The Power of Unrequited Love: The Parasocial Relationship, Trust, and Organizational Identification Between Middle-Level Managers and CEOs.
Previous studies have found that CEOs manage their firms through traditional methods such as leadership and management practices. In this study, we investigate how the parasocial relationship (PSR) between middle-level managers and CEOs affects the organizational trust and the organizational identification (OI) of middle managers. We find that the PSR between middle managers and CEOs has a positive effect on the OI of middle managers, which is mediated by the organizational trust of middle managers. Purpose: Middle managers and CEOs are the key components of a firm and are crucial to firm strategies and control systems. Middle managers play a vital role in information transmission like in the organizational hierarchy while CEOs influence low-level employees through middle managers. In this study, we investigate how the PSR between middle managers and CEOs affects organizational trust and OI. Design/Methodology: In this study, the data concerning OI, integrity perception, and organizational trust are derived from a survey conducted by the internal control research group of the China Securities Regulatory Commission (CSRC). The research group began the survey on September 5, 2014, for the firms listed in the A-share market, accounting firms with securities and future practice qualifications, and institutional investors through the accounting department of the CSRC, the Shanghai Stock Exchange, the Shenzhen Stock Exchange, and the Asset Management Association of China. The research group members surveyed 2,536 A-share firms listed on the Shanghai Stock Exchange and Shenzhen Stock Exchange. As of October 31, 2014, 2,154 sets of questionnaires with a total of 12,551 questionnaires were received, with a response rate of 84.95%. The financial and accounting data are from the China Stock Market and Accounting Research (CSMAR) database. Findings: We find that the PSR between middle managers and CEOs has a positive effect on the OI of middle managers, which is mediated by the organizational trust of middle managers. This study extends the application of the parasocial interaction (PSI) theory, organizational trust theory, and social identity theory in listed firms. Practical Implication: There are practical implications for internal relationship management, corporate governance, and performance management. CEOs should value the influence of organizational trust and improve his/her own social and work abilities on middle-level managers as the organizational trust of middle-level managers has a significant positive impact on their sense of responsibility, ethical behavior, organizational commitment, job satisfaction, and performance. CEOs should adopt various methods to influence different managers because organizational trust mediates the relationship between the PSR and OI. Originality/Value: Our study is one of the first attempts to apply the PSI theory to the corporate world. Given the dynamics of present-day markets and changing stakeholder demands, there is little insight into how this relationship affects organizational health and functioning. Much less what a PSR between CEO and middle management looks like in practice. Our study attempts to fill the gap by investigating how CEOs might come to affect middle managers through their practices and behaviors.


Managing cancer patients with acute venous thromboembolism: exploring safe alternatives to hospitalisation.
Acute venous thromboembolism (VTE) is a common and potentially fatal complication that frequently occurs in cancer patients. Few data are currently available about the optimal management of this category of high-risk patients. In clinical practice, physicians have to deal with many problems related to cancer patients with acute VTE. For instance, cancer patients with deep vein thrombosis (DVT) are frequently admitted to the hospital since their high rate of recurrent thrombotic events and/or bleeding-related therapy; however, most of them would prefer alternatives to prolonged hospitalisation. Then, it is not clearly whether data coming from a non-cancer population (such as that regarding the use of D-dimer test and/or pre-test clinical probability [PCP]), can be reliable applied in cancer patients. Finally, scanty information is present on the feasibility of the "home-treatment program" for DVT in this category of high-risk patients. In our review we present data on a population of cancer patients evaluated at the Emergency Care in whom we have evaluated: 1) the diagnostic accuracy of PCP and D-dimer test; 2) the safety and efficacy of low molecular weight heparins (LMWH) as "protective anticoagulation" in case of deferred imaging for VTE and 3) the safety and efficacy of home treatment.


Pumice as a remarkable substrate for the origin of life.
The context for the emergence of life on Earth sometime prior to 3.5 billion years ago is almost as big a puzzle as the definition of life itself. Hitherto, the problem has largely been addressed in terms of theoretical and experimental chemistry plus evidence from extremophile habitats like modern hydrothermal vents and meteorite impact structures. Here, we argue that extensive rafts of glassy, porous, and gas-rich pumice could have had a significant role in the origin of life and provided an important habitat for the earliest communities of microorganisms. This is because pumice has four remarkable properties. First, during eruption it develops the highest surface-area-to-volume ratio known for any rock type. Second, it is the only known rock type that floats as rafts at the air-water interface and then becomes beached in the tidal zone for long periods of time. Third, it is exposed to an unusually wide variety of conditions, including dehydration. Finally, from rafting to burial, it has a remarkable ability to adsorb metals, organics, and phosphates as well as to host organic catalysts such as zeolites and titanium oxides. These remarkable properties now deserve to be rigorously explored in the laboratory and the early rock record.


SseK3 Is a Salmonella Effector That Binds TRIM32 and Modulates the Host's NF-κB Signalling Activity.
Salmonella Typhimurium employs an array of type III secretion system effectors that facilitate intracellular survival and replication during infection. The Salmonella effector SseK3 was originally identified due to amino acid sequence similarity with NleB; an effector secreted by EPEC/EHEC that possesses N-acetylglucoasmine (GlcNAc) transferase activity and modifies death domain containing proteins to block extrinsic apoptosis. In this study, immunoprecipitation of SseK3 defined a novel molecular interaction between SseK3 and the host protein, TRIM32, an E3 ubiquitin ligase. The conserved DxD motif within SseK3, which is essential for the GlcNAc transferase activity of NleB, was required for TRIM32 binding and for the capacity of SseK3 to suppress TNF-stimulated activation of NF-κB pathway. However, we did not detect GlcNAc modification of TRIM32 by SseK3, nor did the SseK3-TRIM32 interaction impact on TRIM32 ubiquitination that is associated with its activation. In addition, lack of sseK3 in Salmonella had no effect on production of the NF-κB dependent cytokine, IL-8, in HeLa cells even though TRIM32 knockdown suppressed TNF-induced NF-κB activity. Ectopically expressed SseK3 partially co-localises with TRIM32 at the trans-Golgi network, but SseK3 is not recruited to Salmonella induced vacuoles or Salmonella induced filaments during Salmonella infection. Our study has identified a novel effector-host protein interaction and suggests that SseK3 may influence NF-κB activity. However, the lack of GlcNAc modification of TRIM32 suggests that SseK3 has further, as yet unidentified, host targets.


Transmission of Toxoplasma: clues from the study of sea otters as sentinels of Toxoplasma gondii flow into the marine environment.
Toxoplasma gondii affects a wide variety of hosts including threatened southern sea otters (Enhydra lutris nereis) which serve as sentinels for the detection of the parasite's transmission into marine ecosystems. Toxoplasmosis is a major cause of mortality and contributor to the slow rate of population recovery for southern sea otters in California. An updated seroprevalence analysis showed that 52% of 305 freshly dead, beachcast sea otters and 38% of 257 live sea otters sampled along the California coast from 1998 to 2004 were infected with T. gondii. Areas with high T. gondii exposure were predominantly sandy bays near urban centres with freshwater runoff. Genotypic characterisation of 15 new T. gondii isolates obtained from otters in 2004 identified only X alleles at B1 and SAG1. A total of 38/50 or 72% of all otter isolates so far examined have been infected with a Type X strain. Type X isolates were also obtained from a Pacific harbor seal (Phoca vitulina) and California sea lion (Zalophus californianus). Molecular analysis using the C8 RAPD marker showed that the X isolates were more genetically heterogeneous than archetypal Type I, II and III genotypes of T. gondii. The origin and transmission of the Type X T. gondii genotype are not yet clear. Sea otters do not prey on known intermediate hosts for T. gondii and vertical transmission appears to play a minor role in maintaining infection in the populations. Therefore, the most likely source of infection is by infectious, environmentally resistant oocysts that are shed in the feces of felids and transported via freshwater runoff into the marine ecosystem. As nearshore predators, otters serve as sentinels of protozoal pathogen flow into the marine environment since they share the same environment and consume some of the same foods as humans. Investigation into the processes promoting T. gondii infections in sea otters will provide a better understanding of terrestrial parasite flow and the emergence of disease at the interface between wildlife, domestic animals and humans.


What is the impact of systems of care for heart failure on patients diagnosed with heart failure: a systematic review.
Hospital admissions for heart failure are predicted to rise substantially over the next decade placing increasing pressure on the health care system. There is an urgent need to redesign systems of care for heart failure to improve evidence-based practice and create seamless transitions through the continuum of care. The aim of the review was to examine systems of care for heart failure that reduce hospital readmissions and/or mortality. Electronic databases searched were: Ovid MEDLINE, EMBASE, CINAHL, grey literature, reviewed bibliographies and Cochrane Central Register of Controlled Trials for randomised controlled trials, non-randomised trials and cohort studies from 1st January 2008 to 4th August 2015. Inclusion criteria for studies were: English language, randomised controlled trials, non-randomised trials and cohort studies of systems of care for patients diagnosed with heart failure and aimed at reducing hospital readmissions and/or mortality. Three reviewer authors independently assessed articles for eligibility based on title and abstract and then full-text. Quality of evidence was assessed using Newcastle-Ottawa Scale for non-randomised trials and GRADE rating tool for randomised controlled trials. We included 29 articles reporting on systems of care in the workforce, primary care, in-hospital, transitional care, outpatients and telemonitoring. Several studies found that access to a specialist heart failure team/service reduced hospital readmissions and mortality. In primary care, a collaborative model of care where the primary physician shared the care with a cardiologist, improved patient outcomes compared to a primary physician only. During hospitalisation, quality improvement programs improved the quality of inpatient care resulting in reduced hospital readmissions and mortality. In the transitional care phase, heart failure programs, nurse-led clinics, and early outpatient follow-up reduced hospital readmissions. There was a lack of evidence as to the efficacy of telemonitoring with many studies finding conflicting evidence. Redesigning systems of care aimed at improving the translation of evidence into clinical practice and transitional care can potentially improve patient outcomes in a cohort of patients known for high readmission rates and mortality.


