Variation in neural development as a result of exposure to institutionalization early in childhood.
We used structural MRI and EEG to examine brain structure and function in typically developing children in Romania (n = 20), children exposed to institutional rearing (n = 29), and children previously exposed to institutional rearing but then randomized to a high-quality foster care intervention (n = 25). In so doing, we provide a unique evaluation of whether placement in an improved environment mitigates the effects of institutional rearing on neural structure, using data from the only existing randomized controlled trial of foster care for institutionalized children. Children enrolled in the Bucharest Early Intervention Project underwent a T1-weighted MRI protocol. Children with histories of institutional rearing had significantly smaller cortical gray matter volume than never-institutionalized children. Cortical white matter was no different for children placed in foster care than never-institutionalized children but was significantly smaller for children not randomized to foster care. We were also able to explain previously reported reductions in EEG α-power among institutionally reared children compared with children raised in families using these MRI data. As hypothesized, the association between institutionalization and EEG α-power was partially mediated by cortical white matter volume for children not randomized to foster care. The increase in white matter among children randomized to an improved rearing environment relative to children who remained in institutional care suggests the potential for developmental "catch up" in white matter growth, even following extreme environmental deprivation.


Assessment of post-COVID-19 fatigue among female survivors 2 years after hospital discharge: a nested case-control study.
Fatigue is a common symptom of long COVID syndrome. Compared to male survivors, females have a higher incidence of post-COVID fatigue. Therefore, long-term follow-up is necessary to understand which groups of females are more vulnerable to post-COVID fatigue. This is a nested case-control study of female COVID-19 survivors who were discharged from two designated hospitals in Wuhan, China in 2020, and received 2-year follow-up from March 1 to April 6, 2022. All patients completed the Checklist Individual Strength-subscale subjective fatigue (CIS-fatigue), a chronic obstructive pulmonary disease (COPD) assessment test (CAT), and the Hospital Anxiety and Depression Scale (HADS; including the HADS-Anxiety [HADS-A] and the HADS-Depression [HADS-D]). Individuals with CIS-fatigue scores of 27 or higher were classified as cases. The risk factors for fatigue was analysed with multivariable logistic regression analysis. A total of 899 female COVID-19 survivors were enrolled for analysis, including 47 cases and 852 controls. Compared with controls, cases had higher CAT, HADS-A and HADS-D scores, and showed a higher prevalence of symptoms, including anxiety (cases vs. controls, 44.7% vs. 4.0%, p < 0.001), chest tightness (21.2% vs. 2.3%, p < 0.001), dyspnoea (19.1% vs. 0.8%, p < 0.001) and so on. In multivariable logistic regression analysis, age (OR, 1.03; 95% CI, 1.01-1.06; p = 0.02) and cerebrovascular disease (OR, 11.32; 95% CI, 2.87-43.00; p < 0.001) were risk factors for fatigue. Fatigue had a statistically significant moderate correlation with depression (r = 0.44, p < 0.001), but not with CAT ≥ 10. Female COVID-19 patients who had cerebrovascular disease and older age have higher risk of fatigue. Patients with fatigue have higher CAT scores, and are more likely to have concurrent depression.


The 3' untranslated region of alfalfa mosaic virus RNA3 contains a core promoter for minus-strand RNA synthesis and an enhancer element.
The 3' untranslated regions (UTRs) of the three genomic RNAs of alfalfa mosaic virus consist of a 3' homologous sequence of 145 nt and upstream unique sequences 18-34 nt in length. Mutations were made in the 3' UTR of a cDNA clone of RNA3. Point mutations in five AUGC motifs which interfere with specific binding of coat protein to the 3' UTR had no effect on template activity of RNA3 for minus-strand RNA synthesis in vitro by purified viral RNA-dependent RNA polymerase (RdRp). Deletion analysis showed that the 3' homologous sequence of 145 nt was sufficient for a low level of template activity in the in vitro RdRp assay and a similarly low level of RNA3 accumulation in plants. The presence of an additional sequence of nucleotides 145-165 from the 3' end of RNA3 enhanced template recognition by RdRp in vitro and accumulation of RNA3 in vivo to wild-type levels.


Measurement of immunoreactive cytochrome P450 2E1 in human leucocytes.
We describe initial results on a Western blotting method, using a ployclonal antibody and chemiluminescence detection, for the measurement of cytochrome P450 2E1 in human lymphocytes. The method has been used to study the levels of 2E1 in lymphocytes isolated from 5 ml blood samples collected from a small group of well-controlled type 1 diabetics and healthy individuals. The described method offers increased sensitivity compared with a previously published method and does not need in vitro culturing of the lymphocytes prior to 2E1 measurement. The apparent molecular weight of the lymphocyte P450 2E1 was 55 kDa. There was approximately a six-fold difference in expression levels of 2E1 detected by this immunochemical technique across the study population.


