Light effects on the nucleic acids of excised cotton cotyledons.
The effects of light and glucose in the nutrient medium on the nucleic acid metabolism of excised 8-day cotton (Gossypium hirsutum var. Acala 44) cotyledons were determined. The rates of synthesis as affected by light and glucose were determined by brief exposures to C(14)-labeled orotic acid. The nucleic acids were fractionated by homogenizing in Tris-HCl buffer and centrifuging to obtain soluble and microsomal RNA (20,000 x g supernatant) and a particulate nucleic acid fraction (20,000 x g precipitate) or by extracting in phenol followed by 10% NaCl extraction at 100 degrees . The phenol extract was analyzed by density gradient centrifugation. Light and glucose caused parallel changes in nucleic acid levels of the various fractions, in orotic acid-6-C(14) absorption and in rates of synthesis of nucleic acids. Light and glucose appear to enhance binding of the ribosome nucleic acid so that it becomes less extractable in Tris-HCl buffer or phenol. The bound nucleic acids were labeled at a slightly higher rate than the total nucleic acids extracted by Tris-HCl or phenol. However, light treatment for 48 hours promoted a very high labeling rate in the soluble, low molecular weight nucleic acid as shown by density gradient centrifugation of the phenol extractable fraction.It was concluded that a part of the nucleic acid changes were brought about by light acting through the photosynthetic production of carbohydrate. This conclusion was strengthened by the observation that herbicide inhibitors of photosynthesis and limited atmospheric CO(2) concentrations partially inhibited the nucleic acid changes. However, glucose did not cause changes in nucleic acid levels as large as those caused by light and changes were observed to occur in light even though the endogenous sugar levels were maintained at a low level by the inhibition of photosynthesis with herbicides. The data indicated that light may produce changes in nucleic acid levels by other mechanisms additional to those regulating the sugar level in the tissue.


Rapid monitoring of SARS-CoV-2 variants of concern through high-resolution melt analysis.
The current global pandemic of COVID-19 is characterized by waves of infection due to the emergence of new SARS-CoV-2 variants carrying mutations on the Spike (S) protein gene. Since autumn 2020 many Variants of Concern (VOC) have been reported: Alpha/B.1.1.7, Beta/B.1.351, Gamma/P.1, Delta/B.1.617.2, Omicron/B.1.1.529, and sublineages. Surveillance of genomic variants is currently based on whole-genome sequencing (WGS) of viral genomes on a random fraction of samples positive to molecular tests. WGS involves high costs, extended analysis time, specialized staff, and expensive instruments compared to a PCR-based test. To rapidly identify the VOCs in positive samples, six assays based on real-time PCR and high-resolution melting (HRM) were designed on the S gene and applied to 120 oro/nasopharyngeal swab samples collected from October 2020 to June 2022 (106 positive and 14 negative samples). Overall, the assays showed 100% specificity and sensitivity compared with commercial PCR tests for COVID-19. Moreover, 104 samples out of 106 (98.1%) were correctly identified as follows: 8 Wuhan (wild type), 12 Alpha, 23 Delta, 46 Omicron BA.1/BA.1.1, 15 Omicron BA.2/BA.4/BA.5. With our lab equipment, about 10 samples can be processed every 3 h at the cost of less than € 10 ($ 10.60) per sample, including RNA extraction. The implementation of this approach could help local epidemiological surveillance and clinical decision-making.


Functional Omics Identifies Serine Hydrolases That Mobilize Storage Lipids during Rice Seed Germination.
Elucidating proteolipidome dynamics is crucial for understanding the roles of these molecules in plant physiology and disease. Sequence-based functional annotation of the protein is inadequate, since protein activities depend on posttranslational modification. In this study, we applied a gel-free activity-based protein profiling approach to unravel the active lipases, including other Serine hydrolases (SHs), expressed during seed germination in rice (Oryza sativa). We successfully mapped the active sites of 43 active SHs encompassing lipases/esterases, GDSL lipases, proteases, Ser carboxypeptidases, ABHD protein, pectin acetylesterase, and other SHs. The mRNA expression levels of those genes encoding the identified SHs were monitored using microarray analysis. The lipidome analysis revealed distinct patterns of molecular species distribution in individual lipid classes and displayed the metabolic connections between lipid mobilization and rice seedling growth. Changes in the mobilization of storage lipids and their molecular species remodeling were correlated with the expression of the identified lipases and their lipase activity in a time-dependent manner. The physiological significance of the identified SHs was explored during biotic stress with Fusarium verticillioides infection. The fungal infection significantly reduced lipase activity and lipid mobilization, thus impairing the rice seedling. Collectively, our data demonstrate application of the functional proteome strategy along with the shotgun lipidome approach for the identification of active SHs, and thus for deciphering the role of lipid homeostasis during rice seed germination.


Similarity of salivary microbiome in parents and adult children.
Human saliva contains approximately 700 bacterial species. It has been reported that the salivary microbiome of a large family of closely related individuals consisting of multiple households is similar but the relatedness of salivary bacteria between generations of parents and their children has not yet been investigated. The objectives were to investigate the entirety of salivary bacterial DNA profiles and whether and how families share these profiles and also compare these communities between grandparents and their first daughter generations (F1) using 16S rRNA gene amplicon sequencing. The most abundant phyla in two separate families were Firmicutes, Bacteroidetes, Proteobacteria, Fusobacteria and Actinobacteria. Family ties explained 13% of the variance between individuals' bacterial communities (R 2 = 0.13; P = 0.001). Mothers shared more OTUs with adult children compared to fathers, but this linkage seemed to be weaker in the nuclear family with older adult children. We identified 29 differentially abundant genus level OTUs (FDR < 0.05) between families, which accounted for 31% of the total identified genus level OTUs. Our results indicate that adult family members share bacterial communities and adult children were more similar to mothers than fathers. The observed similarity in oral microbiome between parent-child pairs seemed to weaken over time. We suggest that our analysis approach is suitable for relatedness study of multigenerational salivary bacteria microbiome.


Conversion of fatty aldehydes to alka(e)nes and formate by a cyanobacterial aldehyde decarbonylase: cryptic redox by an unusual dimetal oxygenase.
Cyanobacterial aldehyde decarbonylase (AD) catalyzes conversion of fatty aldehydes (R-CHO) to alka(e)nes (R-H) and formate. Curiously, although this reaction appears to be redox-neutral and formally hydrolytic, AD has a ferritin-like protein architecture and a carboxylate-bridged dimetal cofactor that are both structurally similar to those found in di-iron oxidases and oxygenases. In addition, the in vitro activity of the AD from Nostoc punctiforme (Np) was shown to require a reducing system similar to the systems employed by these O(2)-utilizing di-iron enzymes. Here, we resolve this conundrum by showing that aldehyde cleavage by the Np AD also requires dioxygen and results in incorporation of (18)O from (18)O(2) into the formate product. AD thus oxygenates, without oxidizing, its substrate. We posit that (i) O(2) adds to the reduced cofactor to generate a metal-bound peroxide nucleophile that attacks the substrate carbonyl and initiates a radical scission of the C1-C2 bond, and (ii) the reducing system delivers two electrons during aldehyde cleavage, ensuring a redox-neutral outcome, and two additional electrons to return an oxidized form of the cofactor back to the reduced, O(2)-reactive form.


Transcatheter Mitral Valve Replacement After Surgical Repair or Replacement: Comprehensive Midterm Evaluation of Valve-in-Valve and Valve-in-Ring Implantation From the VIVID Registry.
Mitral valve-in-valve (ViV) and valve-in-ring (ViR) are alternatives to surgical reoperation in patients with recurrent mitral valve failure after previous surgical valve repair or replacement. Our aim was to perform a large-scale analysis examining midterm outcomes after mitral ViV and ViR. Patients undergoing mitral ViV and ViR were enrolled in the Valve-in-Valve International Data Registry. Cases were performed between March 2006 and March 2020. Clinical endpoints are reported according to the Mitral Valve Academic Research Consortium (MVARC) definitions. Significant residual mitral stenosis (MS) was defined as mean gradient ≥10 mm Hg and significant residual mitral regurgitation (MR) as ≥ moderate. A total of 1079 patients (857 ViV, 222 ViR; mean age 73.5±12.5 years; 40.8% male) from 90 centers were included. Median STS-PROM score 8.6%; median clinical follow-up 492 days (interquartile range, 76-996); median echocardiographic follow-up for patients that survived 1 year was 772.5 days (interquartile range, 510-1211.75). Four-year Kaplan-Meier survival rate was 62.5% in ViV versus 49.5% for ViR (P<0.001). Mean gradient across the mitral valve postprocedure was 5.7±2.8 mm Hg (≥5 mm Hg; 61.4% of patients). Significant residual MS occurred in 8.2% of the ViV and 12.0% of the ViR patients (P=0.09). Significant residual MR was more common in ViR patients (16.6% versus 3.1%; P<0.001) and was associated with lower survival at 4 years (35.1% versus 61.6%; P=0.02). The rates of Mitral Valve Academic Research Consortium-defined device success were low for both procedures (39.4% total; 32.0% ViR versus 41.3% ViV; P=0.01), mostly related to having postprocedural mean gradient ≥5 mm Hg. Correlates for residual MS were smaller true internal diameter, younger age, and larger body mass index. The only correlate for residual MR was ViR. Significant residual MS (subhazard ratio, 4.67; 95% CI, 1.74-12.56; P=0.002) and significant residual MR (subhazard ratio, 7.88; 95% CI, 2.88-21.53; P<0.001) were both independently associated with repeat mitral valve replacement. Significant residual MS and/or MR were not infrequent after mitral ViV and ViR procedures and were both associated with a need for repeat valve replacement. Strategies to improve postprocedural hemodynamics in mitral ViV and ViR should be further explored.


