamma-Sm. Therefore, the significance of determination on the two markers was manifested. As histological grade influenced the following course, poorly differentiated adenocarcinoma with normalized PAP at 3 months showed better prognosis than those with elevated levels. In conclusion, it is worthwhile to measure multiple markers for predicting the prognosis of stage D2 prostate cancer treated with endocrine therapy.


The association between vitamin K status and knee osteoarthritis features in older adults: the Health, Aging and Body Composition Study.
Vitamin K-dependent (VKD) proteins, including the mineralization inhibitor matrix-gla protein (MGP), are found in joint tissues including cartilage and bone. Previous studies suggest low vitamin K status is associated with higher osteoarthritis (OA) prevalence and incidence. To clarify what joint tissues vitamin K is relevant to in OA, we investigated the cross-sectional and longitudinal association between vitamin K status and knee OA structural features measured using magnetic resonance imaging (MRI). Plasma phylloquinone (PK, vitamin K1) and dephosphorylated-uncarboxylated MGP ((dp)ucMGP) were measured in 791 older community-dwelling adults who had bilateral knee MRIs (mean ± SD age = 74 ± 3 y; 67% female). The adjusted odds ratios (and 95% confidence intervals) [OR (95%CI)] for presence and progression of knee OA features according to vitamin K status were calculated using marginal models with generalized estimating equations (GEEs), adjusted for age, sex, body mass index (BMI), triglycerides and other pertinent confounders. Longitudinally, participants with very low plasma PK (<0.2 nM) were more likely to have articular cartilage and meniscus damage progression after 3 years [OR (95% CIs): 1.7(1.0-3.0), 2.6(1.3-5.2) respectively] compared to sufficient PK (≥ 1.0 nM). Higher plasma (dp)ucMGP (reflective of lower vitamin K status) was associated with higher odds of meniscus damage, osteophytes, bone marrow lesions, and subarticular cysts cross-sectionally [ORs (95% CIs) comparing highest to lowest quartile: 1.6(1.1-2.3); 1.7(1.1-2.5); 1.9(1.3-2.8); 1.5(1.0-2.1), respectively]. Community-dwelling men and women with very low plasma PK were more likely to have progression of articular cartilage and meniscus damage. Plasma (dp)ucMGP was associated with presence of knee OA features but not progression. Future studies are needed to clarify mechanisms underlying vitamin Ks role in OA.


Elevated STAT1 expression but not phosphorylation in lupus B cells correlates with disease activity and increased plasmablast susceptibility.
SLE is characterized by two pathogenic key signatures, type I IFN and B-cell abnormalities. How these signatures are interrelated is not known. Type I-II IFN trigger activation of Janus kinase (JAK) - signal transducer and activator of transcription (STAT). JAK-STAT inhibition is an attractive therapeutic possibility for SLE. We assess STAT1 and STAT3 expression and phosphorylation at baseline and after IFN type I and II stimulation in B-cell subpopulations of SLE patients compared with other autoimmune diseases and healthy controls (HD) and related it to disease activity. Expression of STAT1, pSTAT1, STAT3 and pSTAT3 in B and T cells of 21 HD, 10 rheumatoid arthritis (RA), seven primary Sjögren's (pSS) and 22 SLE patients was analysed by flow cytometry. STAT1 and STAT3 expression and phosphorylation in PBMCs (peripheral blood mononuclear cells) of SLE patients and HD after IFNα and IFNγ incubation were further investigated. SLE patients showed substantially higher STAT1 but not pSTAT1 in B- and T-cell subsets. Increased STAT1 expression in B-cell subsets correlated significantly with SLEDAI and Siglec-1 on monocytes, a type I IFN marker. STAT1 activation in plasmablasts was IFNα dependent while monocytes exhibited dependence on IFNγ. Enhanced expression of STAT1 by B-cell candidates as a key node of two immunopathogenic signatures (type I IFN and B-cells) related to important immunopathogenic pathways and lupus activity. We show that STAT1 is activated upon IFNα exposure in SLE plasmablasts. Thus, Jak inhibitors, targeting JAK-STAT pathways, hold a promise to block STAT1 expression and control plasmablast induction in SLE.