The battle for chitin recognition in plant-microbe interactions.
Fungal cell walls play dynamic functions in interaction of fungi with their surroundings. In pathogenic fungi, the cell wall is the first structure to make physical contact with host cells. An important structural component of fungal cell walls is chitin, a well-known elicitor of immune responses in plants. Research into chitin perception has sparked since the chitin receptor from rice was cloned nearly a decade ago. Considering the widespread nature of chitin perception in plants, pathogens evidently evolved strategies to overcome detection, including alterations in the composition of cell walls, modification of their carbohydrate chains and secretion of effectors to provide cell wall protection or target host immune responses. Also non-pathogenic fungi contain chitin in their cell walls and are recipients of immune responses. Intriguingly, various mutualists employ chitin-derived signaling molecules to prepare their hosts for the mutualistic relationship. Research on the various types of interactions has revealed different molecular components that play crucial roles and, moreover, that various chitin-binding proteins contain dissimilar chitin-binding domains across species that differ in affinity and specificity. Considering the various strategies from microbes and hosts focused on chitin recognition, it is evident that this carbohydrate plays a central role in plant-fungus interactions.


[Do nursing students have entrepreneur profile?].
Descriptive-exploratory study that aimed at knowing the profile of nursing students regarding entrepreneurship. The General Entrepreneurship Trend Test with 54 questions was applied to 41 students. Results demonstrated that 14% present five entrepreneur tendencies, 12% present four entrepreneur tendencies, and 80% do not present entrepreneur tendencies. The majority of student intent to work as clinical nurses, while none of them intent to work in management activities. It was concluded that students have low grade of the entrepreneurship characteristics.


Paget disease of the vulva an analysis of 24 cases.
Paget's disease can arise in the breast (mammary Paget disease) or in other locations (extramammary Paget disease) such as anogenital skin in both males and females (Paget disease of the vulva [PDV]). Underlying adenocarcinoma can be found in some cases. This study aims to report clinical aspects, surgical procedures, outcomes, and recurrences of patients with PDV.A retrospective chart review was conducted on patients with pathologically confirmed diagnosis of PDV managed at the Department of Obstetrics and Gynecology, University of Bari, and the "Giovanni Paolo II" National Cancer Institute in Bari, between 1998 and 2018.Records of 24 cases of PDV were examined. Median age of the patients at diagnosis was 69.3 (range 38-84), diagnosis of synchronous cancer was made in 2 cases and in 2 other cases of metachronous disease. Three patients had previously been diagnosed with other oncological diseases. All patients underwent surgery including wide local excision (6), simple vulvectomy (8), and extended vulvectomy (10). Lymphadenectomy was performed in 2 cases and reconstructions with advancement flaps in 7 cases. Four patients were found to have invasive disease and 1 had inguinal node involvement. Positive margins were found in 11 patients. Wound dehiscence and urethral stenosis were found in 4 and 1 case each. Eight recurrences (33.33%) were observed, regardless of positive surgical margins.PDV has a low rate of malignancy but a high rate of recurrence. It should be diagnosed early to avoid repeated surgery and to reduce symptoms and morbidity.


Chronic hypoxia-induced alterations of the right ventricular myocardium are not aggravated by alimentary obesity in the mouse.
Obesity is a risk factor of cardiopulmonary disorders including left and right ventricular dysfunction and pulmonary hypertension (PH), and PH is associated with right ventricular (RV) hypertrophy and failure. Here, we tested the hypothesis that alterations of the RV capillary network under PH induced by chronic hypoxia are aggravated by alimentary obesity, thereby representing a predisposition for subsequent RV dysfunction. Male, 6-week-old C57BL/6N mice were assigned to one of the following groups: control diet (CD), CD/hypoxia (CD-Hyp), high-fat diet (HFD), HFD/hypoxia (HFD-Hyp). Mice were fed CD or HFD for 30 weeks, CD-Hyp and HFD-Hyp mice were exposed to normobaric hypoxia (13 % O2) during the last 3 weeks of the experiments. Hearts were prepared for light and electron microscopy and right atria and RVs were analyzed by design-based stereology. HFD and hypoxia independently increased RV and cardiomyocyte volume. These changes were further enhanced in HFD-Hyp. The ratio between RV and body weights was similar in CD and HFD but enhanced in both hypoxia groups to a similar extent. The total length of capillaries was elevated in proportion with the RV hypertrophy, thus the area of myocardium supplied by an average capillary was similar in all groups. Similarly, the thickness of the capillary endothelium was not altered by HFD or hypoxia. In conclusion, in experimental PH capillaries of the RV myocardium showed similar adaptations in lean and obese mice. Thus, under chronic hypoxic conditions, obesity had no adverse effect on the capillarization of the right ventricle.