The effects of lead on the developing central nervous system of the rat.
Biochemical and structural development of the cerebral cortex of rat pups is delayed by low levels of lead administered in the dam's drinking water during gestation and suckling periods. These changes in brain development coincide with delays in the development of exploratory and locomotor activity and impaired learning. Subsequent cross-fostering experiments have shown that delays in synaptogenesis and in the development of exploratory behavior were attributed entirely to the prenatal, as opposed to the postnatal, exposure to lead at the low dose levels utilized. Examination of the variations in blood lead concentrations in pups and dams during gestation and until weaning at 21 days of postnatal age indicated that a substantial increase in blood lead concentrations occurred late in pregnancy. At 200 mg of Pb/liter of drinking water, peak blood Pb concentrations were observed to be approximately 60 micrograms/dl in dams and 80 micrograms/dl in pups on the 20th day of gestation. By the 10th postnatal day blood Pb concentrations had decreased to 35 micrograms/dl in dams and 40 microgram/dl in pups despite an increased consumption of drinking water containing the same concentration of Pb during this period. (Delays in cerebral cortical development were observed after 10 days of postnatal age). Tracer studies utilizing 203Pb indicate that the rate of Pb absorption was substantially increased in the pregnant, relative to the non-pregnant, dam. Although a similar increase in 45Ca absorption was also observed during pregnancy, increases in Pb absorption were enhanced by Pb-pretreatment, whereas Ca absorption was independent of Pb-pretreatment. From this data it is concluded that the apparently greater sensitivity of postnatal development on prenatal Pb exposure is secondary to enhanced Pb absorption in the pregnant rat. In vitro metabolic studies in isolated cerebral cortex slices taken from 15 day old rat pups exposed to Pb revealed increased glucose and oxygen consumption in response to elevations in the potassium concentration of the incubation media. This evidence of metabolic uncoupling in the immature rat cerebral cortex may be causally related to the measured delays in brain development.


Validity of Three Survey Questions for Self-Assessed Sedentary Time.
Time spent in sedentary behavior (SB) has increased during the last decades. Accurate assessments are of importance when studying health consequences of SB. This study aimed to assess concurrent validity between three different questions for self-reported sitting and thigh worn accelerometer data. In total, 86 participants wore the ActivPAL accelerometer during three separate weeks, assessing sitting time with different questions each week. The questions used were Katzmarzyk, GIH stationary single-item question (SED-GIH), and a modified version of the single-item from IPAQ short form. In total 64, 57, and 55 participants provided valid accelerometer and questionnaire data at each time-point, respectively, and were included for analysis. Spearman and Pearson correlation was used to assess the validity. The three questions, Katzmarzyk, SED-GIH, and a modified question from IPAQ all showed a weak non-significant correlation to ActivPAL with r-values of 0.26, 0.25, and 0.19 respectively. For Katzmarzyk and SED-GIH, 50% and 37% reported correctly, respectively. For the modified IPAQ, 53% over-reported and 47% under-reported their sitting time. In line with previous research, our study shows poor validity for self-reported sitting-time. For future research, the use of sensor-based data on SB are of high importance.


Abnormal language-related oscillatory responses in primary progressive aphasia.
Patients with Primary Progressive Aphasia (PPA) may react to linguistic stimuli differently than healthy controls, reflecting degeneration of language networks and engagement of compensatory mechanisms. We used magnetoencephalography (MEG) to evaluate oscillatory neural responses in sentence comprehension, in patients with PPA and age-matched controls. Participants viewed sentences containing semantically and syntactically anomalous words that evoke distinct oscillatory responses. For age-matched controls, semantic anomalies elicited left-lateralized 8-30 Hz power decreases distributed along ventral brain regions, whereas syntactic anomalies elicited bilateral power decreases in both ventral and dorsal regions. In comparison to controls, patients with PPA showed altered patterns of induced oscillations, characterized by delayed latencies and attenuated amplitude, which were correlated with linguistic impairment measured offline. The recruitment of right hemisphere temporo-parietal areas (also found in controls) was correlated with preserved semantic processing abilities, indicating that preserved neural activity in these regions was able to support successful semantic processing. In contrast, syntactic processing was more consistently impaired in PPA, regardless of neural activity patterns, suggesting that this domain of language is particularly vulnerable to the neuronal loss. In addition, we found that delayed peak latencies of oscillatory responses were associated with lower accuracy for detecting semantic anomalies, suggesting that language deficits observed in PPA may be linked to delayed or slowed information processing.


Cytokine bioassays: an overview.
Although eclipsed in recent years by immunoassays and molecular biology techniques, bioassays remain a vital research tool for cytokine biology. Like any type of biological system, cytokine bioassays require meticulous technique to obtain accurate and reproducible results. However, these minor difficulties are more than compensated for by their exclusive detection of biologically active molecules, a feature as yet unmatched by other assay methods.


Recurrence of hepatitis B is associated with cumulative corticosteroid dose and chemotherapy against hepatocellular carcinoma recurrence after liver transplantation.
The incidence of hepatitis B (HB) recurrence after a liver transplantation has been reduced by prophylaxis with hepatitis B immunoglobulin (HBIG) and lamivudine. However, the long-term incidence of recurrence is <10%, and the factors associated with HB recurrence are unclear. This study analyzed the factors associated with HB recurrence in 203 recipients who underwent liver transplantation for HB in 3 major centers in Korea over 4 years. Eighty-five patients (41.9%) had a hepatocellular carcinoma (HCC). Preoperative active virus replicators with the HBeAg(+) (46.8%) and/or hepatitis B virus DNA(+) (39.4%) were observed in 136 patients (67.0%). The HB prophylaxis consisted of either HBIG monotherapy (n = 95, HBIG group) or combination therapy with lamivudine (n = 108, combination group). HB recurrence was defined as the appearance of the HBsAg. The follow-up period was 28.3 +/- 13.1 months (mean +/- SD). HB recurred in 21 patients (10.3%) after transplantation. The time from transplantation to recurrence was 16.3 +/- 9.4 months. Pre-LT DNA positivity was more prevalent in HBIG group (55.8%) than in the combination group (39.8%) (P = 0.015). However, the incidence of HB recurrence was similar in the HBIG (6.3%) and combination group (13.8%), as well as between the active replicators (12.5%) and nonreplicators (4.1%) (P < 0.05). There was a far higher incidence of HB recurrence in patients receiving corticosteroid pulse therapy (21.0% vs. 7.9%), patients who experienced HCC recurrence (31.3% vs. 8.6%), and patients receiving chemotherapy to prevent HCC recurrence (25.0% vs. 4.4%) (P < 0.05). The cumulative corticosteroid dose was higher in patients who experienced recurrence of HB (P = 0.002). Multivariable analysis confirmed the effect of the cumulative corticosteroid dose and chemotherapy to be risk factors. Liver transplantation for HB is safe, with low recurrence rates if adequate prophylaxis is used. However, the cumulative corticosteroid dose and the chemotherapy used for HCC were risk factors for HB recurrence, so careful monitoring for HB recurrence is needed in these patients.


Diagnostic performance of 256-row detector coronary CT angiography in patients with high heart rates within a single cardiac cycle: a preliminary study.
To evaluate the image quality and diagnostic performance of coronary computed tomography angiography (CCTA) in patients with high heart rate within a single cardiac cycle using a 256-row detector CT system. Eighty-four consecutive symptomatic patients (mean age 60.4±9.1 years, 52 men) with suspected coronary artery disease and heart rate ≥75 beats/min undergoing CCTA and invasive coronary angiography (ICA) were enrolled retrospectively. Prospective electrocardiography (ECG)-triggered volume CCTA within a single cardiac cycle was performed using a 256-row, 16 cm detector CT system (Revolution CT, GE Healthcare) using automated tube voltage selection (kV Assist selecting 100 or 120 kV) and tube current modulation (Smart mA) techniques, with images reconstructed using 50% of adaptive statistical iterative reconstruction-V (ASiR-V). The image quality of coronary artery segments was evaluated by two reviewers using a four-point scale based on 18-segment model. The diagnostic accuracy of CCTA to detect ≥50% stenosis on ICA was analysed. The sensitivity, specificity, positive predictive value, and negative predictive value of CCTA to detect a ≥50% diameter stenosis on ICA were calculated from the chi-squared test of the contingency table on a per-segment, per-vessel, and per-patient basis. The body mass index was 25.6±3.5 kg/m2; the HR was 82.8±7.9 beats/min, and the mean HR variability was 8.3±4.8 beats/min. All of the coronary artery segments, 98.9% (1044/1056) of coronary segments were rated as having diagnostic image quality. The diagnostic sensitivity, specificity, positive predictive value, and negative predictive value of CCTA, were 91.5%, 95.6%, 77.7%, and 98.5% on a per-segment basis; 95.2%, 93.5%, 87%, and 97.7% on a per-vessel basis; 100%, 85.7%, 93.3%, and 100% on per-patient basis, respectively. The mean effective dose was 1.9±1 mSv. CCTA using a 256-detector row CT with the snapshot freeze (SSF) technique can be performed in a single cardiac cycle with acquisition of images with high diagnostic value and low radiation dose in patients with high heart rates.


Cancer-related stress and complementary and alternative medicine: a review.
A cancer diagnosis elicits strong psychophysiological reactions that characterize stress. Stress is experienced by all patients but is usually not discussed during patient-healthcare professional interaction; thus underdiagnosed, very few are referred to support services. The prevalence of CAM use in patients with history of cancer is growing. The purpose of the paper is to review the aspects of cancer-related stress and interventions of commonly used complementary and alternative techniques/products for amelioration of cancer-related stress. Feasibility of intervention of several CAM techniques and products commonly used by cancer patients and survivors has been established in some cancer populations. Efficacy of some CAM techniques and products in reducing stress has been documented as well as stress-related symptoms in patients with cancer such as mindfulness-based stress reduction, yoga, Tai Chi Chuan, acupuncture, energy-based techniques, and physical activity. Much of the research limitations include small study samples and variety of intervention length and content. Efficacy and safety of many CAM techniques and some herbs and vitamin B and D supplements need to be confirmed in further studies using scientific methodology. Several complementary and alternative medicine therapies could be integrated into standard cancer care to ameliorate cancer-related stress.


Antihirsutism activity of Fennel (fruits of Foeniculum vulgare) extract. A double-blind placebo controlled study.
Idiopathic hirsutism is defined as the occurrence of excessive male pattern hair growth in women who have a normal ovulatory menstrual cycle and normal levels of serum androgens. It may be a disorder of peripheral androgen metabolism. In this study we evaluated the clinical response of idiopathic hirsutism to topical Fennel extract. Fennel, Foeniculum vulgare, is a plant, which has been used as an estrogenic agent. The ethanolic extract of Fennel was obtained by using a soxhlete apparatus. In a double blind study, 38 patients were treated with creams containing 1%, 2% of Fennel extract and placebo. Hair diameter was measured and rate of growth was considered. The efficacy of treatment with the cream containing 2% Fennel is better than the cream containing 1% Fennel and these two were more potent than placebo. The mean values of hair diameter reduction was 7.8%, 18.3% and -0.5% for patients receiving the creams containing 1%, 2% and 0% (placebo) respectively.


