A novel scheme to design the filter for CT reconstruction using FBP algorithm.
The Filtered Back-Projection (FBP) algorithm is the most important technique for computerized tomographic (CT) imaging, in which the ramp filter plays a key role. FBP algorithm had been derived using the continuous system model. However, it has to be discretized in practical applications, which necessarily produces distortion in the reconstructed images. A novel scheme is proposed to design the filters to substitute the standard ramp filter to improve the reconstruction performance for parallel beam tomography. The design scheme is presented under the discrete image model and discrete projection environment. The designs are achieved by constrained optimization procedures. The designed filter can be regarded as the optimal filter for the corresponding parameters in some ways. Some filters under given parameters (such as image size and scanning angles) have been designed. The performance evaluation of CT reconstruction shows that the designed filters are better than the ramp filter in term of some general criteria. The 2-D or 3-D FBP algorithms for fan beam tomography used in most CT systems, are obtained by modifying the FBP algorithm for parallel beam tomography. Therefore, the designed filters can be used for fan beam tomography and have potential applications in practical CT systems.


Evaluation of a pharmacist-led shared decision-making in atrial fibrillation and patients' satisfaction-a before and after pilot study.
Chronic complex diseases like atrial fibrillation have potential long-term economical and personal consequences. Shared decision-making principles may promote therapeutic compliance, satisfaction and outcomes. Pharmacists, as patient-advocates, play a key role in guiding them through complex clinical decisions about their chronic disease management and anticoagulation choices. To evaluate the impact of pharmacist-led shared decision making on patients' satisfaction and appropriateness of their anticoagulation therapy in newly diagnosed atrial fibrillation patients. A prospective 2-phase before and after single-centre study was conducted in an Australian hospital. Phase 1 provided usual care, and patients' satisfaction and appropriateness of their anticoagulation therapy were evaluated. Phase-2 assessed the impact on satisfaction and appropriateness of anticoagulant therapy following pharmacist-led interventions of shared decision making to promote patients' involvement. Patients with pharmacist-led shared decision making reported higher degree of appropriateness of anticoagulation therapy and satisfaction (36% vs 92%, P < 0.001; 25% vs 68, P < 0.001), respectively. Additionally, patients who had a pharmacist input during their hospital stay received guideline-recommended anticoagulant therapy and reported satisfaction with their management was also higher in stage 2 (21% vs 65%, p < 0.001). The study highlights pharmacist-led shared decision making in atrial fibrillation that contributes to patient satisfaction and appropriateness of therapy.


Visual evoked potential pattern generation, recording, and data analysis with a single microcomputer.
A single microcomputer is used to generate multiple sets of checkerboard patterns, simultaneously record EEG data for visual evoked potentials, and analyze the results by fast Fourier transform in very rapid sequence under operator control. This system permits efficient estimates of visual acuity in infants with ophthalmological and neuro-ophthalmological disease.


Studying genetic determinants of natural variation in human gene expression using Bayesian ANOVA.
Standard genetic mapping techniques scan chromosomal segments for location of genetic linkage and association signals. The majority of these methods consider only correlations at single markers and/or phenotypes with explicit detailing of the genetic structure. These methods tend to be limited by their inability to consider the effect of large numbers of model variables jointly. In contrast, we propose a Bayesian analysis of variance (ANOVA) method to categorize individuals based on similarity of multidimensional profiles and attempt to analyze all variables simultaneously. Using Problem 1 of the Genetic Analysis Workshop 15 data set, we demonstrate the method's utility for joint analysis of gene expression levels and single-nucleotide polymorphism genotypes. We show that the method extracts similar information to that of previous genetic mapping analyses, and suggest extensions of the method for mining unique information not previously found.


Effect of myopic anisometropia on anterior and posterior ocular segment parameters.
The purpose of this study is to investigate the differences in anterior and posterior segment parameters of more myopic eyes compared to fellow eyes using spectral domain optical coherence tomography and optical biometer device in patients with myopic anisometropia. This prospective cross-sectional study included 42 myopic anisometropic patients with and without amblyopia, aged between 7 and 40 years old. The refractive error and keratometry values, axial length (AL), central corneal thickness (CCT), peripapillary retinal nerve fiber layer thickness (RNFLT), and central macular thickness (CMT) were evaluated. Eighteen of the patients had myopic anisometropia with amblyopia, and the remaining 24 had myopic anisometropia without amblyopia. There were 23 female and 19 male patients with a mean age as 23.67 ± 10.12 years (range 7-40). The right eyes of the subjects significantly had a higher degree of myopia. There was a significant difference in mean best-corrected visual acuity (0.195 ± 0.234 vs. 0.011 ± 0.025 logMAR, p < 0.001), spherical equivalent refraction (-3.95 ± 1.38 vs. -1.04 ± 0.99 D, p < 0.001), AL (25.06 ± 1.27 vs. 23.99 ± 0.98 mm, p < 0.001), and RNFLT (89.24 ± 12.84 vs. 94.57 ± 10.81 μm, p < 0.001) between the more myopic and fellow eyes in all patients. On the contrary, there was no significant difference in CMT and anterior segment parameters including mean keratometry and CCT in all patients and either group. During the development of the myopic anisometropia, more myopic eyes have significantly more myopic refraction, longer AL and thinner RNFLT compared to the fellow eyes.


The External RNA Controls Consortium: a progress report.
Standard controls and best practice guidelines advance acceptance of data from research, preclinical and clinical laboratories by providing a means for evaluating data quality. The External RNA Controls Consortium (ERCC) is developing commonly agreed-upon and tested controls for use in expression assays, a true industry-wide standard control.


Helical (spiral) CT of the liver.
Helical (spiral) CT of the liver consistently results in high quality scans as a result of the ability to image the liver in a single breath hold. Lesion detection is aided by scanning during the peak of hepatic enhancement, by the lack of respiratory misregistration, and by obtaining overlapping axial reconstructions. Because of these advantages, helical (spiral) CT is the preferred scanning mode for evaluation of hepatic disease.


Next generation immunotherapy: enhancing stemness of polyclonal T cells to improve anti-tumor activity.
The administration of T cells as cellular therapy against advanced cancers has brought clinical benefit to many patients and has progressed the field of cancer research. However, current cell therapy treatments are not curative in most patients, particularly in those with solid tumors, and it remains to be seen how broadly and efficaciously they may be applied going forward. Recent research has begun to elucidate key factors that regulate the efficacy of cell therapy in cancer patients, including T cell stemness and the ability to effectively target tumor antigens and overcome tumor heterogeneity. In this review, we discuss key properties of clinically effective anti-cancer T cell therapies along with strategies to improve T cell characteristics to augment clinical efficacy in solid tumors.


Surgical simulation: where have we come from? Where are we now? Where are we going?
It is now clear to most stakeholders that acquisition of surgical psychomotor skills is best achieved outside of the clinical operating room, in the context of a simulated environment. Endoscopic simulation can be accomplished using simple "box" simulators or video trainers, and virtual reality simulation is now possible using microprocessor-controlled systems. Structured surgical training performed outside of the operating room environment is relatively new to health care, a circumstance different from the process of pilot training, in which simulation has been a mainstay for more than 75 years and in which virtual reality simulation is now the norm. Those charged with surgical education are faced with a dilemma as, while attempting to understand the basic goals of simulation, they are simultaneously faced with choice between relatively inexpensive video trainers and the often prohibitively expensive virtual reality systems. This article explores the history of simulation, reports the results of a modified systematic review of currently available systems and performance, and identifies the gaps in current research and development. It is apparent that available video trainers provide the opportunity for skill development that at present is not surpassed by virtual reality systems. In the future, there will likely be an increasing role for virtual reality; however, challenges remain that include determination of the appropriate metrics and system design, and the fiscal resources necessary for the required hardware and related software development.


von Hippel-Lindau disease: identification of deletion mutations by pulsed-field gel electrophoresis.
Von Hippel-Lindau disease (VHL) is an inherited multisystem neoplastic disorder. We prepared a 2.5-megabase (Mb) restriction map of the region surrounding the VHL gene and identified and characterized overlapping deletions in three unrelated patients affected with VHL. The smallest nested deletion (100 kb) was located within a 510-kb NruI fragment detected by 19-63'. The rearrangements detected will be useful in isolating and evaluating candidate cDNAs for the VHL gene. The detailed physical map will be useful in studying the organization and structure of genes in the VHL region.


Treatment of stable angina pectoris with trimetazidine modified release in Indian primary-care practice.
In primary-care practice, trimetazidine is frequently used in combination with other antianginal drugs to enhance antianginal efficacy because of its metabolic mode of action. This study investigates whether a new twice-daily trimetazidine modified release formulation with improved pharmacokinetic properties is more effective and acceptable than the older thrice-daily immediate-release formulation. In a multicenter prospective study, patients with uncontrolled stable angina pectoris receiving combination antianginal treatment that included the thrice-daily trimetazidine were identified. The immediate-release trimetazidine formulation was substituted with twice-daily trimetazidine modified release (Flavedon) MR), with no other changes in the treatment regimen. Follow-up was for 3 months. The primary outcomes were entirely clinical: frequency of anginal attacks and nitroglycerin (glyceryl trinitrate) consumption. In 279 patients, substitution of thrice-daily trimetazidine with twice-daily trimetazidine modified release reduced mean frequency of angina by four attacks per week (95% CI 3.1, 4.9; p < 0.01) and nitroglycerin consumption by 3.6 tablets per week (95% CI 2.9, 4.3; p < 0.01). The magnitude of these benefits was directly proportional to the number of antianginal drugs used in combination with trimetazidine. There were no withdrawals due to adverse effects, and daily compliance was 98%. The twice-daily trimetazidine modified release is more effective and acceptable than the thrice-daily formulation for the combination treatment of stable angina in primary-care practice.