Changes in purine nucleoside content in human myocardial efflux during pacing-induced ischemia.
Pacing-induced myocardial ischemia in 18 patients resulted in an increase of coronary sinus hypoxanthine levels from 1.20 +/- 0.18 micron during control to 2.41 +/- 0.52 micron (p less than 0.025) during pain. In addition, early lactate production occurred frequently before angina was noted. Neither hypoxanthine nor lactate levels changed in seven nonanginal patients, nor were significant alterations in potassium, inorganic phosphate, glucose, or oxygen saturation found in all patients. Myocardial hypoxanthine production seems a useful indicator of ischemia in the human heart.


Leiomyosarcoma of the left atrium: case report and review of the literature.
Leiomyosarcomas are extremely rare primary cardiac tumours. A 46-year-old woman presenting with symptoms and signs of rapidly progressive left ventricular failure and apparent systemic lupus erythematosus was subsequently found to have a grade III/III left atrial leiomyosarcoma which was confirmed surgically. Pathology showed a cellular neoplasm arranged in fascicles with multinucleated giant cells, with areas of high grade sarcomatous change. The patient died seven months postoperatively with intractable heart failure. At autopsy, tumour infiltrated the pericardium, both atria and the right ventricle, with invasion of the diaphragm and posterior mediastinum. The current world literature is reviewed with respect to this rare and often misdiagnosed tumour.


Marek's disease virus-induced transient paralysis: a comparison of lesions in susceptible and resistant lines of chickens.
A study was conducted to determine the causative lesion of Marek's disease virus-induced transient paralysis. Brain histologic lesions were quantitated and compared in genetically resistant and susceptible inbred chickens. Comparisons were made 11 days post inoculation (PI) of virus when clinical signs were evident in susceptible birds and on day 17 PI when these signs had remitted. Clinically-affected birds from the susceptible line on day 11 PI had consistent evidence of neuropil vacuolation compatible with brain edema; two of these birds also had vasculitis. These lesions were absent in both clinically-recovered birds from this line evaluated on day 17 PI and genetically resistant birds studied on day 11 PI. Our findings suggest that the causative lesion of transient paralysis is vasogenic brain edema.


Timing of Administration: For Commonly-Prescribed Medicines in Australia.
Chronotherapy involves the administration of medication in coordination with the body's circadian rhythms to maximise therapeutic effectiveness and minimise/avoid adverse effects. The aim of this study is to investigate the "time of administration" recommendations on chronotherapy for commonly-prescribed medicines in Australia. This study also aimed to explore the quality of information on the timing of administration presented in drug information sources, such as consumer medicine information (CMI) and approved product information (PI). Databases were searched for original research studies reporting on the impact of "time of administration" of the 30 most commonly-prescribed medicines in Australia for 2014. Further, time of administration recommendations from drug information sources were compared to the evidence from chronotherapy trials. Our search revealed 27 research studies, matching the inclusion and exclusion criteria. In 56% (n = 15) of the research studies, the therapeutic effect of the medicine varied with the time of administration, i.e., supported chronotherapy. For some medicines (e.g., simvastatin), circadian-based optimal administration time was evident in the information sources. Overall, dedicated studies on the timing of administration of medicines are sparse, and more studies are required. As it stands, information provision to consumers and health professionals about the optimal "time" to take medications lags behind emerging evidence.


Clinicopathological and biological significance of mitotic centromere-associated kinesin overexpression in human gastric cancer.
Mitotic centromere-associated kinesin (MCAK) is a microtubule (MT) depolymerase necessary for ensuring proper kinetochore MT attachment during spindle formation. To determine MCAK expression status and its clinicopathological significance, real-time reverse transcriptase-polymerase chain reaction was used in 65 cases of gastric cancer. MCAK gene expression in cancer tissue was significantly higher than expression in non-malignant tissue (P<0.05). Elevated MCAK expression was significantly associated with lymphatic invasion (P=0.01) and lymph node metastasis (P=0.04). Furthermore, patients with high MCAK expression had a significantly poorer survival rate than those with low MCAK expression (P=0.008). Immunohistochemical study revealed that expression of MCAK was primarily observed in cancer cells. Additionally, a gastric cancer cell line (AZ521) that stably expressed MCAK was established and used to investigate the biological effects of the MCAK gene. In vitro results showed that cells transfected with MCAK had a high rate of proliferation (P<0.001) and increased migratory ability (P<0.001) compared to mock-transfected cells. This study demonstrated that elevated expression of MCAK may be associated with lymphatic invasion, lymph node metastasis, and poor prognosis. These characteristics may be due in part to the increased proliferative and migratory ability of cells expressing MCAK.