Skin markings methods and guidelines: A reality in image guidance radiotherapy era.
Preparation of site of radiation delivery is an important process in radiation treatment planning and plays a crucial role during a course of radiotherapy to achieve reproducibility of set-up and accuracy of treatment delivery. The preparation of treatment area is done by markings of field center, field edge or other reference point of planned field. Both non-invasive (marker pen, henna) and invasive methods (tattoo) are available for marking with limitations of each. Tattoo with a needle pricked at angle of 30° to 1-2 mm depth to create tattoo 2-3 mm diameter in size is an ideal procedure. Visibility, permanent nature, social-religious belief, and mobility of skin are one of the main concerns about tattoo. Tattoo removal can be done performed if desirable by patients by various modern ways, which will be esthetically available. Dermabrasion, cryotherapy, surgery, QSRL (Q-switched ruby laser) are common methods of tattoo removal. Esthetic dissatisfaction, allergy, dermatoses, keloids, infection, fanning/fading of tattoo are associated problems. In IMRT and IGRT treatment, delivery dependence on tattoo in reduced and use of surrogate markers including particularly for bony set-up and implanted markers (e.g. gold seeds) for tumor localization and treatment verification is increasing. However, these are complex procedures and require an expertise. Ease of set-up and less time required for tattooing are one of the main advantages of tattoo as compared to external or internal marker set-up. Tattoo still remains a crucial method of positioning, especially in developing countries and in palliative treatment settings.


The pharmacology of acute poisoning in the teenager.
Acute poisoning in the teenager is rarely accidental. Frequently, it is intentional. The pharmacological spectrum includes drugs, chemicals, plants and pollutants, and constantly changes in accordance with the prevailing popularity among the youth, the availability and the financial capability of the young adolescent to purchase the offender. This article discusses the pharmacological properties of drugs and chemicals frequently involved in the acute teenager intoxication, the clinical diagnoses, and outlines the principles of therapeutic management.


APOE ε variants increase risk of warfarin-related intracerebral hemorrhage.
We aimed to assess the effect of APOE ε variants on warfarin-related intracerebral hemorrhage (wICH), evaluated their predictive power, and tested for interaction with warfarin in causing wICH. This was a prospective, 2-stage (discovery and replication), case-control study. wICH was classified as lobar or nonlobar based on the location of the hematoma. Controls were sampled from ambulatory clinics (discovery) and random digit dialing (replication). APOE ε variants were directly genotyped. A case-control design and logistic regression analysis were utilized to test for association between APOE ε and wICH. A case-only design and logistic regression analysis were utilized to test for interaction between APOE ε and warfarin. Receiver operating characteristic curves were implemented to evaluate predictive power. The discovery stage included 319 wICHs (44% lobar) and 355 controls. APOE ε2 was associated with lobar (odds ratio [OR] 2.46; p < 0.001) and nonlobar wICH (OR 1.67; p = 0.04), whereas ε4 was associated with lobar (OR 2.09; p < 0.001) but not nonlobar wICH (p = 0.35). The replication stage (63 wICHs and 1,030 controls) confirmed the association with ε2 (p = 0.03) and ε4 (p = 0.003) for lobar but not for nonlobar wICH (p > 0.20). Genotyping information on APOE ε variants significantly improved case/control discrimination of lobar wICH (C statistic 0.80). No statistical interaction between warfarin and APOE was found (p > 0.20). APOE ε variants constitute strong risk factors for lobar wICH. APOE exerts its effect independently of warfarin, although power limitations render this absence of interaction preliminary. Evaluation of the predictive ability of APOE in cohort studies is warranted.


Psychophysiological correlates of flow during daily activities.
Flow is an optimal experience characterized by the perception of high challenges and high skills, positive affect, complete absorption in the activity carried out and intrinsic motivation. Although much research has examined the psychological features of flow, little is known about its biological underpinnings. The present study aimed at contributing to this gap by investigating the psychophysiological correlates of flow experience during daily routines. To this end, 15 university students took part in an experience sampling study, in which they provided real-time information on daily activities and associated experience while cardiac activity was monitored. After seven days of observation, 32 flow events were identified among 10 participants. A multilevel regression analysis revealed a significant correlation between optimal experience and specific cardiovascular indexes. In particular, the experience of flow was associated with increased heart rate and increased LF/HF ratio, suggesting relative sympathetic enhancement. These findings are in line with those obtained by previous related studies and indicate the feasibility of investigating physiological correlates of subjective experience in ecological contexts.


The effect of TNFalpha blockade in complicated, refractory Kawasaki disease.
In Kawasaki disease (KD), a systemic vasculitis of childhood, serum levels of proinflammatory cytokines such as tumour necrosis factor alpha (TNFalpha) are elevated during the acute phase of the disease. Although the majority of children recover completely from a single dose of intravenous immunoglobulin (IVIG), the treatment is not always effective. In refractory cases of KD there are no documented treatment guidelines. A future role of biological agents directed against proinflammatory cytokines has recently been suggested by the American Heart Association (AHA). We describe two infants with severe KD, complicated by coronary as well as extracoronary aneurysms, who responded neither to repeated treatment with IVIG plus aspirin nor to corticosteroids. The children were subsequently treated with infliximab. In both cases, the effect was prompt and long-lasting. Clinical improvement was seen within a few days after the first dose, and regression of the aneurysms occurred within weeks.


Analysis of the cytolytic T lymphocyte response of melanoma patients to the naturally HLA-A*0201-associated tyrosinase peptide 368-376.
The human tyrosinase gene codes for two distinct antigens that are recognized by HLA-A*0201-restricted CTLs. For one of them, tyrosinase peptide 368-376, the sequence identified by mass spectrometry in melanoma cell eluates differs from the gene-encoded sequence as a result of posttranslational modification of amino acid residue 370 (asparagine to aspartic acid). Here, we used fluorescent tetrameric complexes ("tetramers") of HLA-A*0201 and tyrosinase peptide 368-376 (YMDGTMSQV) to characterize the CD8+ T-cell response to this antigen in lymphoid cell populations from HLA-A2 melanoma patients. Taking advantage of the presence of significant numbers of tetramer-positive CD8+ T cells in tumor-infiltrated lymph node cells from a melanoma patient, we derived polyclonal and monoclonal tyrosinase peptide 368-376-specific CTLs by tetramer-guided flow cytometric sorting. These CTLs efficiently and specifically lysed HLA-A*0201- and tyrosinase-positive melanoma cells. As assessed with tyrosinase peptide variants, the fine antigen specificity of the CTLs was quite diverse at the clonal level. Flow cytometric analysis of PBMCs stained with tetramers showed that tyrosinase peptide 368-376-specific CD8+ T cells were hardly detectable in peripheral blood of melanoma patients. However, significant numbers of such cells were detected after short-term stimulation of CD8+ lymphocytes with tyrosinase peptide 368-376 in 6 of 10 HLA-A2 melanoma patients. Taken together, these findings emphasize the significant contribution of the natural tyrosinase peptide 368-376 to the antigenic specificities recognized by the tumor-reactive CTLs that may develop in HLA-A2 melanoma patients.


Risks of pedestrian serious injuries and fatalities associated with impact velocities of cars in car-versus-pedestrian accidents in Japan.
The first purpose of this study is to clarify the relation between the car impact velocity and pedestrian injury severity or mortality risk. We investigated the frequency of serious injuries and fatalities of pedestrians using vehicle-pedestrian accident data from the database of the Institute for Traffic Accident Research and Data Analysis (ITARDA) in Japan. The vehicle types considered are sedans, minivans, and box vans (ordinary automobiles) and light passenger cars and light cargo vans (light automobiles). The results revealed that a 10-km/h reduction in impact velocity could mitigate severe pedestrian injuries in cases involving impact velocities of 40 km/h or more for the five vehicle types analyzed. Specifically, if the impact velocity was 30 km/h or less, the frequency of serious injuries was less than 27% and the frequency of fatalities was less than 5% for the five vehicle types. Therefore, if the collision damage mitigation braking system (CDMBS) that uses a sensor to detect pedestrians can effectively reduce the impact velocity for various vehicle types, pedestrian injuries will be greatly mitigated. The second purpose of this study is to identify the factors that affect injury risk. Impact experiments were conducted in which a sedan impacted against a pedestrian full-scale dummy at 40 km/h and a pedestrian headform impactor was impacted against a road surface. The results indicated that the risk of pedestrian serious injury was significantly affected by multiple impact conditions, such as the pedestrian height, car impact velocity, car frontal shape, and car stiffness in cases where the car impacted the pedestrian's head, the degrees of influence of which were driven by the vehicle impact velocity.


The growing complexity of COVID-19 drug and vaccine candidates: challenges and critical transitions.
COVID-19 has nowadays affected almost all our societies and global health systems. The latest deadly pandemic has heavily influenced both life and livelihood worldwide. SARS-CoV-2 is the causative organism of COVID-19, that is spreading and infecting significantly higher compared to other coronavirus, due to its constant mutation characteristics. At present although several extensive clinical trials are ongoing, neither approved drug therapy nor any vaccine are available to safely fight SARS-CoV-2. However, a progressive race among numerous research groups to discover a radical cure for the COVID-19 is under way. This review aims to provide an updated insight of the current research, development and trials on repurposing existing drugs and preventive intervention for COVID-19, along with the related issues, complexities and challenges, especially after the observed high transmissibility lately.


Dental microwear texture analysis along reptile tooth rows: complex variation with non-dietary variables.
Dental microwear texture analysis (DMTA) is a powerful technique for reconstructing the diets of extant and extinct taxa. Few studies have investigated intraspecific microwear differences along with tooth rows and the influence of endogenous non-dietary variables on texture characteristics. Sampling teeth that are minimally affected by non-dietary variables is vital for robust dietary reconstructions, especially for taxa with non-occlusal (non-chewing) dentitions as no standardized sampling strategies currently exist. Here, we apply DMTA to 13 species of extant reptile (crocodilians and monitor lizards) to investigate intraspecific microwear differences along with tooth rows and to explore the influence of three non-dietary variables on exhibited differences: (i) tooth position, (ii) mechanical advantage, and (iii) tooth aspect ratio. Five species exhibited intraspecific microwear differences. In several crocodilians, the distally positioned teeth exhibited the 'roughest' textures, and texture characteristics correlated with all non-dietary variables. By contrast, the mesial teeth of the roughneck monitor (Varanus rudicollis) exhibited the 'roughest' textures, and texture characteristics did not correlate with aspect ratio. These results are somewhat consistent with how reptiles preferentially use their teeth during feeding. We argue that DMTA has the potential to track mechanical and behavioural differences in tooth use which should be taken into consideration in future dietary reconstructions.


