Jewish and Middle Eastern non-Jewish populations share a common pool of Y-chromosome biallelic haplotypes.
Haplotypes constructed from Y-chromosome markers were used to trace the paternal origins of the Jewish Diaspora. A set of 18 biallelic polymorphisms was genotyped in 1,371 males from 29 populations, including 7 Jewish (Ashkenazi, Roman, North African, Kurdish, Near Eastern, Yemenite, and Ethiopian) and 16 non-Jewish groups from similar geographic locations. The Jewish populations were characterized by a diverse set of 13 haplotypes that were also present in non-Jewish populations from Africa, Asia, and Europe. A series of analyses was performed to address whether modern Jewish Y-chromosome diversity derives mainly from a common Middle Eastern source population or from admixture with neighboring non-Jewish populations during and after the Diaspora. Despite their long-term residence in different countries and isolation from one another, most Jewish populations were not significantly different from one another at the genetic level. Admixture estimates suggested low levels of European Y-chromosome gene flow into Ashkenazi and Roman Jewish communities. A multidimensional scaling plot placed six of the seven Jewish populations in a relatively tight cluster that was interspersed with Middle Eastern non-Jewish populations, including Palestinians and Syrians. Pairwise differentiation tests further indicated that these Jewish and Middle Eastern non-Jewish populations were not statistically different. The results support the hypothesis that the paternal gene pools of Jewish communities from Europe, North Africa, and the Middle East descended from a common Middle Eastern ancestral population, and suggest that most Jewish communities have remained relatively isolated from neighboring non-Jewish communities during and after the Diaspora.


Safety and efficacy of the Pipeline Embolization Device in 100 small intracranial aneurysms.
OBJECT Flow diverters are increasingly used for treatment of intracranial aneurysms. In most series, the Pipeline Embolization Device (PED) was used for the treatment of large, giant, complex, and fusiform aneurysms. Little is known about the use of the PED in small aneurysms. The purpose of this study was to assess the safety and efficacy of the PED in small aneurysms (≤ 7 mm). METHODS A total of 100 consecutive patients were treated with the PED at the authors' institution between May 2011 and September 2013. Data on procedural safety and efficacy were retrospectively collected. RESULTS The mean aneurysm size was 5.2 ± 1.5 mm. Seven patients (7%) had sustained a subarachnoid hemorrhage. All except 5 aneurysms (95%) arose from the anterior circulation. The number of PEDs used was 1.2 per aneurysm. Symptomatic procedure-related complications occurred in 3 patients (3%): 1 distal parenchymal hemorrhage that was managed conservatively and 2 ischemic events. At the latest follow-up (mean 6.3 months), 54 (72%) aneurysms were completely occluded (100%), 10 (13%) were nearly completely occluded (≥ 90%), and 11 (15%) were incompletely occluded (< 90%). Six aneurysms (8%) required further treatment. Increasing aneurysm size (OR 3.8, 95% CI 0.99-14; p = 0.05) predicted retreatment. All patients achieved a favorable outcome (modified Rankin Scale Score 0-2) at follow-up. CONCLUSIONS In this study, treatment of small aneurysms with the PED was associated with low complication rates and high aneurysm occlusion rates. These findings suggest that the PED is a safe and effective alternative to conventional endovascular techniques for small aneurysms. Randomized trials with long-term follow-up are necessary to determine the optimal treatment that leads to the highest rate of obliteration and the best clinical outcomes.


Angiogenesis in endometrial carcinoma: correlation with survival and clinicopathologic risk factors.
Association among angiogenesis, survival and clinicopathologic parameters in endometrial carcinoma was evaluated. Sixty patients who had been diagnosed as endometrial carcinoma, from 1993 to 1998, were included in the study. All patients had been surgically staged with bilateral pelvic and para-aortic lymph node dissection. All hysterectomy specimens were stained immunohistologically for factor VIII-related antigen. The area with the most intensified microvasculature was determined under low-power (x100) magnification, and the microvessel count of this area under high-power (x200) magnification was determined as the microvessel density (MVD) of the tumor. The mean MVD was 26.2 +/- 13.0 (range 6-68), and it was considered as high (n = 24; 40%), moderate (n = 19; 31.7%) and low (n = 17; 28.3%) when the MVD was >30, between 15-30 and <15, respectively. Statistical analysis included Mann-Whitney, Kruskal-Wallis and Spearman rank correlation tests. The Kaplan-Meier method was used to evaluate the difference between angiogenesis and survival. Multivariate analysis with the Cox regression model was used in MVD values and different clinicopathological parameters. There was positive correlation between MVD increase and surgicopathological stage (p < 0.05). A significant difference was seen between MVD increase and lymph node metastasis (p < 0.05). There were no differences between MVD and age, histological type, grade and lymphovascular invasion. MVD did not change in association with myometrial invasion depth. There was a significant difference in means of survival between the low and high MVD groups (p = 0.01). However, MVD was not an independent prognostic factor in multivariate analysis. Increased angiogenesis was found to be associated with advanced stage and decreased survival in endometrial carcinoma.


Maxillary sinus morphology in differential dental diagnosis.
In this case, the shape of the maxillary sinus was misinterpreted as a periapical pathological condition. Based on this anatomic misinterpretation, conventional endodontic therapy had been performed on two teeth. When the suspected lesion did not resolve, an exploratory procedure revealed the unusual morphology of an otherwise normal maxillary sinus. The anatomy and morphology of the maxillary sinus in differential dental diagnosis are discussed, and surgical exploration is demonstrated. A case of healthy sinus anatomy with abnormal morphology is reported.


GO-Cu7S4 catalyzed ortho-aminomethylation of phenol derivatives with N,N-dimethylbenzylamines: site-selective oxidative CDC.
Copper chalcogenide nanoparticles (Cu7S4) supported on graphene oxide (GO) have been synthesized for the first time from Cu2S, and used as highly efficient heterogeneous catalysts for oxidative ortho-selective C-H aminomethylation of phenols with N,N-dimethylbenzylamines. The NPs (30-80 nm) have been characterized by HRTEM, SEM-EDX, PXRD, FTIR, Raman, ICP-AES and XPS analyses. The NP catalyzed sp2-sp3 cross dehydrogenative coupling (CDC) features a broad substrate scope, excellent functional group tolerance, high yields, use of an inexpensive and reusable copper catalyst, mild conditions, and no need for pre-functionalization of substrates.


Separation anxiety at the centromere.
During mitosis, replicated sister-chromatids must maintain cohesion as they attach to the mitotic spindle. At anaphase, cohesion is lost simultaneously along the entire chromosome, releasing sisters from one another and allowing them to segregate to opposite poles. During meiosis, sisters separate in a two-step process. At anaphase of meiosis I, cohesion is lost along the chromosome arms but is maintained at centromeric regions. Not until meiosis II are sister chromatids able to break the connection at the centromere and separate away from one another. Recent studies suggest that the centromere exhibits dynamics that are very different compared with those of the chromatid arms during both mitosis and meiosis. This review discusses the nature of the specialized chromatid cohesion seen at the centromere.


Intrinsic, light-independent, regional differences in photoreceptor cell degeneration in vitamin A-deficient rat retinas.
The retinas of retinol-deficient rats reared in darkness or cyclic light were examined to determine whether regional degeneration of photoreceptor cells was induced by environmental lighting or resulted from intrinsic differences between ocular hemispheres. Weanling male Sprague-Dawley rats were fed a retinol-adequate or retinol-deficient diet and were reared in either cyclic light or darkness through 29 weeks. The nasal retinal quadrants were examined by light microscopy and the number of photoreceptor nuclei was counted in a 630 micron segment beginning 200 micron from the optic nerve. Retinol-deficient rats reared in darkness for 29 weeks lost 24% of their photoreceptors in the inferior nasal quadrant but only 11% in the superior nasal quadrant. Deficient rats reared in cyclic light for 29 weeks lost 39% of their photoreceptor cells in the inferior nasal quadrant and only 16% in the superior nasal quadrant. Photoreceptor cells degenerated faster in the inferior nasal quadrant than in the superior nasal quadrant in darkness or cyclic light. These results indicate that regional differences in rate of photoreceptor cell loss in retinol-deficient rats are not induced by the lighting conditions but occur as a result of intrinsic differences between the ocular hemispheres.


A standard weight equation to assess the body condition of pejerrey Odontesthes bonariensis.
We developed a standard weight equation Ws to aid in the analysis of pejerrey Odonthestes bonariensis body condition over time and across populations using the relative weight index Wr. Weight--length data were compiled from 73 populations of pejerrey (N=16.022) from the Argentine pampas region. We used the regression-line-percentile technique, which provides a 75th-percentile standard by length intervals of 10 mm, to develop the Ws equation. The proposed equation is log 10 Ws=-5,267+3,163 log10 Lst; Ws is weight in grams and Lst is standard length in millimeters. This equation is proposed for use with pejerrey between 120 and 520 mm of Lst. Values for Wr calculated with the Ws equation did not consistently increase or decrease as function of fish length, indicating absence of length bias. We analyze the values and distribution of Wr for pejerrey and suggest how to interpret its results. The equation of Ws that intends to calculate the index of Wr, represents a useful tool of analysis, because not only it allows to statistically compare the physical condition of the pejerrey, independently of its size, capture moment or the individual origin, but also it facilitates to relate it with other variables.