The ability of flux balance analysis to predict evolution of central metabolism scales with the initial distance to the optimum.
The most powerful genome-scale framework to model metabolism, flux balance analysis (FBA), is an evolutionary optimality model. It hypothesizes selection upon a proposed optimality criterion in order to predict the set of internal fluxes that would maximize fitness. Here we present a direct test of the optimality assumption underlying FBA by comparing the central metabolic fluxes predicted by multiple criteria to changes measurable by a (13)C-labeling method for experimentally-evolved strains. We considered datasets for three Escherichia coli evolution experiments that varied in their length, consistency of environment, and initial optimality. For ten populations that were evolved for 50,000 generations in glucose minimal medium, we observed modest changes in relative fluxes that led to small, but significant decreases in optimality and increased the distance to the predicted optimal flux distribution. In contrast, seven populations evolved on the poor substrate lactate for 900 generations collectively became more optimal and had flux distributions that moved toward predictions. For three pairs of central metabolic knockouts evolved on glucose for 600-800 generations, there was a balance between cases where optimality and flux patterns moved toward or away from FBA predictions. Despite this variation in predictability of changes in central metabolism, two generalities emerged. First, improved growth largely derived from evolved increases in the rate of substrate use. Second, FBA predictions bore out well for the two experiments initiated with ancestors with relatively sub-optimal yield, whereas those begun already quite optimal tended to move somewhat away from predictions. These findings suggest that the tradeoff between rate and yield is surprisingly modest. The observed positive correlation between rate and yield when adaptation initiated further from the optimum resulted in the ability of FBA to use stoichiometric constraints to predict the evolution of metabolism despite selection for rate.


Near-resonance saturation pulse imaging of the extraocular muscles in thyroid-related ophthalmopathy.
We examined the utility of near-resonance saturation pulse imaging (magnetization transfer [MT] and spin lock) in characterizing microstructural changes occurring in the extraocular muscles of patients with thyroid-related ophthalmopathy (TRO). Eight healthy volunteers and 10 patients with TRO were imaged using an off-resonance saturation pulse in conjunction with conventional spin-echo T1-weighted imaging at frequency offsets of 500, 1000, 1500, and 2000 Hz from water resonance. The relative contributions of MT and spin-lock excitation to image contrast at each frequency offset were estimated using a computer simulation model. Suppression ratios were calculated for the control and TRO groups from measurements obtained on two successive coronal sections in the widest portion of the inferior and medial rectus muscles bilaterally. A repeated measures analysis of variance and a parametric correlation analysis were performed to evaluate maximum cross-sectional area, MR-generated signal, and suppression ratios for the extraocular muscles examined. Our computer model suggested that saturation of extraocular muscles was due to pure MT effects with our off-resonance pulse at 2000 and 1500 Hz, to a combination of MT and spin lock at 1000 Hz frequency offset, and, primarily, to spin-lock excitation at 500 Hz frequency offset. Suppression ratios for the extraocular muscles of the TRO patients were significantly lower than that observed for the control subjects at 1500, 1000, and 500 Hz frequency offset. This differential saturation effect was maximal at 500 Hz frequency offset, with mean suppression ratios for the inferior and medial rectus muscles of 27% for the healthy subjects and 20% for the TRO group. Both MT and spin-lock contrast of the extraocular muscles in patients with TRO differ significantly from that observed in control subjects. Near-resonance saturation pulse imaging may enhance our understanding of the microstructural changes occurring in the extraocular muscles of these patients.


Subacute cutaneous lupus erythematosus associated with hepatocellular carcinoma.
A 63-year-old man with a 4-year history of metastatic hepatocellular carcinoma secondary to chronic hepatitis B developed a rash affecting his arms, legs, thorax and back. Both clinical and histological examination suggested a diagnosis of subacute cutaneous lupus erythematosus (SCLE). The association of SCLE and hepatocellular carcinoma has not previously been reported. The SCLE persisted without remission and was still present at his death from metastatic hepatocellular carcinoma 3 months later. We also review other reported cases of SCLE as paraneoplastic dermatoses and apply McLean's criteria for paraneoplastic dermatosis.


Decomposing cryptocurrency high-frequency price dynamics into recurring and noisy components.
This paper investigates the temporal patterns of activity in the cryptocurrency market with a focus on Bitcoin, Ethereum, Dogecoin, and WINkLink from January 2020 to December 2022. Market activity measures-logarithmic returns, volume, and transaction number, sampled every 10 s, were divided into intraday and intraweek periods and then further decomposed into recurring and noise components via correlation matrix formalism. The key findings include the distinctive market behavior from traditional stock markets due to the nonexistence of trade opening and closing. This was manifested in three enhanced-activity phases aligning with Asian, European, and U.S. trading sessions. An intriguing pattern of activity surge in 15-min intervals, particularly at full hours, was also noticed, implying the potential role of algorithmic trading. Most notably, recurring bursts of activity in bitcoin and ether were identified to coincide with the release times of significant U.S. macroeconomic reports, such as Nonfarm payrolls, Consumer Price Index data, and Federal Reserve statements. The most correlated daily patterns of activity occurred in 2022, possibly reflecting the documented correlations with U.S. stock indices in the same period. Factors that are external to the inner market dynamics are found to be responsible for the repeatable components of the market dynamics, while the internal factors appear to be substantially random, which manifests itself in a good agreement between the empirical eigenvalue distributions in their bulk and the random-matrix theory predictions expressed by the Marchenko-Pastur distribution. The findings reported support the growing integration of cryptocurrencies into the global financial markets.


