Changes in malaria epidemiology in France and worldwide, 2000-2015.
In 2015, 212 million new cases of malaria were reported, causing 429,000 deaths. The World Health Organization (WHO) estimated a 41% decrease in the number of new cases worldwide between 2000 and 2015. The number of deaths from malaria fell by 62% worldwide and by 71% in Africa. In mainland France, malaria is mainly imported by travelers or migrants from endemic areas, in particular sub-Saharan Africa (95%). In France, the number of imported malaria cases, mainly due to Plasmodium falciparum (85%), was estimated at about 82,000 for the period 2000-2015. Over the same period, 6,468 cases of malaria were reported in the French armed forces, of which 2,430 cases (37.6%) were considered as imported because occurring outside of endemic areas. The number of malaria cases also fell between 2000 and 2015 in Mayotte and French Guiana, a malaria transmission zone. Mayotte has entered the elimination of malaria with less than 15 cases per year. In French Guiana, between 300 and 500 cases have been reported annually in recent years. The decline in morbidity and mortality is usually attributed to vector control measures and improved access to effective treatments. However, the Anopheles mosquitoes that transmit the disease have developed resistance against most insecticides. Similarly, malaria parasites have developed resistance against most of the antimalarial drugs used as prevention or treatment, even the latest marketed combinations such as artemisinin-based combination therapies.


Receptor-mediated endocytosis of immunoglobulin light chains by renal proximal tubule cells.
We examined the binding, endocytosis, and degradation of immunoglobulin light chains by primary cultures from rat renal kidneys and immortalized human proximal tubule cells. Both the association and dissociation of light chain were rapid and plateaued within 30 min at 4 degrees C. Up to 10(-3) M bovine serum albumin did not inhibit light chain binding to cells. Internalization studies with 125I-labeled kappa- and lambda-light chains by cells using the acid wash technique showed that up to 80% of total cell-associated binding at equilibrium (30 min) is rapidly internalized at 22 degrees C. Comparison of binding and internalization of light chains with transferrin, a ligand known to undergo receptor-mediated endocytosis, showed that both ligands displayed saturable kinetics. In contrast, endocytosis of sucrose, a marker for fluid-phase endocytosis, was unsaturable and nearly 200-fold less efficient than light chain internalization. Scatchard analysis of binding experiments done at 4 degrees C with trace 125I-labeled lambda-light chain in presence of 0 to 3.0 x 10(-3) M cold light chain revealed a single class of binding sites with a dissociation constant of 5.0 +/- 0.8 x 10(-5) and a maximal binding capacity of 1.6 +/- 0.3 x 10(-9) mol/mg cell protein. Hypertonic medium, a maneuver which interferes with the formation of the clathrin lattice, reduced endocytosis of light chain significantly but did not affect endocytosis of sucrose. Chloroquine and bafilomycin A, agents that interfere with vesicular acidification, also significantly suppressed light chain endocytosis. Using acid precipitation method, we observed that endocytosis of 125I-labeled lambda-light chain results in degradation by the rat renal proximal tubule cells. Degradation was maximum at 37 degrees C, significantly reduced at 22 degrees C, and absent at 4 degrees C. Excess light chain inhibited degradation of radiolabel, whereas excess albumin had no effect. These studies document the presence of binding sites for light chains on proximal tubule cells that mediate endocytosis of light chains by proximal tubule cells. The present data suggest that receptor-mediated endocytosis of light chains leads to delivery of this ligand to degradative sites through acidified vesicles.


Awareness and support for post-stroke fatigue among medical professionals in the recovery phase rehabilitation ward.
Sato M, Hyakuta T. Awareness and support for post-stroke fatigue among medical professionals in the recovery phase rehabilitation ward. Jpn J Compr Rehabil Sci 2023; 14: 39-48. To clarify the level of awareness of and support for post-stroke fatigue among medical professionals working in recovery phase rehabilitation wards. We conducted a questionnaire survey targeting all medical professionals (physicians, nurses, physical therapists, occupational therapists, and speech therapists) working in recovery phase rehabilitation wards of three facilities to evaluate their awareness of post-stroke fatigue and the support they were offering to address this. Quantitative data were subjected to statistical analysis and free description data were subjected to content analysis. Of the 130 participants, we obtained responses from 94 (collection rate, 72.3%; valid response rate, 100%). Those who felt that post-stroke patients are always tired or tire easily comprised 63.8%. Those who acknowledged the importance of post-stroke fatigue as a problem and that it is an issue that must be addressed comprised 70.2% and 73.4%, respectively. Issues emerging due to post-stroke fatigue were extracted as follows: "Difficulty continuing with rehabilitation," "Decreased drive," "Difficulty with emotional control/depression," "Fewer interactions with others," and "Loss of goals." Support for post-stroke fatigue was offered by 57.4% of medical professionals, most commonly as individual support such as "Ensure rest." The effects of support were described as "Cannot say either way" (44.4%), with 3.7% noting that they were not very effective. Awareness and support rates among therapists were significantly higher than those among nurses. Post-stroke fatigue is acknowledged by medical professionals as a critical issue that negatively influences the patient's physical, emotional, and daily living functions. Unfortunately, effective support is not currently being offered, demonstrating the need for the development of appropriate interventions.


Structure-based design, optimization of lead, synthesis, and biological evaluation of compounds active against Trypanosoma cruzi.
Chagas' disease affects approximately eight million people throughout the world, especially the poorest individuals. The protozoan that causes this disease-Trypanosoma cruzi-has the enzyme cruzipain, which is the main therapeutic target. As no available medications have satisfactory effectiveness and safety, it is of fundamental importance to design and synthesize novel analogues that are more active and selective. In the present study, molecular docking and the in silico prediction of ADMET properties were used as strategies to optimize the trypanocidal activity of the pyrimidine compound ZN3F based on interactions with the target site in cruzipain. From the computational results, eight 4-amino-5-carbonitrile-pyrimidine analogues were proposed, synthesized (5a-f and 7g-h) and, tested in vitro on the trypomastigote form of the Tulahuen strain of T. cruzi. The in silico study showed that the designed analogues bond favorably to important amino acid residues of the active site in cruzipain. An in vitro evaluation of cytotoxicity was performed on L929 mammal cell lines. All derivatives inhibited the Tulahuen strain of T. cruzi and also exhibited lower toxicity to L929 cells. The 5e product, in particular, proved to be a potent, selective (IC50 = 2.79 ± 0.00 μM, selectivity index = 31.3) inhibitor of T. cruzi. The present results indicated the effectiveness of drugs based on the structure of the receptor, revealing the potential trypanocidal of pyrimidines. This study also provides information on molecular aspects for the inhibition of cruzipain.


A new digital single-axis fluxgate magnetometer according to the cobalt-based amorphous effects.
Fluxgate sensors are currently widely used for weak magnetic field measurement because of their relatively great performance, such as resolution, power consumption, and measurement of vector magnetic fields directly. Since the analog fluxgate sensor has some drawbacks, e.g., it would be influenced by the noise of the analog circuit. Hence, in recent years, the analog circuit is gradually inclined to be realized by digital processing in which the software parameter adjustment is employed to replace the analog components, which can greatly improve the flexibility of the design. This paper proposes a digital single-axis fluxgate sensor according to the cobalt-based amorphous effect. To be specific, the analog signal output by the fluxgate is sampled directly by an analog-to-digital converter to obtain the signal waveform in digital form after amplification. The demodulation, filtering, and integration of the signal are all solved by mathematical algorithms. Based on the working principle of the fluxgate sensor, the selection of the magnetic core material and coil winding method of the fluxgate sensor probe is introduced in detail. The design and function of the excitation circuit and preamplifier circuit, as well as the specific realization of digital signal processing, are described. Finally, the performance test of the digital fluxgate sensor was performed under laboratory conditions, and the magnetic anomaly detection comparison experiment was performed outdoors with commercial fluxgate sensors. To sum up, the linearity of the digital single-axis fluxgate sensor is better than 1 × 10-5, and the root mean square noise value is below 0.1 nT. At the same time, it has good magnetic field tracking performance and is extremely sensitive to the magnetic field of the measurement area.


Complement regulation of T-cell alloimmunity.
The purpose of this review is to summarize recent findings implicating complement as an important regulator of T-cell immune responses. We then provide perspective for how these newly described mechanisms apply to allograft injury and how they could ultimately influence therapy. In addition to known effects of serum complement as an effector arm of antibody-initiated injury, T cells and antigen-presenting cells produce complement proteins and up-regulate complement receptors following cognate interactions. The locally released and activated, immune cell-derived complement signals predominantly through C3a and C5a binding to their receptors expressed on both partners to induce immune cell activation and differentiation. Complement deficiency or blockade limits T-cell-mediated autoimmunity and transplant rejection, whereas removal of the complement regulatory protein decay accelerating factor can enhance T-cell immunity and accelerate graft rejection. Emerging data indicate that immune cell-derived complement physiologically regulates immune cell survival and proliferation, modulating the strength and phenotype of adaptive T-cell immune responses involved in transplant rejection. The recognition of the diversity through which complement participates in allograft injury supports the need for continued design and testing of complement inhibitors in human transplant recipients.


Delayed erythropoietin therapy reduces post-MI cardiac remodeling only at a dose that mobilizes endothelial progenitor cells.
We examined the cardiac effects of chronic erythropoietin (EPO) therapy initiated 7 days after myocardial infarction (MI) in rats. A single high dose of EPO has been shown to reduce infarct size by preventing apoptosis when injected immediately after myocardial ischemia. The proangiogenic potential of EPO has also been reported, but the effects of chronic treatment with standard doses after MI are unknown. In this study, rats underwent coronary occlusion followed by reperfusion or a sham procedure. Infarcted rats were assigned to one of three treatment groups: 1) 0.75 microg/kg darbepoetin (MI+darb 0.75, n = 12); 2) 1.5 microg/kg darbepoetin (MI+darb 1.5, n = 12); 3) vehicle (MI+PBS, n = 16), once a week from day 7 postsurgery. Sham rats received the vehicle alone (n = 10). After 8 wk of treatment, the animals underwent echocardiography, left ventricular pressure-volume measurements, and peripheral blood endothelial progenitor cell (EPC) counting. MI size and capillary density in the border zone and the area at risk (AAR) were measured postmortem. The AAR was similar in the three MI groups. Compared with MI+PBS, the MI+darb 1.5 group showed a reduction in the MI-to-AAR ratio (20.8% vs. 38.7%; P < 0.05), as well as significantly reduced left ventricle dilatation and improved cardiac function. This reduction in post-MI remodeling was accompanied by increased capillary density (P < 0.05) and by a higher number of EPC (P < 0.05). Both darbepoetin doses increased the hematocrit, whereas MI+darb 0.75 did not increase EPC numbers or capillary density and had no functional effect. We found that chronic EPO treatment reduces MI size and improves cardiac function only at a dose that induces EPC mobilization in blood and that increases capillary density in the infarct border zone.


