Shared Decision-Making in Patients Seeking Surgery for Facial Trauma: The Role of Decisional Conflict and Perceived Discrimination.
Background: Shared decision-making (SDM) may facilitate challenging discussions between patients with facial trauma and reconstructive surgeons. Objective: To determine among patients seeking surgical evaluation for facial trauma, whether patient demographics, decisional conflict (DC), or experiences of discrimination in health care are associated with patient perceptions of SDM, as measured by scored responses on the CollaboRATE-10 questionnaire. Methods: English-speaking adults who presented to the offices of five facial trauma surgeons were contacted by telephone after their visit to complete a cross-sectional survey. Results: After screening 247 patients, 131 patients were recruited (53.0%). DC and history of discrimination were associated with lower perceived SDM (p < 0.001 and p = 0.048, respectively). After adjusting for age, sex, race, education, initial emergency department presentation, DC, and past discrimination, patients of older age (odds ratio [OR] 1.1, 95% confidence interval [CI] 1.02-1.09) and non-White race (OR 3.5, 95% CI 1.1-11.4) had higher perceptions of SDM; patients with DC (OR 0.52, 95% CI 0.01-0.20) reported less SDM. Conclusions: Patients who present to clinic for surgical evaluation after facial trauma feel that their physicians involve them less when deciding on a treatment plan if they have experienced discrimination in health care settings in the past, or if they have significant difficulty deciding between treatment options.


Sleeping beauties cited in patents: Is there also a dormitory of inventions?
A 'Sleeping Beauty in Science' is a publication that goes unnoticed ('sleeps') for a long time and then, almost suddenly, attracts a lot of attention ('is awakened by a prince'). In our foregoing study we found that roughly half of the Sleeping Beauties are application-oriented and thus are potential Sleeping Innovations. In this paper we investigate a new topic: Sleeping Beauties that are cited in patents. In this way we explore the existence of a dormitory of inventions. To our knowledge this is the first study of this kind. We investigate the time lag between publication of the Sleeping Beauty and the first citation by a patent. We find that patent citation may occur before or after the awakening and that the depth of the sleep, i.e., citation rate during the sleeping period, is no predictor for later scientific or technological impact of the Sleeping Beauty. A surprising finding is that Sleeping Beauties are significantly more cited in patents than 'normal' papers. Inventor-author self-citations relations occur only in a small minority of the Sleeping Beauties that are cited in patents, but other types of inventor-author links occur more frequently. We develop an approach in different steps to explore the cognitive environment of Sleeping Beauties cited in patents. First, we analyze whether they deal with new topics by measuring the time-dependent evolution in the entire scientific literature of the number of papers related to both the precisely defined topics as well as the broader research theme of the Sleeping Beauty during and after the sleeping time. Second, we focus on the awakening by analyzing the first group of papers that cites the Sleeping Beauty. Third, we create concept maps of the topic-related and the citing papers for a time period immediately following the awakening and for the most recent period. Finally, we make an extensive assessment of the cited and citing relations of the Sleeping Beauty. We find that tunable co-citation analysis is a powerful tool to discover the prince(s) and other important application-oriented work directly related to the Sleeping Beauty, for instance papers written by authors who cite Sleeping Beauties in both the patents of which they are the inventors, as well as in their scientific papers.


Advances in comparative physiology from high-speed imaging of animal and fluid motion.
Since the time of Muybridge and Marey in the last half of the nineteenth century, studies of animal movement have relied on some form of high-speed or stop-action imaging to permit analysis of appendage and body motion. In the past ten years, the advent of megapixel-resolution high-speed digital imaging with maximal framing rates of 250 to 100,000 images per second has allowed new views of musculoskeletal function in comparative physiology that now extend to imaging flow around moving animals and the calculation of fluid forces produced by animals moving in fluids. In particular, the technique of digital particle image velocimetry (DPIV) has revolutionized our ability to understand how moving animals generate fluid forces and propel themselves through air and water. DPIV algorithms generate a matrix of velocity vectors through the use of image cross-correlation, which can then be used to calculate the force exerted on the fluid as well as locomotor work and power. DPIV algorithms can also be applied to images of moving animals to calculate the velocity of different regions of the moving animal, providing a much more detailed picture of animal motion than can traditional digitizing methods. Although three-dimensional measurement of animal motion is now routine, in the near future model-based kinematic reconstructions and volumetric analyses of animal-generated fluid flow patterns will provide the next step in imaging animal biomechanics and physiology.


N-3 fatty acid-rich diet prevents early response of interleukin-6 elevation in trinitrobenzene sulfonic acid-induced enteritis.
Dietary fat is an important factor involved in the pathogenesis of inflammatory bowel disease (IBD). It remains unclear how n-3 and n-6 fatty acids modulate intestinal inflammation. In this study, we investigated the effects of n-3 and n-6 fatty acid-rich diets on trinitrobenzene sulfonic acid (TNBS)-induced enteritis. The rats were fed an n-3 or n-6 rich-diet for 12 days, and then starved for the following 2 days. An intraileal injection of TNBS was administered, and TNBS-enteritis subsequently developed. Macroscopic and histological examination was performed after 24 h. Serum cytokine levels were determined by ELISA. The n-6 fatty acid-rich diet markedly enhanced mucosal damage as compared to the n-3 fatty acid-rich diet. The damage score was significantly higher in the n-6 fatty acid-rich diet group (P<0.05). Histological changes in the mucosa were more severe in the n-6 fatty acid-rich diet group than in the n-3 fatty acid-rich group. Serum IL-6 levels were significantly higher in the n-6 fatty acid-rich diet group than in the n-3 fatty acid-rich group (P<0.05). On the other hand, there were no differences in serum TNF-alpha levels. The n-3 fatty acid-rich diet effectively reduced early mucosal inflammation in TNBS enteritis. The effects of the n-3 fatty acids were associated with blockage of mucosal IL-6 secretion. Our data suggest that n-3 fatty acid-rich diet may be applicable for enteral nutrition in the treatment of IBD patients.


Presentation and outcome of emphysematous renal tract disease in patients with diabetes mellitus.
Emphysematous renal tract disease (ERTD) is a rare necrotizing infection of the renal parenchyma and urinary tract caused by gas-producing organisms. ERTD deserves special attention because of its life-threatening potential. To study the clinical features, radiological classification and prognostic factors of ERTD; and to compare the modalities of management and the outcome among the various radiological classes of ERTD. Twenty consecutive patients with diabetes and ERTD, seen over last 3 years in a tertiary care institute of north India, were included in the study. All patients were subjected to computerized tomography (CT) after initial diagnosis by ultrasonography. They were classified into 5 classes as previously described. All patients included in the study were conservatively managed with appropriate antibiotics and/or percutaneous drainage or surgery if required. Mean age (+/- SD) of these subjects was 54.4 +/- 20.6 years; duration of diabetes mellitus 8.6 +/- 5.8 years, and duration of symptoms related with ERTD ranged from 3 days to 3 months. Two patients had isolated emphysematous cystitis, 13 patients had emphysematous pyelonephritis (EPN), 3 had both EPN and cystitis, and 1 patient had EPN with cholecystitis, and 1 patient had EPN with pyomyositis. Only 7 (35%) patients had a history of pneumaturia. Escherichia coli was the commonest microorganism. The radiological distribution in 18 (2 had isolated cystitis) patients with EPN was: 2 patients had class 1; 1 had class 2; 2 had class 3A; 11 had class 3B, and 2 had class 4. Of 20 patients 11 (55%) survived. However, those patients who died had severe EPN based on radiological class (6 had class 3B and 1 had class 4). There was no significant difference between the survivor and non-survivor groups with respect to age, gender, duration of diabetes mellitus, duration of symptoms, serum creatinine level, total leukocyte count, hemoglobin, platelet count and culture positivity. Computerized tomographic class 3B or 4 is the most reliable predictor of outcome in patients with ERTD.


Evaluation of Leuconostoc citreum HO12 and Weissella koreensis HO20 isolated from kimchi as a starter culture for whole wheat sourdough.
Leuconostoc citreum HO12 and Weissella koreensis HO20 isolated from kimchi were evaluated as starter cultures in the making of whole wheat sourdough bread. After 24h of fermentation at 25 °C, both lactobacilli grew to the final cell numbers of ca. 10(9)cfu/g dough, and both doughs had similar pHs and total titratable acidities. In addition, the fermentation quotient of the dough with Lc. citreum HO12 was slightly lower than that of the dough with W. koreensis HO20 (1.6 versus 2.8). Sourdoughs and bread with 50% sourdough produced with the starter cultures exhibited consistent ability to retard the growth of bread spoilage fungi (Penicillium roqueforti and Aspergillus niger) and rope-forming bacterium (Bacillus subtilis). Sourdough breads underwent a significant reduction in bread firming during storage. It seems that both lactobacilli have the potential to improve the shelf-life of wheat bread. The results indicate that the selected lactobacilli have unique fermentation characteristics and produce sourdough breads with overall satisfactory quality.


The reliability of lymph-node staging in rectal cancer after preoperative chemoradiotherapy.
To determine the prognostic significance of the nodal stage and number of nodes recovered in the surgical specimen after preoperative synchronous chemoradiation (SCRT) and surgery for locally advanced or unresectable rectal cancer. One hundred and eighty-two consecutive patients with locally advanced or unresectable (T3/T4) rectal carcinomas were entered on a prospective database and treated in this department with preoperative chemoradiation, followed 6-12 weeks later by surgical resection. Most patients received chemotherapy in the form of low-dose folinic acid and 5-fluorouracil (5-FU) 350 mg/m2 via a 60-min infusion on days 1-5 and 29-33 of a course of pelvic radiotherapy delivered at a dose of 45 Gy in 25 fractions over 33 days to a planned volume. After resection, patients with a positive circumferential margin (< or = 1 mm), extranodal deposits or Dukes' C histology received adjuvant 5-FU-based-chemotherapy (n = 40). After SCRT, 161 patients underwent resection. Twenty-one patients remained unresectable or refused an exenterative operation. Median follow-up is 36 months. Down-staging was achieved in most patients, with 19 having a complete pathological response (pT0). The median number of lymph nodes recovered for all patients was five (range 0-21). The 3-year survival rate for node-positive patients is 47%, for node-negative patients with less than three lymph nodes recovered is 62% and for node-negative patients with three or more lymph nodes recovered is 70%. Compared with node-positive patients, simple regression models revealed a reduced hazard ratio (HR) of 0.72 (0.36-1.43) for node-negative patients with less than three nodes recovered and 0.48 (0.26-0.89) for node-negative patients with three or more lymph nodes recovered. In a multivariate model, including nodal status, excision status, age and sex only positive excision margins significantly predicted a poor outcome: HR = 3.05 (1.55-5.97). The number of nodes found after preoperative chemoradiation is a significant prognostic factor by univariate analysis. In this study, patients with node-negative histology, and at least three nodes recovered, had better long-term survival than patients in whom two or less nodes were recovered or with positive nodes. This effect was attenuated by the inclusion of excision status in multivariate models.