Multiple noncoding exons 1 of nuclear receptors NR4A family (nerve growth factor-induced clone B, Nur-related factor 1 and neuron-derived orphan receptor 1) and NR5A1 (steroidogenic factor 1) in human cardiovascular and adrenal tissues.
Nuclear receptors are involved in a wide variety of functions, including aldosteronogenesis. Nuclear receptor families NR4A [nerve growth factor-induced clone B (NGFIB), Nur-related factor 1 (NURR1) and neuron-derived orphan receptor 1 (NOR1)] and NR2F [chicken ovalbumin upstream promoter-transcription factor 1 (COUP-TFI), COUP-TFII and NR2F6) activate, whereas NR5A1 [steroidogenic factor 1 (SF1)] represses CYP11B2 (aldosterone synthase) gene transcription. The present study was undertaken to elucidate the mechanism of differential regulation of nuclear receptors between cardiovascular and adrenal tissues. We collected tissues of artery (n = 9), cardiomyopathy muscle (n = 9), heart muscle (noncardiomyopathy) (n = 6), adrenal gland (n = 9) and aldosterone-producing adenoma (APA) (n = 9). 5'-rapid amplification of cDNA ends (RACE) identified transcription start sites. Multiplex reverse-transcription PCR (RT-PCR) determined use of alternative noncoding exons 1 (ANEs). In adrenocortical H295R cells, angiotensin II, KCl or cAMP, all stimulated CYP11B2 transcription and NR4A was upregulated, whereas NR2F and NR5A1 were downregulated. 5'-RACE and RT-PCR revealed four ANEs of NGFIB (NR4A1), three of NURR1 (NR4A2), two of NOR1 (NR4A3) and two of SF1 (NR5A1) in cardiovascular and adrenal tissues. Quantitative multiplex RT-PCR showed NR4A and NR5A1 differentially employed multiple ANEs in a tissue-specific manner. The use of ANEs of NGFIB and NURR1 was significantly different between APA and artery. Changes in use of ANEs of NGFIB and NOR1 were observed between cardiomyopathy and noncardiomyopathy. The NR4A mRNA levels in artery were high compared with cardiac and adrenal tissues, whereas the NR5A1 mRNA level in adrenal tissues was extremely high compared with cardiovascular tissues. NR4A and NR5A1 genes are complex in terms of alternative promoter use. The use of ANEs may be associated with the pathophysiology of the heart and adrenal gland.


Visual stimuli in intervention approaches for pre-schoolers diagnosed with phonological delay.
The aim of this study was to develop and content validate specific speech and language intervention picture cards: The Letter-Sound (L&S) cards. The present study was also focused on assessing the influence of these cards on letter-sound correspondences and speech sound production. An expert panel of six speech and language therapists analysed and discussed the L&S cards based on several criteria previously established. A Speech and Language Therapist carried out a 6-week therapeutic intervention with a group of seven Portuguese phonologically delayed pre-schoolers aged 5;3 to 6;5. The modified Bland-Altman method revealed good agreement among evaluators, that is the majority of the values was between the agreement limits. Additional outcome measures were collected before and after the therapeutic intervention process. Results indicate that the L&S cards facilitate the acquisition of letter-sound correspondences. Regarding speech sound production, some improvements were also observed at word level. The L&S cards are therefore likely to give phonetic cues, which are crucial for the correct production of therapeutic targets. These visual cues seemed to have helped children with phonological delay develop the above-mentioned skills.


Green electrochemical template synthesis of CoPt nanoparticles with tunable size, composition, and magnetism from microemulsions using an ionic liquid (bmimPF6).
Electrodeposition from microemulsions using ionic liquids is revealed as a green method for synthesizing magnetic alloyed nanoparticles, avoiding the use of aggressive reducing agents. Microemulsions containing droplets of aqueous solution (electrolytic solution containing Pt(IV) and Co(II) ions) in an ionic liquid (bmimPF6) define nanoreactors in which the electrochemical reduction takes place. Highly crystalline hcp alloyed CoPt nanoparticles, in the 10-120 nm range with a rather narrow size distribution, have been deposited on a conductive substrate. The relative amount of aqueous solution to ionic liquid determines the size of the nanoreactors, which serve as nanotemplates for the growth of the nanoparticles and hence determine their size and distribution. Further, the stoichiometry (Pt(x)Co(1-x)) of the particles can be tuned by the composition of the electrolytic solution inside the droplets. The control of the size and composition of the particles allows tailoring the room-temperature magnetic behavior of the nanoparticles from superparaparamagnetic to hard magnetic (with a coercivity of HC = 4100 Oe) in the as-obtained state.


Stimulatory effects of neuronally released norepinephrine on renin release in vitro.
Extracellular high potassium inhibits renin release in vitro by increasing calcium concentrations in the juxtaglomerular cells. We found that the decreased response of renin release from rat kidney cortical slices in high potassium solution (20-80 mM) changed to a strikingly increased one in the presence of nifedipine at doses over 10(-6) M. We then examined the stimulatory effect of extracellular high potassium in the presence of nifedipine on renin release. The enhancement of release was significantly suppressed either by propranolol or by metoprolol but not by prazosin. High potassium plus nifedipine-induced increase in renin release was markedly attenuated by renal denervation. The enhancing effect was not observed when the slices were incubated in calcium-free medium. Divalent cations such as Cd2+, Co2+, and Mn2+ (0.1-3.0 mM) blocked this enhancement in a concentration-dependent manner. High potassium elicited an increase in 3H efflux from the slices preloaded with [3H]norepinephrine. The increasing effect was not influenced by nifedipine but was abolished by the removal of extracellular calcium or by the addition of divalent cations. These observations suggest to us that the high potassium plus nifedipine-induced increase in renin release from the slices is mediated by norepinephrine derived from renal sympathetic nerves and that this neuronally released norepinephrine stimulates renin release via activation of beta-adrenoceptors.


Pathologic vs. protective roles of hypoxia-inducible factor 1 in RPE and photoreceptors in wet vs. dry age-related macular degeneration.
It has previously been reported that antioxidant vitamins can help reduce the risk of vision loss associated with progression to advanced age-related macular degeneration (AMD), a leading cause of visual impairment among the elderly. Nonetheless, how oxidative stress contributes to the development of choroidal neovascularization (CNV) in some AMD patients and geographic atrophy (GA) in others is poorly understood. Here, we provide evidence demonstrating that oxidative stress cooperates with hypoxia to synergistically stimulate the accumulation of hypoxia-inducible factor (HIF)-1α in the retinal pigment epithelium (RPE), resulting in increased expression of the HIF-1-dependent angiogenic mediators that promote CNV. HIF-1 inhibition blocked the expression of these angiogenic mediators and prevented CNV development in an animal model of ocular oxidative stress, demonstrating the pathological role of HIF-1 in response to oxidative stress stimulation in neovascular AMD. While human-induced pluripotent stem cell (hiPSC)-derived RPE monolayers exposed to chemical oxidants resulted in disorganization and disruption of their normal architecture, RPE cells proved remarkably resistant to oxidative stress. Conversely, equivalent doses of chemical oxidants resulted in apoptosis of hiPSC-derived retinal photoreceptors. Pharmacologic inhibition of HIF-1 in the mouse retina enhanced-while HIF-1 augmentation reduced-photoreceptor apoptosis in two mouse models for oxidative stress, consistent with a protective role for HIF-1 in photoreceptors in patients with advanced dry AMD. Collectively, these results suggest that in patients with AMD, increased expression of HIF-1α in RPE exposed to oxidative stress promotes the development of CNV, but inadequate HIF-1α expression in photoreceptors contributes to the development of GA.


Synthesis of Spherical Nanoparticle Hybrids via Aerosol Thiol-Ene Photopolymerization and Their Bioconjugation.
Hybrid nanomaterials possess the properties of both organic and inorganic components and find applications in various fields of research and technology. In this study, aerosol photopolymerization is used in combination with thiol-ene chemistry to produce silver poly(thio-ether) hybrid nanospheres. In aerosol photopolymerization, a spray solution of monomers is atomized, forming a droplet aerosol, which then polymerizes, producing spherical polymer nanoparticles. To produce silver poly(thio-ether) hybrids, silver nanoparticles were introduced to the spray solution. Diverse methods of stabilization were used to produce stable dispersions of silver nanoparticles to prevent their agglomeration before the photopolymerization process. Successfully stabilized silver nanoparticle dispersion in the spray solution subsequently formed nanocomposites with non-agglomerated silver nanoparticles inside the polymer matrix. Nanocomposite particles were analyzed via scanning and transmission electron microscopy to study the degree of agglomeration of silver nanoparticles and their location inside the polymer spheres. The nanoparticle hybrids were then introduced onto various biofunctionalization reactions. A two-step bioconjugation process was developed involving the hybrid nanoparticles: (1) conjugation of (biotin)-maleimide to thiol-groups on the polymer network of the hybrids, and (2) biotin-streptavidin binding. The biofunctionalization with gold-nanoparticle-conjugates was carried out to confirm the reactivity of -SH groups on each conjugation step. Fluorescence-labeled biomolecules were conjugated to the spherical nanoparticle hybrids (applying the two-step bioconjugation process) verified by Fluorescence Spectroscopy and Fluorescence Microscopy. The presented research offers an effective method of synthesis of smart systems that can further be used in biosensors and various other biomedical applications.


The effect of individual characteristics on susceptibility to aggressive and/or intimidating approaches: quantifying probability pathways by creating a victimization model.
Background: A significant body of literature has identified multiple factors that contribute to established victimization by aggressive and/or intimidating behaviours. These studies primarily originate from the fields of intimate partner violence (IPV), bullying, sexual abuse, and/or commercial sexual exploitation (CSE), and generally focus on female victims. It appears, however, complicated to quantify the cumulative contribution of these factors on susceptibility to intimidating and/or hostile engagements on an individual level.Objective: To develop a comprehensive risk model to quantify, on an individual level, the cumulative effects of previously reported characteristics on susceptibility to aggressive/intimidating approaches, leading to victimization (e.g. in the context of IPV/sexual abuse).Methods: A Bayesian belief network was developed using data from previous studies, capturing the multivariate contribution of previously reported characteristics on the likelihood of becoming victimized by aggressive and/or intimidating approaches (e.g. in the IPV/CSE context) in female victims aged 12-24 years.Results: The model showed that specific combinations of characteristics may contribute to an increased likelihood of victimization (e.g. in the context of IPV/bullying/sexual abuse or CSE). This likelihood could be quantified and categorized into specific clusters of factors differentiating between victimization by physically violent, non-physical, and/or sexual aggressive/intimidating approaches.Conclusion: The present model appears to be the first to successfully quantify the cumulative contribution of individual characteristics on the likelihood of becoming victimized by aggressive and/or intimidating approaches, typically leading to victimization. Moreover, the present scientific effort and resulting model suggest that there may be a latent variable mediating between the implemented factors and overall outcome, i.e. the susceptibility to aggressive and/or intimidating approaches. From that perspective, the model may also be considered as an initial outline to effectively indicate susceptibility to such approaches.