Efficacy of early neonatal supplementation with vitamin A to reduce mortality in infancy in Haryana, India (Neovita): a randomised, double-blind, placebo-controlled trial.
Vitamin A supplementation in children aged 6 months to 5 years has been shown to reduce mortality. The efficacy of neonatal supplementation with vitamin A to reduce mortality in the first 6 months of life is plausible but not established. We aimed to assess the efficacy of neonatal oral supplementation with vitamin A to reduce mortality between supplementation and 6 months of age. We undertook an individually randomised, double-blind, placebo-controlled trial in Haryana, India. We identified pregnant women through a surveillance programme undertaken every 3 months of all female residents in two districts of Haryana, India, aged 15-49 years, and screened every identified livebirth. Eligible participants were neonates whose parents consented to participate, were likely to stay in the study area until at least 6 months of age, and were able to feed orally at the time of enrolment. Participants were randomly assigned to receive oral capsules containing vitamin A (retinol palmitate 50,000 IU plus vitamin E 9·5-12·6 IU) or placebo (vitamin E 9·5-12·6 IU) within 72 h of birth. Randomisation was in blocks of 20 according to a randomisation list prepared by a statistician not otherwise involved with the trial. Investigators, participants' families, and the data analysis team were masked to treatment allocation. The primary outcome was mortality between supplementation and 6 months of age. Analysis included all participants assigned to study groups. This trial is registered with ClinicalTrials.gov, number NCT01138449, and the Indian Council of Medical Research Clinical Trial Registry, number CTRI/2010/091/000220. Between June 24, 2010, and July 1, 2012 we screened 47,777 neonates and randomly assigned 44,984 to receive vitamin A (22,493) or placebo (22,491). Between supplementation and 6 months of age, 656 infants died in the vitamin A group compared with 726 in the placebo group (29·2 per 1000 vs 32·3 per 1000; difference -3·1 per 1000, 95% CI -6·3 to 0·1; risk ratio 0·90, 95% CI 0·81 to 1·00). We noted no significant interactions between the intervention effect and sex on mortality at 6 months (p=0·409). Supplementation with 50,000 IU vitamin A within the first 72 h of life was generally safe and well tolerated, with the exception of a small excess risk of transient bulging fontanelle (205 cases in the vitamin A group confirmed by physician vs 80 cases in the placebo group, risk ratio 2·56 [95% CI 1·98-3·32]). The findings of this study, done in a population in which vitamin A deficiency is a moderate public health problem, are consistent with a modest reduction in mortality between supplementation and 6 months of age. These findings must be viewed together with similar trials in other populations to enable determination of appropriate public health policy. Bill & Melinda Gates Foundation to WHO.


[Type 4a myocardial infarction].
An increase in the level of cardiac troponins and creatine kinase MB is sometimes observed even after angiographically and clinically uncomplicated percutaneous coronary interventions. This review article deals with the clinical and prognostic implications of type 4a myocardial infarction.


Paediatric gastroesophageal reflux disease and parental mental health: Prevalence and predictors.
The current study aimed to estimate the prevalence of common mental health difficulties in parents who have an infant with Gastroesophageal Reflux Disease (GORD), and to identify psychological predictors of parental anxiety, depression, and well-being, as a platform for subsequent intervention development. Parents of infants with GORD (N = 309) completed online psychometric measures of potential predictors (self-compassion, illness appraisals, and illness uncertainty), potential confounders (sleep quality, relationship satisfaction, social support, and infant feeding satisfaction), and mental health outcomes (anxiety, depression, and wellbeing). The outcome measures were repeated eight-weeks later (N = 103). At the first time-point, 66% of participants exceed the clinical cut off for generalised anxiety disorder and 63% exceeded that for a depressive disorder. Both had significantly reduced eights-weeks later. Greater self-compassion predicted lower anxiety and depression, and better well-being, in both cross-sectional and longitudinal data, including when all confounders were controlled for. Illness uncertainty and illness appraisals were less consistent predictors. No robust differences were found between parents of infants with silent GORD and those with GORD with visible regurgitation. Parents of infants with GORD showed high rates of anxiety and depression, which were elevated compared to those that have been found in perinatal and general population samples. Self-compassion was a consistent predictor of better mental health and has promise as a proximal intervention target. Future research could benefit from examining the efficacy of a compassion-focussed intervention in this population.


Superposition of masking releases.
We are constantly exposed to a mixture of sounds of which only few are important to consider. In order to improve detectability and to segregate important sounds from less important sounds, the auditory system uses different aspects of natural sound sources. Among these are (a) its specific location and (b) synchronous envelope fluctuations in different frequency regions. Such a comodulation of different frequency bands facilitates the detection of tones in noise, a phenomenon known as comodulation masking release (CMR). Physiological as well as psychoacoustical studies usually investigate only one of these strategies to segregate sounds. Here we present psychoacoustical data on CMR for various virtual locations of the signal by varying its interaural phase difference (IPD). The results indicate that the masking release in conditions with binaural (interaural phase differences) and across-frequency (synchronous envelope fluctuations, i.e. comodulation) cues present is equal to the sum of the masking releases for each of the cues separately. Data and model predictions with a simplified model of the auditory system indicate an independent and serial processing of binaural cues and monaural across-frequency cues, maximizing the benefits from the envelope comparison across frequency and the comparison of fine structure across ears.


Mutual Interplay between the Human Cytomegalovirus Terminase Subunits pUL51, pUL56, and pUL89 Promotes Terminase Complex Formation.
Human cytomegalovirus (HCMV) genome encapsidation requires several essential viral proteins, among them pUL56, pUL89, and the recently described pUL51, which constitute the viral terminase. To gain insight into terminase complex assembly, we investigated interactions between the individual subunits. For analysis in the viral context, HCMV bacterial artificial chromosomes carrying deletions in the open reading frames encoding the terminase proteins were used. These experiments were complemented by transient-transfection assays with plasmids expressing the terminase components. We found that if one terminase protein was missing, the levels of the other terminase proteins were markedly diminished, which could be overcome by proteasome inhibition or providing the missing subunit in trans These data imply that sequestration of the individual subunits within the terminase complex protects them from proteasomal turnover. The finding that efficient interactions among the terminase proteins occurred only when all three were present together is reminiscent of a folding-upon-binding principle leading to cooperative stability. Furthermore, whereas pUL56 was translocated into the nucleus on its own, correct nuclear localization of pUL51 and pUL89 again required all three terminase constituents. Altogether, these features point to a model of the HCMV terminase as a multiprotein complex in which the three players regulate each other concerning stability, subcellular localization, and assembly into the functional tripartite holoenzyme.IMPORTANCE HCMV is a major risk factor in immunocompromised individuals, and congenital CMV infection is the leading viral cause for long-term sequelae, including deafness and mental retardation. The current treatment of CMV disease is based on drugs sharing the same mechanism, namely, inhibiting viral DNA replication, and often results in adverse side effects and the appearance of resistant virus strains. Recently, the HCMV terminase has emerged as an auspicious target for novel antiviral drugs. A new drug candidate inhibiting the HCMV terminase, Letermovir, displayed excellent potency in clinical trials; however, its precise mode of action is not understood yet. Here, we describe the mutual dependence of the HCMV terminase constituents for their assembly into a functional terminase complex. Besides providing new basic insights into terminase formation, these results will be valuable when studying the mechanism of action for drugs targeting the HCMV terminase and developing additional substances interfering with viral genome encapsidation.


Prodromal symptoms of recurrent major depressive episodes: a qualitative analysis.
In four focus groups, 16 people with major depressive or bipolar disorder were asked to describe the onset of an acute depressive episode. Findings indicate that those entering a major depressive episode often have difficulty identifying prodromal symptoms, although they experience early warning phases. These phases and described, and implications for clinical intervention are outlined.


Sialoblastoma of the cheek: A case report and review of the literature.
Sialoblastoma is a rare salivary gland tumor that recapitulates the primitive salivary gland anlage. The authors herein report a case of sialoblastoma of a minor salivary gland, clinically presenting with progressive enlargement of a mass in the cheek of a 1-year-old female infant. Histopathologically, the mass consisted of tight clusters of basaloid cells and partially formed ductal and pseudo-ductal spaces separated by thin fibrous bands. Immunohistchemical studies demonstrated the presence of cytokeratin AE1/AE3, p63, CD99, α-fetoprotein (AFP) and Hep Par-1 expression in a considerable number of tumor cells. The clinical and pathological characteristics are presented and relevant literature is reviewed. Early complete surgical excision is recommended for the treatment of sialoblastoma. Radiation may be considered in cases with incomplete resection of the tumor. Chemotherapy may play a vital role in extensive, metastatic, or relapsed cases, or in cases with inadequate excision. The follow-up treatment should be frequent and prolonged. To the best of our knowledge, this is the first reported case of sialoblastoma of the cheek with immunoreactivity for AFP and Hep Par-1, which may be associated with the embryonic origin of the tumor. AFP may be a useful marker of tumor response in patient with sialoblastoma.


[Difficulties in the electrocardiographic diagnosis of a previous posterior myocardial infarct].
A retrospective study was carried out of 39 cases of posterior m.i. from 8 months to 6 years after acute episode. In each case the diagnostic reliability of the standard derivations of a series of parameters was evaluated (duration of Q D3 and Q aVF, Q.100/R ratio in aVF, R/S ratio in V1 and R V1/R V6) and of the following accessory derivations: De Maria, III P of Pescador (classical and in two personal modifications), dorsal and sternal derivations. It is concluded that in many cases, standard derivations do not enable previous posterior m.i. to be diagnosed. The De Maria and III P of Pescador derivations (with the proposed personal modifications) are advisable. In isolated cases, the sternal derivation may also be very useful.