[Pathogenicity factors of enteric Salmonellae].
The number of cases of salmonellosis has steadily increased during the last decade. Until the end of the 70s, the serotype Salmonella typhimurium was most commonly isolated, but since 1986 the serotype S. enteritidis has become more common. Recent research has shown that the colon is more frequently infected than was earlier recognized, but most common is still an acute enterocolitis during an infection with salmonella. In severe cases, salmonella can spread from the gut, the site of infection, to cause a systemic disease. As in vitro studies have shown, gastroenteritic salmonellae seem to possess a number of so-called virulence factors that help them to evade the host's defenses against bacterial infection. Colonisation in the gut seems to be dependent on a 66 kD heat shock protein (HSP), which binds to a 15 kD glycoprotein present in gut mucus. For penetration into the mucosa, by invasion of the epithelial cells, bacterial invasions are newly synthesized. These proteins distort the epithelial membrane and induce a port of entrance. Macrophages will attack and engulf the bacteria, but salmonella can withstand these professional killers, and even grow intracellularly in them. In order to do so, not only LPS is required, but also specific outer membrane proteins (OMP), porins. Moreover, during their intracellular survival the bacteria need to adapt to the new microenvironment, and in reaction to stress, new HSPs are expressed. Finally, the O-specific sugar chains prevent the otherwise lytic action of complement in blood serum.(ABSTRACT TRUNCATED AT 250 WORDS)


Dual-mode security authentication of SrAl2 O4 :Eu,Dy phosphor encapsulated in electrospun cellulose acetate nanofibrous films.
Photochromic inks have been an attractive authentication strategy to improve the anti-counterfeiting efficiency of commercial products. However, recent reports have shown significant disadvantages with photochromic inks, including poor durability and high cost. In this context, we developed novel photochromic nanofibres for advanced anti-counterfeiting applications. Lanthanide-doped strontium aluminate (LdSA) nanoparticles (NPs) were prepared and immobilized into electrospun cellulose acetate nanofibres (CANF). Authentication materials immobilized with inorganic photochromic agents can warranty durability and photostability. Therefore, the ultraviolet-stimulated photochromism of LdSA-encapsulated cellulose acetate nanofibres (LdSA@CANF) demonstrated high reversibility and photostability. A broad range of cellulose acetate nanofibres with unique emission characteristics was developed when applying different ratios of LdSA NPs. LdSA@CANF appeared colourless under visible daylight, whereas a green emission was monitored under ultraviolet-light illumination. The shape and chemical content of the photochromic fibrous films were examined using various analytical techniques. The mechanical characteristics of LdSA@CANF-coated paper were investigated. The emission wavelength was detected at 514 nm to designate green colour, whereas the excitation wavelength was detected at 369 nm to indicate transparency. The prepared cellulose acetate nanofibrous film can be described as an efficient strategy for the anti-counterfeiting of commercialized items.


Testosterone and the heart: friend or foe?
Cardiovascular disease (CVD) is the leading cause of death in women aged 65 years and older. Sex hormones have been implicated as having a critical role in the evolution of CVD, with the focus mainly on estrogens in women. Available data also indicate that low testosterone blood levels may be detrimental to cardiovascular function in women. At blood concentrations considered normal for premenopausal women, testosterone has favorable effects on blood vessel function (relaxation and contraction), much of which is determined by the endothelial cells that line the inside of blood vessels. Testosterone enhances endothelium-dependent and independent brachial artery vasodilation and has an acute systolic blood pressure-lowering effect in postmenopausal women. Advantageous effects of testosterone in animal models have been seen for myocardial function and cardiac electrical signaling. Human data are mainly limited to observational and mechanistic studies, which mostly demonstrate beneficial effects of testosterone on cardiovascular health. Few studies of testosterone use in women, with cardiovascular endpoints as primary outcomes, have been published.


Memotain: A CAD/CAM nickel-titanium lingual retainer.
Approximately 1/2 of maxillary and 1/5 of mandibular multi-stranded lingual retainers fail during retention in some form, either bond failure or wire breakage. Memotain is a new CAD/CAM fabricated lingual retainer wire made of custom-cut nickel-titanium, as an alternative to multi-stranded lingual retainers. It offers numerous perceived advantages to the traditional multi-stranded stainless steel wire, including precision fit, avoidance of interferences, corrosion resistance and even the potential for minor tooth movement as an active lingual retainer.


Insulin detemir enhances proglucagon gene expression in the intestinal L cells via stimulating β-catenin and CREB activities.
Insulin therapy using insulin detemir (d-INS) has demonstrated weight-sparing effects compared with other insulin formulations. Mechanisms underlying these effects, however, remain largely unknown. Here we postulate that the intestinal tissues' selective preference allows d-INS to exert enhanced action on proglucagon (Gcg) expression and the production of glucagon-like peptide (GLP)-1, an incretin hormone possessing both glycemia-lowering and weight loss effects. To test this hypothesis, we used obese type 2 diabetic db/db mice and conducted a 14-day intervention with daily injection of a therapeutic dose of d-INS or human insulin (h-INS) in these mice. The body weight of the mice after 14-day daily injection of d-INS (5 IU/kg) was decreased significantly compared with those injected with the same dose of h-INS or saline. The weight-sparing effect of d-INS was associated with significantly elevated circulating levels of total GLP-1 and reduced food intake. Histochemistry analysis demonstrated that d-INS induced rapid phosphorylation of protein kinase B (Akt) in the gut L cells of normal mice. Western blotting showed that d-INS stimulated Akt activation in a more rapid and enhanced fashion in the mouse distal ileum compared with those by h-INS. In vitro investigation in primary fetal rat intestinal cell (FRIC) cultures showed that d-INS increased Gcg mRNA expression as determined by Northern blotting and real-time RT-PCR. Consistent with these in vivo investigations, d-INS significantly increased GLP-1 secretion in FRIC cultures. Consistently, d-INS was also shown to induce rapid phosphorylation of Akt in the clonal gut cell line GLUTag. Furthermore, d-INS increased β-catenin phosphorylation, its nuclear translocation, and enhanced cAMP response element-binding protein (CREB) phosphorylation in a phosphatidylinositol 3-kinase and/or mitogen-activated protein kinase kinase/extracellular signal-regulated kinase-sensitive manner. We suggest that the weight-sparing benefit of d-INS in mice is related to its intestinal tissues preference that leads to profound stimulation of Gcg expression and enhanced GLP-1 secretion in intestinal L cells, potentially involving the activation of insulin/β-catenin/CREB signaling pathways.


Enhancing shielding of triplet energy transfer to poly(p-phenylene)s from phosphor dopant by addition of branched alcohol for highly efficient electrophosphorescence.
To obtain an efficient electrophosphorescent device, one needs to consider quenching of phosphor phosphorescence brought by the low triplet energy of the host because the exothermic energy transfer can effectively quench phosphor phosphorescence and markedly lower the device efficiency. Here, a facile approach of adding a branched alcohol (3-tert-butyl-2,2,4,4-tetramethylpentan-3-ol, ROH) into green emission phosphor-doped dialkoxyl-substituted poly(para-phenylene)s (PPPs) is demonstrated to effectively enhance shielding of triplet energy transfer to PPPs from the phosphor, resulting from a formation of self-assembly structure that block direct contact between phosphor and the main chains. The green electrophosphorescent device performance can be improved from 7.1 and 32.2 cd/A to 25.1 and 42 cd/A for PPP with dioctoxyl substituents (dC(8)OPPP) and with carbozole (Cz)-capped dialkoxyl-substituents (CzPPP), respectively. The latter result 42 cd/A is the highest record for green emission in polymer light emitting diode. This finding suggests that promotion of specific electro-optical properties for small molecule and polymer can be obtained through a self-assembling interaction in addition to chemical structure modification.


Increasing thermoelectric efficiency: dynamical models unveil microscopic mechanisms.
Dynamical nonlinear systems provide a new approach to the old problem of increasing the efficiency of thermoelectric machines. In this review, we discuss stylized models of classical dynamics, including non-interacting complex molecules in an ergodic billiard, a disordered hard-point gas and an abstract thermoelectric machine. The main focus will be on the physical mechanisms, unveiled by these dynamical models, which lead to high thermoelectric efficiency approaching the Carnot limit.


Cathodoluminescence in the scanning transmission electron microscope.
Cathodoluminescence (CL) is a powerful tool for the investigation of optical properties of materials. In recent years, its combination with scanning transmission electron microscopy (STEM) has demonstrated great success in unveiling new physics in the field of plasmonics and quantum emitters. Most of these results were not imaginable even twenty years ago, due to conceptual and technical limitations. The purpose of this review is to present the recent advances that broke these limitations, and the new possibilities offered by the modern STEM-CL technique. We first introduce the different STEM-CL operating modes and the technical specificities in STEM-CL instrumentation. Two main classes of optical excitations, namely the coherent one (typically plasmons) and the incoherent one (typically light emission from quantum emitters) are investigated with STEM-CL. For these two main classes, we describe both the physics of light production under electron beam irradiation and the physical basis for interpreting STEM-CL experiments. We then compare STEM-CL with its better known sister techniques: scanning electron microscope CL, photoluminescence, and electron energy-loss spectroscopy. We finish by comprehensively reviewing recent STEM-CL applications.


Arthrodesis of the first metatarsophalangeal joint for hallux valgus in rheumatoid arthritis.
We reviewed the results of reconstruction of the fore part of the foot in rheumatoid patients by arthrodesis of the first metatarsophalangeal joint. The follow-up averaged 4.1 years (range, 2.0 to 7.25 years). Eighteen feet in eleven women were operated on. Twelve feet underwent total reconstruction of the fore part: arthrodesis of the first metatarsophalangeal joint and excision of all of the lesser metatarsophalangeal joints. Six feet underwent subtotal reconstruction, which included arthrodesis of the first metatarsophalangeal joint. The results were classified as excellent in fourteen feet, good in two, and fair in two. There were no poor results. Metatarsophalangeal bone fusion was achieved in all but one foot (fusion rate, 94 per cent). The one fibrous ankylosis was painless, with satisfactory function. Interphalangeal degenerative joint disease was a radiographic but not a clinical sequela. Arthrodesis of the first metatarsophalangeal joint provided stability that permanently corrected deformity, permitted the patients to wear ordinary shoes, and, in combination with excisional arthroplasty of involved lesser metatarsophalangeal joints, relieved disabling pain in the fore part of the foot.