Protective effect of a DNA vaccine delivered in attenuated Salmonella typhimurium against Toxoplasma gondii infection in mice.
Infection with the intracellular protozoan parasite Toxoplasma gondii causes serious public health problems and is of great economic importance worldwide. The T. gondii surface antigen protein SAG1 is a significant candidate vaccine against toxoplasmosis. In this study, we evaluated safety, stability of ZJ111/pcDNA3-SAG1, a DNA vaccine delivered in attenuated Salmonella typhimurium, and immune responses induced by immunizing ICR mice orally with ZJ111/pcDNA3-SAG1 of different doses. Mice had no significant differences in body weight between the groups before immunization and at week 4 after the booster immunization. The ZJ111/pcDNA3-SAG1 was eventually eliminated from the spleen and liver on week 6 post-immunization. The plasmid pcDNA3-SAG1 was stably maintained over 90% of the attenuated S. typhimurium population after 100 generations of growth in antibiotic-free media. Oral immunization of mice with ZJ111/pcDNA3-SAG1 elicited specific humoral responses and stimulated proliferation of splenocytes (P<0.05). The cellular immune response was associated with the production of IFN-gamma, indicating that a Th-1 type response was elicited, which was confirmed by the production of large amounts of IgG2a (P<0.01). Mice immunized with ZJ111/pcDNA3-SAG1 displayed significant protection against an intraperitoneally challenge with 500 tachyzoite forms of T. gondii RH strain. Vaccination at 10(7) and 10(8)CFU per mice provided a 20% and 10% survival rate comparing 100% mortality of the non-immunized mice, exhibiting longer living time and better survival rate. These results confirmed a DNA vaccine delivered in attenuated S. typhimurium, ZJ111/pcDNA3-SAG1, can elicit specific immune response as well as provide effective protection against T. gondii infection, and the dosage of 10(7)CFU was a most considerate one.


Portuguese Football Federation consensus statement 2020: nutrition and performance in football.
Nutrition is an undeniable part of promoting health and performance among football (soccer) players. Nevertheless, nutritional strategies adopted in elite football can vary significantly depending on culture, habit and practical constraints and might not always be supported by scientific evidence. Therefore, a group of 28 Portuguese experts on sports nutrition, sports science and sports medicine sought to discuss current practices in the elite football landscape and review the existing evidence on nutritional strategies to be applied when supporting football players. Starting from understanding football's physical and physiological demands, five different moments were identified: preparing to play, match-day, recovery after matches, between matches and during injury or rehabilitation periods. When applicable, specificities of nutritional support to young athletes and female players were also addressed. The result is a set of practical recommendations that gathered consensus among involved experts, highlighting carbohydrates periodisation, hydration and conscious use of dietary supplements.


Deletion of the chemokine receptor CCR1 prolongs corneal allograft survival.
Many corneal grafts undergo immune rejection, and current therapies are associated with many side effects. The purpose of this study was to identify critical chemokine pathways involved in generating the alloimmune response to corneal transplants. Orthotopic corneal transplantation was performed in fully mismatched strains. Cytokine and chemokine receptor gene expression was determined by the RNase protection assay. Knockout (KO) strains for chemokine-chemokine receptors that are upregulated after transplantation underwent corneal transplantation. Results derived from KO murine hosts were compared with cyclosporine (Cy) therapy. In addition to graft survival, graft infiltration, allospecific delayed-type hypersensitivity (DTH), and cytokine expression were compared among the recipient groups. Initial experiments revealed gene upregulation of the chemokine receptors CCR1, -2, and -5 after corneal allorejection. Although CCR1 KO hosts showed a significant increase in graft survival compared with wild-type (WT) hosts, allografts in CCR5, CCR2/CCL3(MIP-1alpha), CXCR3, CXCL10/IP-10, and CCL3/MIP-1alpha KO mice did not show a significant improvement in graft survival. Further, CCR1 KO hosts showed a significantly higher survival rate than with systemic Cy therapy in WT hosts. Moreover, graft infiltration by leukocytes and gene expression of proinflammatory cytokines were reduced in CCR1 KO mice compared with both Cy treated and untreated WT mice, as was the induction of allospecific DTH. These studies provide, for the first time, evidence that targeting of specific chemokine pathways can significantly promote survival of corneal transplants, and suggest that select deletion or suppression of CCR1 can be a useful therapeutic target in corneal transplant immunity.


[Right hemisphere syndrome in children: functional and maturity correlation of non-verbal learning disabilities].
This review presents the maturational model of the right hemisphere syndrome in children, its clinical manifestations and its relationship with non-verbal learning disabilities. The white matter model proposed by Rourke is presented and the clinical symptoms that are generally associated with right hemisphere dysfunction, independent of which hemisphere is affected, are highlighted. It has been proposed that the right hemisphere have proportionally more white matter than the left hemisphere which implies different adaptation processes for each one after brain lesions. There are different factors that determine these results: brain plasticity acts in different ways in each hemisphere; early brain injuries, affect specially right hemispheric functioning in its abilities to be in charge of new material processing and building new schemes that are also used by the left hemisphere. Some pathologies that are related with the clinical manifestations of non-verbal learning disabilities are presented. According with this model, they display basic neuropsychological features, even though their clinical manifestations could change between them. The Attention Deficit Hyperactivity disorder is specially considered as the most recent evidence of right hemispheric dysfunction, although results in this pathology are controversial, from the neuropsychological point of view. In general, the right hemisphere lesion in children has different implications when it is compared with adult's lesions. The white matter model could explain different processes in the plasticity brain mechanism. Preservation of basic language aspects is observed, but a deficit in non-verbal abilities that interferes with normal functioning is a rule. A specific clinical profile of assets and deficits is presented in most of the cases. These characteristics should be considered in treatment implementations.


[Frugivory and seed dispersal Oenocarpus bataua palm (Arecaceae) in a forest from the Colombian Andes].
Seed dispersal is a key process that determines the spatial structure and dynamics of populations of plants, establishes the potential area of recruitment and in this way, the basis for subsequent processes such as predation, germination, competition and growth. The purpose of this research was to identify the guild of frugivores of the Oenocapus bataua palm in fragments of Andean forest, determine the effective dispersers and relate the spatial distribution of palm populations with the dispersion of seeds. To this end, between August 2005-June 2006, observations of the removal of fruits from eight clusters were done, and counting of consumption of fruits beneath 78 palms with mature fruits was undertaken; focal observations of 13 individuals during 90 hours; registration of frugivory with photographic traps during 165 days/nights for a total of 195 photographs and 144 consumption events; experiments with dispersion using 751 perforated fruits/seeds attached to strings and finally, plots to determine spatial distribution all were carried out. In the study area at least five species of mammals ate, dispersed, buried (Sciurus granatensis, Microsciurus mimulus, Dasyprocta punctata y Proechimys sp.), cover (Marmosa robinsoni) and carried the fruits of O. bataua off to caves (Marmosa robinsoni y Proechimys sp.) without damaging the seed. A 21.7% of the fruits were dispersed, 13.2 gnawed or peeled, 5.6% covered, buried and carried to caves. The average distance of removal of seeds and fruits was 3.1m although in a lesser proportion, dispersion events of >50m were recorded. The abundant production of fruits, their size and weight, their intense removal by frugivores, the short dispersion distances, the absence of large size frugivores (reduced by hunting and fragmentation), that might perform long-distance dispersion, and the increase of rodents, especially squirrels, that strongly pressure the fruit resource, generate a spatially restricted seed rain of seeds responsible for the aggregate patterns of distribution of seeds, seedlings and subsequently of juveniles and sub-adults. However the short time and high percentage of seed germination and the robustness of seeds and seedlings give O. bataua the capacity to survive in dense aggregations. Therefore, despite the limitations on dispersion, this is a dominant species in the study area. Populations of O. bataua have been reduced by intense exploitation and by the transformation and reduction of their natural habitat. The over-exploitation of the fruits or the juvenile phases of this palm can affect the age structure and population dynamics. Therefore, the management and exploitation of this palm in the future will depend to large degree on the conservation of forest habitats.


Provider perspective on the role of palliative care in hypoplastic left heart syndrome.
Hypoplastic left heart syndrome is a single ventricle defect. While staged surgical palliative treatments have revolutionised care, patients with hypoplastic left heart syndrome continue to have significant morbidity and mortality. In 2017, the National Pediatric Cardiology Quality Improvement Collaborative recommended all single ventricle patients to receive a prenatal palliative care consult. This study aimed to elucidate provider perspectives on the implementation of prenatal palliative care consults for families expecting a child with hypoplastic left heart syndrome. An online survey was administered to obstetric and paediatric providers of relevant disciplines to assess their experience with palliative care involvement in hypoplastic left heart syndrome cases. Nearly, all physicians (97%) and most registered nurses (79%) agreed that the initial palliative care consult for patients with hypoplastic left heart syndrome should occur during the prenatal period. Respondents also indicated that prenatal palliative care consults should also be offered in a variety of other CHD conditions. Participants believed positive aspects of this new referral protocol included an expanded support network for families, decreased family stress during the postnatal period, increased patient education about what to expect during the postnatal period, and continuity of care. Multidisciplinary healthcare professionals believe that prenatal palliative care consults provide a variety of benefits for patients and families with hypoplastic left heart syndrome. Additional, multi-centre research is necessary to evaluate whether prenatal palliative care consults should become standard of care for families expecting a child with a single ventricle defect.


Standard smoking cessation services in sites participating in the SCIMITAR+ trial for people with severe mental ill health.
Aims and methodThe SCIMITAR+ trial was commissioned to evaluate the effectiveness of a bespoke smoking cessation intervention for people with severe mental ill health compared with usual services. It is difficult to define what constitutes usual care in smoking cessation services. We aimed to define what this was during the trial. Twenty-two National Health Service healthcare providers participated in a bespoke survey asking about usual care in their area. RESULTS: All sites offered smoking cessation support; however, service provider and service type varied substantially. In some cases services were not streamlined, meaning that people received smoking cessation counselling from one organisation and smoking cessation medication from another.Clinical implicationsTo better implement the National Institute for Health and Care Excellence guideline PH48, clearer referral pathways need to be implemented and communicated to patients, staff and carers. People with severe mental ill health need to be able to access services that combine nicotine replacement therapy and behavioural support in a streamlined manner.Declaration of interestNone.