Physical conditions on the early Earth.
The formation of the Earth as a planet was a large stochastic process in which the rapid assembly of asteroidal-to-Mars-sized bodies was followed by a more extended period of growth through collisions of these objects, facilitated by the gravitational perturbations associated with Jupiter. The Earth's inventory of water and organic molecules may have come from diverse sources, not more than 10% roughly from comets, the rest from asteroidal precursors to chondritic bodies and possibly objects near Earth's orbit for which no representative class of meteorites exists today in laboratory collections. The final assembly of the Earth included a catastrophic impact with a Mars-sized body, ejecting mantle and crustal material to form the Moon, and also devolatilizing part of the Earth. A magma ocean and steam atmosphere (possibly with silica vapour) existed briefly in this period, but terrestrial surface waters were below the critical point within 100 million years after Earth's formation, and liquid water existed continuously on the surface within a few hundred million years. Organic material delivered by comets and asteroids would have survived, in part, this violent early period, but frequent impacts of remaining debris probably prevented the continuous habitability of the Earth for one to several hundred million years. Planetary analogues to or records of this early time when life began include Io (heat flow), Titan (organic chemistry) and Venus (remnant early granites).


Caregiver drug use and arrest as correlates of child trauma exposure.
This study proposed to determine the prevalence of substance use and drug-related arrests among caregivers of children referred to Child Protective Services (CPS), examine the relationship between substance use and arrests among caregivers, and examine the main effects and interaction of substance use and arrests in predicting child trauma exposure. Secondary data was collected from CPS files for a randomly selected group of 1127 children. Findings indicated that rates of caregiver substance misuse and arrests were higher than the general population, which was expected. When controlling for demographic and other variables, there was a main effect of substance use and arrests on child trauma exposure, but no significant interaction. Implications for caregivers engaged in substance use and/or involvement with the criminal justice system are discussed, as well as clinical and research implications for children exposed to trauma related to caregiver behaviors.


Kinking nonlinear elastic solids, nanoindentations, and geology.
The physical mechanism responsible for nonlinear elastic, hysteretic, and discrete memory response of nonlinear mesoscopic elastic solids has to date not been identified. We show, by nanoindenting mica single crystals, that this response is most likely due to the formation of dissipative and fully reversible, dislocation-based kink bands. We further claim that solids with high c/a ratios, which per force are plastically anisotropic, should deform by kinking, provided they do not twin. These kinking nonlinear elastic solids include layered ternary carbides, nitrides, oxides, and semiconductors, graphite, and the layered phases, such as mica, present in nonlinear mesoscopic elastic solids.


[Vascularization of the sub-mucosal and mucosal layers of the colon in man].
The vascularization of the submucosal and mucosal layers of the human colon has been studied in 25 cases whose vascular system was injected with gelatinous indian ink. The submucosal layer presents a true vascular crossroads for the arterial and venous anastomotic networks, which are tributaries of the straight vessels. The morphology of these vascular networks is exactly similar. The straight arteries and veins form vascular rings all along the colon, and they anastomose by means of longitudinal and transverse vessels. Many vessels of the muscular and all those of the mucosal layer are tributaries of these vascular networks. The vessels of the mucosal layer include the precapillary arteries, capillary network of the intestinal glands and postcapillary veins. The latter joint and form the mucosal venous trunks, which, in turn, form the mucosal veins, which flow into the submucosal venous network.


Is nicotine replacement therapy overvalued in smoking cessation? Analysis of smokers' and quitters' communication in social media.
Internet discussion forums provide new, albeit less used data sources for exploring personal experiences of illness and treatment strategies. To gain an understanding of how discussion forum participants value nicotine replacement therapy (NRT) in smoking cessation (SC). Finnish national Internet-based discussion forum, STUMPPI, supporting SC and consisting of ten free discussion areas, each with a different focus. The analysis was based on STUMPPI forum participants' postings (n = 24 481) in five discussion areas during January 2007-January 2012. Inductive content analysis of the postings concerning NRT use or comparing NRT to other SC methods. Three major themes related to NRT in SC emerged from the discussions. These were as follows: (I) distrust and negative attitude towards NRT; (II) neutral acceptance of NRT as a useful SC method; and (III) trust on the crucial role of NRT and other SC medicines. The negative attitude was related to following perceptions: NRT use maintains tobacco dependence, fear of NRT dependence or experience of not gaining help from NRT use. NRT was perceived to be useful particularly in the initiation of SC attempts and in dealing with physiological dependence. The most highlighted factors of successful quitting were quitters' own psychological empowerment and peer support from the discussion community. The majority of STUMPPI forum participants had low or balanced expectations towards the role of NRT in SC. More research from the smokers' and quitters' perspective is needed to assess the real value of NRT compared to other methods in SC.


p27Kip1 and human cancers: A reappraisal of a still enigmatic protein.
p27Kip1 is a cell cycle regulator firstly identified as a cyclin-dependent kinase inhibitor. For a long time, its function has been associated to cell cycle progression inhibition at G1/S boundary in response to antiproliferative stimuli. The picture resulted complicated by the discovery that p27Kip1 is an intrinsically unstructured protein, with numerous CDK-dependent and -independent functions and involvement in many cellular processes, such as cytoskeleton dynamics and cell motility control, apoptosis and autophagy activation. Depending on the cell context, these activities might turn to be oncogenic and stimulate cancer progression and metastatization. Nevertheless, p27Kip1 role in cancer biology suppression was underscored by myriad data reporting its down-regulation and/or cytoplasmic relocalization in different tumors, while usually no genetic alterations were found in human cancers, making the protein a non-canonical oncosuppressor. Recently, mostly due to advances in genomic analyses, CDKN1B, p27Kip1 encoding gene, has been found mutated in several cancers, thus leading to a profound reappraisal of CDKN1B role in tumorigenesis. This review summarizes the main p27Kip1 features, with major emphasis to its role in cancer biology and to the importance of CDKN1B mutations in tumor development.


Shrimp oil extracted from the shrimp processing waste reduces the development of insulin resistance and metabolic phenotypes in diet-induced obese rats.
Diet-induced obesity, insulin resistance, impaired glucose tolerance, chronic inflammation, and oxidative stress represent the main features of type 2 diabetes mellitus. The present study was conducted to examine the efficacy and mechanisms of shrimp oil on glucose homeostasis in obese rats. Male CD rats fed a high-fat diet (52 kcal% fat) and 20% fructose drinking water were divided into 4 groups and treated with the dietary replacement of 0%, 10%, 15%, or 20% of lard with shrimp oil for 10 weeks. Age-matched rats fed a low-fat diet (10 kcal% fat) were used as the normal control. Rats on the high-fat diet showed impaired (p < 0.05) glucose tolerance and insulin resistance compared with rats fed the low-fat diet. Shrimp oil improved (p < 0.05) oral glucose tolerance, insulin response, and homeostatic model assessment-estimated insulin resistance index; decreased serum insulin, leptin, hemoglobin A1c, and free fatty acids; and increased adiponectin. Shrimp oil also increased (p < 0.05) antioxidant capacity and reduced oxidative stress and chronic inflammation. The results demonstrated that shrimp oil dose-dependently improved glycemic control in obese rats through multiple mechanisms.


Head-to-tail macrocyclization of albumin-binding domain fused interferon alpha improves the stability, activity, tumor penetration, and pharmacology.
Genetic fusion of a therapeutic protein to albumin can improve its stability and pharmacokinetics, but it usually leads to considerably reduced bioactivity and poor tumor penetration due to increased steric hindrance, resulting in limited antitumor efficacy. Herein we report head-to-tail macrocyclization of albumin-binding domain fused interferon alpha (IFN-ABD) to form a cyclic fusion protein (c-IFN-ABD) with well-retained albumin-binding affinity. Notably, c-IFN-ABD showed not only greater thermal and enzymatic stability and thus antiproliferative activity than IFN-ABD and IFN due to the macrocyclization, but also exhibited considerably better pharmacokinetics than IFN and cyclic IFN owing to the albumin-binding affinity. More importantly, c-IFN-ABD showed deeper tumor penetration, greater tumor retention, and thus higher antitumor efficiency than all the controls without significant systemic side effects in mice bearing melanoma. These results implicate that head-to-tail macrocyclization of ABD fused therapeutic proteins is an enabling strategy for the design of highly potent protein therapeutics for tumor therapy.


Yellow fever virus 17D envelope and NS3 proteins are major targets of the antiviral T cell response in mice.
The yellow fever virus 17D vaccine strain is one of the most effective and safe vaccines available. The immune response after immunization is characterized by long-lasting high titers of neutralizing antibodies. Here, we have initiated a characterization of YFV-17D-specific cellular immune responses. This study makes three points. First, we have identified two CD8 T cell epitopes and one CD4 T cell epitope. An H-2Kb-restricted dominant epitope was mapped in the NS3 protein, whereas the viral envelope protein harbored an H-2Db-restricted subdominant epitope and the I-Ab-restricted CD4 T cell epitope. Second, illustrating the concept of immunodomination, we found that after abrogation of the dominant response in H-2Kb knockout mice, the frequencies of T cells recognizing the subdominant Db-restricted epitope increased dramatically. Finally, the H-2Db-restricted epitope lacks the canonical Asn anchor residue at position 5, indicating that epitopes may be missed by strict application of the H-2Db-binding motif. Identification of these T cell epitopes will facilitate studies on the cellular immunity against YFV-based expression or immunization vectors.


Long dsRNA and silent genes strike back:RNAi in mouse oocytes and early embryos.
RNA interference (RNAi) refers to the selective degradation of mRNA induced by double-stranded RNA (dsRNA), first discovered in Caenorhabditis elegans. Homology-dependent silencing phenomena related to RNAi have been observed in many species from all eukaryotic kingdoms. RNAi and related mechanisms share several conserved components. The hallmark of these phenomena is the presence of short dsRNA molecules (21-25 bp long), termed short interfering RNA (siRNA), which are generated from dsRNA by the activity of Dicer, a specific type III RNAse. These molecules serve as a template for the recognition and cleavage of the cognate mRNA. As it is beyond the scope of a single review to cover all aspects of RNAi, this review will focus on certain steps of the pathway relevant to mammals and on the use of long dsRNA to specifically silence genes in mammalian cells permissive to this technique, such as oocytes and early embryos.


Decoration of carbon nanotubes with metal nanoparticles by wet chemical method: a small-angle neutron scattering study.
Multi-wall carbon nanotubes have been synthesized by catalytic chemical vapour deposition method. Attempts have been made to decorate the walls of these nanotubes with various metal nanoparticles (Ni, Cu and Fe) after functionalizing the nanotubes walls by wet chemical method. Small-Angle Neutron Scattering data reveals chain cluster type morphology of the carbon nanotubes. Transmission electron microscopy, Energy dispersive analysis of X-rays and Small-Angle Neutron Scattering measurements show that decoration of nanotube walls by metallic nano-particles could be realized for Ni and Cu nano-particles. Further, wall decoration by nano-particles of Fe could not be achieved by wet chemical method due to strong agglomeration behavior of Fe nano-particles.