[A dangerous nasal foreign body: the button battery].
The effects of an incorporated button battery as a nasal foreign body with regard to the endonasal structures are serious. The following case report will illustrate this on the case of a 4?-year old boy. The acute treatment consisted of the removal of the battery and the debridement of the necroses. Already these measures required considerable medical expenditure. Reconstructive measures which may be needed in the future, will also require a lot of resources. Button batteries as incorporated nasal foreign bodies can lead to severe damage to the endonasal mucoperichondrium. It can lead to necrosis of the nasal septum cartilage and to consecutive nasal septum perforation. Based on these experiences and a review of literature, the conclusions should be drawn that an incorporated button battery should be considered as an ENT emergency case and the immediate removal of the foreign body should be striven for.


Localization of multiple ships using a vertical array in shallow water.
The blind deconvolution employs conventional plane-wave beamforming using an array, selects a well-resolved angle of arrival for beam steering to estimate the phase component of an unknown source waveform, and then extracts the Green's function between the source and the array. In this letter, the approach is extended to multiple-ship scenarios in which the multipath arrivals from one ship are masked by other ships, adopting the basic concept of successive interference cancellation. Once individual Green's functions are available, the array invariant method based on the beam-time migration can be subsequently applied to estimate each source range. Simultaneous localization of two ships radiating broadband noise (200-900 Hz) is demonstrated using a 16-element, 56-m long vertical array in approximately 100-m deep shallow water.


[The possibility of applying historical concentration of thrombocytes in examination of donors.]
The historical concentration of thrombocytes is an average of three subsequent concentrations of thrombocytes before donation (during two years) in blood of donors. The evaluation was applied to characteristics of historical concentration of thrombocytes concerning concentration of thrombocytes in blood of 99 regular donors before every donation of apheresis thrombocytes. It is established that less than 20% dispersion between historical concentration of thrombocytes and value obtained in day of donation is observed in 96% of regular donors. The average concentration of thrombocytes before three subsequent donations of apparatus apheresis in males is statistically higher than in females: 235,2±6,7 and 222,1±11,0 (× 109 cells/l) correspondingly (p < 0,05). The concentration of thrombocytes has no relationship with intervals between donations. There is no statistically significant differences between historical concentration of thrombocytes and concentration of thrombocytes before fourth donation and in general and between separate donations both in males and females. It is appropriate to analyze quality of concentrates of thrombocytes received through program accounting historical concentration of thrombocytes.


Congenital syphilis: a diagnostic and therapeutic dilemma.
Seventy-eight newborn infants born to mothers with serologic evidence of syphilis (positive serum rapid plasma reagin and fluorescent treponemal antibody-absorption tests) were prospectively evaluated to derive diagnostic and therapeutic criteria for congenital syphilis. Sixty-one infants were asymptomatic with normal serum IgM and normal roentgenograms (Group I). Eight infants had clinical and/or laboratory evidence of infection at birth (Group II). Nine infants presented with late onset infection (Group III). Elevated serum IgM and abnormal roentgenologic findings were consistently present in symptomatic infants in Groups II and III. Cerebrospinal fluid (CSF) examination was normal in all asymptomatic infants and in all infants with late onset disease. One of the eight infants in Group II examined at birth had positive CSF Venereal Disease Research Laboratory determinations, but all other CSF findings were within normal limits, and a second infant with a slight increase in CSF protein had no clinical evidence of central nervous system (CNS) involvement. Of those asymptomatic infants who returned for follow-up 75% and 100% were seronegative by 3 and 6 months, respectively. The symptomatic infants remained seropositive up to 18 months of age. Infants who had no clinical evidence of CNS involvement at birth remained normal at follow-up and had normal CSF findings. The two infants with CNS symptoms at birth continued to have developmental delay despite normal CSF findings. The incidence of CNS involvement in congenital syphilis appears to be extremely low. The value of routine spinal fluid examination is discussed.


Long-Term Visual Outcome in Wet Age-Related Macular Degeneration Patients Depending on the Number of Ranibizumab Injections.
Purpose. To analyse the visual outcome in wet age-related macular degeneration (AMD) patients depending on the number of ranibizumab injections. Methods. 51 naïve wet AMD patients were retrospectively recorded. Visual acuity (VA), central retinal thickness (CRT) measured with spectral domain (SD) optical coherence tomography (OCT), and number of intravitreal injections were compared at 6, 12, 18, 24, 30, and 36 months of follow-up. Kaplan-Meier survival rates (SRs) based on VA outcomes were calculated depending on the number of ranibizumab injections performed. Results. VA improved compared with baseline at 6 and 12 months (P < 0.005). No differences were found at 18, 24, 30, and 36 months (P > 0.05). CRT measured with Cirrus OCT decreased (P < 0.001) at all time points analysed. The mean number of injections received was 6.98 ± 3.69. At 36 months, Kaplan-Meier SR was 76.5% (the proportion of patients without a decrease in vision of more than 0.3 logMAR units). VA remained stable (≤0.01 logMAR units) or improved in 62.7%. Within this group, SR was 92.9% in those who received 7 or more injections versus 51.4% receiving <7 treatments (P = 0.008; log-rank test). Conclusion. Better VA outcomes were found in stable wet AMD patients after 3 years of follow-up if they received ≥7 ranibizumab injections.


Intrinsic stability of unused and retrieved polyethylene glenoid components.
The surface geometry of polyethylene components can be altered by in vivo use. The purpose of this investigation is to document the effects of these changes on the intrinsic stability provided by the glenoid component. We validated a method of measuring the intrinsic stability of glenoid components as indicated by the balance stability angle (the maximal angle between the glenoid centerline and the resultant humeral force before dislocation of the humeral head occurs). We compared observed values with those predicted for unused glenoid components for which the geometry was known. We then applied this method to retrieved glenoid components in which the surface geometry had been altered by in vivo use. The balance stability angles measured in retrieved glenoids were often substantially reduced: 11 of 24 glenoids had diminished balance stability angles of at least 30% in at least one direction. We concluded that the surface geometry of polyethylene glenoid components can be altered by in vivo use in a manner that may compromise their contribution to glenohumeral stability.


Comparison of four sampling methods for the detection of Salmonella in broiler litter.
Experiments were conducted to compare litter sampling methods for the detection of Salmonella. In experiment 1, chicks were challenged orally with a suspension of naladixic acid-resistant Salmonella and wing banded, and additional nonchallenged chicks were placed into each of 2 challenge pens. Nonchallenged chicks were placed into each nonchallenge pen located adjacent to the challenge pens. At 7, 8, 10, and 11 wk of age the litter was sampled using 4 methods: fecal droppings, litter grab, drag swab, and sock. For the challenge pens, Salmonella-positive samples were detected in 3 of 16 fecal samples, 6 of 16 litter grab samples, 7 of 16 drag swabs samples, and 7 of 16 sock samples. Samples from the nonchallenge pens were Salmonella positive in 2 of 16 litter grab samples, 9 of 16 drag swab samples, and 9 of 16 sock samples. In experiment 2, chicks were challenged with Salmonella, and the litter in the challenge and adjacent nonchallenge pens were sampled at 4, 6, and 8 wk of age with broilers remaining in all pens. For the challenge pens, Salmonella was detected in 10 of 36 fecal samples, 20 of 36 litter grab samples, 14 of 36 drag swab samples, and 26 of 36 sock samples. Samples from the adjacent nonchallenge pens were positive for Salmonella in 6 of 36 fecal droppings samples, 4 of 36 litter grab samples, 7 of 36 drag swab samples, and 19 of 36 sock samples. Sock samples had the highest rates of Salmonella detection. In experiment 3, the litter from a Salmonella-challenged flock was sampled at 7, 8, and 9 wk by socks and drag swabs. In addition, comparisons with drag swabs that were stepped on during sampling were made. Both socks (24 of 36, 67%) and drag swabs that were stepped on (25 of 36, 69%) showed significantly more Salmonella-positive samples than the traditional drag swab method (16 of 36, 44%). Drag swabs that were stepped on had comparable Salmonella detection level to that for socks. Litter sampling methods that incorporate stepping on the sample material while in contact with the litter appear to detect Salmonella in greater incidence than traditional sampling methods of dragging swabs over the litter surface.


Axisymmetric Modeling Using MODFLOW-USG.
Axisymmetric groundwater models are used for simulating radially symmetric conditions. Groundwater simulators built specifically to model axisymmetric conditions are most commonly used for simulating aquifer tests. Although some numerical models capable of simulating flow and solute transport that are developed in the cartesian coordinate system framework offer flexibility to simulate axisymmetric conditions, most of the numerical groundwater models, such as the MODFLOW family of codes, are based on structured grids in which axisymmetric flows cannot be directly simulated. Researchers in the past have provided methods to manipulate aquifer properties to mimic axisymmetric conditions. This study presents a methodology that takes advantage of the unstructured grids of MODFLOW-USG to simulate axisymmetric models within the MODFLOW framework. To develop axisymmetric models, the intercell interface area arrays of MODFLOW-USG were calculated to accurately represent coaxial cylindrical model cells. Three examples are presented to demonstrate the application of MODFLOW-USG for axisymmetric modeling: a pumping well with delayed yield effects, a vadose zone flow model simulating an infiltration basin, and a density-dependent saltwater intrusion problem for a circular island. Results were verified against analytical solutions and published numerical codes.


Multimodal analgesia for treatment of allodynia and hyperalgesia after major trauma in a cat.
A 2-year-old polytraumatized male cat was admitted to a teaching hospital for correction of a defective inguinal herniorrhaphy. Upon arrival, the cat showed signs of neuropathic pain, including allodynia and hyperalgesia. Analgesic therapy was initiated with methadone and metamizole; however, 24 h later, the signs of pain continued. Reparative surgery was performed, and a multimodal analgesic regimen was administered (methadone, ketamine, wound catheter and epidural anesthesia). Postoperatively, the cat showed signs of severe pain, assessed using the UNESP-Botucatu multidimensional composite pain scale. Rescue analgesia was initiated, which included methadone, bupivacaine (subcutaneous wound-diffusion catheter) and transversus abdominis plane block. Because the response was incomplete, co-adjuvant therapy (pregabalin and electroacupuncture) was then implemented. Fourteen days after admission, the patient was discharged with oral tramadol and pregabalin for at-home treatment. Neuropathic pain is caused by a primary lesion or dysfunction in the nervous system and is a well-described complication following trauma, surgical procedures such as hernia repair, and inadequate analgesia. The aims of this report are to: (1) describe a presentation of neuropathic pain to highlight the recognition of clinical signs such as allodynia and hyperalgesia in cats; and (2) describe treatment of multi-origin, severe, long-standing, 'mixed' pain (acute inflammatory with a neuropathic component). The patient was managed using multiple analgesic strategies (multimodal analgesia), including opioids, non-steroidal anti-inflammatory drugs, locoregional anesthesia, co-adjuvant drugs and non-pharmacological therapy (electroacupuncture).