Youth outcomes of psychological distress of Albanian adolescents in Albania.
Albania is a country of transition facing many challenges including the development and support of health and social services that will enhance the well-being of its population. Albania has one of the youngest populations in Europe and the young people face difficulties with lack of recognition and care of mental disorders, as well as violent and antisocial behaviours that may reflect violent environmental conditions and nutritional deficiencies leading to developmental problems. In this paper the behaviour of some Albanian adolescents was examined; it is probable that they are more at risk from psychological stress. For many of them the need to make a new start at a point in life at which all resources should be committed to distancing the world of childhood and starting to create a position, means a process of inevitable recession.


Mesenchymal stromal cells orchestrate follicular lymphoma cell niche through the CCL2-dependent recruitment and polarization of monocytes.
Accumulating evidence indicates that infiltrating stromal cells contribute directly and indirectly to tumor growth in a wide range of cancers. In follicular lymphoma (FL), malignant B cells are found admixed with heterogeneous lymphoid-like stromal cells within invaded lymph nodes and BM. In addition, mesenchymal stromal cells (MSCs) support in vitro FL B-cell survival, in particular after their engagement toward lymphoid differentiation. We show here that BM-MSCs obtained from patients with FL (FL-MSCs) display a specific gene expression profile compared with MSCs obtained from healthy age-matched donors (HD-MSCs). This FL-MSC signature is significantly enriched for genes associated with a lymphoid-like commitment. Interestingly, CCL2 could be detected at a high level within the FL-cell niche, is up-regulated in HD-MSCs by coculture with malignant B cells, and is overexpressed by FL-MSCs, in agreement with their capacity to recruit monocytes more efficiently than HD-MSCs. Moreover, FL-MSCs and macrophages cooperate to sustain malignant B-cell growth, whereas FL-MSCs drive monocyte differentiation toward a proangiogenic and lipopolysaccharide-unresponsive phenotype close to that of tumor-associated macrophages. Altogether, these results highlight the complex role of FL stromal cells that promote direct tumor B-cell growth and orchestrate FL-cell niche, thus emerging as a potential therapeutic target in this disease.


Circadian egg production by Echinostoma caproni (Digenea: Echinostomatidae) in ICR mice.
Circadian egg production by Echinostoma caproni was investigated in ICR mice. Four female mice were infected with 25 E. caproni metacercariae, maintained in individual cages on a 12:12 light:dark cycle, and provided food and water ad libitum. Twenty-eight, 51, and 58 days post-infection, mice were transferred to individual, wire-bottomed cages and feces were collected every 2 hr for 24 hr. The feces were weighed and processed immediately to estimate the number of eggs present. Fecal output and egg production were standardized to unit maxima for analysis. Standardized egg count and standardized fecal output followed distinctly circadian patterns and covaried. Egg production was highest from 2200 to 0200 hr and lowest from 1000 to 1800 hr. These correspond to the highest and lowest fecal production, and highest and lowest periods of host activity, respectively. Egg density (eggs/g of feces) covaried weakly with fecal output with an additional peak at 0800-1000 hr, suggesting E. caproni is responding to changes in host physiology in timing of the production and release of eggs into the intestine. The continuous production and release of eggs during the patent period, coupled with the circadian pattern of daily egg release by E. caproni , would result in the widest dispersal of eggs in the host environment and enhance transmission to the first intermediate host.


Tic suppression in the treatment of Tourette's syndrome with exposure therapy: the rebound phenomenon reconsidered.
Exposure and response prevention (ER), a behavioral treatment program consisting of exposure to premonitory sensory experiences during prolonged tic suppression, was shown to be a promising new treatment for tics in Tourette's syndrome (TS). In this study, the commonly reported paradoxical increase in tic frequency following voluntary tic suppression, i.e., rebound phenomenon, was examined. Tic frequency was rated in 20 TS patients during 15-minute videotaped conversations taken both before and following 10 ER sessions. In addition, tic frequency was obtained at home by family members of the patients during 15-minute daily tic frequency registrations. Ratings following ER sessions were compared with ratings obtained before the sessions. Neither the ratings at the institute nor the ratings at home supported a rebound effect following ER tic suppression.


An injectable click-crosslinked hyaluronic acid hydrogel modified with a BMP-2 mimetic peptide as a bone tissue engineering scaffold.
An injectable, click-crosslinking (Cx) hyaluronic acid (HA) hydrogel scaffold modified with a bone morphogenetic protein-2 (BMP-2) mimetic peptide (BP) was prepared for bone tissue engineering applications. The injectable click-crosslinking HA formulation was prepared from HA-tetrazine (HA-Tet) and HA-cyclooctene (HA-TCO). The Cx-HA hydrogel scaffold was prepared simply by mixing HA-Tet and HA-TCO. The Cx-HA hydrogel scaffold was stable for a longer period than HA both in vitro and in vivo, which was verified via in-vivo fluorescence imaging in real time. BP acted as an osteogenic differentiation factor for human dental pulp stem cells (hDPSCs). After its formation in vivo, the Cx-HA scaffold provided a fine environment for the hDPSCs, and the biocompatibility of the hydrogel scaffold with tissue was good. Like traditional BMP-2, BP induced the osteogenic differentiation of hDPSCs in vitro. The physical properties and injectability of the chemically loaded BP for the Cx-HA hydrogel (Cx-HA-BP) were nearly identical to those of the physically loaded BP hydrogels and the Cx-HA-BP formulation quickly formed a hydrogel scaffold in vivo. The chemically loaded hydrogel scaffold retained the BP for over a month. The Cx-HA-BP hydrogel was better at inducing the osteogenic differentiation of loaded hDPSCs, because it prolonged the availability of BP. In summary, we successfully developed an injectable, click-crosslinking Cx-HA hydrogel scaffold to prolong the availability of BP for efficient bone tissue engineering.


Mineralization of flumequine in acidic medium by electro-Fenton and photoelectro-Fenton processes.
The mineralization of flumequine, an antimicrobial agent belonging to the first generation of synthetic fluoroquinolones which is detected in natural waters, has been studied by electrochemical advanced oxidation processes (EAOPs) like electro-Fenton (EF) and photoelectro-Fenton (PEF) with UVA light. The experiments were performed in a cell containing a boron-doped diamond (BDD) anode and an air-diffusion cathode to generate H(2)O(2) at constant current. The Fe(2+) ion added to the medium increased the solubility of the drug by the formation of a complex of intense orange colour and also reacted with electrogenerated H(2)O(2) to form hydroxyl radical from Fenton reaction. Oxidant hydroxyl radicals at the BDD surface were produced from water oxidation. A partial mineralization of flumequine in a solution near to saturation with optimum 2.0mM Fe(2+) at pH 3.0 was achieved by EF. The PEF process was more powerful, giving an almost total mineralization with 94-96% total organic carbon removal. Increasing current accelerated both treatments, but with decreasing mineralization current efficiency. Comparative treatments using a real wastewater matrix led to similar degradation degrees. The kinetics for flumequine decay always followed a pseudo-first-order reaction and its rate constant, similar for both EAOPs, raised with increasing current. Generated carboxylic acids like malonic, formic, oxalic and oxamic acids were quantified by ion-exclusion HPLC. Fe(III)-oxalate and Fe(III)-oxamate complexes were the most persistent by-products under EF conditions and their quicker photolysis by UVA light explains the higher oxidation power of PEF. The release of inorganic ions such as F(-), NO(3)(-) and in lesser extent NH(4)(+) was followed by ionic chromatography.


Hospital admission and the occurrence of delirium in older adults with physical frailty: cross-sectional study.
To analyze the relationship between hospitalization and the occurrence of delirium in older adults with physical frailty. Cross-sectional study carried out in a public hospital in southern Brazil. Hospitalized older adults aged ≥ 60 years participated. Sociodemographic and clinical data were collected, physical frailty phenotype tests were performed and the Confusion Assessment Method was used. Descriptive analyzes were carried out and odds ratio values were estimated for the frailty and delirium variables. Of the 320 older adults evaluated, 21.14% presented delirium, 49% were identified as pre-frail and 36.2% as frail. Of those affected by delirium, 71.6% were classified as frail and 28.3% as pre-frail (p < 0.001). An association was observed between the occurrence of delirium and frailty (OR 1.22; 95% CI 1.07 to 1.38), age ≥ 80 years (OR 1.14; 95% CI 1.01 to 1.32), epilepsy (OR 1.38; 95% CI 1.09 to 1.76), dementia (OR 1.58; 95% CI 1.37 to 1.82), and history of stroke (OR 1.14; 95% CI 1.03 to 1.26). There was a high frequency of pre-frail and frail older adults, and the occurrence of delirium in frail was significantly higher. Special attention should be paid to frail older adults to prevent the occurrence of delirium during hospitalization.


Clonality in lymphocyte predominance Hodgkin's disease.
Abundant evidence has led to the clinical and biological separation of lymphocyte predominance from other types of Hodgkin's disease. However, it is still not clear whether lymphocyte predominance represents a polyclonal reactive lesion (possibly representing an abnormal immune disorder), a polyclonal or oligoclonal preneoplastic disorder or a monoclonal neoplastic disorder. The clinical and histological features are distinctive, but they do not provide clear indications of the nature of lymphocyte predominance. Some immunohistochemical and in situ hybridization studies have shown monotypic light chain restriction in the L&H cells, almost always of kappa type, implying a monoclonal process. Southern blotting studies are of limited utility, given their relatively low sensitivity and the rarity of L&H cells within involved tissues. Polymerase chain reaction studies have yielded conflicting results. Some, but not all, have demonstrated monoclonal populations in tissue extracts. Single cell PCR studies have generally not found monoclonal populations, although one case stands as an exception. Cases of large cell lymphoma complicating lymphocyte predominance have been monoclonal by polymerase chain reaction and clonospecific primers derived from these clones have demonstrated similar populations in the corresponding lymphocyte predominance tissues in some, but not all, studies.