Comparative Evaluation of Fluoride Release from Four Commercially Available Pediatric Dental Restorative Materials.
The aim of this study was to evaluate the fluoride-releasing abilities of commercially available restorative materials such as-Activa™ BioActive-restorative™ material, Zirconomer (Shofu Inc), Beautifil® II (Shofu Inc), GC Gold Label 9 high strength posterior restorative glass ionomer cement (GIC Corp). A total of 40 disk specimens (10 of each material) were placed into distilled/deionized (DI) water and the fluoride release was measured for 30 days. Fluoride ion measurement was performed at the end of the 1st, 3rd, 7th, 15th, and 30th day under normal atmospheric conditions by fluoride ion selective electrode (F-ISE) (Orion 9609 BNWP, Ionplus SureFlow fluoride electrode, Thermo Scientific, United States of America) coupled to a benchtop analyzer (Hachsen Ion+). All the materials included in the study exhibited fluoride release. Although there were differences in the amounts of fluoride released between Activa™, Zirconomer, and GC Gold Label 9 the mean difference between these three groups was not found to be statistically significant. Beautifil® II showed low amounts of fluoride released at all time intervals. Among the above-compared materials Activa™ and Zirconomer exhibit both improved mechanical properties as well as they have fluoride-releasing ability so can be preferred over conventional glass ionomer restorations. Dhumal RS, Chauhan RS, Patil V, et al. Comparative Evaluation of Fluoride Release from Four Commercially Available Pediatric Dental Restorative Materials. Int J Clin Pediatr Dent 2023;16(S-1):S6-S12.


Annual variation in polychlorinated biphenyl (PCB) exposure in tree swallow (Tachycineta bicolor) eggs and nestlings at Great Lakes Restoration Initiative (GLRI) study sites.
Tree swallow (Tachycineta bicolor) eggs and nestlings were collected from 16 sites across the Great Lakes to quantify normal annual variation in total polychlorinated biphenyl (PCB) exposure and to validate the sample size choice in earlier work. A sample size of five eggs or five nestlings per site was adequate to quantify exposure to PCBs in tree swallows given the current exposure levels and variation. There was no difference in PCB exposure in two randomly selected sets of five eggs collected in the same year, but analyzed in different years. Additionally, there was only modest annual variation in exposure, with between 69% (nestlings) and 73% (eggs) of sites having no differences between years. There was a tendency, both statistically and qualitatively, for there to be less exposure in the second year compared to the first year.


The protective role of a natural inhibitor in the fluorescent location of cells possessing a latent form of cell surface protease.
Leukaemia cells possess a latent form of a cell surface protease referred to as guanidinobenzoatase. Latency is due to complex formation between an inhibitor protein and the cell surface enzyme which is stable under acid conditions but is dissociated with formaldehyde treatment. The latent form of the cell surface protease has been used as a protecting mechanism during a preliminary step to stain all the nuclei of cells with haematoxylin. The enzyme-inhibitor complex was then dissociated and a combination of 9-amino acridine and propidium iodide employed to enable the fluorescent location of cells possessing active guanidinobenzoatase. We were thus able to visualise the nuclei by conventional light microscopy and simultaneously visualise the cell surface of leukaemia cells by fluorescent microscopy. This simple model system has provided technology applicable to the more complex analysis of neoplastic cells in cervical smears.


Food waste volume and origin: Case studies in the Finnish food service sector.
We carried out a project to map the volume and composition of food waste in the Finnish food service sector. The amount, type and origin of avoidable food waste were investigated in 51 food service outlets, including schools, day-care centres, workplace canteens, petrol stations, restaurants and diners. Food service outlet personnel kept diaries and weighed the food produced and wasted during a one-week or one-day period. For weighing and sorting, the food waste was divided into two categories: originally edible (OE) food waste was separated from originally inedible (OIE) waste, such as vegetable peelings, bones and coffee grounds. In addition, food waste (OE) was divided into three categories in accordance with its origins: kitchen waste, service waste and customer leftovers. According to the results, about 20% of all food handled and prepared in the sector was wasted. The findings also suggest that the main drivers of wasted food are buffet services and overproduction.


Exogenous Melatonin Treatment Increases Chilling Tolerance and Induces Defense Response in Harvested Peach Fruit during Cold Storage.
The effect of exogenous melatonin on chilling injury in peach fruit after harvest was investigated. To explore the optimum concentration of melatonin for chilling tolerance induction, peach fruit were treated with 50, 100, or 200 μM melatonin for 120 min and then stored for 28 days at 4 °C. The results showed that application of melatonin at 100 μM was most effective in reducing chilling injury of peach fruit after harvest. Peaches treated with melatonin at this concentration displayed higher levels of extractable juice rate and total soluble solids than the non-treated peaches. In addition, melatonin treatment enhanced expression of PpADC, PpODC, and PpGAD and consequently increased polyamines and γ-aminobutyric acid (GABA) contents. Meanwhile, the upregulated transcripts of PpADC and PpODC and inhibited PpPDH expression resulted in the higher proline content in melatonin-treated fruit compared to the control fruit. Our results revealed that melatonin treatment may be a useful technique to alleviate chilling injury in cold-stored peach fruit. The chilling tolerance of harvested peaches induced by melatonin treatment is associated with higher levels of polyamine, GABA, and proline. These data provided here are the first protective evidence of exogenous melatonin in harvested horticultural products in response to direct chilling stress.


Clinical perspective on desmoplastic small round-cell tumor.
Rare diseases are often associated with uninformed medical decisions and poorly executed treatments because of inexperience of the physicians. Desmoplastic small round-cell tumor is a rare disease that is a form of peritoneal surface malignancy usually affecting young males, with a mean survival of 29 months. In order to begin to build a more knowledgeable clinical pathway all 7 patients treated at the Washington Hospital Center were studied and compared to patients described in the medical literature. Clinical and pathological data, tumor distribution, cytoreductive surgery, completeness of cytoreduction and survival were recorded and analyzed. The first most common symptoms were pain, increased abdominal girth and palpable abdominal mass in our patients and in the literature review. The overall survival did not improve with cytoreductive surgery plus intraperitoneal chemotherapy (mean survival 32 months); however, 2 long-term survivors who responded to systemic chemotherapy of 55 and 101 months were recorded. The latter may be the longest survivor reported in the literature. No consistent response to chemotherapy was observed in our patients or in any literature review. Complete surgical removal of this malignancy did not correlate with survival in our patients. The absence of improved survival of our aggressively treated patients as compared to the literature was thought to be a consequence of an advanced stage of the disease. A new comprehensive approach that uses complete clearing of cancer by surgery and perioperative systemic and perioperative intraperitoneal chemotherapy as early as is possible in the natural history of the disease emerged as goals for future management.


Non-union of the clavicle and delayed union of the proximal fifth metatarsal treated with low-intensity pulsed ultrasound in two soccer players.
Operative treatment has become the treatment of choice in athletes and active patients in non-union of the clavicle and delayed union of the proximal fifth metatarsal. The purpose of this study was to review the short- and long-term clinical results of low-intensity pulsed ultrasound treatment in a non-union of the clavicle and in a delayed union of the proximal fifth metatarsal in 2 elite soccer players. In both patients, the treatment sessions were performed with an ultrasound signal that was composed of a burst width of 200+/-10% mus containing 1.5+/-5% MHz sine waves, with a repeating rate of 1+/-10% kHz and a spatial average temporal intensity of 30+/-30% mW/cm2. The application of the ultrasound was performed by the patients at home for 20 min/day for 3 months. The healing of the non-union of the clavicle was followed by MR imaging and of the delayed union of the proximal fifth metatarsal by radiographs. In both of the cases the end-results were excellent and the players could continue playing at the highest level. The ultrasound method was successful and afforded players a quick return to sport activity.


Mechanism of intraparticle synthesis of the rotavirus double-stranded RNA genome.
Rotaviruses perform the remarkable tasks of transcribing and replicating 11 distinct double-stranded RNA genome segments within the confines of a subviral particle. Multiple viral polymerases are tethered to the interior of a particle, each dedicated to a solitary genome segment but acting in synchrony to synthesize RNA. Although the rotavirus polymerase specifically recognizes RNA templates in the absence of other proteins, its enzymatic activity is contingent upon interaction with the viral capsid. This intraparticle strategy of RNA synthesis helps orchestrate the concerted packaging and replication of the viral genome. Here, we review our current understanding of rotavirus RNA synthetic mechanisms.


Eosinophilic cellulitis (Wells' syndrome) successfully treated with low-dose cyclosporine.
Eosinophilic cellulitis (Wells'syndrome) is an uncommon skin disorder. We report two adult male patients who had recurrent erythematous plaques and a nodular lesion on the abdomen. The histopathologic feature of their skin biopsies similarly indicated a marked infiltrate of eosinophils in the dermis with the fashion of "flame figures". One of the patients demonstrated blood eosinophilia. Given the clinicohistological findings, the patients fulfilled the criteria for the diagnosis of eosinophilic cellulitis. The skin lesions remained refractory to medications such as corticosteroids, sulfones, antihistamines, and minocycline. Considering the beneficial effect of cyclosporine in the treatment of eosinophilia-associated dermatoses, we speculated that eosinophilic cellulitis might respond to cyclosporine therapy. Thus, each of the two patients was given cyclosporine (microemulsion formulation) at a daily dose of 1.25 or 2.5 mg/kg, i.e., 100 or 200 mg, respectively. Complete remission of the skin eruptions was obtained in both patients during a 3- or 4-week period of treatment. No side effects were observed. Neither of the patients experienced relapse of the disease at least over 10 months after the discontinuation of the cyclosporine therapy. We suggest that administration of low-dose cyclosporine be a safe and useful therapeutic option in patients with eosinophilic cellulitis.


