An approach to evaluating the introduction of primary nursing in an acute medical unit for the elderly--I. Principles and practice.
The paper reviews the research literature on primary nursing and some of the problems in research methodology which have been identified. It sets out the 10 principles which are the basis on which primary nursing will be introduced in an acute elderly care ward. The problem of outcome measures is discussed and a research design proposed.


Medical staff's sense of awareness of informed consent for adolescent cancer patients and the need for decision-making support practiced from the perspective of trauma-informed approach.
It has not been established how to assess children's and adolescents' decision-making capacity (DMC) and there has been little discussion on the way their decision-making (DM). The purpose of this study was to examine actual situation and factors related to difficulties in explaining their disease to adolescent cancer patients or obtaining informed consent (IC). The cross-sectional questionnaire survey was conducted. Physicians who have been treating adolescent cancer patients for at least five years answered a self-administered questionnaire uniquely developed about clinical difficulties in explaining, IC and factors related patient's refusal of medical treatment (RMT). Descriptive statistics for each item and a polychoric correlation analysis of the problems and factors related to the explanation were conducted. As a result, fifty-six physicians were participated (rate of return: 39%). Explaining the disease and treatment to patients (83.9%), IC to patients (80.4%), and explaining the disease and treatment to parents (78.6%) was particularly problematic. Difficulties to provide support related with patient's refusal of medical treatment and to explain disease and treatment for patient and parents were related to difficulties obtaining IC for the patient. Conclusion: There are clinically difficult to explain for the patient or parents and to obtain IC for the patient. It is necessary to establish a disease acceptance assessment tool for the adolescence generation so that it can be applied in the field.


The effect of parenting styles on adolescent bullying behaviours in China: The mechanism of interpersonal intelligence and intrapersonal intelligence.
Bullying is a problematic public behaviour of great concern worldwide, which occurs commonly in China. Parenting and emotional intelligence have previously been verified as crucial aspects in determining the bullying behaviours of adolescents. However, evidence of the interactive effect of these vital factors needs to be more extensive. This study attempts to analyze the relationships and mechanisms of parenting on bullying through emotional intelligence, which consists of interpersonal and intrapersonal intelligence. Based on Chinese education panel survey data of 8730 adolescents, this paper used OLS regression and SEM methods to estimate the impact and mechanisms of parenting styles on bullying behaviours among adolescents. High-demand and responsive parenting styles can significantly reduce adolescents' bullying behaviours. Intrapersonal and interpersonal intelligence are important mediating variables, and parenting with high demandingness and high responsiveness can significantly improve the interpersonal intelligence of adolescents, thereby reducing children's bullying behaviour. Although low levels of intrapersonal intelligence would increase bullying behaviours in adolescents, high demandingness and high responsiveness of parenting can significantly improve adolescents' intrapersonal intelligence. Parents can reduce adolescents' bullying behaviours by increasing emotional responses and normative requirements. This result provides a new perspective on the solution to the problem of youth bullying.


Telomeres are shorter and associated with number of suicide attempts in affective disorders.
Shorter telomere length is a putative biomarker of accelerated aging and has been associated with affective disorders and mortality. Psychological factors and behaviors associated with telomere shortening are yet to be clarified. Here, we investigate the association between history of suicide attempts and telomere length in patients with affective disorders. Leucocyte telomere length was determined by quantitative real-time Polymerase Chain Reaction (qPCR) in patients with affective disorders (n = 248) including bipolar disorders type I (n = 159), type II (n = 67), major depressive disorder (n = 22), and healthy controls (n = 401). Diagnosis, duration of illness, and age at onset were assessed using the Structural Clinical Interview for DSM-IV (SCID-I). Number of lifetime suicide attempts were based on self-reports. Effect size was calculated using Cohen's d. Telomere length was reduced in patients with affective disorders relative to healthy controls (d = 0.18, F = 5.26, p = 0.02). Among patients, a higher number of suicide attempts was associated with shorter telomere length (β = -0.24, t = -3.83, CI = -0.44 to -0.14, p < 0.001), also when controlling for duration of illness and age at onset (β = -.23, CI = -.42 to -.12, p = 0.001). Multiple suicide attempts were associated with telomere length reduction comparable to eight years lifespan, adjusted for demographic and clinical characteristics. While longitudinal data are needed to clarify the temporal course, previous suicide attempts and related distress may accelerate telomere shortening and aging in patients with affective disorders.


Shock index: a re-evaluation in acute circulatory failure.
To evaluate the relationship between the shock index SI (ratio of heart rate to systolic arterial pressure) and cardiac function and oxygen transport in an experimental model of hemorrhage and clinical septic shock. This study was conducted in a hypovolemic circulatory failure model; 40% hemorrhage in the anesthetized pig and normovolemic hyperdynamic septic patients in the intensive care unit (ICU). Hemodynamic and oxygen transport variables were measured and their relationships to SI was examined. SI was inversely related to blood loss, cardiac index (CI), stroke volume (SV), mean arterial pressure (MAP) and left ventricular stroke work (LVSW) (r = -0.73, -0.75, -0.89 and -0.75, respectively P less than 0.01) following hemorrhage in the anesthetized pig. Oxygen transport variables, i.e. oxygen delivery (DO2) and mixed venous oxygen saturation (SvO2P) (r = -0.68 and -0.74, respectively, P less than 0.01) were also inversely related to the SI. Oxygen consumption (VO2) increased initially with increasing SI and fell when SI was greater than 3.0. In clinical septic shock and following blood volume expansion, the SI was not correlated to CI, SVI, MAP or systemic vascular resistance (SVR) (r = -0.01, -0.47, -0.34 and -0.14, respectively, P-value NS) but was inversely related to LVSWI (r = -0.68, P less than 0.01). There were no relationships between the SI and oxygen transport variables (DO2, SvO2) (r = -0.02 and -0.17, P-value NS) in septic shock. SI provides a non-invasive means to monitor deterioration or recovery of LVSW during acute hypovolemic and normovolemic circulatory failure and its therapy. SI may be of limited value in the assessment of systemic oxygen transport and response to therapy in clinical shock.


Maceration determines diagnostic yield of fetal and neonatal whole body post-mortem ultrasound.
To determine factors in nondiagnostic fetal and neonatal post-mortem ultrasound (PMUS) examinations. All fetal and neonatal PMUS examinations were included over a 5-year study period (2014-2019). Nondiagnostic image quality by body parts (brain, spine, thorax, cardiac, and abdomen) was recorded and correlated with patient variables. Descriptive statistics and logistic regression analyses were performed to identify significant factors for nondiagnostic studies. Two hundred sixty-five PMUS examinations were included, with median gestational age of 22 weeks (12-42 wk), post-mortem weight of 363 g (16-4033 g), and post-mortem interval of 8 days (0-39 d). Diagnostic imaging quality was achieved for 178/265 (67.2%) studies. It was high for abdominal (263/265, 99.2%), thoracic (264/265, 99.6%), and spine (265/265, 100%) but lower for brain (210/265, 79.2%) and cardiac imaging (213/265, 80.4%). Maceration was the best overall predictor for nondiagnostic imaging quality (P < .0001). Post-mortem fetal weight was positively associated with cardiac (P = .0133) and negatively associated with brain imaging quality (P = .0002). Post-mortem interval was not a significant predictor. Fetal maceration was the best predictor for nondiagnostic PMUS, particularly for brain and heart. Fetuses with marked maceration and suspected cardiac or brain anomalies should be prioritised for post-mortem MRI.


Rh-Catalyzed C-H Amidation of 2-Arylbenzo[ d]thiazoles: An Approach to Single Organic Molecule White Light Emitters in the Solid State.
A Rh-catalyzed direct C-H amidation of 2-arylbenzo[ d]thiazoles has been developed. The transformation is characterized by its efficiency, external oxidant-free conditions, and the avoidance of a traditional three-step process consisting of nitration, ammoniation, and amidation. Furthermore, several of the prepared molecules exhibit bright white-light emission in the solid state.


A functional microRNA library screen reveals miR-410 as a novel anti-apoptotic regulator of cholangiocarcinoma.
Cholangiocarcinoma is characterized by late diagnosis and a poor survival rate. MicroRNAs have been involved in the pathogenesis of different cancer types, including cholangiocarcinoma. Our aim was to identify novel microRNAs regulating cholangiocarcinoma cell growth in vitro and in vivo. A functional microRNA library screen was performed in human cholangiocarcinoma cells to identify microRNAs that regulate cholangiocarcinoma cell growth. Real-time PCR analysis evaluated miR-9 and XIAP mRNA levels in cholangiocarcinoma cells and tumors. The screen identified 21 microRNAs that regulated >50 % cholangiocarcinoma cell growth. MiR-410 was identified as the top suppressor of growth, while its overexpression significantly inhibited the invasion and colony formation ability of cholangiocarcinoma cells. Bioinformatics analysis revealed that microRNA-410 exerts its effects through the direct regulation of the X-linked inhibitor of apoptosis protein (XIAP). Furthermore, overexpression of miR-410 significantly reduced cholangiocarcinoma tumor growth in a xenograft mouse model through induction of apoptosis. In addition, we identified an inverse relationship between miR-410 and XIAP mRNA levels in human cholangiocarcinomas. Taken together, our study revealed a novel microRNA signaling pathway involved in cholangiocarcinoma and suggests that manipulation of the miR-410/XIAP pathway could have a therapeutic potential for cholangiocarcinoma.


Validation of Sonography findings of synovitis and tenosynovitis of hands and wrists in patients with systemic sclerosis.
Validating musculoskeletal ultrasound features of the joints and tendons of the hands in a large scleroderma cohort. A total of 81 scleroderma patients participated in this prospective, cross-sectional study. Grayscale and power Doppler musculoskeletal ultrasound images of 13 joints and 5 tendons of the wrist and hand were obtained. Clinical assessment included modified Rodnan skin thickness score, joint count, and Scleroderma Health Assessment Questionnaire. Face validity, content validity, construct validity, and feasibility were assessed. Mean age was 53.8 years (range 22-80), 76.5% were females, and disease duration ranged from 0.25 to 29 years. Mean length of the examination was 36 min. Scleroderma Health Assessment Questionnaire-Disability Index correlated with musculoskeletal ultrasound erosions (r = 0.5, p = 0.0003). Skin score correlated with tendinitis grayscale (r = 0.26, p = 0.02). Intra-reader correlation coefficient for musculoskeletal ultrasound was 0.96 for the joints and could not be calculated for tendons because there were too few positive findings. When tendon changes existed, percent of agreement was 77.7%-83.3%. Musculoskeletal ultrasound of 13 joints and 5 tendons of the hands and wrist has face and content validity. Construct validity was shown for the tendons and erosion scores. Feasibility and reliability were partially validated.