Usefulness of alpha1-antichymotrypsin-PSA complex for predicting bone metastases of prostate cancer.
To determine the usefulness of alpha1-antichymotrypsin-prostate-specific antigen (PSA) complex (PSA-ACT)-based parameters in predicting bone metastasis in patients with prostate cancer. PSA-ACT, total PSA, free PSA, their volume-adjusted values, and alkaline phosphatase were evaluated in 220 consecutive patients with newly diagnosed prostate cancer. Bone metastases were detected by bone scan in 27 (12.3%) of the 220 patients. The serum levels of PSA-ACT, total PSA, free PSA, PSA density, PSA adjusted for transition zone volume, PSA-ACT density, PSA-ACT adjusted for transition zone volume, alkaline phosphatase, PSA-ACT/PSA ratio, and Gleason score in patients with bone metastases were each significantly greater than in those without bone metastases. On receiver operating characteristic analyses, PSA-ACT had the greatest area under the curve (0.88), but the receiver operating characteristic curve demonstrated that the sensitivity and specificity of PSA-ACT were marginally better than those of total PSA at only a few selected cutoff points. At a sensitivity of 93% (2 patients with bone metastasis missed), unnecessary bone scans would have been avoided in 107 and 102 patients using a PSA-ACT cutoff value of 10 ng/mL and total PSA cutoff value of 11.5 ng/mL, respectively. Multivariate logistic regression analysis demonstrated that PSA-ACT and Gleason score were significant independent predictors of bone metastasis. PSA-ACT is as useful as total PSA for identifying patients with a low probability of having bone metastasis. PSA-ACT could replace PSA for predicting negative bone scans in a clinical setting in which PSA-ACT is used for monitoring and screening patients for prostate cancer.


Brief Report: Association Between Autism Spectrum Disorder, Gastrointestinal Problems and Perinatal Risk Factors Within Sibling Pairs.
Autism spectrum disorder (ASD) has been associated with gastrointestinal (GI) problems, but the nature of this association is unclear. Parents to siblings, concordant or discordant for ASD (N = 217), participated in a web survey covering mother's weight gain during pregnancy, maternal viral/bacterial infection and use of antibiotics, duration of breastfeeding, mode of delivery, birth weight and child GI problems. ASD was associated with GI problems and perinatal environmental risk, based on a summation of maternal infection and antibiotic use during pregnancy and/or the breastfeeding period. The association between GI problems and ASD remained within the sibling pairs (β = 1.23; p < .001) in the adjusted model. Our results indicate non-shared environmental effects on the ASD/GI association, but none of the factors examined explained the link.


Effects of tadalafil on lower urinary tract symptoms secondary to benign prostatic hyperplasia in men with or without erectile dysfunction.
To compare the safety and efficacy of the daily erectogenic therapy, tadalafil, on lower urinary tract symptoms secondary to benign prostatic hyperplasia (BPH-LUTS) in men with or without comorbid erectile dysfunction (ED). Following a 4-week placebo run-in period, men with moderate-to-severe BPH-LUTS were randomized to placebo or tadalafil 2.5, 5, 10, or 20 mg once daily for 12 weeks. International Prostate Symptom Scores (IPSS), IPSS quality of life, and BPH Impact Index were measured every 4 weeks. Safety was mainly assessed via spontaneous reports of adverse events. Data from men with (n=716) or without (n=340) ED at baseline were compared in posthoc analyses. Men with ED were older and had more frequent hypertension, hyperlipidemia, coronary artery disease, and diabetes at baseline compared with men without ED. After 12 weeks, changes in IPSS in men with ED (least squares mean change from baseline, placebo: -2.4; tadalafil 2.5, 5, 10, 20 mg: -4.3, -4.8, -5.3, -5.6) and without ED (-2.4, -3.2, -5.3, -5.1, -4.5) were not significantly different (subgroup/interaction P values: .352/.644). Similar effects were observed for IPSS quality of life (with ED: -0.6, -0.9, -0.9, -1.0, -1.1; without ED: -0.6, -0.7, -0.9, -0.8, -0.8; 0.090/0.773) and BPH Impact Index (with ED: -0.7, -0.9, -1.3, -1.3, -1.4; without ED: -1.0, -0.7, -1.3, -1.3, -1.2; 0.753/0.852). Tadalafil was generally well tolerated, and men with or without ED had similar tolerability profiles. Changes in BPH-LUTS after 12 weeks of treatment with placebo or various doses of once daily tadalafil were similar in men with or without comorbid ED.


The effects of Mucuna pruriens extract on histopathological and biochemical features in the rat model of ischemia.
Stroke is considered to be one of the most important causes of death worldwide. Global ischemia causes widespread brain injury and infarctions in various regions of the brain. Oxidative stress can be considered an important factor in the development of tissue damage, which is caused because of arterial occlusion with subsequent reperfusion. Kapikacchu or Mucuna pruriens, commonly known as velvet bean, is well known for its aphrodisiac activities. It is also used in the treatment of snakebites, depressive neurosis, and Parkinson's disease. Although this plant has different pharmacological actions, its neuroprotective activity has received minimal attention. Thus, this study was carried out with the aim of evaluating the neuroprotective action of M. pruriens in bilateral carotid artery occlusion-induced global cerebral ischemia in Wistar rats. The carotid arteries of both sides were occluded for 30 min and reperfused to induce global cerebral ischemia. The methanolic plant extract was administered to the study animals for 10 days. The brains of the Wistar rats were isolated by decapitation and observed for histopathological and biochemical changes. Cerebral ischemia resulted in significant neurological damage in the brains of the rats that were not treated by M. pruriens. The group subjected to treatment by the M. pruriens extract showed significant protection against brain damage compared with the negative control group, which indicates the therapeutic potential of this plant in ischemia.


The associations of maternal warmth and hostility with prosocial and antisocial outcomes in justice-involved adolescents.
Parental warmth and hostility are two key dimensions of parenting for child development, but the differential effects of these parenting dimensions on child prosocial and antisocial development has not been adequately investigated. The current study hypothesized that parental warmth would be uniquely related to child callous-unemotional traits and prosocial behavior, whereas parental hostility would be uniquely related to child delinquency and aggression. These hypotheses were investigated in a diverse sample of 1,216 adolescent males (13 to 17 years old, 46% Latino, 37% Black) with justice-system involvement in the 5 years following their first arrest. Hybrid models estimated within- and between-individual associations over time, while controlling for the overlap between parental warmth and hostility and between child prosocial and antisocial outcomes. Results indicated that maternal warmth showed consistent associations with callous-unemotional traits and prosocial behavior over time, whereas maternal hostility showed consistent associations with delinquency and aggression over time. Further, the findings were similar across racial and ethnic groups. Implications for developmental models of antisocial behavior, particularly for those including the role of callous-unemotional traits, are discussed. (PsycInfo Database Record (c) 2021 APA, all rights reserved).


Histone acetyltransferase activity of p300 is required for transcriptional repression by the promyelocytic leukemia zinc finger protein.
Histone acetyltransferase (HAT) activities of proteins such as p300, CBP, and P/CAF play important roles in activation of gene expression. We now show that the HAT activity of p300 can also be required for down-regulation of transcription by a DNA binding repressor protein. Promyelocytic leukemia zinc finger (PLZF), originally identified as a fusion with retinoic acid receptor alpha in rare cases of all-trans-retinoic acid-resistant acute promyelocytic leukemia, is a transcriptional repressor that recruits histone deacetylase-containing corepressor complexes to specific DNA binding sites. PLZF associates with p300 in vivo, and its ability to repress transcription is specifically dependent on HAT activity of p300 and acetylation of lysines in its C-terminal C2-H2 zinc finger motif. An acetylation site mutant of PLZF does not repress transcription and is functionally deficient in a colony suppression assay despite retaining its abilities to interact with corepressor/histone deacetylase complexes. This is due to the fact that acetylation of PLZF activates its ability to bind specific DNA sequences both in vitro and in vivo. Taken together, our results indicate that a histone deacetylase-dependent transcriptional repressor can be positively regulated through acetylation and point to an unexpected role of a coactivator protein in transcriptional repression.


Disentangling the Individual-Shared and Individual-Specific Subspace of Altered Brain Functional Connectivity in Autism Spectrum Disorder.
Despite considerable effort toward understanding the neural basis of autism spectrum disorder (ASD) using case-control analyses of resting-state functional magnetic resonance imaging data, findings are often not reproducible, largely due to biological and clinical heterogeneity among individuals with ASD. Thus, exploring the individual-shared and individual-specific altered functional connectivity (AFC) in ASD is important to understand this complex, heterogeneous disorder. We considered 254 individuals with ASD and 295 typically developing individuals from the Autism Brain Imaging Data Exchange to explore the individual-shared and individual-specific subspaces of AFC. First, we computed AFC matrices of individuals with ASD compared with typically developing individuals. Then, common orthogonal basis extraction was used to project AFC of ASD onto 2 subspaces: an individual-shared subspace, which represents altered connectivity patterns shared across ASD, and an individual-specific subspace, which represents the remaining individual characteristics after eliminating the individual-shared altered connectivity patterns. Analysis yielded 3 common components spanning the individual-shared subspace. Common components were associated with differences of functional connectivity at the group level. AFC in the individual-specific subspace improved the prediction of clinical symptoms. The default mode network-related and cingulo-opercular network-related magnitudes of AFC in the individual-specific subspace were significantly correlated with symptom severity in social communication deficits and restricted, repetitive behaviors in ASD. Our study decomposed AFC of ASD into individual-shared and individual-specific subspaces, highlighting the importance of capturing and capitalizing on individual-specific brain connectivity features for dissecting heterogeneity. Our analysis framework provides a blueprint for parsing heterogeneity in other prevalent neurodevelopmental conditions.


Evaluation of Surrogate Endpoints Using Information-Theoretic Measure of Association Based on Havrda and Charvat Entropy.
Surrogate endpoints have been used to assess the efficacy of a treatment and can potentially reduce the duration and/or number of required patients for clinical trials. Using information theory, Alonso et al. (2007) proposed a unified framework based on Shannon entropy, a new definition of surrogacy that departed from the hypothesis testing framework. In this paper, a new family of surrogacy measures under Havrda and Charvat (H-C) entropy is derived which contains Alonso's definition as a particular case. Furthermore, we extend our approach to a new model based on the information-theoretic measure of association for a longitudinally collected continuous surrogate endpoint for a binary clinical endpoint of a clinical trial using H-C entropy. The new model is illustrated through the analysis of data from a completed clinical trial. It demonstrates advantages of H-C entropy-based surrogacy measures in the evaluation of scheduling longitudinal biomarker visits for a phase 2 randomized controlled clinical trial for treatment of multiple sclerosis.