Core and region-enriched networks of behaviorally regulated genes and the singing genome.
Songbirds represent an important model organism for elucidating molecular mechanisms that link genes with complex behaviors, in part because they have discrete vocal learning circuits that have parallels with those that mediate human speech. We found that ~10% of the genes in the avian genome were regulated by singing, and we found a striking regional diversity of both basal and singing-induced programs in the four key song nuclei of the zebra finch, a vocal learning songbird. The region-enriched patterns were a result of distinct combinations of region-enriched transcription factors (TFs), their binding motifs, and presinging acetylation of histone 3 at lysine 27 (H3K27ac) enhancer activity in the regulatory regions of the associated genes. RNA interference manipulations validated the role of the calcium-response transcription factor (CaRF) in regulating genes preferentially expressed in specific song nuclei in response to singing. Thus, differential combinatorial binding of a small group of activity-regulated TFs and predefined epigenetic enhancer activity influences the anatomical diversity of behaviorally regulated gene networks.


Detection of histoplasma antigen by a quantitative enzyme immunoassay.
The second-generation Histoplasma antigen immunoassay is semiquantitative, expressing results as a comparison to a negative control, which requires repeat testing of the prior specimen with the current specimen to accurately determine a change in antigen. Reporting results in this manner often is confusing to the ordering physician and laboratory. Development of a quantitative assay could improve accuracy, reduce interassay variability, and eliminate the need to test the prior sample with the current sample in the same assay. Calibrators with known concentrations of Histoplasma antigen were used to quantitate antigen in specimens from patients with histoplasmosis and from controls. Samples from cases of disseminated histoplasmosis or other mycoses and controls were tested to evaluate the performance characteristics of the quantitative assay. Paired specimens were evaluated to determine if quantitation eliminated the need to test the current and prior specimens in the same assay to assess a change in antigen. The sensitivity in samples from patients with AIDS and disseminated histoplasmosis was 100% in urine and 92.3% in serum. Cross-reactions occurred in 70% of other endemic mycoses, but not in aspergillosis. Specificity was 99% in controls with community-acquired pneumonia, medical conditions in which histoplasmosis was excluded, or healthy subjects. A change in antigen level categorized as an increase, no change, or decrease based on antigen units determined in the same assay agreed closely with the category of change in nanograms/milliliter determined from testing current and prior specimens in different assays. Sensitivity, specificity, and interassay precision are excellent in the new third-generation quantitative Histoplasma antigen immunoassay.


Systemic biodistribution of radioiodinated interleukin-2 in the rat.
Interleukin-2 (IL-2) is a lymphokine capable of modulating a variety of immune functions. In vitro and in vivo studies have shown promising cytotoxic potential. Despite numerous ongoing clinical trials, however, little is known about the biodistribution of this lymphokine after in vivo administration. In this study using a rat model, the fate of radioiodinated human recombinant IL-2 (RIL-2) was analyzed by camera imaging, autoradiography, and well counting experiments. Camera imaging demonstrated the liver and kidney to be the organs of greatest radioactivity accumulation with peak liver uptake noted at approximately 10 min from onset of infusion, and peak kidney uptake at approximately 20 min. Autoradiographic assessment of selected organs (kidney, adrenal, liver, lung, and brain) revealed marked heterogeneity of uptake in the kidney and adrenal gland with preponderance of RIL-2 in the cortex of these organs. A more homogeneous distribution of RIL-2 uptake was noted in liver, lung, and brain parenchyma. Well counting confirmed the liver and kidney as the organs of greatest RIL-2 accumulation. Knowledge of the biodistribution of IL-2 may be of benefit both in studying mechanisms of toxicity and in designing novel therapeutic approaches.


Opponent and nonopponent contributions to the zebrafish electroretinogram using heterochromatic flicker photometry.
While some lower vertebrates, such as zebrafish, do not appear to possess anatomically separate pathways of processing visual information (such as M-pathways and P-pathways), it is believed that separate processing of the visual stimulus (such as luminance and chromatic processing) is a basic requirement of vertebrate vision. In this study, spectral sensitivity functions were obtained from electroretinogram responses to heterochromatic flicker photometry stimuli at several flicker rates, including a low flicker rate (2 Hz), in an attempt to predominantly stimulate chromatic processes and a high flicker rate (16 Hz), in an attempt to predominantly stimulate luminance processes. In addition, chromatic adaptation was used to isolate and examine the temporal properties of the different cone-type contributions to the electroretinogram response. Spectral sensitivity functions based on responses to heterochromatic stimuli of a low flicker rate appeared to receive both opponent and nonopponent contributions; however, when the stimulus flicker rate was high, spectral sensitivity appeared to be a function of only nonopponent mechanisms. Also, the differences in cone contributions to the spectral sensitivity functions across the different flicker rates appear to be related to the temporal properties of the cone contributions to the electroretinogram response.


Half-time evaluation of a new 4-year Ph.D. program in nursing and midwifery at the University of Gondar, Ethiopia.
A new four-year Ph.D. programme in nursing and midwifery, the first of its kind in Ethiopia, was started in 2018/2019 at the University of Gondar when eight doctoral students in nursing and midwifery entered the program. We who have been involved see this as an appropriate time to evaluate what has been accomplished to date and to look toward future possibilities. Our aim in carrying out such an evaluation and presenting our findings is in part to determine if similar programs might be developed in other similar settings and in part to learn what modifications to the present program might be considered. The key elements of a questionnaire survey with closed and open response alternatives were based on the content, structure and learning outcomes of the home university Ph.D. programme as described in the curriculum. The questionnaire responses captured changes that would be needed to maintain a fully satisfactory programme that blends onsite instruction and online access to faculty resulting in a twenty-first century blended Ph.D. programme. Improved dialogue between the home university faculty and the external supervisors is needed. The programme can provide a career pathway that midwifery and nursing educators can follow in their own country rather than having to leave to study in another country. The findings provide insight into the feasibility of extending similar Ph.D. programmes to other parts of East Africa and with the SDG 5 in mind with an increased focus on women leadership. The justification for this initiative is to meet the need for more nursing and midwifery faculty who can provide quality midwifery and nursing education in East African countries. Retention of these professionals will help to deal with the shortage of healthcare personnel and will provide better care for the general population.


Bodies in motion: spaces, emotions and representations that (de)construct realities.
OBJECTIVE To analyze the social representations of the body among Brazilian and Costa Rican transsexual people through their life stories. METHOD Qualitative and descriptive multicenter research. The study population consisted of 70 participants. Two organizations cooperated to collect the information, one in Florianópolis, SC-Brazil and one in San José, the capital of Costa Rica. Content Analysis was used to analyze the data. RESULTS Based on the results, a single social representation of corporeality was unveiled: "Modeled bodies: about the elasticity of corporeality". This representation described two clear elementary context units (discourse matrices). The first associates the body with an inconclusive, transitory, volatile, pliable, moldable and fluid object, while the second relates the body with a separate institution, but regulated and controlled by others. CONCLUSION In conclusion, the transsexual body is a volatile, transient, transformable institution, crossed by the marks of a historicizing and historicizable time, which comes within the scope not only of what can be named by means of linguistic signs, but also of what belongs to the unnamable in terms of sociocultural perceptions and feelings.


Different routes of Ca2+ influx in NMDA-mediated generation of nitric oxide and arachidonic acid.
Nitric oxide and arachidonic acid act as inter- and intracellular messengers in the central nervous system. It is well known that the NMDA-mediated generation of nitric oxide and arachidonic acid is dependent on extracellular Ca2+. However, the role of voltage-dependent calcium channels (VDCCs) in this regard is poorly understood. We report here that NMDA-mediated nitric oxide production in striatal neuron cultures is blocked (80%) by the L-type VDCC antagonist nifedipine, but not by omega-conotoxin or omega-agatoxin IVA, antagonists of the N- and P-type VDCCs respectively. By contrast, none of the VDCC antagonists inhibited the NMDA-mediated release of arachidonic acid. These data indicate that permeation through different Ca2+ channels is responsible for the production of arachidonic acid and nitric oxide in striatal neurons.


Cancer-Cell-Specific Nuclear-Targeted Drug Delivery by Dual-Ligand-Modified Mesoporous Silica Nanoparticles.
Mesoporous silica nanoparticles are modified with dual targeting ligands, i.e., folic acid and dexamethasone, to construct a cancer-cell-specific nuclear-targeted delivery system. The resulting nanocarriers can not only enhance the inhibition efficacy of doxorubicin on Hela cells through active nucleus accumulation but also reduce toxic side effects on noncancer cells though receptor-mediated selective cellular uptake.


Partially Reversible Thermal-Induced Oxidation During a Dehydration Process in an H-bonded Supramolecular System.
The thermal behaviour of an H-bonded molecular network A based on [FeII (CN)6 ]4- anions and organic bisamidium cations 12+ was investigated. Heating was found to induce the partial oxidation of [FeII (CN)6 ]4- into [FeIII (CN)6 ]3- , together with a thermochromic effect and also a loss of crystallinity was evidenced from mid and far FT-IR spectroscopic data, XRPD and DSC/TGA analysis. Rehydration also partially reversed the redox reaction and its colour, and after that, a mixture of A with an amorphous phases was observed. FT-IR spectroscopy revealed that the oxidation of Fe(II) was accompanied by a deprotonation of the cation.


Association between Serum Cortisol and DHEA-S Levels and Response to Antipsychotic Treatment in Schizophrenia.
Previous studies suggested that alterations in serum cortisol and DHEA-S levels may play a role in the pathophysiology of schizophrenia. To compare serum cortisol and DHEA-S levels between patients with schizophrenia and healthy controls and to evaluate their association with the response to antipsychotic treatment. In this clinical prospective study were included 60 patients with schizophrenia and 40 healthy age and sex matched control subjects. Clinical evaluation of patients was performed using the Positive and Negative Symptom Scale. A questionnaire for socio-demographic and clinical data collection was used. For the purposes of the study, the examined group was divided in two subgroups: responders and nonresponders. Serum cortisol and DHEA-S levels were measured at baseline in all participants and after 3 and 6 weeks of the antipsychotic treatment in patients with schizophrenia. Patients with schizophrenia had significantly higher serum cortisol and DHEA-S levels in comparison to the control group. Responders had significantly higher serum cortisol and DHEA-S levels compared with nonresponders. Elevated serum cortisol and DHEA-S levels may play a role in the pathophysiology of schizophrenia and they may be related to positive response to antipsychotic treatment in patients with schizophrenia.