ABO blood group incompatibility as an adverse risk factor for outcomes in patients with myelodysplastic syndromes and acute myeloid leukemia undergoing HLA-matched peripheral blood hematopoietic cell transplantation after reduced-intensity conditioning.
ABO incompatibility is not a contraindication to hematopoietic cell transplantation (HCT), but it has been associated with additional risks including delayed engraftment, pure red cell aplasia (PRCA), and higher transfusion needs. Data on these events and on patient survival after reduced-intensity conditioning (RIC) HCT are limited. A total of 127 consecutive patients, 86 with acute myeloid leukemia and 41 with myelodysplastic syndromes, who underwent HLA-matched peripheral blood RIC allogenic HCT between 2005 and 2014 were retrospectively analyzed. Eighty ABO-compatible, 26 major/bidirectional, and 21 minor-ABO-mismatch HCT were identified. Compared to the ABO-compatible group, major/bidirectional mismatches had increased red blood cell (RBC) transfusion requirement during the first 100 days (p = 0.009), delayed RBC and PLT engraftment (p = 0.0011 and p = 0.005, respectively), and higher incidence of grade II to IV acute graft-versus-host disease (aGVHD; p = 0.037). In multivariable analysis, major/bidirectional mismatches had significantly higher non-relapse mortality (NRM) and inferior disease-free survival (DFS) and overall survival (OS) compared with ABO-compatible patients (p = 0.01, p = 0.04, and p = 0.035, respectively). Minor ABO mismatch had no impact on survival (p = 0.99). Four (15%) of 26 major/bidirectional mismatches developed PRCA. There was a significant association between fludarabine plus busulfan conditioning and PRCA (p = 0.0046). Major/bidirectional ABO mismatch is associated with higher NRM and shortened DFS and OS in the setting of RIC HCT. Increased transfusion need, delayed RBC and platelet engraftment, PRCA, and increased severity of aGVHD are additional complications contributing to the morbidity.


Type and timing of systemic therapy use predict overall survival for patients with brain metastases treated with radiation therapy.
This study aimed to investigate whether systemic therapy (ST) use surrounding radiation therapy (RT) predicts overall survival (OS) after RT for patients with brain metastases (BMs). Provincial RT and pharmacy databases were used to review all adult patients in British Columbia, Canada, who received a first course of RT for BMs between 2012 and 2016 (n = 3095). Multivariate analysis on a randomly selected subset was used to develop an OS nomogram. In comparison to the 2096 non-recipients of ST after RT, the median OS of the 999 recipients of ST after RT was 5.0 (95% Confidence interval (CI) 4.1-6.0) months longer (p < 0.0001). Some types of ST after RT were independently predictive of OS: targeted therapy (hazard ratio (HR) 0.42, CI 0.37-0.48), hormone therapy (HR 0.45, CI 0.36-0.55), cytotoxic chemotherapy (HR 0.71, CI 0.64-0.79), and immunotherapy (HR 0.64, CI 0.37-1.06). Patients who discontinued ST after RT had 0.9 (CI 0.3-1.4) months shorter median OS than patients who received no ST before or after RT (p < 0.0001). In the multivariate analysis of the 220-patient subset, established prognostic variables (extracranial disease, performance status, age, cancer diagnosis, and number of BMs), and the novel variables "ST before RT" and "Type of ST after RT" independently predicted OS. The nomogram predicted 6- and 12-month OS probability and median OS (bootstrap-corrected Harrell's Concordance Index = 0.70). The type and timing of ST use surrounding RT predict OS for patients with BMs.


The inner workings of an ethics committee: latest battle over Jehovah's Witnesses.
Jehovah's Witnesses who refuse blood transfusions on religious grounds have long created ethical dilemmas for those in the medical profession trying to serve them. A bioethicist working in a clinical setting explores how one hospital ethics committee grappled with the additional problem of pregnant Jehovah's Witnesses, including the complex interdependence of maternal and fetal rights.


A patient selection profile for the use of speech prostheses in adult dysarthria.
This paper deals with the decision making process involved in patient selection for the use of speech prostheses in adult dysarthria. A candidacy profile is presented and explained. Assessment of all components of dysarthria, including resonance, articulation, phonation, respiration, and prosody, is stressed along with motivational and medical considerations.


Delineation of the phagocyte NADPH oxidase through studies of chronic granulomatous diseases of childhood.
The phagocyte NADPH oxidase is a complex system consisting of membrane and cytosolic components that must assemble at the membrane for proper activation. Studies of patients with chronic granulomatous diseases of childhood have enabled the molecular characterization of these components, which has led to studies defining their interaction during NADPH complex assembly. Understanding NADPH oxidase assembly provides an opportunity to develop therapeutics for the regulation of this important reaction of inflammation.


Cell-cycle kinetics and ultraviolet light survival in UV-1, a Chinese hamster ovary cell mutant defective in post-replication recovery.
UV-I, an ultraviolet-sensitive mutant of CHO-KI, is abnormally slow to recover from the inhibition of DNA synthesis caused by u.v. irradiation. When synchronized UV-I cells are irradiated in G1, their movement into S phase is unaltered, but thymidine incorporation is depressed (compared with that in the parent cell similarly treated). When irradiated in S phase, again incorporation is more depressed, and S phase suffers a greater delay in UV-I than in the parent cell. UV-I and its parent have similar capacities for excision repair of u.v.-induced damage inflicted in G1, and so enter S phase with similar amounts of unrepaired damage. The single-cell survival was measured after irradiation at different points in the cell cycle. The mutant and parent cells have similar values of D0 (mean lethal dose) except in mitosis, when the parent cell shows markedly greater resistance to u.v. irradiation. Dq (quasi-threshold dose) is fairly constant for the parent cell, but in UV-I it falls to a minimum in S phase. The responses of UV-I to u.v. irradiation are generally consistent with its known defect in the process of post-replication recovery, i.e. the ability to join up the abnormally small DNA fragments synthesized on a u.v.-damaged template.


Benzofurans and another constituent from seeds of Styrax officinalis.
The benzofuran constituents of the seeds of Styrax officinalis were investigated. From the hexane extract, two new constituents named 5-(3"benzoyloxypropyl)-7-methoxy-2-(3',4'-methylenedioxyphenyl)-benzofuran (5) and 4-[3"-(1c-methylbutanoyloxy)propyl]-2-methoxy-(3',4'-methylenedioxyphenyl)-1a, 5b-dihydrobenzo-[3,4]-cyclobutaoxirene (6) were isolated together with four known compounds, 5-[3"-(1c-methylbutanoyloxy)propyl]-7-methoxy-2-(3',4'-dimethoxyphenyl)-benzofuran (4), 5-[3"-(1c-methylbutanoyloxy)propyl]-7- methoxy-2-(3',4'-methylenedioxyphenyl)-benzofuran (3), 5-(3"-acetoxypropyl)-7-methoxy2-(3',4'-methylenedioxphenyl)-benzofuran (2) and 5-(3"-hydroxypropyl)-7-methoxy-2-(3',4'-met hylenedioxyphenyl)-benzofuran (1). Although the compounds 1, 2, and 3 have been isolated previously from the seeds of Styrax obassia, this is the first record of their isolation from seeds of Styrax officinalis. The structures of the isolated compounds were established by 1D- and 2D-NMR (HMBC, HMQC, COSY), FABMS and high-resolution ESI FTMS.


ISCOMs: an adjuvant with multiple functions.
Aluminum salts are currently the only widely used adjuvant for human vaccines. Over the past 10-15 years, a large research effort has attempted to find novel adjuvants with ability to induce a broad range of immune responses, including cell-mediated immunity. The immunostimulating complex or ISCOM is one adjuvant with multiple adjuvant properties. ISCOMs are open cage-like complexes typically with a diameter of about 40 nm that are built up by cholesterol, lipid, immunogen, and saponins from the bark of the tree Quillaia saponaria Molina. ISCOMs have been demonstrated to promote antibody responses and induce T helper cell as well as cytotoxic T lymphocyte responses in a variety of experimental animal models, and have now progressed to phase I and II human trials. This review describes recent developments in the understanding of the structure, composition, and preparation of ISCOMs and will cover important aspects of the understanding of the adjuvant functions of ISCOMs and how they act on the immune system.


Macrosomia and mental retardation: evidence of autosomal dominant inheritance in four generations.
We describe a large family with 14 persons presenting macrosomia with or without mental retardation in which dominant transmission is evident over 4 generations. A wide range of phenotypic variability was observed, some patients showing macrosomia and mental impairment, others only macrosomia. The cases will be discussed in relationship with other conditions in which the 2 signs may be present, and above all in Sotos sequence.


[Chronic pancreatitis and its treatment in diseases of terminal segment of the common bile duct].
Clinical observations embrace 77 cases of chronic pancreatitis combined with various pathologic changes of the choledochal terminal portion. The surgical correction of these changes was carried out upon 73 cases. The follow-up lasting from 2 to 6 years has shown the manifestation of chronic pancreatitis either disappear or subside dramatically in the most cases following the surgical correction of the pathologic changes in the choledochal terminal portion.


Studying the Co-presentation of Focal Segmental Glomerulosclerosis and IgA Nephropathy in a Young Female With No Significant Risk Factors.
Focal segmental glomerulosclerosis (FSGS) and IgA nephropathy are among the most common glomerular disorders. FSGS is characterized by focal scarring affecting less than 50% of glomeruli while IgA nephropathy is characterized by the deposition of IgA in the mesangium of glomeruli. The presence of both of these diseases in a single patient is uncommon, but the presence of both in a young individual with no predisposing factors is exceedingly rare. As such, our case report outlines the unusual presentation of both of these disorders in a young Hispanic female with no known risk factors.


Immunogenic and antigenic epitopes of immunoglobulins--V. Reactivity of a panel of monoclonal antibodies with sub-fragments of human Fc gamma and abnormal paraproteins having deletions.
The specificity of a panel of 27 monoclonal antibodies reactive with human Fc gamma has been further defined through reactivity profiles with sub-fragments of Fc gamma and IgG paraproteins having deletions within C gamma 2 or C gamma 3. Antibodies are identified that are directed to discontinuous epitopes requiring native Fc gamma for expression. Other antibodies are reactive with isolated C gamma 2 or C gamma 3 domains. Sub-class specific and sub-class restricted antibodies allow correlation of epitope expression with primary structure.


