Hip joint centre position estimation using a dual unscented Kalman filter for computer-assisted orthopaedic surgery.
In computer-assisted knee surgery, the accuracy of the localization of the femur centre of rotation relative to the hip-bone (hip joint centre) is affected by the unavoidable and untracked pelvic movements because only the femoral pose is acquired during passive pivoting manoeuvres. We present a dual unscented Kalman filter algorithm that allows the estimation of the hip joint centre also using as input the position of a pelvic reference point that can be acquired with a skin marker placed on the hip, without increasing the invasiveness of the surgical procedure. A comparative assessment of the algorithm was carried out using data provided by in vitro experiments mimicking in vivo surgical conditions. Soft tissue artefacts were simulated and superimposed onto the position of a pelvic landmark. Femoral pivoting made of a sequence of star-like quasi-planar movements followed by a circumduction was performed. The dual unscented Kalman filter method proved to be less sensitive to pelvic displacements, which were shown to be larger during the manoeuvres in which the femur was more adducted. Comparable accuracy between all the analysed methods resulted for hip joint centre displacements smaller than 1 mm (error: 2.2 ± [0.2; 0.3] mm, median ± [inter-quartile range 25%; inter-quartile range 75%]) and between 1 and 6 mm (error: 4.8 ± [0.5; 0.8] mm) during planar movements. When the hip joint centre displacement exceeded 6 mm, the dual unscented Kalman filter proved to be more accurate than the other methods by 30% during multi-planar movements (error: 5.2 ± [1.2; 1] mm).


Utilization of immediate post-partum long acting reversible contraceptives and its associated factors among mothers who gave birth in Addis Ababa public hospitals, Ethiopia: An institutional based cross-sectional study.
An immediate postpartum period is a good opportunity to utilize immediate postpartum long-acting reversible contraceptives for women whom they want to delay pregnancy. Long-acting reversible contraceptive methods like intrauterine device, Jaddel and implants can improve maternal and newborn health by preventing unintended pregnancy. Despite on their advantage, evidence on its utilization and associated factors is limited in our study area.Ethiopia. This study assessed the utilization of immediate postpartum long acting reversible contraceptives and its associated factors among mothers who delivered in selected public hospitals of Addis Ababa, Ethiopia, 2022. An institutional-based cross-sectional study design was conducted among 420 study participants to assess the immediate postpartum long-acting reversible contraceptive utilization and its associated factors from August 30- September 25, 2022. Systematic sampling technique was used to select study participants. Data was entered into epi-data version 4.6 and analysis was performed by using SPSS version 25. Descriptive statistics and logistic regression were used. All statistical tests were significant at P-value < 0.05. A total of 417 postpartum women were participated in the study making a response rate of 99.3%. Of the total study participants, 30.7% [95% CI (26.1, 35.3)] utilized immediate postpartum family planning. Women at the age of 25-34 years (AOR = 3.228[95% CI: 1.140-9.136]), had discussion with their partners about family planning (AOR = 1.891[95% CI: 1.003, 3.565]), received counseling about immediate post-partum long acting reversible contraceptive (AOR = 3.146 [95% CI: 1.489, 6.647]), had positive attitude towards immediate post postpartum long acting reversible contraceptive (AOR = 3 [95% CI: 1.770-5.648]) were associated with utilization of immediate post-partum long acting reversible contraceptive. Almost one in three women delivering in health facilities of Addis Ababa Ethiopia started using immediate post-partum long acting reversible contraceptives. Discussion about contraception with partners, getting counseling about family planning on antenatal care, attitude toward contraception and the age of women were all factors that could increase IPPLARC uptake. Healthcare providers clarify any rumors about contraceptives to assure a positive and supportive attitude to increase its uptake.


Complex effects of melatonin on human circadian rhythms in constant dim light.
In humans, the pineal hormone melatonin can phase shift a number of circadian rhythms (e.g., "fatigue", endogenous melatonin, core body temperature) together with the timing of prolactin secretion. It is uncertain, however, whether melatonin can fully entrain all human circadian rhythms. In this study, the authors investigated the effects of daily melatonin administration on sighted individuals kept in continuous very dim light. A total of 10 normal, healthy males were maintained in two separate groups in partial temporal isolation under constant dim light (< 8 lux) with attenuated sound and ambient temperature variations but with knowledge of clock time for two periods of 30 days. In these circumstances, the majority of individuals free run with a mean period of 24.3 h. In a double-blind, randomized crossover design, subjects received 5 mg melatonin at 20:00 h on Days 1 to 15 (Melatonin 1st) followed by placebo on Days 16 to 30 (Placebo 2nd) or vice versa (Placebo 1st, Melatonin 2nd) during Leg 1 with treatment reversed in Leg 2. The variables measured were melatonin (as 6-sulphatoxymelatonin), rectal temperature, activity, and sleep (actigraphy and logs). In the experiment, 9 of the 10 subjects free ran with Placebo 1st, whereas Melatonin 1st stabilized the sleep-wake cycle to 24 h in 8 of 10 individuals. In addition, 2 individuals showed irregular sleep with this treatment. In some subjects, there was a shortening of the period of the temperature rhythm without synchronization. Melatonin 2nd induced phase advances (5 of 9 subjects), phase delays (2 of 9 subjects), and stabilization (2 of 9 subjects) of the sleep-wake cycle with subsequent synchronization to 24 h in the majority of individuals (7 of 9). Temperature continued to free run in 4 subjects. Maximum phase advances in core temperature were seen when the first melatonin treatment was given approximately 2 h after the temperature acrophase. These results indicate that melatonin was able to phase shift sleep and core temperature but was unable to synchronize core temperature consistently. In the majority of subjects, the sleep-wake cycle could be synchronized.


Differential contribution of testosterone and estradiol in the determination of cholesterol and lipoprotein profile in healthy middle-aged men.
The role of endogenous sex steroids in the association between male gender and cardiovascular risk remains unclear. We performed a cross-sectional analysis of the role of endogenous testosterone (T) and estradiol (E2), as well as their respective biologically active fractions, in the determination of lipids and lipoproteins in an occupation-based cohort of 715 healthy middle-aged men. Serum T, sex hormone binding globulin (SHBG) and E(2) were measured by immunoassays; free T (FT) and free E2 (FE2) were calculated using a validated equation. Serum total cholesterol (Chol), HDL-cholesterol (HDL-Chol), apolipoproteins A1 (ApoA1), B (ApoB), E (ApoE), ApoE phenotype, lipoprotein a (Lpa), fibrinogen, C-reactive protein (CRP), systolic (SBP) and diastolic blood pressure (DBP) were assessed. Serum levels of T and FT, correlated positively with HDL-Chol and ApoA1 with Spearman correlation coefficients, partialised for age and body mass index (BMI), ranging between 0.14 and 0.17 (P<0.001); FT was associated with total Chol and ApoB levels (r=0.12 for both T and FT; P<0.01). After adjustment for age and BMI, both serum E2 and FE2 levels correlated significantly with ApoE (r=0.25 and r=0.26 for E2 and FE2, respectively; P<0.001). Free and total E2 were associated with both SBP and DBP with correlation coefficients partialised for age and BMI ranging between 0.11 and 0.13 (P<0.01). No correlation was found between any of the studied sex steroids, fibrinogen, Lpa or CRP. In multiple linear regression analyses, T was the most important independent hormonal determinant of HDL-Chol levels, when E2, SHBG and exogenous factors were considered in the model (P<0.01), whereas E2 contributed mostly in the determination of ApoE levels (P<0.001) and SBP (P<0.01). When FT and FE2 were considered in multivariate analyses as independent hormonal variables, FT was the most significant predictor of HDL-Chol (P<0.01) and ApoB (P<0.01) concentrations. Moreover, in the same multivariate model, ApoE (P<0.001) concentration as well as SBP (P<0.001) was most affected by FE2 levels in comparison with FT. In conclusion, our findings do suggest a differential role of T and E2 in the determination of traditional cardiovascular risk factors in healthy middle-aged men. In the determination of both HDL-Chol and ApoB levels endogenous (F)T may be involved, whereas (F)E2 may contribute to the determination of ApoE levels in this study group of 715 healthy middle-aged men. Regarding the observational design of the study, the physiological relationship of the observed associations between sex steroids and cardiovascular risk factors remains to be unravelled.


Involvement of environmentally relevant toxic metal mixture in Alzheimer's disease pathway alteration and protective role of berberine: Bioinformatics analysis and toxicogenomic screening.
We aimed to examine the molecular basis of the positive effect of berberine against environmentally relevant toxic metal-linked Alzheimer's disease (AD). The Comparative Toxicogenomic Database (CTD) retrieved a set of genes common to lead, cadmium, methylmercury and arsenic linked to AD development and a set of genes through which berberine exerts a therapeutic mode of action in AD. GeneMania prediction server revealed detailed gene interactions, while Metascape highlighted protein-protein interaction enrichment (PPIE). SwissADME evaluated physicochemical properties of berberine. Berberine had an antagonistic effect for the majority of genes mutual for AD and toxic metal mixture: ACHE, APP, BAX, BCL2, CASP3, HMOX1, IL1B, MAPT, SOD2, TNF. Gene network analysis revealed interactions predicted by the server (45.29%) and physical interactions (18.39%) as the most important. Enriched biological processes analysis showed apoptotic signaling pathway, positive regulation of organelle organization and response to oxidative stress as dominant pathways involved in berberine protective effects against toxic metal mixture, while PPIE analysis showed regulation of apoptotic signaling pathway as the main gene ontology process targeted by berberine. Physicochemical properties and pharmacokinetics of berberine are in concordance with its beneficial properties in AD due to the high gastrointestinal absorption and capability to pass the blood-brain barrier.