Virally-vectored vaccine candidates against white-nose syndrome induce anti-fungal immune response in little brown bats (Myotis lucifugus).
White-nose syndrome (WNS) caused by the fungus, Pseudogymnoascus destructans (Pd) has killed millions of North American hibernating bats. Currently, methods to prevent the disease are limited. We conducted two trials to assess potential WNS vaccine candidates in wild-caught Myotis lucifugus. In a pilot study, we immunized bats with one of four vaccine treatments or phosphate-buffered saline (PBS) as a control and challenged them with Pd upon transfer into hibernation chambers. Bats in one vaccine-treated group, that received raccoon poxviruses (RCN) expressing Pd calnexin (CAL) and serine protease (SP), developed WNS at a lower rate (1/10) than other treatments combined (14/23), although samples sizes were small. The results of a second similar trial provided additional support for this observation. Bats vaccinated orally or by injection with RCN-CAL and RCN-SP survived Pd challenge at a significantly higher rate (P = 0.01) than controls. Using RT-PCR and flow cytometry, combined with fluorescent in situ hybridization, we determined that expression of IFN-γ transcripts and the number of CD4 + T-helper cells transcribing this gene were elevated (P < 0.10) in stimulated lymphocytes from surviving vaccinees (n = 15) compared to controls (n = 3). We conclude that vaccination with virally-vectored Pd antigens induced antifungal immunity that could potentially protect bats against WNS.


Fallopian Tube Sperm Perfusion in Treatment of Nontubal Subfertility: Is It Crucial Step prior to ART?
Objective. To evaluate the efficacy of double Fallopian tube sperm perfusion in comparison with single-sperm perfusion in patients with nontubal subfertility undergoing controlled ovarian stimulation. Study Design. Sixty-six patients undergoing standard ovarian stimulation regimen were randomized to receive either single-sperm perfusion group 1 (n = 33) or double-sperm perfusion group 2 (n = 33). The same insemination method was performed in subsequent cycles if the patient does not become pregnant in the first one. A maximum of three cycles was performed. Fallopian tube sperm perfusion was carried out with pediatric Foleys catheter, which prevents reflux of sperm suspension. Semen was prepared by a classical swim-up technique. Results. A total of 133 cycles performed 68 single FSP cycles and 65 FSP cycles. There were group, 19 clinical pregnancies (29.2% per cycle) of which 16 ongoing pregnancies (24.6% per cycle) were obtained. These differences were statistically significant. The prevalence of multiple pregnancies, abortions, and ectopic pregnancies was similar in both groups. Conclusion. The results of this study indicate that there is a significant improvement of pregnancy rates in patients with nontubal subfertility when treated with double-sperm perfusion after controlled ovarian stimulation in comparison with single-sperm perfusion. Double-sperm perfusion is simple, easy to perform, inexpensive, and convenient for the patients with nontubal subfertility before adoption of other methods of assisted reproduction.


Toxic effects of polyethylene terephthalate microparticles and Di(2-ethylhexyl)phthalate on the calanoid copepod, Parvocalanus crassirostris.
Large amounts of plastic end up in the oceans every year where they fragment into microplastics over time. During this process, microplastics and their associated plasticizers become available for ingestion by different organisms. This study assessed the effects of microplastics (Polyethylene terephthalate; PET) and one plasticizer (Di(2-ethylhexyl)phthalate; DEHP) on mortality, productivity, population sizes and gene expression of the calanoid copepod Parvocalanus crassirostris. Copepods were exposed to DEHP for 48h to assess toxicity. Adults were very healthy following chemical exposure (up to 5120µg L-1), whereas nauplii were severely affected at very low concentrations (48h LC50value of 1.04 ng L-1). Adults exposed to sub-lethal concentrations of DEHP (0.1-0.3µg L-1) or microplastics (10,000-80,000 particles mL-1) exhibited substantial reductions in egg production. Populations were exposed to either microplastics or DEHP for 6 days with 18 days of recovery or for 24 days. Populations exposed to microplastics for 24 days significantly depleted in population size (60±4.1%, p<0.001) relative to controls, whilst populations exposed for only 6 days (with 18 days of recovery) experienced less severe depletions (75±6.0% of control, p<0.05). Populations exposed to DEHP, however, exhibited no recovery and both treatments (6 and 24 days) yielded the same average population size at the termination of the experiment (59±4.9% and 59±3.4% compared to control; p<0.001). These results suggest that DEHP may induce reproductive disorders that can be inherited by subsequent generations. Histone 3 (H3) was significantly (p<0.05) upregulated in both plastic and DEHP treatments after 6 days of exposure, but not after 18 days of recovery. Hsp70-like expression showed to be unresponsive to either DEHP or microplastic exposure. Clearly, microplastics and plasticizers pose a serious threat to zooplankton and potentially to higher trophic levels.


Dengue, Japanese encephalitis and Chikungunya virus antibody prevalence among captive monkey (Macaca nemestrina) colonies of Northern Thailand.
The potential of macaque Macaca nemestrina leonina in Thailand to be infected by endemic arboviruses was assessed. The prevalence of antibodies of three arboviruses actively circulating in Thailand was determined by Plaque Reduction Neutralization assay procedures using samples from captive colonies in Northern Thailand. Out of 38 macaques, 9 (24%) presented reacting antibodies against dengue virus, 5 (13%) against Japanese encephalitis virus, and 4 (10%) against Chikungunya virus. Our results indicate that the northern pig-tailed macaque in Thailand can be infected by these arboviruses, inferring therefore that their virus specific vectors have bitten them. Given that, northern pig-tailed macaque represents an abundant population, living in close range to human or in peridomestic setting, they could play a role as potential reservoir host for arboviruses circulating in Thailand.


Developmental expression of latent transforming growth factor beta binding protein 2 and its requirement early in mouse development.
Latent transforming growth factor beta (TGF-beta) binding protein 2 (LTBP-2) is an integral component of elastin-containing microfibrils. We studied the expression of LTBP-2 in the developing mouse and rat by in situ hybridization, using tropoelastin expression as a marker of tissues participating in elastic fiber formation. LTBP-2 colocalized with tropoelastin within the perichondrium, lung, dermis, large arterial vessels, epicardium, pericardium, and heart valves at various stages of rodent embryonic development. Both LTBP-2 and tropoelastin expression were seen throughout the lung parenchyma and within the cortex of the spleen in the young adult mouse. In the testes, LTBP-2 expression was seen within lumenal cells of the epididymis in the absence of tropoelastin. Collectively, these results imply that LTBP-2 plays a structural role within elastic fibers in most cases. To investigate its importance in development, mice with a targeted disruption of the Ltbp2 gene were generated. Ltbp2(-/-) mice die between embryonic day 3.5 (E3.5) and E6.5. LTBP-2 expression was not detected by in situ hybridization in E6.5 embryos but was detected in E3.5 blastocysts by reverse transcription-PCR. These results are not consistent with the phenotypes of TGF-beta knockout mice or mice with knockouts of other elastic fiber proteins, implying that LTBP-2 performs a yet undiscovered function in early development, perhaps in implantation.


Neuropeptidergic regulation of affiliative behavior and social bonding in animals.
Social relationships are essential for maintaining human mental health, yet little is known about the brain mechanisms involved in the development and maintenance of social bonds. Animal models are powerful tools for investigating the neurobiological mechanisms regulating the cognitive processes leading to the development of social relationships and for potentially extending our understanding of the human condition. In this review, we discuss the roles of the neuropeptides oxytocin and vasopressin in the regulation of social bonding as well as related social behaviors which culminate in the formation of social relationships in animal models. The formation of social bonds is a hierarchical process involving social motivation and approach, the processing of social stimuli and formation of social memories, and the social attachment itself. Oxytocin and vasopressin have been implicated in each of these processes. Specifically, these peptides facilitate social affiliation and parental nurturing behavior, are essential for social recognition in rodents, and are involved in the formation of selective mother-infant bonds in sheep and pair bonds in monogamous voles. The convergence of evidence from these animal studies makes oxytocin and vasopressin attractive candidates for the neural modulation of human social relationships as well as potential therapeutic targets for the treatment of psychiatric disorders associated with disruptions in social behavior, including autism.


Impact of Climate Change on Health and Well-Being of People in Hindu Kush Himalayan Region: A Narrative Review.
Climate change and variability affect virtually everyone and every region of the world but the effects are nowhere more prominent than in mountain regions and people living therein. The Hindu Kush Himalayan (HKH) region is a vast expanse encompassing 18% of the world's mountainous area. Sprawling over 4.3 million km2, the HKH region occupies areas of eight countries namely Nepal, Bhutan, Afghanistan, Bangladesh, China, India, Myanmar, and Pakistan. The HKH region is warming at a rate higher than the global average and precipitation has also increased significantly over the last 6 decades along with increased frequency and intensity of some extreme events. Changes in temperature and precipitation have affected and will like to affect the climate-dependent sectors such as hydrology, agriculture, biodiversity, and human health. This paper aims to document how climate change has impacted and will impact, health and well-being of the people in the HKH region and offers adaptation and mitigation measures to reduce the impacts of climate change on health and well-being of the people. In the HKH region, climate change boosts infectious diseases, non-communicable diseases (NCDs), malnutrition, and injuries. Hence, climate change adaptation and mitigation measures are needed urgently to safeguard vulnerable populations residing in the HKH region.


Regional variations in the extent and pattern of grey matter demyelination in multiple sclerosis: a comparison between the cerebral cortex, cerebellar cortex, deep grey matter nuclei and the spinal cord.
Substantial grey matter (GM) demyelination occurs in both the cerebral cortex and spinal cord in multiple sclerosis (MS). GM demyelination also occurs in the cerebellar cortex and the deep GM nuclei of the brain. However, no study has made a direct "within subject" comparison of the extent of GM pathology between these regions. To examine the extent and pattern of GM demyelination in the motor cortex, cingulate gyrus, cerebellum, thalamus and spinal cord in MS. Postmortem study using material from 14 MS cases and three controls. Sections were taken from the five predetermined areas and stained for proteolipid protein. The extent of GM and white matter (WM) demyelination was assessed in each region. Overall, 28.8% of the GM was demyelinated compared with 15.6% of the WM (p<0.001), with demyelination being greater in the GM than in the WM at each of the anatomical sites. There was substantial variation in the extent of demyelination between the different CNS regions. GM demyelination was most extensive in the spinal cord and cerebellum while WM demyelination was most prominent in the spinal cord.