Stress and motivation of cell processing operators: A pilot study of an online questionnaire survey.
Cell processing operators (CPOs) are one of the most important human assets for the industrial development of regenerative therapy since cell processing is still carried out manually. However, investigating the psychological aspects of CPOs to take advantage of this important human asset has not been done. Thus, the objectives of the current study were, first, to investigate the attributes of CPOs, second, to identify the factors that give CPOs mental stress, and third, to identify the motivational factors of CPOs. An online questionnaire was conducted to investigate the attributes of participants, stresses, and motivations; the questionnaire included multiple-choice questions. A survey questionnaire was distributed to 64 operators in 31 CPFs, including universities, clinics, and pharmaceutical companies, from December 2021 to February 2022. Participants responded to the online survey via Microsoft Forms. Approximately half of the CPOs had been employed for two years or less, and they were more likely to experience various stressful situations than CPOs with three or more years of experience. In particular, the wear of dust-free clothing and work in a unique environment of a clean room, where it is difficult to take breaks due to the nature of the closed space, were considered to be particularly stressful situations. However, these CPOs have high motivations based on their pride in being involved in cutting-edge medical care, which is highly expected by society, and in contributing to patient care. While stress with training and education programs for CPOs is an issue that can be resolved through in-house training, other issues that are difficult to resolve immediately, such as mechanization to relieve the stress of human manual operations, were identified. Continued efforts to analyze and alleviate the stress factors identified in this study are expected to improve the quality of CPOs' work and maintain the important human asset of CPOs.


Examination of the role of FMRFamide-related peptides in the circadian clock of the cockroach Leucophaea maderae.
The accessory medulla, the circadian clock of the cockroach Leucophaea maderae, is abundant in neuropeptides. Among these neuropeptides are the FMRFamide-related peptides (FaRPs), which generally share the C-terminal RFamide. As a first step toward understanding the functional role of FaRPs in the circadian clock of the cockroach, immunocytochemistry with antisera against various FaRPs, MALDI-TOF mass spectrometry, and injections of two FaRPs combined with running-wheel assays were performed. Prominent FMRFamide-like immunoreactivity was found in maximally four soma clusters associated with the accessory medulla and in most neuropils of the protocerebrum. By MALDI-TOF mass spectrometry, various extended FMRFamides of the cockroach L. maderae were partially identified in thoracic perisympathetic organs, structures known to accumulate extended FMRFamides in insects. By mass match, several of these peptides were also detected in the accessory medulla. Injections of FMRFamide and Pea-FMRFa-7 (DRSDNFIRF-NH(2)) into the vicinity of the accessory medulla caused time-dependent phase-shifts of locomotor activity rhythms at circadian times 8, 18, and 4. Thus, our data suggest a role for the different FaRPs in the control of circadian locomotor activity rhythms in L. maderae.


The occurrence of 12, 13-epoxytrichothecenes in seeds of safflower infected with Fusarium oxysporum f. sp. carthami.
From the seeds of safflower (Carthamus tinctorius Linn.), infected with Fusarium oxysporum f. sp. carthami, 3 toxic compounds have been isolated in quantities sufficient to cause mycotoxicosis on prolonged ingestion. 2 of these have been identified as diacetoxyscirpenol and T-2 toxin, while the third one has also been partially characterized as a 12, 13-epoxytrichothecene. Additionally, the incidence of secondary fusarial infection of healthy seeds due to contamination with the infected ones has been reported for the first time.


Dependence of mammalian DNA replication on DNA supercoiling. I. Effects of ethidium bromide on DNA synthesis in permeable Chinese hamster ovary cells.
Chinese hamster ovary cells labelled with [14C]thymidine were made permeable, incubated with various concentrations of the intercalating dye ethidium bromide, and centrifuged through neutral sucrose gradients. The gradient profiles of these cells were qualitatively similar to those obtained by centrifuging DNA from untreated, lysed permeable cells through gradients containing ethidium bromide. The sedimentation distance of DNA had a biphasic dependence on the concentration of ethidium bromide, suggesting that the dye altered the amount of DNA supercoiling in situ. The effect of ethidium bromide intercalation on incorporation of [3H]dTMP into acid-precipitable material in an in vitro DNA synthesis mixture was measured. The incorporation of [3H]dTMP was unaffected by less than 1 microgram/ml of ethidium bromide, enhanced up to two-fold by 1--10 microgram/ml, and inhibited by concentrations greater than 10 micrograms/ml. Alkaline sucrose gradient analysis revealed a higher percentage of small DNA fragments (6--20 S) in the cells treated with 2 micrograms/ml ethidium bromide than in control cells. These fragments attained parental size within the same time as the fragments in control cells. In cells treated with 2 micrograms/ml ethidium bromide, a significant fraction of newly synthesized DNA resulted from new starts, whereas in untreated cells practically none of the newly synthesized DNA resulted from new starts. These results suggest that relaxation of DNA supercoiled structures ahead of the replication fork generates spurious initiations of DNA synthesis and that in intact cells the rate of chain elongation is limited by supercoiled regions ahead of the growing point.


Single Particle Observation of SV40 VP1 Polyanion-Induced Assembly Shows That Substrate Size and Structure Modulate Capsid Geometry.
Simian virus 40 capsid protein (VP1) is a unique system for studying substrate-dependent assembly of a nanoparticle. Here, we investigate a simplest case of this system where 12 VP1 pentamers and a single polyanion, e.g., RNA, form a T = 1 particle. To test the roles of polyanion substrate length and structure during assembly, we characterized the assembly products with size exclusion chromatography, transmission electron microscopy, and single-particle resistive-pulse sensing. We found that 500 and 600 nt RNAs had the optimal length and structure for assembly of uniform T = 1 particles. Longer 800 nt RNA, shorter 300 nt RNA, and a linear 600 unit poly(styrene sulfonate) (PSS) polyelectrolyte produced heterogeneous populations of products. This result was surprising as the 600mer PSS and 500-600 nt RNA have similar mass and charge. Like ssRNA, PSS also has a short 4 nm persistence length, but unlike RNA, PSS lacks a compact tertiary structure. These data indicate that even for flexible substrates, shape as well as size affect assembly and are consistent with the hypothesis that work, derived from protein-protein and protein-substrate interactions, is used to compact the substrate.


Cytophotometry of glucose-6-phosphate dehydrogenase activity in individual cells.
With the aid of thin films of polyacrylamide gel containing purified glucose-6-phosphate dehydrogenase subjected to cytochemical procedures for the enzyme using tetranitro blue tetrazolium, arbitrary units of integrated absorbance obtained with a Barr & Stroud GN5 cytophotometer were converted into units of enzyme activity. This conversion enabled cytochemical data to be compared directly with biochemical values. The conversion was applied to the cytochemical estimation of glucose-6-phosphate dehydrogenase activity in isolated rat hepatocytes, mouse oocytes, rabbit thymocytes, human granulocytes and human fibroblasts. Several control procedures were performed to confirm the admissibility of this conversion, such as: the estimation of the absorption characteristics of the formazans of tetranitro blue tetrazolium both in solution and precipitated in biological specimens; the linearity of the relationship between the increase of absorbance and incubation time; and the effect of different incubation conditions on the amount of specific formazan production.


Dual Inhibition And Monitoring Of Beta-amyloid Fibrillation By A Luminescent Iridium(III) Complex.
In this study, we report the synthesis and application of the novel cyclometallated luminescent Ir(III) complex 1 bearing the C^C^C ligand as a probe and inhibitor of Aβ fibrillation. We envisage that this kinetically-inert Ir(III) complex may be potentially developed as a dual-purpose probe and inhibitor of Aβ aggregation for Alzheimer's disease diagnosis and treatment.


Treatment of advanced squamous-cell carcinoma of the head and neck with a combination of cisplatin, vinblastine, and bleomycin.
Fifty patients with advanced, measurable, squamous-cell cancers of the head and neck received treatment with a combination of cisplatin, vinblastine, and bleomycin (PVB). The tumours in 25 patients (50%) responded to treatment (partially in 17 and completely in eight). The median duration of response was 18 weeks, and that of survival was 31 weeks. Toxicity was moderately severe; myelotoxicity occurred in 13 patients, and nausea and vomiting in 22 patients.


Separation by high-performance liquid chromatography of penicillins with C4 to C10 aliphatic side chains.
A suitable and rapid method for the simultaneous determination of different aliphatic penicillins is described. Butyryl-, pentanoyl-, hexanoyl-, heptanoyl-, octanoyl-, nonanoyl- and decanoylpenicillin can be completely separated by high-performance liquid chromatography using an isocratic elution mode (50 mM H2KPO4, pH 5.0:methanol, 45:55 v/v). Under these conditions, retention times for C4 to C10 aliphatic side-chain penicillins were 2.5, 2.8, 4.1, 5.8, 8.9, 15.3, and 28.2 min. The benzylpenicillin retention time was 3.3 min.


Exposure of Staphylococcus aureus to silver(I) induces a short term protective response.
The Ag(I) ion has well established anti-bacterial and antifungal properties. Exposure of Staphylococcus aureus to MIC(80) AgNO(3) (3 μg/ml) lead to an increase in the activity of superoxide dismutase, glutathione reductase and catalase at 30 min but activity declined by 60 min. In addition, exposure of cells to this metal ion for 1 h lead to increased expression of a number of proteins such as elongation factors Ts, Tu and G, fructose-bisphosphate aldolase and triosephosphate isomerase but their expression declined following 4 h exposure. ATP binding cassette transporter protein and oligoendopeptidase F showed increased expression at 4 h. While Ag(I) is a potent antimicrobial agent this work demonstrates that S. aureus can mount a short-term protective response to exposure to the metal ion but that this is eventually overcome.


Is diagnostic ultrasound safe? Current international consensus on the thermal mechanism.
To describe the potential risk of heating during ultrasound examinations and to report the international consensus on the safety of ultrasound in medicine. Literature on the biological effects of hyperthermia and ultrasound. The use of B-mode grey-scale imaging is not contra-indicated on thermal grounds. Some pulsed Doppler equipment has the potential to produce biologically significant temperature increases, specifically at interfaces between bone and soft tissue. Exposures resulting in temperatures less than 38.5 degrees C can be used without reservation.


[Factors associated with mental disorders in the psychiatric department of the university hospital centre of Point G in Mali.]
Mental health is a state of equilibrium and well-being, any alteration of which leads to the appearance of a state of distress and/or mental disorder. The objective of this work was to study familial and environmental factors associated with mental disorders. A cross-sectional study was conducted in the Psychiatry Department of the Point G University Hospital Center from April 1, 2016 to March 31, 2017 among outpatients with a psychiatric disorder in whom factors associated with psychiatric disorders were studied. We included 288 patients. The median age was 33.0 years. The sex ratio was 1.88 in favor of males. Married patients accounted for 45.5%. First born uterine siblings accounted for 26.7%. Patients born of an inbreeding alliance accounted for 25.7%. Cases with a family history of a psychiatric disorder represented 59.0% and those who spent their childhood with their parents accounted for 64.2%. Cases of psychoactive substance use prior to the onset of the mental disorder accounted for 42.7%. The main psychosocial stress factors that preceded the onset of the mental disorder were grief (46.2%) and family conflict (22.6%). Psychotic disorders accounted for 77.8%. Our results show an association of mental disorders with family history of psychiatric disorder among patients followed in psychiatry. Further studies, such as genetic association may prove useful.