The role of dynamic contrast-enhanced MRI in the differential diagnosis of psoriatic and rheumatoid arthritis.
The purpose of this study was to investigate the role of dynamic contrast-enhanced MRI in the differential diagnosis of psoriatic and rheumatoid arthritis in the hand and wrist. Forty-five consecutive patients (31 patients with rheumatoid arthritis and 14 patients with psoriatic arthritis) were examined in a 3-T whole-body MR unit. After contrast injection, a 3D encoded spoiled gradient-echo sequence was used for measurement of the time course of contrast-medium uptake in the synovial tissue. On the basis of the gained uptake curves, the rate of early enhancement was calculated after 35 and 52 seconds, and the relative enhancement rate was calculated after 35 seconds, 52 seconds, 3 minutes, and 15 minutes (late enhancement). Dynamic contrast-enhanced MRI rates of patients with rheumatoid arthritis and psoriatic arthritis were compared and correlated with laboratory and clinical data. A statistically significant difference between the two groups was found regarding the relative enhancement rate after 15 minutes (p < 0.01). In contrast, no difference in relative enhancement rate was found 35 seconds, 52 seconds, or 3 minutes after contrast injection (p = 0.695, p = 0.573, and p = 0.278, respectively). Regarding the rate of early enhancement at 35 and 52 seconds, no significant difference between patients with rheumatoid arthritis and those with psoriatic arthritis was found. Significant correlations were found between inflammatory parameters and dynamic contrast-enhanced parameters in patients with rheumatoid arthritis but not in those with psoriatic arthritis. Fifteen minutes after contrast injection, a statistically significant difference between rheumatoid arthritis and psoriatic arthritis was found in synovial enhancement that might play an important role in differentiating the two diseases.


Comparative Proteomics Analysis Reveals That Lignin Biosynthesis Contributes to Brassinosteroid-Mediated Response to Phytophthora sojae in Soybeans.
Brassinosteroids (BRs) are a group of steroid plant hormones regulating normal growth, development, and stress response in plants. However, the mechanisms by which BRs interfere with the resistance of soybean to Phytophthora sojae (P. sojae) remain largely unknown. The present study analyzed the role of BRs in soybean response against P. sojae by comparative proteomic approaches. A total of 52,381 peptides were obtained by trypsin digestion of 9,680 proteins, among which 6,640 proteins were quantified, and 402 proteins were identified as differentially expressed proteins (DEPs). Further analysis revealed that DEPs were significantly involved in the lignin biosynthesis pathway. The expression of the majority of key enzymes involved in lignin biosynthesis was upregulated by BR-pretreatment and P. sojae infection, and lignin accumulation was faster in BR-pretreated soybeans than in untreated controls. Additionally, accumulation of lignin was consistent with these enzyme expressions levels and resistance phenotype. These findings advance the understanding of the role of BRs in the interaction between soybeans and P. sojae.


Linguistic Empathy: Behavioral measures, neurophysiological correlates, and correlation with Psychological Empathy.
Relations among behavioral, psychological, and electrophysiological correlates of Linguistic Empathy were examined in two experiments using lateralized stimuli. Linguistic Empathy is defined as a linguistic manifestation of the point of view the speaker assumes toward the content of the utterance, and of the speaker's attitude toward/identification with the referents therein. Linguistic choices made by the speaker among multiple logically and referentially synonymous lexical and grammatical options reveal the speaker's perspectives. In experiment 1, acceptability ratings were measured for Context-Target sentence pairs that did or did not violate two Empathy Hierarchies (Person Empathy Hierarchy and Topic Empathy Hierarchy); the Empathy Quotient (EQ) test of Psychological Empathy was also administered. Ratings were lower for sentence pairs that violated both hierarchies than for those violating neither and were intermediate for sentences violating only one hierarchy. Linguistic Empathy (LE) was operationalized as the difference in ratings between sentences violating both vs. neither empathy hierarchy; this measure correlated positively with EQ. Experiment 2 replicated those results with new participants and measured reaction time and EEG during ratings. While there were no effects of hemisphere or visual field on the linguistic variables, the amplitude of a positive event-related potential deflection at 380 ms provided a partial electrophysiological correlate for LE. Its difference measure correlated with behavioral LE but not with EQ. Though preliminary, these experiments show that Linguistic Empathy may share information processing computations with Psychological Empathy and have an electrophysiological correlate.