Chromosomal location and cloning of the gene (trmD) responsible for the synthesis of tRNA (m1G) methyltransferase in Escherichia coli K-12.
The trmD gene, which governs the formation of 1-methyl-guanosine(m1G) in transfer ribonucleic acid (tRNA), has been located by phage P1 transduction at 56 min on the chromosomal map of Escherichia coli. Cotransduction to tyrA at 56 min is 80%. From the Clarke and Carbon collection a ColE1-tyrA+ hybrid plasmid was isolated, which carried the trmD+ gene and was shown to over-produce the tRNA(m1G)methyltransferase. By subcloning restriction enzyme fragments in vitro, the trmD+ gene was located to a 3.4 kb DNA fragment 6.5 kb clockwise from the tyrA+ gene. The mutation trmD1, which renders the tRNA(m1G)methyltransferase temperature-sensitive both in vivo and in vitro could be complemented by trmD+ plasmids. These results suggest that the gene trmD+ is the structural gene for the tRNA(m1G)methyltransferase (EC 184.108.40.206.1).


Serotypes of bovine rotaviruses distinguished by serum neutralization.
Fourteen cytopathic bovine rotaviruses isolated from naturally affected calves were characterized serologically by serum neutralization. Antisera were prepared in guinea pigs against the three isolates and the Lincoln strain of bovine rotavirus. These four rotaviruses were segregated into at least two distinct serotypes (designated types 1 and 2) by serum neutralization. The remaining 11 isolates were also placed into two groups according to neutralization specificity by using the antisera against types 1 and 2 bovine rotavirus. When colostrum-deprived calves were experimentally inoculated with type 1 or 2 bovine rotavirus, respectively, the calves produced neutralizing antibodies against the inoculated serotype but not against the other serotype. Calf sera obtained from six herds with naturally occurring rotavirus infections possessed neutralizing antibodies against type 1 or 2 or both. Thus, distinct serotypes of bovine rotavirus were demonstrated by serum neutralization. The possible role of serotypes in the epidemiology of rotavirus infection among bovine species is discussed.


Clinical characteristics of breast cancer patients with mental disorders.
Severe mental disorders are thought to affect the diagnosis and treatment of breast cancer because of their lower awareness and understanding of the disease and their reduced ability to cooperate with medical staff. We analyzed the clinical features of patients with breast cancer and pre-existing mental disorders such as schizophrenia, dementia, and intellectual disability. We reviewed the records of 46 patients who were diagnosed with schizophrenia, dementia, or intellectual disability, before being diagnosed with breast cancer. Three patients had more than 2 mental disorders. All patients underwent curative surgical treatment between September 1992 and January 2015. Patients' clinicopathological information was compared with a control group of 727 breast-cancer patients without mental disorders seen during the same period. Patients with mental disorders were less likely to be aware of their own breast cancer; the lesions were often found by other people such as family, care staff, and medical staff. Breast cancer patients with mental disorders had significantly more advanced T factors and overall stage at the time of surgery than their counterparts without mental illness, more patients underwent total mastectomy, and fewer patients underwent postoperative adjuvant chemotherapy and radiation. Biological markers such as estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 (HER2) expression were not significantly different between groups. Disease-free survival and overall survival were not significantly different between groups. Patients with mental disorders receive less postoperative adjuvant chemotherapy; however, their outcomes were not worse than those of patients without mental disorders.


A review of the currently recognised opecoelid cercariae, including the identification and emergence ecology of Cercaria capricornia XII (Digenea: Opecoelidae) from Nassarius olivaceus (Gastropoda: Nassariidae) in Central Queensland, Australia.
A new opecoelid cercaria, Cercaria capricornia XII, is reported from Nassarius olivaceus in Capricornia, Central Queensland, Australia. Combined molecular and morphological data indicate that this cercaria is a member of the subfamily Opecoelinae. Cercaria capricornia XII is the first known opecoeline cercaria reported from a nassariid gastropod. Cercaria capricornia XII can be distinguished from other opecoelid cercariae by the combination of the presence of a 2-pointed stylet, body length and width, and the size of the tail. The emergence pattern for C. capricornia XII in captivity was erratic; rapid emergences of thousands of cercariae were interspersed by periods that sometimes exceeded a month in which no emergence occurred. There was no detectable pattern to or stimulus of the emergence. The molluscan host range of opecoelids is analysed in detail. Gastropods from the Buccinoidea, Cerithioidea and Rissooidea are hosts to both opecoeline and plagioporine cercariae, but the dominant subfamily infecting the Cerithioidea and Rissooidea is the Plagioporinae. The dominant marine host gastropod superfamily for opecoeline cercariae is the Buccinoidea; the family Nassariidae is contained in the Buccinoidea. The range of gastropod superfamilies known as hosts of plagioporines is much broader than that for opecoelines, which may be explained by the relative size of the two opecoelid families and perhaps by indications that the Plagioporinae is polyphyletic.


Treatment outcome for nasopharyngeal carcinoma in University Malaya Medical Centre from 2004-2008.
Nasopharyngeal carcinoma (NPC) is the commonest radiocurable cancer in Malaysia. This study aimed to determine the treatment outcomes and late effects of radiotherapy for NPC patients treated in University Malaya Medical Centre (UMMC). All newly diagnosed patients with NPC referred for treatment to the Oncology unit at UMMC from 2004-2008 were retrospectively analyzed. Treatment outcomes were 5 years overall survival (OS), disease free survival (DFS), cause-specific survival (CSS), loco- regional control (LRC) and radiotherapy-related late effects. The Kaplan-Meier method was used for survival analysis and differences in survival according to AJCC stage was compared using the log-rank test. A total of 176 patients with newly diagnosed NPC were treated in UMMC during this period. Late presentation was common, with 33.5% presenting with T3-4 disease, 84.7% with N1-3 disease and 75.6% with AJCC stage 3-4 disease. Radical RT was given to 162 patients with 22.7% having RT alone and 69.3% having CCRT. The stipulated OTT was 7 weeks and 72.2% managed to complete their RT within this time period. Neoadjuvant chemotherapy was given to 14.8% while adjuvant chemotherapy was administered to 16.5%. The 5 years OS was 51.6% with a median follow up of 58 months. The 5 years OS according to stage were 81.8% for stage I, 77.9% for stage II, 47.4% for stage III and 25.9% for stage IV. The 5 years overall CSS, DFS and LRC were 54.4%, 48.4% and 70.6%, respectively. RT related late effects were documented in 80.2%. The commonest was xerostomia (66.7%). Other documented late effects were hearing deficit (17.3%), visual deficit (3.1%), neck stiffness (3.1%) , dysphagia (3.4%), cranial nerve palsy (2.5%), pneumonitis (0.6%) and hypothyroidism (1.2%). The 5 years OS and LRC in this study are low compared to the latest studies especially those utilizing IMRT. Implementation of IMRT for NPC treatment should be strongly encouraged.


A contraindication for the use of hydroxyapatite cement in the pediatric population.
The authors report on their experience with a particular hydroxyapatite cement in the pediatric population and review cases that elucidate potential limitations of its use in this population. In all patients, the implant was used for recontouring and augmenting the cranial vault. Seven of 15 patients had a direct communication between sinus mucosa and the implant at the time of surgery. Three of the seven patients developed late postoperative inflammatory reactions of the surgical site with delamination of the implant. Each patient required an aggressive irrigation and débridement with removal of the delaminated hydroxyapatite. Pathologic findings showed evidence of a foreign body inflammatory reaction in the tissue, and mixed bacterial flora were identified in all specimens. No late problems with the cement were seen in patients without a communication to the sinuses. Our findings suggest that the use of BoneSource, an essentially nonviable, nonvascularized implant, in areas exposed to bacterial contamination is contraindicated in the pediatric population. BoneSource and other similar hydroxyapatite biomaterials do have a role as implants in the craniofacial skeleton. The indications and contraindications of these substances will need to be further defined for wide acceptance to occur.


Adrenal function in sepsis and septic shock.
To review diagnostic criteria and treatment of adrenal insufficiency in pediatric patients with severe sepsis and septic shock. Articles were selected using MEDLINE (1966-June 2007), Embase (1994-2007) and Cochrane Library (2000-2007) databases. following key words were utilized: septic shock, sepsis, corticosteroids, adrenal insufficiency and children. There are no well established and accepted criteria to define adrenal insufficiency in critically ill patients. Incidence of adrenal insufficiency varies according to different criteria, and it may range between low values of 15% and high values of 61%. The rapid corticotropin stimulation test is widely used as a method to identify adrenocortical hyporesponsiveness, but controversy exists as to the corticotropin dose to be used. The 250 microg dose is the standard dose. Low doses of corticotropin (1microg) have recently been proposed, suggesting that they may have higher sensitivity. There are still doubts as to the efficacy of low doses of corticosteroids in children with catecholamine-refractory shock. Further studies are needed to determine whether the treatment of these patients would change morbidity and/or mortality. Adrenal insufficiency is common in children with severe sepsis and septic shock and may contribute to the development of catecholamine-refractory shock. However, doubts still persist regarding the efficacy of replacement therapy with low-doses steroids.


Improvement of multisource localization of magnetic particles in an animal.
In this simulation work, the linearized Bregman iterative algorithm was applied to solve the magnetic source distribution problem of a magnetic particle imaging (MPI) system for small animals. MPI system can apply an excitation magnetic field, and the induced magnetic field from the magnetic nanoparticles (MNPs) can be detected by the sensors of MPI system. With a gaussian distribution source at the upper side of the mouse brain, sensors set above the mouse brain and the constant excitation magnetic field, the average deviation of the calculated source distribution from the multiplane scanning along the axis away from the mouse brain and the closest plane scanning are 2.78 × 10-3 and 2.84 × 10-3 respectively. The simulated result showed that combination of multiplane scanning hardly improves the accuracy of the source localization. In addition, a gradient scan method was developed that uses gradient magnetic field to scan the mouse brain. The position of the maximum of the lead field matrix will be controlled by the gradient field. With a set up gaussian distribution source at the bottom of the mouse brain, the average deviation of the calculated source distribution from the gradient scan method and the constant field are 4.42 × 10-2 and 5.05 × 10-2. The location error from the two method are 2.24 × 10-1 cm and 3.61 × 10-1 cm. The simulation showed that this method can improve the accuracy compared to constant field when the source is away from the sensor and having a potential for application.