An economic evaluation of transdermal glyceryl trinitrate in the prevention of intravenous infusion failure.
A common cause of peripheral intravenous infusion failure is due to the patient developing phlebitis or extravasation. Recent clinical trials indicate that the use of transdermal glyceryl trinitrate (GTN patches) can reduce the incidence of infusion failure and hence the costs of re-infusion. In this study we conduct an economic evaluation of this new pharmaceutical application to determine whether the use of such patches results in hospital resource cost savings. Time-to-first infusion failure probabilities from a placebo-controlled trial are used to model the sequential failure problem as a Markov process. Using estimated staff and materials costs for first and subsequent infusions, we calculate the expected cost per infused patient to time t for treatment and control groups. Using this simple comparative cost method, results indicate that the net impact on hospital resources from patch usage is dependent upon the total required length of infusion time. Analysis of infusion time thresholds indicates that for patients requiring long-term (t greater than 50 hours) periods of infusion the use of patches is likely to generate resource savings. We conclude that to realize such resource savings clinical decisions to infuse with GTN patches should incorporate the prior probability that the total required length of infusion time exceeds 50 hours.


Quality of life and distress assessed with self and external assessment screening tools in patients with hematologic malignancies attending treatment in an acute hospital.
In this study, we examined distress levels and quality of life (QoL) of patients with hematologic malignancies under treatment in an acute setting. We used external- and self-assessment instruments for distress. Additionally, we investigated the relation between distress and QoL as well as whether highly distressed patients differed from less distressed patients concerning their QoL. A cross-sectional study with patients of the Medical Clinic II of the University Hospital Frankfurt was conducted. One hundred and nine patients were assessed with an expert rating scale and completed self-report questionnaires. Data were exploratively analyzed and group comparisons between patients who scored above the cut-off of the respective screening instruments and those who did not were conducted. Patients with hematologic malignancies experience high levels of distress and low QoL. Especially, role and social functioning are affected. Patients suffer most from fatigue, appetite loss, and insomnia. Using established cut-offs, all screening instruments were able to differentiate between patients regarding distress and QoL. Patients scoring above the cut-off were significantly more distressed and had a lower QoL. There was a medium-to-strong correlation between distress and QoL indicators. Cancer-specific screening instruments seem to be able to identify treatment needs more specifically. They also allowed a better differentiation concerning QoL. The close link between distress and QoL needs to be recognized to enable a holistic approach to treatment and thereby optimize the quality of treatment.


Foxh1 Occupies cis-Regulatory Modules Prior to Dynamic Transcription Factor Interactions Controlling the Mesendoderm Gene Program.
The interplay between transcription factors and chromatin dictates gene regulatory network activity. Germ layer specification is tightly coupled with zygotic gene activation and, in most metazoans, is dependent upon maternal factors. We explore the dynamic genome-wide interactions of Foxh1, a maternal transcription factor that mediates Nodal/TGF-β signaling, with cis-regulatory modules (CRMs) during mesendodermal specification. Foxh1 marks CRMs during cleavage stages and recruits the co-repressor Tle/Groucho in the early blastula. We highlight a population of CRMs that are continuously occupied by Foxh1 and show that they are marked by H3K4me1, Ep300, and Fox/Sox/Smad motifs, suggesting interplay between these factors in gene regulation. We also propose a molecular "hand-off" between maternal Foxh1 and zygotic Foxa at these CRMs to maintain enhancer activation. Our findings suggest that Foxh1 functions at the top of a hierarchy of interactions by marking developmental genes for activation, beginning with the onset of zygotic gene expression.


[The value of measurements of oscillatory resistance in the evaluation of lung function. A comparative study in adults and children (author's transl)].
Measurements of total oscillatory impedance (ROS) together with spirometric and body plethysmographic determinations were made in adults and children and the results were compared. In adults (n = 260) correlation was less close (r = 0.53) than it was in 88 children (r = 0.82). Even if ROS was of similar magnitude the phase shift between pressure and flow tended to be more negative than it was in children. These differences are presumably due to anatomical differences between the adult and the growing lung. In interpretation of the results it is suggested that the differences in the ratio: airways compliance/airways resistance reflect changes arising from age and disease processes.


The eye and visual system in the preeclampsia/eclampsia syndrome: What to expect?
The preeclampsia/eclampsia syndrome is a multisystem disorder that can include cardiovascular changes, hematologic abnormalities, hepatic and renal impairment, and neurologic or cerebral manifestations. It also can affect the eye and visual pathways. Visual symptoms concern up to 25% of patients with severe preeclampsia and 50% of patients with eclampsia. This review discusses the ophthalmic complications of preeclampsia/eclampsia with focus on the hypertensive retinopathy, exudative retinal detachment and cortical blindness.


Spinal shrinkage as a measure of spinal loading in male Saudi university students and its relationship with body mass index.
To compare spinal shrinkage in obese and non-obese young male adults and to find any correlation between them. In 2006, 123 second-year male students studying in the Colleges of Medicine and Dentistry, King Faisal University, Dammam, Kingdom of Saudi Arabia, were examined for their weights, standing heights, and recumbent lengths. In this cross-sectional observational study, the students were grouped according to body mass index (BMI): normal range BMI <25; overweight BMI = 25-29.9; obese-BMI >30. Spinal shrinkage was calculated as the difference between standing height and the recumbent length of the subject. Influence of BMI on the magnitude of spinal shrinkage was compared by analysis of variance, and the relationship between spinal shrinkage and BMI was tested with Pearson's correlation test. The obese group presented a significantly greater reduction in standing height (1.6% of recumbent length) compared to the normal group (1%) (p=0.019). Spinal shrinkage was found to be positively correlated with level of obesity (r=0.369). Spinal shrinkage is positively correlated to BMI, which represents a persistent load on the spine in obese individuals. This conveniently demonstrable adverse effect of obesity might well be used as an instrument to inspire individuals to change their lifestyles.


A PD-L1 Negative Advanced Gastric Cancer Patient With a Long Response to PD-1 Blockade After Failure of Systematic Treatment: A Case Report.
It was widely accepted that programmed death-ligand 1 (PD-L1) positive, tumor mutational burden-high (TMB-H) or microsatellite instability-high (MSI-H) tumor are prone to have better treatment response to immune checkpoint blockade. The value of immune checkpoint blockade in PD-L1 negative gastric cancer patients has been questioned due to lower objective response rate (ORR). We report an unusual case of a PD-L1 negative, proficient mismatch repair (pMMR)/microsatellite stability (MSS), tumor mutational burden-low (TMB-L) gastric cancer patient who achieved good response to immune checkpoint blockade after failure of systematic treatment. Multiple lymph nodes and bone metastases are the main characteristics of this patient. The patient survived for more than 30 months after diagnosis. This case suggested that PD-L1 negative gastric cancer patient may also benefit from immune checkpoint blockade. In gastric cancer, patients with lymph node metastasis may be potential beneficiaries.


The optimality of different strategies for supplemental staging of non-small-cell lung cancer: a health economic decision analysis.
To assess the expected costs and outcomes of alternative strategies for staging of lung cancer to inform a Danish National Health Service perspective about the most cost-effective strategy. A decision tree was specified for patients with a confirmed diagnosis of non-small-cell lung cancer. Six strategies were defined from relevant combinations of mediastinoscopy, endoscopic or endobronchial ultrasound with needle aspiration, and combined positron emission tomography-computed tomography with F18-fluorodeoxyglucose. Patients without distant metastases and central or contralateral nodal involvement (N2/N3) were considered to be candidates for surgical resection. Diagnostic accuracies were informed from literature reviews, prevalence and survival from the Danish Lung Cancer Registry, and procedure costs from national average tariffs. All parameters were specified probabilistically to determine the joint decision uncertainty. The cost-effectiveness analysis was based on the net present value of expected costs and life years accrued over a time horizon of 5 years. At threshold values of around €30,000 for cost-effectiveness, it was found to be cost-effective to send all patients to positron emission tomography-computed tomography with confirmation of positive findings on nodal involvement by endobronchial ultrasound. This result appeared robust in deterministic sensitivity analysis. The expected value of perfect information was estimated at €52 per patient, indicating that further research might be worthwhile. The policy recommendation is to make combined positron emission tomography-computed tomography and endobronchial ultrasound available for supplemental staging of patients with non-small-cell lung cancer. The effects of alternative strategies on patients' quality of life, however, should be examined in future studies.


Penetrating atherosclerotic ulcer in the juxtarenal abdominal aorta and coronary artery disease: emergency one-stage repair with off-pump coronary surgery.
An 82 year-old woman suddenly developed severe back pain. Enhanced computed tomography and aortography revealed penetrating atherosclerotic ulcer (PAU), that was a localized contrast-filled outpouching in the juxtarenal abdominal aorta and intramural hematoma within the aortic wall. Coronary angiography revealed significant stenosis in the left anterior descending artery and right coronary artery. Urgent aortic repair was required; therefore we performed the combined operations of coronary artery bypass grafting and aortic repair. PAUs typically occur in elderly patients with a history of hypertension, and are frequently complicated by coronary artery disease. However, few cases have been reported in the literature, such as cases involving combined operations. In this study, we report on a successful case of emergency repair involving concomitant juxtarenal abdominal aortic replacement for PAU and off-pump coronary artery bypass grafting.


Research on the Effects of Alcohol and Sexual Arousal on Sexual Risk in Men who have Sex with Men: Implications for HIV Prevention Interventions.
The purpose of this paper was to describe and appraise the research evidence on the effects of acute alcohol intoxication and sexual arousal on sexual risk behaviors in men who have sex with men (MSM) and to examine its implications for design of HIV prevention interventions that target MSM. Toward that end, the paper begins with a discussion of research on sexual arousal in men and alcohol and their acute effects on sexual behaviors. This is followed by a review of empirical evidence on the combined acute effects of alcohol and sexual arousal in heterosexual men (the large majority of studies) and then in MSM. The empirical evidence and related theoretical developments then are integrated to derive implications for developing effective HIV prevention interventions that target MSM.