Non-pharmacological nurse-led interventions to manage anxiety in patients with advanced cancer: A systematic literature review.
Anxiety is a common symptom in patients with advanced cancer. Although pharmacological and psychosocial interventions are recommended, it remains unclear which role nurses can play in supporting patients with anxiety. The objective was to provide an inventory of non-pharmacological nurse-led interventions and evaluate the effectiveness in managing anxiety in advanced cancer patients. A systematic literature review was performed from xx-xx-xxxx until March 2013. Four databases (MEDLINE, CINAHL, PsycINFO and Cochrane) were searched using predefined search terms without date limits. Randomized controlled trials, focusing on non-pharmacological nurse-led interventions in the management of anxiety in patients with advanced cancer were identified. Due to the heterogeneity of the included studies, results are presented in a descriptive way. A total of seven studies were included. The interventions were categorized into patient education, telemonitoring, psychotherapy, complementary care or a combination of these. Two studies showed significant improvements in anxiety levels in patients who received a psychoeducational intervention and in those who participated in a telemonitoring program. However, both studies were judged with a high risk of bias due to attrition, the randomization process and the lack of blinding which was not described. A complementary care intervention, a focused narrative interview and a telemonitoring program identified improvement in anxiety after each time the intervention was provided. However, no significant differences between intervention and control group were found. Although there is no firm evidence due to the high risk of bias, two studies showed that nurses could play a meaningful role in the management of anxiety with regard to early recognition and even in a specific set of psychotherapeutic interventions. Obviously, interventions should be adapted to the underlying cause of anxiety. However, the results of this systematic literature review show a limited degree of evidence to realize this goal. Future research should focus on the interpretation of the findings in order to understand why certain interventions are effective. Furthermore, clarification of which nurse competencies are needed to perform these interventions successfully must be defined. Nevertheless, this systematic literature review encourages nurses to take a key role in the management of anxiety and shows that it is worthwhile to investigate the difference that can be made by nurses in supporting advanced cancer patients with anxiety.


Presence and localization of apelin and its cognate receptor in canine testes using immunohistochemical and RT-PCR techniques.
Apelin, a member of the adipokine family, is a novel endogenous peptide which regulates the male reproductive system of mammals by interacting with a specific receptor. Recent studies have highlighted that apelin may play a role in the regulation of reproduction by reducing testosterone production and inhibiting LH secretion. To the best of our knowledge, there is no available data on the presence of the apelin and its receptor in canine testes. Therefore, the aim of this study was to reveal the presence of apelin and evaluate its distribution in the canine testes using immunohistochemical and RT-PCR techniques. For this purpose, five fertile and healthy male dogs were subjected to elective orchiectomy. The immunohistochemical reaction revealed the presence of apelin and its receptor in the canine testes. Apelin was localized in spermatids and spermatozoa with a positive signal in the "acrosomal bodies". As regards the apelin receptor, a positive immunoreaction was detected in the cytoplasm of the cells localized near to the basal membrane of the seminiferous tubules and in the cytoplasm of Leydig cells. The RT-PCR analysis showed the presence of transcripts for apelin and apelin receptor in all of the samples under study. A 35kDa band confirmed apelin receptor protein expression in all of the samples analysed. In conclusion, the paracrine and endocrine role of apelin and its cognate receptor on male reproduction reported in humans and laboratory animals could also be hypothesized in dogs.


Exploring the dual effect of novel 1,4-diarylpyranopyrazoles as antiviral and anti-inflammatory for the management of SARS-CoV-2 and associated inflammatory symptoms.
COVID-19 and associated substantial inflammations continue to threaten humankind triggering death worldwide. So, the development of new effective antiviral and anti-inflammatory medications is a major scientific goal. Pyranopyrazoles have occupied a crucial position in medicinal chemistry because of their biological importance. Here, we report the design and synthesis of a series of sixteen pyranopyrazole derivatives substituted with two aryl groups at N-1 and C-4. The designed compounds are suggested to show dual activity to combat the emerging Coronaviruses and associated substantial inflammations. All compounds were evaluated for their in vitro antiviral activity and cytotoxicity against SARS-CoV infected Vero cells. As well, the in vitro assay of all derivatives against the SARS-CoV Mpro target was performed. Results revealed the potential of three pyranopyrazoles (22, 27, and 31) to potently inhibit the viral main protease with IC50 values of 2.01, 1.83, and 4.60 μM respectively compared with 12.85 and 82.17 μM for GC-376 and lopinavir. Additionally, in vivo anti-inflammatory testing for the most active compound 27 proved its ability to reduce levels of two cytokines (TNF-α and IL-6). Molecular docking and dynamics simulation revealed consistent results with the in vitro enzymatic assay and indicated the stability of the putative complex of 27 with SARS-CoV-2 Mpro. The assessment of metabolic stability and physicochemical properties of 27 have also been conducted. This investigation identified a set of metabolically stable pyranopyrazoles as effective anti-SARS-CoV-2 Mpro and suppressors of host cell cytokine release. We believe that the new compounds deserve further chemical optimization and evaluation for COVID-19 treatment.


Neurologic examination in the elderly.
Clinical evaluation of neurologic disorders in the elderly requires seeking a thorough history and performing an age-appropriate neurologic examination with special attention to changes that occur with normal aging. The history should be obtained from the patient as well as collateral sources close to the patient to ensure accuracy and should include contextual elements such as medical history, social, economic, and psychological background, as well as an assessment of current functional state beyond activities of daily living. The safety of the patient, including the presence of physical, psychological, and financial threats, should be addressed during the interview. The neurological examination in older adults may need to be modified to circumvent disabilities such as hearing and visual impairment. Some elements of the neurological examination are expected to be affected by the process of aging, including pupillary reactivity, presbyopia, difficulty with ocular pursuit and up-gaze, reduced or absent distal reflexes, slower motor speed, and reduced ability to tandem walk, among others. In addition to a screening neurological assessment, evaluation of older adults with a particular complaint may require additional interview queries and examination manoeuvres. Common symptoms in the elderly include cognitive difficulties, balance and gait disorders, tremors, and neuropathy. A specialized approach to patients with cognitive difficulties must include assessment of each cognitive domain, including attention, executive function, learning and memory, perceptual-motor function, and social cognition. Balance and gait are essential parts of the neurological examination, and in patients with a history of falls or mobility issues, should become a central part of the evaluation. In patient with tremors, careful observation of the tremor quality (amplitude, frequency, and alleviating/exacerbating factors such as rest, movement, and posture) can aid diagnosis. Evaluation of neuropathy includes determining modality (numbness, tingling, pain, and weakness) and the distribution of symptoms in order to localize the site of nerve injury, which can be supplemented with nerve conduction studies/electromyography, to guide further diagnostic workup and treatment. A combination of detailed history and examination often will suggest a likely underlying neurodegenerative disorder and guide further diagnostic workup to establish a specific diagnosis.


Bone infection site targeting nanoparticle-antibiotics delivery vehicle to enhance treatment efficacy of orthopedic implant related infection.
Orthopedic implants account for 99% of orthopedic surgeries, however, orthopedic implant-related infection is one of the most serious complications owing to the potential for limb-threatening sequelae and mortality. Current antibiotic treatments still lack the capacity to target bone infection sites, thereby resulting in unsatisfactory therapeutic effects. Here, the bone infection site targeting efficacy of D6 and UBI29-41 peptides was investigated, and bone-and-bacteria dual-targeted nanoparticles (NPs) with D6 and UBI29-41 peptides were first fabricated to target bone infection site and control the release of vancomycin in bone infection site. The results of this study demonstrated that the bone-and-bacteria dual-targeted mesoporous silica NPs exhibit excellent bone and bacteria targeting efficacy, excellent biocompatibility and effective antibacterial properties in vitro. Furthermore, in a rat model of orthopedic implant-related infection with methicillin-resistant Staphylococcus aureus, the growth of bacteria was evidently inhibited without cytotoxicity, thus realizing the early treatment of implant-related infection. Hence, the bone-and-bacteria dual-targeted molecule-modified NPs may target bacteria-infected bone sites and act as ideal candidates for the therapy of orthopedic implant-related infections.


MicroRNA-129-5p suppresses proliferation, migration and invasion of retinoblastoma cells through PI3K/AKT signaling pathway by targeting PAX6.
Retinoblastoma (RB) is the most common primary intraocular malignancy in children. Accumulating evidences have clarified that microRNAs (miRNAs) modulated signaling molecules by acting as oncogenes or tumor-suppressor genes in RB. Thus, in our study, we aimed to investigate the function of miR-129-5p in RB cells through PI3K/AKT signaling pathway by targeting PAX6. Two RB cell lines, Y79 and WERI-Rb-1, were selected in our study, followed by transfection of miR-129-5p inhibitor or si-PAX6 to explore the regulatory role of miR-129-5p in RB cell proliferation, invasion and migration. Dual-luciferase assay was used for the detection of targeting relationship between miR-129-5p and PAX6. Besides, western blot analysis was applied to detect expression of cell cycle-related factors (CDK2 and Cyclin E) and PI3K/AKT signaling pathway-related factors (p-AKT and AKT). Nude mice tumorigenesis experiment was used to evaluate the effect of miR-129a-5p on RB growth in vivo. miR-129-5p was down-regulated in RB cell lines. miR-129-5p directly targeted the 3'-untranslated region of PAX6. Artificial down-regulation of miR-129-5p promoted cell proliferation, migration and invasion in RB cell lines Y79 and WERI-Rb-1, and promoted RB growth in vivo via PI3K/AKT signaling pathway, which could be reversed by transfection with silencing PAX6. This study provides evidences that RB progression was suppressed by overexpressed miR-129-5p via direct targeting of PAX6 through PI3K/AKT signaling pathway, which may provide a molecular basis for better treatment for RB.


Comparison effectiveness of custom-made versus conventional aluminum splint for distal phalange injury.
Finger splint is a simple and common method for finger immobilization. The flexible aluminum foam-padded splint is a convenient off-the-shelf inexpensive splint. But there're some studies favor expensively custom-made thermoplastic splint due to its less likely result in treatment failure. Therefore the authors have modified the conventional aluminum finger splint in the foam-padded part to improve the fitting and compliance of the patients. To compare the fitting of custom-made aluminum finger splint with conventional aluminum finger splint. Sixty volunteers were randomized to apply 30 conventional or custom-made aluminum splints on 4th digit in non dominated hand for one week. The fitting of each splint was measured by displacement of the splint between initial placement and one week later. Patient satisfaction and pain was measured by visual analog score (VAS). The slip and deviation in custom-made group were less than the conventional group significantly (mean of slip 0.86 mm vs. 2.23 mm, p < 0.001, mean of deviation 1.1 degrees vs. 2.23 degrees,p < 0.001) but the longitudinal migration was not significantly difference between both groups (mean 1.6 mm in custom-made group vs. 1.46 mm in conventional group, p = 0.67). The patient satisfaction demonstrated no significant difference between both groups (mean VAS 7.76 in custom-made group vs. 7.3 in conventional group, p = 0.31). Two patients terminated from the present study before one week in custom-made group and one patient in the conventional group (6.67% vs. 3.33%, p = 0.554). The custom-made aluminum finger splint can improve the fitting to the finger pulp. However, patient satisfaction and compliance are not significantly different between both groups.