Determination of fluoroquinolones in milk samples by postcolumn derivatization liquid chromatography with luminescence detection.
A liquid chromatography (LC) method with luminescence detection for the determination of eight quinolone antibiotics is reported. The system encompasses three consecutive steps: (a) chromatographic separation using reverse-phase mode (RP-LC), (b) postcolumn derivatization reaction, and (c) luminescence detection by monitoring fluorescence (FL) and time-resolved (TR) signals. The derivatization step is based on the reaction between quinolones and terbium(III) to form luminescent chelates, which were determined at lambda(ex) 340 and lambda(em) 545 nm (FL mode) or at lambda(ex) 281 and lambda(em) 545 nm (TR mode). Dynamic ranges of the calibration graphs, obtained with standard solutions of analytes and FL and TR modes, respectively, were 190-3500 and 316-2000 ng mL-1 for marbofloxacin, 8-3500 and 8.1-1500 ng mL-1 for ciprofloxacin, 6.2-3500 and 13-1500 ng mL-1 for danofloxacin, 7.4-3500 and 8.4-1500 ng mL-1 for enrofloxacin, 14-3500 and 20-2000 ng mL-1 for sarafloxacin, 12.5-3500 and 13.9-1200 ng mL-1 for difloxacin, 7.6-3500 and 13-3000 ng mL-1 for oxolinic acid, and 9-2000 and 130-3000 ng mL-1 for flumequine. Limit of detection values obtained using FL and TR modes, respectively, were 60 and 95 ng mL-1 for marbofloxacin, 2 and 2.4 ng mL-1 for ciprofloxacin, 1.9 and 3.9 ng mL-1 for danofloxacin, 2.2 and 2.5 ng mL-1 for enrofloxacin, 3.8 and 7 ng mL-1 for sarafloxacin, 4 and 4.2 ng mL-1 for difloxacin, 2.3 and 4 ng mL-1 for oxolinic acid, and 2.7 and 40 ng mL-1 for flumequine. The precision was established at two concentration levels of each analyte and expressed as the percentage of relative standard deviation with values ranging between 1.9 and 7.8%. The validation procedure for the analysis of samples was carried out using European Community recommendations, and the decision limit and detection capability were calculated for bovine whole milk. The method was applied to whole, semiskimmed, and skimmed milk samples spiked with the target analytes, and the recoveries ranged between 93.3 and 106.0%.


The properties of acoustically responsive cells in the anterior suprasylvian gyrus of the cat.
The properties of acoustically responsive neurons were studied in the anterior part of the suprasylvian gyrus ( ASG ) of cats anaesthetized with pentobarbital or chloralose-urethan. The acoustic responsiveness of the cells was screened with click stimuli. Whenever an acoustic response occurred, its properties were further analysed with the aid of spectrally pure tone pulses. The most important features of the responses given to pure tones of different frequencies were (a) short latency and (b) sharp tuning to well defined frequencies. In this respect the cells showed a close resemblance to those in the primary acoustic area (AI) and differed considerably from neurons of the middle suprasylvian association field (AMSA), which lacked well defined best frequency (BF) and responded with longer latencies. At the same time the ASG neurons showed responses to somatosensory stimuli thus representing a transition between neurons of primary sensory and association areas.


A high-risk group for prostatism: a population-based epidemiological study in Korea.
To evaluate the effect of sociodemographic, dietary and physical factors on prostatism in Korean men aged 50 and over. A community-based cross-sectional epidemiological study was performed in Yonchon County, Korea. The Korean version of the International Prostate Symptom Score (IPSS) was used to assess the severity of prostatism. Data on occupation, marital status, education, smoking habits, alcohol intake, daily consumption of nutrients, body mass index, abdominal circumference, waist-to-hip ratio, blood pressure, serum glucose, cholesterol, triglyceride and high-density lipoprotein (HDL) levels were analysed. The age-adjusted relative risk of these factors was calculated for moderate to severe prostatism (IPSS > or = 8). A multivariate analysis of all significant factors was performed to examine the joint effect of risk factors. Of 514 subjects, 119 (23.2%) had moderate to severe prostatism, the risk for which was related to age and alcohol consumption; waist-to-hip ratio (which represents the degree of abdominal obesity) and the serum level of HDL showed a biphasic association with prostatism in the multivariate analysis. In addition to previously reported risk factors, these data suggest that there might be an association between the development of prostatism and abnormal lipid metabolism.