Histopathology of Veins Obtained at Hemodialysis Arteriovenous Fistula Creation Surgery.
Stenosis from venous neointimal hyperplasia is common in native arteriovenous fistulas (AVFs). However, the preexisting histologic characteristics of veins at fistula creation, and associations thereof with baseline patient factors, have not been well characterized. In this study, we conducted histologic analysis of a segment of the vein used for anastomosis creation, obtained during AVF creation from 554 of the 602 participants in the multicenter Hemodialysis Fistula Maturation Cohort Study. We quantified intimal and medial areas and lengths of the internal and external elastic lamina by morphometry and assessed venous wall cells by immunohistochemistry, extracellular matrix with Movat stain, and calcium deposition by alizarin red stain. We also studied a representative subset of veins for markers of monocyte/macrophage content, cell proliferation, apoptosis, and neoangiogenesis. Neointima occupied >20% of the lumen in 57% of fully circumferential vein samples, and neointimal hyperplasia associated positively with age and inversely with black race. The neointima was usually irregularly thickened, sometimes concentric, and contained α-smooth muscle actin-expressing cells of smooth muscle or myofibroblast origin. Proteoglycans admixed with lesser amounts of collagen constituted the predominant matrix in the neointima. In 82% of vein samples, the media of vessel walls contained large aggregates of collagen. A minority of veins expressed markers of inflammation, cell proliferation, cell death, calcification, or neoangiogenesis. In conclusion, we observed preexisting abnormalities, including neointimal hyperplasia and prominent accumulation of extracellular matrix, in veins used for AVF creation from a substantial proportion of this cohort.


Relationship between model for end-stage liver disease score and 30-day outcomes for patients undergoing elective colorectal resections: an American college of surgeons-national surgical quality improvement program study.
Patients with liver disease face significant risk of complications and death when considering elective colorectal resection for benign or malignant indications. We sought to determine the relationship between Model of End-Stage Liver Disease score and 30-day outcomes in patients undergoing elective colorectal resections. This was a retrospective cohort study. The study included hospitals participating in the National Surgical Quality Improvement Program. Adult patients who underwent elective colorectal resection from 2005 to 2011 were identified from the National Surgical Quality Improvement Program database. Patients missing laboratory values necessary to calculate the Model of End-Stage Liver Disease score were excluded (61% of 81,346 patients identified). Differences in patient- and disease-related characteristics by Model of End-Stage Liver Disease categories were assessed with χ analyses. Thirty-day mortality and major morbidity were examined using logistic regression. Of 31,950 patients undergoing elective colorectal resections (14% including proctectomy), most (60%) were performed for colon or rectal cancer; other benign indications included diverticulitis (20%), polyp (10%), and IBD (10%). A total of 58% of patients had a Model of End-Stage Liver Disease score of ≥7. Increasing scores were associated with older age; higher BMI; higher ASA class; lower albumin level; and higher incidence of diabetes mellitus, pulmonary and cardiac disease, hypertension, and dependent functional status. In univariate analysis, patients with higher scores had a greater risk of 30-day mortality (score = 6 (0.69%); 7-11 (1.62%); 11-15 (4.52%); >15, (5.01%); p < 0.0001). After controlling for other comorbidities, Model of End-Stage Liver Disease score remained a significant predictor of 30-day mortality, major complications, and respiratory complications. This was a retrospective analysis of administrative data, limiting some access to clinically relevant data. Consistent with previous reports, patients with higher Model of End-Stage Liver Disease scores have a significantly higher risk of death and major morbidity in the 30 days after elective colorectal resection (see Video, Supplemental Digital Content, http://links.lww.com/DCR/A180).


Comparison of Sepsis-1, 2 and 3 for Predicting Mortality in Septic Patients of a Middle-Income Country: A Retrospective Observational Cohort Study.
The diagnosis of sepsis is based on expert consensus and does not yet have a "gold standard." With the aim of improving and standardizing diagnostic methods, there have already been three major consensuses on the subject. However, there are still few studies in middle-income countries comparing the methods. This study describes the characteristics of patients diagnosed with sepsis and evaluates and compares the performance of Sepsis-1, 2, and 3 criteria in predicting 28 days, and in-hospital mortality. A retrospective observational cohort study was conducted in the intensive care unit of a tertiary hospital. All admissions between January 1, 2018, and December 31, 2019, were reviewed. Patients diagnosed with sepsis were included. During the study period, 653 patients diagnosed with sepsis (by any of the studied criteria) were included in the study. The 28 days mortality rate was 45.8%, and the in-hospital mortality rate was 59.7%. We observed that 72.1% of patients met the minimum criteria for diagnosing sepsis according to the three protocols, and this group also had the highest mortality rate. Age and comorbidities such as cancer and liver cirrhosis were significantly associated with in-hospital mortality. The most common microorganisms were Escherichia coli, Klebsiella spp., and Staphylococcus spp. The study found that most patients met the diagnostic criteria for sepsis using the three methods. Sepsis-2 showed greater sensitivity to predict mortality, while Sequential Organ Failure Assessment showed low accuracy, but was the only significant one. Furthermore, quick Sequential Organ Failure Assessment (qSOFA) had the highest specificity for mortality. Overall, these findings suggest that, although all three methods contribute to the diagnosis and prognosis of sepsis, Sepsis-2 is particularly sensitive in predicting mortality. Sepsis-3 shows some accuracy but requires improvement, and qSOFA exhibits the highest specificity. More research is needed to improve predictive capabilities and patient outcomes.


mROS‑calcium feedback loop promotes lethal ventricular arrhythmias and sudden cardiac death in early myocardial ischemia.
Lethal ventricular arrhythmia‑sudden cardiac death (LVA‑SCD) occurs frequently during the early stage of myocardial ischemia (MI). However, the mechanism underlying higher LVA‑SCD incidence is still poorly understood. The present study aimed to explore the role of mitochondrial reactive oxygen species (mROS) and Ca2+ crosstalk in promoting LVA‑SCD in early MI. RyR2 S2814A mice and their wild‑type littermates were used. MitoTEMPO was applied to scavenge mitochondrial ROS (mROS). Mice were subjected to severe MI and the occurrence of LVA‑SCD was evaluated. Levels of mitochondrial ROS and calcium (mitoCa2+), cytosolic ROS (cytoROS), and calcium (cytoCa2+), RyR2 Ser‑2814 phosphorylation, CaMKII Met‑282 oxidation, mitochondrial membrane potential (MMP), and glutathione/oxidized glutathione (GSH/GSSG) ratio in the myocardia were detected. Dynamic changes in mROS after hypoxia were investigated using H9c2 cells. Moreover, the myocardial phosphoproteome was analyzed to explore the related mechanisms facilitating mROS‑Ca2+ crosstalk and LVA‑SCD. There was a high incidence (~33.9%) of LVA‑SCD in early MI. Mice who underwent SCD displayed notably elevated levels of myocardial ROS and mROS, and the latter was validated in H9c2 cells. These mice also demonstrated overloads of cytoplasmic and mitochondrial Ca2+, decreased MMP and reduced GSH/GSSG ratio, upregulated RyR2‑S2814 phosphorylation and CaMKII‑M282 oxidation and transient hyperphosphorylation of mitochondrial proteomes in the myocardium. mROS‑specific scavenging by a mitochondria‑targeted antioxidant agent (MitoTEMPO) corrected these SCD‑induced alterations. S2814A mice with a genetically inactivated CaMKII phosphorylation site in RyR2 exhibited decreased overloads in cytoplasmic and mitochondrial Ca2+ and demonstrated similar effects as MitoTEMPO to correct SCD‑induced changes and prevent SCD post‑MI. The data confirmed crosstalk between mROS and Ca2+ in promoting LVA‑SCD. Therefore, we provided evidence that there is a higher incidence of LVA‑SCD in early MI, which may be attributed to a positive feedback loop between mROS and Ca2+ imbalance.


Future environmental challenges of the urban protected area Great War Island (Belgrade, Serbia) based on valuation of the pollution status and ecosystem services.
The Great War Island (GWI) is an area of importance for the protection of the environment, cultural and historical heritage of Belgrade, Serbia. According to the International Union for Conservation of Nature (IUCN) this area belongs to the IV category - Habitats and Other Regulated Areas. The main objectives of this paper are to evaluate the potential impacts of pollution on ecosystem services of the Great War Island and to explore different scenarios for future urban development of the Great War Island that will have implication for human well-being. The aims of this paper are set up based on the evaluation of ecosystem services of the Great War Island and assessment of the pollution status of the Great War Island. In order to evaluate pollution status of the GWI inorganic and organic composition of sediments were examined. Additionally, the content of microelements was determined in the leaves of the Salix alba L. Pollution indices indicate that all investigated sampling sites are polluted and correspond to high and very high degree of contamination. Cd and Cu show high to extremely high degree of contamination while Sb has extremely high degree of contamination. Content of As, Co, Cu, Ni and Zn in leaves of Salix alba L. is in sufficient to normal range, while content of Cd is between the sufficient and excessive values generalized for various species. Typical oil distributions of terpanes and steranes and values of the corresponding maturity parameters clearly indicated that the sediments of the GWI, in addition to native organic matter, contained oil pollutants of anthropogenic origin. GWI provides provisioning, regulating, supporting and cultural ecosystem services. In relation to ecosystem services two possible scenarios can be predicted: first - losing the status of a protected area due to urbanization; and the second - increasing the degree of protection by admission into international protection lists.


The repair process of osteonecrosis after a transtrochanteric rotational osteotomy.
Many studies have reported the factors influencing the progression of collapse and development of osteoarthritis after a transtrochanteric rotational osteotomy. It is not well understood how the healing process of the osteonecrotic area occurs after this procedure. We evaluated (1) the osteonecrotic area after a successful transtrochanteric rotational osteotomy radiographically; and (2) determined whether specific perioperative clinical and radiographic factors related to the difference(s) in the healing process after a transtrochanteric rotational osteotomy. We retrospectively reviewed 64 patients (70 hips) among 402 patients (507 hips) who had a transtrochanteric rotational osteotomy between 1981 and 1996 and showed no evidence of progression of collapse or joint space narrowing at 10 years after the osteotomy. Forty-eight hips (45 patients) were males and 22 (19 patients) were females, with a mean age of 37 years (range, 12-57 years) at the time of surgery. An anterior rotational osteotomy was performed for 57 hips and a posterior rotational osteotomy was performed for 13 hips. We recorded various perioperative factors potentially influencing repair and assessed the radiographs at last followup for various features indicating repair. Ten years after the transtrochanteric rotational osteotomy, the osteonecrotic area in 50 hips (71%) had osteosclerotic changes radiographically (Group I), while 20 hips (29%) had normal bony architecture without sclerotic changes (Group II). We observed no difference between Groups I and II with regard to the age, gender, use of corticosteroids, etiology, and radiographic stage. Although the reason for this difference in the healing patterns remains unknown, this study indicates the majority of the hips showed osteosclerosis after a transtrochanteric rotational osteotomy, while approximately 30% of the hips showed a normal bony architecture.