Expression of CTLA-4 by human monocytes.
Cytotoxic T lymphocyte-associated molecule-4 (CTLA-4) is a receptor present on T cells that plays a critical role in the downregulation of antigen-activated immune responses. CTLA-4 interacts with the ligands CD80 and CD86 on antigen-presenting cells (APC), and also directs the assembly of inhibitory signalling complexes that lead to quiescence or anergy. In this study, we show that human monocytes constitutively express CTLA-4. About 3% of monocytes expressed CTLA-4 on the cell surface, whereas the intracellular expression was higher and present in about 20% of the monocytes. The sequences of the cDNAs from human monocytes were identical to the sequences of CTLA-4 from T cells. Expression of CTLA-4 was also confirmed in the activated myelomonocytic cell lines U937 and THP-1. Monocytes, but not T cells, activated by interferon (IFN)-gamma also secreted soluble CTLA-4 in vitro. The CTLA-4 expression was upregulated upon treatment with phorbol 12-myristate 13-acetate (PMA) and IFN-gamma. This increased expression could be partially abolished by staurosporine, an inhibitor of protein kinase C (PKC). Ligation of CTLA-4 in the monocyte-like cell-line U937 with antibodies against CTLA-4 partially inhibited the proliferation of cells and the upregulation of cell-surface markers CD86, CD54, HLA-DR and HLA-DQ induced by IFN-gamma and Staphylococcus aureus, Cowan I strain (SAC). Ligation of CTLA-4 suppressed the PMA-stimulated activation of transcription activator protein 1 (AP-1) and nuclear factor (NF)-kappaB in the U937 cell line, indicating the involvement of an inhibitory signal transduction. These data provide the first evidence that CTLA-4 is constitutively expressed by monocytes and thus might be important for the regulation of immune mechanisms associated with monocytes.


Evoked potential evidence for differences in binocularity between striate and prestriate regions of human visual cortex.
For two components of the visual evoked potential elicited by the onset of a stationary pattern the degree of interocular transfer of the attenuation caused by prior exposure to a similar pattern was measured. The results show almost complete interocular transfer for component CII, thought to originate in prestriate cortex, but only partial transfer of CI, thought to be of striate cortical origin. This suggests that in man, as in monkey, monocularly driven neurones are more common in striate than in prestriate cortex.


Comparison analysis between conventional ultrasonography and ultrasound elastography of thyroid nodules.
To compare the effectiveness of conventional ultrasonography and ultrasound elastography in differential diagnosis of thyroid nodular diseases. 244 patients with 291 thyroid nodules were examined by ultrasonography and ultrasound elastography respectively; the examination results were compared against pathological findings to determine the effectiveness of these two examination methods. The sensitivity and positive predictive value of conventional ultrasonography is higher than those of ultrasound elastography, but its specificity, accuracy, and negative predictive value is lower than those of the later. Ultrasound elastography is superior to conventional ultrasonography in differential diagnosis of thyroid nodules. However, ultrasonography is the basis of examination; only on this basis, an additional ultrasound elastography examination could greatly improve the diagnostic rate of thyroid nodular diseases.


DNA isolation by a rapid method from human blood samples: effects of MgCl2, EDTA, storage time, and temperature on DNA yield and quality.
The isolation of DNA from whole blood by a modified rapid method (RM) was tested using various detergents and buffer conditions. Extraction of DNA with either NP-40 or Triton X-100 gave a high yield of undegraded DNA in less than an hour. The concentration of magnesium ion in the buffers was critical to obtaining intact, high molecular weight (HMW) DNA. Greater than 10 mM MgCl2 led to degradation. Addition of EDTA to the buffer inhibits this degradation. Preparation of DNA from blood stored at room temperature or incubated at 37 degrees C for 24 hr resulted in the same amount and quality of DNA as from samples frozen at -70 degrees C. DNA from blood samples that had undergone more than four freeze-thaw cycles was found to be partially degraded. The modified RM can be applied to extract DNA from as little as 10 microliters of blood (340 ng of DNA) and from dried blood samples. DNA samples remained intact and undegraded for longer times when DNA was dissolved in higher concentrations of EDTA.


Effect of adding screening ultrasonography to screening mammography on patient recall and cancer detection rates: a retrospective study in Japan.
To determine whether adding screening ultrasonography to screening mammography can reduce patient recall rates and increase cancer detection rates. We analyzed the results of mammography and ultrasonography breast screenings performed at the Total Health Evaluation Center Tsukuba, Japan, between April 2011 and March 2012. We also reviewed the modalities and results of diagnostic examinations from women with mammographic abnormalities who visited the Tsukuba Medical Center Hospital for further testing. Of 11,753 women screened, cancer was diagnosed in 10 (0.22%) of the 4529 participants who underwent mammography alone, 23 (0.37%) of the 6250 participants who underwent ultrasonography alone, and 5 (0.51%) of the 974 participants who underwent mammography and ultrasonography. The recall rate due to mammographic abnormalities was 4.9% for women screened only with mammography and 2.6% for those screened with both modalities. The cancer detection rate was 0.22% for women screened only with mammography (positive predictive value, 4.5%) and 0.31% for those screened with both modalities (positive predictive value, 12.0%). Of the 211 lesions presenting as mammographic abnormalities investigated further, diagnostic ultrasonography found no abnormalities in 63 (29.9%) and benign findings in 69 (33.7%). The rest 36.4% needed mammography, cytological or histological examinations or follow-up in addition to diagnostic ultrasonography. It is possible to reduce the recall rate in screening mammography by combining mammography and ultrasonography for breast screening.


Source of cholesterol for the ocular lens, studied with U18666A: a cataract-producing inhibitor of lipid metabolism.
Cholesterol is the major lipid component of the ocular lens. The source of lens cholesterol during the first month of post-natal life of the rat was investigated by use of U18666A, a potent inhibitor of cholesterol biosynthesis which can also produce cataracts. Lenses from rats treated with U18666A at a level known to produce cataracts were of smaller size and accumulated total sterol at about one-half the rate of untreated controls. The lens content of phospholipid also lagged behind that of controls. Desmosterol accounted for 50-75% of the total sterol in lens of all treated rats, this paralleled the percent content of desmosterol in liver and serum of these animals. Lenses taken from 20-day-old treated rats and incubated in vitro synthesized little digitonide-precipitable sterol (DPS) from 3H2O as compared to lenses from age-matched controls. The steady state concentration of U18666A in lens was found to be 1-2 X 10(-6) M; this concentration almost completely blocked sterol synthesis in vitro when added to normal lenses. Although U18666A inhibited lens synthesis in vitro of phospholipids from 1,3-[3H]-glycerol and 32Pi, it did so only at levels much higher than those encountered in vivo. Thus, the changes seen in lens phospholipids appear secondary to the decreases in sterols. Since lenses of treated rats synthesized little if any sterol but accumulated sterol at one-half the rate of control lens, we conclude that during early post-natal development of the rat the ocular lens possesses the potential to satisfy about one-half of its sterol requirements from sources outside of the lens, perhaps from lipoproteins in aqueous humor. This conclusion is consistent with our earlier work which indicated that the rat's lens can furnish 50-100% of its total cholesterol by synthesis de novo during the first two weeks of life and less thereafter. The relationship of the inhibition of sterol synthesis to production of the U18666A-induced cataract is discussed.


High-speed low-noise optical respiratory monitoring for spot scanning proton therapy.
To investigate a novel optical markerless respiratory sensor for surface guided spot scanning proton therapy and to measure its main technical characteristics. The main characteristics of the respiratory sensor including sensitivity, linearity, noise, signal-to-noise, and time delay were measured using a dynamic phantom and electrical measuring equipment on a laboratory stand. The respiratory signals of free breathing and deep-inspiration breath-hold patterns were acquired for various distances with a volunteer. A comparative analysis of this sensor with existing commercially available and experimental respiratory monitoring systems was carried out based on several criteria including principle of operation, patient contact, application to proton therapy, distance range, accuracy (noise, signal-to-noise ratio), and time delay (sampling rate). The sensor provides optical respiratory monitoring of the chest surface over a distance range of 0.4-1.2 m with the RMS noise of 0.03-0.60 mm, SNR of 40-15 dB (for motion with peak-to-peak of 10 mm), and time delay of 1.2 ± 0.2 ms. The investigated optical respiratory sensor was found to be appropriate to use in surface guided spot scanning proton therapy. This sensor combined with a fast respiratory signal processing algorithm may provide accurate beam control and a fast response in patients' irregular breathing movements. A careful study of correlation between the respiratory signal and 4DCT data of tumor position will be required before clinical implementation.


Influence of the metal center and linker on the intracellular distribution and biological activity of organometal-peptide conjugates.
Organometallic complexes conjugated to cell-penetrating peptides (CPPs) are promising systems for diagnostic imaging and therapeutic applications in human medicine. Recently, we reported on the synthesis of cymantrene(CpMn(CO)(3))-CPP conjugates with biological activity on different cancer cell lines. However, the precise mechanism of cytotoxicity remained elusive in these studies. To investigate the role of the metal center and the linker between the CpM(CO)(3) moiety and the peptide, a number of derivatives with manganese replaced by rhenium and the keto linker originally used substituted by a methylene group were prepared and fully characterized by (1)H NMR spectroscopy, infrared spectroscopy, electrospray ionization mass spectrometry, and elemental analysis as well as X-ray structure determination. The organometal-peptide conjugates as well as carboxyfluorescein-labeled derivatives thereof were prepared by solid-phase peptide synthesis, purified by high-performance liquid chromatography, and analyzed by mass spectrometry. Fluorescence microscopy studies of MCF-7 human breast cancer cells revealed an efficient cellular uptake and pronounced nuclear localization of the bioconjugates with the methylene linker compared with systems with the keto group. In addition, the latter also showed a higher cytotoxicity. In contrast, the variation of the metal center from manganese to rhenium had a negligible effect. The structure-activity relationships determined in the present work will aid in the further tuning of the biological activity of organometal-peptide conjugates.