Sacroiliac joint: pain referral maps upon applying a new injection/arthrography technique. Part II: Clinical evaluation.
A pain referral map generated from Part I of this study was tested in 54 consecutive patients. Pain diagrams, completed by each patient, were compared to the map generated from sacroiliac injections in 10 volunteers (Part I). Two clinicians, blinded to the examination of each individual, selected the diagrams most consistent with the pain map. To determine the applicability of a pain referral map as a screening tool for sacroiliac joint dysfunction. Two independent examiners, blinded to the patients' examinations, selected 16 individuals whose pain diagrams most represented the map generated in Part I. There was a 100% concordance of patients selected. All 16 patients selected had a provocation-positive SI joint injection. Ten of these individuals also received lumbar discography and lumbar facet injections. Only the SI injection on the symptomatic side was provocation positive. Patients selected for evaluation based on pain mapping received sacroiliac joint injection. Provocation-positive injections were used to confirm the diagnosis of sacroiliac joint dysfunction. Ten subjects subsequently underwent lumbar discography and lumbar facet joint injections to further confirm the diagnosis. Few studies involving low back pain have used pain referral maps. In the present study, patients were successfully screened for sacroiliac joint dysfunction using a pain referral map generated from provocation of asymptomatic volunteers. Patients can be successfully screened for sacroiliac joint dysfunction based on comparison with a pain referral map. Further study on the false negative rates of sacroiliac pain maps is needed.


The anthelmintic drug flubendazole induces cell apoptosis and inhibits NF-κB signaling in esophageal squamous cell carcinoma.
The nuclear factor kappa B (NF-κB) signaling is activated in esophageal squamous cell carcinoma (ESCC) and can be used as a potential target for anti-ESCC drug discovery. In this study, we aimed to investigate the function of flubendazole as a novel NF-κB inhibitor in ESCC cells. Cell Counting Kit-8 assay was carried out to assess cell viability of ESCC cells. Flow cytometry and immunoblotting were performed to examine cell apoptosis. Immunoblotting assay was used to analyze the protein expression of NF-κB signaling. Luciferase assay was performed to explore the activation of NF-κB. Plasmids were transfected into ESCC cells using Lipofectamine® 2000. In this study, the anthelmintic drug flubendazole was found to inhibit the activation of IκBα kinases (IKKs), block the activation of IκBα, and decrease the phosphorylation of NF-κB p65, which could be a novel NF-κB inhibitor in ESCC cells. We also found that flubendazole inhibited the cell survival of different ESCC cells and induced cell apoptosis in both EC9706 and TE1 cells. Moreover, overexpression of constitutively activated IKKβ markedly decreased the cytotoxic effect of flubendazole on EC9706 and TE1 cells. In addition, flubendazole also showed a synergistic effect on ESCC cells when combined with doxorubicin. The results above demonstrated that flubendazole showed its anti-tumor action by suppressing the NF-κB signaling pathway and suggested that flubendazole might be re-purposed for anti-ESCC therapy in clinic as a single agent or in combination with other anti-tumor drugs.


Neural Mechanisms of Motion Processing in the Mammalian Retina.
Visual motion on the retina activates a cohort of retinal ganglion cells (RGCs). This population activity encodes multiple streams of information extracted by parallel retinal circuits. Motion processing in the retina is best studied in the direction-selective circuit. The main focus of this review is the neural basis of direction selectivity, which has been investigated in unprecedented detail using state-of-the-art functional, connectomic, and modeling methods. Mechanisms underlying the encoding of other motion features by broader RGC populations are also discussed. Recent discoveries at both single-cell and population levels highlight the dynamic and stimulus-dependent engagement of multiple mechanisms that collectively implement robust motion detection under diverse visual conditions.


A memory like a female Fur Seal: long-lasting recognition of pup's voice by mothers.
In colonial mammals like fur seals, mutual vocal recognition between mothers and their pup is of primary importance for breeding success. Females alternate feeding sea-trips with suckling periods on land, and when coming back from the ocean, they have to vocally find their offspring among numerous similar-looking pups. Young fur seals emit a 'mother-attraction call' that presents individual characteristics. In this paper, we review the perceptual process of pup's call recognition by Subantarctic Fur Seal Arctocephalus tropicalis mothers. To identify their progeny, females rely on the frequency modulation pattern and spectral features of this call. As the acoustic characteristics of a pup's call change throughout the lactation period due to the growing process, mothers have thus to refine their memorization of their pup's voice. Field experiments show that female Fur Seals are able to retain all the successive versions of their pup's call.


Multiple cry Genes in Bacillus thuringiensis Strain BTG Suggest a Broad-Spectrum Insecticidal Activity.
The properties of Bacillus thuringiensis strains as a biopesticide with potent action against moths, beetles, and mosquitoes have been known for decades, with individual subspecies showing specific activity against a particular pest. The aim of the present work is to characterize strains that can be used for broad-spectrum pest control in agriculture. Twenty strains of B. thuringiensis were isolated from Bulgarian soil habitats. The strains were screened for genes encoding 12 different crystal (Cry) endotoxins by PCR with specific primer pairs. Seven of the isolates contained cry genes in their genomes. B. thuringiensis strains PL1, PL3, and PL20 contained at least three different cry genes, while B. thuringiensis serovar galleriae BTG contained at least four. Moreover, scanning electron microscopy (SEM) investigation revealed the production of bipyramidal (PL1, PL3, PL20), polygonal (PL1), cubic (BTG), and spherical crystals (BTG and PL20). Potentially containing the most cry genes, the BTG genome was sequenced and annotated. It comprises 6,275,416 base pairs, does not contain plasmids, has a GC content of 35.05%, and contained 7 genes encoding crystal toxins: cry1Ab35, cry1Db, cry1Fb, cry1Ib, cry2Ab, cry8Ea1, and cry9Ba. This unique combination would possibly enable the simultaneous pesticidal action against pest species from orders Lepidoptera, Coleoptera, Diptera, and Hemiptera, as well as class Gastropoda. Whole-genome sequencing provided accurate information about the presence, localization, and classification of Cry toxins in B. thuringiensis BTG, revealing the great potential of the strain for the development of new broad-spectrum bio-insecticides.


Improved photovoltaic performance of Pb-free AgBi2I7 based photovoltaics.
Hybrid perovskites based on bismuth are good candidates for developing lead-free and air-stable photovoltaics, but they have historically been constrained by poor surface morphologies and large band-gap energies. Monovalent silver cations are incorporated into iodobismuthates as part of a novel materials processing method to fabricate improved bismuth-based thin-film photovoltaic absorbers. However, a number of fundamental characteristics prevented them from achieving better efficiency. We examine bismuth iodide perovskite made of silver with improvements in surface morphology and a narrow band gap, and we achieve high power conversion efficiency. AgBi2I7 perovskite was used in the fabrication of PSCs as a material for light absorption, and its optoelectronic proficiencies were also studied. We reduced the band gap to 1.89 eV and achieved a maximum power conversion efficiency of 0.96% using the solvent engineering approach. Additionally, simulation studies verified an efficiency of 13.26% by using AgBi2I7 as a light absorber perovskite material.


Staphylococcus aureus SasA is responsible for binding to the salivary agglutinin gp340, derived from human saliva.
Staphylococcus aureus is a major human pathogen that can colonize the nasal cavity, skin, intestine, and oral cavity as a commensal bacterium. gp340, also known as DMBT1 (deleted in malignant brain tumors 1), is associated with epithelial differentiation and innate immunity. In the oral cavity, gp340 induces salivary aggregation with several oral bacteria and promotes bacterial adhesion to tissues such as the teeth and mucosa. S. aureus is often isolated from the oral cavity, but the mechanism underlying its persistence in the oral cavity remains unclear. In this study, we investigated the interaction between S. aureus and gp340 and found that S. aureus interacts with saliva- and gp340-coated resin. We then identified the S. aureus factor(s) responsible for binding to gp340. The cell surface protein SasA, which is rich in basic amino acids (BR domain) at the N terminus, was responsible for binding to gp340. Inactivation of the sasA gene resulted in a significant decrease in S. aureus binding to gp340-coated resin. Also, recombinant SasA protein (rSasA) showed binding affinity to gp340, which was inhibited by the addition of N-acetylneuraminic acid. Surface plasmon resonance analysis showed that rSasA significantly bound to the NeuAcα(2-3)Galβ(1-4)GlcNAc structure. These results indicate that SasA is responsible for binding to gp340 via the N-acetylneuraminic acid moiety.


Extensive Sequestration Chronic Maxillary Osteomyelitis in an Uncontrolled Diabetic Patient: Comprehensive Case Management of a Rare Entity.
The hallmark of osteomyelitis was progressive bone destruction and sequestrum formation. In the underlying disease, like diabetes mellitus, osteomyelitis becomes severe and exacerbates the condition. It was essential for the oral and maxillofacial surgeon to comprehend its complex medical and surgical management to achieve complete disease eradication. The aim of this article was to report a rare case and comprehensive management of extensive sequestrating maxillary osteomyelitis with uncontrolled diabetes mellitus patients. A 58-year-old male patient with pain and swelling accompanied by discharge of pus in the sinistra maxilla region. The systemic disease was identified as uncontrolled diabetes mellitus, and had a history of unhealing wounds 1 year ago after upper left molar extraction. Computed tomography scan result showed extensive sequester formation and bony destruction in the right extending to the left maxilla. Microbial culture results were Klebsiella pneumoniae and Morganella morganii. Subsequently, extensive sequestrectomy and multiple extractions of the involved jaw and teeth were performed after diabetes mellitus was regulated. A suspension suture against oral and nasal mucosa was performed to avoid dead space formation. Comprehensive perioperative management in maxillary osteomyelitis in uncontrolled diabetes mellitus includes sequestrectomy, definitive antibiotic therapy based on culture results, and diabetes regulation to improve the successful management of this case.


