The lower Saint Lawrence River region of Quebec, a hot spot for sheepfold-associated Q fever in Canada: Review of 258 cases.
The lower Saint Lawrence river region (LSLRR), in Quebec, has a 10-fold higher incidence of Q fever compared to the provincial rate. This study aimed to review clinical cases and the Q fever risk exposure in this region. Data were retrieved from microbiology laboratory, medical records from Rimouski Regional Hospital and Public Health reports between 1991 and 2018. They were analyzed with Epi Info 220.127.116.11. Patients with confirmed acute, probable acute, and chronic Q fever were classified using standard case definitions and mapped according to the postal code, to assess the correlation between cases and sheep distribution. Out of 295 cases, 258 were included (241 confirmed acute, seven probable acute, 10 chronic). Median age was 49 years, 76% were male. For acute cases, the prominent symptoms were fever (99%), headache (83%), chills (80%), sweating (72%), myalgia (69%), and fatigue (67%). Clinical presentation was mostly febrile syndrome with mild hepatitis (84%). A seasonal peak was observed from May to July (56% of acute cases). Most cases (56%) occurred within the two counties where sheep production was highest. Exposure to sheep was prominent 93%, including 64% direct contact (15% shepherds, 49% sheepfold visitors), 14% indirect contact, and 15% sheepfold neighbors. To our knowledge, this is one of the largest retrospective studies of Q fever cases reported in Canada. Q fever in Quebec LSLRR is associated mainly with sheep exposure. Fever and hepatitis were the most common manifestations. Preventive measures should be considered in this region to protect sheepfold workers, visitors, and their neighbors.


The concept of 'glomerulonephritis'. the fascinating history of evolution and emergence of a specialist's nosology focus on Italy and Torino.
Though the term 'nephritis' first appeared in the 19th century, this word did not bear the same meaning as it does today; indeed, for many years it was used to indicate 'renal diseases' (in the sense of Bright's disease) in a larger sense. This review summarizes the long gestation of the concept of 'glomerulonephritis' from the prehistory of medicine up to the beginning of the second half of the 20th century with emphasis on Italy and, in particular, on Torino, which was the capital of the Kingdom of Italy from 1861 to 1865. To the best of our kowledge, this is the first study reporting an epidemiology survey of Bright's disease in Italy from 1880 up to 1960. Towards the end of the 19th century, Bright's disease accounted for 26 deaths/year/10(5) population (in comparison with more than 200 from tuberculosis) in Italy, roughly paralleling that reported in the USA. At the beginning of the 20th century, Bright's disease was the seventh cause of death (almost 1% of total deaths) in Italy. Furthermore, in Italy, as elsewhere, autopsy studies showed a higher percentage of deaths attributed to Bright's disease (5-7%) in comparison with those obtained from vital statistics. In 1960, just before the beginning of renal replacement therapy, Bright's disease accounted for 15.7 deaths/year/10(5) population (= 1.46% of all deaths), roughly paralleling that reported in the United Kingdom (13.8/10(5) population = 1.25% of deaths). Probably, it was difficult to recognize the real incidence of chronic renal diseases leading to death in the 1960s, and vital statistics were able to furnish only approximate estimates. However, noteworthy is the fact that these values were very close to those estimated as being the annual need for renal replacement therapy (10-20 cases/year/10(5) population).


Theory of transmission of light by sub-wavelength cylindrical holes in metallic films.
This paper presents theory and finite-difference time-domain (FDTD) calculations for a single and arrays of sub-wavelength cylindrical holes in metallic films presenting large transmission. These calculations are in excellent agreement with experimental measurements. This effect has to be understood in terms of the properties exhibited by the dielectric constant of metals which cannot be treated as ideal metals for the purpose of transmission and diffraction of light. We discuss the cases of well-differentiated metals silver and tungsten. It is found that the effect of surface plasmons or other surface wave excitations due to a periodical set of holes or other roughness at the surface is marginal. The effect can enhance but also can depress the transmission of the arrays as shown by theory and experiments. The peak structure observed in experiments is a consequence of the interference of the wavefronts transmitted by each hole and is determined by the surface array period independently of the material. Without large transmission through a single hole there is no large transmission through the array. We found that in the case of Ag which at the discussed frequencies is a metal there are cylindrical plasmons at the wall of the hole, as reported by Economu et al 30 years ago, that enhanced the transmission. But it turns out, as will be explained, that for the case of W which behaves as a dielectric, there is also a large transmission when compared with that of an ideal metal waveguide at large wavelengths. To deal with this problem one has to use the measured dielectric function of the metals. We discuss thoroughly all these cases and compare with the data. We notice that to discuss these data, for a single hole's transmission, in terms of the Bethe approximation of ideal metals is misleading. Therefore, the extraordinary enhancement of the transmission for the holes arrays versus the single hole does not exist.


[Sebaceous carcinoma. Study of two cases].
A 94-year-old woman, who had had a chalazion for a period of 8 months, presented because of thickening of the eyelid with necrosis, madarosis and adenopathy. A 67-year-old woman, previously operated on for a sebaceous carcinoma, presented because of reddening of the conjunctiva and eyelid. Clinical evaluation revealed inflammation of the eyelid and an irregular and erythematous superior bulbar conjunctiva with disruption of the limbal architecture. A sebaceous carcinoma is a tumour which is difficult to diagnose and treat, because it can be patchy and has a tendency to pagetoid dissemination. Diagnosis requires a biopsy of the lesion and mapping of biopsies from the conjunctiva of the eyelid and eyebrow. The subsequent treatment depends on the extent of the tumour, and may involve simple cleavage, topical mitomycin C, radiotherapy or exenteration of the eyebrow.


Effect of a plant fortifier (Boundary) on pests and predators of greenhouse vegetable crops.
Boundary, a plant fortifier composed of extracts of Sophora flavescens Aiton and brown algae, was tested for control of the leaf miner Tuta absoluta (Meyrick) on tomato (three trials) and of the red spider mite Tetranychus urticae Koch on eggplant (one trial) and for side effects on the whitefly predator Macrolophus pygmaeus (Kambur) (two trials) on tomato and on the thrips predators Orius laevigatus (Fieber) and Amblyseius swirskii Athias-Henriot (two trials) on pepper, all in cold greenhouses in South Italy. Control rates for T. absoluta were moderate (40-70%) in the autumn crop but very high and comparable to those for emamectin benzoate in the spring crops (96-100%). Boundary compared well with abamectin against T. urticae, with near complete control. M. pygmaeus was moderately injured in late autumn, but not in early autumn. At the tested application rate and predator population density Boundary was safe for O. laevigatus and A. swirskii.


The gating of polycystin signaling complex.
Mutations in either polycystin-2 (PC2) or polycystin-1 (PC1) proteins cause severe, potentially lethal, kidney disorders (autosomal dominant polycystic kidney disease, ADPKD) and multiple extrarenal disease phenotypes. PC2, a member of the transient receptor potential channel superfamily and PC1, an orphan membrane receptor of largely unknown function, are thought to be part of a common signalling pathway. Here, I show that co-assembly of full-length PC with PC2 forms an ion channel signalling complex in which PCI regulates PC2 channel gating through a structural rearrangement of the polycystin complex (Delmas et al., 2004a). These polycystin complexes function either as a receptor-cation channel or as a G-protein-coupled receptor. Thus, PC acts as a prototypical membrane receptor that regulates G-proteins and plasmalemmal PC2, a bimodal mechanism that may account for the multifunctional roles of polycystin proteins in various cell types. Genetic alteration of polycystin proteins such as those occurring in kidney diseases may impede polycystin signalling, thereby providing a likely mechanistic explanation to the pathogenesis of ADPKD. Our proposed mechanism may also be paradigmatic for the function of polycystin orthologues and other polycystin-related proteins in a variety of nonrenal cell types, including sperm, muscle cells and sensory neurons.


Nek2-mediated GAS2L1 phosphorylation and centrosome-linker disassembly induce centrosome disjunction.
Centrosome disjunction occurs in late G2 to facilitate bipolar spindle formation and is mediated by the NIMA-related kinase Nek2. Here, we show that GAS2L1, a microtubule- and F-actin-binding protein required for centrosome disjunction, undergoes Nek2-mediated phosphorylation at Ser352 in G2/M. The phosphorylation is essential for centrosome disjunction in late G2 and for proper spindle assembly and faithful chromosome segregation in mitosis. GAS2L1 contains a calponin-homology (CH) domain and a GAS2-related (GAR) domain, which bind to F-actin and microtubules, respectively. Notably, the CH and GAR domains bind to each other to inhibit the functions of both domains, and Ser352 phosphorylation disrupts the interaction between the two domains and relieves the autoinhibition. We dissected the roles of the GAS2L1 phosphorylation and of centrosome-linker disassembly, which is another Nek2-mediated event, and found that these events together trigger centrosome disjunction. Therefore, our findings demonstrate the concerted Nek2 actions that split the centrosomes in late G2.


Matrix metalloproteinases and the activity of their tissue inhibitors in patients with ST-elevation myocardial infarction treated with primary angioplasty.
Matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) play a role in heart remodelling after acutemyocardial infarction (MI). Their activity is connected with outcome and heart failure development. There is little data on MMP and TIMP activity changes in the setting of ST elevation MI (STEMI) treated with primary percutaneous coronary intervention (pPCI). To assess the dynamics of activity of MMP-2 and MMP-9 and their endogenous inhibitors TIMP-1 and TIMP-2 in the course of invasive treatment of STEMI. The study included 95 patients (age 61.8 ± 12.4 years; 35 women) treated with pPCI with stent implantation due to 100% closure of the target vessel in a setting of STEMI. We measured the activity of MMP-2 and MMP-9 (by zymography,expressed with arbitrary units, AU), CK-MB (U/L), troponin I (ng/mL), TIMP-1, TIMP-2 (ng/mL) concentrations in a peripheral blood before the pPCI, immediately after and 3, 6, 12, 24 and 48 h after the procedure. Left ventricular ejection fraction(LVEF) was estimated at the hospital discharge using the Simpson method. There were two control groups: 15 healthy persons and 15 patients with stable coronary artery disease matched for age and sex with the studied group. The abrupt opening of the target vessel did not produce an early increase in the activity of the MMPs. Their activity was high at the beginning and slowly lowered with time after pPCI so that at 12, 24 and 48 h after pPCI their activity was significantly lower than before and immediately after the pPCI (p < 0.05 for all comparisons). The abrupt opening of the target vessel did not produce significant changes in the TIMP concentration. Only the TIMP-1 showed a slow increase in concentration and achieved a significantly higher level 48 h after the procedure compared to its concentration before and immediately after pPCI (p < 0.05). In 14 patients (15% of the studied group), the post procedure TIMI flow was estimated as lower than 3 (TIMI 1 or 2). There was significantly higher MMP-9 activity in this group before, immediately after and up to 3 h after PCI compared to the group with good angiographic effect (TIMI = 3 after procedure). Patients with lowered LVEF(< 50%) at hospital discharge had higher MMP-9 activity immediately after and 3 h after pPCI compared to patients with preserved LVEF. The same relation was observed for TIMP-2 level, where patients with a higher level before and immediately after pPCI had lowered LVEF at discharge. 1. The activity level of MMP-2 and MMP-9 is elevated during the STEMI acute phase and falls 12 h after successful pPCI, while TIMP-1 concentration only rises 48 h after the procedure. 2. The abrupt opening of the target vessel in STEMI does not produce acute changes in MMP-2, MMP-9 activity or TIMP-1 and TIMP-2 concentration. 3. The 'no-reflow'phenomenon in STEMI patients occurs more often in those with higher MMP-9 activity before pPCI. 4. Lowered LVEF at hospital discharge is observed in patients with higher periprocedural MMP-9 activity and TIMP-2 level.