Advances in the Diagnosis and Management of Influenza.
Vaccines are the mainstay of influenza prevention. In the treatment of a likely or certain case of influenza, ion channel inhibitors (amantadine and rimantadine) and neuraminidase inhibitors (oseltamivir and zanamivir) can be effective in reducing the duration of illness in adults. In the absence of a likely or certain influenza diagnosis, ion channel inhibitors or neuramindase inhibitors have lower effectiveness, and symptom relief becomes the rationale for treatment of influenza-like illness. Because both influenza and influenza-like illness are self-limiting, safety of interventions is paramount, especially in children. Echinacea extracts, steam, chicken soup, ipatropium bromide, and oxymetazoline in adults are the interventions that appear to have the best empirical evidence.


Binding of the amino-terminal region of myosin alkali 1 light chain to actin and its effect on actin-myosin interaction.
The role of the amino-terminal region of myosin alkali 1 light chain (A1) in the interaction between actin and myosin subfragment-1 (S-1) was explored. Papain digestion of skeletal myosin filaments produced S-1 whose A1 was found to lose the basic 13 amino-terminal amino acid residues (A1'). We obtained three types of papain S-1 isoenzymes differing in their alkali light chain content: recombined papain S-1 (A1), papain S-1 (A1'), and papain S-1 (A2). Both the maximum turnover rate (Vmax) and the dissociation constant (Km) for actin-activated papain S-1 (A1') ATPase activity were similar to those for papain S-1 (A2) and remarkably larger than those for recombined papain S-1 (A1). The 13 amino-terminal residue peptide of A1 (N-pep) was isolated and characterized. 1H-NMR spectroscopy suggested that the N-pep was relatively immobilized in the presence of actin filaments. A cross-linking study suggested that N-pep binds to actin. The addition of N-pep to acto-S-1 (A1) made Km and Vmax for the actin-activated ATPase activity close to those for S-1 (A2). Removal of the trimethyl group from the N-pep suppressed the above effect on the actin-S-1 interaction. Our findings suggest that the amino-terminal region of A1 binds to the actin molecule to affect the mechanism of actin-activated S-1 ATPase.


Novel splice-site mutation in TTLL5 causes cone dystrophy in a consanguineous family.
To report the clinical and genetic findings of one family with autosomal recessive cone dystrophy (CD) and to identify the causative mutation. An institutional study of three family members from two generations. The clinical examination included best-corrected Snellen visual acuity measurement, fundoscopy, the Farnsworth D-15 color vision test, a full-field electroretinogram (ERG) that incorporated the International Society for Clinical Electrophysiology of Vision standards and methodology, fundus autofluorescence (FAF) and infrared (IR), and spectral-domain optical coherence tomography (SD-OCT). Genetic findings were achieved with DNA analysis using whole exome sequencing (WES) and Sanger sequencing. The proband, a 9-year-old boy, presented with a condition that appeared to be congenital and stationary. The clinical presentation initially reflected incomplete congenital stationary night blindness (icCSNB) because of myopia, a decrease in visual acuity, abnormal oscillatory potentials, and reduced amplitudes on the 30 Hz flicker ERG but was atypical because there were no clear electronegative responses. However, no disease-causing mutations in the genes underlying icCSNB were identified. Following WES analysis of family members, a homozygous splice-site mutation in intron 3 of TTLL5 (c.182-3_182-1delinsAA) was found cosegregating within the phenotype in the family. The distinction between icCSNB and CD phenotypes is not always straightforward in young patients. The patient was quite young, which most likely explains why the progression of the CD was not obvious. WES analysis provided prompt diagnosis for this family; thus, the use of this technique to refine the diagnosis is highlighted in this study.