Recommendations on the use of exercise testing in clinical practice.
Evidence-based recommendations on the clinical use of cardiopulmonary exercise testing (CPET) in lung and heart disease are presented, with reference to the assessment of exercise intolerance, prognostic assessment and the evaluation of therapeutic interventions (e.g. drugs, supplemental oxygen, exercise training). A commonly used grading system for recommendations in evidence-based guidelines was applied, with the grade of recommendation ranging from A, the highest, to D, the lowest. For symptom-limited incremental exercise, CPET indices, such as peak O(2) uptake (V'O(2)), V'O(2) at lactate threshold, the slope of the ventilation-CO(2) output relationship and the presence of arterial O(2) desaturation, have all been shown to have power in prognostic evaluation. In addition, for assessment of interventions, the tolerable duration of symptom-limited high-intensity constant-load exercise often provides greater sensitivity to discriminate change than the classical incremental test. Field-testing paradigms (e.g. timed and shuttle walking tests) also prove valuable. In turn, these considerations allow the resolution of practical questions that often confront the clinician, such as: 1) "When should an evaluation of exercise intolerance be sought?"; 2) "Which particular form of test should be asked for?"; and 3) "What cluster of variables should be selected when evaluating prognosis for a particular disease or the effect of a particular intervention?"


Differentiation of Streptomyces coelicolor A3(2) under nitrate-limited conditions.
The life cycle of Streptomyces coelicolor during development on solid medium has been studied from a physiological perspective. A biphasic growth pattern was demonstrated, evidenced by a continuous transition from an initial exponential growth period into a slower phase of biomass accretion. The switch between the two phases coincided with the exhaustion of nitrate from the medium. The depletion of nitrate from the medium coincided with the initiation of aerial mycelium formation within the cultures and the development of hydrophobic surface properties. During secondary growth, cultures remained metabolically active, continuing to accumulate DNA, despite a cessation in the levels of RMA and cell protein accretion. In addition, the accumulation of glycogen and lipid contributed to the observed accretion of biomass in this phase. The depletion of nitrate also marked an increase in the production of α-ketoglutarate by the culture and a coincident decrease in medium pH. Latter stages of the secondary growth phase saw the development of spores within the culture, this in turn was associated with a decrease in cellular glycogen. This supported previous observations that glycogen degradation and spore maturation were intimately associated.


The Corynebacterium glutamicum aecD gene encodes a C-S lyase with alpha, beta-elimination activity that degrades aminoethylcysteine.
S-(beta-Aminoethyl)-cysteine (AEC) resistance was achieved in Corynebacterium glutamicum by cloning a chromosomal 1.5-kb EcoRV-BglII DNA fragment on a multicopy plasmid. DNA sequence analysis of the 1.5-kb DNA fragment revealed an open reading frame (ORF326) which represents the AEC resistance gene, designated aecD. The aecD gene directs the synthesis of a 36-kDa protein which was visualized by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The aecD gene is a nonessential gene and mediates AEC resistance only in an amplified state. C. glutamicum strains harboring an amplified aecD gene can utilize AEC as an alternative nitrogen source, indicating that the AEC resistance mechanism is due to AEC degradation. Since the AEC degradation products analyzed by high-pressure liquid chromatography were found to be pyruvate and aminoethanethiol (cysteamine), it was concluded that the aecD gene encodes a C-S lyase with alpha, beta-elimination activity. Besides AEC, the C-S lyase was also able to use cysteine, cystine, and cystathionine as substrates.


Acetaminophen reduces the protein levels of high affinity amino acid permeases and causes tryptophan depletion.
In yeast, toxicity of acetaminophen (APAP), a frequently used analgesic and antipyretic drug, depends on ubiquitin-controlled processes. Previously, we showed a remarkable overlap in toxicity profiles between APAP and tyrosine, and a similarity with drugs like rapamycin and quinine, which induce degradation of the amino acid permease Tat2. Therefore, we investigated in yeast whether APAP reduced the expression levels of amino acid permeases. The protein levels of Tat2, Tat1, Mup1 and Hip1 were reduced, while the expression of the general permease Gap1 was increased, consistent with a nutrient starvation response. Overexpression of Tat1 and Tat2, but not Mup1, Hip1 and Gap1 conferred resistance to APAP. A tryptophan auxotrophic strain trp1Δ was more sensitive to APAP than wild-type and addition of tryptophan completely restored the growth restriction of trp1∆ upon APAP exposure, while tyrosine had an additive effect on APAP toxicity. Furthermore, intracellular aromatic amino acid concentrations were reduced upon APAP exposure. This effect was less prominent in ubiquitin-deficient yeast strains that were APAP resistant and showed a reduced degradation of high affinity amino acid permeases. APAP-induced changes in intracellular amino acid concentrations were also detected in hepatoma HepG2 cells indicating significance for humans.


Regulation of antioxidants in cancer.
Scientists in this field often joke, "If you don't have a mechanism, say it's ROS." Seemingly connected to every biological process ever described, reactive oxygen species (ROS) have numerous pleiotropic roles in physiology and disease. In some contexts, ROS act as secondary messengers, controlling a variety of signaling cascades. In other scenarios, they initiate damage to macromolecules. Finally, in their worst form, ROS are deadly to cells and surrounding tissues. A set of molecules with detoxifying abilities, termed antioxidants, is the direct counterpart to ROS. Notably, antioxidants exist in the public domain, touted as a "cure-all" for diseases. Research has disproved many of these claims and, in some cases, shown the opposite. Of all the diseases, cancer stands out in its paradoxical relationship with antioxidants. Although the field has made numerous strides in understanding the roles of antioxidants in cancer, many questions remain.


Tripterygium glycosides for safely controlling disease activity in systemic lupus erythematosus: a systematic review with meta-analysis and trial sequential analysis.
Background: Tripterygium glycosides have been used to treat systemic lupus erythematosus (SLE) for a long time, showing the effects of immune regulation. We aimed to evaluate the benefits and risks of Tripterygium Glycosides Tablets (TGT) for patients with SLE. Methods: We searched electronic databases and clinical trial registries for relevant randomized controlled trials (RCTs). We identified eligible RCTs and assessed risk of bias. We conducted a meta-analysis to estimate the pooled effects. The Trial Sequential Analysis (TSA) 0.9.5.10 software was used to verify the reliability of the results. Results: Eight RCTs encompassing 538 patients with SLE were included. TGT combined with conventional treatments (CTs) was superior to CTs alone in reducing lupus activity (MD = -1.66, 95% CI = -2.07 to -1.26, p < 0.00001, low-certainty evidence) and improving overall response rate (ORR) (RR = 1.21, 95% CI = 1.11 to 1.32, p < 0.0001, moderate-certainty evidence). The robustness of the results was confirmed by TSA. Regarding safety, there was no statistical difference in the overall incidence of adverse reactions between the two groups. Conclusion: In patients with SLE, TGT might safely reduce disease activity. However, further high-quality studies are needed to firmly establish the clinical efficacy of TGT. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022300474; Identifier: CRD42022300474.


Application of a diamond detector to brachytherapy dosimetry.
The feasibility of using a diamond detector for the dosimetry of brachytherapy sources has been investigated. A high-activity 192Ir source was selected for this purpose. The dosimetric characteristics measured included the photon fluence anisotropy in air, transverse dose profiles in planes parallel to the plane containing the HDR source and isodose distributions. The 'in-air' anisotropy of the photon fluence relative to seed orientation was measured at 5 and 10 cm from the source centre and compared with TLD measurements. Transverse dose distributions in planes parallel to the plane containing the source long axis were measured in a water phantom and compared with calculations performed with a treatment planning system. Isodose distributions were also measured in several planes around the 192Ir source. Measurements on two sources indicate that the 'in-air' photon fluence anisotropy measured by the diamond detector and the TLDs is very similar. Dose profiles measured at several distances from the source are also found to be in good agreement with the calculated dose profiles and isodose distributions. Results of this feasibility study indicate that the diamond detector, with its excellent spatial resolution and nearly tissue equivalent and isotropic radiation response, is an appropriate detector for dose measurements around brachytherapy sources.


[Patient satisfaction after inpatient rehabilitation: different results at different follow-up times?].
Different Results at Different Times of Questioning? In 1994 a quality assurance programme for the German medical rehabilitation system was introduced by the national association of pension funds. One of its five parts focussed on patients' satisfaction and health effects. Both domains were to be assessed by postal questionnaires. The first section of the instrument enquired about patients' perceptions and evaluations of both rehabilitation structures and processes. It is well known that satisfaction surveys tend to underestimate the true level of criticism due to social desirability bias. This is especially problematic in the context of quality assurance programmes where criticism can be seen as one driving force of improvement. The magnitude of the bias depends on many factors. In this study we tested the influence of different time intervals between discharge from rehabilitation clinic and first postal contact. We conducted an experimentally varied satisfaction survey among four groups of rehabilitands. If necessary, the first postal questionnaire was followed by two reminders. One Bavarian pension fund for blue collar workers. 520 rehabilitands were recruited from various rehabilitation clinics specialized in muskuloskeletal disorders. About 70% suffered from nonspecific back pain. They were randomly allocated to one of the following time intervals between discharge and postal questionnaire: one, four, eight and twelve weeks. INSTRUMENTS AND TARGET VARIABLES: All patients received an identical questionnaire with 67 items and several subscales. We compared the extent of dissatisfaction between the four groups. The response rate (after two reminders) showed a linear decrease from 97% (postal questionnaire after one week) to 83% (12 weeks). The extent of dissatisfaction did not change systematically though there was a (statistically nonsignificant) tendency towards higher levels of criticism at week twelve. An experimental variation of time intervals between discharge from rehabilitation and first postal contact does not seem to influence the extent of reported dissatisfaction though it clearly influences the response rate: The later the sending out the lower the response rate. Taking into account additional administrative and organisational aspects of the programme we propose to send out satisfaction questionnaires between 8 and 10 weeks after rehabilitation.