Reduction of learned helplessness by central administration of quaternary naltrexone.
Prior research has established that escape impairment resulting from prior inescapable shock (IS) could be reversed by the peripheral administration of the opiate antagonist naltrexone (NTX), but not the quaternary form of naltrexone (QNTX), which when systemically administered, does not readily pass the blood-brain barrier. As it was unclear whether the failure of systemically administered QNTX to reduce shuttle escape deficits following exposure to IS could be attributed to reasons other than the restricted access of QNTX to receptor sites in the brain, rats were affixed with chronic indwelling ventricular cannulae to allow direct brain administration of QNTX. The present experiment found a significant attenuation of the escape deficit produced by prior inescapable shock following the intracerebroventricular (ICV) administration of QNTX (10 micrograms/rat). These data provide further evidence of a mediational role for central opiate receptors in the expression of escape interference following inescapable shock.


Valve disease in cardiac amyloidosis: an echocardiographic score.
Cardiac amyloidosis (CA) may affect all cardiac structures, including the valves. From 423 patients undergoing a diagnostic workup for CA we selected 2 samples of 20 patients with amyloid transthyretin (ATTR-) or light-chain (AL-) CA, and age- and sex-matched controls. We chose 31 echocardiographic items related to the mitral, aortic and tricuspid valves, giving a value of 1 to each abnormal item. Patients with ATTR-CA displayed more often a shortened/hidden and restricted posterior mitral valve leaflet (PMVL), thickened mitral chordae tendineae and aortic stenosis than those with AL-CA, and less frequent PMVL calcification than matched controls. Score values were 15.8 (13.6-17.4) in ATTR-CA, 11.0 (9.3-14.9) in AL-CA, 12.8 (11.1-14.4) in ATTR-CA controls, and 11.0 (9.1-13.0) in AL-CA controls (p = 0.004 for ATTR- vs. AL-CA, 0.009 for ATTR-CA vs. their controls, and 0.461 for AL-CA vs. controls). Area under the curve values to diagnose ATTR-CA were 0.782 in patients with ATTR-CA or matched controls, and 0.773 in patients with LV hypertrophy. Patients with ATTR-CA have a prominent impairment of mitral valve structure and function, and higher score values. The valve score may help identify patients with ATTR-CA among patients with CA or unexplained hypertrophy.


Indirect evidence for a physiological role exerted by a "testicular gonadotropin-releasing hormone" in the frog, Rana esculenta.
The possible physiological role of a putative testicular gonadotropin-releasing hormone (GnRH)-like material was studied in the frog, Rana esculenta. We have investigated (a) changes of mitotic index (MI) of primary spermatogonia (SPG) in GnRH agonist (GnRH-Ag)-treated testes in vitro; (b) changes of androgen concentrations in testes of intact frogs treated with a GnRH antagonist (GnRH-Ant); (c) variations of mitotic index of primary SPG in intact GnRH-Ant-injected animals and in testes incubated with GnRH-Ant; (d) changes of MI in hypophysectomized (PDX) animals treated with hypophysis (PD) homogenate, and hCG alone or in combination with GnRH-Ant; and (e) changes of androgen concentrations in plasma PDX frogs treated with hCG and hCG plus GnRH-Ant. Our results indicate that while GnRH-Ag induced accumulation of primary SPG mitosis, GnRH-Ant inhibited androgen production and natural occurring mitosis accumulation. Therefore, GnRH-Ant may counteract an endogenous peptide working into the testis.


Childhood amnesia and distinctions between forms of memory: a comment on Wood, Brown, and Felton.
Recently, Wood and his colleagues (1989) presented a case of childhood amnesia as evidence against the distinction between declarative and procedural memory that has sometimes been applied to human amnesia. Their argument was based on the observation that their patient showed some progress in school over the years, i.e., acquired some declarative knowledge, despite severely impaired day-to-day memory ability. We briefly review their case, together with a carefully studied second case of childhood amnesia not mentioned by Wood et al. Their argument is wrong in several ways. First, the utility of the declarative/procedural distinction for amnesia, or the utility of any other distinction between memory systems, depends on whether or not one kind of memory is impaired selectively, not on the severity of the impairment. In particular there is no requirement that one kind of memory be totally absent. Second, they have not provided the data necessary to support their argument; namely, data showing that the amount of declarative knowledge accumulated during years in school was better than would have been expected given the capacity for moment-to-moment or day-to-day memory. Indeed, the patient's moment-to-moment memory ability is better than represented, and the patient's progress in school was abnormally slow. Third, it is not clear that academic achievement scores provide a direct measure of declarative memory abilities (skill learning and recovery of function may also have contributed). We conclude that the evidence from childhood amnesia is fully consistent with the proposal that amnesia reflects a selective impairment in the formation of long-term declarative memory.


Trends in evolution of the Triatomini tribe (Hemiptera, Triatominae): reproductive incompatibility between four species of geniculatus clade.
The geniculatus clade, composed by the rufotuberculatus, lignarius, geniculatus and megistus groups, relates evolutionarily the species of the genus Panstrongylus and Nesotriatoma. Several studies have shown that triatomine hybrids can play an important role in the transmission of Chagas disease. Natural hybrids between species of the geniculatus clade have never been reported to our knowledge. Thus, carrying out experimental crosses between species of the geniculatus clade can help to elucidate the taxonomic issues as well as contribute to the epidemiological knowledge of this group. Experimental crosses were carried out between species of the megistus and lignarius groups to evaluate the reproductive compatibility between them. A phylogenetic reconstruction was also performed with data available in GenBank for the species of the geniculatus clade to show the relationships among the crossed species. Phylogenetic analysis grouped the species of the geniculatus clade into four groups, as previously reported. In the interspecific crosses performed there was no hatching of eggs, demonstrating the presence of prezygotic barriers between the crossed species and confirming their specific status. In contrast to the other groups of the Triatomini tribe, as well as the Rhodniini, there are prezygotic barriers that prevent the formation of hybrids between species of the megistus and lignarius groups. Thus, the geniculatus clade may represent an important evolutionary model for Triatominae, highlighting the need for further studies with greater sample efforts for this clade (grouping the 17 species of Panstrongylus and the three of Nesotriatoma).


Physiological variability in yearling alligators: clutch differences at rest and during activity.
The adult phenotype of an organism is the result of its genotype, the environment, and the interaction between the two. Assessing the relative contribution of these factors to the final adult phenotype continues to occupy researchers. Studies have shown clutch effects early in development but few have investigated the persistence of clutch effects on a longer time scale. Five clutches of American alligators were reared for 1 year in a common environment then assessed for the presence of clutch effects as they related to morphological and physiological characteristics. After 1 year, significant clutch effects were evident in all size related variables despite open access to food. Additionally, lung and liver masses remained different between clutches after animal mass was taken into account. Although clutch had no effect on resting heart rate, it significantly contributed to mean arterial pressure. During swimming and exhaustive exercise, the resulting respiratory and metabolic acidoses were strongly dependent on clutch. Therefore, while the environment can have significant influences on the American alligator from hatching to death, the measureable contribution of genetics to the morphology and physiology of the organism remains evident, even after 1 year of common rearing conditions. It behooves researchers to acknowledge and control for clutch effects when designing experiments.


X-ray microanalysis of cardiocytes in the Snell dwarf mouse.
X-ray microanalysis has been used to determine elemental content in the nucleus, myofibrillar cytoplasm and mitochondrially enriched cytoplasm of cardiocytes in Snell dwarf mice in comparison with phenotypically normal mice from the same strain. It was found that there was significantly lower chlorine concentration in all three subcellular locations and significantly lower sodium concentration in the nucleus of dwarf mouse cardiocytes. In both normal and dwarf mice, statistically significant subcellular compartmentalization was found for phosphorus, sulfur, and potassium.


Affinity isolation and mass spectral analysis of 1,10-phenanthroline (OP)-stimulated UV-damaged-DNA binding proteins expressed in zebrafish (Danio rerio) embryos.
Our earlier studies indicated the high expression of a UV-damaged-DNA binding activity in zebrafish (Danio rerio) embryos at 12 h postfertilization (hpf). Two 30- to 35-kDa polypeptides homologous to the N-terminal lipovitellin 1 (Lv1) domain of the 150-kDa zebrafish vitellogenin 1 (zfVg1) were identified as the damage recognition factors in zebrafish extracts, and the metal-chelating agent 1,10-phenanthroline (OP) was found to inhibit the embryonic UV-damaged-DNA binding activity. This study further explored the DNA damage-sensing components in 12 hpf zebrafish extracts. UV-damaged-DNA binding proteins were enriched from zebrafish extracts by isoelectrofocusing. Both OP-sensitive and OP-stimulated, UV-damaged-DNA binding activities were detected in fractionated zebrafish extracts. Two-dimensional gel electrophoresis of proteins captured by an immobilized oligonucleotide carrying a UV-induced (6-4)photoproduct (6-4PP) revealed a 25-kDa polypeptide as the major 6-4PP-binding factor in an OP-stimulated fraction. Three 25-kDa factors that bound weakly to 6-4PPs were also isolated. The four polypeptides having pIs between 7.0 and 7.3 were unreactive to an anti-zfVg1 antibody targeting the Lv1 domain. Mass spectral analysis showed the appearance of amino acid sequences LPIIVTTYAK and IPEITMSK in all 25-kDa polypeptides and sequences exactly matching those contained in the four factors exist only in the C-terminal Lv2 domain of zfVg1, reflecting the origination of these factors from enzymatic cleavage of the Lv2 domain at slightly different positions. The OP-stimulated fraction produced a much stronger UV-dependent DNA incision activity in the presence than in the absence of OP, suggesting the association of these factors with DNA damage repair under metal-deficient conditions.