Collaborative investigation of the accuracy and reproducibility of Sceptor Breakpoint susceptibility panels.
A combination Sceptor Breakpoint/ID panel (Johnston Laboratories, Inc., Towson, Md.), which determines interpretive susceptibility results (susceptible, moderately susceptible, and resistant) using two to three selected concentrations of antimicrobial agents, was tested in comparison with full-range Sceptor microdilution MIC panels. The inter- and intralaboratory interpretive reproducibilities for 24 control strains tested in three laboratories on three consecutive days were 97.0 and 95.7%, respectively. The equivalency of breakpoint results to category results obtained by the microdilution MIC procedure for 10,368 control organism-antimicrobial agent comparisons was 94.1%. The level of interpretive agreement between breakpoint and MIC category results using 101 fresh clinical isolates was 97.0% for 51 gram-negative and 50 gram-positive bacteria. Among the total 4,872 clinical organism-antimicrobial agent comparisons, major and very major discrepancies were seen in 0.2% of gram-negative bacteria and very major discrepancies were seen in 0.9% of gram-positive bacteria. All very major discrepancies with gram-positive organisms were associated with trailing endpoints using trimethoprim or sulfisoxazole and staphylococci. The breakpoint concept of testing selective antimicrobial agent concentrations was highly reproducible and accurate and allows for placement of more antimicrobial agents into a panel than is possible with full-dilution MIC testing.


Progressive external ophthalmoplegia - A case report.
Progressive external ophthalmoplegia is a slowly progressive hereditary mitochondrial myopathy. Most mitochondrial disorders overlap clinically, enzymatically, and genetically. The most common enzyme defect is the combined deficit of complexes I and IV. Progressive external ophthalmoplegia particularly affects the extraocular muscles and is characterised by ophthalmoplegia, and bilateral ptosis. The ptosis and ophthalmoplegia is unresponsive to anticholinergics, with no effective treatment, but corrective surgery for ptosis as a palliative one. In this article, we report a rare case of a 16-year-old female with characterstic histological features consistent with progressive external ophthalmoplegia.


The effect of femoral nerve block on fracture healing via expressions of growth factors and β-catenin.
Many patients of all ages are admitted to hospital due to bone fractures. The etiology of fracture has a very wide spectrum, ranging from motor accidents to pathological conditions such as tumors, osteoporosis, and others. Bone fracture healing is a well-programmed and well-organized process, but is also long and intractable. The outcome of this process is therefore affected by many factors, such as the patient's age, ethnicity, nutritional status, and extent of the fracture. At present, regional analgesic techniques are frequently applied in order to avoid the complications of systemic opioid administration, central block applications. Femoral block is one of the regional analgesic techniques frequently applied by anesthesiologists when the lower extremities are involved. In this study, we evaluated the effect of femoral nerve block on the healing of an experimental non-stabilized femur fracture via expression of TGF-β, VEGF, and β-catenin and bone histomorphometry in rats. In the control group, only the femoral fracture was performed and the bone was not fixated, similarly as in other groups. In the One-Day Block group, a one-time femoral nerve block was applied after the femoral fracture. In the Three-Day Block group, a daily femoral nerve block was performed for three days after the femoral fracture. On Days 4, 7, and 13, femurs were excised. The bone sections were stained with hematoxylin-eosin to evaluate bone tissue and Safranin O to assess callus tissue, cartilaginous tissue, and new bone areas. TGF-β, VEGF, and β-catenin were assessed by immunohistochemistry. Histomorphometric analysis revealed that femoral block application had a positive impact on bone healing. TGF-β expression in the One-Day and Three-Day Block Groups was significantly higher than in the control group at all times, as was also the case with VEGF expression. On day 13, β-catenin expression was significantly higher in the Three-Day Block group than the others. The results of the study suggests that the applications of a femoral nerve block for perioperative analgesia, for either one day or three days, resulted in better and more rapid bone healing.


Development and Validation of a Daily Pain Catastrophizing Scale.
To date, there is no validated measure for pain catastrophizing at the daily level. The Pain Catastrophizing Scale (PCS) is widely used to measure trait pain catastrophizing. We sought to develop and validate a brief, daily version of the PCS for use in daily diary studies to facilitate research on mechanisms of catastrophizing treatment, individual differences in self-regulation, and to reveal the nuanced relationships between catastrophizing, correlates, and pain outcomes. After adapting the PCS for daily use, we evaluated the resulting 14 items using 3 rounds of cognitive interviews with 30 adults with chronic pain. We refined and tested the final daily PCS in 3 independent, prospective, cross-sectional, observational validation studies conducted in a combined total of 519 adults with chronic pain who completed online measures daily for 14 consecutive days. For study 1 (N = 131), exploratory factor analysis revealed adequate fit and-unexpectedly-unidimensionality for item responses to the daily PCS. Study 2 (N = 177) correlations indicated adequate association with related constructs (anger, anxiety, pain intensity, depression). Similarly, results for study 3 (N = 211) revealed expected correlations for daily PCS and measures of daily constructs including physical activity, sleep, energy level, and positive affect. Results from complex/multilevel confirmatory factor analysis confirmed good fit to a unidimensional model. Scores on the daily PCS were statistically comparable with and more parsimonious than the full 14-item version. Next steps include evaluation of score validity in populations with medical diagnoses, greater demographic diversity, and in patients with acute pain. This article describes the development and validation of a daily PCS. This daily measure may facilitate research that aims to characterize pain mechanisms, individual differences in self-regulation, adaptation, and nuanced relationships between catastrophizing, correlates, and pain outcomes.


[Role of the hypothalamus and pituitary gland in the development of pancreatic islet sensitivity to glucose in fetal rats].
Differences in the pattern of the development of three enzymes of the plasma membrane have been established. The activity of Na, K-ATPase progressively increases, that of adenylate cyclase decreases, whereas the activity of 5-nucleotidase undergoes only slight changes during embryogenesis. Differences between these enzymes were also found with respect to the development of their sensitivity to the regulatory effects of catecholamines. Adrenaline reactivity of adenylate cyclase may be detected already in embryogenesis; it is lower than that in definite muscle tissue increasing during further ontogenesis. Catecholamine reactivity was not found in Na, K-ATPase and 5-nucleotidase up to the 17th day of incubation of chick embryos. The effect of adrenalin was observed at later stages of ontogenesis, it may be initiated by exogeneous cAMP and protein kinase. At postembryonic stages, similarity in the behavior of these enzymes was found with respect to the presence and pattern of their reaction to adrenalin (stimulation), as well as with respect to temporal dynamics of the effect. The data obtained indicate the existence of close connections between these enzymes, which are realized in the sequence adrenoreceptor-adenylate cyclase-cAMP-protein kinase-effector proteins.


Chromatin-Remodeling Components of the BAF Complex Facilitate Reprogramming.
Reprogramming of somatic cells achieved by combination of the four transcription factors Oct4, Sox2, Klf4, and c-Myc has very low efficiency. To increase the reprogramming efficiency and better understand the process, we sought to identify factors that mediate reprogramming with higher efficiency. We established an assay to screen nuclear fractions from extracts of pluripotent mouse cells based on Oct4 reactivation. Using proteomics, we identified components of the ATP-dependent BAF chromatin-remodeling complex, which significantly increases reprogramming efficiency when used together with the four factors. The reprogrammed cells could transmit to the germline and exhibited pluripotency. Reprogramming remained highly efficient when c-Myc was not present but BAF components were overexpressed. BAF complex components mediate this effect by facilitating enhanced Oct4 binding to target promoters during reprogramming. Thus, somatic cell reprogramming using chromatin-remodeling molecules represents an efficient method of generating reprogrammed cells.


Population Genetics and Anastomosis Group's Geographical Distribution of Rhizoctonia solani Associated with Soybean.
Rhizoctonia solani is a species complex composed of many genetically diverse anastomosis groups (AG) and their subgroups. It causes economically important diseases of soybean worldwide. However, the global genetic diversity and distribution of R. solani AG associated with soybean are unknown to date. In this study, the global genetic diversity and distribution of AG associated with soybean were investigated based on rDNA-ITS sequences deposited in GenBank and published literature. The most prevalent AG, was AG-1 (40%), followed by AG-2 (19.13%), AG-4 (11.30%), AG-7 (10.43%), AG-11 (8.70%), AG-3 (5.22%) and AG-5 (3.48%). Most of the AG were reported from the USA and Brazil. Sequence analysis of internal transcribed spacers of ribosomal DNA separated AG associated with soybean into two distinct clades. Clade I corresponded to distinct subclades containing AG-2, AG-3, AG-5, AG-7 and AG-11. Clade II corresponded to subclades of AG-1 subgroups. Furthermore, AG and/or AG subgroups were in close proximity without corresponding to their geographical origin. Moreover, AG or AG subgroups within clade or subclades shared higher percentages of sequence similarities. The principal coordinate analysis also supported the phylogenetic and genetic diversity analyses. In conclusion, AG-1, AG-2, and AG-4 were the most prevalent AG in soybean. The clade or subclades corresponded to AG or AG subgroups and did not correspond to the AG's geographical origin. The information on global genetic diversity and distribution will be helpful if novel management measures are to be developed against soybean diseases caused by R. solani.


Results of the transsternal approach to cervicothoracic junction lesions.
Surgery for lesions involving the anterior column of the cervicothoracic junction is still challenging. The median transsternal approach provides a direct approach to this junction. The aim of this study was to present the results of cases operated using the median transsternal approach. There were 8 cases (7 males, 1 female) aged between 18-39 (mean 28.2) years. The compression to the spinal cord was secondary to trauma in 3 cases, infection in 3 cases, and tumor in 2 cases. Median sternotomy was performed from the right side in 6 cases, and the left side in 2 cases. 14 level corpectomies were performed in 8 cases. Reconstructions were performed using a fibula allograft in 6 cases, and an iliac autograft in 2 cases. The mean follow-up duration was 104 months. A progressive delayed kyphosis requiring posterior stabilization occurred in one case. Postoperative neurological evaluation revealed improvement in 6 cases, and no change in 2 cases. Median sternotomy is an appropriate and safe approach for selected cases with lesions involving the anterior column of the cervicothoracic junction. The sternal-splitting approach remains the best method for equal exposure of the anterior thoracic and cervical spine from C4 to Th4 vertebrae through a single incision.