Wave chaos enhanced light trapping in optically thin solar cells.
Enhancing the energy output of solar cells increases their competitiveness as a source of energy. Producing thinner solar cells is attractive, but a thin absorbing layer demands excellent light management in order to keep transmission- and reflection-related losses of incident photons at a minimum. We maximize absorption by trapping light rays to make the mean average path length in the absorber as long as possible. In chaotic scattering systems, there are ray trajectories with very long lifetimes. In this paper, we investigate the scattering dynamics of waves in a model system using principles from the field of quantum chaotic scattering. We quantitatively find that the transition from regular to chaotic scattering dynamics correlates with the enhancement of the absorption cross section and propose the use of an autocorrelation function to assess the average path length of rays as a possible way to verify the light-trapping efficiency experimentally.


Recent progress in trivalent europium (Eu3+)-based inorganic phosphors for solid-state lighting: an overview.
Narrow band red-emitting phosphors are significant constituents but still a bottleneck for next-generation smart displays and high-performance lighting (solid-state lighting based white light-emitting diodes (WLEDs)) technology. This review emphasizes the fundamental understanding and comprehensive overview of the recent progress and challenges associated with inorganic phosphors or down (wavelength) convertors, providing special attention to narrowband red-emitting oxide phosphors for phosphor-converted WLEDs (pc-WLEDs). In this context, the comprehensive progress on trivalent europium (Eu3+, in scheelite and double perovskite structures) based oxide phosphors with special emphasis on structure-composition-property-correlations is briefly reviewed. Furthermore, the challenges faced in the design of new oxide red phosphors and strategies to improve their absorption, emission efficiency, and future research direction are highlighted.


[Continuous propofol infusion versus enflurane in children operated on for strabismus. Comparison of the quality of anesthesia and recovery conditions].
In children, the use of a continuous infusion of propofol has not yet been reported. A study was therefore designed to compare the characteristics of anaesthesia and recovery when either propofol or enflurance was used as the main anaesthetic agent. All 42 children (14 girls, 28 boys), ASA I and scheduled for corrective squint surgery under general anaesthesia, received 350 micrograms.kg-1 midazolam and 40 micrograms.kg-1 atropine intrarectally 20 min before induction, which was carried out with 3 mg.kg-1 propofol intravenously in 20 s. The patients were then randomly assigned to two groups, according to the drug used for maintenance: group P (n = 21) received a continuous intravenous infusion of propofol, 18 mg.kg-1.h-1 for the first 30 min and 15 mg.kg-1.h-1 thereafter; group E (n = 21) received 2.5%, then, after 30 min, 2% enflurane. Both groups were given 15 micrograms.kg-1 dextromoramide and 0.09 mg.kg-1 vecuronium. During anaesthesia, the following parameters were monitored: systolic (Pasys), diastolic (Padia) and mean arterial (Pa) pressures, heart rate (fc), the presence or not of an oculocardiac reflex with or without a 20% fall in fc which responded to 10-15 micrograms.kg-1 atropine, the appearance of a cardiac dysrhythmia, duration of anaesthesia and the delay before extubation. Recovery was assessed 1, 2, 4 and 6 h postoperatively by using both clinical and psychomotor criteria, the latter being adapted to children having one or both eyes occluded.(ABSTRACT TRUNCATED AT 250 WORDS)


Phase control of nonadiabaticity-induced quantum chaos in an optical lattice.
The qualitative nature (i.e., integrable vs chaotic) of the translational dynamics of a three-level atom in an optical lattice is shown to be controllable by varying the relative laser phase of two standing-wave lasers. Control is explained in terms of the nonadiabatic transition between optical potentials and the corresponding regular-to-chaotic transition in mixed classical-quantum dynamics. The results are of interest to both areas of coherent control and quantum chaos.


Next-generation sequencing diagnosis of severe pneumonia from fulminant psittacosis with multiple organ failure: a case report and literature review.
This study includes a retrospective analysis of the diagnosis and treatment of a case of severe pneumonia from fulminant psittacosis with multiple organ failure. Next-generation sequencing (NGS) of the pathogen was conducted. The purpose of this study was to summarize the clinical, laboratory, and imaging characteristics of the case and to improve understanding of the value of NGS in the diagnosis of severe community-acquired pneumonia (CAP). Fulminant psittacosis can be manifested as severe pneumonia with rapid progression, acute respiratory distress syndrome, sepsis, and multiple organ failure. Imaging shows unilateral lung consolidation, which is difficult to differentiate from CAP caused by common pathogens. The NGS technology can early detect rare pathogens, thus reducing unnecessary use of antibiotics and shortening the course of the disease.


An evolutionary perspective on maladaptive traits and cultural conformity.
The problem of maladaptive cultural traits is explored through the notion of adaptive psychological mechanisms. It is suggested that the theory of a specific conformity mechanism is plausible, supported by multidisciplinary data, and helpful in explaining the proliferation and persistence of human maladaptive behavior. © 1996 Wiley-Liss, Inc.


Self-regulation of agonist activity at the Y receptors.
Neuropeptide Y (NPY) is one of the most abundant neuropeptides, and is likely to be present at nanomolar levels over extended periods in the synaptic space of many forebrain areas. This might be linked to an evolved generalized toning activity through a number of other peptide receptors that use C-terminally amidated agonists (with LHRH and orexin receptors and GIR as examples). However, the Y1 and Y2 receptors (which constitute the bulk of Y receptors active in the neural matrix) possess subnanomolar affinities that, at saturating NPY levels, could produce excessive signaling, as well as receptor losses via repeated endocytosis. The related Y4 receptor shows an even higher agonist affinity, and faces the same problem in visceral and neural locations accessible to pancreatic polypeptide (PP). An examination of agonist peptide interaction with Y receptors shows that Y1 and Y4 receptors in particular (as located on either the intact cells, or on particulates derived from various cell types) develop a blockade dependent on ligand concentration, with the blocking ranks of [NPY]>>[peptide YY] (PYY) for the Y1, and [human PP]>>>[PYY-related Y4 agonist] for the Y4 receptor. This blockade is also echoed in a concentration-related reduction in biological activity of primary agonists (NPY and PP), resembling a partial agonism, and is influenced especially by the allosteric interactivity of agonists. With the Y2 receptor, the blocking by agonists is less pronounced, but the signaling by NPY-related peptides is apparently less than with PYY-related agonists. The extended occupancy and self-attenuation of primary agonist activity at Y receptors could represent an evolutionary solution contributing to a balancing of metabolic signaling, agonist clearance and receptor conservation.


Morphological Traits Around Patellofemoral Joint in Indian Femora and their Implications.
Knowledge of structural variations around patellofemoral joint has helped to understand postural behavior patterns of various population groups. The biomechanical impact of postures may lead to certain skeletal modifications which may contribute to knee pathologies like patellofemoral arthritis, patellar subluxation and trochlear dysplasia. This study was conducted to report the incidence of skeletal non-metric markers on femur in Indian population and to understand their correlation with some pathologies of patellofemoral joint. The traits studied were Martin's facet, Peritrochlear groove and Supratrochlear facet. The study material was a collection of 152 adult femora from osteology museum in Department of Anatomy, Maulana Azad Medical College, New Delhi, India, with equal percentage of bones from each side and gender. All bones were evaluated for the above mentioned traits and results were obtained as percentage of incidence and Chi-Square test using SPSS version 17. The data showed that Martin's facet and Peritrochlear groove showed a higher occurrence in male femora. However, Supratrochlear facet was more commonly found in female bones. Martin's facet had an equal incidence on femora of each side while peritrochlear groove and supratrochlear facet had higher percentage of occurrence on right side. Supratrochlear facet revealed significant side variation. These data suggest that casual or occupational postures may impose structural adaptations around patell- ofemoral joint. The stress of these postures may have causal,consequential or co-incidental relationship with joint pathologies. The gender, special occupations like sports and genetic predisposition may possibly have a role to play.


Guidelines for antiemetic treatment of chemotherapy-induced nausea and vomiting: past, present, and future recommendations.
Clinicians should be aware that chemotherapy-induced nausea and vomiting (CINV) is still one of the most feared side effects of chemotherapy. With the correct use of antiemetics, CINV can be prevented in almost 70% to up to 80% of patients. Treatment guidelines are useful tools that enable physicians to integrate the latest clinical research into their practices. The large volume of rapidly evolving clinical data has been summarized and incorporated into treatment recommendations by well-known and reliable institutions, including the Multinational Association of Supportive Care in Cancer, the American Society of Clinical Oncology, and the National Comprehensive Cancer Network. Despite the availability of such guidelines, however, there is evidence that adherence to and implementation of treatment recommendations are less than optimal. This review focuses, in particular, on the conformity and differences of these three guidelines. Furthermore, open questions and trends in the field of antiemesis are discussed as well.


[THE EFFECT OF PREGNANCY ON BREAST CANCER].
Cancer and pregnancy coincide in about one in 1,000 pregnancies. One of the most common malignancies associated with pregnancy is breast cancer. Women with pregnancy-associated breast cancer (PABC) have a higher likelihood of being diagnosed with metastatic disease and estrogen receptor (ER) negative tumors than do non-pregnant women. Controversies exist regarding the effect of pregnancy on breast cancer prognosis. Some researchers suggest that pregnancy does not affect breast cancer prognosis, whereas others claim the opposite. Although PABC is usually discovered in an advanced stage, breast cancer metastasis on the placenta is a rare event. During cancer progression, the surrounding microenvironment co-evolves into an activated state through continuous communication with the malignant cells, thereby promoting tumor growth. The effect of pregnancy and placental environment on breast cancer biology is the issue of this review. Placental and cancer cells implantation processes share similar molecular pathways. This suggests that placental factors may affect breast cancer cells biology. Previously, we analyzed the effect of first trimester human placenta on breast cancer cells. Breast cancer cells were co-cultured with placental explants during their implantation on matrigel substrate. We found that the placenta reduced ER expression on the cancer cells and induced their migration and invasion abilities. As a result of it, breast cancer cells migrated away from the placental implantation sites. Hormonal pathways were involved in these phenomena. These results may explain the high incidence of metastases during pregnancy in on the one hand and the rarity of metastases on the placenta on the other hand.