Recent advances in the synchronization of estrus and ovulation in dairy cows.
Synchronization programs have become standard components in the current breeding management of cows in the dairy herds of most dairy industries. Many are based on protocols that allow timed inseminations (TAI) so as to circumvent the practical difficulties associated with estrus detection. These difficulties are exacerbated in modern herds of high producing cows either because of increasing herd size in which individual animal monitoring is difficult and often subjective, or because small intensively managed herds are milked in robotic systems that minimize animal: staff interactions. Additional reasons arise from high producing cows having less obvious symptoms of estrus, partly because of housing systems combined with intensive feeding and milking, partly because of higher metabolic clearance rates of reproductive hormones like estradiol and partly because of the increasing prevalence of prolonged post-partum anestrus and reproductive tract pathology. The most recently developed programs include protocols for resynchronization following first or subsequent inseminations. These re-synchronization protocols may involve selected forms of hormonal intervention during the diestrous and pro-estrous periods following TAI, or following pregnancy diagnosis by ultrasound from 28 days after TAI. The latter form of re-synchronization has become increasingly important with the recognition that late embryonic/early foetal death has become a major factor compromising the reproductive performance of high producing Holstein cows in many dairy industries. Although cows detected in estrus without any hormonal treatment before insemination have higher conception rates than those inseminated following synchronization and TAI, the low detection rates combined with embryonic death means that intervals from calving to conception (days open) are usually less when synchronization programs have been successfully implemented. One of the significant factors affecting a program's success is the compliance rate that may sometimes be less than 70%. Almost all programs involve strategically timed injections of prostaglandin F2alpha (PGF) and gonadotropin releasing hormone (GnRH). Injections of an estradiol ester and progesterone supplementation per vaginum may be included in some programs. The basic program is the "Ovsynch" regimen. Numerous variations have been tested and developed. Many involve increasingly complex protocols that increase the risk of non-compliance, none has consistently achieved conception rates that exceed 40% and few have reduced the incidence of embryonic death. These synchronization programs are the best that are currently available. They have not been able to overcome the consequences of lowered fertility associated with high levels of milk yield, forms of nutrition and environmental factors like heat stress that have profound effects on the physiology and metabolism of the high producing dairy cow.


Differential regulation of human NK cell-mediated cytotoxicity by the tyrosine kinase Itk.
NK cells are effector lymphocytes that can recognize and eliminate virally infected and transformed cells. NK cells express distinct activating receptors, including an ITAM-containing FcR complex that recognizes Ab-coated targets, and the DNAX-activating protein of 10 kDa-containing NKG2D receptor complex that recognizes stress-induced ligands. The regulatory role of specific tyrosine kinases in these pathways is incompletely understood. In this study, we show that, in activated human NK cells, the tyrosine kinase IL-2-inducible T cell kinase (Itk), differentially regulates distinct NK-activating receptors. Enhanced expression of Itk leads to increases in calcium mobilization, granule release, and cytotoxicity upon stimulation of the ITAM-containing FcR, suggesting that Itk positively regulates FcR-initiated cytotoxicity. In contrast, enhanced Itk expression decreases cytotoxicity and granule release downstream of the DNAX-activating protein of 10 kDa-containing NKG2D receptor, suggesting that Itk is involved in a pathway of negative regulation of NKG2D-initiated granule-mediated killing. Using a kinase mutant, we show that the catalytic activity of Itk is required for both the positive and negative regulation of these pathways. Complementary experiments where Itk expression was suppressed also showed differential regulation of the two pathways. These findings suggest that Itk plays a complex role in regulating the functions initiated by distinct NK cell-activating receptors. Moreover, understanding how these pathways may be differentially regulated has relevance in the setting of autoimmune diseases and antitumor immune responses where NK cells play key regulatory roles.


Making evidence-based medicine (EBM) doable in developing countries: a locally-tailored workshop for EBM in a Pakistani institution.
To demonstrate that evidence-based medicine (EBM) training can be imparted in developing countries using minimal resources. Development of a minimal cost workshop with validation of gain in EBM skills using the Berlin questionnaire. Teaching hospital in Pakistan. Multidisciplinary faculty from The Shifa College of Medicine and Nursing, Pakistan. A 14-hour locally-tailored McMaster-style workshop, using a problem-based, learner-focused small group format, with pre- and post-workshop evaluation of EBM skills. Analysis of the pre- and post-Berlin questionnaires of the participants revealed that the pre-workshop Berlin questionnaire score for the group was 4.7+/-2.3, with a post-workshop Berlin score of 7.6+/-1.0 (p<0.001). EBM workshops can be locally-tailored in developing countries, where access to such workshops is generally not available. Workshops can serve to promote EBM skills in faculty, who can then help to disseminate and model concepts. The process increases awareness and interest in EBM, which in this case resulted in formation of a national platform for EBM.


Ovulation suppression for endometriosis.
Endometriosis is the finding of endometrial glands or stroma in sites other than the uterine cavity. Endometriosis appears to be an oestrogen dependent condition. This hormonal dependency has prompted the therapeutic use of ovulation suppression agents, in an effort to improve subsequent fertility. To assess the effectiveness of ovulation suppression agents, including danazol, progestins and oral contraceptives, in the treatment of endometriosis-associated subfertility in improving pregnancy outcomes including live birth. We searched the Cochrane Menstrual Disorders and Sub-fertility Group's specialised register of trials (searched October 5th, 2007) the Cochrane Register of Controlled Trials (The Cochrane Library, Issue 3, 2007), MEDLINE (1966-October 2007), EMBASE (1980 - October 2007) and reference lists of articles. Randomised trials comparing an ovulation suppression agent with placebo or no treatment, or a suppressive agent with danazol or a GnRH with oral contraception in women with endometriosis. A total of twenty three RCTs comparing an ovulation suppression agent with placebo or no treatment, or a suppressive agent with danazol or a GnRH with oral contraception were identified. Two review authors independently extracted data and assessed quality. We contacted study authors for additional information. Quality was assessed by of method of randomization,allocation concealment, blinding, completeness of follow-up, presence or absence of crossover and co-intervention. 2 x 2 tables were generated for all relevant outcomes. Odds ratios were generated using the Peto modified Mantel-Haenszel technique. Statistical heterogeneity was assessed using the I(2) test of heterogeneity. Subgroup analysis was conducted on those couples clearly identifiable as infertile or wanting to conceive. Twenty four trials were included. The odds ratio for pregnancy following ovulation suppression versus placebo or no treatment for all women randomised was 0.79 (95% CI 0.54 to 1.14), P = 0.21 and 0.80 (95% CI 0.51 to 1.24), P = 0.32 respectively for subfertile couples only despite the use of a variety of suppression agents. There was no evidence of benefit from the treatment. The common odds ratio for pregnancy following all agents versus danazol for all women randomised was 1.38 (95% CI 1.05 to 1.82), P = 0.02 and OR 1.37 (95% CI 0.94 to 1.99), P = 0.10 for subfertile couples only. When GnRHa and danazol were directly compared, OR was 1.45 (95% CI 1.08 to 1.95) P = 0.01 for all women randomised and OR 1.63( 95% CI 1.12 to 2.37), P = 0.01 for subfertile couples only in favour of GnRH. No effect was observed for GnRH compared with oral contraception; OR 0.99 (95% CI 0.52 to 1.89), P = 0.98 for all women randomised and OR 0.79 ( 95% CI 0.37 to 1.69), P = 0.55. In all analyses the data were statistically homogeneous (I(2)=0%). There is no evidence of benefit in the use of ovulation suppression in subfertile women with endometriosis who wish to conceive.


A Mindfulness-Based Intervention for Student Depression, Anxiety, and Stress: Randomized Controlled Trial.
University students are experiencing higher levels of distress and mental health disorders than before. In addressing mental health needs, web-based interventions have shown increasing promise in overcoming geographic distances and high student-to-counselor ratios, leading to the potential for wider implementation. The Mindfulness Virtual Community (MVC) program, a web-based program, guided by mindfulness and cognitive behavioral therapy principles, is among efforts aimed at effectively and efficiently reducing symptoms of depression, anxiety, and perceived stress in students. This study's aim was to evaluate the efficacy of an 8-week MVC program in reducing depression, anxiety, and perceived stress (primary outcomes), and improving mindfulness (secondary outcome) in undergraduate students at a large Canadian university. Guided by two prior randomized controlled trials (RCTs) that each demonstrated efficacy when conducted during regular university operations, this study coincided with a university-wide labor strike. Nonetheless, the students' response to an online mental health program on a disrupted campus can provide useful information for anticipating the impact of other disruptions, including those related to the COVID-19 pandemic as well as future disruptions. In this parallel-arm RCT, 154 students were randomly allocated to an 8-week MVC intervention (n=76) or a wait-list control (WLC) condition (n=78). The MVC intervention included the following: (1) educational and mindfulness video modules, (2) anonymous peer-to-peer discussions, and (3) anonymous, group-based, professionally guided, 20-minute videoconferences. Study outcomes were evaluated at baseline and at 8-week follow-up using the following: Patient Health Questionnaire-9 (PHQ-9), the Beck Anxiety Inventory (BAI), the Perceived Stress Scale (PSS), and the Five Facets Mindfulness Questionnaire Short Form (FFMQ-SF). Generalized estimation equations with an AR (1) covariance structure were used to evaluate the impact of the intervention, with outcome evaluations performed on both an intention-to-treat (ITT) and per-protocol (PP) basis. Participants (n=154) included 35 males and 117 females with a mean age of 23.1 years. There were no statistically significant differences at baseline between the MVC and WLC groups on demographics and psychological characteristics, indicating similar demographic and psychological characteristics across the two groups. Results under both ITT and PP approaches indicated that there were no statistically significant between-group differences in PHQ-9 (ITT: β=-0.44, P=.64; PP: β=-0.62, P=.053), BAI (ITT: β=-2.06, P=.31; PP: β=-2.32, P=.27), and FFMQ-SF (ITT: β=1.33, P=.43; PP: β=1.44, P=.41) compared to WLC. There was a significant difference for the PSS (ITT: β=-2.31, P=.03; PP: β=-2.38, P=.03). During a university labor strike, the MVC program led to statistically significant reductions in PSS compared to the WLC group, but there were no other significant between-group differences. Comparisons with previous cycles of intervention testing, undertaken during nondisrupted university operations, when efficacy was demonstrated, are discussed. ISRCTN Registry ISRCTN92827275; https://www.isrctn.com/ISRCTN92827275.