Suppression of glucocorticoid secretion induces a behaviorally depressive state in rotarod performance in rat.
Glucocorticoid hormones are important in the maintenance of many brain functions, and their receptors distribute abundantly throughout the brain. In patients with several neuropsychiatric disorders such as depression, dysregulation of the glucocorticoid negative feedback system is the consistent observations, which is thought to be caused by reduced glucocorticoid response at the several feedback sites including the brain. In the present study, we examined whether reduced glucocorticoid actions via suppression of circulating glucocorticoids by adrenalectomy (ADX) induced a behavioral depressive state using the rotarod test. We found that ADX impaired the rotarod performance while it did not affect the traction performance and locomotor activity. Moreover, this impairment was significantly reversed by corticosterone replacement treatment and was ameliorated by the infusion of D1 receptor agonist SKF 81297 into the prefrontal cortex (PFC) in a dose-dependent manner. Considering the previous findings that ADX reduces dopaminergic transmission in the PFC, the present results suggest that suppression of circulating glucocorticoids induces a behaviorally depressive state that is caused by a D1 receptor-mediated hypodopaminergic mechanism in the PFC. This finding would help to understand the involvement of the dysregulated feedback system in the pathogenesis of depression.


Quantitative computed tomography detects interstitial lung diseases proven by biopsy.
Background: The Quantitative chest CT (QCT) is emerging as a promising tool in the assessment of interstitial lung disease (ILD). However, the precise relationship between QCT parameters and the fibrosis detectable in lung tissue, remains to be established. Objectives: The aim of this study was to compare QCT and histopathological features in patients with ILD. Moreover we verified if the QCT assessment is similar in patients with or without a ILD diagnosis proven by a biopsy. Methods: Twenty patients affected by ILD who underwent a chest CT and, later, a lung biopsy, were enrolled. Patients were divided according to the histopathological findings (IPF vs sarcoidosis) in two groups (respectively bIPF and bSarc). Other 20 patients with a radiological diagnosis of IPF were included in a control group (rIPF). All CTs were post-processed with a free software (Horos) in order to obtain an ILD quantitative assessment. Results: There were no differences in terms of gender, smoking habit and spirometric values between patients' groups. rIPF subjects were older than the other: 70 vs 59 and 47 years (p<0.001). A different distribution of QCT parameters was observed between bIPF and bSarc (p<0.01) while it was comparable within bIPF and rIPF. Conclusions: QCT parameters were similar in subjects affected by the same type of ILD detected with biopsy and with CT alone. These findings make stronger the assumption that QCT can identify the presence of pulmonary fibrosis and, ultimately, that it can represent an useful and effective tool to assess ILD. (Sarcoidosis Vasc Diffuse Lung Dis 2018; 35: 16-20).


Differential Distribution of Somatostatin-like Immunoreactivity in the Visual Sector of the Thalamic Reticular Nucleus in Galago.
Immunocytochemical methods were used to compare the distributions of somatostatin-14 (SOM) and glutamic acid decarboxylase (GAD) in the medial and lateral tiers of the visual sector of the thalamic reticular nucleus in the bushbaby, Galago. As expected, all of the neurons in the visual sector were immunoreactive for GAD, the synthesizing enzyme for GABA, but the distribution of SOM-immunoreactive cells was not uniform. It appeared that every cell in the medial tier was immunoreactive for SOM, but that very few cells in the lateral tier contained this neuropeptide. The significance of the difference in reticular neuron SOM content could be related to the functional differences between the dorsal lateral geniculate nucleus, which is connected reciprocally with the lateral tier, and the pulvinar nucleus, which is connected reciprocally with the medial tier.


Durability of responses following donor lymphocyte infusions for patients who relapse after allogeneic stem cell transplantation for chronic myeloid leukemia.
An analysis was performed of the response to treatment with donor lymphocyte infusions (DLI) and the survival in 66 consecutive patients who relapsed after primary treatment by allogeneic stem cell transplantation for BCR-ABL-positive chronic myeloid leukemia. The transplant donor was an HLA-identical sibling (n = 35) or a "matched" unrelated volunteer (n = 31). Fifty-seven patients were transplanted in chronic phase, eight in accelerated phase, and one in second chronic phase. The recognition of relapse was based on precise molecular, cytogenetic, or hematologic criteria. The median interval from transplant to relapse was 12 months (range 3-85). The median interval from relapse to initiation of DLI was 9.4 months (range 1-70). Patients received DLI from their original transplant donors on a bulk-dose (n = 34) or on an escalating-dose (n = 32) regimen. Patients were monitored serially by hematologic, cytogenetic, and molecular criteria. Molecular remission was defined by the finding of negative results by nested primer reverse transcriptase polymerase chain reaction (RT-PCR) for BCR-ABL transcripts on two consecutive occasions, subject to satisfactory controls. Forty-four patients (67%) achieved molecular remission. Patients who had relapsed to advanced phase disease and patients with short intervals between transplant and relapse had significantly lower probabilities of achieving molecular remission. Of the 44 patients who achieved molecular remission, 4 reverted to a PCR-positive status at 15, 18, 37, and 87 weeks after remission. The probability of survival for patients who achieved molecular remission was significantly better than for those who failed to do so (95% versus 53% at 3 years post-DLI, P = .0001). We conclude that the majority of molecular remissions after DLI are durable, and thus the majority of responding patients may prove to have been cured. (Blood. 2000;96:2712-2716)