Behavioral effects of infection with interferon-gamma adenovector.
Anxiety and depression of unknown etiology are frequent complications of the systemic autoimmune disease lupus erythematosus (SLE). To elucidate key pathogenic factors we study the "autoimmunity-associated behavioral syndrome" (AABS) in lupus-prone MRL-lpr mice. Based on the evidence that serum levels of the neuroactive cytokine interferon-gamma (IFN-gamma) are increased both in human and murine forms of SLE, the present study examines whether sustained IFN-gamma production in non-autoimmune mice induces deficits comparable to AABS, particularly in tasks reflective of emotional reactivity and motivated behavior. For this purpose, wild-type and IFN-gamma knockout C57BL/6J mice were infected with adenovirus carrying the cDNA for murine IFN-gamma (i.p. 2 x 10(8) pfu of virus per mouse) and shortly thereafter tested in the behavioral battery used in the detection of AABS. Serum levels of IFN-gamma were found to peak 24 h after the infection, normalized within 5 days. Although all infected animals showed reduced food/water intake and body weight, the recovery rate was slower in groups injected with IFN-gamma virus. No deficits were observed in the models of anxiety, but blunted responsiveness in the sucrose preference test (a putative model of anhedonia) lasted well beyond the IFN-gamma clearance period. These results suggest that a relatively brief elevation in systemic IFN-gamma levels impairs ingestive behavior and leads to prolonged changes in motivated behavior. As such, they are consistent with the hypothesis that upregulation in synthesis of pro-inflammatory cytokines contributes to induction of AABS and more specifically, to limbic system dysfunction during lupus-like disease.


Human neutrophil dysfunction with giant granules and defective activation of the respiratory burst.
We describe a patient whose peripheral blood neutrophils and bone marrow precursors (beyond promyelocytes) contained multiple large azurophilic granules. There were also giant granules in eosinophils, basophils, melanocytes, renal tubules, thyroid, and neurones, but not lymphocytes or monocytes. His clinical course included recurrent (ultimately fatal) infections and severe neurologic impairment. Immunofluorescent staining with fluoroscein- and rhodamine-conjugated antisera to primary and secondary granule markers showed virtually all of the granulocyte granules and rare monocyte granules to be fusion products containing both markers. Electron microscopy showed the granules to be large peroxidase-containing lysosomes. Only rare normal primary and secondary granules were present. Superoxide generation in response to opsonized zymosan was 7.3 nmole/min/10(6) cells (control 8.9); but in response to phorbol myristate acetate, only 2.2 (control 9.4). Nitroblue tetrazolium slides showed 3+ dye reduction in response to opsonized zymosan by 90% of granulocytes (control 91%) and to phorbol myristate acetate by 22% (control 99%), with 71% producing only a minimal 1+ response. Cellular contents of myeloperoxidase and beta-glucuronidase were elevated, but the percent release during exocytic degranulation was equivalent to control. Ingestion of complement-opsonized Staphylococcus aureus and zymosan was also normal. Killing of Staphylococcus aureus was 60% at 90-min incubation (control 92%). Granulocyte cyclic adenosine monophosphate (AMP) content was 4 pmole/10(7) cells (control 3.1). In order to determine whether these characteristics derived from the cells' genetic program or their environment, the patient's bone marrow was grown in long-term culture. Granulocytes produced in vitro demonstrated the same morphology, same defect in activation of nitroblue tetrazolium reduction, and same normal cyclic AMP level as those harvested from peripheral blood. These studies describe a new disorder of granulocytes; the structural similarity to, but biochemical differences from, Chediak-Higashi disease indicate the probable heterogeneity of mechanisms for the same morphological abnormality.


Association of conventional goals and perceptions of pregnancy with female teenagers' pregnancy avoidance behavior and attitudes.
Fostering conventional goals is a key component of pregnancy prevention interventions for teenagers. However, research has not shown whether having goals independently influences sexual behavior, or whether the perception that pregnancy represents an impediment to achieving goals mediates any association. In 1999-2001, a racially mixed group of 351 sexually experienced female teenagers who were inadequate contraceptive users completed surveys about goals, the anticipated impact of childbearing on these goals, and protective behaviors and attitudes. Chi-square, regression and two-by-two table analyses assessed associations between goals and perceptions of early childbearing and pregnancy avoidance measures. Three-fourths of respondents had educational or vocational goals. Eight in 10 of these teenagers perceived their goals to be achievable, but fewer than half thought pregnancy would be an impediment to achieving these goals. Teenagers who had goals were more likely than others to have used a contraceptive at last intercourse (odds ratio, 1.9), but controlling for the perception of pregnancy as an impediment eliminated this association. In contrast, considering pregnancy an impediment was associated with an increased likelihood of supporting each pregnancy avoidance measure (2.1-9.6), and of intending to avoid pregnancy and to have an abortion if pregnant, regardless of whether teenagers had goals (8.3-13.8). Conventional goals appear to motivate teenagers to avoid getting pregnant only if they believe pregnancy will be an impediment. Thus, it may be less important to encourage young women to formulate goals than to ensure that they consider adolescent childbearing a threat to their plans.


Recovery of a wild fish population from whole-lake additions of a synthetic estrogen.
Despite widespread recognition that municipal wastewaters contain natural and synthetic estrogens, which interfere with development and reproduction of fishes in freshwaters worldwide, there are limited data on the extent to which natural populations of fish can recover from exposure to these compounds. We conducted whole-lake additions of an active component of the birth control pill (17α-ethynylestradiol; EE2) that resulted in the collapse of the fathead minnow (Pimephales promelas) population. Here we quantify physiological, population, and genetic characteristics of this population over the 7 years after EE2 additions stopped to determine if complete recovery was possible. By 3 years post-treatment, whole-body vitellogenin concentrations in male fathead minnow had returned to baseline, and testicular abnormalities were absent. In the spring of the fourth year, adult size-frequency distribution and abundance had returned to pretreatment levels. Microsatellite analyses clearly showed that postrecovery fish were descendants of the original EE2-treated population. Results from this whole-lake experiment demonstrate that fish can recover from EE2 exposure at the biochemical through population levels, although the timelines to do so are long for multigenerational exposures. These results suggest that wastewater treatment facilities that reduce discharges of estrogens and their mimics can improve the health of resident fish populations in their receiving environments.


Amyotrophic lateral sclerosis mortality rates in Chile: A population based study (1994-2010).
Our objective was to describe amyotrophic lateral sclerosis (ALS) mortality rates in the Chilean population over a 17-year period. Chilean death records (1994-2010) were reviewed for the ICD-10 diagnosis G.12.2 (including motor neuron disease and similar conditions), and weighted with population data. Crude and standardized mortality rates by ALS were calculated at the nationwide level and by geographic zone. A risk analysis was performed in successive cohorts from 1910-1919 to 1960-1969, comparing mortality slopes. One thousand six hundred and seventy-one deaths were recorded during 1994-2010, with an average of 1.13 per 100,000, a 1.2:1 male/female ratio, and a statistically significant increase in mortality rate. According to geographical distribution, the Austral area, with a larger population of European origin, showed higher mortality rates compared to the national average. The cohort analysis showed an increasing risk of dying from ALS for all cohorts, and highest above 64 years of age, becoming a competitive cause of death in older ages. In conclusion, as expected, the mortality rate in Chile by ALS is higher than that reported previously in our country, and similar to other Latin American countries. ALS mortality rate has increased over time probably due to the aging of the population and decline in rates for competing causes of death.


Mapping human mobility during the third and second millennia BC in present-day Denmark.
We present results of the largest multidisciplinary human mobility investigation to date of skeletal remains from present-day Denmark encompassing the 3rd and 2nd millennia BC. Through a multi-analytical approach based on 88 individuals from 37 different archaeological localities in which we combine strontium isotope and radiocarbon analyses together with anthropological investigations, we explore whether there are significant changes in human mobility patterns during this period. Overall, our data suggest that mobility of people seems to have been continuous throughout the 3rd and 2nd millennia BC. However, our data also indicate a clear shift in mobility patterns from around 1600 BC onwards, with a larger variation in the geographical origin of the migrants, and potentially including more distant regions. This shift occurred during a transition period at the beginning of the Nordic Bronze Age at a time when society flourished, expanded and experienced an unprecedented economic growth, suggesting that these aspects were closely related.


Different marine heterotrophic nanoflagellates affect differentially the composition of enriched bacterial communities.
We studied the effects of predation on the cytometric and phylogenetic features of two enriched bacterial communities obtained from two cultures of marine heterotrophic nanoflagellates: Jakoba libera and a mixed culture of Cafeteria sp. and Monosiga sp. Protists were harvested by flow cytometric cell sorting and eight different treatments were prepared. Each bacterial community was incubated with and without protists, and we added two treatments with protists and the bacteria present after the sorting procedure (cosorted bacteria). The bacterial community derived from the culture of Jakoba libera had higher green fluorescence per cell (FL1) than that derived from the mixed culture of Cafeteria sp. and Monosiga sp. When the experiment began all treatments presented bacterial communities that increase in fluorescence per bacterium (FL1); after that the FL1 decreased when bacteria attained maximal concentrations; and, finally, there was a new increase in FL1 toward the end of the experiment. Cosorted bacteria of Jakoba libera had the same fluorescence as the bacterial community derived from this protist, while the bacteria derived from the mixed culture of Cafeteria sp. and Monosiga sp. was nearly twice as fluorescent than that of the parental community. All treatments presented a general decline of SSC along the incubation. Therefore, there was a small influence of protists on the cytometric signature of each bacterial community. However, each bacterial community preyed by Jakoba libera or the mixed culture of Cafeteria sp. and Monosiga sp. led to four different phylogenetic fingerprint. Besides, the final Communities were different from the fingerprint of controls without protists, and most of them diverge from the fingerprint of cosorted bacteria. Our results confirm that changes in the phylogenetic composition of marine bacterial communities may depend on the initial communities of both bacteria and protists.