Simultaneous Activation of Iron- and Thiol-Based Sensor-Regulator Systems by Redox-Active Compounds.
Bacteria in natural habitats are exposed to myriad redox-active compounds (RACs), which include producers of reactive oxygen species (ROS) and reactive electrophile species (RES) that alkylate or oxidize thiols. RACs can induce oxidative stress in cells and activate response pathways by modulating the activity of sensitive regulators. However, the effect of a certain compound on the cell has been investigated primarily with respect to a specific regulatory pathway. Since a single compound can exert multiple chemical effects in the cell, its effect can be better understood by time-course monitoring of multiple sensitive regulatory pathways that the compound induces. We investigated the effect of representative RACs by monitoring the activity of three sensor-regulators in the model actinobacterium Streptomyces coelicolor; SoxR that senses reactive compounds directly through oxidation of its [2Fe-2S] cluster, CatR/PerR that senses peroxides through bound iron, and an anti-sigma factor RsrA that senses RES via disulfide formation. The time course and magnitude of induction of their target transcripts were monitored to predict the chemical activities of each compound in S. coelicolor. Phenazine methosulfate (PMS) was found to be an effective RAC that directly activated SoxR and an effective ROS-producer that induced CatR/PerR with little thiol-perturbing activity. p-Benzoquinone was an effective RAC that directly activated SoxR, with slower ROS-producing activity, and an effective RES that induced the RsrA-SigR system. Plumbagin was an effective RAC that activated SoxR, an effective ROS-producer, and a less agile but effective RES. Diamide was an RES that effectively formed disulfides and a weak RAC that activated SoxR. Monobromobimane was a moderately effective RES and a slow producer of ROS. Interestingly, benzoquinone induced the SigR system by forming adducts on cysteine thiols in RsrA, revealing a new pathway to modulate RsrA activity. Overall, this study showed that multiple chemical activities of a reactive compound can be conveniently monitored in vivo by examining the temporal response of multiple sensitive regulators in the cell to reveal novel activities of the chemicals.


Simultaneous electrochemical sensing of heavy metal ions based on a g-C3N4/CNT/NH2-MIL-88(Fe) nanocomposite.
The presence of Cd2+, Pb2+, Cu2+ and Hg2+ in drinking-water can be harmful to human health, even if their concentration is fairly low. Hence, it is significant to detect these heavy metal ions in sewage to evaluate the quality of water. Herein, amino-functionalized metal-organic frameworks (NH2-MIL-88(Fe)) embedded with graphitic carbon nitride (g-C3N4) nanosheets and acid-functionalized carbon nanotubes were prepared via a one-pot synthesis. The composite can be directly modified on the surface of glass carbon electrodes without the assistance of Nafion or other binders. The modified glass carbon electrodes can be used to simultaneously detect Cd2+, Pb2+, Cu2+ and Hg2+ in water via square wave stripping voltammetry. The doping of g-C3N4 in the composite, rich in N-containing functional groups, participates in the adsorption of metal ions on the surface of the electrodes. The porous composite provides accommodation room for metals generated by electro-reduction. The detection limit for Cd2+, Pb2+, Cu2+ and Hg2+ is 39.6 nM, 7.6 nM, 11.9 nM, and 9.6 nM, respectively. And the sensitivity for Cd2+, Pb2+, Cu2+ and Hg2+ is 0.0789 mA μM-1 cm-2, 0.4122 mA μM-1 cm-2, 0.2616 mA μM-1 cm-2, and 0.3251 mA μM-1 cm-2, respectively. This work not only enriches the functional design of Fe-MOF materials, but also develops a method for the determination of metal ions using the adsorption sites in g-C3N4.


Self-related health, physical activity, BMI and musculoskeletal complaints: a comparison between foreign and Swedish high school students.
Physical activities during leisure time and school hours as well as nutritional habits have changed over the past years by adolescents being less physically active and adopting a sedentary life-style. The aim of the present study was to investigate possible differences between foreign and Swedish high school students in terms of self-related health, physical activity, overweight, and possible complaints from the musculoskeletal system. 1,090 high school students, 450 with foreign background and 640 with Swedish background, aged 16-26 years answered a questionnaire. A higher percentage of students with foreign background reported poor self-related health compared with students with Swedish background (p = .038). Students with a foreign background were to a greater extent less physically active than students of Swedish background (p = .003). No differences were found between the groups regarding musculoskeletal complaints. Students with foreign background were more often overweight than students with Swedish background and overweight was more frequent among males than females. Physical activity (moderate and high level) was concluded to be a factor with significant positive effect on self-related general health (moderate level p = .042, high level (p < .001), and musculoskeletal complaints were negative factors on self-related general health (p < .001). The results suggest that adolescents with foreign background should participate in physical activity to prevent overweight and thereby improve physical health.


Microglia in degenerative neurological disease.
Microglia express many leukocyte surface antigens which are upregulated in such chronic degenerative neurological diseases as Alzheimer's disease (AD) and amyotrophic lateral sclerosis (ALS). These surface antigens include leukocyte common antigen, immunoglobulin Fc receptors, MHC class I and class II glycoproteins, beta 2-integrins, and the vitronectin receptor. Ligands for these receptors are also found. They include immunoglobulins, complement proteins of the classical pathway, T lymphocytes of the cytotoxic/suppressor and helper/inducer classes, and vitronectin. T lymphocytes marginate along capillary venules, with some penetrating into the tissue matrix. Immunoglobulins and complement proteins are synthesized locally in brain, although they may also come from the bloodstream if the blood-brain barrier is compromised. The membrane attack complex, which is formed from C5b-9, the terminal components of complement, has been identified in AD and multiple sclerosis brain tissue. In addition, proteins designed to defend against bystander lysis caused by the membrane attack complex, including protectin, C8 binding protein, clusterin, and vitronectin, are associated with damaged neuronal processes in AD. Autodestruction may play a prominent part in these 2 diseases.


[Homesickness, immigration, and the construction of a Portuguese foreign community].
"Based on ethnohistorical research (1910-1990) conducted in New Bedford, an industrial town of New England, U.S.A., this paper is directed at unveiling an apparent paradox: on the one hand, the analysis of domestic structures indicated that there has been since the late 1970's both an intensification of old and the emergence of new forms of transnationalism among [New Bedford's] Portuguese families; and, on the other hand, the observation of grass-roots 'community events' sugggested a simultaneous and progressive increase of ethnic insularity." (SUMMARY IN ENG)


3D angiography. Clinical interest. First applications in interventional neuroradiology.
3D angiography is a true technical revolution that allows improvement in the quality and safety of diagnostic and endovascular treatment procedures. 3D angiography images are obtained by reconstruction of a rotational angiography acquisition done on a C-arm (GE Medical Systems) spinning at 40 degrees per second. The carotid or vertebral selective injection of a total of 15 ml of non-ionic contrast media at 3 ml/sec over 5 seconds allows the selection of the "arterial phase". Four hundred sixty 3D angiographic studies were performed from December 1996 to September 1998 on 260 patients and have been analyzed in MIP (Maximum Intensity Projection) and SSD (Shaded Surface Display) views. The exploration of intracranial aneurysms is simplified and only requires, for each vascular axis, a biplane PA and Lateral run followed by a single rotational angiography run. The 3D angiography image is available on the workstation's screen (Advantage Workstation 3.1, GE Medical Systems) in less than 10 minutes after the acquisition of the rotational run. It therefore allows one to analyze, during the intervention, the aneurysm's angioarchitecture, in particular the neck, and select the best therapeutic technique. When endovascular treatment is the best indication, 3D angiography allows one to define the optimal angle of view and accurately select the microcoils dimensions. 3D angiography replaces the multiple oblique views that used to be required to analyze the complex aneurysms and therefore allows a reduction of the total contrast medium quantity, the patient X-ray dose and the length of the intervention time which is a safety factor. Also, in particular for complex cases, it brings additional elements complementing the results of standard 2D DSA and rotational angiograms. In the cervical vascular pathology, 3D angiography allows for a better assessment of the stenosis level and of dissection lesions. Our current research activities focus on the matching without stereotactic frame between 3D X-ray angiography and volumetric MR acquisition, which should allow us to improve the treatment of intracerebral arterio-venous malformations (AVMs).


The small bowel enema: a ten year review.
In a retrospective study the radiological reports of small bowel enema (enteroclysis) examinations of 1465 patients were reviewed and compared with the subsequent clinical outcome, and where possible with findings at laparotomy. A sensitivity of 93.1% and a specificity of 96.9% was found, based on whether the small intestine was reported as normal or an abnormality was diagnosed to account for the patient's clinical presentation. The correct specific diagnosis was made in 67.5% of the examinations that were considered abnormal. We believe that these figures support the use of small bowel enema as the routine barium examination for suspected disorders of the small intestine.


[Antiandrogen withdrawal syndrome in the hormonal treatment of metastatic prostatic cancer in hormonal escape].
A fall in the PSA level after stopping antiandrogens has been described at the stage of hormonal escape of prostatic cancer treated by complete androgen inhibition. The authors report a new case. The patient was offtially treated by pulpectomy and nitulamide for N+ prostatic carcinoma (PSA: 165 ng/ml). At the stage of hormonal escape, discontinuation of nitulamide induced a reduction of the PSA. Replacement of nitulamide by cytoproterone acetate was followed by a renewed increase of PSA, which again decreased after stomming cyproterone acetate. Three years later, the PSDA level was 3.5 ng/mg. This syndrome is probably due to mutation of the androgen receptor. In hormonal escape, suspension of all antiandrogens apart from LHRH analogues is recommended and can be followed by a temporary fall of PSA. No other antiandrogen must be administered in the place of the previous drug.


Effects of alpha-tocopherol and beta-carotene supplements on cancer incidence in the Alpha-Tocopherol Beta-Carotene Cancer Prevention Study.
The Alpha-Tocopherol Beta-Carotene (ATBC) Cancer Prevention Study was a placebo-controlled, randomized intervention trial testing the hypothesis that beta-carotene and alpha-tocopherol (vitamin E) supplements prevent lung and other cancers. The study is predicated on a substantial body of evidence supporting a role in cancer prevention for these micronutrients. Based on the 2 x 2 factorial study design, 29,133 eligible male cigarette smokers aged 50-69 y were randomly assigned to receive beta-carotene (20 mg), alpha-tocopherol (50 mg), beta-carotene and alpha-tocopherol, or placebo daily for 5-8 y. Capsule compliance was high (median = 99%). beta-Carotene treatment did not result in a decrease in cancer at any of the major sites but rather in an increase at several sites, most notably lung, prostate, and stomach (number of cases 474 compared with 402, 138 compared with 112, and 70 compared with 56, respectively). The vitamin E group had fewer incident cancers of the prostate and colorectum compared with the group not receiving vitamin E (number of cases 99 compared with 151 and 68 compared with 81, respectively), but more cancers of the stomach (70 compared with 56). In contrast to these intervention-based findings for beta-carotene and vitamin E supplements, we observed lower lung cancer rates in men with higher amounts of both serum and dietary beta-carotene and vitamin E at baseline.