Evaluation of core concepts of physiology in undergraduate physiology curricula: results from faculty and student surveys.
Unlike other STEM (Science, Technology, Engineering, Mathematics) disciplines, program guidelines for undergraduate physiology degree programs have yet to be firmly established. The purpose of this study was to examine the use of physiology core concepts within undergraduate physiology curricula to discern whether a common subset could be broadly recommended for inclusion in programmatic guidelines. A curricular survey tool was developed to evaluate the depth to which each core concept was included in physiology curricula. Seven self-selected physiology programs assessed core concept inclusion across all courses within the major (0 = not covered, 1 = minimally covered, and 2 = covered to a great extent). The top core concepts ranked by each institution varied considerably, but all were robustly represented across programs. The top five combined rankings for all institutions were as follows: 1) interdependence (1.47 ± 0.63); 2) structure/function (1.46 ± 0.72); 3) homeostasis (1.45 ± 0.71); 4) scientific reasoning (1.44 ± 0.70); and 5) cell-cell communication (1.38 ± 0.75). No common subset of specific core concepts was evident among the seven participating institutions. Next, results were compared with recent Physiology Majors Interest Group (P-MIG) faculty and student surveys that ascertained perceptions of the top five most important core concepts. Three core concepts (homeostasis, structure/function, cell-cell communication) appeared in the top five in more than one-half of survey questions included. We recommend that future programmatic guidelines focus on inclusion of the core concepts of physiology as general models to scaffold learning in physiology curricula, but the programmatic guidelines should allow flexibility in the core concepts emphasized based on program objectives.


Germination of Candida albicans induced by proline.
Blastospores of Candida albicans germinated in proline-biotin-buffer medium incubated at 37 C. Certain other amino acids in the glatamate, asparate, and pyruvate families also fostered germinaton but generally to a lesser extent than did proline. L-Cysteine, D-proline, and certain structural analogues of L-proline inhibited proline-stimualted germination. The concentration of phosphate and glucose was crucial to amino acid-stimulated germination of C. albicans. Clinical isolates and stock cultures varied in their response to the germ tube-inducing activity of proline or other amino acids. The proline-buffer medium cannot be used in a diagnostic test for production of germ tubes by isolates of yeasts.


Intussusception in children: current concepts in diagnosis and enema reduction.
Intussusception cannot be reliably ruled out with clinical examination and plain radiography. However, a contrast material enema study and ultrasonography (US) allow definitive diagnosis of intussusception. The components of an intussusception produce characteristic appearances on US scans. These appearances include the multiple concentric ring sign and crescent-in-doughnut sign on axial scans and the sandwich sign and hayfork sign on longitudinal scans. Indicators of ischemia and irreducibility are trapped fluid at US and absence of blood flow at Doppler imaging. The aim of enema therapy is to reduce the greatest number of intussusceptions without producing perforation. Barium, water-soluble contrast media, water, electrolyte solutions, or air may be used with radiographic or US guidance. The differences in reduction and perforation rates between the various types of enemas are probably due more to perforations that occurred before enema therapy and the pressure exerted within the colon than to the contrast material used. The pressure within the colon is more constant with hydrostatic reduction than with air reduction; this fact may explain the lower risk of perforation with hydrostatic reduction. Radiation exposure is lower with air enema therapy than with barium enema therapy and is absent in US-guided enema therapy.


GATA1 directly mediates interactions with closely spaced pseudopalindromic but not distantly spaced double GATA sites on DNA.
The transcription factor GATA1 helps regulate the expression of thousands of genes involved in blood development, by binding to single or double GATA sites on DNA. An important part of gene activation is chromatin looping, the bringing together of DNA elements that lie up to many thousands of basepairs apart in the genome. It was recently suggested, based on studies of the closely related protein GATA3, that GATA-mediated looping may involve interactions of each of two zinc fingers (ZF) with distantly spaced DNA elements. Here we present a structure of the GATA1 ZF region bound to pseudopalindromic double GATA site DNA, which is structurally equivalent to a recently-solved GATA3-DNA complex. However, extensive analysis of GATA1-DNA binding indicates that although the N-terminal ZF (NF) can modulate GATA1-DNA binding, under physiological conditions the NF binds DNA so poorly that it cannot play a direct role in DNA-looping. Rather, the ability of the NF to stabilize transcriptional complexes through protein-protein interactions, and thereby recruit looping factors such as Ldb1, provides a more compelling model for GATA-mediated looping.


Light and magnetic fields in a neonatal intensive care unit.
Effects of light and electromagnetic fields (EMFs) on pineal function could have implications for long-term risk of breast cancer, reproductive irregularities, or depression. Health-care workers in a neonatal intensive care unit (NICU) were interviewed to determine the tasks, work locations, and practices in their work environment as well as the care provided to the infants. After an initial visit, methods for measuring illuminance, luminance, and broadband resultant magnetic fields throughout the NICU were developed. Measurements were made of one nursery during a daytime (1:00 p.m.) and a night-time (12:30 a.m.) visit. Measurements relevant to both nurses and premature infants in the NICU were made. Some measurements could not be completed so as not to interfere with nurses' duties in the NICU. Illuminances measured during the daytime and nighttime averaged 184 and 34 lux (lx), respectively, much lower than those reported in other studies of illuminance in NICUs, with a maximum illuminance of 747 lx. Peak levels may be consistent with those thought to suppress melatonin. There was a high degree of variability in EMF levels, which exceeded 1,000 mG close to certain hospital equipment but averaged 1-2 mG at the nurses' workstation. Fields within incubators exceeded 10 mG.


Phenotypic characterization of DFNA24: prelingual progressive sensorineural hearing impairment.
This article describes the hearing impairment (HI) phenotype which segregates in a large multi-generation Swiss-German family with autosomal dominant nonsyndromic HI. The locus segregating within this pedigree is located on chromosome 4q35-qter and is designated as DFNA24. For this pedigree, audiometric data on 25 hearing-impaired family members are available. It was demonstrated that within this kindred the HI is sensorineural, bilateral, prelingual in onset, and progressive throughout life. Age-related typical audiograms depict steeply down-sloping curves, with moderate high-frequency HI at birth, then steady progression to moderate HI in the low frequencies, severe HI at mid-frequencies and profound HI at high frequencies by age 70. Annual threshold deterioration was approximately 0.5 dB/year at 1-2 kHz after correction for presbycusis.


Detection of Foodborne Pathogens and Mycotoxins in Eggs and Chicken Feeds from Farms to Retail Markets.
Contamination by foodborne pathogens and mycotoxins was examined in 475 eggs and 20 feed samples collected from three egg layer farms, three egg-processing units, and five retail markets in Korea. Microbial contamination with Salmonella species, Escherichia coli, and Arcobacter species was examined by bacterial culture and multiplex polymerase chain reaction (PCR). The contamination levels of aflatoxins, ochratoxins, and zearalenone in eggs and chicken feeds were simultaneously analyzed with high-performance liquid chromatography coupled with fluorescence detection after the post-derivatization. While E. coli was isolated from 9.1% of eggs, Salmonella species were not isolated. Arcobacter species were detected in 0.8% of eggs collected from egg layers by PCR only. While aflatoxins, ochratoxins, and zearalenone were found in 100%, 100%, and 85% of chicken feeds, their contamination levels were below the maximum acceptable levels (1.86, 2.24, and 147.53 μg/kg, respectively). However, no eggs were contaminated with aflatoxins, ochratoxins, or zearalenone. Therefore, the risk of contamination by mycotoxins and microbes in eggs and chicken feeds is considered negligible and unlikely to pose a threat to human health.


A Case of Statin-Associated Autoimmune Myopathy: Management and Treatment.
Elevated lipid panels are associated with an increased risk of cardiovascular disease. Management of heart disease with lipid lowering agents play a vital role in medicine. Statins are one group of medications that are widely utilized in the medical field to decrease the risk of atherosclerotic disease. Statins work by inhibiting the hepatic enzyme 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR). Although statins are one of the most effective drugs for secondary and primary prevention of heart disease, they are not without risks and side effects such as hepatotoxicity and myopathy. We present a case of a male patient who developed progressively worsening muscle weakness and elevated muscle enzyme markers upon initiation of a statin. His symptoms persisted despite a trial of an alternative statin and subsequent discontinuation of all statin medications. A multitude of possible etiologies were considered and ranged from infectious, autoimmune, cancerous, to congenital in nature. Environmental factors, such as exposure to medications or toxins, were also considered as one of the possible precipitating factors. The association between his statin consumption and muscle weakness were not easily apparent at first. He required further workup including physical examination, electromyography, panel of myositis antibodies, and muscle biopsy. After clinical suspicion and elevated antibodies to HMGCR beyond the normal limit, he was discovered to have statin-associated autoimmune myopathy. The patient improved with the treatment of immunosuppressive agent's prednisone and methotrexate.


Scaling PatientsLikeMe via a "Generalized Platform" for Members with Chronic Illness: Web-Based Survey Study of Benefits Arising.
Launched in 2006 for patients with amyotrophic lateral sclerosis, PatientsLikeMe is an online community offering patient-reported outcomes, symptom tracking, and social features. Every member of the site can see all the data reported by every other member, view aggregated reports, identify "patients like them," and learn about treatment options in order to live better with their condition. In previous studies, members reported benefits such as improved condition knowledge, increased medication adherence, and better management of side effects. However, the site evolved in 2011 from condition-specific "vertical" communities consisting only of people with the same disease to a "generalized platform," in which every patient could connect with every other patient regardless of condition and with generic, rather than condition-specific, data tools. Some, but not all, communities received further custom tracking tools. We aimed to understand (1) whether members of PatientsLikeMe using the generalized platform still reported similar benefits and (2) assess factors associated with benefits, such as community customization, site use, and patient activation. A cross-sectional retrospective custom survey was fielded to 377,625 members between 2016 and 2017 including the Patient Activation Measure (PAM). A benefit index was developed for comparability across conditions. The invitation was viewed by 26,048 members of whom 11,915 did not respond, 5091 opted out, 1591 provided partial data, and 17 were screened out. Complete responses were received from 7434 participants. Users perceived greatest benefit in understanding how their condition may affect them (4530/6770, 66.91% participants, excluding "does not apply" answers), understanding what might help them live better with their condition (4247/6750, 62.92%), which treatments were available (4143/6898, 60.06%), understanding treatment side effects (4182/6902, 60.59%), and important factors in making treatment decisions (3919/6813, 57.52%). The benefit index was 29% higher for the "most activated" patients (PAM level 4 vs PAM level 1; relative risk [RR]=1.29, P<.001), 21% higher for conditions with some community customization versus none (RR=1.21, P<.001), and 11% higher in those using the site most often versus least (RR=1.11, P<.001). Members of the generalized platform reported a range of benefits related to improved knowledge and understanding of their condition and treatment management. Condition-specific customization may improve their experience still further. Future studies will explore longitudinal changes to patient activation.