Test-retest reliability of skeletal muscle oxygenation measurement using near-infrared spectroscopy during exercise in patients with sport-related iliac artery flow limitation.
The ankle-brachial index is an accurate tool for detecting claudication in atherosclerotic patients. However, this technique fails to identify subtle flow limitations of the iliac arteries (FLIA) in endurance athletes. Near-infrared spectroscopy (NIRS) is a noninvasive technique that measures skeletal muscle tissue oxygenation status. The aim of the present study is to examine the absolute and relative test-retest reliability of NIRS and evaluate its potential as a diagnostic tool in FLIA. NIRS-derived exercise variables were analyzed during exercise and recovery in FLIA 17 patients and 19 healthy controls. The relative reliability of absolute variables (such as the maximal value) were slight to yet predominantly substantial (intraclass correlation coefficient [ICC], ICC range: 0.06-0.76) with good to excellent absolute reliability (absolute limits of agreement [ALoA], ALoA range: 0.8 ± 10.2 to 0.7 ± 13.1; coefficient of variation [CV], CV range: 5%-11%). Absolute values encompassing signal amplitudes showed moderate to almost perfect relative reliability (ICC range: 0.51-0.89) and poor to good absolute reliability (ALoA range: -1.3 ± 7.0 to -2.5 ± 15.7; CV range: 15%-32%). Kinetic variables showed moderate to almost perfect relative reliability for most recovery kinetics variables (ICC range: 0.54-0.86) with fair to good absolute reliability (ALoA range: 0.4 ± 12.2 to 3.9 ± 37.9; CV range: 18%-27%). Particularly, kinetic variables showed significant differences between patients and healthy subjects. NIRS is found to be a reliable method for examining muscle tissue oxygenation variables. Given the significant differences in especially recovery kinetics between normal subjects and patients, NIRS may contribute to diagnosing FLIA in endurance athletes.


Angiotensin II receptor subtypes in renal cortex of rats and rhesus monkeys.
The angiotensin II (ANG II) receptor has recently been shown to exhibit subtypes with respect to antagonist binding. Of particular interest are the potent nonpeptide antagonists, DUP 753 and PD 121981, which exhibit selectivity for the subtype 1 (AT1) and subtype 2 (AT2) receptors, respectively. We used these high-affinity antagonists in competition with 125I-[Sar1,Ile8]ANG II to determine autoradiographically the distribution of these ANG II-receptor subtypes in the renal cortex of rats and rhesus monkeys. Binding of the radioligand to receptor in sections of rat renal cortex was inhibited by DUP 753; inhibition by PD 121981 was not detected. By contrast, AT1 and AT2 receptors are present in the renal cortex of rhesus monkeys in regionally distinct structures. DUP 753 inhibited binding to the ANG II receptor in glomeruli. PD 121981 inhibited binding to arterial smooth muscle and the juxtaglomerular (JG) apparatus. The JG apparatus also exhibits radioligand binding, which is inhibited by DUP 753. The effect of DUP 753 and PD 123177 (a more water-soluble analogue of PD 121981) on changes in plasma renin activity was examined to determine if one or both of these subtypes participate in the ANG II-mediated negative feedback of control of renin release. Although DUP 753 increased plasma renin activity to the same extent as the angiotensin-converting enzyme inhibitor, enalaprilat, in rats and rhesus monkeys, the AT2 antagonists did not affect renin release in either species. Thus both subtypes of ANG II receptor are present in rhesus monkey cortex, but a function for only the AT1 subtype was demonstrated.


Biomimetic Gradient Scaffolds Containing Hyaluronic Acid and Sr/Zn Folates for Osteochondral Tissue Engineering.
Regenerative therapies based on tissue engineering are becoming the most promising alternative for the treatment of osteoarthritis and rheumatoid arthritis. However, regeneration of full-thickness articular osteochondral defects that reproduces the complexity of native cartilage and osteochondral interface still remains challenging. Hence, in this work, we present the fabrication, physic-chemical characterization, and in vitro and in vivo evaluation of biomimetic hierarchical scaffolds that mimic both the spatial organization and composition of cartilage and the osteochondral interface. The scaffold is composed of a composite porous support obtained by cryopolymerization of poly(ethylene glycol) dimethacrylate (PEGDMA) in the presence of biodegradable poly(D,L-lactide-co-glycolide) (PLGA), bioactive tricalcium phosphate β-TCP and the bone promoting strontium folate (SrFO), with a gradient biomimetic photo-polymerized methacrylated hyaluronic acid (HAMA) based hydrogel containing the bioactive zinc folic acid derivative (ZnFO). Microscopical analysis of hierarchical scaffolds showed an open interconnected porous open microstructure and the in vitro behaviour results indicated high swelling capacity with a sustained degradation rate. In vitro release studies during 3 weeks indicated the sustained leaching of bioactive compounds, i.e., Sr2+, Zn2+ and folic acid, within a biologically active range without negative effects on human osteoblast cells (hOBs) and human articular cartilage cells (hACs) cultures. In vitro co-cultures of hOBs and hACs revealed guided cell colonization and proliferation according to the matrix microstructure and composition. In vivo rabbit-condyle experiments in a critical-sized defect model showed the ability of the biomimetic scaffold to promote the regeneration of cartilage-like tissue over the scaffold and neoformation of osteochondral tissue.


Pseudo-aneurysm of the carotid bifurcation secondary to radiation.
Pseudoaneurysms of the extracranial carotid vessels have a varied etiopathogenesis. Cases have been attributed to spontaneous rupture, following tonsillectomy or peritonsillar abscesses, trauma, postanastamotic and, rarely, postirradiation, and ECMO. The authors present a case of a pseudoaneurysm involving the carotid artery bifurcation following radiation therapy. A saphenous vein graft was used to establish continuity between the common and the internal carotid arteries. A vascular shunt was used to maintain cerebral perfusion during surgery. This case highlights the technical difficulties encountered in correcting this condition. This case exemplifies the technical difficulties that are encountered in a complicated case such as this. Numerous previous operations and radiotherapy compounded the hazards of the surgical procedure. Although technically challenging, every attempt must be made to resect pseudoaneurysms caused by radiation induced vascular damage.


The new era of nanotechnology, an alternative to change cancer treatment.
In the last few years, nanostructures have gained considerable interest for the safe delivery of therapeutic agents. Several therapeutic approaches have been reported, such as molecular diagnosis, disease detection, nanoscale immunotherapy and anticancer drug delivery that could be integrated into clinical use. The current paper aims to highlight the background that supports the use of nanoparticles conjugated with different types of therapeutic agents, applicable in targeted therapy and cancer research, with a special emphasis on hematological malignancies. A particular key point is the functional characterization of nonviral delivery systems, such as gold nanoparticles, liposomes and dendrimers. The paper also presents relevant published data related to microRNA and RNA interference delivery using nanoparticles in cancer therapy.


Inhibiting geranylgeranyl diphosphate synthesis reduces nuclear androgen receptor signaling and neuroendocrine differentiation in prostate cancer cell models.
Following androgen deprivation for the treatment of advanced adenocarcinoma of the prostate, tumors can progress to neuroendocrine prostate cancer (NEPC). This transdifferentiation process is poorly understood, but trafficking of transcriptional factors and/or cytoskeletal rearrangements may be involved. We observed the role of geranylgeranylation in this process by treatment with digeranyl bisphosphonate (DGBP), a selective inhibitor of geranylgeranyl pyrophosphate synthase which blocks the prenylation of small GTPases such as Rho and Rab family proteins, including Cdc42 and Rac1. We examined the therapeutic potential of DGBP in LNCaP, C4-2B4, and 22Rv1 cell culture models. Cell morphology and protein expression were quantified to observe the development of the neuroendocrine phenotype in androgen-deprivation and abiraterone-treated LNCaP models of NEPC development. Luciferase reporter assays were utilized to examine AR activity, and immunofluorescence visualized the localization of AR within the cell. Essential genes in the isoprenoid pathway, such as HMGCR, MVK, GGPS1, and GGT1, were highly expressed in a subset of castration resistant prostate cancers reported by Beltran et al. Under treatment with DGBP, nuclear localization of AR decreased in LNCaP, 22Rv1, and C4-2B4 cell lines, luciferase reporter activity was reduced in LNCaP and 22Rv1, and AR target gene transcription also decreased in LNCaP. Conversely, nuclear localization of AR was enhanced by the addition of GGOH. Finally, induction of the NEPC structural and molecular phenotype via androgen deprivation in LNCaP cells was inhibited by DGBP in a GGOH-dependent manner. DGBP is a novel compound with the potential to reduce AR transcriptional activity and inhibit PCa progression to NEPC phenotype. These results suggest that DGBP may be used to block cell growth and metastasis in both hormone therapy sensitive and resistant paradigms.


Inhibition of Src family kinases improves cognitive function after intraventricular hemorrhage or intraventricular thrombin.
Intraventricular hemorrhage causes spatial memory loss, but the mechanism remains unknown. Our recent studies demonstrated that traumatic brain injury activates Src family kinases, which cause spatial memory loss. To test whether the spatial memory loss was due to blood in the ventricles, which activated Src family kinases, we infused autologous whole blood or thrombin into the lateral ventricles of adult rats to model non-traumatic intraventricular hemorrhage. Hippocampal neuron loss was examined 1 day to 5 weeks later. Spatial memory function was assessed 29 to 33 days later using the Morris water maze. Five weeks after the ventricular injections of blood or thrombin, there was death of most hippocampal neurons and significant memory deficits compared with sham operated controls. These data show that intraventricular thrombin is sufficient to kill hippocampal neurons and produce spatial memory loss. In addition, systemic administration of the non-specific Src family kinase inhibitor PP2 or intraventricular injection of siRNA-Fyn, a Src family kinase family member, prevented hippocampal neuronal loss and spatial memory deficits following intraventricular hemorrhage. The data support the conclusions that thrombin mediates the hippocampal neuronal cell death and spatial memory deficits produced by intraventricular blood and that these can be blocked by non-specific inhibition of Src family kinases or by inhibiting Fyn.