Association between adverse experiences during Hurricane María and mental and emotional distress among adults in Puerto Rico.
To evaluate the association between adverse experiences during Hurricane María and mental and emotional distress in Puerto Rico. This cross-sectional study used baseline data from adult (30-75 years) participants of the Puerto Rico Observational Study of Psychosocial, Environmental, and Chronic Disease Trends (PROSPECT). Enrolled individuals prior to COVID-19 who completed a 33-item questionnaire on Hurricane María-related experiences (sub-categorized as personal, service, or property losses), depression symptomatology, post-traumatic stress disorder (PTSD), and anxiety were included for analysis (n = 456). Most participants experienced fear for their family's safety, damage to their home and personal items, communication outages, and water shortages. Each additional stressor was significantly associated with higher odds of depression symptoms, PTSD, and anxiety. Personal losses were significantly associated with higher likelihood of all outcomes, while services losses were associated with depression symptoms and anxiety; property loss was not significantly associated with any outcome. Adverse experiences during a major natural disaster are associated with mental and emotional distress. Strategies to minimize hardships during natural disasters, especially personal and service losses, are essential to preserve mental health. Post-disaster psychological support to individuals is crucial.


Efficacy of recombinant human erythropoietin in critically ill patients: a randomized controlled trial.
Anemia is common in critically ill patients and results in a large number of red blood cell (RBC) transfusions. Recent data have raised the concern that RBC transfusions may be associated with worse clinical outcomes in some patients. To assess the efficacy in critically ill patients of a weekly dosing schedule of recombinant human erythropoietin (rHuEPO) to decrease the occurrence of RBC transfusion. A prospective, randomized, double-blind, placebo-controlled, multicenter trial conducted between December 1998 and June 2001. A medical, surgical, or a medical/surgical intensive care unit (ICU) in each of 65 participating institutions in the United States. A total of 1302 patients who had been in the ICU for 2 days and were expected to be in the ICU at least 2 more days and who met eligibility criteria were enrolled in the study; 650 patients were randomized to rHuEPO and 652 to placebo. Study drug (40 000 units of rHuEPO) or placebo was administered by subcutaneous injection on ICU day 3 and continued weekly for patients who remained in the hospital, for a total of 3 doses. Patients in the ICU on study day 21 received a fourth dose. The primary efficacy end point was transfusion independence, assessed by comparing the percentage of patients in each treatment group who received any RBC transfusion between study days 1 and 28. Secondary efficacy end points identified prospectively included cumulative RBC units transfused per patient through study day 28; cumulative mortality through study day 28; change in hemoglobin from baseline; and time to first transfusion or death. Patients receiving rHuEPO were less likely to undergo transfusion (60.4% placebo vs 50.5% rHuEPO; P<.001; odds ratio, 0.67; 95% confidence interval [CI], 0.54-0.83). There was a 19% reduction in the total units of RBCs transfused in the rHuEPO group (1963 units for placebo vs 1590 units for rHuEPO) and reduction in RBC units transfused per day alive (ratio of transfusion rates, 0.81; 95% CI, 0.79-0.83; P =.04). Increase in hemoglobin from baseline to study end was greater in the rHuEPO group (mean [SD], 1.32 [2] g/dL vs 0.94 [1.9] g/dL; P<.001). Mortality (14% for rHuEPO and 15% for placebo) and adverse clinical events were not significantly different. In critically ill patients, weekly administration of 40 000 units of rHuEPO reduces allogeneic RBC transfusion and increases hemoglobin. Further study is needed to determine whether this reduction in RBC transfusion results in improved clinical outcomes.


[Selectivity of rural migrants from the Sierra of Ecuador].
"This paper examines characteristics of recent rural-urban out-migrants leaving households in the Sierra of Ecuador. A large, household survey focussing specifically on migration is utilized, allowing detailed crosstabulations by sex and origin-destination combination and providing information about migrants generally not found in more generic surveys or censuses. Differences are noted between migrants and non-migrants in basic demographic characteristics, reasons for migrating, and economic activities prior to and subsequent to moving. Differences in the characteristics of migrants moving between various types of place of origin and place of destination are also noted." (SUMMARY IN ENG)


Establishment of a set of combined immunodeficient DA/Slc-Foxn1(rnu) Lyst(bg) congenic rat strains.
The congenitally athymic nude rat is used for studying cancer and transplantation owing to its hairlessness and T-cell defective function caused by the Foxn1(rnu) gene. However, NK cell activity of the nude rat is markedly increased. It is known that NK cells play a major role in rejection of xenografts and in cytotoxicity against tumor cells. Thus, the athymic nude rat with impaired NK cell activity should be a useful model for extensive studies. The DA-Lyst(bg)/Lyst(bg) rat, a model for human Chediak-Higashi syndrome (CHS) is characterized by diluted-coat color and impairment of NK cell activity. We planned to establish a combined immunodeficient double mutant rat introgressed with the Foxn1(rnu) and Lyst(bg) genes and a set of congenic strains having an identical genetic backgrounds simultaneously. Based on the phenotypic and genetic characteristics of the parental rat strains, the new strains were produced using continuous backcross and diagnosis with molecular genetic techniques. Each disease gene was diagnosed with PCR-RFLP or the long-nested PCR method. Furthermore, we used a marker-assisted congenic strategy based on scanning the genetic backgrounds of the parental rats with 461 rat microsatellite markers. We think that the newly established DA/Slc-Foxn1(rnu)/Foxn1(rnu) Lyst(bg)/Lyst(bg) double mutant will be useful as a severe disease model for human CHS, and the set of DA/Slc-Foxn1(rnu) Lyst(bg) congenic strains which have impaired NK cell activity and/or defective T cell function should be useful for studying in cancer research, xenotransplantation, immune function and other wide-ranging studies.


Women caught in a culture of violence in Guatemala.
Violence against women is prevalent around the world. In Guatemala it is pervasive. Living in a culture of violence oppresses women, children, the economy and society as a whole. It destroys families and can effect women emotionally and spiritually, as well as physically. Nurses have the power to intervene and influence change on a global level by taking action against abuse and oppression of women. By examining the pervasive nature of intimate partner violence and femicide in Guatemala, nurses can identify actions and interventions to combat violence on a global basis.


The latest proposals for changing the British NHS: a health service manager's view of the White Paper.
The nature of the plans for change detailed in the National Health Service review White Paper, Working for Patients, which was presented to the British Parliament on 1 February 1989, are examined in this paper. Seven key measures are identified and outlined. The author extrapolates from the nature of the plans contained within the White Paper, the types of problems within the NHS that are attracting government attention. Questions are raised as to the appropriateness and likelihood of success of the White Paper plans in view of the problems currently besetting the NHS.


Multiple micronutrient supplementation during pregnancy in low-income countries: a meta-analysis of effects on stillbirths and on early and late neonatal mortality.
Multiple micronutrient deficiencies are common among women in low-income countries and may adversely affect pregnancy outcomes. To conduct a meta-analysis of the effects on stillbirths and on early and late neonatal mortality of supplementation during pregnancy with multiple micronutrients compared with iron-folic acid in recent randomized, controlled trials. Twelve randomized, controlled trials were included in the analysis (Bangladesh; Burkina Faso; China; Guinea-Bissau; Indramayu and Lombok, Indonesia; Mexico; Sarlahi and Janakur, Nepal; Niger; Pakistan; and Zimbabwe), all providing approximately 1 recommended dietary allowance (RDA) of multiple micronutrients or iron-folic acid to presumed HIV-negative women. Supplementation providing approximately I RDA of multiple micronutrients did not decrease the risk of stillbirth (OR = 1.01; 95% CI, 0.88 to 1.16), early neonatal mortality (OR = 1.23; 95% CI, 0.95 to 1.59), late neonatal mortality (OR = 0.94; 95% CI, 0.73 to 1.23), or perinatal mortality (OR = 1.11; 95% CI, 0.93 to 1.33). Our meta-analysis provides consistent evidence that supplementation providing approximately 1 RDA of multiple micronutrients during pregnancy does not result in any reduction in stillbirths or in early or late neonatal deaths compared with iron-folic acid alone.


Optical-fibre scanning near-field optical microscope for cryogenic operation.
We have developed a new type of scanning near-field optical microscope (SNOM) utilizing optical fibres. The probe tip is controlled by shear force feedback with a fibre interferometer and signal light is collected directly by a multimode fibre. These features make the SNOM head more compact and less sensitive to vibration. Further advantages of this new type of SNOM are that it obviates the need for optical windows in the cryostat and offers easy optical alignment.


Gender matters. Sex-related differences in immunotherapy outcome in patients with non-small cell lung cancer.
Emerging evidence identified sex as a variable that can regulate immune system functions and modulate response to immunotherapy in cancer patients. This retrospective study analysed sex-related differences in immunotherapy outcome in a real-world population of non-small cell lung cancer (NSCLC) patients treated with immune checkpoint inhibitors (ICIs). We retrospectively investigated clinical data of 99 patients with advanced NSCLC and treated with single agent nivolumab and pembrolizumab, at Medical Oncology Unit, Careggi University Hospital, Florence (Italy), between April 2014 to August 2019. Main clinical characteristics and clinical outcomes were analysed. Our study showed that efficacy of ICI treatment differed according to gender. A trend for better median progression free survival (mPFS) was reported in males (mPFS 5.0 months, 95% Confidence Interval [CI] 4.0-11.0) than females (mPFS 4.5 months, 95% CI 2.0-9.0) (p=0.133), while no significant difference for overall survival (OS) between the two sex groups was observed (p=0.622). In the nivolumab cohort we showed a statistically significant difference for a longer PFS in men compared to women (log-rank p=0.054), HR for PFS in females versus males was 1.81 (95% CI 0.97-3.37, p=0.062). Disease control rate (DCR) was achieved in 55.7% and 45.7% in men and women, respectively, while disease progression was registered in 44.3% of males and 54.3% of females (p=0.386). Gender is a variable that should be taken into account in the choice of immunotherapy. Future prospective randomized trials testing tailored sex-based immunotherapy strategies are required to validate our findings before integrating into clinical practice.


Feet injuries in rock climbers.
While injuries of the upper extremity are widely discussed in rock climbers, reports about the lower extremity are rare. Nevertheless almost 50 percent of acute injuries involve the leg and feet. Acute injuries are either caused by ground falls or rock hit trauma during a fall. Most frequently strains, contusions and fractures of the calcaneus and talus. More rare injuries, as e.g., osteochondral lesions of the talus demand a highly specialized care and case presentations with combined iliac crest graft and matrix associated autologous chondrocyte transplantation are given in this review. The chronic use of tight climbing shoes leads to overstrain injuries also. As the tight fit of the shoes changes the biomechanics of the foot an increased stress load is applied to the fore-foot. Thus chronic conditions as subungual hematoma, callosity and pain resolve. Also a high incidence of hallux valgus and hallux rigidus is described.