Performance comparison of two herbal and industrial medicines using nanoparticles with a starch/cellulose shell and alginate core for drug delivery: In vitro studies.
In this study, the performance of two kinds of industrial and herbal drugs encapsulated in nanoparticles with a shell of starch and cellulose and an alginate core were examined as a new technique for nanoparticle drug delivery. The test method involved creating a suspension of starch and alginate, which was then dried, mixed with cellulose, and heated to form core-shell nanoparticles. The industrial drug calcitonin and an extract of the herb Amaranthus retroflexcus L. were added separately and in combination to the nanoparticles, and the performance of each configuration was evaluated. Variables like shape, size of nanoparticle, and pH were examined for their effect in vitro. Response surface methodology (RSM) was employed for optimization of parameters. The properties of the nanoparticles were studied by scanning electron microscopy (SEM) and Ultraviolet-visible spectroscopy (UV-vis). The most optimal conditions for formation of the smallest nanoparticles were found to be pH 4 with a concentration of 0.15g starch, 0.04g alginate, and 0.01g cellulose, which resulted in a spherical nanoparticle size of 25.6-68.7nm. This novel method for helping bone regeneration offers a potentially major advance in the medical treatment of osteoporosis. The results of optimization indicated that the most optimal conditions of the tests were performed at pH 4, CA=0.04, CS=0.21, and CC=0.01. In acidic pH the size of nanoparticles was less than 100nm.


Incompatibility with formin Cdc12p prevents human profilin from substituting for fission yeast profilin: insights from crystal structures of fission yeast profilin.
Expression of human profilin-I does not complement the temperature-sensitive cdc3-124 mutation of the single profilin gene in fission yeast Schizosaccharomyces pombe, resulting in death from cytokinesis defects. Human profilin-I and S. pombe profilin have similar affinities for actin monomers, the FH1 domain of fission yeast formin Cdc12p and poly-L-proline (Lu, J., and Pollard, T. D. (2001) Mol. Biol. Cell 12, 1161-1175), but human profilin-I does not stimulate actin filament elongation by formin Cdc12p like S. pombe profilin. Two crystal structures of S. pombe profilin and homology models of S. pombe profilin bound to actin show how the two profilins bind to identical surfaces on animal and yeast actins even though 75% of the residues on the profilin side of the interaction differ in the two profilins. Overexpression of human profilin-I in fission yeast expressing native profilin also causes cytokinesis defects incompatible with viability. Human profilin-I with the R88E mutation has no detectable affinity for actin and does not have this dominant overexpression phenotype. The Y6D mutation reduces the affinity of human profilin-I for poly-l-proline by 1000-fold, but overexpression of Y6D profilin in fission yeast is lethal. The most likely hypotheses to explain the incompatibility of human profilin-I with Cdc12p are differences in interactions with the proline-rich sequences in the FH1 domain of Cdc12p and wider "wings" that interact with actin.


Association of Specific Comorbidities with Monosodium Urate Crystal Deposition in Urate-Lowering Therapy-Naive Gout Patients: A Cross-Sectional Dual-Energy Computed Tomography Study.
(1) Background: To determine which factors are associated with the volume of monosodium urate (MSU) crystal deposition quantified by dual-energy computed tomography (DECT) in urate-lowering therapy (ULT)-naive gout patients. (2) Methods: In this multicenter cross-sectional study, DECT scans of knees and feet/ankles were prospectively obtained from ULT-naive gout patients. Demographic, clinical (including gout history and comorbidities), and biological data were collected, and their association with DECT MSU crystal volume was analyzed using bivariate and multivariate analyses. A second bivariate analysis was performed by splitting the dataset depending on an arbitrary threshold of DECT MSU volume (1 cm3). (3) Results: A total of 91 patients were included. In the bivariate analysis, age (p = 0.03), gout duration (p = 0.003), subcutaneous tophi (p = 0.004), hypertension (p = 0.02), diabetes mellitus (p = 0.05), and chronic heart failure (p = 0.03) were associated with the total DECT volume of MSU crystal deposition. In the multivariate analysis, factors associated with DECT MSU volumes ≥1 cm3 were gout duration (odds ratio (OR) for each 10-year increase 3.15 (1.60; 7.63)), diabetes mellitus (OR 4.75 (1.58; 15.63)), and chronic heart failure (OR 7.82 (2.29; 31.38)). (4) Conclusion: Specific comorbidities, particularly chronic heart failure and diabetes mellitus, are more strongly associated with increased MSU crystal deposition in knees and feet/ankles than gout duration, regardless of serum urate level.


[Adhesiveness of yeast-like fungi in the system "Candida albicans--vaginal epitheliocytes"].
The influence of vaginal liquid on adhesive reactions in the system "Candida albicans - vaginal epitheliocytes". Preliminary treatment of C. albicans by mucin, natural or absorbed vaginal liquid resulted in decrease of adhesive activity (p<0.05). C. albicans did not change its adhesive properties in case of preliminary treatment of vaginal epitheliocytes by the same substances. In the system "Candida albicans - vaginal epitheliocytes" vaginal liquid has the expressed antiadhesive effect, which probably belongs to mucin.


Verbal peaks and visual valleys in theory of mind ability in Williams syndrome.
Research on theory of mind (TOM) has provided a major contribution to the understanding of developmental disorders characterized by atypical social behaviour. Yet, there is still little consensus relative to TOM abilities in Williams syndrome (WS). This study used visual and verbal tasks to investigate attribution of intentions in individuals with WS relative to mental age-matched typically developing individuals. Results showed that individuals with WS perform as accurately as controls on the verbal but not on the visual task. Such modality differences did not affect WS group's performance on a control condition not requiring TOM neither were found for the control group. These results suggest the existence of a verbal peak and a visual valley in TOM ability in WS.


Platelet releasate promotes breast cancer growth and angiogenesis via VEGF-integrin cooperative signalling.
Selective platelet release of pro- or anti-angiogenic factors distinctly regulated angiogenesis. We hypothesised that selective release of platelet angiogenic factors could differently regulate tumour growth. Breast cancer cell proliferation, cancer cell-induced endothelial tube formation in vitro, and tumour growth in vivo were studied in the presence of protease-activated receptor 1-stimulated platelet releasate (PAR1-PR; rich in pro-angiogenic factors) or PAR4-PR (rich in anti-angiogenic factors). The PAR1-PR and PAR4-PR supplementation (10%) similarly enhanced cell proliferation of MCF-7 and MDA-MB-231 breast cancer cells. The cancer cells triggered capillary-like tube formation of endothelial cells that was further enhanced by pro-angiogenic factor-rich PAR1-PR. The VEGF, but not SDF-1α, receptor blockade abolished PAR1-PR/PAR4-PR-enhanced cancer cell proliferation. Integrin blockade by RGDS had identical effects as VEGF inhibition. The Src and ERK inhibition diminished, whereas PI3K and PKC blockade abolished platelet releasate-enhanced cancer cell proliferation. Using a model of subcutaneous implantation of MDA-MB-231 cells in nude mice, PAR1-PR enhanced tumour growth more markedly than PAR4-PR, and seemed to achieve the exaggeration by promoting more profound tumour angiogenesis. Platelet releasate increases breast cancer cell proliferation through VEGF-integrin cooperative signalling. Pro-angiogenic factor-rich platelet releasate enhances cancer cell-induced angiogenesis more markedly, and thus exaggerates tumour growth in vivo.


Behavioral and Neural Correlates of Executive Function: Interplay between Inhibition and Updating Processes.
This study investigated the interaction between two executive function processes, inhibition and updating, through analyses of behavioral, neurophysiological, and effective connectivity metrics. Although, many studies have focused on behavioral effects of executive function processes individually, few studies have examined the dynamic causal interactions between these two functions. A total of twenty participants from a local university performed a dual task combing flanker and n-back experimental paradigms, and completed the Operation Span Task designed to measure working memory capacity. We found that both behavioral (accuracy and reaction time) and neurophysiological (P300 amplitude and alpha band power) metrics on the inhibition task (i.e., flanker task) were influenced by the updating load (n-back level) and modulated by working memory capacity. Using independent component analysis, source localization (DIPFIT), and Granger Causality analysis of the EEG time-series data, the present study demonstrated that manipulation of cognitive demand in a dual executive function task influenced the causal neural network. We compared connectivity across three updating loads (n-back levels) and found that experimental manipulation of working memory load enhanced causal connectivity of a large-scale neurocognitive network. This network contains the prefrontal and parietal cortices, which are associated with inhibition and updating executive function processes. This study has potential applications in human performance modeling and assessment of mental workload, such as the design of training materials and interfaces for those performing complex multitasking under stress.


[Dynamics of the genetic demographic structure of the Kursk province population: migration processes].
Marriage records from parish books of the second half of the 19th century and marriage records of 1967-1970 and 1993-1995 obtained from registry offices were used to analyze the dynamics of genetically significant parameters of migration and marriage structure with respect to spouses' birthplaces in populations of different hierarchical levels in the Kursk oblast. It was found that, among the persons contracting marriage (both males and females), the proportions of those who were born in the same population and those who were born in any population of the Kursk oblast decreased by about one third and one fifth, respectively, for the 130-year period. In rural and small urban populations, the coefficients of marriage migration in the 19th century were an order of magnitude lower than in the 20th century. The immigration to urban populations was maximum in the late 1960s (m = 0.745 in small towns and m = 0.680 in Kursk), and that to rural populations, in the 1990s (m = 0.344). In both urban and rural populations, the mean distance between the spouses' birthplaces has increased by several times for the period studied. The endogamy level has decreased approximately twofold: from 0.797 to 0.380 in Kursk, from 0.897 to 0.419 in small towns, and from 0.958 to 0.440 in rural districts. The marriage assortativeness with respect to birthplace was maximum in the late 19th century (K = 0.393-0.491) and minimum in the 1960s (K = 0.155-0.246). The increase in genetic diversity of the urban population of the Kursk oblast due to migration has been slowing down since the late 20th century, whereas the outbreeding level is still increasing in rural populations.