Ultrastructure of the monkey vas deferens.
The testicular and prostatic ends of the vasa deferentia of two male monkeys weighing 3-4 kg were examined ultrastructurally, using the method described by Richards & Tranzer (1975). The general ultrastructure of the vas deferens resembles that described previously. In addition, new features were observed. These include (i) shedding of parts of the apical portions of the epithelial cells; (ii) darkening of mitochondria-rich cells in the epithelium; (iii) presence of secretory granule-like structures in the principal cells of the epithelium; (iv) mast cells which may be associated with blood vessels or smooth muscle cells, and (v) presence of dense osmiophilic cells in the lamina propria and muscle coat, but predominantly in the former. The last-mentioned cells are stellate, having many branching processes, and are characterised by the appearance of many caveolae on their surface membranes. Basal lamina may or may not be seen to surround the cell membranes. The cells are contacted by nerve varicosities which resemble those of cholinergic and purinergic fibres.


Testing a Self-Determination Theory Model of Healthy Eating in a South African Township.
The burden of type 2 diabetes is growing rapidly in sub-Saharan Africa. Healthy eating has been shown to prevent the disease but is challenging to maintain. Self-determination theory offers a motivational framework for maintaining a healthy diet based on evidence from western settings. This study aims to assess whether self-determination theory can explain healthy diet behavior in a disadvantaged urban South African population. Cross-sectional data from a South African township population (N = 585; pre-diabetes = 292, diabetes = 293, age 30-75) were analyzed using structural equation modeling, while controlling for socio-demographic factors. Measures included self-reported autonomous and controlled motivation, perceived competence (measured through barrier self-efficacy), perceived relatedness (measured through perceived participation of significant others) and, as indicator for healthy diet, frequency of fruit, vegetable, and non-refined starch intake. Healthy eating was positively associated (β = 0.26) with autonomous motivation, and negatively associated (β = -0.09) with controlled motivation. Perceived competence and relatedness were positively associated with healthy eating (β = 0.49 and 0.37) and autonomous motivation (β = 0.65 and 0.35), and negatively associated with controlled motivation (β = -0.26 and -0.15). Autonomous motivation mediated the effect of perceived competence and relatedness on healthy eating. The model supported a negative association between controlled and autonomous motivation. This is the first study providing evidence for self-determination theory explaining healthy eating in a disadvantaged sub-Saharan African setting among people at risk of or with diabetes type two. Our findings suggest that individuals who experience support from friends or family and who feel competent in adopting a healthy diet are more likely to become more motivated through identifying the health benefits of healthy eating as their goal. This type of autonomous motivation was associated with a healthier diet compared to individuals whose motivation originated in pressure from others or feelings of guilt or shame. Our recommendations for public health interventions include: focus on the promotion of diet-related health benefits people can identify with; encourage social support by friends or family; reinforce people's sense of competence and skills; and avoid triggering perceived social pressure or feelings of guilt.


[The effect of family factors on school retardation in the Cartuja quarter of Granada].
The possible influence of the family on school retardation was evaluated in the Cartuja quarter in Granada for the academic term 1988-89. The study was performed on 258 schoolchildren of the 7th and 8th primary courses in the four public schools from the quarter. Data were collected with a questionnaire including the following variables: school retardation, sex, number of siblings, ordinal number among siblings, educational level of the parents, and work of the mother outside the household. To evaluate family function the APGAR questionnaire was used. A remarkably high (45.7%) school retardation was found, higher than that in the rest of Spain. School retardation cannot be related with the family dysfunction detected by the familial APGAR. It was related, rather, with the child's sex, the educational level of the mother, the number of siblings and the ordinal place of the child among them.


Schematic eye with a gradient-index lens and aspheric surfaces.
A new schematic eye with aspheric surfaces and a radially varying refractive-index distribution lens is proposed. Image quality and spherical aberration are determined by use of ray tracing, and the results are presented as spot diagrams and compared with five existing model eyes. The proposed model provides the best image quality and lowest spherical aberration.


Inch-sized high-quality perovskite single crystals by suppressing phase segregation for light-powered integrated circuits.
The triple-cation mixed-halide perovskite (FA x MA y Cs1-x-y )Pb(IzBr1-z )3 (FAMACs) is the best composition for thin-film solar cells. Unfortunately, there is no effective method to prepare large single crystals (SCs) for more advanced applications. Here, we report an effective additive strategy to grow 2-inch-sized high-quality FAMACs SCs. It is found that the judiciously selected reductant [formic acid (FAH)] effectively minimizes iodide oxidation and cation deprotonation responsible for phase segregation. Consequently, the FAMACs SC shows more than fivefold enhancement in carrier lifetimes, high charge mobility, long carrier diffusion distance, as well as superior uniformity and long-term stability, making it possible for us to design high-performance self-powered integrated circuit photodetector. The device exhibits large responsivity, high photoconductive gain, excellent detectivity, and fast response speed; all values are among the highest reported to date for planar-type single-crystalline perovskite photodetectors. Furthermore, an integrated imaging system is fabricated on the basis of 12 × 12 pixelated matrixes of the single-crystal photodetectors.


Epithelial-mesenchymal transition delayed by E-cad to promote tissue formation in hepatic differentiation of mouse embryonic stem cells in vitro.
Hepatic differentiation of embryonic stem cells (ESCs) usually results in a single cell lineage, and the formation of liver tissues remains difficult. Here, we examine the role of epithelial-mesenchymal transition (EMT) that is regulated by epithelial cadherin (E-cad) expression in hepatic tissue formation from ESCs. E-cad was transfected into mouse ESCs to enable a stable expression of E-cad. Hepatic differentiation of ESCs was then induced by hepatic growth factors. Wnt/β-catenin signaling and EMT speed were examined to determine the differentiation process. Hepatic and angiogenesis markers, as well as differentiated cell-adhesive force were also examined to identify the hepatic tissue differentiation. In our results, E-cad expression gradually decreased in normal ESC (N-ESC) differentiation, but remained stable in the E-cad transfected ESC (EC-ESC) group. In EC-ESC differentiation, expressions of cytoplastic β-catenin and EMT were much lower and significantly prolonged. Angiogenesis markers vascular endothelial growth factor receptor-1 (VEGFR-1) and CD31/PECAM-1 were expressed only on day 5-13 in N-ESC differentiation, whereas VEGFR-1 and CD31/PECAM-1 were expressed prolonged on day 5-17 in the EC-ESC group and were coincident with the expression of hepatic markers. Finally, EC-ESC differentiation maintained multilayer-growth patterns, and abundant vascular network structures appeared and migrated in albumin-positive cell areas. The cellular adhesion forces between embryonic body cells in EC-ESC differentiation during day 13-17 were similar to those of mouse liver tissue. In conclusion, accelerated EMT due to the decreased E-cad expression may partially contribute to the failure of hepatic tissue formation in N-ESC differentiation. E-cad can act in synergy with hepatic growth factors and facilitate the early-stage formation of hepatic tissues through down-regulating Wnt/β-catenin signaling and delaying EMT. This work provides a new insight into hepatic tissue differentiation that is mediated by E-cad from ESC.


Explaining unexplained pain to fibromyalgia patients: finding a narrative that is acceptable to patients and provides a rationale for evidence based interventions.
As the cause of fibromyalgia is controversial, communicating with patients can be challenging, particularly if the patient adopts the narrative 'I am damaged and so I need a more powerful pain killer'. Research shows that providing patients with alternative narratives can be helpful, but it remains unclear what particular narratives are most acceptable to patients and at the same time provide a rationale for evidence based psychological and exercise interventions. This article described the development of a new narrative and the written comments made about the narrative by fibromyalgia patients. The narrative derives from a complexity theory model and provides an alternative to biogenic and psychogenic models. The model was presented to 15 patients whose comments about comprehensibility led to the final format of the narrative. In the final form, the body is presented as 'a very, very clever computer' where fibromyalgia is caused by a software rather than a hardware problem. The software problem is caused by the body adapting when people have to 'keep going' despite 'stop signals', such as pain and fatigue. The narrative provides a rationale for engaging in psychological and exercise interventions as a way of correcting the body's software. This way of explaining fibromyalgia was evaluated by a further 25 patients attending a 7-week 'body reprogramming' intervention, where the therapy was presented as correcting the body's software, and included both exercise and psychological components. Attendance at the course was 85%. Thematic analysis of written patient feedback collected after each session showed that patients found the model believable and informative, it provided hope and was empowering. Patients also indicated that they had started to implement lifestyle change with perceived benefit. Fibromyalgia patients appear to respond positively to a technology-derived narrative based on the analogy of the body as a computer.


Modeling the effect of temperature and wetness on Guignardia pseudothecium maturation and ascospore release in citrus orchards.
Ascospores are the most important inoculum source of citrus black spot (CBS), caused by Guignardia citricarpa, but pseudothecium maturation and ascospore release are inadequately studied. Guignardia ascospore trapping and concomitant weather data were obtained for three localities over three seasons (July to March 2006 to 2009) in the Limpopo province of South Africa. Degree-days accumulated until first seasonal ascospore discharge (>10°C with 1 July as biofix) (DDtemp), and DDtemp accumulated on rainy (rainfall >0.1 mm) (DDrain) and moist days (vapor pressure deficit <5 hPa) (DDvpd) were used in two Gompertz models to predict onset of ascospore release: a temperature model [Event = exp(-exp(-(-2.725 + 0.004 × DDtemp)))] and a temperature/moisture model [Event = exp(-exp(- (-3.238 + 0.008 × DDvpd + 0.004 × DDtemp - 0.009 × DDrain)))] (R(2) = 0.608 and 0.658, respectively). Both models predicted a delay in pseudothecium maturation in climates with colder winters and springs. A Gompertz equation was also used to predict the proportion of Guignardia ascospores trapped (PAT) per season from DDtemp data accumulated on wet or moist days (DDwet2) from the first seasonal ascospore discharge [PAT = exp(-4.096 × exp(-0.005 × DDwet2); R(2) = 0.908]. The PAT model predicted lag phases and 7-day peaks in ascospore release patterns with reasonable accuracy. These models can be used to predict the onset and dynamics of ascospore release in climatically diverse regions.