The Unintended Significance of Race: Environmental Racial Inequality in Detroit.
This article addresses shortcomings in the literature on environmental inequality by (a) setting forth and testing four models of environmental inequality and (b) explicitly linking environmental inequality research to spatial mismatch theory and to the debate on the declining significance of race. The explanatory models ask whether the distribution of blacks and whites around environmental hazards is the result of black/white income inequality, racist siting practices, or residential segregation. The models are tested using manufacturing facility and census data from the Detroit metropolitan area. It turns out that the distribution of blacks and whites around this region's polluting manufacturing facilities is largely the product of residential segregation which, paradoxically, has reduced black proximity to manufacturing facility pollution.


Variability in DNA repair and individual susceptibility to genotoxins.
DNA repair is an important mechanism of cellular protection from the effects of genotoxic chemicals. Although extensive evidence from studies in experimental systems indicates that variation in DNA repair can significantly influence susceptibility to genotoxins, corresponding studies in human populations are so far limited, mainly because of methodological difficulties. One system, using observations of the accumulation and repair of DNA damage in cancer patients treated with alkylating cytostatic drugs, has provided useful information for assessing the effects of interindividual variation in DNA repair activity on the induction of genotoxic effects in humans. The most detailed studies of this kind have been carried out on patients with cancer (i.e., Hodgkin disease, malignant melanoma) treated with the methylating cytostatic drugs procarbazine or dacarbazine; these studies have provided detailed information on dose-response relationships. They have also demonstrated the protective role of the repair enzyme O6-alkylguanine-DNA alkyltransferase against the accumulation of the premutagenic methylated DNA lesion O6-methylguanine in patients' DNA. Given the strong evidence that exposure of the general population to environmental methylating agents may be extensive, as indicated by the frequent discovery of methylated DNA adducts in human DNA, data on DNA damage and repair in alkylating drug-treated patients and their modulation by host factors may prove useful in efforts to assess the possible carcinogenic risks posed by exposure to environmental methylating agents.


[Quality of medical records in the "Medical Information System Program": application of the lot quality assurance sampling method].
The aim of this study was to validate a new method of quality control of medical records of the "Medicalisation of Information System Program" (P.M.S.I.) in Limoges university hospital. Lot quality assurance sampling (L.Q.A.S.), developed to meet industrial quality control needs, has been applied. This method allows to give an opinion on the quality of a lot from a sample randomised in this lot. Ten hospital units have been randomised. During three months, these medical units have recoded ten medical units abstracts (R.U.M.) which were randomised each month within their stays. If five or more R.U.M. had been modified on Principal Diagnosis (D.P.), Associated Significant Diagnosis (D.A.S.) or Diagnosis Related Group (D.R.G.), the lot was rejected. The hospital unit had then less 70% R.U.M. of good quality (alpha=5%). The global errors rates were compared to the results of usually performed quality control (1998). Nine hospital units were included. Hospital units which already had a low quality rate during the 1998 quality control had also an insufficient quality by L.Q.A.S. method. Among these, 33.7 [CI(95%): 21.6-45.8] R.U.M. have been modified. Medical units had a poorer data quality than surgical ones. No statistically significant difference was shown between 1998 errors rates and L.Q.A.S. rates, except for D.P. (p=0.002). L.Q.A.S. is easy to apply, could be repeated more frequently than usual controls, and allows to detect hospital units which require a faster action. This process could be applied to P.M.S.I., in which the search of quality is necessary because of the new cost model which includes secondary D.R.G.


Analysis of the effects of alpha 1-adrenoceptor antagonists on noradrenaline-mediated contraction of rat small mesenteric artery.
1. In this study, we examined the interaction between noradrenaline (NA) and phenylephrine (PE) with seven antagonists (prazosin, tamsulosin, phentolamine, WB-4101, 5-methylurapidil, spiperone and HV 723) in an attempt to characterize the alpha 1-adrenoceptor population of the rat isolated small mesenteric artery (SMA) preparation. 2. Six of the seven antagonists investigated produced concentration-dependent, parallel, rightward shift of the NA concentration-effect (E/[A]) curves. The exception was tamsulosin, which produced significant decrease of the upper asymptote. In the case of 5-methylurapidil and HV723, the Schild plot slope parameters were not significantly different from unity over the range of concentrations used. However, the Schild plot slopes obtained for the other antagonists were all significantly greater than unity, inconsistent with expectations for simple competitive antagonism. 3. HV723, prazosin and tamsulosin were also tested using PE as an agonist. All three antagonists produced concentration-dependent, parallel, rightward shifts of the PE curves and Schild analysis yielded slope parameters not significantly different from unity. The pKB estimates obtained for tamsulosin and prazosin were not significantly different from the pA2 values obtained when NA was used as agonist. In the case of HV723, the 95% confidence intervals for the pKB values yielded with NA and PE did not overlap (pKB = 8.80-9.13 and 8.15-8.77 for NA and PE, respectively). 4. In the absence of evidence to indicate that the steep Schild plots were due to failure to satisfy the basic criteria for quantitative analysis in a one-receptor system, we considered the possibility that the complexity was caused by an action of NA at inhibitory D1 receptors. The selective D1 receptor antagonists, SCH-23390 (10 nM), had no significant effect on the NA E/[A] control curve, but the apparent potency of 100 nM prazosin was reduced by approximately 3.5 fold. 5. This study indicates that the steep Schild plots obtained from the interaction between NA and alpha 1-adrenoceptor antagonists were due to the simultaneous activation of inhibitory D1 receptors by NA. Notwithstanding this complexity, our explanatory model of the system (see Appendix) suggests that the antagonist affinity values estimated in the absence of D1 receptor block were not significantly affected by this other action of NA. The low affinity estimate obtained for prazosin suggests that the pharmacologically-defined alpha IL-subtype operates in the SMA.


Pattern of serum protein gene expression in mouse visceral yolk sac and foetal liver.
We have shown by molecular hybridisation that the mRNAs for albumin, transferrin, apolipoprotein-A1, and alpha 1-antitrypsin are expressed at high levels in mouse visceral yolk sac. In contrast, the mRNAs for contrapsin (a plasma protease inhibitor) and the major urinary proteins (MUPs) are not detected in the visceral yolk sac at any stage of embryonic development. Contrapsin and MUP mRNAs both appear late in liver development. These differences in expression suggest that the visceral yolk sac is more similar to the foetal than adult mouse liver in its pattern of gene expression. However, the developmental time course of expression of these mRNAs is different between the foetal liver and the yolk sac. Evidence is also presented that the visceral yolk sac synthesises and secretes other apolipoproteins in addition to apolipoprotein-A1. These results suggest that the visceral yolk sac and foetal liver, two tissues with different embryological lineages, perform similar functions but are independently programmed for expression of the same set of serum protein genes.


Sleep apnea syndrome. A critical review of the apnea index as a diagnostic criterion.
The utility of the apnea index (number of apneic events per hour of sleep) in diagnosing sleep apnea syndrome is reviewed. Data from currently extant reports indicate that many otherwise normal, aging subjects may be classified as having sleep apnea syndrome based on the current diagnostic threshold of five apneic episodes per hour: A chi 2 analysis suggests a relationship between age and level of sleep apnea. Several other reports indicate that use of a threshold of five apneic episodes per hour does not reliably predict increased health risk or somnolence in aging subjects. Adjustment of the apnea index, based on studies of aging normal subjects and of aging patients with sleep apnea syndrome is necessary to ensure reliable results in clinical and research applications.


Inflammatory pathways are activated during cardiomyocyte hypertrophy and attenuated by peroxisome proliferator-activated receptors PPARalpha and PPARdelta.
Accumulating evidence indicates an important role for inflammation in cardiac hypertrophy and failure. Peroxisome proliferator-activated receptors (PPARs) have been reported to attenuate inflammatory signaling pathways and, as such, may interfere with cardiac remodeling. Accordingly, the objectives of the present study were to explore the relationship between cardiomyocyte hypertrophy and inflammation and to investigate whether PPARalpha and PPARdelta are able to inhibit NF-kappaB activation and, consequently, the hypertrophic growth response of neonatal rat cardiomyocytes (NCM). mRNA levels of markers of both hypertrophy and inflammation were increased following treatment with the pro-hypertrophic factor phenylephrine (PE) or the chemokine TNF-alpha. Induction of inflammatory genes was found to be fast (within 2 h after stimulation) and transient, while induction of hypertrophic marker genes was more gradual (peaking at 24-48 h). Inflammatory and hypertrophic pathways appeared to converge on NF-kappaB as both PE and TNF-alpha increased NF-kappaB binding activity as measured by electrophoretic mobility shift assay. Following transient transfection, the p65-induced transcriptional activation of a NF-kappaB reporter construct was significantly blunted after co-transfection of PPARalpha or PPARdelta in the presence of their respective ligands. Finally, adenoviral overexpression of PPARalpha and PPARdelta markedly attenuated cell enlargement and the expression of hypertrophic marker genes in PE-stimulated NCM. The collective findings reveal a close relationship between hypertrophic and inflammatory signaling pathways in the cardiomyocyte. It was shown that both PPARalpha and PPARdelta are able to mitigate cardiomyocyte hypertrophy in vitro by inhibiting NF-kappaB activation.


The Rural PILL Program: A Postdischarge Telepharmacy Intervention for Rural Veterans.
To evaluate the efficacy of the Rural Pharmacological Intervention in Late Life (PILL) program, a quality improvement initiative in which a Boston-based pharmacist provided postdischarge telepharmacy care to veterans from rural Maine. Using an automated screening tool, we identified 100 veterans aged 65 and older who had an acute care admission to VA medical centers in Boston or Maine and were at risk of problems with medication management. The PILL pharmacist called patients the week after hospital discharge to reconcile medications, assess adherence, and identify potentially inappropriate drugs. The pharmacist worked with each veteran's family and providers to resolve problems and increase support. To determine whether the intervention decreased acute care admissions, rehospitalizations, or deaths, we matched 1 unique control to each PILL patient by age, hospital location, length of stay, admitting service, and reason for admission. Logistic regression was performed to determine the OR and 95% CI of the outcomes. Patients were discharged on an average of 16 medications and with 4.4 medication changes. Overall, 61% of patients had clerical errors in the discharge summary, and potential clinical concerns were identified in over 75%. Veterans who received the intervention were 70% less likely than controls to have an acute care visit at 30 days postdischarge (7 vs 20 patients; OR = 0.30; 95% CI: 0.12-0.75). There was no difference in rates of hospital readmission or mortality. This pharmacist-led phone-based program was effective in decreasing acute care utilization within 30 days after hospital discharge.