Reduced volume intensity-modulated radiotherapy with simultaneous integrated boost for patients with high-grade glioma: A retrospective observational study.
Radiotherapy (RT) is an essential treatment for patients with high-grade gliomas. however, a consensus on the target area of RT has not yet been achieved. In this study, we aimed to analyze progression-free survival (PFS), recurrence patterns, and toxicity in patients who received reduced volume intensity-modulated radiotherapy with simultaneous integrated boost (rvSIB-IMRT). In addition, we attempted to identify prognostic factors for recurrence. Twenty patients with high-grade gliomas who received rvSIB-IMRT between July 2011 and December 2021 were retrospectively analyzed. For rvSIB-IMRT, clinical target volume 1/2 was set at a 5 to 10 mm margin on each gross tumor volume (GTV) 1 (resection cavity and enhanced lesion) and GTV2 (high-signal lesion of T2/fluid-attenuated inversion recovery). RT doses were prescribed to 60 Gy/30 fractions (fxs) for planning target volume (PTV)1 and 51 to 54 Gy/30 fxs for PTV2. The median PFS and overall survival of the total cohorts were 10.6 and 13.6 months, respectively. Among the 12 relapsed patients, central, in-field, and marginal recurrences were identified in 8 (66.7%), 2 (16.7%), and 1 patient (8.3%), respectively. Distant recurrence was identified in 3 patients. Gross total resection (GTR) and high Ki-67 index (>27.4%), and subventricular involvement (SVI) were identified as significant factors for PFS in the multivariate analysis. During the follow up, 4 patients showed pseudoprogression and 1 patient showed radiation necrosis. The rvSIB-IMRT for high-grade gliomas resulted in comparable PFS and tolerable toxicity. Most recurrences were central/in-field (10 cases of 12, 83.4%). GTR, high Ki-67 index (>27.4%), and SVI were significant factors for recurrence.


Impact of frustrated singularities on magnetic island evolution.
The growth of magnetic islands is explored using the magnetohydrodynamic model in a simple slab system in which the value of the tearing mode stability parameter Delta' can be varied continuously. Unless the system is close to marginal stability reconnection is controlled by Sweet-Parker current layers, whose formation is a consequence of the inherent singular structure of magnetic island equilibria.


Trabecular bone deterioration in differentiated thyroid cancer: Impact of long-term TSH suppressive therapy.
Conflicting results has been reported regard osteoporosis and fractures in patients with Differentiated Thyroid Cancer (DTC). Our objective was to evaluate the long-term effects of TSH suppression therapy with Levothyroxine (LT4) on trabecular bone score (TBS) and bone mineral density (BMD) in females with DTC after thyroidectomy. About 145 women with resected DTC and receiving long-term TSH therapy, were stratified according to the degree of TSH suppression. Mean duration of follow-up was 12.3 ± 6.1 years. BMD and TBS, were assessed using dual-energy X-ray absorptiometry (DXA) and TBS iNsight (Med-Imaps), at baseline (1-3 months after surgery) and at the final study visit. In patients stratified by duration of TSH suppression therapy (Group I, 5-10 years; Group II, >10 years), slight increases from baseline TSH levels were observed. Significant decreases in LS-BMD and FN-BMD were seen in patients after >10 years. TBS values were lower in Groups I (1.289 ± 0.122) and II (1.259 ± 0.129) compared with baseline values (P = .0001, both groups). Regarding the degree of TSH suppression, TBS was significantly reduced in those with TSH < 0.1 µU/mL (P = .0086), and not in patients with TSH suppression of 0.1.-0.5 or >0.5 µU/mL. We found deterioration of trabecular structure in patients with DTC and TSH suppression therapy below 0.1 µU/mL and after 5-10 years of follow-up. Significant changes in BMD according to TSH levels were not observed. Trabecular Bone Score is a useful technique for identifying thyroid cancer patients with risk of bone deterioration.


Targeted sequencing reveals the mutational landscape responsible for sorafenib therapy in advanced hepatocellular carcinoma.
Rationale: The existence of primary and acquired drug resistance is the main obstacle for the effect of multi-kinase inhibitor sorafenib and regorafenib in advanced hepatocellular carcinoma (HCC). However, plenty of patients did not significantly benefit from sorafenib treatment and little is known about the mechanism of drug resistance. Methods: Laser capture microdissection was used to acquire matched normal liver and tumor tissues on formalin-fixed paraffin-embedded specimens collected before sorafenib therapy from the first surgery of 119 HCC patients. Ultra-deep sequencing (~1000×) targeting whole exons of 440 genes in microdissected specimens and siRNA screen in 7 cell lines were performed to find mutations associated with differential responses to sorafenib. Patient-derived xenograft models were employed to determine the role of TP53 in response to sorafenib. Lentiviruses harboring wild-type and c.G52C-mutant OCT4 were applied to explore the function of OCT4 in resistance to sorafenib. ChIP-PCR assay for analysis of OCT4 transcriptional activity was performed to explore the affinity with the KITLG promoter. Statistical analyses were used to associate levels of p53 and OCT4 with tumor features and patient outcomes. Results: Total 1,050 somatic mutations and 26 significant driver genes were identified. SiRNA screening in 7 HCC cell lines was further performed to identify mutations associated with differential responses to sorafenib. A recurrent nonsynonymous mutation c.G52C in OCT4 (OCT4mut) was strongly associated with good response to sorafenib, whereas the stop-gain mutation in TP53 showed the opposite outcome both in vitro and in vivo. OCT4wt-induced stem cell factor (encoded by KITLG gene, SCF) expression and cross-activation of c-KIT/FLT3-BRAF signals were identified indispensably for sorafenib resistance, which could be reversed by the combination of c-KIT tyrosine kinase inhibitors or neutralizing antibody against SCF. Mechanistically, an OCT4 binding site in upstream of KITLG promoter was identified with a higher affinity to wildtype of OCT4 rather than G52C-mutant form, which is indispensable for OCT4-induced expression of KITLG and sorafenib resistance. Conclusion: Our study reported a novel somatic mutation in OCT4 (c.G52C) responsible for the sorafenib effect, and also shed new light on the treatment of HCC through the combination of specific tyrosine kinase inhibitors according to individual genetic patterns.


Determination of charge on asphaltene nanoaggregates in air using electrostatic force microscopy.
In this paper, we provide measurement of charge of asphaltene nanoaggregates in air using electrostatic force microscopy. We obtain the average surface charge density of the nanoaggregates as 43.7 nC/cm(2). Among the different aspects of asphaltene, one of the least known is its charge and the effect of solvent and compositional variability (of asphaltene) in dictating this charge. For aqueous systems, asphaltene charge demonstrates a strong dependence on the pH and the salt concentration, indicating that a possible ionization of the surface groups leads to this charging. On the contrary, for asphaltene in nonpolar media (e.g., toluene and heptane), it is believed that asphaltene native charge is central in dictating this charging. This native charge is the solvent-independent charge or the asphaltene charge in air. Our measurements, therefore, provide the first direct quantification (i.e., a quantification of charge not from the measurement of the asphaltene mobilities, which in turn requires specification of the nonuniform asphaltene size distribution) of this asphaltene native charge by conducting the measurements in air. Similar measurements in a solvent may introduce a solvent-dependent value, thereby forbidding not only the exact quantification of this native charge but also the understanding of the specific role of the solvent. This measurement, therefore, will provide a useful starting point to quantify the mechanism of asphaltene charging in nonpolar solvents with important ramifications in deciphering the role of asphaltene in transport and handling of crude and heavy oils.


Truncated RAR beta isoform enhances proliferation and retinoid resistance.
We previously reported the existence of a truncated isoform of the retinoic acid receptor beta, termed beta prime. Beta prime lacks the N-terminal domains of beta 2 and beta 4, including the DNA-binding domain. However, beta prime is able to heterodimerize and interact with transcription cofactors. To determine the effects of different retinoic acid receptor isoforms on cell proliferation and apoptosis, we transduced retinoid sensitive (MCF7) and retinoid-resistant (MDA-MB-231) cells with retinoic acid receptor beta 2, beta 4, or beta prime. Expression of the truncated beta prime isoform induces resistance to retinoic acid treatment in retinoid sensitive MCF7 cells. In both retinoid sensitive and resistant cells, expression of full-length beta 2 and beta 4 isoforms results in elevated sensitivity to retinoic acid treatment and caspase-independent cell death. Cell death in beta 4 transduced MDA-MB-231 cells was accompanied by metaphase chromosome decondensation and breakage suggestive of mitotic catastrophe. Our results provide evidence that: (a) the truncated form of the retinoic acid receptor beta induces retinoid resistance rather than sensitivity; and (b) alternative pathways of cell death are mediated by different isoforms in breast cancer cells.


Influence of organic amendments on diuron leaching through an acidic and a calcareous vineyard soil using undisturbed lysimeters.
The influence of different organic amendments on diuron leaching was studied through undisturbed vineyard soil columns. Two composts (A and D), the second at two stages of maturity, and two soils (VR and Bj) were sampled. After 1 year, the amount of residues (diuron+metabolites) in the leachates of the VR soil (0.19-0.71%) was lower than in the Bj soil (4.27-8.23%), which could be explained by stronger diuron adsorption on VR. An increase in the amount of diuron leached through the amended soil columns, compared to the blank, was observed for the Bj soil only. This result may be explained by the formation of mobile complexes between diuron and water-extractable organic matter (WEOM) through the Bj soil, or by competition between diuron and WEOM for the adsorption sites in the soil. For both soils, the nature of the composts and their degree of maturity did not significantly influence diuron leaching.


Clinical Study of Congenital Esophageal Stenosis: Comparison according to Association of Esophageal Atresia and Tracheoesophageal Fistula.
Congenital esophageal atresia (CES) is a rare congenital disease. The severity of symptoms is variable; thus, diagnosis is difficult and tends to be delayed. CES is frequently accompanied by esophageal atresia (EA) with/without tracheoesophageal fistula (TEF). We investigated the characteristics of CES by reviewing our experience with CES patients and researched the differences between CES with EA-TEF and isolated CES. A total of 31 patients underwent operations for CES were reviewed retrospectively. The patients were divided into two groups according to the association with EA-TEF, and compared the differences. Sixteen boys and 15 girls were included. The mean age at symptom onset was 8 months old, and the mean age at diagnosis was 21 months old. Nine patients with EA-TEF were included group A, whereas the other 22 patients were assigned to group B. There were no differences in sex, gestational age, associated anomalies and pathologic results between the groups. In group A, the age at diagnosis and age at surgery were younger than in group B despite the age at symptom occurrence being similar. Postoperative complications occurred only in group A. In this study, symptoms occurred during the weaning period, and vomiting was the most frequent symptom. CES patients with EA-TEF tended to be diagnosed and treated earlier despite the age at symptom occurrence being similar. CES patients with EA-TEF had more postoperative complications; therefore, greater attention should be paid during the postoperative period.