First-Principles Study on O2 Adsorption and Dissociation Processes over Rh(100) and Rh(111) Surfaces.
Through DFT calculations, a systematic description of O2 adsorption and dissociation processes over Rh(100) and Rh(111) surfaces has been provided. The dominance of parallel orientation in molecularly adsorbed states and during the impinging processes has been identified, along with the explicit adsorption configurations and preferred impinging trajectories on both surfaces. The dissociation of O2 is found to occur either by precursor-mediated adsorption or by direct dissociation. O2 in its initial precursor state dissociates facilely on Rh(100), but this is a little harder on Rh(111) by going through a two-step process. The latter can be described as a preliminary rotation and subsequent dissociation, with the final locations of two O atoms disturbed easily by coadsorbed O atoms surrounding the dissociating O2 molecule due to the existence of a relatively flat potential energy surface stage along the way. The present work may provide the basis for kinetic modeling to investigate the catalytic properties on a realistic scale.


Prevalence of food insecurity and association with mental health in an indigenous population in Panamá.
Understanding food insecurity and its health consequences is important for identifying strategies to best target support for individuals and communities. Given the limited information that exists for indigenous groups in Latin America, this study aimed to understand the association between food insecurity and mental health in an indigenous population in Panama. Cross-sectional data were collected using a survey conducted with Kuna Indians residing off the coast of Panama. Data sources included measures from the Panamanian prevalence of risk factors associated with CVD survey, and validated measures for psychosocial factors and standardised health outcome measures. Regression models with each of the mental health outcomes (depression, serious psychological distress, perceived stress) were used to examine the association between food insecurity and mental health outcomes. Indigenous Kuna community residing on the San Blas Islands of Panama. Two-hundred nine adults. Food insecurity was reported by 83 % of the participants. Across demographic categories, the only significant difference was by age with higher prevalence in younger ages. After adjusting for demographics, higher food insecurity was significantly associated with higher number of depressive symptoms and more serious psychological distress, but not with levels of perceived stress. Based on these findings, treatment for mental health in the Kuna community may need to account for social determinants of health and be tailored to meet the needs of younger age groups in this population. In addition, interventions designed to decrease food insecurity should be considered as a possible means for improving mental health.


Osteorticular amyloidosis in a patient under dialysis treated by total hip arthroplasty: case report and review of the literature.
The authors present the case of a patient affected by kidney failure, who had been undergoing dialysis for several years when areas of osteolysis and bone resorption in the proximal femur and pathologic fracture appeared. She was treated surgically by hybrid total hip arthroplasty. The patient also complained of pains in other joints. The bone tissue taken from the osteolytic area was examined histologically. The test showed the presence of an amyloid substance. Microradiography and X-ray diffractometry carried out on the same samples confirmed the lack of mineralisation due to the presence of aluminum ions, presumably derived from dialysis. The high concentration of this element was confirmed by resum assay with spectrophometry in atomic absorption. Considering the results of the aforementioned tests, the patient was put on dialysis using a polymethylmethacrylate filter.