Botulinum Toxin in the Management of Sialorrhoea in Acquired Brain Injury.
Sialorrhoea as a consequence of severe acquired brain injury can significantly negatively impact on quality of life. Medications used in its management have many side effects which can cause problems in the severely disabled. Botulinum toxin is an effective treatment of sialorrhoea in a number of neurological conditions but may also have a role to play in the management of sialorrhoea following severe ABI. We report on 4 cases of sialorrhoea following acquired brain injury causing a variety of problems, whose parotid glands were injected with Botulinum toxin type A (Dysport) 50mu each, under ultrasound guidance. All cases had a clinically and statistically significant reduction in drooling as measured by the teacher drooling scale (p=0.005) and carers Visual Analogue Scale (p=0.012). There were no side effects reported. Botulinum toxin is an effective treatment for sialorrhoea associated with acquired brain injury.


Renal Ultrasound, Dialysis Catheter Placement, and Kidney Biopsy Experience of US Nephrology Fellows.
Procedures are a key component to the practice of nephrology. The Accreditation Council for Graduate Medical Education (ACGME) requires nephrology fellows to acquire skills and demonstrate competency in the performance of several procedures during fellowship training, including temporary hemodialysis catheter placement, biopsy of native and transplanted kidneys, and various dialytic therapies. It is also required that fellows acquire competency in the interpretation of renal imaging, including renal ultrasound, during their training. To gain a more recent perspective of nephrology fellows' experiences regarding renal ultrasonography, dialysis catheter placement, and kidney biopsies, we carried out a national survey of nephrology fellows in May 2014. A majority of the programs did not offer formal clinical training in renal ultrasonography. In addition, a significant percentage of fellows in adult nephrology may not be acquiring the required procedural skills and competency during fellowship training. In this perspective, we explore some of the reasons for this occurrence and propose some measures that the nephrology training community can take to enhance procedural skills and competency of fellows.


Appropriate Targets for Search Advertising as Part of Online Gatekeeping for Suicide Prevention.
Gatekeeper training is an effective suicide prevention strategy. However, the appropriate targets of online gatekeeping have not yet been clarified. We examined the association between the outcomes of online gatekeeping using the Internet and the characteristics of consultation service users. An advertisement to encourage the use of e-mail-based psychological consultation services among viewers was placed on web pages that showed the results of searches using suicide-related keywords. All e-mails received between October 2014 and December 2015 were replied to as part of gatekeeping, and the obtained data (responses to an online questionnaire and the content of the received e-mails) were analyzed. A total of 154 consultation service users were analyzed, 35.7% of whom were male. The median age range was 20-29 years. Online gatekeeping was significantly more likely to be successful when such users faced financial/daily life or workplace problems, or revealed their names (including online names). By contrast, the activity was more likely to be unsuccessful when it was impossible to assess the problems faced by consultation service users. It may be possible to increase the success rate of online gatekeeping by targeting individuals facing financial/daily life or workplace problems with marked tendencies for self-disclosure.


Electrocardiographic changes during upper gastrointestinal endoscopy in ambient hypoxia.
Electrocardiographic (ECG) changes were studied in 120 consecutive subjects during and after upper GI endoscopy done in ambient hypoxia (PO2-120 mmHg) at Shimla (2200 m). No premedication was given to any of the subjects. There were 75 men and 44 women. Fifty three subjects were aged 40 years or below (Group I) and 67 subjects were above 40 (Group II). There were 29 subjects with and 91 subjects without cardiac diseases. Increase in heart rate was seen in 96.6% of subjects. Maximum rise in heart rate was found in cardiac patients. ST depression was seen in 14.2%, T wave inversion in 13.3%, supraventricular tachycardia in 5.8% and ventricular ectopics in 1.6%. ST depression was more frequent in cardiac than in non cardiac patients (P less than 0.001) and T wave inversion was more frequent in women than in men (P less than 0.001). All the changes reverted to normal within 10 minutes. ECG changes notwithstanding, upper GI endoscopy without premedication in the presence of ambient hypoxia is a safe procedure.


Does the 5-2-1 criteria identify patients with advanced Parkinson's disease? Real-world screening accuracy and burden of 5-2-1-positive patients in 7 countries.
The burden of Parkinson's disease (PD) worsens with disease progression. However, the lack of objective and uniform disease classification challenges our understanding of the incremental burden in patients with advanced Parkinson's disease (APD) and suboptimal medication control. The 5-2-1 criteria was proposed by clinical consensus to identify patients with advancing PD. Our objective was to evaluate the screening accuracy and incremental clinical burden, healthcare resource utilization (HCRU), and humanistic burden in PD patients meeting the 5-2-1 screening criteria. Data were drawn from the Adelphi Parkinson's Disease Specific Program (DSP™), a multi-country point-in-time survey (2017-2020). People with PD who were naive to device-aided therapy and on oral PD therapy were included. Patients meeting the 5-2-1 screening criteria had one or more of the three clinical indicators of APD: (i) ≥5 doses of oral levodopa/day, OR (ii) "off" symptoms for ≥2 h of waking day, OR (iii) ≥1 h of troublesome dyskinesia. Clinician assessment of PD stage was used as the reference in this study. Clinical screening accuracy of the 5-2-1 criteria was assessed using area under the curve and multivariable logistic regression models. Incremental clinical, HCRU, and humanistic burden were assessed by known-group comparisons between 5 and 2-1-positive and negative patients. From the analytic sample (n = 4714), 33% of patients met the 5-2-1 screening criteria. Among physician-classified APD patients, 78.6% were 5-2-1 positive. Concordance between clinician judgment and 5-2-1 screening criteria was > 75%. 5-2-1-positive patients were nearly 7-times more likely to be classified as APD by physician judgment. Compared with the 5-2-1-negative group, 5-2-1-positive patients had significantly higher clinical, HCRU, and humanistic burden across all measures. In particular, 5-2-1-positive patients had 3.8-times more falls, 3.6-times higher annual hospitalization rate, and 3.4-times greater dissatisfaction with PD treatment. 5-2-1-positive patients also had significantly lower quality of life and worse caregiver burden. 5-2-1 criteria demonstrated potential as a screening tool for identifying people with APD with considerable clinical, humanistic, and HCRU burden. The 5-2-1 screening criteria is an objective and reliable tool that may aid the timely identification and treatment optimization of patients inadequately controlled on oral PD medications.


Overparenting, Parent-Child Conflict and Anxiety among Chinese Adolescents: A Cross-Lagged Panel Study.
Overparenting is an emerging parenting style in which parents over-protect their children from difficulties and challenges by intruding into their lives and providing extensive assistance to them. Unfortunately, longitudinal studies related to overparenting were severely lacking, particularly on its impacts on early adolescents. Moreover, studies examining the mediational pathways through which overparenting is associated with adolescent anxiety are scant. This study examined the mediating role of parent-child conflict (father-child and mother-child) in the relationship between overparenting (paternal and maternal) and adolescent anxiety over time. Based on a three-wave longitudinal data of 1074 Chinese early adolescents in Hong Kong, the relationships among paternal and maternal overparenting, father- and mother-child conflict, and adolescent anxiety were assessed. Mother-child conflict mediated the relationship between maternal overparenting and adolescent anxiety over time. Besides, a reverse association of prior adolescent anxiety with subsequent maternal overparenting via mother-child conflict was also identified. In addition, adolescent gender and family intactness did not moderate the relationships among overparenting, parent-child conflict, and adolescent anxiety. This present study identified that the bidirectional relationship between maternal overparenting and adolescent anxiety via mother-child conflict over time, which sheds new light on the study of overparenting on adolescent well-being in the Chinese communities.


Clinical utility of the memory complaints inventory to detect invalid test performance.
This investigation was designed to examine the classification statistics of Memory Complaints Inventory (MCI) scores relative to the Medical Symptom Validity Test (MSVT) and the Non-Verbal Medical Symptom Validity Test (NV-MSVT), as well as various validity scales on the Personality Assessment Inventory (PAI) and Minnesota Multiphasic Personality Inventory-2 Restructured Form(MMPI-2-RF). The sample consisted of 339 active duty service members with a history of concussion who completed performance validity tests (PVTs), symptom validity tests (SVTs), and the MCI. Those who failed the MSVT and NV-MSVT had significantly higher scores across all MCI scales. In addition, those who scored above specified cut scores on the evaluated PAI and MMPI-2-RF validity scales also had significantly higher MCI scale scores. Receiver operator characteristics analysis demonstrated acceptable area under the curve (AUC) across the evaluated SVTs for the mean of all MCI subtests with values ranging from (.77 to .86), with comparable findings for PVTs (MSVT AUC = .75; NV-MSVT AUC = .72). In general the MCI scales demonstrated better classification statistics relative to SVTs vs. PVTs, which is consistent with the nature of the MCI as a self-report instrument.


Remarkable decrease in the viscosity of waxy crude oil under an electric field.
Uninterrupted transport of waxy crude oil through pipelines remains a pressing concern for the petroleum industry. When the ambient temperature falls below the pour point of the crude, deposition of wax particles may lead to complete blockage of the pipeline. We demonstrate that the application of a DC electric field to waxy crude below its pour point can effectively break the wax network and also reduce the viscosity by up to two orders of magnitude. We have studied the dynamics of the change in viscosity during and after application of an electric field. Three regimes are observed. First is the induction regime, where viscous stresses dominate and the viscosity remains unchanged. During the intermediate and final regimes, the decrease in viscosity follows first order kinetics with rate constants proportional to the strength of the electric field and to the square of the strength, respectively. Microscopic evidence shows that some network connections break during the intermediate regime, whereas in the final regime, further fragmentation of the pieces of the broken network occurs. This is accompanied by aggregation of fine wax fragments. After cessation of the field, the viscosity increases gradually. The rate and the extent of recovery of viscosity depend only on the value of viscosity at the point of cessation of the field. That the breakage of the network occurs, even in the absence of shear, has been demonstrated. Through measurement of the dielectric constants and conductivities of the crude oil and its component phases, we have shown that the wax network experiences compressive Maxwell stress, which is dominated by the electric field within the wax particles.