Tadalafil once daily and intralesional verapamil injection: A new therapeutic direction in Peyronie's disease.
The aim of this study was to evaluate the combination of intralesional verapamil injection (IVI) therapy with and tadalafil in men affected by Peyronie's disease (PD). In this study, 59 patients diagnosed with PD, were divided into three groups. Group A (GA) counted 23 patients treated with IVI; Group B (GB) treated 19 patients with tadalafil 5 mg once a day, and Group C (GC) treated 17 patients with IVI and tadalafil for 3 months. There were assessed at baseline and follow-up: Erectile function, presence and severity of painful erections, penile plaque size and penile curvature degree. After 3 months pain resolved completely in 57% cases of GA, 61% of GB and 76% of GC; the final mean curvature degree further decreased in all groups without statistically significant differences; mean plaque size remained stable in GA: 1.57 versus 1.59 at baseline (P = 0.364) and GB: 1.51 versus 1.52 at baseline (P = 0,265), while a further decrease was evident in GC: 1.46 versus 1.58 at baseline (P = 0.03). Mean International Index of Erectile Function-5 score further improved significantly in the group treated with verapamil plus tadalafil: 23.1 versus 14.4 of GA and 18.2 of GB (P ≤ 0.01). The association of IVI and tadalafil showed better pain control while reducing penile curvature and erectile function, improving the quality of life.


Abnormalities of cognitive functions in IDDM revealed by P300 event-related potential analysis. Comparison with short-latency evoked potentials and psychometric tests.
The possible influence of diabetes on the higher mnestic and cognitive functions has been investigated. The P300 wave latency, an endogenous electrophysiological event, was explored and compared with the multimodal short-latency evoked potential (EP) recordings (visual [VEP], brainstem auditory [BAEP], and median and tibial nerve somatosensory EPs [mSEP and tSEP, respectively]) and psychometric test measures in 16 insulin-dependent diabetic (IDDM) patients, in 16 age- and (IDDM) sex-matched nondiabetic subjects, and in a large normal reference population. The age of subjects, the duration of IDDM, and the metabolic control of patients were taken into account. P300 values were significantly increased in IDDM versus matched control subjects (P less than 0.001), and 3 patients showed values above the reference value range. Abnormal VEP recordings were present in 1 of 16 patients, BAEP in 3 of 16, mSEP in 7 of 16, and tSEP in 6 of 16. Digit-span backward test results were significantly (P less than 0.02) modified in the diabetic cohort. There was no tendency for anomalies of P300, short-latency EPs, and psychometric test values to be contemporarily present, except in 1 patient. Electrophysiological or psychometric abnormalities were not clearly correlated with the duration of IDDM or the degree of short-term metabolic control. These findings give evidence that 1) higher cognitive functions may be affected in diabetes as documented by P300 analysis and short-term memory tests, 2) endogenous electrophysiological analysis highlights neuropsychological changes not detectable by psychometric tests, 3) an alteration of evoked potentials was present in half of the IDDM subjects studied, and 4) anomalies of the CNS are patchily distributed in diabetes.


Acute effects of warm-up stretch protocols on balance, vertical jump height, and range of motion in dancers.
The aim of this study was to examine the acute effects of static stretching (SS), dynamic stretching (DS), and a combined (static and dynamic) stretch protocol on vertical jump (VJ) height, balance, and range of motion (ROM) in dancers. A no-stretch (NS) intervention acted as the control condition. It was hypothesized that the DS and combination stretch protocols would have more positive effects on performance indicators than SS and NS, and SS would have negative effects as compared to the NS condition. Ten trained female dancers (27 ± 5 years of age) were tested on four occasions. Each session began with initial measurements of hamstring ROM on the dominant leg. The participants subsequently carried out a cardiovascular (CV) warm-up, which was followed by one of the four randomly selected stretch conditions. Immediately after the stretch intervention the participants were tested on VJ performance, hamstring ROM, and balance. The data showed that DS (p < 0.05) and the combination stretch (p < .05) produced significantly greater VJ height scores as compared to SS, and the combination stretch demonstrated significantly enhanced balance performance as compared to SS (p < 0.05). With regard to ROM, a one-way ANOVA indicated that SS and the combination stretch displayed significantly greater changes in ROM than DS (p < 0.05). From comparison of the stretch protocols used in the current study, it can be concluded that SS does not appear to be detrimental to a dancer's performance, and DS has some benefits but not in all three key area's tested, namely lower body power (VJ height), balance, and range of motion. However, combination stretching showed significantly enhanced balance and vertical jump height scores and significantly improved pre-stretch and post-stretch ROM values. It is therefore suggested that a combined warm-up protocol consisting of SS and DS should be promoted as an effective warm-up for dancers.


Does maltreatment in childhood affect sexual orientation in adulthood?
Epidemiological studies find a positive association between physical and sexual abuse, neglect, and witnessing violence in childhood and same-sex sexuality in adulthood, but studies directly assessing the association between these diverse types of maltreatment and sexuality cannot disentangle the causal direction because the sequencing of maltreatment and emerging sexuality is difficult to ascertain. Nascent same-sex orientation may increase risk of maltreatment; alternatively, maltreatment may shape sexual orientation. Our study used instrumental variable models based on family characteristics that predict maltreatment but are not plausibly influenced by sexual orientation (e.g., having a stepparent) as natural experiments to investigate whether maltreatment might increase the likelihood of same-sex sexuality in a nationally representative sample (n = 34,653). In instrumental variable models, history of sexual abuse predicted increased prevalence of same-sex attraction by 2.0 percentage points [95 % confidence interval (CI) = 1.4-2.5], any same-sex partners by 1.4 percentage points (95 % CI = 1.0-1.9), and same-sex identity by 0.7 percentage points (95 % CI = 0.4-0.9). Effects of sexual abuse on men's sexual orientation were substantially larger than on women's. Effects of non-sexual maltreatment were significant only for men and women's sexual identity and women's same-sex partners. While point estimates suggest much of the association between maltreatment and sexual orientation may be due to the effects of maltreatment on sexual orientation, confidence intervals were wide. Our results suggest that causal relationships driving the association between sexual orientation and childhood abuse may be bidirectional, may differ by type of abuse, and may differ by sex. Better understanding of this potentially complex causal structure is critical to developing targeted strategies to reduce sexual orientation disparities in exposure to abuse.


Composite IS1 elements encoding hydroxamate-mediated iron uptake in FIme plasmids from epidemic Salmonella spp.
Eleven FIme plasmids representative of those identified in epidemic strains of Salmonella wien and Salmonella typhimurium isolated in North Africa, Europe, and the Middle East have been examined for the presence of determinants of toxigenicity, adherence, and iron-sequestering mechanisms. Chemical and genetic data indicated that all plasmids code for a hydroxamate-mediated iron assimilation system. Detailed analysis of derivative plasmids and cloned fragments of FIme plasmid pZM61 demonstrated that the general genetic and structural organization of the DNA region containing the genes for hydroxamate biosynthesis and cloacin DF13 receptor was virtually identical to that described for the aerobactin-mediated iron uptake system of pColV-K30. This DNA region is part of a composite element that is 16.7 kilobases long and carries its IS1 modules as inverted repeats. A very similar element is present in either orientation in all nine FIme plasmids analyzed.


Improving functional skills and physical fitness in children with Rett syndrome.
To investigate the feasibility of a physical exercise programme with treadmill for persons with Rett syndrome (RS) in order to promote fitness and health. A daily training programme on a treadmill was designed for four females with RS over a period of 2 months with tests performed in three intervals, at time 1, 2 and 3, 2 months apart with intervention taking place between tests 2 and 3. Participants were four girls with RS aged 8.5-11 years (mean: 10 years) attending the educational facility Beit Issie Shapiro, Raanana, Israel, all with independent mobility and with typical characteristics of RS stage III. The training took place at the educational facility, on a 1400 model treadmill (Trimline, capable of very low speeds < 0.5 k/h), with very long side rails. Special low side rails were adapted to the treadmill in order to fit the height of the children and velcro straps were added to assist in safely placing the hands. Pulse was monitored constantly during exercise by an A3 polar pulse belt. Pulse measurements at rest during training were considered as evaluators of aerobic physical condition. Functional measurement was based on a scale specially established for the present study. The scale was a 31-item motor-functioning tool that measures the ability of participants to knee walk and knee stand, to get up to a standing position, duration of walking different paths, and to go up and down stairs and slopes. The study showed that physical fitness of the children at the end of the training programme had improved considerably (P < 0.05). Tests showed that general functional abilities had improved considerably (P < 0.0001). Although all items of the functional ability measure showed impressive positive change, some of the 31 items on it showed statistically significant improvement (knee walking, going up and down stairs and speed of walking for 25 m. Pearson correlation showed high linkage (r = -0.76) between functional improvement and change in physical fitness. Physical fitness programme executed on a daily basis is capable of improving functional ability of children with RS. Nonprofessional personnel can execute such a programme under supervision of a qualified physical therapist.