Βeta-glucan stimulation induces trained immunity markers in common carp, Cyprinus carpio.
Trained immunity refers to the memory acquired by innate immune cells, leading to cross-protection and non-specific responses to subsequent infection, thereby improving host survival. Trained immunity induction is a combined effect of immune signaling, metabolic changes, and epigenetic modifications. The present study evaluated the induction of markers of the phenomenon of trained immunity in common carp, which is trained using β-glucan. The mammalian target of rapamycin (mtor) and hypoxia-inducible factor (hif1α), the metabolic basis of trained immunity; the histone deacetylase (hdac7), one of the markers of epigenetic modifications, metabolic activity of activated cells and expression profiles of proinflammatory cytokines viz. il6a, tnfαa2, and ifnγ were targeted in the study and analyzed in vivo. Besides in vivo analysis, in vitro analysis of mtorc2, hif1α, hdac7, and ifnγ were analyzed. In vitro analyses were performed on head kidney macrophages isolated and maintained in L-15 media and double trained with β-glucan at 100μg/mL. The culture supernatant was collected at different time intervals and processed for expression studies. Healthy common carp were injected with β-glucan at 20 mg/kg body weight for training followed by a resting phase for 6 days and were restimulated with the same dose. Head kidney was collected from the fish post-induction as well as post-restimulation. The expression profile of mtorc2, hdac7, and hif1α were found elevated post-stimulation of β-glucan. Further, a significantly upregulated expression profile of proinflammatory cytokines (ifnγ, il6a and tnfαa2) was observed. Increased glycolysis in the cells post-β-glucan stimulation was confirmed by the high lactate and LDH production detected in the cell culture supernatant. Overall, the study revealed the expression profile of the trained immunity markers and the increased metabolic activity in cells induced with β-glucan, which further validates that the action of trained immunity is indispensable in fish on encounter with a potential ligand. The study supports the existing reports on trained immunity in teleost fish with evidence at the genomic level. However, further studies are required to understand the responses and actions of trained immune cells during infection in detail.


Esterase-like and fibronectin-like polypeptides share similar sex-cell-biased patterns in the gonad of hermaphroditic and gonochoric species of bivalve mollusks.
The mechanism of sexualization of the tubular gonad in seawater bivalves is unknown, and no information regarding the genes involved in this process is yet available, except for the identification of esterase (Est)-like "male-associated polypeptide" in the male gonad of Mytilus galloprovincialis. Our present work reveals distinct protein profiles specific for the testicular or ovarian portion of the ovotestis of Pecten maximus. Two proteins exhibiting testis- or ovary-dependent enrichment in the ovotestis have been identified and partially characterized as Est-like and fibronectin (Fn)-like polypeptides, respectively. Immunofluorescence has demonstrated a close association between the localization of these polypeptides and the gonad tubule network and interstitial stroma of the ovotestis of P. maximus. We also present evidence of Est-like and Fn-like protein enrichment, respectively, in testicular and ovarian tissue in hermaphroditic, sex-reversal, and gonochoric species of seawater bivalves. Together, the results (1) strongly suggest that sex-cell-biased expression of Est-like and Fn-like polypeptides in gonad tissue is a widespread phenomenon among bivalve mollusks, despite the high diversification of their sexual patterns, (2) confirm and expand our previous demonstration of sex-biased protein expression in M. galloprovincialis, and (3) indicate a direct link between germ cell differentiation and sexual specialization of the bivalve somatic gonad.


Are diurnal changes in foot sole sensation dependent on gait activity?
The foot sole is loaded during stance and gait and plantar cutaneous mechanoreceptors sense the local stress distribution. It is not clear whether the perception thresholds of these mechanoreceptors change during the day and how they respond to walking activities. The primary aim of the present study was to investigate diurnal changes of plantar sensitivity. Furthermore, the aim was to find out whether daily changes depend on the individual level of step activity. Twenty-six healthy subjects, 17 women and 9 men, aged 28.6±6.7 years participated in the study. Detection thresholds to light touch were measured in six plantar regions with Semmes-Weinstein monofilaments in the morning, noon and afternoon. Step activity was recorded with a StepWatch™ Activity Monitor and analyzed for three periods (8 a.m.-4 p.m., 8 a.m.-12 p.m., 12 p.m.-4 p.m.). The hallux, the 3rd metatarsal head and the heel showed significantly decreased detection thresholds from 8 a.m. to 4 p.m. (p≤0.05). A fair correlation between the decrease of detection threshold and the total number of steps was found for the 3rd metatarsal head and the heel (p≤0.05). Foot sole sensation appears to improve during the day and seems to be associated with the step activity. This may reflect an improving transfer of afferent information to the central nervous system during the day as well as an adaptation of receptors to gait activity.


Using a 3D tool to document and determine graft loss: A mini-review and case report.
In severe burns, accurate determination of burn wound size and areas of debridement and graft loss is challenging. In this case report, we describe the use of 3D wound measurement software (BurnCase 3D, RISC Software GmbH, Hagenberg, Austria) in a 29-year-old patient with burns covering 92% of the total body surface area. BurnCase 3D was used to assess burn and monitor all surgical interventions. The software allowed us to calculate areas of graft loss and graft take throughout the acute hospitalization (until 90% of the wounds were covered with homografts). It also enabled preoperative planning for wound coverage and blood loss. Thus, BurnCase 3D appears to be a useful tool for accurate determination of burn wound areas and preoperative planning. However, whether the benefit of more efficient preoperative planning overcomes the disadvantage of the additional time needed to document the wound using the software needs to be evaluated further.


Purine Nucleoside Phosphorylase Deficient Severe Combined Immunodeficiencies: A Case Report and Systematic Review (1975-2022).
Purine nucleoside phosphorylase deficient severe combined immunodeficiency (PNP SCID) is one of the rare autosomal recessive primary immunodeficiency disease, and the data on epidemiology and outcome are limited. We report the successful management of a child with PNP SCID and present a systematic literature review of published case reports, case series, and cohort studies on PNP SCID listed in PubMed, Web of Science, and Scopus from 1975 until March 2022. Forty-one articles were included from the 2432 articles retrieved and included 100 PNP SCID patients worldwide. Most patients presented with recurrent infections, hypogammaglobulinaemia, autoimmune manifestations, and neurological deficits. There were six reported cases of associated malignancies, mainly lymphomas. Twenty-two patients had undergone allogeneic hematopoietic stem cell transplantation with full donor chimerism seen mainly in those receiving matched sibling donors and/or conditioning chemotherapy before the transplant. This research provides a contemporary, comprehensive overview on clinical manifestations, epidemiology, genotype mutations, and transplant outcome of PNP SCID. These data highlight the importance of screening for PNP SCID in cases presented with recurrent infections, hypogammaglobulinaemia, and neurological deficits.


Elevated LILRB1 expression predicts poor prognosis and is associated with tumor immune infiltration in patients with glioma.
Leukocyte immunoglobulin-like receptor subfamily B1 (LILRB1) is regarded as an inhibitory molecule. However, the importance of LILRB1 expression in glioma has not yet been determined. This investigation examined the immunological signature, clinicopathological importance and prognostic value of LILRB1 expression in glioma. We used data from the UCSC XENA database, the Cancer Genome Atlas (TCGA) database, the Chinese Glioma Genome Atlas (CGGA) database, the STRING database, the MEXPRESS database and our clinical glioma samples to perform bioinformatic analysis and used vitro experiments to examine the predictive value and potential biological roles of LILRB1 in glioma. Higher LILRB1 expression was considerably present in the higher WHO grade glioma group and was linked to a poorer prognosis in patients with glioma. Gene set enrichment analysis (GSEA) revealed that LILRB1 was positively correlated with the JAK/STAT signaling pathway. LILRB1 combined with tumor mutational burden (TMB) and microsatellite instability (MSI) may be a promising indicator for the effectiveness of immunotherapy in patients with glioma. Increased LILRB1 expression was positively linked with the hypomethylation, M2 macrophage infiltration, immune checkpoints (ICPs) and M2 macrophage makers. Univariate and multivariate Cox regression analyses determined that increased LILRB1 expression was a standalone causal factor for glioma. Vitro experiments determined that LILRB1 positively enhanced the proliferation, migration and invasion in glioma cells. MRI images demonstrated that higher LILRB1 expression was related with larger tumor volume in patients with glioma. Dysregulation of LILRB1 in glioma is correlated with immune infiltration and is a standalone causal factor for glioma.


Development of a new advanced animal cradle for small animal multiple imaging modalities: acquisition and evaluation of high-throughput multiple-mouse imaging.
The physiological conditions of small animals are an essential component to be considered when acquiring images for pre-clinical studies, and they play a vital role in the overall results of a study. However, several previous studies did not consider these conditions. In this study, a new animal cradle that can be modified and adjusted to suit multiple imaging modalities such as positron emission tomography (PET)/computed tomography (CT) and magnetic resonance imaging (MRI) was developed. Unlike previous cradles where only one mouse can be imaged at a time, a total of four mice can be imaged simultaneously using this new cradle. Additionally, fusion images with high-throughput multiple-mouse imaging (MMI) of PET/MRI and PET/CT images can be acquired using this newly developed cradle. The dynamic brain images were also acquired simultaneously by applying PET dynamic imaging technology to high-throughput MMI methods. The results of this study suggest that the newly developed small animal cradle can be widely used in pre-clinical studies.


Chemical constituents with antibacterial activity from Euphorbia sororia.
A group of ceramide (1) was isolated from the aerial parts of Euphorbia sororia. On the basis of spectroscopic data, chemical methods and GC-MS analysis, the structure of 1 was characterised as (2S,3S,4R,8E)-2-(eicosanoyl approximately octacosanoyl amino)-1,3,4-octadecanetriol-8-ene. In addition, four known ellagic acid derivatives 3,3'-di-O-methylellagic acid (2), 3,3',4'-tri-O-methylellagic acid (3), 4-O-sulfooxy-3,3'-di-O-methylellagic acid (4) and 4-O-sulfooxy- 3,3',4'-tri-O-methylellagic acid (5) were isolated from the plant. Biological screening of all compounds revealed moderate antibacterial activity.


Ultrasonographic fine-needle aspiration of pathological masses in the head and neck region.
Two hundred and eight ultrasonographic fine-needle aspiration biopsies were performed in patients with head and neck masses and examined cytologically. The average minimum diameter of the masses was 1.5 cm. The smallest punctured lymph node located in the perivascular sheath had a diameter of 0.4 cm. In none of the patients were complications observed. Ninety-seven percent of the diagnoses based on cytological examination were confirmed in the histological examination of surgical biopsies or in the further clinical course.