Victims of disaster: can ethical debriefings be of help to care for their suffering?
Victims of disaster suffer, not only at the very moment of the disaster, but also years after the disaster has taken place, they are still in an emotional journey. While many moral perspectives focus on the moment of the disaster itself, a lot of work is to be done years after the disaster. How do people go through their suffering and how can we take care of them? Research on human suffering after a major catastrophe, using an ethics of care perspective, is scarce. People suffering from disasters are often called to be in distress and their emotional difficulties 'medicalised'. This brings them often into a situation of long term use of medication, and one can wonder if medication is of help to them in the long run. In our paper, we will explore another moral perspective, focusing on the importance of the victims' narrative and their lived experiences. We will use Paul Ricoeur's phenomenological reflections from 'Suffering is not the same as pain' for conceptualizing human suffering and how to apply it to victims of disaster. Ricoeur suggests that suffering is not a quantity that can be measured, but a characteristic that should be studied qualitatively in interpersonal and narrative contexts. Above all, the perspective of care and listening could offer an opportunity to reconcile people from their loss and suffering.


Plant immunity triggered by microbial molecular signatures.
Pathogen/microbe-associated molecular patterns (PAMPs/MAMPs) are recognized by host cell surface-localized pattern-recognition receptors (PRRs) to activate plant immunity. PAMP-triggered immunity (PTI) constitutes the first layer of plant immunity that restricts pathogen proliferation. PTI signaling components often are targeted by various Pseudomonas syringae virulence effector proteins, resulting in diminished plant defenses and increased bacterial virulence. Some of the proteins targeted by pathogen effectors have evolved to sense the effector activity by associating with cytoplasmic immune receptors classically known as resistance proteins. This allows plants to activate a second layer of immunity termed effector-triggered immunity (ETI). Recent studies on PTI regulation and P. syringae effector targets have uncovered new components in PTI signaling. Although MAP kinase (MAPK) cascades have been considered crucial for PTI, emerging evidence indicates that a MAPK-independent pathway also plays an important role in PTI signaling.


Bodyweight change as an adverse effect of drug treatment. Mechanisms and management.
A number of drugs are capable of changing bodyweight as an adverse effect of their therapeutic action. Bodyweight gain is more of a problem than bodyweight loss. As bodyweight gain during drug treatment for any kind of disease may be the reflection of improvement of the disease itself, we will try to separate these effects from those due to drug-induced alterations of the mechanisms regulating bodyweight. Bodyweight gain may jeopardise patient compliance to the prescribed regimen and it may pose health risks. The body mass index (BMI) is determined by dividing bodyweight in kilograms by height in metres squared. A BMI of > or = 27 kg/m2 warrants therapeutic action; nutritional counselling and programmed physical exercise can be used as a basis. In general, if basic therapeutic measures are unsuccessful at controlling bodyweight gain then a change of drug might help. Finally, an anoretic drug may serve to support dietary measures. However, safety and efficacy has been demonstrated for only a few anorectic drugs when used as an adjunct to caloric restriction in the treatment of drug-induced obesity. Bodyweight is determined by complex mechanisms regulating energy balance. A number of neurotransmitter systems acting in several hypothalamic nuclei are pivotal to the regulation of body fat stores. Most drugs that are capable of changing bodyweight interfere with these neurotransmitter systems. The increment is dependent on the type and dose of the drug concerned. Some antidepressant drugs induce bodyweight gain, which may amount to 20 kg over several months of treatment. Monoamine oxidase inhibitors appear to cause less bodyweight change than tricyclic antidepressants. Selective serotonin (5-hydroxytryptamine; 5-HT) reuptake inhibitors cause bodyweight loss instead of bodyweight gain. Lithium may cause large increases in bodyweight. Generally speaking, the bodyweight change induced by antipsychotics is more often of clinical significance than the bodyweight change associated with the use of antidepressants. Again, the changes of bodyweight are dependent upon the type and dose of the antipsychotic drug involved. Although almost all antipsychotics induce bodyweight gain, molindone and loxapine appear to induce bodyweight loss. Anticonvulsants, especially valproic acid (sodium valproate) and carbamazepine, induce bodyweight gain in a considerable percentage of patients. Treatment with corticosteroids is associated with dose-dependent bodyweight gain in many patients. Corticosteroid-induced obesity aggravates other corticosteroid-associated health risks. Insulin therapy in diabetic patients usually increases bodyweight. Finally, sulphonurea derivatives, antineoplastic agents used for the treatment of breast cancer and several drugs used in migraine prophylaxis may cause bodyweight gain as well.


[Suicides among patients with mental disorders - case studies].
Suicides around the world are a major public health problem. They are the most serious causes of death among patients with mental disorders. In many European countries, national programs and strategies for suicide prevention were developed. The progress of civilisation, changes in political and economic life, a too fast pace of life negatively affect human, causing the liberation of self-destructive behaviours. The aim of this study, which was based on medical records, was to analyse the course of psychiatric disorders, that ended with suicide. Descriptions of the course of mental disorders which ended with suicide and self-harm codes according to ICD-10 in randomly selected patients have been presented. 1. A 68 year old patient with schizophrenia - the intending self-harm by hanging (X70); 2. A 46 years old patient with a diagnosis of schizoaffective disorder - the intentional self-harm by drug poisoning (X61); 3. A 51 years old patient with a diagnosis of bipolar disorder - suicide death under the wheels of the train (X8 1). Risk of suicide in mental disorders requires the implementation conduct standards in a suicide crisis. In each case, it is necessary to assess the risk on the basis of the identification of suicide risk factors. Evaluation of risk factors is the basis of therapeutic action and determines how to support patients with a risk of suicidal death. Despite advances in the treatment of mental disorders, in some cases, there is still limited effectiveness of suicide preventio.


Characterization of uranyl(VI) nitrate complexes in a room temperature ionic liquid using attenuated total reflection-Fourier transform infrared spectrometry.
Room temperature ionic liquids form potentially important solvents in novel nuclear waste reprocessing methods, and the solvation, speciation, and complexation behaviors of actinides and lanthanides in room temperature ionic liquids is of current interest. In this study, the coordination environment of uranyl(VI) in solutions of the room temperature ionic liquid 1-butyl-3-methylimidazolium bis(trifluoromethylsulfonyl)imide containing either tetrabutylammonium nitrate or nitric acid was characterized using attenuated total reflection-Fourier transform infrared spectrometry. Both UO(2)(NO(3))(2) and UO(2)(NO(3))(3)(-) species were detected in solutions containing tetrabutylammonium nitrate. ν(as)(UO(2)) for these two species were found to lie at 951 and 944 cm(-1), respectively, while ν(as)(UO(2)) arising from uranyl(VI) coordinated by bis(trifluoromethylsulfonyl)imide anions in 1-butyl-3-methylimidazolium bis(trifluoromethylsulfonyl)imide was found to lie at 968 cm(-1). In solutions containing nitric acid, only UO(2)(NO(3))(2) was detected, due to the high water content. The UO(2)(NO(3))(+) species was not detected under the conditions used in this study. From the results shown here, we conclude that infrared spectroscopy forms a valuable addition to the suite of tools currently used to study the chemical behavior of uranyl(VI) in room temperature ionic liquids.


Ambulatory blood pressure monitoring in the assessment of antihypertensive therapy.
Before an antihypertensive drug is approved for use in clinical practice it must undergo rigorous clinical testing. Basic pharmacokinetic data are usually first obtained in healthy, normal individuals and thereafter in patients with renal or hepatic disease or in sub-groups such as the young or elderly. Acute dosing studies over a wide dosage range are then required prior to initiating longer-term studies. After one or more dosage levels have been selected and the appropriate dosing interval established, investigators may proceed with studies of four to twelve weeks duration, comparing the new drug with placebo or other standard therapies such as a thiazide diuretic or a beta-blocker. A key element in the evaluation process is the assessment of the drug


Estuarine phytoplankton group-specific responses to sublethal concentrations of the agricultural herbicide, atrazine.
Atrazine is a common agricultural herbicide that is readily transported into estuaries through surface water runoff. In this study, we determined the short-term (24-48 h) sublethal effects of atrazine on estuarine phytoplankton biomass and community composition. Phytoplankton group-specific responses to atrazine exposure (25 microgh(-1)) were measured using natural water samples collected from two locations in Galveston Bay, Texas. Addition bioassays, coupled with HPLC pigment analysis, were used to quantify changes in the relative abundances of algal groups. For all algal groups except prasinophytes, the addition of atrazine in combination with nitrate was not significantly different from nitrate additions alone. These results suggest no significant negative effect of atrazine on phytoplankton under the specified environmental conditions for the bioassays. Although low concentrations of atrazine may have minimal impacts on phytoplankton, herbicide loadings need to be further characterized before generalizations can be applied to estuarine and coastal ecosystems.


[Recurrence of right breast cancer at the thoracic wall successfully treated with intra-arterial infusion of doxorubicin hydrochloride--a case report].
We report a recurrent case of breast cancer successfully treated with intra-arterial infusion of doxorubicin hydrochloride (ADM) combined with systemic CAF therapy. The patient, a 37-year-old woman, was diagnosed with a recurrence at the thoracic wall 55 months after curative resection for right breast cancer. She was treated with intra-arterial infusion chemotherapy of ADM, 30 mg, combined with systemic CAF therapy of cyclophosphamide, 100 mg from days 1 to 14, ADM, 30 mg on days 1 and 8, and 5-fluorouracil, 500 mg on days 1 and 8, as one course. Two courses of the treatment resulted in a complete response of the tumor. This result suggests that local and systemic chemotherapy could be effective for the treatment of local recurrence of breast cancer.


[Therapeutic effects of Anastrozole in patients with advanced and recurrent breast cancer].
We reviewed therapeutic effects and harmful side effects in 33 patients with advanced or recurrent breast cancer who underwent treatment with Anastrozole 1 mg/day in our department. The patients ranged in age from 40 to 83 years old (median, 59). The Performance Status was 0-2, and there was 1 case of advanced breast cancer and 32 cases of recurrent breast cancer. The duration of disease was from 5 to 233 months (median, 50 months). The estrogen and/or progesterone receptor-positive rate was 72.7%. Metastatic sites were in multiple organs in 9 cases, in the lung only in 1 case, in bone only in 12 cases, and in soft tissue only in 10 cases. First-line therapy was used in 10 cases, second-line therapy in 6 cases, and above third-line therapy in 17 cases. There was a complete response in 3 cases, partial response in 5 cases, no long change in 13 cases, no change in 9 cases, and progressive disease in 3 cases. The response rate was 24.3%, The response period ranged from 2 to 22 months (median, 8 months), and clinical benefit was achieved in 63.7%. The clinical benefit rates for first-line were 60%, second-line 83.3% and above third-line therapy 58.8%. The response rate for patients with breast cancer resistant to Anthracyclines and/or Taxanes was 20%. Time-to-progression ranged from 2 to 28 months (median, 11 months), and overall survival ranged from 7 to 30 months (median, 15 months). The most frequent harmful side effects were rise in total cholesterol, general fatigue, hot flashes and arthralgia (9.1%). In this study, we confirmed the availability and safety of Anastrozole, which was suggested to be a useful drug in salvage therapy for patients having resistance to Anthracyclines and/or Taxanes, not only but also useful as a first- or second-line therapy.