Using Disposable Membrane Cell Collector to Enrich Lung Adenocarcinoma Cells in Bloody Pleural Effusion for Anaplastic Lymphoma Kinase Fusion Gene Detection.
For anaplastic lymphoma kinase (ALK) gene detection, the centrifugal sedimentation method (CSM) and cell block method (CBM) are commonly used to process samples of bloody pleural effusions (BPEs). However, in practice, the impurity content in the processed samples often affects the results and even leads to the detection failure. The purpose of this study was to establish a cell enrichment method (CEM) by using a disposable membrane cell collector to remove blood and inflammatory cells and enrich lung adenocarcinoma cells in BPE for more efficient RNA extraction and ALK gene detection. CEM proposed in this study and the traditional CSM and CBM were used to treat BPE samples collected from 37 lung adenocarcinoma patients. A DeNovix DS-11 ultraviolet spectrophotometer was used to measure the concentration and purity of extracted RNA. Amplification refractory mutation systems (ARMS) and ABI 7500 fluorescence qPCR were used to detect ALK gene. Through statistical analysis, the CEM was compared with the CSM and CBM in RNA concentration, purity, and ALK gene detection results. The concentration of RNA extracted by using the CEM was significantly higher than that extracted by using the CBM and CSM (p < 0.001). The purity of RNA extracted by using the CEM was significantly higher than that by the other 2 methods (p = 0.011, p = 0.005). ALK gene testing with PCR was successful in all the samples using the CEM, but 2 cases by the CSM and 1 case by the CBM failed. Using the disposable membrane cell collector to process BPE of lung adenocarcinoma patients for RNA extraction and ALK gene detection is more effective and successful compared with the traditional methods, and it is suggested to be further applied and popularized in clinical practice.


Successful Use of Cangrelor and Heparin for Cardiopulmonary Bypass in a Patient With Heparin-Induced Thrombocytopenia and End-Stage Renal Disease: A Case Report.
Heparin is the only well-established anticoagulant medication for cardiopulmonary bypass making selecting an alternative anticoagulant challenging in patients with heparin-induced thrombocytopenia. Other anticoagulant medications can cause significant postoperative bleeding, especially in patients with end-stage renal disease. We present a case of a 63-year-old woman requiring aortic valve replacement with a history of heparin-induced thrombocytopenia and end-stage renal disease. Cangrelor and heparin were successfully used during cardiopulmonary bypass, offering an option for anticoagulation management for a uniquely challenging patient population.


Translational Bioinformatics to Enable Precision Medicine for All: Elevating Equity across Molecular, Clinical, and Digital Realms.
Over the past few years, challenges from the pandemic have led to an explosion of data sharing and algorithmic development efforts in the areas of molecular measurements, clinical data, and digital health. We aim to characterize and describe recent advanced computational approaches in translational bioinformatics across these domains in the context of issues or progress related to equity and inclusion. We conducted a literature assessment of the trends and approaches in translational bioinformatics in the past few years. We present a review of recent computational approaches across molecular, clinical, and digital realms. We discuss applications of phenotyping, disease subtype characterization, predictive modeling, biomarker discovery, and treatment selection. We consider these methods and applications through the lens of equity and inclusion in biomedicine. Equity and inclusion should be incorporated at every step of translational bioinformatics projects, including project design, data collection, model creation, and clinical implementation. These considerations, coupled with the exciting breakthroughs in big data and machine learning, are pivotal to reach the goals of precision medicine for all.


No excess mortality in patients aged 50 years and older who received treatment for ductal carcinoma in situ of the breast.
Background. The incidence of ductal carcinoma in situ (DCIS) has increased at a fast rate.The aim of this study was to assess the incidence and treatment in the Netherlands and estimate the excess mortality risk of DCIS. Methods. From the Netherlands Cancer Registry, adult female patients (diagnosed 1997-2005) with DCIS were selected. Treatment was described according to age. Relative mortality at 10 years of follow-up was calculated by dividing observed mortality over expected mortality. Expected mortality was calculated using the matched Dutch general population. Results. Overall, 8421 patients were included in this study. For patients aged 50-64, and 65-74 an increase in breast-conserving surgery was observed over time (P < 0.001). For patients over 75 years of age, 8.0% did not undergo surgery; this percentage remained stable over time (P = 0.07). Overall, treated patients aged >50 years experienced no excess mortality regardless of treatment (relative mortality 1.0). Conclusion. The present population-based study of almost 8500 patients showed no excess mortality in surgically treated women over 50 years with DCIS.


Cigarette smoking among U.S. adults, 1985-1990, and smoking among selected occupational groups, 1990.
Cigarette smoking rates among U.S. adults continue declining, and in 1990 dropped to an all-time low of an estimated 28 percent for men and 23 percent for women. Analysis of data from the 1990 and 1985 Health Promotion and Disease Prevention supplemental questionnaires to the National Health Interview Survey conducted by the National Center for Health Statistics (NCHS), indicate decreases in smoking rates in the majority of selected demographic categories. Between survey years, the only groups in which the rates rose were men aged 18-24, women aged 65 and over, persons with less than 12 years of schooling and adults of Hispanic origin. Increased smoking cessation efforts should be tailored to and directed at these "at risk" groups. By occupational category, close to 40 percent of men employed as handlers/laborers or transportation/material movers were current smokers versus 17 and 21 percent, respectively, of professionals and executives. Similar to the men, the lowest current smoking rates were among women professionals, technical persons and executives. For both sexes, income was generally inversely related to current smoking status.


Platelet count/spleen diameter ratio to predict the presence of esophageal varices in patients with cirrhosis: a systematic review.
Esophageal variceal bleeding remains the leading cause of acute mortality in patients with cirrhosis. Platelet count to spleen diameter (PC/SD) ratio less than 909 is one of several parameters proposed for the noninvasive prediction of esophageal varices. The aim of this study is to systematically review the evidence on the diagnostic accuracy of the 909 ratio. We identified relevant studies from a MEDLINE search and performed a meta-analysis to estimate the pooled sensitivity, specificity, and positive and negative likelihood ratios (LRs) using Meta-Disc software. Eight studies met the inclusion criteria and included a total of 1275 patients. Meta-analysis yielded a pooled sensitivity of 89% [95% confidence interval (CI) 87-92%; I2 statistic 92.9%] and a pooled specificity of 74% (95% CI 70-78%; I2 statistic 94.5%). The pooled positive LR was 3.5 (95% CI 1.92-6.25; I2 statistic 94.0%) and the pooled negative LR was 0.12 (95% CI 0.05-0.32; I2 statistic 90.8%). The quality of the evidence as assessed by the GRADE methodology was low. In its present form, the test characteristics of PC/SD ratio of 909 may not be adequate to completely replace esophagogastroduodenoscopy as a noninvasive screening tool for esophageal varices, given the low grade of evidence. However, it may be potentially useful as part of a prediction rule incorporating other clinical characteristics or varying PC/SD cutoffs. When compared with other noninvasive predictor tools, the PC/SD ratio is elegant, simple, and inexpensive. With some minor modifications, it may become a helpful tool to limit the number of endoscopies in primary prophylaxis to be performed in patients with portal hypertension.


Synthesis and biological activity of simplified belactosin C analogues.
Successful biochemical studies of the natural products belactosin A and C and their acylated congeners have shown a β-lactonecarboxamide moiety to be a possible core structure of powerful proteasome inhibitors. As a part of further investigations, variously decorated simplified β-lactonecarboxamides have been synthesized in order to understand structure-biological activity relations in detail, to find ways of improving their biological activity and stability and to reduce the complexity of their preparation. Biological tests showed that the best compounds possess a high potential against phytopathogenic fungi in the greenhouse.


Growth and some physiological attributes of pea (Pisum sativum L.) as affected by salinity.
The effects of salt stress were studied on growth and physiology of pea (Pisum sativum L. cv. Green Arrow) in a pot study. Pea plants were treated with NaCl at 0, 10, 30, 50 and 70 mM in Hoagland solution. Plants were harvested after 21 days for measurements of physiological parameters. The highest NAR and RGR were found in 10 mM NaCl. However, in 70 mM NaCl, RGR and RLGR were significantly decreased in respect of other concentrations of NaCl. In 50 and 70 mM NaCl, chlorophylls contents and photosynthetic rate, were significantly decreased and CO2 compensation concentration and respiration rate increased in comparison with control. In 10 and 30 mM NaCl gas exchanges and chlorophyll contents were not significantly decrease in respect of control. Results indicated that Pisum sativum L. cv. Green Arrow can tolerate to 70 mM NaCl, also growth of plants in 10 and 30 mM NaCl was better than that of those in 0 mM NaCl.


The role of explainability in creating trustworthy artificial intelligence for health care: A comprehensive survey of the terminology, design choices, and evaluation strategies.
Artificial intelligence (AI) has huge potential to improve the health and well-being of people, but adoption in clinical practice is still limited. Lack of transparency is identified as one of the main barriers to implementation, as clinicians should be confident the AI system can be trusted. Explainable AI has the potential to overcome this issue and can be a step towards trustworthy AI. In this paper we review the recent literature to provide guidance to researchers and practitioners on the design of explainable AI systems for the health-care domain and contribute to formalization of the field of explainable AI. We argue the reason to demand explainability determines what should be explained as this determines the relative importance of the properties of explainability (i.e. interpretability and fidelity). Based on this, we propose a framework to guide the choice between classes of explainable AI methods (explainable modelling versus post-hoc explanation; model-based, attribution-based, or example-based explanations; global and local explanations). Furthermore, we find that quantitative evaluation metrics, which are important for objective standardized evaluation, are still lacking for some properties (e.g. clarity) and types of explanations (e.g. example-based methods). We conclude that explainable modelling can contribute to trustworthy AI, but the benefits of explainability still need to be proven in practice and complementary measures might be needed to create trustworthy AI in health care (e.g. reporting data quality, performing extensive (external) validation, and regulation).


Application of wireless energy transmission technology into central venous ports with light-emitting diodes.
Implantable central venous (CV) ports are widely used for chemotherapy and parenteral nutrition. Generally, CV ports are used safely; however, some patients suffer from drug leakage around the port septum due to mispuncture. Therefore, we developed a CV port that is visible under the skin. We created a prototype of a CV port using a 3D printer. Three red light-emitting diodes (LEDs) were attached around the septum that made the puncture site visible by applying wireless energy transmission technology using electromagnetic resonance. The CV port was implanted under the skin of pork rose meat. The thickness of the skin of pork loin was measured. Fifteen medical doctors participated in the study to visually confirm the lighted CV port. The visibility of the center of the septum with and without lights was scored 0 as non-diagnostic; 1, slightly visible; 2, well visible; and 3, obviously visible. The visibility with or without lights was assessed. The relationship between the years of experience and the visibility score was assessed. The Wilcoxon test was used for statistical analysis. LEDs were easily transmitted through the skin of pork rose meat. The median visibility scores with or without lights were 2 (range, 1-3) and 3 (range, 1-3), respectively (p = 0.005). No significant relationship was found between experience and visibility score (p = 0.289). CV ports with LEDs can be easily recognized compared with those without LEDs. This technique may contribute to medical safety by improving its visibility to avoid mispuncture.