Implications of Tumor Surgery in Horseshoe Kidneys: A Comparative Study of Outcomes and Surgical Practices.
To contrast surgical outcomes of Horseshoe Kidney (HSK) patients with localized renal masses suspected of cancer with nonfused nonectopic kidney patients, emphasizing safe surgical practices for HSKs. The study examined solid tumors from the Mayo Clinic Nephrectomy registry between 1971 and 2021. Each HSK case was matched to three non-HSK patients based on various factors. The outcomes measured included complications within 30days of surgery, change in estimated glomerular filtration rate, and overall, cancer-specific, and metastasis-free survival rates. Thirty of the 34 HSKs had malignant tumors compared with 90 of the 102 patients in the nonfused nonectopic referent cohort. Accessory isthmus arteries were present in 93% of HSK cases, with 43% exhibiting multiple arteries and 7% with 6 or more arteries. Estimated blood loss and surgery duration were significantly higher in HSKs (900 vs 300 mL, P = .004; 246 vs 163 minutes, P < .001, respectively). The HSK group demonstrated an overall complication rate of 26% (vs 17% in referents, P = .2) and a median change in estimated glomerular filtration rate at 3months of - 8.5 (vs -8.1 in referents, P = .8). At 5-year follow-up, survival rates for HSK patients were 72%, 91%, and 69% for overall, cancer-specific, and metastasis-free survival, respectively. The corresponding rates were 79%, 86%, and 77%, respectively, for matched referent patients (P > .05). HSK tumor management is technically challenging with higher blood loss; however, the data demonstrate comparable outcomes for patients with HSK tumors, including complications and survival, to those without HSKs in experienced centers.


Dose-effect relationship for cataract induction after single-dose total body irradiation and bone marrow transplantation for acute leukemia.
To determine a dose-effect relationship for cataract induction, the tissue-specific parameter, alpha/beta, and the rate of repair of sublethal damage, mu value, in the linear-quadratic formula have to be known. To obtain these parameters for the human eye lens, a large series of patients treated with different doses and dose rates is required. The data of patients with acute leukemia treated with single-dose total body irradiation (STBI) and bone marrow transplantation (BMT) collected by the European Group for Blood and Marrow Transplantation were analyzed. The data of 495 patients who underwent BMT for acute leukemia, who had STBI as part of their conditioning regimen, were analyzed using the linear-quadratic concept. The end point was the incidence of cataract formation after BMT. Of the analyzed patients, 175 were registered as having cataracts. Biologic effective doses (BEDs) for different sets of values for alpha/beta and mu were calculated for each patient. With Cox regression analysis, using the overall chi-square test as the parameter evaluating the goodness of fit, alpha/beta and mu values were found. Risk factors for cataract induction were the BED of the applied TBI regimen, allogeneic BMT, steroid therapy for >14 weeks, and heparin administration. To avoid the influence of steroid therapy and heparin on cataract induction, patients who received steroid or heparin treatment were excluded, leaving only the BED as a risk factor. Next, the most likely set of alpha/beta and mu values was obtained. With this set, the cataract-free survival rates were calculated for specific BED intervals, according to the Kaplan-Meier method. From these calculations, cataract incidences were obtained as function of the BED at 120 months after STBI. The use of BED instead of the TBI dose enabled the incidence of cataract formation to be predicted in a reasonably consistent way. With Cox regression analysis for all STBI data, a maximal chi-square value was obtained for alpha/beta = 1.75 Gy and mu = 0.75 h(-1). When Cox regression analysis was applied for patients who had no steroid treatment after BMT, a maximal chi-square value was obtained for alpha/beta = 1 Gy and mu = 0.6 h(-1). Cox regression analysis was repeated using the data of patients who had not received posttransplant steroid treatment and also no heparin administration; we found alpha/beta = 0.75 Gy and mu= 0.65 h(-1). An increased cataract incidence was observed after steroid treatment of >14 weeks and heparin administration. The alpha/beta value of 0.75 Gy and mu value of 0.65 h(-1) found for the eye lens are characteristic for late-responding tissues. The incidence of cataract formation can now be quantified, taking into account the values calculated for alpha/beta and mu, TBI dose, and dose rate. Also, the reduction in cataract incidence as a result of lens dose reduction by eye shielding can be estimated.


Knowledge, attitudes, and practices towards COVID-19 among primary school students in Hubei Province, China.
This study was aimed to investigate the knowledge, attitudes, and practices (KAP) towards coronavirus disease 2019 (COVID-19) among school-aged children in the Hubei province when children were being confined to their homes. The questionnaire included questions of KAP about COVID-19, depressive and anxiety symptoms scales. Multivariable generalized linear regressions models were applied to estimate the unstandardized regression coefficients (β) of KAP. The awareness rates about COVID-19 were 70.1%-99.5% for all 1650 valid questionnaires. 37.2% of the participants quite worried about being infected with COVID-19. Approximately 96% of them washed hands in certain situations, while 85.6% of them washed hands after coughing or sneezing. Compared to the students without depressive symptoms, those who had depressive symptoms scored lower of total KAP, knowledge, attitudes, and practice. The findings suggest that primary students had a relatively good awareness of COVID-19 during the epidemic, as well as optimistic attitudes and appropriate practices. However, some items of appropriate practices still needed to be enhanced.


Enhanced antitumor efficacy of folate targeted nanoparticles co-loaded with docetaxel and curcumin.
The current study aimed to investigate whether the novel folate (FT) modified nanoparticles (NPs) co-loaded with docetaxel (DT) and curcumin (CU) (named as FT-NPs) could enhance the delivery efficiency to tumor compared with the NPs without FT (non-targeted NPs). FT-NPs were successfully formulated in this article. In vitro cytotoxic activity against A549 cells and in vivo antitumor activity of FT-NPs in S180 cell bearing mice were conducted. Cellular uptake test was used to evaluate uptake efficiency of FT-NPs. Histological observation was used to determine the lung security. Besides, the physical chemical properties such as stability, particle size, zeta potential, drug encapsulation efficiency, transmission electron microscopy (TEM) were also conducted. FT-NPs exhibited stronger growth inhibition effects on A549 cells compared with non-targeted NPs, moreover, the novel FT-NPs indicated more effective antitumor efficacy in inhibiting tumor growth. Confocal laser scanning microscopy indicated that the uptake of FT-NPs was facilitated and effective. Histological observation meant that FT-NPs were biocompatible and appropriate for pulmonary administration. These results confirmed that FT-NPs with relatively high drug loading capacity could effectively inhibit tumor growth and reduce toxicity. The novel FT-NPs could produce as an outstanding nanocarrier for the targeted treatment of cancers.


RGD conjugates of the H2dedpa scaffold: synthesis, labeling and imaging with 68Ga.
The rekindled interest in the (68)Ga generator as an attractive positron emission tomography generator system has led us and others to investigate novel chelate systems for (68)Ga. We have previously reported our findings with the acyclic, rapidly coordinating chelate H(2)dedpa and its model derivatives. In this report, we describe the synthesis of the corresponding bifunctional chelate scaffolds (H(2)dp-bb-NCS and H(2)dp-N-NCS) as well as the radiolabeling properties, transferrin stability, binding to the target using in vitro cell models and in vivo behavior the corresponding conjugates with the α(v)β(3) targeting cyclic pentapeptide cRGDyK (monomeric H(2)RGD-1 and dimeric H(2)RGD-2). The ability of the conjugated ligands to coordinate Ga isotopes within 10 min at room temperature at concentrations of 1 nmol was confirmed. Complex [(67)Ga(RGD-1)](+) was more stable (92% after 2 h) than [(67)Ga(RGD-2)](+) (73% after 2 h) in a transferrin challenge experiment. IC(50) values for both conjugates (H(2)RGD-1 and H(2)RGD-2) and nonconjugated RGD were determined in a cell-based competitive binding assay with (125)I-echistatin using U87MG cells, where enhanced specific binding was observed for the multivalent H(2)RGD-2 conjugate compared to the monovalent H(2)RGD-1 and nonconjugated cRGDyK. The U87MG cell line was also used to generate subcutaneous xenograft tumors on RAG2M mice, which were used to evaluate the in vivo properties of [(68)Ga(RGD-1)](+) and [(68)Ga(RGD-2)](+). After 2 h of dynamic imaging, both block and nonblock mice were sacrificed to collect select organs at the 2-h time point. Although the uptake is specific, as judged from the ratios of nonblock to block (2.36 with [(67)Ga(RGD-1)](+), 1.46 with [(67)Ga(RGD-2)](+)), both conjugates display high uptake in blood. We have successfully synthesized and applied the first bifunctional versions of H(2)dedpa for conjugation to a targeting vector and subsequent imaging of the corresponding conjugates.


Dynamical biomarkers in teams and other multiagent systems.
Effective team behavior in high-performance environments such as in sport and the military requires individual team members to efficiently perceive the unfolding task events, predict the actions and action intents of the other team members, and plan and execute their own actions to simultaneously accomplish individual and collective goals. To enhance team performance through effective cooperation, it is crucial to measure the situation awareness and dynamics of each team member and how they collectively impact the team's functioning. Further, to be practically useful for real-life settings, such measures must be easily obtainable from existing sensors. This paper presents several methodologies that can be used on positional and movement acceleration data of team members to quantify and/or predict team performance, assess situation awareness, and to help identify task-relevant information to support individual decision-making. Given the limited reporting of these methods within military cohorts, these methodologies are described using examples from team sports and teams training in virtual environments, with discussion as to how they can be applied to real-world military teams.


Prostaglandin D2 increases Cl secretion across canine tracheal epithelium through cyclo-oxygenase stimulation and cAMP production.
Prostaglandin (PG) D2 is one cyclo-oxygenase product of arachidonic acid metabolites that may play a role in the pathogenesis of asthma. To determine the effect of PGD2 on ion transport by airway epithelium and its mechanism of action, we measured bioelectric properties of canine cultured tracheal epithelium under short-circuit conditions in vitro. PGD2 (10(-7) M) increased short-circuit current (Isc) from 5.5 +/- 1.2 to 14.1 +/- 2.9 microA cm-2 (means +/- SE, P less than 0.01) when added to the mucosal solution, and to 22.2 +/- 3.8 microA cm-2 (P less than 0.001) when added to the submucosal solution, an effect that was accompanied by the corresponding increases in transepithelial potential difference and conductance. These effects were dose-dependent. The PGD2-induced increase in Isc was not altered by preincubation of cells with autonomic antagonists (phentolamine, propranolol, atropine), the lipoxygenase inhibitor AA-861, the protein kinase C inhibitor H-7, or the Na channel blocker amiloride, but it was inhibited by each of indomethacin, piroxicam, the Cl channel blocker diphenylamine-2-carboxylate, the Cl transport inhibitor furosemide, and Cl-free medium. Intracellular adenosine 3',5'-cyclic monophosphate (cAMP) levels were dose-dependently increased by PGD2. These results suggest that PGD2 may selectively stimulate airway epithelial Cl secretion via cyclo-oxygenase- and cAMP-dependent pathway.