Analysis of risk factors for infant mortality in the 1992-3 and 2002-3 birth cohorts in rural Guinea-Bissau.
Though still high, the infant mortality rate in Guinea-Bissau has declined. We aimed to identify risk factors including vaccination coverage, for infant mortality in the rural population of Guinea-Bissau and assess whether these risk factors changed from 1992-3 to 2002-3. The Bandim Health Project (BHP) continuously surveys children in rural Guinea-Bissau. We investigated the association between maternal and infant factors (especially DTP and measles coverage) and infant mortality. Hazard ratios (HR) were calculated using Cox regression. We tested for interactions with sex, age groups (defined by current vaccination schedule) and cohort to assess whether the risk factors were the same for boys and girls, in different age groups in 1992-3 and in 2002-3. The infant mortality rate declined from 148/1000 person years (PYRS) in 1992-3 to 124/1000 PYRS in 2002-3 (HR = 0.88;95%CI:0.77-0.99); this decline was significant for girls (0.77;0.64-0.94) but not for boys (0.97;0.82-1.15) (p = 0.10 for interaction). Risk factors did not differ significantly by cohort in either distribution or effect. Mortality decline was most marked among girls aged 9-11 months (0.56;0.37-0.83). There was no significant mortality decline for girls 1.5-8 months of age (0.93;0.68-1.28) (p = 0.05 for interaction). DTP and measles coverage increased from 1992-3 to 2002-3. Risk factors did not change with the decline in mortality. Due to beneficial non-specific effects for girls, the increased coverage of measles vaccination may have contributed to the disproportional decline in mortality by sex and age group.


Phase II enzyme expression in rat liver in response to the antiestrogen tamoxifen.
The genotoxicity and carcinogenicity of tamoxifen have been attributed to metabolic activation of tamoxifen to an electrophile. Phase II enzymes are known to be involved in the metabolism of the drug and possibly in the formation or elimination of the active metabolite. To determine the effects of tamoxifen on phase II enzyme expression, the drug was administered to F344 rats, and hepatic glutathione S-transferase (GST), UDP-glucuronosyltransferase (UGT), and sulfotransferase (ST) expression was evaluated. Some of the tamoxifen-induced effects, including dramatic suppression of selected GST enzymes and activity, were observed at a dose in rats that is directly equivalent, on a mg/kg b.w. basis, to the doses used for breast cancer treatment. Most of the observed responses are not consistent with the previously described phenobarbital-like properties of tamoxifen and could be the result of the partial agonist activity of tamoxifen at the estrogen receptor. Northern blot analysis was performed with isozyme-specific oligonucleotide probes for rat GST, ST, and UGT. In addition, GST subunit protein levels were assayed by high-performance liquid chromatography. In females, tamoxifen treatment resulted in a 60% suppression of GST Ya1 mRNA and protein levels and a 40% suppression of GST Ya2 levels. In males, tamoxifen treatment suppressed GST Ya1 expression approximately 60%, and GST Ya2 expression was suppressed at low doses but induced above control at high doses. Male GST Yc1 was induced approximately 80% over control. The expression of all other major forms of rat hepatic GST subunit protein, including GST Yb1, Yb2, Yb3, Yp, and Yl, was unaffected by tamoxifen treatment. GST conjugation activity toward delta 5-androstene-3,17-dione, a GST Ya1- and Ya2-specific substrate, was suppressed approximately 40% in both sexes, consistent with our protein and mRNA data. Total GST activity, as measured by the rate of chlorodinitrobenzene conjugation, was not changed. Tamoxifen also produced a dose-dependent increase in UGT2B1 mRNA, a phenobarbital-inducible enzyme; mRNA levels reached 210 and 420% of control in females and males, respectively. In addition, mRNA levels for ST2A2, a female-specific ST gene, were suppressed 50% in females and induced 120% over control in males. mRNA expression for all other forms of rat liver UGT and ST isozymes that were tested was not significantly affected by tamoxifen treatment. Overall, these results demonstrate that tamoxifen has significant effects on hepatic phase II enzyme expression that may have implications for the carcinogenicity and/or therapeutic activity of the drug.