Genomic stability of adipogenic human adenovirus 36.
Human adenovirus Ad36 increases adiposity in several animal models, including rodents and non-human primates. Importantly, Ad36 is associated with human obesity, which has prompted research to understand its epidemiology and to develop a vaccine to prevent a subgroup of obesity. For this purpose, understanding the genomic stability of Ad36 in vivo and in vitro infections is critical. Here, we examined whether in vitro cell passaging over a 14-year period introduced any genetic variation in Ad36. We sequenced the whole genome of Ad36-which was plaque purified in 1998 from the original strain obtained from American Type Culture Collection, and passaged approximately 12 times over the past 14 years (Ad36-2012). This DNA sequence was compared with a previously published sequence of Ad36 likely obtained from the same source (Ad36-1988). Compared with Ad36-1988, only two nucleotides were altered in Ad36-2012: a T insertion at nucleotide 1862, which may induce early termination of the E1B viral protein, and a T➝C transition at nucleotide 26 136. Virus with the T insertion (designated Ad36-2012-T6) was mixed with wild-type virus lacking the T insertion (designated Ad36-2012-T5) in the viral stock. The transition at nucleotide 26 136 does not change the encoded amino acid (aspartic acid) in the pVIII viral protein. The rate of genetic variation in Ad36 is ∼2.37 × 10(-6) mutations/nucleotide/passage. Of particular importance, there were no mutations in the E4orf1 gene, the critical gene for producing obesity. This very-low-variation rate should reduce concerns about genetic variability when developing Ad36 vaccines or developing assays for detecting Ad36 infection in populations.


Dispersion engineering of spoof plasmonic metamaterials via interdigital capacitance structures.
This work presents an approach to realize the dispersion engineering of spoof plasmonic metamaterials with controllable cutoff frequencies. Interdigital capacitance structures are applied to construct the unit cells. Dispersion properties are firstly analyzed to investigate the effects of interdigital capacitance, and the influence of the geometrical parameters of the proposed unit cell on the cutoff frequencies is studied. Then, a spoof surface plasmon polariton (SSPP) transmission line (TL) is developed based on the proposed unit cell together with a smooth transition. The matching principles of the transition are explained by the dispersion curves and the normalized impedance of the corresponding matching unit cells. Finally, the transmission characteristics of the TL are simulated and measured to validate the feasibility of the proposed strategy. Both the lower and upper cutoff frequencies can be tuned jointly by the extra degrees of freedom provided by the interdigital capacitance structures. In comparison with designs based on a substrate-integrated waveguide (SIW), the proposed strategy can reduce the transversal dimension by a factor of two under the same conditions. This work can greatly accelerate the development of versatile microwave integrated circuits and systems based on spoof plasmonic metamaterials.


A decomposition of income-related health inequality applied to EQ-5D.
Income-related inequality in health and its relationship to sociodemographic characteristics have received considerable attention in the health economic literature. Recently a method was suggested for decomposing income-related health inequality to contributions from individual characteristics via additive dimensions, and this was applied to a Finnish case based on 15D health scores, where health is considered to be a sum of 15 individual health dimensions. The present study adds to this literature in several ways. First, we apply the decomposition approach to a Danish case which can be benchmarked to the Finnish. Second, we show how to apply the method to EQ-5D scores, which deviate from 15D scores by expressing health as individual depreciations of an equal endowment of perfect health. Third, we add life-style factors to the determinants of income-related health inequality. The empirical part of the study reveals discrepancies which can be attributed to differences between Finland and Denmark and to differences between the construction of 15D and EQ-5D scores. Finally, evidence of impact of life-style factors on income-related health inequality is found.


Optimal conditions and specificity of interaction of a distinct class of nonhistone chromosomal proteins with DNA.
A subclass of nonhistone chromatin proteins with high DNA affinity has been isolated from rat liver. The interaction of the isolated proteins with DNA in vitro was characterized utilizing a nitrocellulose filter binding technique. The temperature, time, concentration, ionic strength, and pH dependence were characterized. Optimal interaction was observed at 0.19 M naCl, pH 7.5 with a protein to DNA ratio of 13 (w/w). Equilibrium and kinetic competition experiments indicated that these proteins interact optimally with A-T rich and single-stranded DNA. The data also suggest that these proteins might affect the helixcoil transiton of DNA.


African swine fever and outdoor farming of pigs.
This opinion describes outdoor farming of pigs in the EU, assesses the risk of African swine fewer (ASF) introduction and spread associated with outdoor pig farms and proposes biosecurity and control measures for outdoor pig farms in ASF-affected areas of the EU. Evidence was collected from Member States (MSs) veterinary authorities, farmers' associations, literature and legislative documents. An Expert knowledge elicitation (EKE) was carried out to group outdoor pig farms according to their risk of introduction and spread of ASF, to rank biosecurity measures regarding their effectiveness with regard to ASF and propose improvements of biosecurity for outdoor pig farming and accompanying control measures. Outdoor pig farming is common and various farm types are present throughout the EU. As there is no legislation at European level for categorising outdoor pig farms in the EU, information is limited, not harmonised and needs to be interpreted with care. The baseline risk of outdoor pig farms for ASFV introduction and its spread is high but with considerable uncertainty. The Panel is 66-90% certain that, if single solid or double fences were fully and properly implemented on all outdoor pig farms in areas of the EU where ASF is present in wild boar and in domestic pigs in indoor farms and outdoor farms (worst case scenario not considering different restriction zones or particular situations), without requiring any other outdoor-specific biosecurity measures or control measures, this would reduce the number of new ASF outbreaks occurring in these farms within a year by more than 50% compared to the baseline risk. The Panel concludes that the regular implementation of independent and objective on-farm biosecurity assessments using comprehensive standard protocols and approving outdoor pig farms on the basis of their biosecurity risk in an official system managed by competent authorities will further reduce the risk of ASF introduction and spread related to outdoor pig farms.


Gender sameness and difference in recovery from heroin dependence: a qualitative exploration.
In recent years, 'recovery' has become a central, yet controversial, concept within the international drug and alcohol field. This paper explores gender sameness and difference in recovery from heroin dependence with reference to gender theory, the existing literature on women and drugs, and the concept of recovery capital. Data were generated from 77 qualitative interviews conducted with 40 current or ex-heroin users (21 men and 19 women). Coded data were analysed using framework and key themes were mapped onto the four components of recovery capital: social capital, physical capital, human capital, and cultural capital. Differences between the views and experiences of male and female participants were then explored. Participants had limited social, physical and human capital but greater cultural resources. Although women reported more physical and sexual abuse than the men, they had better family and social relationships and more access to informal support, including material assistance and housing. Women also seemed to be better at managing money and more concerned with their physical appearance. Despite the salience of gender, individuals had diverse recovery resources that reflected a complex mix of intrapersonal, interpersonal and structural factors. Findings are consistent with increasing feminist interest in intersectionality and contribute to a more gender-sensitive understanding of recovery. Gender was an important structure in shaping our participants' experiences, but there was no evidence of an 'essential' female recovery experience and women did not necessarily have less recovery resources than men. Whilst useful, the concept of recovery capital has a number of definitional and conceptual limitations that indicate a need for more empirical research to improve its utility in policy and practice.


Evaluating program integration and the rise in collaboration: case study of a palliative care network.
There is increasing global interest in using regional palliative care networks (PCNs) to integrate care and create systems that are more cost-effective and responsive. We examined a PCN that used a community development approach to build capacity for palliative care in each distinct community in a region of southern Ontario, Canada, with the goal of achieving a competent integrated system. Using a case study methodology, we examined a PCN at the structural level through a document review, a survey of 20 organizational administrators, and an interview with the network director. The PCN identified 14 distinct communities at different stages of development within the region. Despite the lack of some key features that would facilitate efficient palliative care delivery across these communities, administrators largely viewed the network partnership as beneficial and collaborative. The PCN has attempted to recognize specific needs in each local area. Change is gradual but participatory. There remain structural issues that may negatively affect the functioning of the PCN.


Reproducibility of peak power output during a 10-s cycling maximal effort using different sampling rates.
The study was aimed to investigate the reproducibility of performance parameters obtained from 10-s maximal cycling effort against different braking forces in young adult athletes. The sample (n = 48) included male athletes aged 18.9-29.9 years (175.5 ± 6.9 cm, 76.2 ± 10.1 kg). The exercise protocol was performed in a cycle-ergometer against a random braking force (4% to 11% of body mass). Intra-individual variation was examined from repeated tests within one week. Descriptive statistics were computed and differences between sessions were tested using paired t-test. The coefficient of correlation between repeated measures, technical error of measurement (TEM), coefficient of variation and ICC were calculated. Agreement between trials was examined using the Bland-Altman procedure. Mean values of peak power were relatively stable when obtained from sampling rates of 50 Hz and ranged between 1068 watt and 1082 watt (t(47) = 1.149, p = 0.256, ES-r = 0.165) or while corresponding to a sampling rate of 1 Hz (t(47) = 0.742, p = 0.462, ES-r = 0.107). Correlations between repeated measures were high (+0.907, 95% CI: +0.839 to +0.947) and TEM about 59.3 watt (%CV = 5.52%; ICC = 0.951, 95% CI: 0.912 to 0.972). The present study suggests that reproducibility of peak power in male adult athletes tended to be acceptable and within individual error appeared unrelated to braking force.