Machine learning in cardiology: Clinical application and basic research.
Machine learning is a subfield of artificial intelligence. The quality and versatility of machine learning have been rapidly improving and playing a critical role in many aspects of social life. This trend is also observed in the medical field. Generally, there are three main types of machine learning: supervised, unsupervised, and reinforcement learning. Each type of learning is adequately selected for the purpose and type of data. In the field of medicine, various types of information are collected and used, and research using machine learning is becoming increasingly relevant. Many clinical studies are conducted using electronic health and medical records, including in the cardiovascular area. Machine learning has also been applied in basic research. Machine learning has been widely used for several types of data analysis, such as clustering of microarray analysis and RNA sequence analysis. Machine learning is essential for genome and multi-omics analyses. This review summarizes the recent advancements in the use of machine learning in clinical applications and basic cardiovascular research.


Ecological footprint model of heavy metal pollution in water environment based on the potential ecological risk index.
Social heavy metal pollution poses a significant threat to aquatic ecosystems. Heavy metals are easily adsorbed by sediments and have cumulative effects on aquatic organisms, which is different with the hypothesis of the conventional ecological footprint model that the pollutants are independently degraded by water bodies. To solve this problem, an ecological footprint for heavy metal pollution (EFHM) is constructed based on the potential ecological risk index (PERI). EFHM is defined as the sediment area to control the cumulative ecological risk of heavy metals within the allowable limit. And then, EFHM uses ecological footprint index (EFI) and ecological footprint contribution rate (EFCR) to quantify the hazard of social heavy metal load and recognize the key risk factor. EFHM is applied for assessing the heavy metal pollution of Central China. The results show that (i) the EFHM model can effectively evaluate the cumulative ecological hazards of heavy metals in sediment. (ii) The EFHM values of Central China in 2015 and 2020 are 20,764.56 and 17,358.59 km2, respectively. (iii) Compared with 2015, the EFI values of Hunan Province and Jiangxi Province in 2020 decrease from 1.53 to 0.87 to 1.23 and 0.39, respectively, both of which are improved by one grade. The EFI values of Hubei Province increases from 0.42 to 1.34, which is deteriorated by one grade. (iv) In 2020, both of the key risk factors of Hunan Province and Hubei Province are Hg, and the crucial hazard source of Jiangxi Province is Cd. (v) The mine pollution control in Central China should be further consolidated, and the wastewater treatment of electronics and machinery industries should be strengthened.


Patient Satisfaction After Femoral Arterial Access Site Closure Using the ExoSeal(®) Vascular Closure Device Compared to Manual Compression: A Prospective Intra-individual Comparative Study.
To intra-individually compare discomfort levels and patient satisfaction after arterial access closure using the ExoSeal(®) vascular closure device (VCD) and manual compression (MC) in a prospective study design. Patients undergoing two planned interventions from 07/2013 to 09/2014 could participate in the study. Access closure was performed with an ExoSeal(®)-VCD in one and MC in the other intervention. Patients were clinically and sonographically examined and were given questionnaires 1 day after intervention [groin- and back-pain during bedrest (100-point visual analog scale; 0: no pain); comfortability of bedrest (10-point Likert scale, 1: comfortable), satisfaction with closure (10-point Likert scale, 1: very satisfied)]. Results were analyzed in a cross-over design. 48 patients (29 male, median age 62.5 (32-88) years) were included. An ExoSeal(®)-VCD was used first in 25 cases. As four of these subsequently refused MC as second intervention, data from 44 patients could be analyzed. All closures were technically successful (successful device deployment) without major complications. Groin- and back-pain after VCD-use/MC was 0 (0-15) vs. 10 (0-80) and 0 (0-75) vs. 25 (0-90), respectively (p < 0.0001). Bedrest after VCD-use was more comfortable than after MC [1 (range 1-7) vs. 6 (2-10); p < 0.0001]. Satisfaction with the closure procedure and with the intervention in general was higher after VCD-use compared to MC [1 (1-3) vs. 5 (2-10) and 1 (1-2) vs. 2 (1-4), respectively; p < 0.0001]. Intra-individual comparison showed pain levels and discomfort to be significantly lower after ExoSeal(®) use compared to MC. VCD closure was associated with higher satisfaction both with the closure itself and with the intervention in general.


A statistical method for determining the proportions of gray matter, white matter, and CSF using computed tomography.
The brain may be considered as a collection of volume elements (voxels) containing unknown proportions of gray matter (GM), white matter (WM), and cerebrospinal fluid (CSF). If one assumes that (1) the attenuation coefficients for voxels with the same proportions of GM, WM, and CSF follow a Gaussian distribution whose mean is a weighted average of the mean attenuation coefficients of pure GM, WM, and CSF and (2) the voxel-to-voxel variation in proportion follows a Dirichlet probability distribution, then the overall proportions of GM, WM, and CSF can be calculated by optimizing the parameters of a compound Dirichlet-Gaussian distribution. This approach permits a quantitative analysis of the compartmental composition of the brain and may be useful in the evaluation of patients with cerebral edema, hydrocephalus, and leukoencephalopathy.


Effect of concomitant polyethylene glycol and celecoxib on colonic aberrant crypt foci and tumors in F344 rats.
We investigated whether celecoxib augments the protective effect of polyethylene glycol (PEG) on colonic aberrant crypt foci (ACF) and tumor formation in F344 rats treated with azoxymethane (AOM). Three groups of rats received AOM: I (AOM alone), II (PEG), and III (PEG/celecoxib). PEG reduced the mean number of total ACF per colon from 190 to 141 (P < 0.05; 26% reduction) and > or = 4-crypt ACF from 95 to 58 (P < 0.01; 39%). Group III rats had a greater proportion of their ACF distally; whereas transverse colon ACF were reduced approximately 50%, distal ACF were reduced by only approximately 8% (P < 0.05). Of 13 large bowel tumors, 8 were in Group I, 4 in Group II, and 1 in Group III rats (P = 0.02). Thus in AOM-treated rats celecoxib appeared to enhance the PEG-induced reduction in colonic tumor formation, and in transverse but not distal or whole-colon ACF.


Iatrogenic post-intubation tracheal rupture treated conservatively without intubation: a case report.
Tracheal rupture is a rare but life-threatening complication that most commonly occurrs after blunt trauma to the chest, but which may also complicate tracheal intubation. We report a case of post-intubation tracheal rupture after cataract surgery under general anesthesia treated conservatively. Four hours after extubation, a 67 year-old woman developed subcutaneous emphysema of the facial, bilateral laterocervical and upper anterior chest. Tracheobronchial fiberendoscopy showed a posterior tracheal transmural rupture 4 cm long located 2.5 cm above the carina that opened in inspiration. The location of the lesion and features of the patient favoured conservative treatment with antibiotic cover. The patient made a full and uncomplicated recovery and was discharged fourteen days after the original injury. Two therapeutic strategies are currently employed for post-intubation tracheal rupture: a non-surgical strategy for small injuries and a surgical strategy for larger injuries. This case report presented the non-surgical therapeutic strategy of a large tracheal injury.


The influence of ambient temperature, seed composition and body size on water balance and seed selection in coexisting heteromyid rodents.
The water balance of three different sized coexisting species of heteromyid rodents (Dipodomys merriami ca. 39 g;Perognathus fallax ca. 23 g;Perognathus longimembris ca. 9 g) was assessed while consuming two different diets (either wheat or hulled sunflower) at ambient temperatures of 15-30°C. The metabolism of wheat as the sole food source was calculated to provide a greater metabolic water production (MWP) than the consumption of sunflower seed because of their different composition. The state of water balance was assessed by measuring urine concentrations and body weight maintenance on each diet at each temperature. Both measures showed that (i) all species were able to maintain a more positive water on the higher MWP seed, (ii) for all species there was an ambient temperature above which water balance could no longer be maintained, (iii) that this temperature was higher with the higher MWP food source and (iv) water regulatory efficiency was negatively correlated with body mass.Dipodomys showed a reduced digestive efficiency compared toPerognathus. When presented with both seedsDipodomys showed no preference for either seed irrespective of the state of water balance whilst thePerognathus species showed a tendency for an increased preference for the high MWP food source at the higher ambient temperatures. The ecological implications of these findings are discussed.


Heavy metals in a typical city-river-reservoir system of East China: Multi-phase distribution, microbial response and ecological risk.
The rapid construction of artificial reservoirs in metropolises has promoted the emergence of city-river-reservoir systems worldwide. This study investigated the environmental behaviors and risks of heavy metals in the aquatic environment of a typical system composed of main watersheds in Suzhou and Jinze Reservoir in Shanghai. Results shown that Mn, Zn and Cu were the dominant metals detected in multiple phases. Cd, Mn and Zn were mainly presented in exchangeable fraction and exhibited high bioavailability. Great proportion and high mobility of metals were found in suspended particulate matter (SPM), suggesting that SPM can greatly affect metal multi-phase distribution process. Spatially, city system (CiS) exhibited more serious metal pollution and higher ecological risk than river system (RiS) and reservoir system (ReS) owing to the diverse emission sources. CiS and ReS were regarded as critical pollution source and sink, respectively, while RiS was a vital transportation aisle. Microbial community in sediments exhibited evident spatial variation and obviously modified by exchangeable metals and nutrients. In particular, Bacteroidetes and Firmicutes presented significant positive correlations with most exchangeable metals. Risk assessment implied that As, Sb and Ni in water may pose potential carcinogenic risk to human health. Nevertheless, ReS was in a fairly safe state. Hg was the main risk contributor in SPM, while Cu, Zn, Ni and Sb showed moderate risk in sediments. Overall, Hg, Sb and CiS were screened out as priority metals and system, respectively. More attention should be paid to these priority issues to promote the sustainable development of the watershed.


Short scales for measuring schizotypy.
This study reports short scales for measuring several dimensions of schizotypy in the normal population based on a large twin sample. The four short scales use items drawn from a longer instrument, the Oxford-Liverpool Inventory of Feelings and Experiences. Using concordance estimates from MZ and DZ pairs, the items were selected both to have a high heritability and to offer broad coverage of each trait domain. Preliminary descriptive statistics are reported for the short scales and suggest adequate reliability. New scales offer a time efficient and reliable method of studying proneness to psychosis in large N designs.