A computational study of a recreated G protein-GEF reaction intermediate competent for nucleotide exchange: fate of the Mg ion.
Small G-proteins of the superfamily Ras function as molecular switches, interacting with different cellular partners according to their activation state. G-protein activation involves the dissociation of bound GDP and its replacement by GTP, in an exchange reaction that is accelerated and regulated in the cell by guanine-nucleotide exchange factors (GEFs). Large conformational changes accompany the exchange reaction, and our understanding of the mechanism is correspondingly incomplete. However, much knowledge has been derived from structural studies of blocked or inactive mutant GEFs, which presumably closely represent intermediates in the exchange reaction and yet which are by design incompetent for carrying out the nucleotide exchange reaction. In this study we have used comparative modelling to recreate an exchange-competent form of a late, pre-GDP-ejection intermediate species in Arf1, a well-characterized small G-protein. We extensively characterized three distinct models of this intermediate using molecular dynamics simulations, allowing us to address ambiguities related to the mutant structural studies. We observed in particular the unfavorable nature of Mg2+ associated forms of the complex and the establishment of closer Arf1-GEF contacts in its absence. The results of this study shed light on GEF-mediated activation of this small G protein and on predicting the fate of the Mg ion at a critical point in the exchange reaction. The structural models themselves furnish additional targets for interfacial inhibitor design, a promising direction for exploring potentially druggable targets with high biological specificity.


A 5-year follow-up of depressed and bipolar patients with alcohol use disorder in an Irish population.
Alcohol use disorders (AUDs) and affective disorders commonly co-occur, and this co-occurrence is mutually detrimental. To date, few long-term outcome studies exist involving patients with these comorbid disorders. We wished to determine treatment outcomes 5 years after inpatient integrated treatment in patients with these co-occurring disorders, and identify prognostic factors associated with long-term outcome. Two hundred and five depressed and bipolar patients with AUD who completed an inpatient integrated treatment program for dual diagnosis were assessed at baseline, posttreatment discharge, and at 3 months, 6 months, 2 years, and 5 years after treatment. The retention rate at 3 months postdischarge was 95.6%, 75.6% at 6 months, 70.2% at 2 years, and 55.6% at 5 years. Depression, elation, anxiety, and craving scores all fell over the 5-year period, as did the drinking outcome measures in both the depressed and bipolar alcoholics. Each of the primary drinking outcome measures had independent prognostic factors: abstinence at 2 years predicted abstinence at 5 years; number of drinking days at 6 months and 2 years predicted number of drinking days at 5 years; number of drinks per drinking day at 6 months and 2 years predicted number of drinks per drinking day at 5 years. Moreover, the majority of nonabstinent light drinkers at 3 months, who had significantly reduced their mean weekly alcohol consumption since baseline, remained light drinkers at 5 years and very few went on to be heavy drinkers. Indeed, if they did alter category by 5 years, they tended to become abstinent. Dual diagnosis of AUD and depression or bipolar disorder may be treated successfully together with intensive intervention and follow-up, and various prognostic factors emerge. Early abstinence predicts later abstinence, and the vast majority of those who achieve light drinking early in recovery remain light drinkers or become abstinent at 5 years.


Tissue-engineered bone using mesenchymal stem cells versus conventional bone grafts in the regeneration of maxillary alveolar bone: A systematic review and meta-analysis.
The aim of this study was to compare tissue-engineered bone using mesenchymal stem cells (MSCs) and conventional bone grafts in terms of histomorphometric outcome, bone gained, and implant failure in the atrophic maxilla. A systematic review and meta-analysis of randomized clinical trials (RCTs) was conducted. An electronic search of several databases was performed. RCTs comparing tissue-engineered bone using MSCs to bone graft alone in rehabilitation of the atrophic maxilla were included. Outcome variables were a mean percentage of new bone formation, residual graft particles, and connective tissue. Bone gained and implant failure rate were also assessed. Risk ratio (RR) or standardized mean differences (SMD) were statistically analyzed. A total of 190 augmented sites enrolled in 12 RCTs were included in this study. Nine of the 12 RCTs included 153 maxillary sinuses that underwent sinus elevation, and three RCTs included 28 patients with bone grafting only. There was no significant increase in new bone formation between the two groups at 3 to 4 months (SMD = -0.232, CI, -0.659 to 0.195, low-quality evidence). However, at 6 months postgrafting, a statistically significant increase in new bone formation was found in favor of the tissue-engineered bone using the MSC group (SMD = 0.869%, CI, -1.98 to 9.310, moderate-quality evidence). No substantial difference was found between the two groups with respect to residual graft particles, connective tissue, bone gained, and implant failure rate (RR = 2.8, CI: 0.517 to 16.6, P = .226, very low-quality evidence). There is moderate- to very low-quality evidence supporting the use of tissue-engineered bone using MSC therapy in maxillary alveolar bone regeneration compared with conventional bone grafting without MSCs.


Noninvasive Urinary Monitoring of Progression in IgA Nephropathy.
Standard methods for detecting and monitoring of IgA nephropathy (IgAN) have conventionally required kidney biopsies or suffer from poor sensitivity and specificity. The Kidney Injury Test (KIT) Assay of urinary biomarkers has previously been shown to distinguish between various kidney pathologies, including chronic kidney disease, nephrolithiasis, and transplant rejection. This validation study uses the KIT Assay to investigate the clinical utility of the non-invasive detection of IgAN and predicting the progression of renal damage over time. The study design benefits from longitudinally collected urine samples from an investigator-initiated, multicenter, prospective study, evaluating the efficacy of corticosteroids versus Rituximab for preventing progressive IgAN. A total of 131 urine samples were processed for this study; 64 urine samples were collected from 34 IgAN patients, and urine samples from 64 demographically matched healthy controls were also collected; multiple urinary biomarkers consisting of cell-free DNA, methylated cell-free DNA, DMAIMO, MAMIMO, total protein, clusterin, creatinine, and CXCL10 were measured by the microwell-based KIT Assay. An IgA risk score (KIT-IgA) was significantly higher in IgAN patients as compared to healthy control (87.76 vs. 14.03, p < 0.0001) and performed better than proteinuria in discriminating between the two groups. The KIT Assay biomarkers, measured on a spot random urine sample at study entry could distinguish patients likely to have progressive renal dysfunction a year later. These data support the pursuit of larger prospective studies to evaluate the predictive performance of the KIT-IgA score in both screening for non-invasive diagnosis of IgAN, and for predicting risk of progressive renal disease from IgA and utilizing the KIT score for potentially evaluating the efficacy of IgAN-targeted therapies.


Charged single alpha-helix: a versatile protein structural motif.
A few highly charged natural peptide sequences were recently suggested to form stable alpha-helical structures in water. In this article we show that these sequences represent a novel structural motif called "charged single alpha-helix" (CSAH). To obtain reliable candidate CSAH motifs, we developed two conceptually different computational methods capable of scanning large databases: SCAN4CSAH is based on sequence features characteristic for salt bridge stabilized single alpha-helices, whereas FT_CHARGE applies Fourier transformation to charges along sequences. Using the consensus of the two approaches, a remarkable number of proteins were found to contain putative CSAH domains. Recombinant fragments (50-60 residues) corresponding to selected hits obtained by both methods (myosin 6, Golgi resident protein GCP60, and M4K4 protein kinase) were produced and shown by circular dichroism spectroscopy to adopt largely alpha-helical structure in water. CSAH segments differ substantially both from coiled-coil and intrinsically disordered proteins, despite the fact that current prediction methods recognize them as either or both. Analysis of the proteins containing CSAH motif revealed possible functional roles of the corresponding segments. The suggested main functional features include the formation of relatively rigid spacer/connector segments between functional domains as in caldesmon, extension of the lever arm in myosin motors and mediation of transient interactions by promoting dimerization in a range of proteins.


Dual-band planar electric metamaterial in the terahertz regime.
We present the design, fabrication, and measurement of a dual-band planar metamaterial with two distinct electric resonances at 1.0 and 1.2 THz, as a step towards the development of frequency agile or broadband THz materials and devices. A method of defining the effective thickness of the metamaterial layer is introduced to simplify the material design and characterization. Good agreement between the simulated and measured transmission is obtained for the fabricated sample by treating the sample as multi-layer system, i. e. the effective metamaterial layer plus the rest of the substrate, as well as properly modeling the loss of the substrate. The methods introduced in this paper can be extended to planar metamaterial structures operating in infrared and optical frequency ranges.


A cross-sectional screening by next-generation sequencing reveals Rickettsia, Coxiella, Francisella, Borrelia, Babesia, Theileria and Hemolivia species in ticks from Anatolia.
Ticks participate as arthropod vectors in the transmission of pathogenic microorganisms to humans. Several tick-borne infections have reemerged, along with newly described agents of unexplored pathogenicity. In an attempt to expand current information on tick-associated bacteria and protozoans, we performed a cross-sectional screening of ticks, using next-generation sequencing. Ticks seeking hosts and infesting domestic animals were collected in four provinces across the Aegean, Mediterranean and Central Anatolia regions of Turkey and analyzed by commonly used procedures and platforms. Two hundred and eighty ticks comprising 10 species were evaluated in 40 pools. Contigs from tick-associated microorganisms were detected in 22 (55%) questing and 4 feeding (10%) tick pools, with multiple microorganisms identified in 12 pools. Rickettsia 16S ribosomal RNA gene, gltA, sca1 and ompA sequences were present in 7 pools (17.5%), comprising feeding Haemaphysalis parva and questing/hunting Rhipicephalus bursa, Rhipicephalus sanguineus (sensu lato) and Hyalomma marginatum specimens. A near-complete genome and conjugative plasmid of a Rickettsia hoogstraalii strain could be characterized in questing Ha. parva. Coxiella-like endosymbionts were identified in pools of questing (12/40) as well as feeding (4/40) ticks of the genera Rhipicephalus, Haemaphysalis and Hyalomma. Francisella-like endosymbionts were also detected in 22.5% (9/40) of the pools that comprise hunting Hyalomma ticks in 8 pools. Coxiella-like and Francisella-like endosymbionts formed phylogenetically distinct clusters associated with their tick hosts. Borrelia turcica was characterized in 5% (2/40) of the pools, comprising hunting Hyalomma aegyptium ticks. Co-infection of Coxiella-like endosymbiont and Babesia was noted in a questing R. sanguineus (s.l.) specimen. Furthermore, protozoan 18S rRNA gene sequences were detected in 4 pools of questing/hunting ticks (10%) and identified as Babesia ovis, Hemolivia mauritanica, Babesia and Theileria spp. Our metagenomic approach enabled identification of diverse pathogenic and non-pathogenic microorganisms in questing and feeding ticks in Anatolia.