Update on anti-angiogenic therapy in non-small cell lung cancer: Are we making progress?
Non-small cell lung cancer (NSCLC) remains a leading cause of death worldwide among patients diagnosed with malignancy. Despite new chemotherapy regimens and new cytotoxic combinations investigated in multiple clinical trials in recent years, no significant improvement in the prognosis of patients with lung cancer was achieved. The five-year survival rate for all patients diagnosed with NSCLC is about 15%, only 5% better than that of more than 40 years ago. New therapeutic approaches that target various different aspects of tumor progression and metastasis are of particular interest in to NSCLC patients. Drugs that block tumor vascularization (angiogenesis) or interfere with the activity of growth factor receptors and molecular pathways that are triggered by activation of these receptors are already used in clinical practice. In this review we will briefly discuss briefly the basic mechanisms of lung cancer angiogenesis, rationale for using drugs that block this process and present the most current recent data on their clinical efficacy.


Heat shock 70 kDa protein cognate 5 involved in WSSV toleration of Litopenaeus vannamei.
The expression levels of 97 unigenes encoding heat shock proteins of Litopenaeus vannamei was scanned, and ten of them were significantly induced by white spot syndrome virus (WSSV). Among these genes, heat shock 70 kDa protein cognate 5 (LvHSC70-5) was upregulated to the highest extent and subjected to further studies. Subcellular localization assay revealed that LvHSC70-5 was located in the mitochondria. Aside from WSSV infection, unfolded protein response activation and thermal stress could also upregulate LvHSC70-5. Results of reporter gene assay demonstrated that promoter of LvHSC70-5 was activated by L. vannamei heat shock factor protein 1, activating transcription factor 4 and thermal stress. A decrease in the expression of LvHSC70-5 could reduce the aggregation of proteins in hemocytes and the cumulative mortality of WSSV-infected L. vannamei. LvHSC70-5 in L. vannamei hemocytes was upregulated by mild thermal stress. In addition, mild thermal stress, decreased the copy number of WSSV in shrimp muscle and the cumulative mortality of WSSV-infected L. vannamei. Therefore, collecting results suggested that LvHSC70-5 should be involved in WSSV toleration of shrimp L. vannamei.


AFP-L3 as a Prognostic Predictor of Recurrence in Hepatoblastoma: A Pilot Study.
The α-fetoprotein (AFP) level is a sensitive biomarker of active hepatoblastoma (HB). This study aimed to clarify whether the Lens culinaris agglutinin A-reactive fraction of AFP (AFP-L3) after complete resection is a prognostic predictor of HB recurrence. Fourteen HB patients who underwent complete resection of HB were divided into the recurrence group (RG, n=4) and the non-recurrence group (NRG, n=10). The AFP level and AFP-L3 before and after radical surgery were compared between the 2 groups. There was no significant difference in AFP levels in the early postoperative period between the 2 groups (P=0.54), and AFP was not an early prognostic factor for HB recurrence. At 2 months after surgery, the AFP-L3 fell below the detection limit only in the NRG (7/10 cases) (NRG=70.0% vs. RG=0%, P=0.03). In addition, there were some cases of recurrence in those whose AFP level decreased to the normal range, but none in those whose AFP-L3 fell below the detection limit. In conclusion, the AFP-L3 decreased earlier than did the AFP level; thus, the AFP-L3 after complete resection may be a predictor for HB recurrence.


Therapeutic Approaches with Intravitreal Injections in Geographic Atrophy Secondary to Age-Related Macular Degeneration: Current Drugs and Potential Molecules.
The present review focuses on recent clinical trials that analyze the efficacy of intravitreal therapeutic agents for the treatment of dry age-related macular degeneration (AMD), such as neuroprotective drugs, and complement inhibitors, also called immunomodulatory or anti-inflammatory agents. A systematic literature search was performed to identify randomized controlled trials published prior to January 2019. Patients affected by dry AMD treated with intravitreal therapeutic agents were included. Changes in the correct visual acuity and reduction in geographic atrophy progression were evaluated. Several new drugs have shown promising results, including those targeting the complement cascade and neuroprotective agents. The potential action of the two groups of drugs is to block complement cascade upregulation of immunomodulating agents, and to prevent the degeneration and apoptosis of ganglion cells for the neuroprotectors, respectively. Our analysis indicates that finding treatments for dry AMD will require continued collaboration among researchers to identify additional molecular targets and to fully interrogate the utility of pluripotent stem cells for personalized therapy.


Extracorporeal high-frequency combined with contrast-enhanced ultrasound: a novel imaging method for detection and treatment evaluation of patients with cervical trachea-associated relapsing polychondritis.
This study aims to evaluate the clinical utility of extracorporeal high-frequency ultrasound (EHFU) combined with contrast-enhanced ultrasound (CEUS) for the diagnosis and treatment of cervical trachea-associated relapsing polychondritis (CT-RP). From January 2013 to January 2020, 24 patients with CT-RP diagnosed clinically and pathologically were retrospectively reviewed. We used EHFU to measure the thickness of trachea cartilage and the minimum internal transverse diameter of trachea and compared it with CT. The EHFU and CEUS imaging features were compared before and after treatment and used to evaluate the effects of therapy. EHFU revealed the entire cervical tracheal cartilage (136 rings, of which 124 were abnormal). The average thickness of the 124 tracheal cartilage rings was 3.657±0.52 mm on EHFU and 3.32±0.76 mm on CT (t=1.482, P>0.05), while the diameter of the tracheal segment was 11.98±3.22 mm on EHFU and 10.8±2.92 mm on CT (t=1.005, P>0.05). After treatment, most patients (75%) showed no recurrence, and ultrasound revealed that the tracheal ring thickness was restored and the transverse diameter of the tracheal cavity was widened. Differences in EHFU measurements before and after treatment were statistically significant (both P<0.01). CEUS revealed that the tracheal cartilage layer was damaged in six cases (25%) and included structural destruction, deformation, and thinning. Follow-up evaluation revealed that the treatment outcomes of these cases were poor. The mean ultrasound examination time per patient was 10.0±2.3 min. EHFU combined with CEUS clearly and quickly revealed the CT-RP cervical tracheal wall, diameter of the trachea, and microstructural changes in tracheal cartilage. The effects of treatment can be reliably assessed by measuring reductions in tracheal cartilage thickening and echo changes before and after treatment. Dynamic monitoring of the condition provides timely and detailed information on cervical tracheal wall lesions and is valuable for clinical evaluation.


Serum Bcl-2 concentrations in overweight-obese subjects with nonalcoholic fatty liver disease.
To shed some light on the relationship between anti-apoptotic serum Bcl-2 concentrations and metabolic status, anthropometric parameters, inflammation indices, and non-alcoholic fatty liver disease severity were investigated in 43 young individuals with fatty liver (FL) and 41 with nonalcoholic steatohepatitis (NASH). Circulating levels of Bcl-2 were detected in 84 patients with ultrasonographic findings of "bright liver" and/or hyper-transaminasemia of unknown origin and/or increase in γ-glutamyl-transpeptidase (γ-GT) strictly in the absence of other acute or chronic liver disease, whose age was not advanced, who gave consent to liver biopsy and were then divided on the basis of the histological results into two groups (43 with FL and 41 with NASH). Twenty lean subjects, apparently healthy and young, were chosen as controls. Serum Bcl-2 concentrations were significantly higher in the FL group than in the NASH group. Insulin resistance and γ-GT activity were significantly higher in NASH subjects. Apoptotic hepatocytes were significantly more numerous in NASH patients. NASH patients presented with larger spleens and augmented C-reactive protein (CRP) concentrations than healthy subjects. Steatosis grade at histology was similar in both NASH and FL populations. The number of apoptotic cells was significantly related to anti-apoptotic Bcl-2 protein values in FL patients. Bcl-2 serum levels positively correlated to body mass index (BMI) values (P ≤ 0.0001) but not to age of the population. Triglycerides/HDL ratio correlated well to waist circumference in males (P = 0.0008). γ-GT activity was associated with homeostatic metabolic assessment (HOMA) (P = 0.0003) and with serum ferritin (P = 0.02). Bcl-2 concentrations were not related to either spleen size or CRP values. NASH patients presented a weak negative correlation between lobular inflammation and Bcl-2 levels. A prediction by low values of serum Bcl-2 towards a greater presence of metabolically unhealthy overweight/obese patients (MUOs) was evidenced. HOMA, BMI and uric acid, in that sequence, best predicted serum Bcl-2 concentrations. MUOs could be detected by Bcl-2 levels. By favoring the life span of hepatocytes, and enhancing triglyceride formation, the anti-apoptotic process inhibits free fatty acids toxicity in FL.


Relationship between quality of life and adolescent glycolipid metabolism disorder: A cohort study.
The prevalence of glucolipid metabolic disorders (GLMDs) in children and adolescents has a recognized association with cardiovascular diseases and type 2 diabetes mellitus in adulthood. Therefore, it is important to enhance our under-standing of the risk factors for GLMD in childhood and adolescence. To explore the relationship between quality of life (QoL) and adolescent GLMD. This study included 1956 samples in 2019 from a cohort study established in 2014. The QoL scale and glycolipid indexes were collected during follow-up; other covariates of perinatal factors, physical measures, and socioeconomic indicators were collected and adjusted. A generalized linear regression model and logistic regression model were used to analyse the correlation between QoL and GLMD. Higher scores of QoL activity opportunity, learning ability and attitude, attitude towards doing homework, and living convenience domains correlated negatively with insulin and homeostasis model assessment insulin resistance (IR) levels. Psychosocial factors, QoL satisfaction factors, and total QoL scores had significant protective effects on insulin and IR levels. Activity opportunity, learning ability and attitude, attitude towards doing homework domains of QoL, psychosocial factor, and total score of QoL correlated positively with high density lipoprotein. In addition, the attitude towards doing homework domain was a protective factor for dyslipidaemia, IR > 3, and increased fasting blood glucose; four factors, QoL and total QoL score correlated significantly negatively with IR > 3. In subgroup analyses of sex, more domains of QoL correlated with insulin and triglyceride levels, dyslipidaemia, and IR > 3 in females. Poor QoL was associated with an increased prevalence of GLMD, and the effect was more pronounced in males than in females. Measures to improve the QoL of adolescents are essential to reduce rates of GLMD. Our study revealed that QoL scores mainly correlate negatively with the prevalence of GLMD in adolescents of the healthy population. The independent relationship between QoL and GLMD can be illustrated by adjusting for multiple covariates that may be associated with glycaemic index. In addition, among females, more QoL domains are associated with glycaemic index.