[Associations of Crohn's disease with DR4 and DR5 gene polymorphisms].
To assess the associations of death receptor DR4 and DR5 gene polymorphisms with Crohn's disease (CD). A total of 295 CD patients and 490 healthy controls were recruited. Three single nucleotide polymorphisms (SNPs) of the DR4 (rs13278062, rs20575) and DR5 (rs1047266) genes were determined with a SNaPshot method. Unconditional logistic regression analysis was carried out for determining the allelic and genotypic differences of the three SNPs between CD patients and the controls, as well as the influence of the DR4 and DR5 gene polymorphisms on the clinical features of CD patients. Linkage disequilibrium and haplotype analysis were calculated by haplotype 4.2 and R language software. A gene-gene interaction model was established to analyze whether the three SNPs can exert a synergistic effect on the susceptibility to CD. The mutant allele (T) and genotype (GT+TT) of DR4 (rs13278062) were increased among CD patients compared to the controls (37.12% vs. 32.04%, P = 0.040, 95%CI: 1.010-1.550; 62.71% vs. 54.90%, P = 0.032, 95%CI: 1.028-1.855, respectively). However, the allelic and genotypic frequencies of DR4 (rs20575) and DR5 (rs1047266) did not differ between the two groups (all P > 0.05). Based on the Montreal Classification Standards, the CD patients were stratified by locations and behaviors of the disease. After multiple comparison correction (P < 0.0125), compared to ileocolonic CD patients respectively, the mutant allele (T) and genotype (GT+TT) of the rs13278062 polymorphism were significantly increased in colonic CD patients (41.04% vs. 25.64%, P = 0.002, 95%CI: 0.315-0.778; 66.04% vs. 41.03%, P = 0.001, 95%CI: 0.196-0.655, respectively) and terminal ileum CD patients (41.44% vs. 25.64%, P = 0.002, 95%CI: 0.311-0.762; 74.77% vs. 41.03%, P < 0.001, 95%CI: 0.126-0.437, respectively). In comparison to penetrating CD patients, the mutant allele (T) and genotype (GT+TT) of DR4 (rs13278062) were significantly decreased in stricturing CD patients (32.29% vs. 48.91%, P = 0.007, 95%CI: 0.300-0.828; 57.29% vs. 86.96%, P = 0.001, 95%CI: 0.078-0.520, respectively). A similar conclusion was drawn for the mutant genotype (GT+TT) of DR4 (rs13278062) in non-stricturing, non-penetrating CD patients (58.82% vs. 86.96%, P = 0.001, 95%CI: 0.086-0.536). Haplotype analysis indicated that the CT haplotype formed by rs20575 and rs13278062 was increased in CD patients compared to the controls (37.1% vs. 31.8%, P = 0.029, OR=1.279, 95%CI: 1.022-1.600). The outcome of a gene-gene interaction model indicated that the mutant genotype (GT+TT) of DR4 (rs13278062) and mutant genotype (CT+TT) of DR5 (rs1047266) may play a negatively synergistic role in CD patients (B = - 0.483, OR = 0.617, P = 0.030). The rs13278062 polymorphism of the DR4 gene not only can confer an increased risk for CD, but may also influence the location of the lesions and the disease behaviors. The CT haplotype formed by rs20575 and rs13278062 may be an independent risk factor for CD. Furthermore, the mutant genotype (GT+TT) of DR4 (rs13278062) and mutant genotype (CT+TT) of DR5 (rs1047266) may exert a negative synergistic effect on CD.


Comprehensive approach to intrinsic charge carrier mobility in conjugated organic molecules, macromolecules, and supramolecular architectures.
Si-based inorganic electronics have long dominated the semiconductor industry. However, in recent years conjugated polymers have attracted increasing attention because such systems are flexible and offer the potential for low-cost, large-area production via roll-to-roll processing. The state-of-the-art organic conjugated molecular crystals can exhibit charge carrier mobilities (μ) that nearly match or even exceed that of amorphous silicon (1-10 cm(2) V(-1) s(-1)). The mean free path of the charge carriers estimated from these mobilities corresponds to the typical intersite (intermolecular) hopping distances in conjugated organic materials, which strongly suggests that the conduction model for the electronic band structure only applies to μ > 1 cm(2) V(-1) s(-1) for the translational motion of the charge carriers. However, to analyze the transport mechanism in organic electronics, researchers conventionally use a disorder formalism, where μ is usually less than 1 cm(2) V(-1) s(-1) and dominated by impurities, disorders, or defects that disturb the long-range translational motion. In this Account, we discuss the relationship between the alternating-current and direct-current mobilities of charge carriers, using time-resolved microwave conductivity (TRMC) and other techniques including field-effect transistor, time-of-flight, and space-charge limited current. TRMC measures the nanometer-scale mobility of charge carriers under an oscillating microwave electric field with no contact between the semiconductors and the metals. This separation allows us to evaluate the intrinsic charge carrier mobility with minimal trapping effects. We review a wide variety of organic electronics in terms of their charge carrier mobilities, and we describe recent studies of macromolecules, molecular crystals, and supramolecular architecture. For example, a rigid poly(phenylene-co-ethynylene) included in permethylated cyclodextrin shows a high intramolecular hole mobility of 0.5 cm(2) V(-1) s(-1), based on a combination of flash-photolysis TRMC and transient absorption spectroscopy (TAS) measurements. Single-crystal rubrene showed an ambipolarity with anisotropic charge carrier transport along each crystal axis on the nanometer scale. Finally, we describe the charge carrier mobility of a self-assembled nanotube consisting of a large π-plane of hexabenzocoronene (HBC) partially appended with an electron acceptor. The local (intratubular) charge carrier mobility reached 3 cm(2) V(-1) s(-1) for the nanotubes that possessed well-ordered π-stacking, but it dropped to 0.7 cm(2) V(-1) s(-1) in regions that contained greater amounts of the electron acceptor because those molecules reduced the structural integrity of π-stacked HBC arrays. Interestingly, the long-range (intertubular) charge carrier mobility was on the order of 10(-4) cm(2) V(-1) s(-1) and monotonically decreased when the acceptor content was increased. These results suggest the importance of investigating charge carrier mobilities by frequency-dependent charge carrier motion for the development of more efficient organic electronic devices.