Adrenomedullin 2/intermedin is a slow off-rate, long-acting endogenous agonist of the adrenomedullin2 G protein-coupled receptor.
Adrenomedullin 2/intermedin (AM2/IMD), adrenomedullin (AM), and calcitonin gene-related peptide (CGRP) have functions in the cardiovascular, lymphatic, and nervous systems by activating three heterodimeric receptors comprising the class B GPCR CLR and a RAMP1, -2, or -3 modulatory subunit. CGRP and AM prefer the RAMP1 and RAMP2/3 complexes, respectively, whereas AM2/IMD is thought to be relatively nonselective. Accordingly, AM2/IMD exhibits overlapping actions with CGRP and AM, so the rationale for this third agonist for the CLR-RAMP complexes is unclear. Here, we report that AM2/IMD is kinetically selective for CLR-RAMP3, known as the AM2R, and we define the structural basis for its distinct kinetics. In live cell biosensor assays, AM2/IMD-AM2R elicited longer-duration cAMP signaling than the other peptide-receptor combinations. AM2/IMD and AM bound the AM2R with similar equilibrium affinities, but AM2/IMD had a slower off-rate and longer receptor residence time, thus explaining its prolonged signaling capacity. Peptide and receptor chimeras and mutagenesis were used to map the regions responsible for the distinct binding and signaling kinetics to the AM2/IMD mid-region and the RAMP3 extracellular domain (ECD). Molecular dynamics simulations revealed how the former forms stable interactions at the CLR ECD-transmembrane domain interface and how the latter augments the CLR ECD binding pocket to anchor the AM2/IMD C terminus. These strong binding components only combine in the AM2R. Our findings uncover AM2/IMD-AM2R as a cognate pair with unique temporal features, reveal how AM2/IMD and RAMP3 collaborate to shape CLR signaling, and have significant implications for AM2/IMD biology.


Locking plates and their effects on healing conditions and stress distribution: A femoral neck fracture study in cadavers.
Implants are used to stabilize femoral neck fractures to achieve successful fracture healing, but there is still a high rate of fracture non-unions. We compared micromotions in femurs with fractured femoral necks stabilized with three screws with or without a locking plate. We also investigated whether osteoporosis was associated with micromotion magnitudes, and explored the influence of implants on load distribution in the upper femur. Twelve pairs of human cadaver femurs with femoral neck fractures (AO/OTA 31-B1) were allocated to fracture fixation by three locked screws or three individual screws. All femurs underwent dual energy X-ray absorptiometry. Physiological subject-specific axial load and torque was applied for 10,000cycles. Micromotion of the head fragment was measured every 100cycles with high-resolution optical motion detection. Load distribution was measured with strain-gauge rosettes attached to the lateral and medial proximal diaphysis. The locking plate group showed reduced micromotion about the femoral neck axis (P=0.035, effect size=0.62). No differences were found in valgus-varus or antegrade-retrograde rotations, or in the three translations. Micromotion magnitudes were not associated with osteoporosis. The overall micromotions of the upper femur and the load distribution in the proximal diaphysis were not influenced by fixation type. The locking plate group showed increased resistance to shear forces compared with the screw group. This effect was not associated with a diagnosis of osteoporosis. The locking plate did not affect the load distribution in the proximal femur.


Yersinia pestis YadC: a novel vaccine candidate against plague.
Current subunit vaccines provide partial protection against pneumonic plague if the infecting Y. pestis strain is encapsulated (F1+). Here we describe YadC, a novel Y. pestis outer membrane protein that provides partial protection against a F1(-) Y. pestis strain. Swiss-Webster mice were immunized subcutaneously with glutathione S-transferase (GST) or His6-tagged (HT) purified fusion proteins (GST-YadC137-409 or HT-LcrV) or buffer emulsified with Alhydrogel. Intravenous challenge with 1 x 10(4) F1(-) Deltapgm Y. pestis CO99-3015 revealed no protection for those mice immunized with GST-Alhydrogel alone, full protection for HT-LcrV-immunized mice, and partial protection for GST-YadC137-409-immunized mice. Similarly, C57BL/6 mice were immunized with GST-YadC137-409, HT-LcrV, or GST all with Alhydrogel adjuvant. After intranasal challenge with 3 x 10(3) F1(-) Y. pestis CO99-3015, 87% of GST-YadC137-409-immunized mice survived pneumonic plague. This is compared to the GST control group (0 surviving mice) and the LcrV-immunized group where 50% survived the challenge. This protection was correlated with a predominantly IgG1 response in LcrV-immunized mice and an IgG1/IgG3 antibody response in YadC-immunized mice. Additionally, we report the cytokine response from HT-LcrV- and GST-YadC137-409-stimulated peripherally derived macrophages. YadC-stimulated cells demonstrated a predominant pro-inflammatory cytokine production. This mixed Thl/Th2 response suggests that YadC's protection may involve a different adaptive immune response than the LcrV protein that currently is part of plague vaccines.


Predictors of new atherosclerotic carotid plaque development in patients with rheumatoid arthritis: a longitudinal study.
Rheumatoid arthritis (RA) is associated with increased cardiovascular morbidity and mortality attributed to both classical risk factors and chronic inflammation. We assessed longitudinally the factors associated with new carotid plaques in nondiabetic RA patients and apparently healthy individuals. In our present prospective observational study, carotid plaques were identified by ultrasonography at baseline and follow-up end, separated by an average of 3.6 ± 0.2 years, in 64 patients (mean age 59.2 ± 12.0 and disease duration at baseline 7.8 ± 6.2 years, 83% women, clinical and laboratory evaluation every 3 to 6 months). In a substudy, 35 of the patients were matched 1:1 for traditional cardiovascular risk factors with 'healthy' controls and were studied in parallel. New atherosclerotic plaques formed in 30% of patients (first plaque in 9%) who were significantly older than the remaining patients. Tobacco use, blood pressure, body mass index, average cumulative low-density lipoprotein, high-sensitivity C-reactive protein, erythrocyte sedimentation rate level, RA stage, functional class, disease duration and treatment modalities during follow-up did not differ significantly between subgroups after application of the Bonferroni correction. RA was in clinical remission, on average, for approximately 70% of the follow-up time and was not different between subgroups. Multivariate analysis including all the above parameters revealed that age (P = 0.006), smoking (P = 0.009) and duration of low-dose corticosteroid use (P = 0.016) associated independently with new plaque formation. RA patients displayed similar numbers of newly formed carotid plaques to the tightly matched for traditional cardiovascular risk factors 'healthy' controls, although more patients than controls had carotid plaques at baseline. Formation of new atherosclerotic plaques in this small cohort of patients with well-controlled RA depended mainly on traditional cardiovascular risk factors and corticosteroid use, whereas an adverse effect of residual systemic inflammation was not readily detectable.


Low-level laser therapy for treatment of chemotherapy-induced oral mucositis in childhood: a randomized double-blind controlled study.
The aim of this study was to verify if low-level laser therapy could be useful to reduce chemotherapy-related oral mucositis grading and pain in childhood undergoing chemotherapy. A randomized double-blind clinical trial was carried out. Patients from 3 to 18 years of age undergoing cancer therapy and presenting OM grade 2 or more were eligible for this study. Patients were randomly divided in two groups: group A received laser therapy from the day of OM diagnosis and other 3 consecutive days (830 nm wavelength, power 150 mW, spot size 1 cm(2), 30 s per cm(2), energy density 4.5 J/cm(2)); group B received sham therapy (placebo) with the same timing. Two blind clinicians performed OM scoring and pain evaluation at day 1 (immediately before the beginning of laser treatment-T0), day 4 (after finishing laser therapy cycle-T1) and at day 7 (T2) as follow-up. A total of 123 patients were included in the study. Group A was composed of 62 children while group B is 61; in both groups, there was a progressive reduction in grade of OM, and at day 7, not every mucosal lesion disappeared. The difference in the decline of OM grading between the two groups resulted not statistically significant (p = 0.07). A statistically significant difference in pain reduction between two groups both at T1 and at T2 (p < 0.005) was observed. This study demonstrated the efficacy of LLLT in reducing pain due to chemotherapy-induced oral mucositis in children, while no significant benefit was noted in reducing OM grade.


Field control of plant growth and development through the laser activation of phytochrome.
Helium-neon lasers emitting at 632.8 nm can influence the phytochrome controlled growth and development of plants more than a quarter of a mile away. It may therefore be possible to control the growth of crops using lasers to activate the phytochrome system.


Assessing the energetic costs and trade-offs of a PHA-induced inflammation in the subterranean rodent Ctenomys talarum: immune response in growing tuco-tucos.
A traditional approach used to assess whether immune defense is costly is to explore the existence of trade-offs between immunity and other functions; however, quantitative studies of the energetic costs associated with the activation of the immune system are scarce. We assessed the magnitude of a PHA-triggered immune response and the associated energetic costs in 60-day old Ctenomys talarum. We expected that the magnitude of the macroscopic inflammatory response to PHA is lower in young tuco-tucos compared with that of adults, given the allocation of substantial energy to growth, and that the magnitude of the inflammation is lower in male pups compared to females, due to the higher investment in growth of the larger sex. Concomitantly, we expected that the pups challenged with PHA show an increase in oxygen consumption compared to control animals and that a positive association exists between magnitude of the PHA-induced inflammation and oxygen consumption. Contrary to what was expected, young tuco-tucos mounted a higher inflammatory response compared with adults and there were no differences in the magnitude of this response between sexes. The inflammatory response induced by a PHA injection did not represent a significant energetic cost for young tuco-tucos. There were no differences in oxygen consumption between PHA-injected and control animals, and tuco-tucos that mounted a higher inflammatory response to PHA did not show higher oxygen consumption. Energy expenditure, however, is not the only physiological cost involved in trade-offs between immune response and various functions of the organism, and other currencies are discussed.


Comparison of the morphology of three coronaviruses.
The morphology of three coronaviruses, avian infectious bronchitis virus strain Connecticut (IBV Conn), human coronavirus strain 229E (HCV 229E) and mouse hepatitis virus strain 3 (MHV3), were examined by negative staining. Significant differences were found in the sizes of the three coronaviruses. Furthermore, three types of surface projection of the same lengths, but varying widths and morphology, were observed. Both IBV Conn and HCV 229E had bulbous projections characteristic of coronaviruses, although the projections of HCV 229E were somewhat thinner than those of IBV Conn. On the other hand, MHV3 particles had thin, cone-shaped surface projections, that were completely unlike typical coronavirus projections. The significance of these results is discussed.