Bayesian dose-finding designs for combination of molecularly targeted agents assuming partial stochastic ordering.
Molecularly targeted agent (MTA) combination therapy is in the early stages of development. When using a fixed dose of one agent in combinations of MTAs, toxicity and efficacy do not necessarily increase with an increasing dose of the other agent. Thus, in dose-finding trials for combinations of MTAs, interest may lie in identifying the optimal biological dose combinations (OBDCs), defined as the lowest dose combinations (in a certain sense) that are safe and have the highest efficacy level meeting a prespecified target. The limited existing designs for these trials use parametric dose-efficacy and dose-toxicity models. Motivated by a phase I/II clinical trial of a combination of two MTAs in patients with pancreatic, endometrial, or colorectal cancer, we propose Bayesian dose-finding designs to identify the OBDCs without parametric model assumptions. The proposed approach is based only on partial stochastic ordering assumptions for the effects of the combined MTAs and uses isotonic regression to estimate partially stochastically ordered marginal posterior distributions of the efficacy and toxicity probabilities. We demonstrate that our proposed method appropriately accounts for the partial ordering constraints, including potential plateaus on the dose-response surfaces, and is computationally efficient. We develop a dose-combination-finding algorithm to identify the OBDCs. We use simulations to compare the proposed designs with an alternative design based on Bayesian isotonic regression transformation and a design based on parametric change-point dose-toxicity and dose-efficacy models and demonstrate desirable operating characteristics of the proposed designs.


Gamma Radiation Processed Polymeric Materials for High Performance Applications: A Review.
The polymeric properties are tailored and enhanced by high energy radiation processing, which is an effective technique to tune the physical, chemical, thermal, surface, and structural properties of the various thermoplastic and elastomeric polymeric components. The gamma and electron beam radiation are the most frequent radiation techniques used for crosslinking, compatibilizing, and grafting of various polymer blends and composites systems. The gamma radiation-induced grafting and crosslinking are the effective, rapid, clean, user-friendly, and well-controlled techniques for the polymeric materials for their properties improvement for high performance applications such as nuclear, automobile, electrical insulation, ink curing, surface modification, food packaging, medical, sterilization, and health-care in a different environment. Similarly, electron beam radiations crosslinking has been a well-known technique for properties development and has economic benefits over chemical crosslinking techniques. This review focuses on the development of polymeric multi component systems (functionalized polymer, blends, and nanohybrids), where partially nanoscale clay incorporation can achieve the desired properties, and partially by controlled high energy radiations crosslinking of blends and nanocomposites. In this review, various investigations have been studied on the development and modifications of polymeric systems, and controlled dose gamma radiation processed the polymer blends and clay-induced composites. Radiation induced grafting of the various monomers on the polymer backbone has been focused. Similarly, comparative studies of gamma and electron beam radiation and their effect on property devlopment have been focused. The high energy radiation modified polymers have been used in several high performance sectors, including automotive, wire and cable insulation, heat shrinkable tube, sterilization, biomedical, nuclear and space applications.


Extended Anterior Inferior Approach to Endoscopic Medial Maxillectomy for Maxillary Sinus Lesions.
Myriad open and endoscopic approaches are employed to resect maxillary sinus lesions, each with associated advantages and disadvantages. The inferior and anterior portion of the sinus remains a challenging space to access. To describe the extended anterior inferior approach to endoscopic medial maxillectomy (EAMM) as a novel and valuable addition to a stepwise approach for minimizing surgical morbidity without compromising tumor outcomes. To report the outcomes of patients treated with this approach. A retrospective case series study of 9 patients who underwent EAMM between 2016 and 2019 at a tertiary care referral center was performed. The endoscopic technique is described. The duration of follow-up ranged from 1 to 53 months. Intraoperative steps, including transection of the nasolacrimal duct and execution of an intraoperative dacryocystorhinostomy, were reviewed. Postoperative outcomes, including patient symptoms at follow-up and tumor recurrence, were recorded. Adequate exposure with gross total tumor resection or margin-negative tumor resection was achieved in all cases. Sparing of the nasolacrimal duct was achieved in 2 patients. No patients reported persistent epiphora, empty nose syndrome, or changes in cosmesis such as alar or nasal tip collapse. One patient reported unilateral V2 hypoesthesia at 6 months postoperatively that had resolved by his next follow-up 18 months after surgery. Postoperative tumor surveillance was achieved by endoscopic examinations in all patients and there was no evidence of tumor recurrence at a median follow-up of 22 months. The EAMM provides improved access to the inferior-posterior-medial maxillary sinus. This approach minimizes the risk of hypoesthesia and change in cosmesis present in other approaches, and obviates division of the nasolacrimal duct for inferior, posterior-medial attached lesions. This progressive escalation of approach for maxillary sinus lesions minimizes injury to nasal and nasolacrimal structures without compromising tumor outcomes.


[Acoustic image of common rosefinch Carpodacus erythrinus (Pall.)].
Acoustic analysis of the species-specific call of common rosefinch Carpodacus erythrinus was carried out. We compared calls of 12 individuals from the same habitat. The individual-specific elements were revealed in the calls. At the same time, species-specific elements were also recognized in all individuals. These elements compose the acoustic image of common rosefinch call including four syllables with intervals.


[Pilot study to evaluate the efficiency of insecticide-treated mosquito net fences for the protection of horses against nuisance insects in northern Brandenburg].
A fence of black mosquito netting of 100 cm height, pre-treated with 80 mg/m2 of deltamethrin and UV-protected, was used to shelter horses from nuisance and biting insects on pasture in northern Brandenburg. The netting material was attached to the surrounding poles of the existing fences at a height of 15 cm above ground. Three trial groups were selected grazing in spatially separated areas with comparable densities of insect populations. One paddock was completely fenced apart from a wall of 170 cm height and 70 m length. The second pasture had only partial protection with 126 m (13.4%) of fence out of a total perimeter of 942 m. The third pasture served as control. Trap catches outside the fully or partially protected pasture were by at least 60% lower than those recorded for the control pasture. Digital pictures from five different anatomical regions indicated fewer flies on horses kept at the completely or partially protected areas as compared to the control area. The average attack rate in the protected areas amounted to 4.4 and 7.6 flies per horse at the completely or partially protected areas, respectively, as opposed to horses on the control pasture with 172.1 flies. In comparison to the control pasture the horses grazing on the protected areas showed fewer defensive movements, grazing in an undisturbed manner.


A Solid-State Protein Junction Serves as a Bias-Induced Current Switch.
A sample-type protein monolayer, that can be a stepping stone to practical devices, can behave as an electrically driven switch. This feat is achieved using a redox protein, cytochrome C (CytC), with its heme shielded from direct contact with the solid-state electrodes. Ab initio DFT calculations, carried out on the CytC-Au structure, show that the coupling of the heme, the origin of the protein frontier orbitals, to the electrodes is sufficiently weak to prevent Fermi level pinning. Thus, external bias can bring these orbitals in and out of resonance with the electrode. Using a cytochrome C mutant for direct S-Au bonding, approximately 80 % of the Au-CytC-Au junctions show at greater than 0.5 V bias a clear conductance peak, consistent with resonant tunneling. The on-off change persists up to room temperature, demonstrating reversible, bias-controlled switching of a protein ensemble, which, with its built-in redundancy, provides a realistic path to protein-based bioelectronics.


Comparison of cetraxate-based and pantoprazole-based triple therapies in the treatment of Helicobacter pylori infection.
Recent studies suggest that cetraxate possesses anti-Helicobacter pylori (H. pylori) activity. We therefore conducted this pilot study to investigate the efficacy of a cetraxate-based triple therapy and to compare the regimen with proton pump inhibitor-based triple therapy. From April 2001 to January 2002, a total of 58 H. pylori-infected patients were randomly assigned to 1 of 2 regimens for 1 week: cetraxate plus clarithromycin and amoxicillin (CCA group) or pantoprazole plus clarithromycin and amoxicillin (PCA group). Follow-up endoscopy was performed at 8 weeks after the end of treatment to assess the treatment response. Intention-to-treat analysis showed that the eradication rates of the CCA group (n = 27) and PCA group (n = 31) were 70.4% and 93.5%, respectively. The CCA group had a significantly lower eradication rate than the PCA group (p = 0.03). Per-protocol analysis also showed similar results (69.2% vs. 96.7%, p = 0.01). However, the frequency of adverse events in the CCA group was lower than that of the PCA group (3.7% vs. 25.8%, p = 0.03). Univariate analysis showed that the eradication rate was significantly related to proton pump inhibitor therapy (93.5% vs. 70.4%, p = 0.03 ) and smoking habit (66.7 % vs. 88.4%, p = 0.05), but multivariate analysis disclosed that proton pump inhibitor therapy was the only independent factor predicting treatment success (p < 0.05). Cetraxate-based triple therapy is less effective than pantoprazole-based triple therapy in the treatment of H. pylori infection. However, the former has a lower frequency of adverse effects than the latter.


Endogenous and exogenous control of gastrointestinal epithelial function: building on the legacy of Bayliss and Starling.
Transport of fluid and electrolytes in the intestine allows for appropriate adjustments in luminal fluidity while reclaiming water used in digesting and absorbing a meal, and is closely regulated. This article discusses various endogenous and exogenous mechanisms whereby transport is controlled in the gut, placing these in the context of the ideas about the neurohumoral control of alimentary physiology that were promulgated by William Bayliss and Ernest Starling. The article considers three themes. First, mechanisms that intrinsically regulate chloride secretion, centred on the epidermal growth factor receptor (EGFr), are discussed. These may be important in ensuring that excessive chloride secretion, with the accompanying loss of fluid, is not normally stimulated by intestinal distension as the meal passes through the gastrointestinal tract. Second, mechanisms whereby probiotic microorganisms can impart beneficial effects on the gut are described, with a focus on targets at the level of the epithelium. These findings imply that the commensal microbiota exert important influences on the epithelium in health and disease. Finally, mechanisms that lead to diarrhoea in patients infected with an invasive pathogen, Salmonella, are considered, based on recent studies in a novel mouse model. Diarrhoea is most likely attributable to reduced expression of absorptive transporters and may not require the influx of neutrophils that accompanies infection. Overall, the goal of the article is to highlight the many ways in which critical functions of the intestinal epithelium are regulated under physiological and pathophysiological conditions, and to suggest possible targets for new therapies for digestive disease states.


Lignans from Euphorbia hirta L.
Five new lignans, euphorhirtins A-D (1-4), 5-methoxyvirgatusin (5), three artefacts, 7S-ethoxyisolintetralin (6), 7R-ethoxyisolintetralin (7), and 7R-ethoxy-3-methoxyisolintetralin (8), together with 13 known ones (9-21) were isolated from the medicinal plant Euphorbia hirta L. The structures of the compounds were elucidated by means of extensive spectroscopic analysis, including 1D and 2D NMR and HR-ESI-MS experiments. The absolute configurations of compound 1 was determined by ECD calculation. The isolates were evaluated for their inhibitory effects against the proliferation of the cancer cell lines (Hep G2, A549, and DU145) and compounds 14 and 18 showed inhibitory activity against the Hep G2 cells with IC50 values 7.2 ± 0.17 and 8.5 ± 0.36 μM.