[New therapeutic approaches in the treatment of shock: hypertonic hyperoncotic solutions and vasopressin].
The extreme disturbance of hemodynamics in shock leads to a minimized oxygen delivery to several vital organs. If this state is not rapidly lifted, a multi-organ-failure can occur. In addition to the removal of the underlying causes, for example, bleeding or septic focus, measures must be started to stabilize hemodynamics. In most cases shock can be successfully treated with standard therapeutic interventions including the use of crystalloid or colloid solutions as well as the infusion of inotropes or vasopressors. Up to now, there is not enough evidence to show that hypertonic/hyperoncotic solutions are better for treating hypovolemic shock than standard infusions, other than in situations, where only an inadequate equipment is available. Experimental data support the use of vasopressin instead of fluid loading in case of uncontrolled intra-abdominal bleeding. According to these studies vasopressin seems to be associated with an improved hemodynamic stabilization and a significantly lower mortality rate. However, no clinical tests have been done so far to confirm these results. In septic shock the plasma-levels of vasopressin are low. It has been shown that the infusion of vasopressin contributes to stabilization of hemodynamics in septic shock, in lower, as well as in higher concentrations. On the other hand vasopressin worsens splanchnic perfusion. Therefore the routine use of vasopressin in the treatment of sepsis can not be recommended.


Primary extramedullary hematopoiesis manifesting as massive bilateral chylothorax.
Intrathoracic extramedullary hematopoiesis is a rare entity, mostly observed in patients with hematologic disorders. Extramedullary hematopoiesis is usually asymptomatic and is often located in the lower paravertebral sulci and rarely in the pleura. We report the case of a 54-year-old man without hematologic disorder or pleural malignancy who had a massive bilateral chylothorax develop due to primary pleural extramedullary hematopoiesis. He was successfully treated by bilateral video thoracoscopic talc pleurodesis and low-dose radiotherapy.


Magnetic nanomaterials for wireless thermal and mechanical neuromodulation.
Magnetic fields are very attractive for non-invasive neuromodulation because they easily penetrate trough the skull and tissue. Cell specific neuromodulation requires the magnetic field energy to be converted by an actuator to a biologically relevant signal. Miniaturized actuators available today range from small, isotropic magnetic nanoparticles to larger, submicron anisotropic magnetic nanomaterials. Depending on the parameters of external magnetic fields and the properties of the nanoactuators, they create either a thermal or a mechanical stimulus. Ferromagnetic nanomaterials generate heat in response to high frequency alternating magnetic fields associated with dissipative losses. Anisotropic nanomaterials with large magnetic moments are capable of exerting forces at stationary or slowly varying magnetic fields. These tools allow exploiting thermosensitive or mechanosensitive neurons in circuit or cell specific tetherless neuromodulation schemes. This review will address assortment of available magnetic nanomaterial-based neuromodulation techniques that rely on application of external magnetic fields.


The potential for tailored screening to reduce bowel cancer mortality for Aboriginal and Torres Strait Islander peoples in Australia: Modelling study.
Australian Aboriginal and Torres Strait Islander peoples experience health and socioeconomic disparities, including lower life-expectancy, have a younger mean age of colorectal cancer (CRC) diagnosis, and lower CRC survival than non-Indigenous Australians. The National Bowel Cancer Screening Program (NBCSP) provides biennial CRC screening for Australians aged 50-74 years to reduce the burden of CRC. The 2019 participation rate was 42% nationwide and 23% in Aboriginal and Torres Strait Islander peoples. For Aboriginal and Torres Strait Islander peoples, this study aims to estimate the health outcomes and cost-effectiveness of the current NBCSP and extensions to include people < 50 years. An existing microsimulation model, Policy1-Bowel, was adapted to the Aboriginal and Torres Strait Islander population and was used to evaluate three strategies assuming biennial iFOBT screening from 50-74, 45-74, or 40-74 years under two participation scenarios: 23% and 42% per screening round (psr.). At 23-42% participation psr., the current NBCSP was predicted to reduce lifetime CRC incidence and mortality by 14-24% and 23-39%, respectively, be cost-effective (incremental cost-effectiveness ratio <$13,000/life-year saved), and be associated with a benefits-and-burden balance of 51-53 number-needed-to-colonoscope (NNC) per CRC death prevented of . Lowering the screening start age to 40(45) would further reduce CRC incidence and CRC mortality by 7-11(4-5) percentage points, be cost-effective, and be associated with an incremental NNC- of > 95 (> 60). For Aboriginal and Torres Strait Islander peoples, the current NBCSP is cost-effective but participation is limited. Lowering the screening start age will further reduce CRC incidence and mortality. These findings highlight a need to increase NBCSP participation whilst exploring the feasibility and acceptability of lowering the NBCSP start age for Aboriginal and Torres Strait Islander peoples. These findings could inform new co-designed, community-led strategies to improve CRC outcomes for Aboriginal and Torres Strait Islander peoples.


Plasmapheresis for the Treatment of Acute Pancreatitis due to Severe Hypertriglyceridemia.
Severe hypertriglyceridemia (HTG) is associated with acute pancreatitis (AP). Treatment options include total plasma exchange (TPE). We report a case of AP due to severe HTG treated with TPE.


The evidence strength of a meta-analysis of aspirin for primary prevention of cancer.
Dr. Tarek Haykal et al. (145:1795-1809, 2019) reported a meta-analysis of aspirin for the primary prevention of cancer in individuals without known cancer. The authors found that aspirin use was not associated with significant reduction in cancer mortality or incidence, but with higher rates of bleeding. The findings of this study added some evidence to the clinical practice. However, several issues might have compromised the strength of the evidence of this systematic review. If the investigators could have further clarified the inclusion and exclusion criteria, included all eligible studies, extracted data more meticulously, and performed more necessary sensitivity analyses to confirm the robustness of their findings, the strength of evidence of this meta-analysis would have been stronger.


Fractures of the elbow.
Elbow fractures encompass a spectrum of severity from low energy nondisplaced fractures to high energy fractures with associated severe soft-tissue injury. Treatment is based on fracture pattern, patient age, bone quality, associated soft-tissue injuries, and associated fractures. The basis for treatment relies on the knowledge of the complex osseous and soft-tissue anatomy of the elbow. The goals of operative and nonoperative treatment are to achieve a stable, anatomic reduction that allows early motion to maximize function.


New strategies in the treatment of graft-versus-host disease.
GVHD continues to be a major complication after allogeneic hematopoietic stem cell transplantation even when the recipient is given immunosuppression for the prophylaxis of this severe disease. There have been many advances in the prevention and treatment of GVHD, using compounds such as cyclosporine, FK506, mycophenolate mofetil or monoclonal IL-2 receptor antagonist. New strategies seem to include sequential therapy involving the blocking of both endogenous cytokines and alloreactive donor cells. However, further clinical and laboratory studies are needed in order to improve the therapy of established GVHD.


Calculating numbers of tissue progenitor cells using chimaeric animals.
Experimental chimaeras have been used to estimate the number of tissue progenitors from the variation in the proportions of cells of each genotype that can be found in a given tissue. However, because of a failure to appreciate the importance of assessing the extent of agreement required between the predictions made by a specific mathematical model and the actual data, we believe that the statistical procedures were inappropriate and have led to unjustified conclusions. We illustrate our argument by reference to published data on the number of progenitor cells in the facial nerve nucleus of the mouse (K. Herrup, T. Diglio, A. Letsou, (1984). Dev. Biol. 103, 329-336).


Subproteomic analysis of the cellular proteins associated with the 3' untranslated region of the hepatitis C virus genome in human liver cells.
The 3' untranslated region (UTR) of the hepatitis C virus (HCV) is believed to function in the initiation and regulation of viral RNA replication and protein translation by interacting with the viral and host components. To examine host proteins interacting with the HCV 3'UTR, biotinylated 3'(+)UTR, and its reverse complementary 5'(-)UTR were used in RNA pull-down assay. Cellular proteins from Huh7 cells pulled down by biotinylated RNAs were identified by 2DE/MALDI-TOF MS and 1DE/LC/MS methods. Totally, 10 proteins could be identified from both methods, among which six bound specifically to the 3'(+)UTR, three proteins to the 5'(-)UTR only, and one protein bound to both. Three identified proteins (PCBP2, G3BP1, and DDX1) were selected for further investigation into their possible roles on the HCV replication. Differently regulating effects on HCV replication by siRNA-mediated silencing of these proteins were observed, indicating a complex role of 3'UTR binding proteins on HCV replication.


Stem cell population asymmetry can reduce rate of replicative aging.
Cycling tissues such as the intestinal epithelium, germ line, and hair follicles, require a constant flux of differentiated cells. These tissues are maintained by a population of stem cells, which generate differentiated progenies and self-renew. Asymmetric division of each stem cell into one stem cell and one differentiated cell can accomplish both tasks. However, in mammalian cycling tissues, some stem cells divide symmetrically into two differentiated cells and are replaced by a neighbor that divides symmetrically into two stem cells. Besides this heterogeneity in fate (population asymmetry), stem cells also exhibit heterogenous proliferation-rates; in the long run, however, all stem cells proliferate at the same average rate (equipotency). We construct and simulate a mathematical model based on these experimental observations. We show that the complex steady-state dynamics of population-asymmetric stem cells reduces the rate of replicative aging of the tissue-potentially lowering the incidence of somatic mutations and genetics diseases such as cancer. Essentially, slow-dividing stem cells proliferate and purge the population of the fast-dividing - older - cells which had undertaken the majority of the tissue-generation burden. As the number of slow-dividing cells grows, their cycling-rate increases, eventually turning them into fast-dividers, which are themselves replaced by newly emerging slow-dividers. Going beyond current experiments, we propose a mechanism for equipotency that can potentially halve the rate of replicative aging. Our results highlight the importance of a population-level understanding of stem cells, and may explain the prevalence of population asymmetry in a wide variety of cycling tissues.


Copper blocks quinolinic acid neurotoxicity in rats: contribution of antioxidant systems.
Reactive oxygen species and oxidative stress are involved in quinolinic acid (QUIN)-induced neurotoxicity. QUIN, a N-methyl-D-aspartate receptor (NMDAr) agonist and prooxidant molecule, produces NMDAr overactivation, excitotoxic events, and direct reactive oxygen species formation. Copper is an essential metal exhibiting both modulatory effects on neuronal excitatory activity and antioxidant properties. To investigate whether this metal is able to counteract the neurotoxic and oxidative actions of QUIN, we administered copper (as CuSO(4)) intraperitoneally to rats (2.5, 5.0, 7.5, and 10.0 mg/kg) 30 min before the striatal infusion of 1 microliter of QUIN (240 nmol). A 5.0 mg/kg CuSO(4) dose significantly increased the copper content in the striatum, reduced the neurotoxicity measured both as circling behavior and striatal gamma-aminobutyric acid (GABA) depletion, and blocked the oxidative injury evaluated as striatal lipid peroxidation (LP). In addition, copper reduced the QUIN-induced decreased striatal activity of Cu,Zn-dependent superoxide dismutase, and increased the ferroxidase activity of ceruloplasmin in cerebrospinal fluid from QUIN-treated rats. However, copper also produced significant increases of plasma lactate dehydrogenase activity and mortality at the highest doses employed (7.5 and 10.0 mg/kg). These results show that at low doses, copper exerts a protective effect on in vivo QUIN neurotoxicity.