Effects of multiple firings on mechanical properties and resin bonding of lithium disilicate glass-ceramic.
This study aimed to evaluate the effects of different firing cycles on surface hardness, fracture toughness, and roughness of lithium disilicate glass-ceramic, as well as their bond strength to resin. A total of 320 polished lithium disilicate glass-ceramic plates were assigned to four main groups (n = 60) to receive one, two, three, or four firing cycles, respectively. Ceramic plates of the four groups were conditioned with HF acid followed by silanization. The pre-treated ceramic plates were cemented with composite resin cylinders using conventional or self-adhesive resin cements to build bonded specimens, and submitted to shear-bond-strength (SBS) testing after water storage for 24 h or 3 mo at 37 °C. The ceramic received different firing cycles after polishing or HF etching was observed using a scanning electron microscope, and their surface roughnesses were determined by a profilometer. The surface Vickers hardness, fracture toughness, and related Weibull analysis results of the polished ceramics after undergoing different firing-cycle times were compared. One sintering significantly increased fracture toughness of lithium disilicate glass-ceramic; however, multiple firing cycles failed to increase it further. Weibull analysis revealed a significant difference in terms of structural reliability among the specimens receiving 0-4 firing cycles. Specimens that received no firing cycle showed the highest surface hardness. Multiple firing cycles had no significant influence on the surface Vickers hardness and surface roughness. HF etching increased surface roughness, and the roughened surface improved the resin SBS of lithium disilicate glass-ceramic. Multiple firing cycles had no significant effect on surface roughness. Furthermore, multiple firing cycles and 3-mo water storage had no significant effect on the SBS. The mechanical properties of lithium disilicate glass-ceramics would be partially affected by multiple firing cycles, while their resin bonding would not be.


Leiomyosarcoma of the tongue: a case report.
Primary leiomyosarcomas arising from within the tongue are extremely rare. Only eight cases have been previously reported on Medline to our knowledge. We describe a case of a 46-year-old woman who presented with a lesion rapidly increasing in size on the lateral aspect of her tongue, which was excised. We present a completed-5-year follow-up.


How does consciousness for action relate to attention for action?
The interesting target article by Morsella et al. addresses critical issues that impact our understanding of consciousness. It is surprising, however, to see no treatment of the relationship between attention and consciousness, particularly given available models. Whether olfaction is most suitable as a model system to study consciousness for action also seems questionable. These issues are elaborated in the present commentary.


Patients and caregivers perspectives of the connection between home and the transplant journey.
For many heart failure patients, a heart transplant is required. Few hospitals in Canada perform heart transplants; thus, patients and caregivers must relocate to access transplant care. This study explores Canadian patients' and caregivers' experiences of to access transplant care and how patients and caregivers define home. The study's goal is to gain insights from the patient and caregiver experience and identify opportunities to improve the experience for those who relocate to access heart transplants. The research question was: How is the concept of home connected to the heart transplant journey? We conducted 18 interviews with advanced heart failure patients and caregivers, to explore patient and caregiver experiences of relocating to access transplant care. Patients and caregivers ranged in ages from 20's to 60's and had left their home of origin to move to a new location where medical care was available. 7 patients were male, 3 were female. All caregivers were female. Patients and caregivers identified three supports during relocation: other patients and caregivers, medical team and family. Patients and caregivers defined home as friends, family, community, warmth, safety, belonging and comfort. During relocation, patients and caregivers were supported by: other patients and caregivers, their medical team and family, and how these people made them feel: safe, warm, comfortable and that they belonged is how they defined home. The supports and definitions of home are connected; thus, a sense of home is inextricably linked to the transplant journey for patients and caregivers.


Influence of the antioxidant quercetin in vivo on the level of nitric oxide determined by electron paramagnetic resonance in rat brain during global ischemia and reperfusion.
We characterized the changes in nitric oxide (NO) levels in the brain during global forebrain ischemia and reperfusion and tested the ability of the natural flavonoid, quercetin, and a synthetic flavonoid, FB277, to increase the amount of available NO by elimination of the superoxide radicals produced during reperfusion. In Sprague-Dawley rats, we used a four-vessel occlusion model of forebrain ischemia (15 min) and reperfusion (30 min). Brain NO was measured on samples of cerebral cortex and cerebellum ex vivo by electron paramagnetic resonance (EPR) spectroscopy. The spin trap used was diethyldithiocarbamate sodium salt (DETC) associated with ferrous citrate. The complex Fe(DETC)2NO was detected at 77 K as a triplet signal at g = 2.035. Groups of animals were treated with quercetin or FB277 (3-morpholinomethyl-3',4',5,7tetramethoxyflavone) or polyethylene glycol-conjugated superoxide dismutase (PEG-SOD). In control (intact anesthetized animals), the signal was about 3 times greater in the cortex than in the cerebellum. During ischemia, the signal rose to 110% in cortex (NS) and 283% in cerebellum (P < 0.05). In reperfusion, it fell again to 91% of control in cerebellum (NS) and 35% in cortex (P < 0.05). Treatment by quercetin (5 mg/kg i.v.) of intact and ischemia-reperfusion groups did not significantly change the signal amplitude in the cerebellum, but did double it in the cortex (to 76% of control) for the ischemia-reperfusion group (P < 0.05). In contrast, FB277 (3.75 mg/kg i.v.) did not increase the signal in the cortex during ischemia-reperfusion, but did do so in the cerebellum (to 152% of control, P < 0.05). The results obtained for PEG-SOD (10,000 U/kg i.v.) were similar to those for FB277. In separate in vitro measurements, we found that quercetin but not FB277 efficiently scavenged superoxide. We hypothesize that quercetin but not FB277 scavenged superoxide anions released in the cortex during reperfusion, thus diminishing the amount of NO removed by the formation of peroxynitrite. The lack of effect of PEG-SOD may be related to the need for chronic treatment to obtain protection.


New insights into the human metabolism of the Fusarium mycotoxins deoxynivalenol and zearalenone.
This study reports on the detailed investigation of human deoxynivalenol (DON) and zearalenone (ZEN) in vivo metabolism through the analysis of urine samples obtained from one volunteer following a naturally contaminated diet containing 138μg DON and 10μg ZEN over a period of four days. Based on the mycotoxin intake and the concentrations of mycotoxin conjugates in urine, a mass balance was established. The average rates of DON excretion and glucuronidation were determined to be 68 and 76%, respectively. The investigation of formed glucuronides revealed DON-15-glucuronide as main conjugation product besides DON-3-glucuronide. Furthermore, for the first time in human urine a third DON-glucuronide was detected and the fate of ingested masked DON forms (3-acetyl-DON and DON-3-glucoside) was preliminary assessed. The mean excretion rate of ZEN was determined to be 9.4%. ZEN was mainly present in its glucuronide form and in some samples ZEN-14-glucuronide was directly determined 3-10h after exposure. For the first time concrete figures have become available for the excretion pattern of DON and ZEN-glucuronides throughout a day, the comparison of total DON in 24h and first morning urine samples and the urinary excretion rate of total ZEN in humans following exposure through naturally contaminated food. Therefore, valuable preliminary information has been obtained through the chosen experimental approach although the study involved only one single individual and needs to be confirmed in larger monitoring studies. The presented experiment contributes to a better understanding of human DON and ZEN in vivo metabolism and thereby supports advanced exposure and risk assessment to increase food safety and examine the relationship between these mycotoxins and potentially associated chronic diseases in the future.


Migration and ultrastructure of the acanthocephalan Echinorhynchus gadi Zoega in Müller, 1776 in intermediate host under experimental conditions.
Amphipods Eogammarus tiuschovi were experimentally infected by the acanthocephalan Echinorhynchus gadi (Acanthocephala: Echinorhynchidae). Within the first four days post-infection, acanthors of the acanthocephalan caused the cellular response of the host, which ended with their complete encapsulation on day 4 post-infection. The acanthors obtained through the experiment were examined ultrastructurally. Two syncytia (frontal and epidermal) and a central nuclear mass are found in the acanthor's body. The frontal syncytium has 3-4 nuclei and contains secretory granules with homogeneous, electron-dense contents. Since the secretory granules occupy only the anterior one-third of this syncytium, it is suggested that the contents of these granules are involved in the acanthor's migration through the gut wall of the amphipod. The central nuclear mass consists of an aggregation of fibrillar bodies and a few electron-light nuclei distributed on the periphery. Some of these nuclei, located near the central nuclear mass, are assumed to be a source of the acanthocephalan's internal organs. The epidermal syncytium surrounds the frontal syncytium and the central nuclear mass. It is represented by a superficial cytoplasmic layer, but the bulk of the cytoplasm is concentrated in the posterior one-third of the acanthor's body. Syncytial nuclei are evenly distributed throughout the cytoplasm. The muscular system of the acanthors consists of 10 longitudinal muscle fibers located below the superficial cytoplasmic layer and two muscle retractors crossing the frontal syncytium.


Comparative chemometric and quantitative structure-retention relationship analysis of anisotropic lipophilicity of 1-arylsuccinimide derivatives determined in high-performance thin-layer chromatography system with aprotic solvents.
Numerous structurally different amides and imides including succinimide derivatives exhibit diverse bioactive potential. The development of new compounds requires rationalization in the design in order to provide structural changes that guarantee favorable physico-chemical properties, pharmacological activity and safety. In the present research, a comprehensive study with comparison of the chromatographic lipophilicity and other physico-chemical properties of five groups of 1-arylsuccinimide derivatives was conducted. The chemometric analysis of their physico-chemical properties was carried out by using unsupervised (hierarchical cluster analysis and principal component analysis) and supervised pattern recognition methods (linear discriminant analysis), while the correlations between the in silico molecular features and chromatographic lipophilicity were examined applying linear and non-linear Quantitative Structure-Retention Relationship (QSRR) approaches. The main aim of the conducted research was to determine similarities and dissimilarities among the studied 1-arylsuccinimides, to point out the molecular features which have significant influence on their lipophilicity, as well as to establish high-quality QSRR models which can be used in prediction of chromatographic lipophilicity of structurally similar 1-arylsuccinimides. This study is a continuation of analysis and determination of the physico-chemical properties of 1-arylsuccinimides which could be important guidelines in further in vitro and eventually in vivo studies of their biological potential.