Management of 80 sinonasal undifferentiated carcinomas. Retrospective multicentre study of the French Network of Rare Head and Neck Cancers (REFCOR).
Sinonasal undifferentiated carcinoma (SNUC) is a rare and aggressive disease requiring multimodal treatment, and multiple new entities once included in the spectrum of SNUC, such as SWI/SNF-deficient carcinomas, are emerging. We aimed to provide new data regarding the role of chemotherapy and surgery and the prognostic factors of disease-free survival. This study was based on data from the REFCOR database and included patients with SNUC treated with curative intent from 2007 to 2021 across 22 centres in France. A total of 80 patients were included in the analysis. Among the entire cohort, the 5-year disease-free survival (DFS) and overall survival (OS) rates were 58% and 63%, respectively. Of 100% of the patients treated with irradiation, 29% underwent surgery, 56% neoadjuvant chemotherapy (82% had either a partial or a complete response) and 76% chemoradiotherapy. No treatment modality was associated with a better OS or DFS, including surgery (p = 0.34). There was a trend for a better DFS for the patients treated with chemotherapy (neoadjuvant or concomitant, p = 0.062). Overall survival at 3 years was 58% for SWI/SNF deficient group and 86% for non deficient group (p = 0.14). The locoregional relapse rate without distant metastases was 21% in the exclusive radiotherapy group and 26% in the surgery group. Grade 3 or higher toxicities concerned 9%, 32% and 29% of patients for surgery, radiotherapy and chemotherapy respectively. In the management of localised SNUC among all patients treated with irradiation, surgery yielded no benefit, whereas the addition of chemotherapy tended to improve disease-free survival.


Pyrrolopyrrole aza-BODIPY analogues: a facile synthesis and intense fluorescence.
Pyrrolopyrrole aza-BODIPY analogues were synthesized from diketopyrrolopyrrole and heteroaromatic amines in the presence of titanium tetrachloride. These novel compounds exhibit intense absorption in the visible region and strong emission with high fluorescence quantum yields greater than 0.8.