Concordance among hematopathologists in classifying blasts plus promonocytes: A bone marrow pathology group study.
Enumeration of blasts and promonocytes is essential for World Health Organization (WHO) classification of myelomonocytic neoplasms. The accuracy of distinguishing blasts, promonocytes and monocytes, including normal vs abnormal monocytes, remains controversial. The objective of this analysis is to assess concordances between experienced hematopathologists in classifying cells as blasts, promonocytes, and monocytes according to WHO criteria. Each of 11 hematopathologists assessed glass slides from 20 patients [12 with chronic myelomonocytic leukemia (CMML) and 8 with acute myeloid leukemia (AML)] including blood and BM aspirate smears, and limited nonspecific esterase (NSE) stains. All cases were blindly reviewed. Fleiss' extension of Cohen's kappa for multiple raters was used on these variables, separately for peripheral blood (PB) and bone marrow (BM). Spearman's rank correlation was used to assess correlations between each pair of hematopathologists for each measurement. For the classification based on the sum of blasts and promonocytes in the BM, Fleiss' kappa was estimated as 0.744. For PB, categorizing patients according to the sum of blasts and promonocytes, Fleiss' kappa was estimated as 0.949. Distinction of abnormal monocytes from normal monocytes in PB did not achieve a good concordance and showed strong evidence of differences between hematopathologists (P < .0001). The hematopathologists achieved a good concordance rate of 74% in CMML vs AML classification and a high k rate, confirming that criteria for defining the blasts equivalents (blasts plus promonocytes) could be applied consistently. Identification of monocyte subtypes (abnormal vs normal) was not concordant. Our results support the practice of combining blasts/promonocytes into a single category.


Electrophysiological indices of response inhibition in a Go/NoGo task predict self-control in a social context.
Recent research demonstrates that response inhibition-a core executive function-may subserve self-regulation and self-control. However, it is unclear whether response inhibition also predicts self-control in the multifaceted, high-level phenomena of social decision-making. Here we examined whether electrophysiological indices of response inhibition would predict self-control in a social context. Electroencephalography was recorded as participants completed a widely used Go/NoGo task (the cued Continuous Performance Test). Participants then interacted with a partner in an economic exchange game that requires self-control. Results demonstrated that greater NoGo-Anteriorization and larger NoGo-P300 peak amplitudes-two established electrophysiological indices of response inhibition-both predicted more self-control in this social game. These findings support continued integration of executive function and self-regulation and help extend prior research into social decision-making processes.


Deposition of mouse amyloid beta in human APP/PS1 double and single AD model transgenic mice.
The deposition of amyloid beta (Abeta) peptides and neurofibrillary tangles are the two characteristic pathological features of Alzheimer's disease (AD). To investigate the relation between amyloid precursor protein (APP) production, amyloid beta deposition and the type of Abeta in deposits, i.e., human and/or mouse, we performed a histopathological analysis, using mouse and human specific antibodies, of the neocortex and hippocampus in 6, 12 and 19 months old APP/PS1 double and APP and PS1 single transgenic mice. There was a significant correlation between the human amyloid beta deposits and the intrinsic rodent amyloid beta deposits, that is, all plaques contained both human and mouse Abeta, and the diffuse amyloid beta deposits also colocalized human and mouse Abeta. Furthermore, some blood vessels (mainly leptomeningeal vessels) show labeling with human Abeta, and most of these vessels also label with mouse Abeta. Our findings demonstrate that the human amyloid deposits in APP/PS1 transgenic mice are closely associated with mouse Abeta, however, they do not precisely overlap. For instance, the core of plaques consists of primarily human Abeta, whereas the rim of the plaque contains both human and mouse amyloid beta, similarly, human and mouse Abeta are differentially localized in the blood vessel wall. Finally, as early as amyloid beta deposits can be detected, they show the presence of both human and mouse Abeta. Together, these data indicate that mouse Abeta is formed and deposited in significant amounts in the AD mouse brain and that it is deposited together with the human Abeta.


Utility of fecal lactoferrin in identifying Crohn disease activity in children.
Fecal lactoferrin (FL) is a noninvasive biomarker that is elevated in Crohn disease (CD) compared to irritable bowel syndrome. The purpose of this study was to evaluate FL in identifying children with active versus inactive CD. Fresh stool samples were collected from children with CD scheduled for endoscopy or a clinic visit, and from new outpatients who were scheduled for colonoscopy. FL was determined using a polyclonal antibody-based enzyme-linked immunosorbent assay. Physical global assessment, endoscopic findings, erythrocyte sedimentation rate (ESR), and the Pediatric CD Activity Index (PCDAI) were recorded for patients with CD. The PCDAI scores symptoms, laboratory parameters, physical examination, and extraintestinal manifestations. A score of ≤10 is inactive disease, 11 to 30 is mild active, and ≤31 is moderate to severe active. Of 101 study patients (4- to 20-year-old, 66 boys), 31 had active CD, 23 had inactive CD, and 37 had noninflammatory bowel disease (non-IBD) conditions. Four patients with ulcerative colitis and 6 patients with polyposis were excluded from analysis. FL was significantly elevated in CD versus non-IBD (P < 0.001) and in active versus inactive CD (P < 0.001). The PCDAI and ESR were higher in active CD than in inactive CD (both P < 0.001). Using an FL cutoff of 7.25 μg/g, FL has 100% sensitivity and 100% negative predictive value in detecting active CD. Using an FL cutoff level of 60 μg/g, FL had 84% sensitivity, 74% specificity, 81% positive predictive value, and 77% negative predictive value for detecting active CD. FL is a promising biomarker of active CD and may be more practical to use when it is not feasible to obtain all of the necessary clinical information for the PCDAI.


Bone density in haemophilia: a single institutional cross-sectional study.
Haemophilia has been associated with low bone mineral density (BMD). However, prior clinical studies of this population have neither clearly elucidated risk factors for development of low BMD nor identified who may warrant screening for osteoporosis. The aim of the study was to evaluate the relationship between BMD and haemophilic arthropathy and other demographic and clinical variables. We undertook a cross-sectional study of BMD in adult men with haemophilia. Measures of predictor variables were collected by radiographic studies, physical examination, patient questionnaires and review of medical records. Among 88 enrolled subjects, the median age was 41 years (IQR: 20); median femoral neck BMD (n = 87) was 0.90 g cm(-2) (IQR: 0.24); and median radiographic joint score was 7.5 (IQR: 18). Among subjects <50 years (n = 62), after controlling for BMI, alcohol, HIV and White race, BMD decreased as radiographic joint score increased (est. β = -0.006 mg cm(-2) ; 95% CI -0.009, -0.003; partial R(2) = 0.23). Among subjects ≥50 years (n = 26), 38% had osteoporosis (T score less than or equal to -2.5) and there was no association between BMD and arthropathy. Risk factors for low BMD in men with haemophilia <50 years include haemophilic arthropathy, low or normal BMI and HIV. Men with haemophilia over age 50 years should have routine screening for detection of osteoporosis.


Acute pancreatitis induced by etoposide-lobaplatin combination chemotherapy used for the treatment of lung cancer: A case report and literature review.
Drug-induced pancreatitis (DIP) is a rare type of pancreatitis that is not usually observed in the clinical practice. It is generally difficult to distinguish from acute pancreatitis (AP) induced by other causes. Here, we report a 62-year-old Chinese female patient with "small cell lung cancer" as the initial presentation. Because the patient could not bear the surgical treatment, the chemotherapy composed of lobaplatin and etoposide was performed. Three days later, the patient displayed sudden abdominal pain, distension, nausea, and vomiting without obvious inducements. Laboratory tests showed that the levels of serum and urine amylase were enhanced; abdominal computed tomography (CT) result showed the enlargement of the pancreas, peripancreatic effusion, and a rough edge, which suggested the diagnosis of AP. The patient had no history of biliary tract disease, alcoholism, binge overeating, hyperlipidemia, and hereditary pancreatitis. The patient was diagnosed with DIP. The chemotherapy was stopped at once and we performed fluid resuscitation, pain alleviation, prophylactic antibiotics, and nutritional support, etc on the patient. Later, the patient's clinical symptoms were obviously relieved, and she recovered successfully. The chemotherapy was continued, but later, the patient showed abdominal pain, distension, nausea, and vomiting again. The levels of serum amylase and urine amylase were enhanced again. Further imaging examination strongly indicated the recurrence of AP. We should raise awareness of the clinicians regarding DIP, thereby enabling its timely diagnosis and accurate treatment, as well as promoting the rational and safe use of drugs.


Adenovirus-retrovirus hybrid vectors achieve highly enhanced tumor transduction and antitumor efficacy in vivo.
Murine leukemia virus (MLV)-based replication-competent retrovirus (RCR) vectors have been shown to mediate efficient, selective, and persistent tumor transduction, thereby achieving significant therapeutic benefit in a wide variety of cancer models. To further augment the efficiency of this strategy, we have developed a delivery method employing a gutted adenovirus encoding an RCR vector (AdRCR); thus, tumor cells transduced with the adenoviral vector transiently become RCR vector producer cells in situ. As expected, high-titer AdRCR achieved significantly higher initial transduction levels in human cancer cells both in vitro and in vivo, as compared to the original RCR vector itself. Notably, even at equivalent initial transduction levels, more secondary RCR progeny were produced from AdRCR-transduced cells as compared to RCR-transduced cells, resulting in further acceleration of subsequent RCR replication kinetics. In pre-established tumor models in vivo, prodrug activator gene therapy with high-titer AdRCR could achieve enhanced efficacy compared to RCR alone, in a dose-dependent manner. Thus, AdRCR hybrid vectors offer the advantages of high production titers characteristic of adenovirus and secondary production of RCR in situ, which not only accelerates subsequent vector spread and progressive tumor transduction, but can also significantly enhance the therapeutic efficacy of RCR-mediated prodrug activator gene therapy.


Development and psychometric properties of the Multidimensional Schizotypy Scale: A new measure for assessing positive, negative, and disorganized schizotypy.
This article reports on the development of a new self-report questionnaire measure of schizotypy - the Multidimensional Schizotypy Scale (MSS). Schizotypy offers a useful and unifying construct for understanding schizophrenia-spectrum psychopathology. Questionnaire measures have been widely used to assess schizotypy and have greatly informed our understanding of the construct. However, available measures suffer from a number of limitations, including lack of a clear conceptual framework, outdated wording, unclear factor structure, and psychometric shortcomings. The MSS is based on current conceptual models and taps positive, negative, and disorganized dimensions of schizotypy. The derivation sample included 6265 participants sampled from four universities and Amazon Mechanical Turk. A separate sample of 1000 participants from these sources was used to examine the psychometric properties of the final subscales. Scale development employed classical test theory, item response theory, and differential item function methods. The positive schizotypy and negative schizotypy subscales contain 26 items each, and the disorganized schizotypy subscale contains 25 items. The psychometric properties were almost identical in the derivation and validation samples. All three subscales demonstrated good to excellent reliability, high item-scale correlations, and good item and test curve characteristics. The MSS appears to provide a promising measure for assessing schizotypy.