The limbic system and aggression in humans.
This paper reviews the clinical literature relevant to the association between aggressive behavior and the limbic system in humans. Specific areas of review include aggressive behavior related to: (1) naturally occurring and iatrogenic brain lesions; (2) electrical disturbances; (3) pharmacologic intervention; and (4) central neurochemical concentrations which may implicate limbic lobe involvement.


Screening for sexually transmitted infections.
The high prevalence of STI in many developed countries; their costly physical, psychological, and relationship sequelae; and their association with the acquisition and transmission of HIV necessitate the introduction of screening programs, especially those that encourage opportunistic screening in diverse health care and community settings. This requirement is accompanied by the need for better awareness and education of health care professionals, especially those working in primary care or in sexual health disciplines, and knowledge of local prevalence and other epidemiologic factors to allow cost-effective targeting of high-risk groups. Such programs should be accompanied by the development of effective clinical alliances between those undertaking screening, the diagnostic microbiology laboratories, and clinicians with local responsibility for case management and public health control. The development of new molecular methods of diagnosis for the common bacterial STI permits screening in the community to be extended. This will help detect those asymptomatic persons who would not otherwise access health services but who may act as important vectors in STI spread and who continue to maintain local reservoirs.


Long-term antipsychotic use and brain changes in schizophrenia - a systematic review and meta-analysis.
The association between long-term antipsychotic treatment and changes in brain structure in schizophrenia is unclear. Our aim was to conduct a systematic review and a meta-analysis on long-term antipsychotic effects on brain structures in schizophrenia focusing on studies with at least 2 years of follow-up between MRI scans. Studies were systematically collected using 4 databases, and we also contacted authors for unpublished data. We calculated correlations between antipsychotic dose and/or type and brain volumetric changes and used random effect meta-analysis to study correlations by brain area. Thirty-one publications from 16 samples fulfilled our inclusion criteria. In meta-analysis, higher antipsychotic exposure associated statistically significantly with parietal lobe decrease (studies, n = 4; r = -.14, p = .013) and with basal ganglia increase (n = 4; r = .10, p = .044). Most of the reported correlations in the original studies were statistically nonsignificant. There were no clear differences between typical and atypical exposure and brain volume change. The studies were often small and highly heterogeneous in their methods and seldom focused on antipsychotic medication and brain changes as the main subject. Antipsychotic medication may associate with brain structure changes. More long-term follow-up studies taking into account illness severity measures are needed to make definitive conclusions.


Facial fracture classification according to skeletal support mechanisms.
To construct, propose, and evaluate the usefulness of a new clinical facial fracture classification scheme to accurately denote, communicate, and compare facial fractures. A retrospective, consecutive sample study with application of the proposed classification scheme to denote maxillary and zygomatic fractures with computed tomography. Metropolitan tertiary care trauma center. A total of 213 consecutive adult patients with facial fractures evaluated by means of 2-dimensional computed tomography. The classification scheme is defined according to fractures of vertical buttresses and horizontal beams. The scheme uses 3 primary descriptors of laterality and support sites to denote the clinical pattern of the fractures. This scheme was accurately applied and sufficient to describe 87 midfacial fracture patterns in this study. In addition, 118 (98%) of 120 mock fracture patterns were correctly transcribed and reproducibly communicated among 12 participating physicians. This newly proposed facial fracture classification scheme provides a convenient, specific, descriptive, and reproducible method of denoting fracture patterns. This scheme may be used to accurately communicate and compare, in greater detail than permitted using current independent classification schemes, the essential site and degree-of-severity characteristics of facial fractures critical to their surgical reduction and reconstruction. The usefulness of this classification scheme in determining optimal methods and subsequent outcomes in midfacial fracture reduction requires further investigation.


Interplay of gene expression and regulators under salinity stress in gill of Labeo rohita.
Labeo rohita is the most preferred freshwater carp species in India. The concern of increasing salinity concentration in freshwater bodies due to climate change may greatly impact the aquatic environment. Gills are one of the important osmoregulatory organs and have direct contact with external environment. Hence, the current study is conducted to understand the gill transcriptomic response of L. rohita under hypersalinity environment. Comprehensive analysis of differentially expressed long non-coding RNAs (lncRNAs), microRNAs (miRNAs) and mRNAs was performed in gills of L. rohita treated with 2, 4, 6 and 8ppt salinity concentrations. Networks of lncRNA-miRNA-mRNA revealed involvement of 20, 33, 52 and 61 differentially expressed lncRNAs, 11, 13, 26 and 21 differentially expressed miRNAs in 2, 4, 6 and 8ppt groups between control and treatment respectively. These lncRNA-miRNA pairs were regulating 87, 214, 499 and 435 differentially expressed mRNAs (DE mRNAs) in 2, 4, 6 and 8ppt treatments respectively. Functional analysis of these genes showed enrichment in pathways related to ion transportation and osmolyte production to cope with induced osmotic pressure due to high salt concentration. Pathways related to signal transduction (MAPK, FOXO and phosphatidylinositol signaling), and environmental information processing were also upregulated under hypersalinity. Energy metabolism and innate immune response pathways also appear to be regulated. Protein turnover was high at 8ppt as evidenced by enrichment of the proteasome and aminoacyl tRNA synthesis pathways, along with other enriched KEGG terms such as apoptosis, cellular senescence and cell cycle. Altogether, the RNA-seq analysis provided valuable insights into competitive endogenous (lncRNA-miRNA-mRNA) regulatory network of L. rohita under salinity stress. L. rohita is adapting to the salinity stress by means of upregulating protein turnover, osmolyte production and removing the damaged cells using apoptotic pathway and regulating the cell growth and hence diverting the essential energy for coping with salinity stress.


Glycemic control is not associated with neurocognitive decline after cardiac surgery.
Whether perioperative glycemic control is associated with neurocognitive decline (NCD) after cardiac surgery was examined. Thirty patients undergoing cardiac surgery utilizing cardiopulmonary bypass (CPB) were screened for NCD preoperatively and on postoperative day 4 (POD4). Indices of glucose control were examined. Serum cytokine levels were measured and human transcriptome analysis was performed on blood samples. Neurocognitive data are presented as a change from baseline to POD4 in a score standardized with respect to age and gender. A decline in neurocognitive function was identified in 73% (22/30) of patients on POD4. There was no difference in neurocognitive function between patients with elevated HbA1c levels preoperatively (p = .973) or elevated fasting blood glucose levels the morning of surgery (>126 mg/dl, p = .910), or a higher maximum blood glucose levels during CPB (>180 mg/dl, p = .252), or higher average glucose levels during CPB (>160 mg/dl, p = .639). Patients with postoperative leukocytosis (WBC ≥ 10.5) had more NCD when compared to their baseline function (p = .03). Patients with elevated IL-8 levels at 6 h postoperatively had a significant decline in NCD at POD4 (p = .04). Human transcriptome analysis demonstrated unique and differential patterns of gene expression in patients depending on the presence of DM and NCD. Perioperative glycemic control does not have an effect on NCD soon after cardiac surgery. The profile of gene expression was altered in patients with NCD with or without diabetes.


Lymphocyte function and response to chemo-immunotherapy in patients with metastatic melanoma.
Thirty-eight patients with metastatic melanoma were investigated for lymphocyte function immediately prior to chemo-immunotherapy. The pre-treatment immune tests were compared with normal control values and with response to therapy. The "non-responder" group (but not "responder") had significantly reduced values for lymphocyte, null-cell and E-rosette-cell counts compared with controls. Lymphocytoxicity ( using a Chang target cell) showed the same pattern, with depression of direct and K-cell cytotoxic capacity in non-responders compared with controls. Eight patients were studied sequentially whilst on treatment, and demonstrated considerable change (not statistically significant) in lymphocytotoxicity, an untreated "control" patient showed little variation. "Recall"-antigen skin testing showed no statistically significant difference between the patient groups. The data indicate that "non-T-cell activity" may be associated with response to chemo-immunotherapy.


Reciprocal regulation of NO signaling and TXNIP expression in humans: impact of aging and ramipril therapy.
Impaired tissue responsiveness to nitric oxide (NO) occurs in many cardiovascular diseases as well as with advanced age and is a correlate of poor outcomes. This phenomenon results from oxidative stress, with NO "scavenging" and dysfunction of soluble guanylate cyclase (sGC). Thioredoxin-interacting protein (TXNIP) is a major intracellular regulator of inflammatory activation and redox stress, but its interactions with NO/sGC are poorly understood. We have now evaluated the relationship between platelet TXNIP expression and function of the NO/sGC axis in subjects of varying age and during therapy with ramipril. Young (n=42) and aging (n=49) subjects underwent evaluation of platelet TXNIP content. Aging subjects additionally had measurements of platelet NO responsiveness and routine biochemistry. Platelet TXNIP content was greater (376±33 units) in the aging compared to younger subjects (289±13 units; p<0.05). In the aging subjects there was a significant negative correlation (r=-0.50, p<0.001) between platelet TXNIP content and NO responsiveness. In a separate cohort of 15 subjects two week treatment with ramipril, which reversed platelet NO resistance and potentiated sGC activity, also decreased platelet TXNIP content by 40% (p=0.011). Platelet TXNIP content increases with aging, varies inversely with responsiveness to NO, and diminishes rapidly following treatment with ramipril. These data suggest that TXNIP-induced oxidative stress may be a critical modulator of tissue resistance to NO, a fundamental basis for cardiovascular disease. Analogously suppression of TXNIP expression can potentially be utilized as an index of restoration of cardiovascular homeostasis.


Possibilities for Sociological Research to Reduce Inequalities: Observations from the Immigration Scholarship.
This commentary brings immigration research to the conversation on sociology's possibilities to respond to inequality. It argues that legal status today has become an important dimension of inequality given its enduring impact across most areas of life and effects that extend laterally to all members of a family and across generations. The piece highlights the possibilities for sociologists to contribute to policy discussions but also the limitations of research in policy spaces given the antiscience resistance in the sociopolitical context today.