Paravertebral Block for Inguinal Herniorrhaphy: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.
Paravertebral block (PVB) is a safe and effective anesthetic technique for thoracotomy and mastectomy. However, no systematic review or meta-analysis has focused on PVB for inguinal herniorrhaphy. Our study compares PVB with general anesthesia/systemic analgesia, neuraxial blocks, and other peripheral nerve blocks. We analyzed 14 randomized controlled trials from PubMed, MEDLINE, CENTRAL, EMBASE, and CINAHL up to February 2015, without language restriction, comparing PVB under sedation with general anesthesia/systematic analgesia (135 vs 133 patients), neuraxial blocks (191 vs 186 patients), and other peripheral nerve blocks (119 vs 117 patients). We investigated pain scores, consumption of postoperative analgesia, incidence of postoperative nausea and vomiting (PONV), length of hospital stay, postanesthesia care unit bypassing rate, time to perform blocks, intraoperative hemodynamics, and incidence of urinary retention. Joint hypothesis testing was adopted for pain and analgesics, PONV, and hemodynamic variables. All analyses were performed with RevMan 5.2.11 (Cochrane Collaboration, Copenhagen). Hartung-Knapp-Sidik-Jonkman method was used for post hoc testing. PVB reduced PONV (nausea: risk ratio [RR] = 0.22; 95% confidence interval [CI], 0.05-0.93; numbers needed to treat [NNT] = 4.5; I = 15% and vomiting: RR = 0.15; 95% CI, 0.03-0.76; NNT = 8.3; I = 0%) compared with general anesthesia/systematic analgesia (quality of evidence [QoE]: high). Compared with neuraxial blocks, PVB resulted in less postoperative nausea (RR = 0.34 [95% CI, 0.13-0.91], NNT = 8.3, I = 0%) and urinary retention (RR = 0.14 [95% CI, 0.05-0.42], NNT = 7.4, I = 0%) than neuraxial blocks (QoE: high). More time was needed to perform PVB than neuraxial blocks (standardized mean difference = 1.90 [95% CI, 0.02-3.77], I = 92%; mean difference = 5.33 minutes; QoE: moderate). However, the available data could not reject the null hypothesis of noninferiority on all pain scores and analgesic requirements for both PVB versus general anesthesia/systematic analgesia and PVB versus neuraxial blocks (QoE: low), as well as on hemodynamic outcomes for PVB versus neuraxial blocks (QoE: moderate). Our systematic review showed that PVB decreased postoperative pain scores and analgesic requirement as compared with ilioinguinal block and transversus abdominis plane block. This meta-analysis shows that PVB provides an anesthesia with fewer undesirable effects for inguinal herniorrhaphy. The choice between general anesthesia/systematic analgesia, neuraxial blocks, PVB, and other peripheral nerve blocks should be based on time available to perform the block and a complete coverage over the relevant structures by the blocks.


Parallel motion processing for the initiation of short-latency ocular following in humans.
With the scleral search coil technique, we recorded ocular following responses elicited by either grating or plaid pattern motions. Grating motion elicited tracking responses at short latencies ( approximately 85 msec). Type I plaid motion made by summing two orthogonal moving gratings elicited ocular following with identical short latencies. Trial-by-trial vector decomposition showed that plaid-driven responses were best predicted by a vector average of the component-driven responses. Similar results were found with micropatterns made of 16 Gabor patches with drifting carriers of two different orientations. "Unikinetic" plaids were constructed by summing a moving and stationary grating, with a 45 degrees orientation difference, so that component and pattern motion directions were separated by 45 degrees. Eye movements exhibited two components. Ocular following was first initiated in the grating motion direction, at ultra-short latency. A second component was initiated approximately 20 msec later, curving the responses toward the pattern motion direction. The later component was specifically, and independently, affected by both relative spatial frequency and contrast between component gratings. The early response components showed a much steeper contrast response function than the late component. These results suggest that initial ocular following is underpinned by parallel processing of component- and pattern-related velocities followed by an integrative stage that computes the two-dimensional surface motion.


Sumoylation at the host-pathogen interface.
Many viral proteins have been shown to be sumoylated with corresponding regulatory effects on their protein function, indicating that this host cell modification process is widely exploited by viral pathogens to control viral activity. In addition to using sumoylation to regulate their own proteins, several viral pathogens have been shown to modulate overall host sumoylation levels. Given the large number of cellular targets for SUMO addition and the breadth of critical cellular processes that are regulated via sumoylation, viral modulation of overall sumoylation presumably alters the cellular environment to ensure that it is favorable for viral reproduction and/or persistence. Like some viruses, certain bacterial plant pathogens also target the sumoylation system, usually decreasing sumoylation to disrupt host anti-pathogen responses. The recent demonstration that Listeria monocytogenes also disrupts host sumoylation, and that this is required for efficient infection, extends the plant pathogen observations to a human pathogen and suggests that pathogen modulation of host sumoylation may be more widespread than previously appreciated. This review will focus on recent aspects of how pathogens modulate the host sumoylation system and how this benefits the pathogen.


Invasive IPMN and MCN: same organ, different outcomes?
The efficacy of surgery for invasive mucinous neoplasms is unclear. We examined the natural history of invasive mucinous cystic neoplasms (MCN) and invasive intraductal papillary mucinous neoplasms (IPMN) in patients who underwent pancreatic resection. The Surveillance, Epidemiology, and End Results (SEER) database (1996-2006) was queried for cases of resected invasive MCN and IPMN. Demographics, tumor characteristics, and overall survival were examined using log-rank analysis and multivariate Cox regression model. Of 185 MCN cases and 641 IPMN cases, 73% and 48%, respectively, were women (P < 0.0001). Most (73%) IPMN were in the head of the pancreas; most (64%) MCN were in the tail/body (P < 0.0001). Lymph node metastasis was more common for IPMN than MCN (46% vs. 24%, P < 0.0001). Overall survival after resection was better for patients with stage I MCN vs. stage I IPMN (P = 0.0005), and it was better for patients with node-negative MCN vs. node-negative IPMN (P = 0.0061). There was no significant difference in survival of patients with stage IIA MCN vs. stage IIA IPMN (P = 0.5964), stage IIB MCN vs. stage IIB IPMN (P = 0.2262), or node-positive MCN vs. node-positive IPMN (P = 0.2263). Age older than 65 years (hazards ratio (HR) 1.71, P = 0.0046), high tumor grade (HR 2.68, P < 0.0001), higher T stage (HR 2.11, P < 0.0001), and IPMN histology (HR 1.90, P = 0.0040) predicted worse outcome in node-negative patients. Our findings suggest that survival is better after resection of invasive MCN versus invasive IPMN when disease is localized within the pancreas, but this difference disappears in the presence of nodal metastasis or extrapancreatic extension.


Emergency determination of decision-making capacity: balancing autonomy and beneficence in the emergency department.
The determination of decision-making capacity (DMC) is an essential component of securing voluntary informed consent, for either treatment or refusal of care. Decision-making capacity should be determined on some level during each patient encounter. Decision-making capacity includes the ability to receive, process, and understand information, the ability to deliberate, the ability to make choices, and the ability to communicate those preferences. For patients in whom DMC may be uncertain, a more explicit approach to determination of DMC is recommended. However, DMC determination must neither compromise patient safety nor delay needed care. When DMC determination is challenging, or when the ramifications of a decision are serious, the assistance of a third party (such as a surrogate, a consultant, or another clinician) may be valuable in discerning the most appropriate action. In addition to the obvious clinical utility of DMC assessment, the steps taken in the very establishment of DMC may promote patient trust, professionalism, and humanistic clinical practice. While DMC may be conditional, the compassion and respect we have for our patients must be unconditional.


Assessing sensory blockade with alcohol and pinprick after subarachnoid block.
The purpose of this study was to determine the accuracy of alcohol swabs in assessing dermatome levels in comparison to pinprick after subarachnoid block. Room temperature alcohol swabs and pinprick were used to determine dermatome levels at 5, 10, and 15 minutes after a 15-mg hyperbaric bupivacaine subarachnoid block was administered with the patient in the sitting position. The sample population consisted of 53 men scheduled for elective transurethral resection of the prostate or bladder tumor with an ASA classification of I to IV. Subjects were assessed while they were in the preoperative holding area for the ability to discriminate pinprick and cold sensation. Data were analyzed using the Wilcoxon signed rank test. There was a statistically significant difference between alcohol and pinprick at the 10- and 15-minute assessments. (P < .05).


Spatially co-registered wide-field nonlinear optical imaging of living and complex biosystems in a total internal reflection geometry.
Nonlinear optical microscopy that leverages an objective based total internal reflection (TIR) excitation scheme is an attractive means for rapid, wide-field imaging with enhanced surface sensitivity. Through select combinations of distinct modalities, one can, in principle, access complementary chemical and structural information for various chemical species near interfaces. Here, we report a successful implementation of such a wide-field nonlinear optical microscope system, which combines coherent anti-Stokes Raman scattering (CARS), two-photon fluorescence (TPF), second harmonic generation (SHG), and sum frequency generation (SFG) modalities on the same platform. The intense optical fields needed to drive these high order nonlinear optical processes are achieved through the use of femtosecond pulsed light in combination with the intrinsic field confinement induced by TIR over a large field of view. The performance of our multimodal microscope was first assessed through the experimental determination of its chemical fidelity, intensity and polarization dependences, and spatial resolution using a set of well-defined model systems. Subsequently, its unique capabilities were validated through imaging complex biological systems, including Hydrangea quercifolia pollen grains and Pantoea sp. YR343 bacterial cells. Specifically, the spatial distribution of different molecular groups in the former was visualized via vibrational contrast mechanisms of CARS, whereas co-registered TPF imaging allowed the identification of spatially localized intrinsic fluorophores. We further demonstrate the feasibility of our microscope for wide-field CARS imaging on live cells through independent characterization of cell viability using spatially co-registered TPF imaging. This approach to TIR enabled wide-field imaging is expected to provide new insights into bacterial strains and their interactions with other species in the rhizosphere in a time-resolved and chemically selective manner.


Diagnostic criteria for anorexia nervosa: looking ahead to DSM-V.
In considering possible revisions to the diagnostic criteria for anorexia nervosa (AN), questions can be raised regarding the 85% cutoff and consideration could be given to using a body mass index (BMI) score instead. The criterion most likely to change in the 4th ed. of the Diagnostic and Statistical Manual of Mental Disorders (Washington, DC: American Psychiatric Association) is the amenorrhea criterion because this does not appear to add to the diagnostic specificity.