P020 Proton Pump Inhibitor Therapy: Providing "Acid" Outcomes in Patients With Inflammatory Bowel Disease Under Infliximab Treatment.
A recent meta-analysis has suggested that proton pump inhibitor (PPI) therapy is associated with lower clinical remission rates and a higher number of hospitalizations in patients with inflammatory bowel disease (IBD) under infliximab therapy. We aimed to assess if these differences kept their significance when adjusted for other possible confounders. Cohort study of consecutive patients with Crohn's disease (CD) and Ulcerative Colitis (UC) under infliximab therapy. A minimum follow-up of 54 weeks after introduction of infliximab treatment was required. The analyzed outcomes were deep remission at week 54 and the need of IBD-related hospitalization, corticosteroid treatment or abdominal surgery under infliximab treatment. Collected possible confounders were age, gender, smoking habits, perianal disease, extra-intestinal manifestations, familiar history of IBD and concomitant use of immunomodulators. Our final sample included 104 patients, 56 (53.8%) of them females, with a mean age of 38.2±13.1 years. From these, 77 (74.0%) had CD and 27 (26.0%) had UC. PPI therapy was described in 21 (20.2%) of the patients under infliximab treatment. On univariate analysis, PPI users were found to have significantly lower rates of deep remission at week 54 (7.7 vs 28.3%; p = 0.034) and higher IBD-related hospitalization rates (47.6 vs 21.7%; p = 0.034). No differences were found regarding the need of corticosteroid therapy (4.8 vs 10.8%; p = 0.398) or abdominal surgery (33.7 vs 21.7; p = 0.201). When adjusted for the collected confounders by multivariate analysis, while not significantly influencing deep remission at week 54 (OR = 0.16; 95%CI = 0.02-1.63; p = 0.121), concomitant PPI therapy was a significant independent risk factor for IBD-related hospitalization (OR = 3.22; 95%CI = 1.11-9.34; p = 0.04). Despite not conducting to significantly different deep remission rates, concomitant PPI therapy was associated with a three-fold increase in hospitalization rates in IBD patients under infliximab treatment, even when adjusted for classical risk factors for adverse outcomes in IBD. These findings emphasize the importance of restricting PPI treatment to those with a clear clinical indication, especially in this set of patients.


Energy cost of speec skating and efficiency of work against air resistance.
The energy expenditure during speed ice skating (PB=650 mmHg; T=-5 degrees C) was measured on 13 athletes (speed range: 4-12 m/s) from VO2 and (for speeds greater than 10 m/s) from blood lactic acid concentration. The energy spent (O2 equivalents) per unit body wt and unit distance (Etot/V, ml/kg-min) increases with the speed (v, m/s): Etot/v=0.049 + 0.44 X 10(-3) V2. At 10 m/s, Vtot/v amounts then to 0.093 ml/kg-m: about half the value of running. The constant 0.049 ml/kg-m is interpreted as the energy spent against gravitational and inertial forces. The term 0.44 X 10(-3) v2 indicates the energy spent against the wind, the constant 0.44 X 10(-3) ml-s2-kg-1-m-3 being a measure of k/e, where k is the coefficient relating drag to v2, and e the efficiency of work against the wind. From a direct estimate of k in a wind tunnel, e was calculated as 0.11. In running, skating, and cycling k/e is similar (approximately 0.020 ml-s2-m-3 per m2 body area), hence at a given speed the energy spent against the wind is equal. On the contrary, the energy spent against other forces decreases in the above order: 0.19, 0.05, 0.018 ml-m-1 per kg body wt. This explains the different speeds attained in these exercises with the same power output.


Invited review: Advances and applications of random regression models: From quantitative genetics to genomics.
An important goal in animal breeding is to improve longitudinal traits; that is, traits recorded multiple times during an individual's lifetime or physiological cycle. Longitudinal traits were first genetically evaluated based on accumulated phenotypic expression, phenotypic expression at specific time points, or repeatability models. Until now, the genetic evaluation of longitudinal traits has mainly focused on using random regression models (RRM). Random regression models enable fitting random genetic and environmental effects over time, which results in higher accuracy of estimated breeding values compared with other statistical approaches. In addition, RRM provide insights about temporal variation of biological processes and the physiological implications underlying the studied traits. Despite the fact that genomic information has substantially contributed to increase the rates of genetic progress for a variety of economically important traits in several livestock species, less attention has been given to longitudinal traits in recent years. However, including genomic information to evaluate longitudinal traits using RRM is a feasible alternative to yield more accurate selection and culling decisions, because selection of young animals may be based on the complete pattern of the production curve with higher accuracy compared with the use of traditional parent average (i.e., without genomic information). Moreover, RRM can be used to estimate SNP effects over time in genome-wide association studies. Thus, by analyzing marker associations over time, regions with higher effects at specific points in time are more likely to be identified. Despite the advances in applications of RRM in genetic evaluations, more research is needed to successfully combine RRM and genomic information. Future research should provide a better understanding of the temporal variation of biological processes and their physiological implications underlying the longitudinal traits.