Periodically tailored titania nanotubes for enhanced drug loading and releasing performances.
The structural engineering of titania nanotubes (TNTs) using electrochemical anodization was performed to generate periodically modulated (p-TNTs) internal structures by applying an oscillatory voltage during the anodization process to demonstrate their improved drug-loading and drug-releasing properties. Drug loading and in vitro drug release studies compared with conventional TNTs with flat structures suggested considerable improvement with increased drug loading, reduced burst release and extended drug release for over 2 weeks. Furthermore, p-TNTs arrays were fractured by ultrasonication into liberated TNTs capsules and their potential applications as drug micro/nano-carriers for targeted and localized drug delivery is proposed. The presented electrochemical approach for structural engineering of TNTs provides new prospects in designing TNTs drug releasing implants with advanced drug-loading/release characteristics for localized drug delivery. Such implant modifications can further be tailored to cater for various implant challenges and bone therapies like: inflammation, infection and poor implant integration.


Novel Mutant Phospholipase D from Hemiscorpius lepturus Acts as A Highly Immunogen in BALB/c Mice Against the Lethality of Scorpion Venom.
Hemiscorpius lepturus (H. lepturus) which belongs to the Scorpionidae family, is the deadliest scorpion in Iran. It causes pathological manifestations like dermonecrosis, hemolysis, renal failure, necrotic ulcers, and in some cases, even death. The venom of this scorpion is well-known for its cytotoxic effects in comparison with the other venomous scorpions which show significant neurotoxic effects. Due to the painless nature of the sting of this scorpion, the clinical symptoms occur in victims 24 to 72 h post-sting. In our previous studies during the last decade, we demonstrated that the medical complications are attributable to the presence of phospholipase D (PLD) as a major toxin in the venom. With the purpose of designing and constructing a vaccine against H. lepturus for humans, animal model experiments were performed. To achieve this goal, non-toxic PLD was developed by mutation of two critical catalytic residues-His12 and His48-into alanines and the product was then denominated mut-rPLD1. The in-vivo tests showed that the mice immunized with interval doses of 10 µg of mut-rPLD1, were completely protected against 10× the LD100 of the venom. In conclusion, this mutant may be an effective vaccine candidate against scorpion envenomation by H. lepturus in future clinical studies.


Photoletter to the editor: Dermoscopy of atypical lichen sclerosus involving the tongue.
Involvement of tongue during the course of lichen sclerosus is extremely rare, with only five - to our knowledge - described cases in the English literature. We present clinical and dermoscopic findings of a female patient who concomitantly developed genital, skin and oral lesions of lichen sclerosus. Tongue involvement consisted of a linear atrophic whitish plaque, strikingly mimicking "en coupe de sabre" scleroderma. Dermoscopic examination revealed a well demarcated, linear, dense, white, homogenous area, with papillae projections hardly seen in the affected area. Dermoscopy of lesions located on the trunk revealed whitish plaques with comedo-like openings in the center and an erythematous halo at the periphery. Since clinical differentiation of oral LS and other oral diseases appearing as white atrophic plaques is almost impossible without using histology, we believe that dermoscopy might represent an additional tool, contributing to the final diagnosis, and thus avoiding an ablative procedure at this site-sensitive localization.


Pharmacological activation of the GABAergic system does not affect GH and PRL release in acromegaly.
An extensive hypothalamic neurotransmitter impairment has been proposed in acromegaly. However, at the moment, the hypothalamic GABAergic system has been little investigated in this disorder. Since GABA has been shown to modulate growth hormone (GH) and prolactin (PRL) secretion in human subjects, it seemed reasonable to investigate hypothalamic GABAergic functioning through the assessment of basal GH and PRL responses to pharmacological activation of this system. 800 mg of sodium valproate (SV), a drug with GABA facilitating properties, were administered orally to 7 acromegalic patients and 9 healthy volunteers. Blood samples were collected before and after the drug administration for the measurement of plasma GH and PRL levels. SV induced a clear-cut rise in basal GH and a decrease in basal PRL in healthy subjects, but it did not induce any change in the basal levels of these hormones in acromegalics. These results suggest that the response of GH and PRL to SV in acromegaly is qualitatively different from normal controls.


Crayfish aggression and the androgenic gland in a behavior lab for non-majors.
Male Procambarus clarkii were matched by size and largest claw length and observed interacting in pair matches before and after removal of the androgenic gland or a sham operation. Although results were not significant, trends suggested that males showed less aggression after the removal of the androgenic gland. Average bout duration did not decrease, but mean intensity of interaction decreased. This exercise was part of a student lab for non-majors. Students were positive about the lab, indicating that they learned about quantifying behavior, about hormonal involvement in aggression, and that the lab made them want to do more science.


Synthesis of novel protected Nalpha(omega-thioalkyl) amino acid building units and their incorporation in backbone cyclic disulfide and thioetheric bridged peptides.
General methods for the preparation of protected Nalpha(omega-thioalkyl) amino acids building units for backbone cyclization using reductive alkylation and on-resin preparation are described. The synthesis of non-Gly Fmoc-protected S-functionalized N-alkylated amino acids is based on the reaction of readily prepared protected omega-thio aldehyde with the appropriate amino acid. Preparation of Fmoc-protected S-functionalized N-alkylated Gly building units was carried out using two methods: reaction of glyoxylic acid with Acm-thioalkylamine and an on-resin reaction of bromoacetyl resin with Trt-thioalkylamines. Three model peptides were prepared using these building units. The GlyS2 building unit was incorporated into a backbone cyclic analog of somatostatin that contains a disulfide bridge. Formation of the disulfide bridge was performed by on-resin oxidation using 12 or Tl(CF3COO-)3. Both methods resulted in the desired product in a high degree of purity in the crude. The AspS3 building unit was also successfully incorporated into a model peptide. In addition, the in situ generation of sulfur containing Gly building units was demonstrated on a Substance P backbone cyclic analog containing a thioether bridge.


Net gain analysis, an addition to responder analysis--The case of antipsychotic treatment of acute mania.
Net Gain Analysis (NGA) is proposed as an alternative to Responders Analysis (RA) as a more comprehensive method to tap clinical relevance of the effect of treatment. NGA is the group difference in responders minus the group difference in deteriorators; while RA is the group difference in responders. We examined the performance of these two methods in a dataset consisting of individual patient data from 10 randomized controlled trials (N = 2666) of five different antipsychotics in patients with acute mania by comparing the rank ordering of the five compounds according to both systems (NGA and RA). The rank order did not differ between the 2 systems but the inferiority of one compound was revealed more evidently by the NGA in comparison to the RA.


Breaking up of prolonged sitting over three days sustains, but does not enhance, lowering of postprandial plasma glucose and insulin in overweight and obese adults.
To compare the cumulative (3-day) effect of prolonged sitting on metabolic responses during a mixed meal tolerance test (MTT), with sitting that is regularly interrupted with brief bouts of light-intensity walking. Overweight/obese adults (n=19) were recruited for a randomized, 3-day, outpatient, cross-over trial involving: (1) 7-h days of uninterrupted sitting (SIT); and (2) 7-h days of sitting with light-intensity activity breaks [BREAKS; 2-min of treadmill walking (3.2 km/h) every 20 min (total: 17 breaks/day)]. On days 1 and 3, participants underwent a MTT (75 g of carbohydrate, 50 g of fat) and the incremental area under the curve (iAUC) was calculated from hourly blood samples. Generalized estimating equation (GEE) models were adjusted for gender, body mass index (BMI), energy intake, treatment order and pre-prandial values to determine effects of time, condition and time × condition. The glucose iAUC was 1.3 ± 0.5 and 1.5 ± 0.5 mmol·h·l(-1) (mean differences ± S.E.M.) higher in SIT compared with BREAKS on days 1 and 3 respectively (condition effect: P=0.001), with no effect of time (P=0.48) or time × condition (P=0.8). The insulin iAUC was also higher on both days in SIT (day 1: ∆151 ± 73, day 3: ∆91 ± 73 pmol·h·l(-1), P=0.01), with no effect of time (P=0.52) or time × condition (P=0.71). There was no between-treatment difference in triglycerides (triacylglycerols) iAUC. There were significant between-condition effects but no temporal change in metabolic responses to MTT, indicating that breaking up of sitting over 3 days sustains, but does not enhance, the lowering of postprandial glucose and insulin.


Role of Rac GTPase activating proteins in regulation of NADPH oxidase in human neutrophils.
Precise spatiotemporal regulation of O2(-)-generating NADPH oxidases (Nox) is a vital requirement. In the case of Nox1-3, which depend on the small GTPase Rac, acceleration of GTP hydrolysis by GTPase activating protein (GAP) could represent a feasible temporal control mechanism. Our goal was to investigate the molecular interactions between RacGAPs and phagocytic Nox2 in neutrophilic granulocytes. In structural studies we revealed that simultaneous interaction of Rac with its effector protein p67(phox) and regulatory protein RacGAP was sterically possible. The effect of RacGAPs was experimentally investigated in a cell-free O2(-)-generating system consisting of isolated membranes and recombinant p47(phox) and p67(phox) proteins. Addition of soluble RacGAPs decreased O2(-) production and there was no difference in the effect of four RacGAPs previously identified in neutrophils. Depletion of membrane-associated RacGAPs had a selective effect: a decrease in ARHGAP1 or ARHGAP25 level increased O2(-) production but a depletion of ARHGAP35 had no effect. Only membrane-localized RacGAPs seem to be able to interact with Rac when it is assembled in the Nox2 complex. Thus, in neutrophils multiple RacGAPs are involved in the control of O2(-) production by Nox2, allowing selective regulation via different signaling pathways.


Hypertension in the recently weaned Dahl salt-sensitive rat despite a diet deficient in sodium chloride.
The Dahl rat is used as a model of hypertension that is "sensitive" to dietary salt (sodium chloride, NaCl). When dietary salt is supplemented in the Dahl rat, the arterial blood pressure of the "salt-sensitive" strain (S) becomes much greater than that of the "salt-resistant" strain (R). It has been widely reported that arterial blood pressure of the young Dahl S rat is not greater than that of the young Dahl R rat before dietary salt is supplemented. In the present study, however, mean arterial pressure directly measured in unanesthetized, unrestrained S rats was greater than in R rats, both when they had been recently weaned and for at least 10 weeks thereafter, despite their having been fed a diet frankly deficient in salt. In weanling S rats, the ratio of heart weight to body weight was also significantly greater than that in weanling R rats, suggesting that the greater blood pressure in the S rat causes cardiac hypertrophy. Thus, biologic differences demonstrated between the S rat and the R rat after weaning, including the phenomenon of salt-sensitivity, could be a consequence of, or be dependent on, an already extant difference in arterial blood pressure between the two strains.