The identification of Bacteroides ureolyticus from patients with non-gonococcal urethritis by conventional biochemical tests and by DNA and protein analyses.
Twenty-seven strains of gram-negative anaerobic bacteria isolated from patients with non-gonococcal urethritis (NGU-associated strains) were compared with reference strains of Bacteroides ureolyticus and representatives of other species of Bacteroides and Fusobacterium. Conventional biochemical tests, electrophoretic (PAGE) protein profiles and DNA base compositions of 29.5 +/- 1.2 mol% G + C indicated striking similarities between the NGU-associated strains and B. ureolyticus. Three of the reference strains previously assigned to that species were atypical in some respects as was one of the strains from urethritis and one strain, NCTC 10939, was incorrectly classified as B. ureolyticus. Casein hydrolysis by B. ureolyticus was the principal test difference between the two sets of strains. DNA-DNA hybridisation results of greater than or equal to 72% at optimum temperature conditions provided further evidence of the close relationship between B. ureolyticus and the NGU-associated strains and we conclude that these organisms should be identified as B. ureolyticus. There was insufficient evidence for recognising subspecies or biotypes within this revised concept of B. ureolyticus although several types (PAGE-type I, 17 strains; type II, 6 strains; type III, 3 strains) were detected which might provide the basis for future studies of hospital strains. The DNA base composition and hybridisation data indicated that B. ureolyticus was not related to other species of Bacteroides or Fusobacterium.


Chrysophanol inhibits endoplasmic reticulum stress in cerebral ischemia and reperfusion mice.
Endoplasmic reticulum (ER) stress plays a critical role in mediating ischemia/reperfusion (I/R) damage in the brain. Our previous study showed that Chrysophanol (CHR) alleviated cerebral ischemic injury in mice and nuclear factor-κB (NF-κB) involved in its neuroprotective effect, but the precise mechanism remains not fully understood. The present study investigated the effect of CHR treatment on I/R-induced ER stress. Mice were subjected to middle cerebral artery occlusion (MCAO) for 45min and received either vehicle or CHR (0.1mg/kg) for 14 days after reperfusion. Terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick end labeling (TUNEL) was used to detect apoptotic cells in penumbral tissue. The expression of ER stress-related factors including glucose-regulated protein 78 (GRP78), phosphorylated eukaryotic initiation factor 2α (p-eIF2α), CCAAT-enhancer-binding protein homologous protein (CHOP), and caspase-12 as well as inhibitory κB-α (IκB-α), the inhibitor of NF-κB, was assessed. Our results demonstrated that CHR treatment reduced MCAO-induced upregulation of GRP78, p-eIF2α, CHOP, and caspase-12 in the ischemic brain. Moreover, the TUNEL-positive neuronal cells, which were colocalized with CHOP and caspase-12, decreased in response to CHR treatment, indicating that CHR protects against I/R injury by inhibiting ER stress-associated neuronal apoptosis. In addition, CHR reversed the decrease in IκB-α level induced by MCAO, which was attributed at least in part to the attenuation of translational inhibition induced by eIF2α phosphorylation, indicating that CHR exerts anti-inflammatory effects following I/R by inhibiting ER stress response. These results suggest that attenuation of ER stress may be involved in the mechanisms of neuroprotective effects of CHR.


Evidence for distinct behaviour of phosphatidylcholine and sphingomyelin at the low density lipoprotein surface.
This study demonstrates that the use of high field 1H NMR spectroscopy permits individual detection of phosphatidylcholine and sphingomyelin molecules at the surface of native low density lipoprotein (LDL) particles. Distinct behaviour was observed for the choline head group -N(CH3)3 resonances of these different phospholipids revealing preferential immobilisation for phosphatidylcholine. This suggests the existence of reversible and irreversible phosphatidylcholine-apolipoprotein B interactions and is consistent with microdomain formation at the surface monolayer of LDL. The novel resonance assignment and results show that 1H NMR can provide efficient and practical means for future studies on the structure and dynamics at the LDL surface.


The cortisol response to anticipated intergroup interactions predicts self-reported prejudice.
While prejudice has often been shown to be rooted in experiences of threat, the biological underpinnings of this threat-prejudice association have received less research attention. The present experiment aims to test whether activations of the hypothalamus-pituitary-adrenal (HPA) axis, due to anticipated interactions with out-group members, predict self-reported prejudice. Moreover, we explore potential moderators of this relationship (i.e., interpersonal similarity; subtle vs. blatant prejudice). Participants anticipated an interaction with an out-group member who was similar or dissimilar to the self. To index HPA activation, cortisol responses to this event were measured. Then, subtle and blatant prejudices were measured via questionnaires. Findings indicated that only when people anticipated an interaction with an out-group member who was dissimilar to the self, their cortisol response to this event significantly predicted subtle (r = .50) and blatant (r = .53) prejudice. These findings indicate that prejudicial attitudes are linked to HPA-axis activity. Furthermore, when intergroup interactions are interpreted to be about individuals (and not so much about groups), experienced threat (or its biological substrate) is less likely to relate to prejudice. This conclusion is discussed in terms of recent insights from social neuroscience.


Development and characterisation of soluble polymeric particles for pulmonary peptide delivery.
Pulmonary administration of protein and peptide drugs using inhaled dry powder particles is an interesting alternative to parenteral delivery. The stabilisation of these molecules is essential to the maintenance of biological activity in such inhalation formulations. Here salmon calcitonin (sCT) was co-spray dried with linear or branched PEG (L-PEG and B-PEG) and PVP in order to formulate aerosolisable particles of the bioactive peptide. Co-spray drying L-PEG and PVP resulted in porous particles, with minimal D(50) (median volume diameter) and MMAD (mass median aerodynamic diameter) values obtained for a PEG/PVP w/w ratio of 1. For particles based on both L-PEG and B-PEG, an increase in acetone, a poor solvent for the PVP, up to 70wt% of the spray dried solution led to a decrease in D(50) and MMAD. Crystallinity of PEG in the particles ranged between 90 and 97% when the PVP content varied between 15 and 70wt%, indicating a low degree of interaction between PVP and PEG. Additionally, dynamic vapour sorption analysis showed that an increase in PVP content increased the particle surface hygroscopicity. Hence, particle properties were adjusted by altering the water/acetone and PEG/PVP ratio in the spray dried solutions. PVP present at the particles surface protects them from melting during the spray drying process but also increases their hygroscopicity, adversely affecting their aerodynamic properties. Targeting a 5wt% of sCT loading resulted in a loading efficiency of 77.9 and 83.6% with L-PEG and B-PEG-based particles, respectively. Loading of sCT in L-PEG or B-PEG-based particles modified particle roughness and D(50), leading to an increase in MMAD of the L-PEG-based particles. However, particles were still considered to be suitable for aerosolisation as their FPFs (fine particle fractions) were higher than 30%. These particles formulated with PVP and PEG allowed sCT biological activity to be maintained when evaluated by measuring cAMP production by T47D cells.


Combined Glaucoma Tube Shunt (Ahmed) and Fluocinolone Acetonide (Retisert™) Implantation Compared to Ahmed Alone in Uveitic Glaucoma.
Glaucoma is a known complication of uveitis, and may require glaucoma tube shunt implantation for intraocular pressure (IOP) control. The success of glaucoma tube shunt implantation in the setting of a local ocular steroid depot in uveitic glaucoma remains unknown. The purpose of this study was to determine whether patients who underwent combined glaucoma tube shunt (Ahmed) and fluocinolone acetonide (Retisert™, Bausch + Lomb, Bridgewater, NJ, USA) implantation have superior outcomes compared to patients with Ahmed implants only in the setting of uveitic glaucoma. All participants were studied retrospectively and underwent Ahmed implantation alone or with existing/concurrent Retisert implantation (combined group) at a single academic institution. The main outcome measures were IOP, visual acuity (VA), number of IOP-lowering medications, and adverse events at 6 months after Ahmed implantation. Secondary outcome measures included adverse events and surgical success at 6 months after Ahmed implantation. Mean IOP at 6 months after Ahmed implantation was 15.3 ± 4.8 and 15.1 ± 4.9 mm Hg in the Ahmed only group (n = 17) and the combined group (n = 17), respectively (p = 0.89). The mean number of IOP-lowering medications at 6 months after Ahmed implantation was 1.7 ± 1.0 and 1.8 ± 1.0 in the Ahmed only group and the combined group, respectively (p = 0.86). Mean VA at 6 months after Ahmed implantation was 0.35 ± 0.29 and 0.42 ± 0.33 log mean angle of resolution in the Ahmed only group and the combined group, respectively (p = 0.50). No significant differences in surgical success or adverse events were noted between the two groups. At 6 months, no significant differences in mean IOP, mean number of IOP-lowering medications, VA, surgical success, or adverse events were noted between Ahmed implantation alone or combined Ahmed and Retisert implantation in patients with uveitic glaucoma.


Multipathway of Nitrogen Metabolism Revealed by Genome-Centered Metatranscriptomics from Pyrite-Guided Mixotrophic Partial Denitrification/Anammox Installations.
Further reducing the organic requirements is essential for the sustainable development of partial denitrification/anammox technology. Here, an innovative mixotrophic partial denitrification/anammox (MPD/A) installation fed with pyrite and few organics was realized, and the average nitrogen and phosphorus removal rates were as high as 96.24 ± 0.11% and 79.23 ± 2.06%, respectively, with a C/N ratio of 0.5. To understand the nature by which MPD/A achieves efficient nitrogen removal and organic conservation, the electron transfer-dependent nitrogen escape and energy metabolism were first elucidated using multiomics analysis. Apart from heterotrophic denitrification and anammox, the results revealed some unexpected metabolic couplings of MPD/A systems, in particular, putative nitrate-dependent organic and pyrite oxidation among nominally heterotrophic Denitratisoma (PRO3) strains, which accelerated nitrate gasification with a low-carbon supply. Additionally, Candidatus Brocadia (AMX) employed extracellular solid-state electron acceptors as terminal electron sinks for high-rate ammonium removal. AMX transported ammonium electrons to extracellular γFeO(OH) (generated from pyrite oxidation) through the transient storage of menaquinoline pools, cytoplasmic migration via multiheme cytochrome(s), and OmpA protein/nanowires-mediated electron hopping on cell surfaces. Further investigation observed that extracellular electron flux resulted in the transfer of more energy from the increased oxidation of the electron donor to the ATP, supporting nitrite-independent ammonium removal.