The effect of HLA on immunological response to hepatitis B vaccine in healthy people: a meta-analysis.
Evidence is accumulating that several markers in the human leukocyte antigen (HLA) region have been associated with decreased or increased antibody response to hepatitis B vaccine in different individuals. This meta-analysis is to assess the associations of HLA class II DRB1 and DQB1 alleles with immunologic response to hepatitis B vaccine in healthy people. A systematic review of cohort studies in healthy people was performed. We searched databases for relevant studies that were published in English or Chinese up to February 17, 2012. Odds ratios (ORs) with corresponding 95% confidence intervals (CIs) of HLA alleles response to hepatitis B vaccine were pooled by using of a fixed-effects or random-effects model depending on absence or presence of significant heterogeneity. All statistical tests were two-sided. Fifteen studies were included in this meta-analysis after scanning 774 potentially relevant articles. A total of 2308 subjects (including 1215 responders, 873 nonresponders and 220 control populations) were included. For DRB1 alleles, pooled ORs showed that three HLA variants, DRB1*01, DRB1*1301 and DRB1*15 were associated with a significant increase antibody response to hepatitis B vaccine, their pooled ORs were 2.73, 5.94 and 2.29 respectively. While DRB1 *03 (DRB1*0301), DRB1*04, DRB1*07 and DRB1*1302 were opposite, their pooled ORs were 0.55(0.42), 0.57, 0.24 and 0.25 respectively. And for DQB1 alleles, pooled ORs showed that DQB1*05 (DQB1*0501), DQB1*06, DQB1*0602 were associated with a significant increase antibody response to hepatitis B vaccine. Their merger ORs were 1.85, 2.35, 2.34 and 3.32 respectively. While DQB1*02 (pooled OR=0.27) was adverse. Sensitivity and specificity analysis of HLA alleles showed that DRB1*1301and DQB1*0602 had high specificity (94.2% and 90.1%) but low sensitivity (25.1% and 26.3%), respectively. It was suggested that specific HLA class II alleles (DRB1 and DQB1) were associated with antibody response to HepB.


Interfacing Carbon Dots for Charge-Transfer Processes.
Carbon dots (CDs) are a booming material and the most recent incomer in the big family of carbon nanostructures. Specifically, CDs are nanosized fluorescent core-shell nanoparticles with tunable absorption and emission spectra, with high solubility in aqueous media and common organic solvents. Herein, the origins and the development of these unique nanoscale structures are discussed, key synthetic routes are briefly described, and the utilization of CDs in light-induced charge-transfer schemes is mainly focused upon. Beyond the impact of the CD's surface on the photoluminescence properties, functionalization, by covalent or supramolecular means, permits controllable incorporation of new functionalities with novel photophysical properties. Furthermore, the dual nature of CDs as electron donating or electron accepting species, unveiled upon interfacing them with organic chromophores, highlights their potentiality in managing diverse charge-transfer processes. Novel mechanisms, such as symmetry-breaking photoinduced charge-transfer can be activated upon covalent functionalization of CDs with organic dyes. Without a doubt, participation of CDs in energy conversion schemes opens up a wide avenue that may lead to the development of novel prototype devices suitable for technological applications and related to photonics and optoelectronics.


Sexuality, contraceptive choice and AIDS awareness among Nigerian undergraduates.
A survey of 2388 Nigerian undergraduates revealed that 87% were sexually active and 66% had more than one sexual partner, while 17.5% have had clandestine abortions. All respondents were quite knowledgeable about HIV/AIDS but few sexually active ones took precautions to prevent HIV transmission. Majority (87.5%) were knowledgeable about contraception and approved of its use, but only 34.2% were current users of contraceptives. About 58% of these cited pharmacy shops as their source of contraceptives. The attitudes of the students were below expectation. Specially designated centres for the provision of appropriate contraceptive services to students by trained personnel are needed in the institutions in order to tackle their reproductive health problems.


Examination of the external and internal load indicators' association with overuse injuries in professional soccer players.
Research in professional soccer focusing on the relevance of external and internal load indicators for injury prevention is scarce. This study examined the relationship between load indicators and overuse injuries. Prospective cohort study. Data were collected from 35 professional male soccer players over two seasons. Following load indicators were examined: total distance covered (TD), distance covered at high speed (THSR; >20kmh-1), number of accelerations (ACCeff; >1ms-2), number of decelerations (DECeff; <-1ms-2), and rating of perceived exertion (RPE) multiplied by duration. Cumulative 1-, 2-, 3-, 4-weekly loads and acute:chronic workload ratios (ACWR) were calculated and split into low, medium and high groups. Only overuse injuries were included in the analysis to focus on their specific relationship with the load indicators. Generalized estimating equations were applied to analyse the relationship between load indicators and overuse injuries in the subsequent week. In total, 64 overuse injuries were registered. For cumulative loads, results indicated an increased injury risk for higher 2- to 4-weekly loads as indicated by TD, DECeff, and RPE multiplied by duration. For ACWR, a high ratio for THSR (>1.18) resulted in a higher injury risk. In contrast, a lower injury risk was found when comparing medium ratios for ACCeff (0.87-1.12), DECeff (0.86-1.12), and RPE x duration (0.85-1.12) to low ratios. Findings demonstrate that mainly external load indicators are associated with increased or decreased injury risk. The monitoring of various load indicators is recommended for injury prevention in professional soccer.


Comprehensive analyses of prognostic biomarkers and immune infiltrates among histone lysine demethylases (KDMs) in hepatocellular carcinoma.
Histone lysine demethylases (KDMs) are closely related to the occurrence and development of different tumors through epigenetic mechanisms. However, the prognosis and immune infiltration of KDMs in hepatocellular carcinoma (HCC) remain undefined. In the current study, we analyzed the expression of KDMs on HCC patients using the Oncomine, GEPIA, UALCAN, Kaplan-Meier Plotter, cBioPortal, GeneMANIA, STRING, Metascape, GSEA, and TIMER databases. Finally, we investigated KDM expression in HCC by qRT-PCR, Western blotting, and IHC. We found that KDM3A/3B/5A/5B and KDM6A were upregulated in HCC patients, while KDM6B and KDM8 were downregulated. The high expressions of KDM1A/2B/3B/5B/5C were markedly related to tumor stages and grades of HCC patients. The abnormal expression of KDM1A/1B/3A/4A/5A/5C/6A/6B/7A and KDM8 were associated with HCC patients' prognosis. Also, we found that HCC tissues presented higher expression levels of KDM1A/2A/5A/5B and lower expression levels of KDM6B. The function of KDMs was primarily related to the histone demethylase activity and cell cycle, p53 signaling pathway, pathways in cancer, transcriptional mis-regulation in cancer, viral carcinogenesis, and FoxO signaling pathway. Furthermore, we indicated that the pathways most involved were the mitotic spindle and DNA repair. Additionally, we found that the expression of KDM1A/1B/3A/4A/5B/5C and KDM6A were significantly correlated with HCC immune infiltration. Overall, our current results indicated that KDM1A/1B/3A/4A/5B/5C and KDM6A could be novel prognostic biomarkers and provide insights into potential immunotherapy targets to HCC patients.


[The different effects of glutamine on macrophage cytokines release in vivo and in vitro].
To evaluate the effects of glutamine (Gln) on macrophages cytokines release and heat shock protein 72 (HSP72) expression in vivo and in vitro, and explore the anti-inflammation mechanisms of Gln during sepsis. In experiment one, mouse peritoneal macrophage cell line RAW264.7 cells were divided into 0, 0.5 and 8 mmol/L Gln groups, and cells and supernatants were harvested at 0, 1, 4, 12 and 24 hours after lipopolysaccharide (LPS) challenge. In experiment two, forty-five Kunming mice were randomized into sham-operation group (Sham), sepsis model group, and Gln group. Sepsis was induced by cecal ligation and puncture (CLP). Either Gln 0.75 g/kg (Gln group) or saline (Sham and model group) was administered immediately after CLP via tail-vein injection. Blood sample was collected at 6 hours, and macrophages were harvested by peritoneal lavage. Tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6) and IL-10 contents in supernatant, serum and cell lysate were analyzed with enzyme-linked immunosorbent assay (ELISA), macrophages HSP72 expression was assessed with Western blotting. Gln promoted RAW264.7 cells to release TNF-alpha, IL-6 and IL-10 in a dose-dependent and time-dependent manner in vitro (P<0.05 or P<0.01), and significantly increased HSP72 expression in 8 mmol/L Gln group at 4 hours after LPS stimulation (both P<0.01). In vivo, in animals given Gln intracellular TNF-alpha and IL-6 levels were significantly lower than sepsis animals (P<0.01 and P<0.05), but there was no statistically significant difference in intracellular IL-10 levels among three groups. The serum levels of TNF-alpha in Gln group were significantly lower than in model group (P<0.05), while serum IL-6 and IL-10 levels were similar between two groups. Gln treatment led to significant HSP72 expression compared to model and Sham groups (both P<0.01). Gln can promote inflammatory cytokines release from macrophages in vitro, which cannot be attenuated by HSP72 expression induced by Gln in LPS challenged RAW264.7 macrophages. Gln treatment significantly decreases intracellular TNF-alpha and IL-6 levels in vivo during sepsis. HSP72 expression increases after Gln treatment both in vivo and in vitro. These data implicate that HSP72 may not play a major role in attenuating the inflammatory response after Gln administration in sepsis.


Effect of second-generation antipsychotics on cognition: current issues and future challenges.
Generalized cognitive impairments are stable deficits linked to schizophrenia and key factors associated with functional disability in the disorder. Preclinical data suggest that second-generation antipsychotics could potentially reduce cognitive impairments; however, recent large clinical trials indicate only modest cognitive benefits relative to first-generation antipsychotics. This might reflect a limited drug effect in humans, a differential drug effect due to brain alterations associated with schizophrenia, or limited sensitivity of the neuropsychological tests for evaluating cognitive outcomes. New adjunctive procognitive drugs may be needed to achieve robust cognitive and functional improvement. Drug discovery may benefit from greater utilization of translational neurocognitive biomarkers to bridge preclinical and clinical proof-of-concept studies, to optimize assay sensitivity, enhance cost efficiency, and speed progress in drug development.