Extraocular muscle recession with a suture loop in dogs.
Extraocular muscle recessions with loops of silk suture were performed in 10 dogs. When, after a 5-mm section of the medial rectus muscle was resected, suture loops 5 mm long were inserted near the functional equator (8 mm behind the muscle's original insertion) an effective pseudotendon was produced in 71% of the eyes. This procedure may be a useful addition to the surgical methods of correcting horizontal strabismus.


Single-drug chemotherapy with 5-FU and adriamycin in metastatic bladder cancer.
Either 5-fluorouracil (5-FU) or Adriamycin was used as single-drug treatment in 10 and 15 patients respectively with measurable metastatic bladder carcinoma. In the 5-FU group there were one complete and 2 partial remissions. Six partial remissions were observed in patients treated with Adriamycin. The duration of the remissions was usually short. Gastrointestinal and haematological side effects were more pronounced in the Adriamycin group. The results are discussed in relation to other reports on cytostatic treatment of bladder carcinoma, with emphasis on general problems concerning chemotherapy of this disease.


[Chest trauma: analysis of 592 cases].
Thoracic traumas constitute an important part of the patients who are being admitted to the emergency units and deaths due to trauma. The aim of this study was to compare our clinical experience and results of the literature. 592 patients with thoracic trauma who were admitted to our clinic between 1996 and 2000 were evaluated retrospectively. 449 patients (75.8%) had blunt and 43 patients (24.2%) had penetrating thorax trauma. There was rib fracture in 448 patients (75.7%), clavicula fracture in 55 (9.2%), scapula fracture in 31 (5.2%) and sternal fracture in 20 (3.4%). In addition, flail chest was detected in 79 cases (13.3%). The most frequent complications were pneumothorax (n: 158; 26.7%), and hemothorax ( n: 119; 20.1% ). Three hundred and thirty - nine patients (57.2%) were treated by tube thoracostomy and 190 by conservative management (32.1%). Surgical treatment was performed in 99 (16.7%) patients. Morbidity was 18.4% ( n: 109 ) and mortality, 6.4% ( n: 38 ). Mean hospital stay time was 13.4 days (2 - 93 days). Thoracic traumas can cause vital organ injuries and impaired cardio-respiratory hemodynamics should be treated immediately.


Positive and relaxed selection associated with flight evolution and loss in insect transcriptomes.
The evolution of powered flight is a major innovation that has facilitated the success of insects. Previously, studies of birds, bats, and insects have detected molecular signatures of differing selection regimes in energy-related genes associated with flight evolution and/or loss. Here, using DNA sequences from more than 1000 nuclear and mitochondrial protein-coding genes obtained from insect transcriptomes, we conduct a broader exploration of which gene categories display positive and relaxed selection at the origin of flight as well as with multiple independent losses of flight. We detected a number of categories of nuclear genes more often under positive selection in the lineage leading to the winged insects (Pterygota), related to catabolic processes such as proteases, as well as splicing-related genes. Flight loss was associated with relaxed selection signatures in splicing genes, mirroring the results for flight evolution. Similar to previous studies of flight loss in various animal taxa, we observed consistently higher nonsynonymous-to-synonymous substitution ratios in mitochondrial genes of flightless lineages, indicative of relaxed selection in energy-related genes. While oxidative phosphorylation genes were not detected as being under selection with the origin of flight specifically, they were most often detected as being under positive selection in holometabolous (complete metamorphosis) insects as compared with other insect lineages. This study supports some convergence in gene-specific selection pressures associated with flight ability, and the exploratory analysis provided some new insights into gene categories potentially associated with the gain and loss of flight in insects.


Optimizing QT Interval Measurement for the Preparticipation Screening of Young Athletes.
Sudden cardiac death is the leading cause of death in athletes. Long QT syndrome (LQTS) is one of the most common cardiogenetic diseases that can lead to sudden cardiac death and is identified by QT interval prolongation on an ECG. Recommendations for QT monitoring in athletes are adopted from nonathlete populations. To improve screening, ECG data of athletes are assessed to determine a more appropriate method for QT interval estimation. ECG (CardeaScreen) data were collected from June 2010 to March 2015. ECG data with HR greater than 100 bpm were excluded. Fiducial points of outliers were manually corrected if the QRS onset or the T wave offset was misidentified. A model of best fit was determined and compared across four QT correction factors. Classification analysis was used to compare the Bazett's corrected QT interval to the 99th percentile of uncorrected QT interval. High school (n = 597), college (n = 1207), and professional athletes (n = 273) (N = 2077) were analyzed. Mean age was 19 ± 3.5 yr. QT interval varied by cohort (HS = 388 ± 30, Col = 410 ± 33, Pro = 407 ± 27, p < 0.0001). A nonlinear power function with a cubic exponent of -0.349 fit the data the best (R = 0.64). Of the four common correction factors, Fridericia had the lowest residual dependence to HR (m = -0.10). With standard screening, 75% of athletes within the top 1% for QT interval were not identified for further investigation for LQTS. Up to 75% of athletes possessing an uncorrected QT interval greater than 99% of the population are not identified for investigation for LQTS using the recommended criteria. We propose a new method of risk stratification that replaces QT interval correction. Further study is needed to establish QT interval distributions and risk thresholds in athletes.


Hormonal stimulation of carp is accompanied by changes in seminal plasma proteins associated with the immune and stress responses.
Hormonal stimulation in common carp is a routine practice to enhance sperm production and control gamete maturation. This study aimed to compare the proteome of carp seminal plasma between control and Ovopel-induced males using two-dimensional differential in-gel electrophoresis. Ovopel induction increased sperm volume, total sperm count, seminal plasma osmolality, and pH and decreased seminal plasma protein concentration. In total, 36 spots were identified (23 up- and 13 downregulated), corresponding to 23 proteins differentially abundant in seminal plasma after Ovopel induction (p < .05; fold change 1.2). The majority of proteins were associated with the immune and stress responses including the transport protein (hephaestin), antiproteases (fetuin, α2-macroglobulin, TIMP2), complement components (C3, complement factor B/C2A), regulator of the coagulation cascade (plasminogen), modulators of the innate immune response, such as intelectin, ApoA and ApoE, and the cathepsin/cystatin system, and stress response (enolase1). In addition, hormonal stimulation seems to be related to the proteins involved in lipid metabolism, signal transduction, and tissue remodeling. Our results suggest that hormonal stimulation is not just concomitant with the hydration of testis but also induces the synthesis and secretion of seminal plasma proteins involved in sperm maturation and protection against stress induced by administration of the exogenous hormone. SIGNIFICANCE: It is well known that hormonal stimulation of male fish induces the final maturation of spermatozoa. However, molecular and biochemical basis underlying hormone-induced changes in semen is unknown at present. This study for the first time reveals, using proteomic approach, that hormonal stimulation in addition to hydration of testis is accompanied by significant changes in seminal plasma proteins related mainly to immune and stress response, lipid metabolism, signal transduction and tissue remodeling. These changes are associated with gene expression and synthesis and secretion of seminal plasma proteins by reproductive tissues. Overall, our results provide a framework for understanding the molecular mechanism responsible for hormonal stimulation in the reproductive tract of fish males.


Accuracy of quantification of risk using a single-pollutant Air Quality Index.
Health risks associated with short-term exposure to ambient air pollution are communicated to the public by the US EPA through the Air Quality Index (AQI), but it remains unclear whether the current regulatory-based, single-pollutant AQI fully represents the actual risks of air pollution-related illness. The objective of this study is to quantify cardiovascular hospital admissions attributable to PM2.5 at each AQI category. Based on National Ambient Air Quality Standards (NAAQS), the highest AQI value among criteria pollutants (driver pollutant) is reported daily. We investigated excess cardiovascular hospital admissions attributable to fine particulate matter (PM2.5) exposure from 2000 to 2010 in Bronx, Erie, Queens, and Suffolk counties of New York. Daily total, unscheduled cardiovascular hospital admissions (principal diagnosis) for individuals aged 20-99 years, concentration-response functions for PM2.5, and estimated quarterly effective daily concentrations were used to calculate excess cardiovascular hospital admissions when PM2.5 was reported as the driver pollutant and when PM2.5 was not reported as the driver pollutant at each AQI category. A higher proportion of excess hospital admissions attributable to PM2.5 occurred when PM2.5 was the driver pollutant (i.e., ~70% in Bronx County). The majority of excess hospital admissions (i.e., >90% in Bronx County) occurred when the AQI was <100 ("good" or "moderate" level of health concern) regardless of whether PM2.5 was the driver pollutant. During the warm season (April-September), greater excess admissions in Suffolk County occurred when PM2.5 was not the AQI driver pollutant. These results indicate that a single-pollutant index may inadequately communicate the adverse health risks associated with air pollution.


Neonatal estrogen treatment and its consequences for thymus development, serum level of autoantibodies to cardiolipin, and the delayed-type hypersensitivity response.
Eight-week-old female and male NMRI mice treated neonatally with the synthetic estrogen diethylstilbestrol (DES), estradiol-17beta, or tamoxifen displayed an enlarged thymus when compared with controls (approximately 1.5-fold). In control females, either ovariectomy or adrenalectomy increased thymus weight to the level characteristic for DES-treated females, but these endocrine ablations had no significant effect in DES females. The serum estrogen levels were similar in intact DES, ovariectomized DES, and ovariectomized female controls; serum corticosterone was similar in controls and DES females. The expression of the Thy1.2+ marker and the percentages of CD4+CD8+ DP and CD4+ and CD8+ SP cell subsets were similar in thymocyte populations from 8-wk-old controls and DES females; the CD4+ and CD8+ SP subsets were similar in splenocyte populations. The levels of serum immunoglobulin (Ig) G and IgM autoantibodies to cardiolipin showed age-dependent fluctuations but were similar in controls and DES females; however, the IgG autoantibodies in DES females were qualitatively different from those in controls with respect to sensitivity to bovine serum (a source of beta2-glycoprotein I). Contrary to females, DES-treated males had higher levels of autoantibodies than controls. The delayed-type hypersensitivity (DTH) response to oxazolone was similar in controls and DES animals at 8 wk, increased in DES females and males at 6 mo, but was reduced in DES females at 1 yr. Thus, even though adult mice with thymus enlargement after neonatal estrogen treatment do not differ from controls with respect to the expression of the Thy1.2 marker or percentages of CD4+/CD8+ DP or SP subsets in thymus and spleen, qualitative and quantitative differences occur in immune parameters (autoantibodies to cardiolipin) and a T-cell-dependent immune response (DTH).