Cloning and characterization of human adenosine 5'-triphosphate-binding cassette, sub-family A, transporter 2 (ABCA2).
We have isolated the full-length cDNA for human ATP-binding cassette, sub-family A, member 2 transporter (ABCA2). The ORF of this cDNA encodes a protein consisting of 2436 amino acids with apparent molecular weight of M(r) 270,000. Accordingly, ABCA2 is the largest known mammalian ABC transporter described thus far. Analysis of mRNA expression levels indicated that ABCA2 is highest in human brain and has a broad expression pattern in a panel of tumor cell lines. Using specific antibodies to ABCA2 and various organelle marker proteins, ABCA2 was found to colocalize with the lysosomal/endosomal marker LAMP1, forming discrete, punctate intracellular vesicles. In ABCA2-transfected cells, the transporter also colocalized with a fluorescently labeled steroid analogue, estramustine. The sequestration of the steroid into the lysosomal/endosomal compartment indicates a potential substrate specificity for ABCA2. Furthermore, the presence of a lipocalin signature motif in the ABCA2 sequence suggests a possible broad role for this protein in the transport of steroids, lipids, and related molecules.


Aromatic components produced by non-Saccharomyces Cerevisiae derived from natural fermentation of grape.
Aromatic components are important functional products during the wine fermentation process. In the current study, nine strains (Y10, Y5, Y21, Y2, Y19, Y16, Y3, Y13 and Y4) of non-Saccharomyces were isolated from Cabernet Sauvignon grape wine. Aromatic components from Cabernet sauvignon-fermented wine were determined the phylogenetic evolution status of different non-Saccharomyces based on 26S rDNA and D1/D2 sequence analysis and analysed by a gas chromatography-mass spectrometry analysis, and they were grouped into one category with four different yeast genus which were Meyerozyma guilliermondii, Brettanomyces naardenensis, Pichia guilliermondi and Candida fermentati. A total of 102 kinds of aroma components were detected, including 39 kinds of esters, 31 kinds of alcohols, 8 kinds of ketones, 10 kinds of alkanes, 15 kinds of acids and 4 kinds of other aroma substances.


Forces and pressures on the horse's back during bareback riding.
The objectives of this study were to measure forces and pressure profiles when riding with a conventional saddle compared to bareback riding. An electronic pressure mat was used to compare contact area, mean total force and pressure variables for one rider riding seven horses at sitting trot with a conventional saddle or bareback. The use of a saddle was associated with a larger contact area and higher mean total force compared with the bareback condition. Mass normalized mean total force for bareback riding was lower than expected based on the rider's body mass, suggesting that shear forces exerted by the rider's thighs were not being registered by the pressure mat. In spite of the lower total force, the bareback condition was associated with higher average pressure, higher maximal pressure and larger area with mean pressure >11 kPa. Focal pressure concentrations were present beneath the rider's ischial tuberosities in the area of the horse's epaxial muscles when riding bareback but not when using a saddle. It was concluded that bareback riding was associated with focal pressure concentrations that may increase the risk of pressure-induced injury to the horse's epaxial musculature. The findings also emphasized that researchers should remain cognizant of shear forces, which may not be registered by the pressure mat, but may contribute to the effects of riding on the horse's back.


Familial autoimmunity in pedigrees of idiopathic inflammatory myopathy patients suggests common genetic risk factors for many autoimmune diseases.
To test the hypothesis that many autoimmune diseases share common genetic risk factors and to define the frequency and distribution of autoimmune diseases in relatives of patients with very rare disorders, the idiopathic inflammatory myopathies (IIM). We evaluated, in a prospective case-control study, consecutive patients with IIM who were referred to our center and ascertained without regard to family history or known risk factors for autoimmunity, and all available family members. We used a standardized assessment to determine the presence and type of autoimmune disease in each subject. A matched comparison group of control subjects without autoimmune disease who were referred to our center and their families were similarly assessed. Autoimmune diseases were significantly increased in prevalence (21.9%) in the 151 first-degree relatives of the 21 IIM probands compared with the prevalence (4.9%) in the 143 relatives of the 21 control probands (odds ratio [OR] by regression analysis 7.9, 95% confidence interval [95% CI] 2.9-21.9, P < 0.001). Women had more autoimmune disease than men (OR by regression analysis 4.6, 95% CI 2.3-9.0) and the odds ratio for autoimmune disease increased 0.02 per year of age. These disorders tended to follow the frequency distribution of autoimmune diseases in the general population. Genetic modeling studies showed that a non-Mendelian polygenic inheritance pattern for autoimmune disease was most consistent with these data. Autoimmune diseases are significantly increased in frequency in first-degree relatives of IIM patients, affect more women than men, increase with age, and are distributed in a pattern similar to that in the general population. Many autoimmune disorders share genes that together act as polygenic risk factors for autoimmunity.


Immunogenicity of single vaccination with BNT162b2 or ChAdOx1 nCoV-19 at 5-6 weeks post vaccine in participants aged 80 years or older: an exploratory analysis.
In several countries, extended interval COVID-19 vaccination regimens are now used to accelerate population coverage, but the relative immunogenicity of different vaccines in older people remains uncertain. In this study we aimed to assess the antibody and cellular responses of older people after a single dose of either the BNT162b2 vaccine (tozinameran; Pfizer-BioNTech) or ChAdOx1 nCoV-19 vaccine (Oxford University-AstraZeneca). Participants aged 80 years or older, who did not live in a residential or care home or require assisted living, and had received a single dose of either the BNT162b2 vaccine or ChAdOx1 nCoV-19 vaccine were eligible to participate. Participants were recruited through local primary care networks in the West Midlands, UK. Blood samples and dried blood spots were taken 5-6 weeks after vaccination to assess adaptive immune responses using Elecsys electrochemiluminescence immunoassay and cellular responses by ELISpot. Primary endpoints were percentage response and quantification of adaptive immunity. Between Dec 29, 2020, and Feb 28, 2021, 165 participants were recruited and included in the analysis. 76 participants had received BNT162b2 (median age 84 years, IQR 82-89; range 80-98) and 89 had received ChAdOx1 nCoV-19 (median age 84 years, 81-87; 80-99). Antibody responses against the spike protein were detectable in 69 (93%) of 74 BNT162b2 vaccine recipients and 77 (87%) of 89 ChAdOx1 nCoV-19 vaccine recipients. Median antibody titres were of 19·3 U/mL (7·4-79·4) in the BNT162b2 vaccine recipients and 19·6 U/mL (6·1-60·0) in the ChAdOx1 nCoV-19 vaccine recipients (p=0·41). Spike protein-specific T-cell responses were observed in nine (12%) of 73 BNT162b2 vaccine recipients and 27 (31%) of 88 ChAdOx1 nCoV-19 vaccine recipients, and median responses were three-times higher in ChAdOx1 nCoV-19 vaccine recipients (24 spots per 1 × 106 peripheral blood mononuclear cells) than BNT162b2 vaccine recipients (eight spots per 1 × 106 peripheral blood mononuclear cells; p<0·0001). Humoral and cellular immune responses against spike protein were correlated in both cohorts. Evidence of previous SARS-CoV-2 infection was seen in eight participants (n=5 BNT162b2 recipients and n=3 ChAdOx1 nCoV-19 recipients), and was associated with 691-times and four-times increase in humoral and cellular immune responses across the whole cohort. Single doses of either BNT162b2 or ChAdOx1 nCoV-19 in older people induces humoral immunity in most participants, and is markedly enhanced by previous infection. Cellular responses were weaker, but showed enhancement after the ChAdOx1 nCoV-19 vaccine at the 5-6 week timepoint. Medical Research Council, National Institute for Health Research, and National Core Studies.


[Chronic gastroduodenitis in children with atopic dermatitis].
The results of investigation of 49 children suffering from chronic gastroduodenitis and atopic dermatitis are presented. All the child underwent serological blood analyses for Epsteine-Barr virus antibodies and fibrogastroduodenoscopy with antral and duodenal mucosal biopsy. Hystomorphological and immunohystochemical studies of mucosal biopsy specimens for Epsteine-Barr virus were carried out. The role of Epsteine-Barr virus in genesis of chronic gastroduodenitis is detected.


Long-term passages of Plantago asiatica mosaic virus alter virulence and multiplication in Nicotiana benthamiana plants.
We demonstrated the infectivity and host adaptation of a viola isolate of Plantago asiatica mosaic virus (PlAMV-Vi) in an asymptomatic host, Nicotiana benthamiana, through long-term serial passages. Serial passaging of a green fluorescent protein-tagged full-length cDNA clone of PlAMV-Vi (PlAMV-ViGFP) in N. benthamiana plants resulted in the appearance of a new virus line inducing leaf-crinkle symptoms, the Leaf Crinkle (LC) line. Virus titers were higher for both in the LC and the 14th passage line(s) of PlAMV-ViGFP compared with the original line. The LC line was found to have seven unique nucleotide mutations that may have contributed to its higher virulence and multiplication rate in N. benthamiana.


Effects of salience are short-lived.
A salient event in the visual field tends to attract attention and the eyes. To account for the effects of salience on visual selection, models generally assume that the human visual system continuously holds information concerning the relative salience of objects in the visual field. Here we show that salience in fact drives vision only during the short time interval immediately following the onset of a visual scene. In a saccadic target-selection task, human performance in making an eye movement to the most salient element in a display was accurate when response latencies were short, but was at chance when response latencies were long. In a manual discrimination task, performance in making a judgment of salience was more accurate with brief than with long display durations. These results suggest that salience is represented in the visual system only briefly after a visual image enters the brain.


The characterization of tumor apoptosis after experimental radiosurgery.
We sought to evaluate whether radiosurgery induces apoptosis in an experimental glioma model and to elucidate the time course of this radiobiologic phenomenon. Fischer 344 rats harboring established intracranial 9L gliosarcomas underwent radiosurgery (n = 42) or no radiosurgery (n = 45). Animals were sacrificed at 3, 6, 12, 24, 48, 72 h, and 1 or 2 weeks after treatment and in situ tumor apoptosis was assessed by specific staining. Tumor apoptosis was noted to be statistically higher in radiosurgery-treated animals relative to controls at the 6-, 24-, and 48-hour time points following radiosurgery. Radiosurgery induces apoptosis in the rat intracranial 9L gliosarcoma in a time-dependent fashion. The time course of this radiobiologic phenomenon begins at approximately 6 h following radiosurgery, continues up to 48 h, and begins to decline by 72 h.