Nature apps: Waiting for the revolution.
Apps are small task-orientated programs with the potential to integrate the computational and sensing capacities of smartphones with the power of cloud computing, social networking, and crowdsourcing. They have the potential to transform how humans interact with nature, cause a step change in the quantity and resolution of biodiversity data, democratize access to environmental knowledge, and reinvigorate ways of enjoying nature. To assess the extent to which this potential is being exploited in relation to nature, we conducted an automated search of the Google Play Store using 96 nature-related terms. This returned data on ~36 304 apps, of which ~6301 were nature-themed. We found that few of these fully exploit the full range of capabilities inherent in the technology and/or have successfully captured the public imagination. Such breakthroughs will only be achieved by increasing the frequency and quality of collaboration between environmental scientists, information engineers, computer scientists, and interested publics.


Synthesis and Evaluation of Cytotoxicity of Novel Coumarin Peptide Alcohol Derivatives.
Coumarins are naturally occurring biologically active heterocyclic molecules endowed with a wide range of biological properties, including antibacterial, antifungal, and antitumor activities. The present work was aimed to synthesize new coumarin-containing compounds and to investigate their cytotoxic activity. Coumarin peptide and coumarin amino alcohols were prepared by treating epoxidecontaining coumarin derivatives with suitable aromatic amines and peptides in trifluoroethanol as a solvent at 50°C. These derivatives were evaluated for their cytotoxic activity on three different cell lines: HeLa, MDA-MB-231 and L-132. Cell viability was determined by MTT (3-(4,5- dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay. A new protocol was developed for the synthesis of thirteen novel coumarin peptide and coumarin amino alcohol derivatives. Among the tested compounds, three derivatives showed significant activity against all the tested cell lines. Docking studies indicated favorable interactions of the disubstituted peptide coumarin derivatives with the Asp 351 and Thr 347 amino acids at the active site of the human estrogen receptor. The results suggest that the synthesized compounds may be promising candidates in the research of new antitumor compounds.


Interocular equality of tonic accommodation and consensuality of accommodative hysteresis.
Interocular differences in tonic accommodation were assessed before and after a 10 minute period of sustained monocular fixation. The fixation task was carried out once for each eye using a high-contrast target at near, and once for each eye using an empty illuminated field. Tonic accommodation increased significantly as a result of fixating the high contrast target at near, but remained stable when viewing the empty field. Close correspondence was found between the two eyes with respect to both prefixation tonic level and magnitude of tonic after-effect. Absence of interocular differences clearly demonstrates the consensuality of accommodative hysteresis.


The quality of carp (Cyprinus carpio L.) cultured in various Polish regions.
Although environmental factors greatly affect the quality of carp meat, no regulations impose labelling the place of cultivation of freshwater fish. That is why the purpose of this study was to determine the quality of carp meat cultivated in several regions of Poland as well as to assess the necessity of implementing such regulations. The influence of the cultivation region on colour, nutrition value, health safety and sensory quality of carp meat was assessed. The analysis included colour measurement, determination of fatty acid profile and sensory evaluation of carp muscle. Moreover, microbiological analysis of the fish surface was performed. The results show that the place of cultivation does not influence the lightness (L*) of fillet, but has an impact on other colour parameters (a*, b*). The microbiological quality of fish from all studied farms was satisfactory, since no pathogenic microorganisms were observed on the fish surface. The fatty acid profile was fairly varied (P < 0.01), depending on the place of cultivation. Since final results seem ambiguous, further analyses of quality features of carp from various regions and cultures should be performed, before any recommendation for the necessity of labelling the place and method of cultivation should be suggested.


Structure and energy transfer pathways of the Dunaliella Salina photosystem I supercomplex.
Oxygenic photosynthesis evolved more than 3 billion years ago in cyanobacteria. The increased complexity of photosystem I (PSI) became apparent from the high-resolution structures that were obtained for the complexes that were isolated from various organisms, ranging from cyanobacteria to plants. These complexes are all evolutionarily linked. In this paper, the researchers have uncovered the increased complexity of PSI in a single organism demonstrated by the coexistance of two distinct PSI compositions. The Large Dunaliella PSI contains eight additional subunits, six in PSI core and two light harvesting complexes. Two additional chlorophyll a molecules pertinent for efficient excitation energy transfer in state II transition were identified in PsaL and PsaO. Short distances between these newly identified chlorophylls correspond with fast excitation transfer rates previously reported during state II transition. The apparent PSI conformations could be a coping mechanism for the high salinity.


[Treatment of advanced digestive cancer with fluorouracil and methyl-CCNU].
We relate the experience obtained by treatment of 20 advanced digestive cancer patients, with the association of 5 fluorouracil and methyl-C.C.N.U. Objective response was found in 4 patients (20%). Toxicity consisted of leucopenia in 3 patients, allergic phenomena in 2 and diarrhea in 1 patient. Mean survival is increased in 3 months in responders, when compared with non-responders, although this difference has not statistical value.


Audit of healthcare provision for UK prisoners with suspected epilepsy.
To describe the prevalence and nature of epileptic seizure disorders in a typical UK prison and compare the care offered to prisoners to the recommendations of the National Institute for Clinical Excellence (NICE). Over a 14-month period, all prisoners identified as having epilepsy were registered by prison primary healthcare services at a category 'C' prison holding 640 male adults. Prison and National Health Service health records were reviewed, prisoners were re-assessed by members of a specialist secondary care service based in the local general hospital NHS. Twenty-six prisoners were thought to have epilepsy. 61.5% of diagnoses had not been made by epilepsy specialists, 73.1% had uncontrolled seizures, only 19.2% had had computed tomography, none magnetic resonance imaging. At review, 30.8% of prisoners were thought to require neuroimaging, 19.2% cardiac investigations. The diagnosis of epilepsy was confirmed in only 57.9% of those prisoners considered to have the condition by prison healthcare services. 53.8% of those prisoners confirmed as having epilepsy had not had a medical review in the past 12 months; 63.2% required a change in their antiepileptic drugs (AEDs). Although the prevalence of epilepsy in this prison population appeared high at first sight, a critical review of the diagnoses reduced the difference to the prevalence of epilepsy in the population at large. Fewer prisoners than expected achieved seizure control. Collaboration with specialist epilepsy services was poor. There were significant discrepancies between the healthcare provision in prison and the NICE epilepsy guidelines.


Degradation of 5hmC-marked stalled replication forks by APE1 causes genomic instability.
Synthetic lethality between poly(ADP-ribose) polymerase (PARP) inhibition and BRCA deficiency is exploited to treat breast and ovarian tumors. However, resistance to PARP inhibitors (PARPis) is common. To identify potential resistance mechanisms, we performed a genome-wide RNAi screen in BRCA2-deficient mouse embryonic stem cells and validation in KB2P1.21 mouse mammary tumor cells. We found that resistance to multiple PARPi emerged with reduced expression of TET2 (ten-eleven translocation), which promotes DNA demethylation by oxidizing 5-methylcytosine (5mC) to 5-hydroxymethycytosine (5hmC) and other products. TET2 knockdown in BRCA2-deficient cells protected stalled replication forks (RFs). Increasing 5hmC abundance induced the degradation of stalled RFs in KB2P1.21 and human cancer cells by recruiting the base excision repair-associated apurinic/apyrimidinic endonuclease APE1, independent of the BRCA2 status. TET2 loss did not affect the recruitment of the repair protein RAD51 to sites of double-strand breaks (DSBs) or the abundance of proteins associated with RF integrity. The loss of TET2, of its product 5hmC, and of APE1 recruitment to stalled RFs promoted resistance to the chemotherapeutic cisplatin. Our findings reveal a previously unknown role for the epigenetic mark 5hmC in maintaining the integrity of stalled RFs and a potential resistance mechanism to PARPi and cisplatin.


The arches of chaos in the Solar System.
Space manifolds act as the boundaries of dynamical channels enabling fast transportation into the inner- and outermost reaches of the Solar System. Besides being an important element in spacecraft navigation and mission design, these manifolds can also explain the apparent erratic nature of comets and their eventual demise. Here, we reveal a notable and hitherto undetected ornamental structure of manifolds, connected in a series of arches that spread from the asteroid belt to Uranus and beyond. The strongest manifolds are found to be linked to Jupiter and have a profound control on small bodies over a wide and previously unconsidered range of three-body energies. Orbits on these manifolds encounter Jupiter on rapid time scales, where they can be transformed into collisional or escaping trajectories, reaching Neptune's distance in a mere decade. All planets generate similar manifolds that permeate the Solar System, allowing fast transport throughout, a true celestial autobahn.


Diagnostic and Therapeutic Challenges of Vasculitis.
Systemic vasculitis can be a challenge to differentiate from other forms of vasculopathy. Because treatment for systemic vasculitis is disparate from that for other forms of vasculopathy, clinicians should strive for high diagnostic certainty. This review article aims to highlight the clinical, radiographic, and histologic clues to distinguish systemic vasculitis from mimics. Vasculitis should be considered in patients with preexisting conditions including autoimmune connective tissue diseases, multisystem manifestations, unexplained ischemic events, unusual radiographic findings, or signs of systemic inflammation. A multidisciplinary approach can be used among rheumatologists, vascular cardiologists, radiologists, and vascular interventionalists to raise diagnostic certainty in cases with large- and/or medium-vessel involvement. Recognition of cardiac manifestations, including myocarditis seen in forms of small-vessel vasculitis (eg, eosinophilic granulomatosis with polyangiitis) or coronary arteritis seen in forms of medium-vessel vasculitis (eg, polyarteritis nodosa and Kawasaki disease) is important owing to the associated mortality. Clinical phenotype, radiographic features, laboratory tests, and histology can help to differentiate vasculitis from noninflammatory vasculopathies and define the etiology of the vasculitis to help guide appropriate treatment. Various modalities of imaging can give clues to aid in diagnosis of vasculitis and can be considered in the context of physician preference and patient comorbidity. While conventional angiography can give important details regarding luminal anatomy and pressure gradients in medium- and large-vessel vasculitis, noninvasive imaging modalities such as computed tomographic angiography, magnetic resonance angiography, color Doppler ultrasound, and positron emission tomography/computed tomography are commonly used for both diagnosis and follow-up. Treatment for systemic vasculitis should be coordinated with an experienced rheumatologist.