The impact of podoconiosis, lymphatic filariasis, and leprosy on disability and mental well-being: A systematic review.
Leprosy, podoconiosis, and lymphatic filariasis (LF) are among the priority neglected tropical diseases (NTDs) in Ethiopia. The disability, psychosocial, and mental health status of people affected by these NTDs are still overlooked in global NTD discourse. The objective of this systematic review was to synthesize the existing evidence describing the disability, psychosocial, and mental health status of people affected by leprosy, podoconiosis, and LF prior to developing a holistic physical and psychosocial care package for these individuals. We searched papers reporting on disability, psychosocial, and mental health status linked to these 3 NTDs. The protocol was registered in PROSPERO with registration number CRD42019128400. Peer-reviewed articles were searched and extracted from Medline, PsycINFO, Global Health, and Embase. Articles published in English, irrespective of the year of publication, using a quantitative study methodology, were included. Abstracts and full texts were reviewed by 2 reviewers. Data were extracted and narratively summarized, as the studies were heterogeneous and used different outcome measures. Out of 1,318 titles/abstracts screened and 59 full text studies reviewed, 24 fulfilled the inclusion criteria. Fourteen studies provided evidence of the disability associated with leprosy, podoconiosis, or LF. Ten studies provided evidence on the association between the 3 NTDs and mental health or psychosocial outcomes. The prevalence of grade 2 disability varied from 3.9% to 86%. The most commonly reported mental health impacts were depression and mental distress. A high burden of mental illness was reported, varying from 12.6% to 71.7%; the suicidal ideation was also high (18.5%). In conclusion, disability and poor psychosocial and mental health status are associated with leprosy, podoconiosis, and LF. For optimum management of these NTDs, holistic care including both physical and psychosocial interventions is vital.


17Beta-estradiol inhibits IL-8 in cystic fibrosis by up-regulating secretory leucoprotease inhibitor.
An unexplained gender gap is observed in cystic fibrosis (CF). Females have poorer lung function, decreased survival, and earlier Pseudomonas colonization. To evaluate the effect of 17beta-estradiol (E(2)) on CF bronchial epithelial cells in vitro and in vivo. On exposure of CFBE41o- cultures to physiological concentrations of E(2), there was a significant dose-dependent inhibition of IL-8 release induced by toll-like receptor agonists, CF bronchoalveolar lavage fluid, or Pseudomonas-conditioned media. Estrogen receptor (ER)-alpha and -beta expression was quantified in cell lines and bronchial brushings from CF and non-CF patients. Both receptors were expressed in vitro and in vivo, although ERbeta expression was significantly higher in CF. Using ER isoform-specific agonists and antagonists, we established that ERbeta mediates the inhibition of CF bronchoalveolar lavage fluid-induced IL-8 release. We also showed that secretory leucoprotease inhibitor gene expression and protein localization to the nucleus increased in response to E(2). Secretory leucoprotease inhibitor knockdown abrogated the inhibitory effects of E(2). E(2) inhibits IL-8 release by ERbeta in CF bronchial epithelial cells through up-regulation of secretory leucoprotease inhibitor, inhibition of nuclear factor (NF)-kappaB, and IL-8 gene expression. These data implicate a novel anti-inflammatory mechanism for E(2) in females with CF, which predisposes to infection and colonization. This could, in part, account for the observed gender dichotomy in CF.


Cryo-EM structures of PRC2 simultaneously engaged with two functionally distinct nucleosomes.
Epigenetic regulation is mediated by protein complexes that couple recognition of chromatin marks to activity or recruitment of chromatin-modifying enzymes. Polycomb repressive complex 2 (PRC2), a gene silencer that methylates lysine 27 of histone H3, is stimulated upon recognition of its own catalytic product and has been shown to be more active on dinucleosomes than H3 tails or single nucleosomes. These properties probably facilitate local H3K27me2/3 spreading, causing heterochromatin formation and gene repression. Here, cryo-EM reconstructions of human PRC2 bound to bifunctional dinucleosomes show how a single PRC2, via interactions with nucleosomal DNA, positions the H3 tails of the activating and substrate nucleosome to interact with the EED subunit and the SET domain of EZH2, respectively. We show how the geometry of the PRC2-DNA interactions allows PRC2 to accommodate varying lengths of the linker DNA between nucleosomes. Our structures illustrate how an epigenetic regulator engages with a complex chromatin substrate.


Patients' and clinicians' experiences of wound care in Canada: a descriptive qualitative study.
This study sought to explore patients' and clinicians' perceptions and experiences with the provision of standard care by a home care nurse alone or by a multidisciplinary wound care team. The interviews were conducted using an in-depth semi structured format; following a funnel idea of starting out broad and narrowing down, ensuring that all the necessary topics were covered by the end of the interview. A purposive sample of 16 patients with different wound types were interviewed to ensure that the data would reflect the range and diversity of treatment and care experience. To reflect the diversity of experiences 12 clinicians from various clinical backgrounds were interviewed. Based on the analysis of the interviews, there are four overarching themes: wound care expertise is required across health-care sectors, psychosocial needs of patients with chronic wounds are key barriers to treatment concordance, structured training, and a well-coordinated multidisciplinary team approach. Results of this qualitative study identified different barriers and facilitators that affect the experiences of community-based wound care.


Cardiopulmonary exercise testing in the evaluation of high risk patients with lung cancer.
It is still unclear whether pulmonary function tests (PFTs) are sufficient for predicting perioperative risk, and whether all patients or only a subset of them need a cardiopulmonary exercise test (CPET) for further assessment. Thus, this study was designed to evaluate the CPET and compare the results of CPET and conventional PFTs to identify which parameters are more reliable and valuable in predicting perioperative risks for high risk patients with lung cancer. From January 2005 to August 2008, 297 consecutive lung cancer patients underwent conventional PFTs (spirometry + single-breath carbon monoxide diffusing capacity of the lungs (DLCOsb) for diffusion capacity) and CPET preoperatively. The correlation of postoperative cardiopulmonary complications with the parameters of PFT and CPET was retrospectively analyzed using the chi-square test, independent sample t test and binary Logistic regression analysis. Of the 297 patients, 78 did not receive operation due to advanced disease stage or poor cardiopulmonary function. The remaining 219 underwent different modes of operations. Twenty-one cases were excluded from this study due to exploration alone (15 cases) and operation-related complications (6 cases). Thus, 198 cases were eligible for evaluation. Fifty of the 198 patients (25.2%) had postoperative cardiopulmonary complications. Three patients (1.5%) died of complications within 30 postoperative days. The patients were stratified into groups based on VO(2)max/pred (≥ 70.0%, < 70.0%); VO(2)max×kg(-1)×min(-1) (≥ 20.0 ml, 15.0 - 19.9 ml, < 15.0 ml) and FEV1 (≥ 2.0 L, 1.2 - 1.99 L, < 1.2 L), respectively. The rate of postoperative cardiopulmonary complications was significantly higher in the group with VO(2)max/pred< 70.0% or VO(2)max×kg(-1)×min(-1) < 15.0 ml or FEV1 < 1.2 L than that in the group with VO(2)max/pred ≥ 70.0% or VO(2)max×kg(-1)×min(-1) ≥ 15.0 ml or FEV1 ≥ 1.2 L, respectively. Logistic regression analysis revealed that postoperative cardiopulmonary complications were significantly correlated with age, comorbidities, and poor PFT and CPET results. FEV1 in spirometry, VO(2)max×kg(-1)×min(-1) and VO(2)max/pred in cardiopulmonary exercise tests can all be used to stratify the patients' cardiopulmonary function status and to predict the risk of postoperative cardiopulmonary complications for the high risk patients with lung cancer. FEV1 and VO(2)max×kg(-1)×min(-1) are better than VO(2)max/pred in predicting perioperative risk. If available, cardiopulmonary exercise testing is strongly suggested for high-risk lung cancer patients in addition to conventional pulmonary function tests, and both should be combined to assess cardiopulmonary function status.


Mood disorders and obesity: understanding inflammation as a pathophysiological nexus.
The aim of this review is to evaluate the evidentiary base supporting the hypothesis that the increased hazard for obesity in mood disorder populations (and vice versa) is a consequence of shared pathophysiological pathways. We conducted a PubMed search of all English-language articles with the following search terms: obesity, inflammation, hypothalamic-pituitary-adrenal axis, insulin, cognition, CNS, and neurotransmitters, cross-referenced with major depressive disorder and bipolar disorder. The frequent co-occurrence of mood disorders and obesity may be characterized by interconnected pathophysiology. Both conditions are marked by structural and functional abnormalities in multiple cortical and subcortical brain regions that subserve cognitive and/or affective processing. Abnormalities in several interacting biological networks (e.g. immuno-inflammatory, insulin signaling, and counterregulatory hormones) contribute to the co-occurence of mood disorders and obesity. Unequivocal evidence now indicates that obesity and mood disorders are chronic low-grade pro-inflammatory states that result in a gradual accumulation of allostatic load. Abnormalities in key effector proteins of the pro-inflammatory cascade include, but are not limited to, cytokines/adipokines such as adiponectin, leptin, and resistin as well as tumor necrosis factor alpha and interleukin-6. Taken together, the bidirectional relationship between obesity and mood disorders may represent an exophenotypic manifestation of aberrant neural and inflammatory networks. The clinical implications of these observations are that, practitioners should screen individuals with obesity for the presence of clinically significant depressive symptoms (and vice versa). This clinical recommendation is amplified in individuals presenting with biochemical indicators of insulin resistance and other concurrent conditions associated with abnormal inflammatory signaling (e.g. cardiovascular disease).


Mucopolysaccharidosis IVA (Morquio A): identification of novel common mutations in the N-acetylgalactosamine-6-sulfate sulfatase (GALNS) gene in Italian patients.
Mucopolysaccharidosis IVA (MPS IVA) is a lysosomal storage disorder caused by the deficiency of N-acetylgalactosamine-6-sulfate sulfatase (GALNS). Mutation screening of the GALNS gene was performed by RT-PCR with one amplicon and direct sequence analyses using cDNA samples from 15 Italian MPS IVA patients. Each mutation was confirmed at the genomic level. In this study, 13 different gene mutations with four common mutations (over 10% of mutant alleles) were identified in 12 severe and three milder (attenuated) MPS IVA patients. The gene alterations in 12 out of 13 were found to be point mutations and only one mutation was deletion. Ten of 13 mutations were novel. The c.1070C>T (p.Pro357Leu) mutation coexisted with c.1156C>T (p.Arg386Cys) mutation on the same allele. Together they accounted for 100% of the 30 disease alleles of the patients investigated. Four common mutations accounted for 70% of mutant alleles investigated. Urine keratan sulfate (KS) concentrations were elevated in all patients investigated. These data provide further evidence for extensive allelic heterogeneity and importance of relation among genotype, phenotype, and urine KS excretion as a biomarker in MPS IVA.