Mixture Design Applied to the Development of Chickpea-Based Gluten-Free Bread with Attractive Technological, Sensory, and Nutritional Quality.
The aim of the study was utilized chickpea to create appealing, nutritious, and palatable gluten-free bread (GFB). The performance of chickpea flour (CF) in single and composite GFB formulations was studied with a mixture design and response surface methodology. Six simplex-centroid designs for 3 ingredients were used to identify the ideal proportions of CF in various blends with cassava starch (CS), maize starch (MS), potato starch (PS), and rice flour (RF) achieving the best physical properties. For each design, 3 single, 3 binary, and 3 ternary formulations were prepared. The results showed that CF alone is suitable for bread production, resulting in GFB with higher volume and crumb firmness and lower crumb moisture than single formulations of other raw materials. However, the interactions between CF and PS or CS enhanced the loaf volume and decreased the crumb firmness values. The GFB prepared with only CF was accepted (overall acceptability score of 7.1- on a 10-cm scale). Nevertheless, the composite formulations prepared with CF75:PS25 or CF75:CS25 (flour basis) received overall acceptability scores of 8.2, like those of their white GFB, prepared with RF50:PS50 blend (flour basis), and wheat bread counterparts, used as positive controls. Compared to white GFB, both composite formulations presented nearly a twofold increase in ash and protein contents and a threefold increase in total fiber content. These results show that blends of CF75:PS25 or CF75:CS25 can be used to develop GFB with a good physical and sensory properties, as well as an enhanced nutritional composition. Gluten-free bread (GFB) made with 75% chickpea flour (CF) blend with 25% potato or cassava starch showed improved total minerals, protein and dietary fiber content and bread quality characteristics. Therefore, CF is a valuable ingredient for food technologists in manufacturing better-tasting and healthy GFB, which is important for consumers with gluten-related disorders since GFB often lack nutrition content, appearance, texture, and mouthfeel.


Class III antiarrhythmic drug dronedarone inhibits cardiac inwardly rectifying Kir2.1 channels through binding at residue E224.
Dronedarone is a novel class III antiarrhythmic drug that is widely used in atrial fibrillation. It has been shown in native cardiomyocytes that dronedarone inhibits cardiac inwardly rectifying current IK1 at high concentrations, which may contribute both its antifibrillatory efficacy and its potential proarrhythmic side effects. However, the underlying mechanism has not been studied in further detail to date. In the mammalian heart, heterotetrameric assembly of Kir2.x channels is the molecular basis of IK1 current. Therefore, we studied the effects of dronedarone on wild-type and mutant Kir2.x channels in the Xenopus oocyte expression system. Dronedarone inhibited Kir2.1 currents but had no effect on Kir2.2 or Kir2.3 currents. Onset of block was slow but completely reversible upon washout. Blockade of Kir2.1 channels did not exhibit strong voltage dependence or frequency dependence. In a screening with different Kir2.1 mutants lacking specific binding sites within the cytoplasmic pore region, we found that residue E224 is essential for binding of dronedarone to Kir2.1 channels. In conclusion, direct block of Kir2.1 channel subunits by dronedarone through binding at E224 may underlie its inhibitory effects on cardiac IK1 current.


[Treatment of chronic critical ischemia by neuroischemic form of the diabetic foot syndrome].
Treatment results of 203 patients with critical ischemia by neuroischemic form of the diabetic foot sindrome were analyzed. 45 patients had open, endovascular or hybrid vascular reconstructions. The method was decised basing on the results of angiographic studies. The support function was saved in 34 (75,6%) cases of 45 operated patients. Revascularization proved to be an effective and reasonable method of surgical intervention by critical ischemia caused by the neuroischemic form of the diabetic foot syndrome.


Comparison of knee SPECT and MRI in evaluating meniscus injuries in soldiers.
Medical evaluation of a suspected meniscus injury begins with a history-taking and physical examination. Suspected meniscus injuries not responding to treatment are usually sent for imaging to confirm the diagnosis before arthroscopy. Tc-MDP bone single photon emission computed tomography (SPECT) scan has been suggested as an alternative to magnetic resonance imaging (MRI) in evaluating suspected knee meniscus tears. To examine the accuracy of knee SPECT as a tool to identify meniscus tears versus that of MRI as compared to the gold standard of arthroscopy. The Israel Defense Forces database for 2005 through 2009 was searched using the key words: knee MRI, knee SPECT and knee arthroscopy. We identified 330 subjects who had undergone both a single knee SPECT and a single knee MRI prior to knee surgery. The medical files of 193 of the 330 subjects were randomly selected for review. A comparison was made between the preoperative SPECT and MRI studies and the arthroscopic finding. The sensitivity, specificity and accuracy were calculated. The subjects' age was 21.3 ± 3.9. The agreement between SPECT and arthroscopy was 0.14 forthe medial meniscus and 0.29 for the lateral meniscus. The agreement between MRI and arthroscopy was 0.59 for the medial meniscus and 0.69 for the lateral meniscus. SPECT scan was found to be 61% sensitive, 54% specific and 58% accurate in detecting common knee pathology, whereas MRI was found to be 95% sensitive, 67% specific and 85% accurate. Knee SPECT has a lower sensitivity, specificity and accuracy than MRI in evaluating meniscal injuries and its use can result in increased unnecessary surgery.


Circumcision.
Circumcision is one of the oldest and the most controversial surgical procedures performed worldwide and is almost universal among Muslim and Jewish men. Most medical institutions in various countries agree that although there may be health benefits, there is no medical justification for routine circumcision in neonates or children. It should be performed only for established medical reasons and should not be universally recommended. There are modern techniques that provide safer, simpler, quicker, and cheaper alternatives to the traditional means of circumcision with good functional and cosmetic results. Female genital mutilation (FGM) includes procedure that alters or injures female genital organs for nonmedical reasons. Various degrees of FGM are prevalent, the most mutilating one being infibulation. There are numerous gynecologic and obstetrical complications with infibulation. FGM also plays a significant role in facilitating the transmission of HIV infection through numerous mechanisms. Health care providers have an important role to play in the eradication of this practice. Increased professional and public awareness about such a practice is required.


EGR-1 is regulated by N-methyl-D-aspartate-receptor stimulation and associated with patient survival in human high grade astrocytomas.
Early growth response-1 (EGR-1) is considered a central regulator in tumor cell proliferation, migration and angiogenesis and a promising candidate for gene therapy in human astrocytomas. However, conflicting data have been reported suggesting that both tumor promoting and anti-tumor activity of EGR-1 and its regulation, expression and prognostic significance still remain enigmatic. Our study explored EGR-1 expression and regulation in astrocytomas and its association with patient survival. As we detected two EGR-1 mRNA variants, one containing a N-methyl-D-aspartate-receptor (NMDA-R) responsive cytoplasmic polyadenylation element (CPE), further experiments were performed to determine the functional role of this pathway. After NMDA stimulation of SV-FHAS and neoplastic astrocytes, real-time polymerase chain reaction showed an increase of the CPE, containing EGR-1 splice variant only in astrocytoma cells. The surface expression and functionality of NMDA-R were demonstrated by flow cytometric analysis and measurement of increased intracellular Ca(2+). EGR-1 was mainly restricted to tumor cells expressing NMDA-R and significantly up-regulated in astrocytic tumors compared with normal brain. Further, EGR-1 expression was significantly (P < 0.007) associated with enhanced patient survival and was an independent prognostic factor in multivariate analysis in high grade astrocytomas. The NMDA-R-mediated EGR-1 expression, therefore, seems to be a promising target for novel clinical approaches to astrocytoma treatment.


Liver Expression of a MiniATP7B Gene Results in Long-Term Restoration of Copper Homeostasis in a Wilson Disease Model in Mice.
Gene therapy with an adeno-associated vector (AAV) serotype 8 encoding the human ATPase copper-transporting beta polypeptide (ATP7B) complementary DNA (cDNA; AAV8-ATP7B) is able to provide long-term copper metabolism correction in 6-week-old male Wilson disease (WD) mice. However, the size of the genome (5.2 kilobases [kb]) surpasses the optimal packaging capacity of the vector, which resulted in low-yield production; in addition, further analyses in WD female mice and in animals with a more advanced disease revealed reduced therapeutic efficacy, as compared to younger males. To improve efficacy of the treatment, an optimized shorter AAV vector was generated, in which four out of six metal-binding domains (MBDs) were deleted from the ATP7B coding sequence, giving rise to the miniATP7B protein (Δ57-486-ATP7B). In contrast to AAV8-ATP7B, AAV8-miniATP7B could be produced at high titers and was able to restore copper homeostasis in 6- and 12-week-old male and female WD mice. In addition, a recently developed synthetic AAV vector, AAVAnc80, carrying the miniATP7B gene was similarly effective at preventing liver damage, restoring copper homeostasis, and improving survival 1 year after treatment. Transduction of approximately 20% of hepatocytes was sufficient to normalize copper homeostasis, suggesting that corrected hepatocytes are acting as a sink to eliminate excess of copper. Importantly, administration of AAVAnc80-miniATP7B was safe in healthy mice and did not result in copper deficiency. Conclusion: In summary, gene therapy using an optimized therapeutic cassette in different AAV systems provides long-term correction of copper metabolism regardless of sex or stage of disease in a clinically relevant WD mouse model. These results pave the way for the implementation of gene therapy in WD patients.


Value-directed human behavior analysis from video using partially observable Markov decision processes.
This paper presents a method for learning decision theoretic models of human behaviors from video data. Our system learns relationships between the movements of a person, the context in which they are acting, and a utility function. This learning makes explicit that the meaning of a behavior to an observer is contained in its relationship to actions and outcomes. An agent wishing to capitalize on these relationships must learn to distinguish the behaviors according to how they help the agent to maximize utility. The model we use is a partially observable Markov decision process, or POMDP. The video observations are integrated into the POMDP using a dynamic Bayesian network that creates spatial and temporal abstractions amenable to decision making at the high level. The parameters of the model are learned from training data using an a posteriori constrained optimization technique based on the expectation-maximization algorithm. The system automatically discovers classes of behaviors and determines which are important for choosing actions that optimize over the utility of possible outcomes. This type of learning obviates the need for labeled data from expert knowledge about which behaviors are significant and removes bias about what behaviors may be useful to recognize in a particular situation. We show results in three interactions: a single player imitation game, a gestural robotic control problem, and a card game played by two people.