A multifunctional tetrametallic Ru-Pt supramolecular complex exhibiting both DNA binding and photocleavage.
A new tetrametallic supramolecular complex, [{(bpy)2Ru(dpp)}2Ru(dpp)PtCl2](PF6)6 (bpy = 2,2'-bipyridine, dpp = 2,3-bis(2-pyridyl)pyrazine), has been prepared and characterized. This supramolecular assembly is multifunctional, forming coordinate covalent bonds to DNA through its cis-PtCl2 moiety and photocleaving DNA through its Ru polypyridine chromophores. Electronic absorption spectroscopy shows ligand-based pi-->pi* transitions in the UV with Ru-based metal-to-ligand charge transfer transitions throughout much of the visible. The Ru-->dpp CT transitions center at 542 nm (eta = 35 000 M-1 cm-1). This complex has a HOMO localized on peripheral Ru with E(1/2)oxd = 1.58 V vs Ag/AgCl, and a LUMO based on the mu-dpp connecting Ru and Pt, E(1/2)red = -0.40 V. Gel electrophoresis analysis shows the tetrametallic coordinates to pUC18 DNA and, when excited with visible light, cleaves DNA through an oxygen-mediated pathway.


Visceral organ mass and cellularity in growth-restricted and refed beef steers.
Beef steers were fed in two phases to compare the effects of diet and intake on growth and cellularity of visceral organs. During the growing phase (237 to 327 kg), steers were fed either a high (C) or low (F) concentrate diet. Diet F was available ad libitum (FA), whereas diet C was available either ad libitum (CA) or on a limited basis (CL) to match live weight gains of the FA group. During the finishing phase (327 to 481 kg), all steers received diet C either ad libitum (CA-CA, CL-CA, and FA-CA) or restricted (CL-CL and FA-CL) to 70% of the intakes of corresponding CA steers. Marked nutritional effects on liver growth (e.g., -25 and -15% in CL and FA, respectively, relative to CA) were due mainly to changes in cell size (i.e., protein:DNA), with smaller changes in cell numbers (i.e., DNA). Hyperplasia and hypertrophy played a role in growth of the forestomachs, although cell numbers and sizes tended to change in opposite directions, limiting magnitudes of changes in organ mass. Protein synthetic capacity (i.e., RNA) varied as well, often in parallel with cell number. This result differed from that observed in intestines, which maintained constant cell sizes but underwent marked changes in cell number. For liver, amounts of absorbed nutrients seemed to be the main factor driving hypertrophy. The organs of the gastrointestinal tract responded to physical and chemical signals, as shown by the effects of dietary fiber on growth of the forestomachs and intestines. Forestomachs responded mainly to diet fiber content, whereas the intestines responded to diet type and nutrient supply. Feeding programs for beef animals often include changes in diet type and periods of feed limitation, and these in turn affect visceral organ growth and metabolism. Because visceral organs are a major contributor to whole-body energy expenditures, factors affecting these tissues must be understood. This study supports the concept that workload determines organ size, but dietary factors influencing workload clearly vary for each organ.


A pathogenetic model for erosive synovitis: lessons from animal arthritides.
Adjuvant arthritis, streptococcal cell wall-induced arthritis, and Erysipelothrix insidiosa arthritis are laboratory models of relapsing, erosive synovitis. A review of the experimental literature suggests that their pathogenesis is similar. The persistence in macrophages in the pannus of nonbiodegradable microbial cell wall components containing the peptidoglycan moeity is the central event. Based on this experimental literature, a model for the pathogenesis of these arthritides is developed. This model is testable and relevant to erosive synovitis in man.


Staging soft tissue sarcoma: evolution and change.
Soft tissue sarcoma (STS) is an extremely heterogeneous group of rare tumors that share a putative mesenchymal cell origin. STS can occur in any soft tissue in the body, yet all share a common feature of primarily disseminating hematogenously, particularly to the lungs. Staging for STS is particularly useful in prognosis, design of effective multimodality treatment programs, and comparing treatment outcomes from different centers and different eras. The current iteration of AJCC STS staging includes Tumor, Grade, Node, and Metastasis with "a" indicating superficial and "b" indicating deep designations. Further opportunities to improve this process exist, particularly as molecular considerations become more apparent, and future evolution into an even more useful STS staging system can be anticipated.