Alternaria alternata in a case of mass in the lung.
A 50-year-old woman, an agriculture worker with diabetes and asthma presented to us with complaints of fever with chills, cough with scanty, mucopurulent sputum and dull aching chest pain in right mammary area radiating to axilla. Chest X-ray and computed tomography scan revealed mass in the right lung. Ultrasound guided fine-needle aspiration cytology was done and the greenish fluid on direct wet mount and inoculation on Sabouraud's dextrose agar isolated Alternaria species. Serum specimen was evaluated for immunoglobulin E specific titres for Alternaria species which was high. Patient was treated with fluconazole for 6 weeks after which the symptoms disappeared and chest X-ray was normal.


Towards testing the "honeycomb rippling model" in cerrado.
Savannas are tropical formations in which trees and grasses coexist. According to the "honeycomb rippling model", inter-tree competition leads to an effect of trees growing and dying due to competition, which, at fine spatial scale, would resemble honeycomb rippling. The model predicts that the taller the trees, the higher the inter-tree distances and the evenness of inter-tree distances. The model had been corroborated in arid savannas, in what appears to be caused by uneven distribution of rains, but had not yet been tested in seasonal savannas, such as the cerrado, which could be caused by the irregular occurrence of fire.A basic assumption of the model is that strong inter-tree competition affects growth (estimated by height) and mortality (estimated by inter-tree distances). As a first step towards testing this model in the cerrado, we tested this assumption in a single cerrado patch in southeastern Brazil. We placed 80 quadrats, each one with 25 m², in which we sampled all shrubs and trees. For each individual, we measured its height and the distance to its nearest neighbour--the inter-tree distance. We did not find correlations between tree height and both inter-tree distances and evenness of inter-tree distances, refuting the honeycomb rippling model. Inter-tree distances were spatially autocorrelated, but height was not. According to our results, the basic assumption of the model does not apply to seasonal savannas. If, in arid savannas, rainfall events are rare and unpredictable, in seasonal savannas, the rainy season is well-defined and rainfall is considerable. We found horizontal structuring in the community, which may be due to soil nutrient heterogeneity. The absence of vertical structuring suggests that competition for light among adult trees is not as important as competition for nutrients in the soil. We tested the basic assumption of the model in a single patch and at a single moment. To test the model effectively, we suggest this assumption to be tested in many patches over time.


Dynamic structure of methane/n-nonane clusters during nucleation and growth.
We report results on nucleation, growth, and structure formation of methane/n-nonane clusters in an expanding system investigated by molecular dynamics simulation. From bulk phase equilibria data, it is expected that the concentration of the less volatile substance n-nonane in the clusters is very high. However, analyses of experimental data in the literature suggest somewhat higher methane content at onset of nucleation. Our simulations show that the methane mole fraction is actually very high and increases even further at the beginning of the cluster growth. On the other hand, in this transient state after nucleation the methane mole fraction in the cluster core decreases, leaving a n-nonane rich core, i.e., we observe the phase separation inside the growing cluster. Methane is squeezed out from the core to the surface and then evaporates from the surface shell during expansion of the system.


[Expression of E-cadherin, β-catenin and p120ctn in so-called pulmonary sclerosing hemangioma].
So-called pulmonary sclerosing hemangioma (PSH) is a rare kind of pulmonary tumor. Its histological origin and nature, which have become research hot spots for many years, are still uncertain. The aim of this study is to investigate the immunophenotype of cuboidal cells and polygonal cells through observing the expression of E-cadherin, β-catenin and p120ctn in cuboidal cells and polygonal cells of PSH. Expression of E-cadherin, β-catenin and p120 ctn was detected in 25 cases of PSH samples and 8 cases of pulmonary inflammatory pseudotumor samples by immunohistochemistry. Immunohistochemistry results showed that the surface cuboidal cells of PSH were strongly positive on membrane for E-cadherin, β-catenin and p120 ctn , with cytoplasmic positive expression of β-catenin. However,the polygonal cells were negative for E-cadherin, cytoplasmic positive for β-catenin and predominantly cytoplasmic positive and weakly membranous positive for p120ctn . In polygonal cells, all the three adhesion molecules showed heterogenicity staining. The cytoplasm and membrane of inner covering cells in the hemorrhagic pattern were positively stained for E-cadherin, β-catenin and p120ctn . The expression of the three adhesion molecules in hyperplastic type II alveolar cells of pulmonary inflammatory pseudotumor was similar to cuboidal cells of PSH. It is concluded that cuboidal cells of PSH may be the hyperplastic type II alveolar cells, whereas polygonal cells are true tumor cells lacking the E-cadherin/catenin complex which is expressed in well differentiated epithelial cells. The inner covering cells in the hemorrhagic pattern of PSH are perhaps epithelial cells as cuboidal cells rather than vascular endothelial cells.


[N(omega)-nitro-L-arginine methyl ester inhibits the up-regulated expression of neuronal nitric oxide synthase/NMDA receptor in the morphine analgesia tolerance rats].
The effect of systemic administration of nonspecific nitric oxide synthase inhibitor (N(omega)-nitro-L-arginine methyl ester, L-NAME) on morphine analgesia tolerance was observed by using the thermal tail-flick method, and the roles of NO and NMDA receptors in morphine analgesia tolerance were evaluated on the basis of the expressions of nNOS mRNA, NR1A mRNA and NR2A mRNA in spinal cord and midbrain. Thirty-six healthy adult Sprague-Dawley rats were randomly divided into six groups (6 rats per group). Group 1, control group, received a subcutaneous (s.c.) injection of normal saline (1 ml); Groups 2, 3, 4, 5 and 6, the treatment groups received s.c. injection of L-NAME 10 mg/kg, L-NAME 20 mg/kg, morphine 10 mg/kg, L-NAME 10 mg/kg + morphine 10 mg/kg, and L-NAME 20 mg/kg + morphine 10 mg/kg, respectively. All rats received s.c. injections twice per day (8:00 and 17:00). The tail-flick latency (TFL) was measured in each rat before the injection as a baseline value, and then TFL at 50 min after the 1st injection every day as the measuring values. The animals (except for groups 2 and 5) were decapitated at 80 min after the last injection on the 8th day. The spinal segments and midbrain were removed for analysis of nNOS mRNA, NR1A mRNA and NR2A mRNA expressions by the RT-PCR method. The results showed that TFL remained unchangeable in group 2 compared with baseline value during the 7-day observation, while increased significantly on the 7th day in group 3. In group 4, TFL was longest on the 1st day, then decreased gradually from the 2nd day to the 6th day, and restored to the baseline value on the 6th day. In group 5, TFL showed a decreasing tendency during the 7-day observation, but was still significantly longer than the baseline value on the 7th day. The changes of TFL obtained in group 6 were similar to those in group 5. The results of RT-PCR showed that as compared with group 1, nNOS mRNA expressions in spinal cord and midbrain were significantly down-regulated in group 3, but the expressions of the NR1A mRNA and NR2A mRNA in both groups were similar, while the nNOS mRNA, NR(1A) mRNA and NR(2A) mRNA expressions were all significantly up-regulated in group 4. As compared with group 4, the expressions of nNOS mRNA, NR(1A) mRNA and NR(2A) mRNA were significantly inhibited in group 6. These results suggest that the expressions of nNOS and NMDA receptors in spinal cord and midbrain were significantly up-regulated in the rats with morphine analgesia tolerance. Chronic co-administration of L-NAME could effectively inhibit the morphine-induced overexpressions of nNOS and NMDA receptors, and postpone the development of morphine analgesia tolerance. Based on the results of this study, it is concluded that NO/NMDA receptor in spinal cord and midbrain is closely related to the development of morphine analgesia tolerance.


Allostasis as a conceptual framework linking bipolar disorder and addiction.
Bipolar disorders (BDs) and addictions constitute reciprocal risk factors and are best considered under a unitary perspective. The concepts of allostasis and allostatic load (AL) may contribute to the understanding of the complex relationships between BD and addictive behaviors. Allostasis entails the safeguarding of reward function stability by recruitment of changes in the reward and stress system neurocircuitry and it may help to elucidate neurobiological underpinnings of vulnerability to addiction in BD patients. Conceptualizing BD as an illness involving the cumulative build-up of allostatic states, we hypothesize a progressive dysregulation of reward circuits clinically expressed as negative affective states (i.e., anhedonia). Such negative affective states may render BD patients more vulnerable to drug addiction, fostering a very rapid transition from occasional drug use to addiction, through mechanisms of negative reinforcement. The resulting addictive behavior-related ALs, in turn, may contribute to illness progression. This framework could have a heuristic value to enhance research on pathophysiology and treatment of BD and addiction comorbidity.


Human endothelial nitric oxide synthase gene transfer inhibits vascular smooth muscle cell proliferation and neointima formation after balloon injury in rats.
Loss of endothelial NO production after arterial injury may contribute to restenosis, characterized by neointima formation and elastic recoil. Adenovirus-mediated transfer of the gene encoding NO synthase (NOS) in balloon-injured arteries may restore NO production and inhibit neointima formation. After balloon injury, rat carotid arteries were transduced with 3x10(10) pfu/mL recombinant adenovirus carrying the human endothelial constitutive NOS cDNA (AdCMVceNOS, n=8) or no cDNA (AdRR5, n=8). ceNOS expression was confirmed by immunoblot analysis of vascular extracts and was localized by immunostaining in 30% of medial smooth muscle cells (SMCs) and in the adventitia of AdCMVceNOS-transduced arteries. Vascular cGMP levels were reduced from 3.9 pmol/g wet wt in uninjured arteries to 0.7 pmol cGMP/g after AdRR5 but were restored after ceNOS gene transfer (3.8 pmol cGMP/g wet wt, P<.05 versus AdRR5). Intima-to-media ratio 2 weeks after injury was significantly reduced (0.19+/-0.02 in AdCMVceNOS-infected versus 0.69+/-0.07 in AdRR5-infected arteries, P<.05). In vitro, BrdU incorporation of AdCMVceNOS-infected SMCs was reduced by 28% compared with AdRR5-infected SMCs. Transduced cells from injured carotid arteries subjected to FACS sorting showed a significantly lower BrdU labeling index in ceNOS-infected rats (29+/-6% versus 43+/-5% and 45+/-4% in control, injured, and AdRR5-infected rats, respectively, P<.05). AdCMVceNOS gene transfer to balloon-injured rat carotid arteries restores vascular NO production and reduces neointima formation, at least in part because of an antiproliferative effect on medial SMCs. Adenovirus-mediated ceNOS gene transfer might reduce arterial restenosis after balloon angioplasty.