Can we manage gut microbiome imbalances in patients with bipolar disorder with pharmacotherapy?
A novel new area of exploration in the treatment of bipolar disorder is the gut brain axis. Studies have shown significant differences between the gut microbiome in those with bipolar disorder and those without the illness, as well as documented microbiome changes associated with the effects of bipolar pharmacotherapy and targeted microbial interventions. Although we have evidence suggesting the bi-directional relationship between the gut microbiome and psychiatric disorders, we are still unable to utilize this understanding clinically. We need to better understand the factors that impact the microbiome in this illness and vice versa. Additionally, changes in gut microbiome in bipolar disorder might be used for biomarker identification with a potential to help in diagnosis and monitoring of the condition. It is an important area for further research and may provide improved therapeutic outcomes.


Bounded Solidarity as an Asset for Public Health Care Intervention.
The relationship between social capital and public health has been extensively analyzed. However, not much has been written about the formation of social capital among citizens and public health workers in times of a pandemic. Our aim is to analyze social capital development through the prism of bounded solidarity and seek its manifestations toward public health workers. A qualitative self-administered survey was used to analyze what actions, practices, attitudes, and reasons inspired citizens to behave as they did with respect to public health workers during the first weeks of lockdown under the COVID-19 pandemic. Respondents, mostly from European countries, reveal that citizens aimed to prevent the collapse of the public health system through reinforcing trust toward institutions, legitimizing health care personnel expertise, practicing reciprocity and altruism, giving recognition to public health workers, and providing them with means. Finally, recommendations for public health communication on risks and crises are discussed.


Patient and family-centered care for children: A concept analysis.
Family-centered care has evolved into patient and family-centered care. Although this is not a new concept; however, its application to nursing practice is very challenging among nurses due to its ambiguity. This study aimed to clarify the concept of patient and family-centered care for children. Walker and Avant's concept analysis method was used. A literature search was also done using the following databases: Google Scholar, ProQuest, ScienceDirect, and Scopus, for articles published from 2011 to 2021. The defining attributes of patient and family-centered care are partnership, communication, respect, and compassion. Antecedents include patient and family involvement, readiness to collaborate and participate, competency and desire of the care professional team, supportive environment, and policies. Consequences of the patient and family-centered care include improved child outcomes and quality of life, promotion of patient safety, increased patient and family satisfaction, enhancement of humanistic values, reduction of hospitalization cost and length of stay, and decreased stress, anxiety, and depression in family members. Four attributes of patient and family-centered care, its antecedents, and consequences may aid researchers in better understanding the concept and its application in nursing practice. This concept can also be used to establish quality care delivery strategies and promote professional relationships between nurses, patients, and families in clinical settings.


Personality and Incident Alzheimer's Disease: Theory, Evidence, and Future Directions.
Personality, especially the dimensions of neuroticism and conscientiousness, has prospectively predicted the risk of incident Alzheimer's disease (AD). Such a relationship could be explained by personality and AD risk having a common cause such as a gene; by personality creating a predisposition for AD through health behavior or inflammation; by personality exerting a pathoplastic effect on the cognitive consequences of neuropathology; or by AD and personality change existing on a disease spectrum that begins up to decades before diagnosis. Using the 5-dimensional taxonomy of personality, the present review describes how these models might arise, the evidence for each, and how they might be distinguished from one another empirically. At present, the evidence is sparse but tends to suggest predisposition and/or pathoplastic relationships. Future studies using noninvasive assessment of neuropathology are needed to distinguish these 2 possibilities.


In vitro and in vivo interaction between murine fibrosarcoma cells and natural killer cells.
Murine fibrosarcoma cells were examined for sensitivity to killing by natural killer (NK) and natural cytotoxic lymphocytes from mouse spleens. These tumor cell lines were sensitive to killing by effector cells which were nonadherent to plastic or nylon wool, Thy-1 negative, asialo-GM1 negative, and present in the spleens of beige mice, nude mice, and A/J mice, as well as in the spleens of normal syngeneic and allogeneic control mice. This indicates that the cytotoxic effects were due to natural cytotoxic lymphocytes rather than to NK lymphocytes, T-cells, or macrophages. Although the fibrosarcoma cells were not killed in vitro by endogenous NK cells, these tumor cells were able to "cold target" compete for Yac-1 (an NK-sensitive target) killing and to bind to asialo-GM1-positive, nonadherent spleen lymphocytes in a target cell binding assay. This suggests that the fibrosarcoma cells were recognized by NK cells. In addition, these cell lines were killed in a 4-h NK cytotoxicity assay by polyinosinic-polycytidylic acid-activated effector lymphocytes. The interaction between NK cells and the murine fibrosarcoma cells may have in vivo significance. When syngeneic mice were treated with anti-asialo-GM1 serum to eliminate NK activity and then given i.v. injections of the fibrosarcoma cells, many more lung tumors developed than in control animals. The structural basis for the recognition of the murine fibrosarcoma cells by the NK effector cells is not known. However, laminin may be involved. When the fibrosarcoma cells, which have receptors for the laminin molecule, were preincubated with laminin, they were reduced in their ability to compete for the killing of Yac-1 cells by the NK effectors and had reduced capacity to bind to NK cells in a target cell binding assay.


Rational design and simple chemistry yield a superior, neuroprotective HDAC6 inhibitor, tubastatin A.
Structure-based drug design combined with homology modeling techniques were used to develop potent inhibitors of HDAC6 that display superior selectivity for the HDAC6 isozyme compared to other inhibitors. These inhibitors can be assembled in a few synthetic steps, and thus are readily scaled up for in vivo studies. An optimized compound from this series, designated Tubastatin A, was tested in primary cortical neuron cultures in which it was found to induce elevated levels of acetylated alpha-tubulin, but not histone, consistent with its HDAC6 selectivity. Tubastatin A also conferred dose-dependent protection in primary cortical neuron cultures against glutathione depletion-induced oxidative stress. Importantly, when given alone at all concentrations tested, this hydroxamate-containing HDAC6-selective compound displayed no neuronal toxicity, thus, forecasting the potential application of this agent and its analogues to neurodegenerative conditions.


Lathyrus sativus transcriptome resistance response to Ascochyta lathyri investigated by deepSuperSAGE analysis.
Lathyrus sativus (grass pea) is a temperate grain legume crop with a great potential for expansion in dry areas or zones that are becoming more drought-prone. It is also recognized as a potential source of resistance to several important diseases in legumes, such as ascochyta blight. Nevertheless, the lack of detailed genomic and/or transcriptomic information hampers further exploitation of grass pea resistance-related genes in precision breeding. To elucidate the pathways differentially regulated during ascochyta-grass pea interaction and to identify resistance candidate genes, we compared the early response of the leaf gene expression profile of a resistant L. sativus genotype to Ascochyta lathyri infection with a non-inoculated control sample from the same genotype employing deepSuperSAGE. This analysis generated 14.387 UniTags of which 95.7% mapped to a reference grass pea/rust interaction transcriptome. From the total mapped UniTags, 738 were significantly differentially expressed between control and inoculated leaves. The results indicate that several gene classes acting in different phases of the plant/pathogen interaction are involved in the L. sativus response to A. lathyri infection. Most notably a clear up-regulation of defense-related genes involved in and/or regulated by the ethylene pathway was observed. There was also evidence of alterations in cell wall metabolism indicated by overexpression of cellulose synthase and lignin biosynthesis genes. This first genome-wide overview of the gene expression profile of the L. sativus response to ascochyta infection delivered a valuable set of candidate resistance genes for future use in precision breeding.


Clostridium septicum foot gangrene associated with colorectal cancer.
Since the second half of the 20th century, an association between the occurrence of Clostridium septicum and Streptococcus gallolyticus infections in patients with colorectal cancer has been described in specialist literature. Infections are manifested by bacteremia, septic embolism, cellulitis, myonecrosis, and gas gangrene of the limbs. The authors present a case of a rare association between lower limb gangrene caused by the septic embolization of a Clostridium septicum infection and malignancy of colon ascendens in a polymorbid patient. Gangrene of the lower limb led to septic shock requiring acute amputation treatment. After managing the acute condition, the patient was operated on for a malignant colon tumour. The process of carcinogenesis often takes years and is almost asymptomatic. The occurrence of S. bovis/S. equinus (SBSEC) and C. septicum bacteremia, respectively, is relatively rare, but their presence is often associated with the occurrence of malignancy, most often of the lower gastrointestinal tract. This paraneoplastic symptom may be the first manifestation of a malignant disease. The effect of exotoxins can lead to sepsis or even septic shock with a mortality of 48-56%. Clostridium septicum and Streptococcus gallolyticus infections are rare in clinical practice. However, their presence can be a first paraneoplastic symptom, and therefore the doctor should look for a possible oncological disease when they are detected. The main diagnostic methods include colonoscopy and imaging, especially CT scan.


Prevalence of metabolic syndrome among breast cancer survivors in East Coast of Peninsular Malaysia.
To date, limited data are available on metabolic syndrome prevalence among breast cancer survivors in Malaysia. Therefore, this study was conducted to determine the prevalence of metabolic syndrome and abnormal metabolic syndrome components among breast cancer survivors in East Coast of Peninsular Malaysia. This cross-sectional study included 95 breast cancer survivors (age 53.7 ± 7.6 years) who have completed main cancer treatments for ≥6 months. Cancer survivors were recruited from two main government hospitals in Kelantan and Terengganu using a purposive sampling method. According to the Harmonized criteria, the metabolic syndrome prevalence was 50.5%. Among those with metabolic syndrome, the most prevalent abnormal metabolic components were triglycerides (91.2%), fasting blood glucose (79.6%) and HDL-c level (78.4%). Except for total cholesterol and LDL-c, all other metabolic syndrome components were significantly different (p < 0.05) between those with and without metabolic syndrome. Significant differences between metabolic syndrome and non-metabolic syndrome groups were found for weight, BMI, waist circumference, body fat percentage and cancer stages (p < 0.05). However, no significant relationship was reported between sociodemographic, clinical parameters and metabolic syndrome among breast cancer survivors in this study. Metabolic syndrome was highly prevalent among breast cancer survivors. It is recommended for health care professionals to closely monitor and improve the triglycerides, blood glucose and HDL-c level of the breast cancer survivors under their care to control the detrimental effect of metabolic syndrome.