Long-term cardiovascular safety of psychostimulants in children with attention deficit hyperactivity disorder.
Objective: Side effects are a concern during psychostimulant treatment. Unfortunately, many previous studies only investigated short-term effects of psychostimulants in laboratory settings which lack clinical daily routines. Methods: We examined 1042 patient records of patients with attention deficit hyperactivity disorder (ADHD) who were referred to a pediatric-psychiatry practice over 12 years. Data analysis was based on 466 children with ADHD who were newly treated with psychostimulants and who were not in treatment for elevated blood pressure. We analysed blood pressure percentiles, heart rate and BMI percentiles. Results: There was a decrease in systolic and diastolic blood pressure percentiles. Heart rate was not affected. BMI slightly declined in girls. Conclusions: In general psychostimulants were safe. To further elucidate negative effects of psychostimulants, long-term controlled and randomized studies in naturalistic settings are of interest.


Retirement saving and mental health in China.
The Chinese population is aging rapidly while both the pension system is underdeveloped and the traditional family care arrangement is in retreat. This article's objective is to assess the relationship between concerns over retirement saving sufficiency and the mental health status of middle-aged and older Chinese adults, and identify the socioeconomic and demographic profile of those with insufficient retirement savings. A survey from about 2000 respondents collected information on self-assessed physical and mental health status based on the EQ-5D-5L framework, self-assessed longevity, retirement plans and financial preparedness and socioeconomic status. Multivariate ordered logistic regressions are used to identify the relationship between mental health status, financial preparedness for retirement and self-assessed longevity, as well as socioeconomic factors associated with mental health status and financial preparedness for retirement respectively. It is found that 59% of the respondents thought that they have not saved, or will not be able to save enough for their retirement. For these people, the odds of having less anxiety or depression are 0.36 (95% CIs: 0.16-0.43) times lower than those who are financially prepared. Having more external sources of financial assistance including family and governments, did not help ease mental distress. Rural people are half as likely to be financially prepared for retirement, regardless of whether they remain in rural areas or migrate to cities. Health promotion strategies should consider the role for financial planning in improving mental health.


Toll-Like Receptors Serve as Biomarkers for Early Diagnosis and Prognosis Assessment of Kidney Renal Clear Cell Carcinoma by Influencing the Immune Microenvironment: Comprehensive Bioinformatics Analysis Combined With Experimental Validation.
Background: Toll-like receptors (TLRs) are important initiators of innate and acquired immune responses. However, its role in kidney renal clear cell carcinoma (KIRC) remains unclear. Methods: TLRs and their relationships with KIRC were studied in detail by ONCOMINE, UALCAN, GEPIA, cBioPortal, GeneMANIA, FunRich, LinkedOmics, TIMER and TRRUST. Moreover, we used clinical samples to verify the expressions of TLR3 and TLR4 in early stage of KIRC by real-time fluorescence quantitative polymerase chain reaction (RT-qPCR), flow cytometry (FC) and immunohistochemistry (IHC). Results: The expression levels of TLRs in KIRC were generally different compared with adjacent normal tissues. Moreover, the expressions of TLR3 and TLR4 elevated significantly in the early stage of KIRC. Overexpressions of TLR1, TLR3, TLR4 and TLR8 in KIRC patients were associated with longer overall survival (OS), while inhibition of TLR9 expression was related to longer OS. Additionally, overexpressions of TLR1, TLR3 and TLR4 in KIRC patients were associated with longer disease free survival (DFS). There were general genetic alterations and obvious co-expression correlation of TLRs in KIRC. The PPI network between TLRs was rather complex, and the key gene connecting the TLRs interaction was MYD88. The GO analysis and KEGG pathway analysis indicated that TLRs were closely related to adaptive immunity, innate immunity and other immune-related processes. RELA, NFKB1, IRF8, IRF3 and HIF1A were key transcription factors regulating the expressions of TLRs. What's more, the expression levels of all TLRs in KIRC were positively correlated with the infiltration levels of dendritic cells, macrophages, neutrophils, B cells, CD4+ T cells and CD8+ T cells. Finally, the results of RT-qPCR, FC and IHC confirmed that TLR3 and TLR4 were significantly elevated in the early stage of KIRC. Conclusion: The occurrence and development of KIRC are closely related to TLRs, and TLRs have the potential to be early diagnostic biomarkers of KIRC and biomarkers for judging the prognosis and immune status of KIRC. This study may provide new insights into the selection of KIRC immunotherapy targets.


Molecular mechanisms of regulation of sulfate assimilation: first steps on a long road.
The pathway of sulfate assimilation, which provides plants with the essential nutrient sulfur, is tightly regulated and coordinated with the demand for reduced sulfur. The responses of metabolite concentrations, enzyme activities and mRNA levels to various signals and environmental conditions have been well described for the pathway. However, only little is known about the molecular mechanisms of this regulation. To date, nine transcription factors have been described to control transcription of genes of sulfate uptake and assimilation. In addition, other levels of regulation contribute to the control of sulfur metabolism. Post-transcriptional regulation has been shown for sulfate transporters, adenosine 5'phosphosulfate reductase, and cysteine synthase. Several genes of the pathway are targets of microRNA miR395. In addition, protein-protein interaction is increasingly found in the center of various regulatory circuits. On top of the mechanisms of regulation of single genes, we are starting to learn more about mechanisms of adaptation, due to analyses of natural variation. In this article, the summary of different mechanisms of regulation will be accompanied by identification of the major gaps in knowledge and proposition of possible ways of filling them.


Gene expression profiling of the rewarding effect caused by methamphetamine in the mesolimbic dopamine system.
Methamphetamine, a commonly used addictive drug, is a powerful addictive stimulant that dramatically affects the CNS. Repeated METH administration leads to a rewarding effect in a state of addiction that includes sensitization, dependence, and other phenomena. It is well known that susceptibility to the development of addiction is influenced by sources of reinforcement, variable neuroadaptive mechanisms, and neurochemical changes that together lead to altered homeostasis of the brain reward system. These behavioral abnormalities reflect neuroadaptive changes in signal transduction function and cellular gene expression produced by repeated drug exposure. To provide a better understanding of addiction and the mechanism of the rewarding effect, it is important to identify related genes. In the present study, we performed gene expression profiling using microarray analysis in a reward effect animal model. We also investigated gene expression in four important regions of the brain, the nucleus accumbens, striatum, hippocampus, and cingulated cortex, and analyzed the data by two clustering methods. Genes related to signaling pathways including G-protein-coupled receptor-related pathways predominated among the identified genes. The genes identified in our study may contribute to the development of a gene modeling network for methamphetamine addiction.


Virgin soil: the spread of visceral leishmaniasis into Uttar Pradesh, India.
We conducted a cross-sectional study to determine the incidence of visceral leishmaniasis (VL) and risk factors in two villages in Uttar Pradesh, India reported to have had a recent outbreak. In 245 households with 2,203 people, we detected 3 current VL cases, 32 past cases, and 8 VL deaths since 2001 (annual incidence = 6 per 1,000). Risk factors included living in the same household as a VL case (odds ratio [OR] = 76, P < 0.0005 in one village and OR = 22, P < 0.0005 in the other village), sleeping downstairs and outside in the summer (OR = 4.7, P = 0.004), and an age > or = 15 years old (OR = 2.9, P = 0.024). Increasing cattle density was a risk factor in one village but not the other. We were not able to determine the route by which VL entered the villages. Our data demonstrate a new spread of VL in previously unaffected areas. We recommend carefully supervised spraying with DDT, surveillance to pinpoint other affected villages, and efforts to increase availability of diagnostic and treatment facilities.


[Emerging mental disorders in a community sample of young adults in Italy: help-seeking in a Generalist Community Mental Health setting].
Delays in the admission to care of young adults with emerging mental disorders represent one of the current major concern in psychiatry. This delay, often experienced in clinical practice, has several determinants. One of these is "unexpressed help-seeking" that is influenced by cultural and historical backgrounds and by the characteristics of the disorder itself, but most of all by the way community mental health services are developed. The aims are to identify: level of stress and mental unease and main determinants of unexpressed help-seeking within a community sample of young adults in a national contest of generalist community mental health model. the sample is made up of 3,446 university students. An explorative questionnaire together with SVS (Stress related Valuation Scale) for the assessment of subjective stress and GHQ-12 for the evaluation of mental health status were given. A descriptive analysis was carried out followed by correlations between unexpressed help-seeking variable and other variables. A logistic regression was carried out on the subsample with GHQ-12 ≥4 utilizing "non help-seeking" as a dependent variable. 46.8% of the sample had a GHQ-12 ≥4 score. The amount of unexpressed help-seeking is equal to 63.6% and ends up being significantly correlated to: male sex, nonresident student, high SVS score, absence of Youth Mental Health Services, distrust manifested in relation to existing Services. A modification of the Community Mental Health Services in the sense of setting up more appropriate contexts for young users, could lead to a reduction of unexpressed help-seeking.


Cholinergic systems are essential for late-stage maturation and refinement of motor cortical circuits.
Previous studies reported that early postnatal cholinergic lesions severely perturb early cortical development, impairing neuronal cortical migration and the formation of cortical dendrites and synapses. These severe effects of early postnatal cholinergic lesions preclude our ability to understand the contribution of cholinergic systems to the later-stage maturation of topographic cortical representations. To study cholinergic mechanisms contributing to the later maturation of motor cortical circuits, we first characterized the temporal course of cortical motor map development and maturation in rats. In this study, we focused our attention on the maturation of cortical motor representations after postnatal day 25 (PND 25), a time after neuronal migration has been accomplished and cortical volume has reached adult size. We found significant maturation of cortical motor representations after this time, including both an expansion of forelimb representations in motor cortex and a shift from proximal to distal forelimb representations to an extent unexplainable by simple volume enlargement of the neocortex. Specific cholinergic lesions placed at PND 24 impaired enlargement of distal forelimb representations in particular and markedly reduced the ability to learn skilled motor tasks as adults. These results identify a novel and essential role for cholinergic systems in the late refinement and maturation of cortical circuits. Dysfunctions in this system may constitute a mechanism of late-onset neurodevelopmental disorders such as Rett syndrome and schizophrenia.