Catecholamine-sensitive adenylate cyclase in frontal cortex of primate brain.
Adenylate cyclase activity (AC) of homogenates of monkey frontal cortex was stimulated by catecholamines (dopamine, norepinephrine and isoproterenol), apomorphine, clonidine, NaF and GPP(NH)P. The increment in activity due to dopamine was enhanced in the presence of GPP(NH)P. The AC was also stimulated by 0.2-0.4 mM Ca2+ in the presence of 0.2 mM EGTA; at 0.8 mM Ca2+ had little or no influence on basal or NaF-stimulated activity. However, as Ca2+ concentration was increased from 0.2 to 0.8 mM stimulation by dopamine or GPP(NH)P was progressively inhibited. These results suggest a possible function of Ca2+ in modulating neurotransmitter stimulation of AC in the monkey frontal cortex. The AC exhibited higher sensitivity to dopamine than to norepinephrine or isoproterenol; however dopamine and norepinephrine caused the same maximum stimulation of the enzyme, a stimulation womewhat greater than that produced by isoproterenol. An additivity in stimulating AC was observed for dopamine and isoproterenol but not for dopamine and norepinephrine. Norepinephrine- or dopamine-stimulated AC was effectively blocked by fluphenazine and other dopamine-receptor blocking agents (relative potency for blockade; fluphenazine, haloperidol greater than clozapine, thioridazine greater than pimozide) but not by propranolol, a beta-receptor blocker. In contrast, isoproterenol-stimulated AC was antagonized by propranolol or alprenolol but not by fluphenazine. On the basis of these results, at least two distinct receptors appear to be associated with AC of monkey frontal cortex: (1) a beta-receptor stimulated by isoproterenol and (2) a new type of dopamine or dopamine-norepinephrine receptor, stimulated by either dopamine or norepinephrine. This latter system differs from more typical dopamine receptors found in caudate, retina and limbic cortex in that (a) it is not stimulated by 1-(3,4-dihydroxybenzyl)-4-(2-pyrimidinyl) piperazine (S584); (b) it is stimulated significantly by the putative alpha-receptor agonist, clonidine; (c) it is more sensitive to blockade by clozapine than primate retina or caudate; also the sensitivity to haloperidol is greater than has been reported for non-primate caudate; (d) it is very sensitive to stimulation by norepinephrine and to blockade by phentolamine (an alpha-receptor blocker).


Clinical trials on the efficacy of pharmacologic intervention reducing mortality from cardiovascular diseases.
Results of recent clinical trials on secondary prevention of ischemic heart disease indicate that judicious, long-term administration of adrenergic beta blockers and platelet-active drugs such as aspirin and Persantine (dipyridamole) would seem to yield protection against mortality associated with acute myocardial infarction, including sudden death. These drugs are beneficial also in prevention of recurrent myocardial infarction, especially among patients with unstable angina. These drugs should be considered as soon as the diagnosis of myocardial infarction or unstable angina is confirmed clinically. In terms of primary prevention of ischemic heart disease and cerebrovascular disease (stroke), the results of the Hypertension Detection and Follow-Up Program provide an excellent set of data on the efficacy of rigorous treatment of hypertension, especially those with mild hypertension. To be effective, treatment must start before there is evidence of target end organ damage, such as left ventricular hypertrophy. Recent data from the Australian Therapeutic Trial in Mild Hypertension also confirms these findings.


Comparison of extraction protocols to determine differences in wine-extractable tannin and anthocyanin in Vitis vinifera L. cv. Shiraz and Cabernet Sauvignon grapes.
Cabernet Sauvignon and Shiraz grapes were sourced from different regions within Australia, and microvinified with a skin contact period of 6 days. Grape samples were extracted using two protocols: a 15% v/v ethanol, 10 g/L tartaric acid extract of gently crushed berries (wine-like, WL) and a 50% v/v ethanol, pH 2 extract of grape berry homogenate. It was found that in WL extracts, grape tannin and anthocyanin concentrations were strongly related to wine tannin, anthocyanin and color density achieved during the skin contact period. No relationship was observed for grape tannin concentration analyzed in homogenate extracts and wine tannin, but a strong, positive relationship was found for anthocyanin concentration. When the data obtained from homogenate extraction was treated separately by grape variety, a stronger relationship between grape and wine tannin concentration was observed. Tannin compositional analysis in wines indicated that higher tannin concentrations were due to the extraction of tannin of higher molecular mass during fermentation, most likely from grape skins.


Mechanisms by which T7 lysozyme specifically regulates T7 RNA polymerase during different phases of transcription.
Bacteriophage T7 lysozyme binds to T7 RNA polymerase (RNAP) and regulates its transcription by differentially repressing initiation from different T7 promoters. This selective repression is due in part to a lysozyme-induced increase in the KNTP of the initiation complex (IC) and to intrinsically different NTP concentration requirements for efficient initiation from different T7 promoters. While lysozyme represses initiation, once the enzyme has left the promoter and formed an elongation complex (EC) it is generally resistant to the effects of lysozyme. The mechanism by which the inhibitory effects of lysozyme are largely restricted to the initiation phase of transcription is not well understood. We find that T7 lysozyme destabilizes initial transcription complexes (ITCs) and increases the rate of release of transcripts from these complexes but does not destabilize ECs. However, if the RNA:RNAP interaction proposed to be important for EC stability is disrupted by proteolysis of the RNA-binding domain or use of templates which interfere with establishment of this RNA:RNAP interaction, the EC becomes sensitive to lysozyme. Comparison of the X-ray structures of T7RNAP and of a T7RNAP:T7 lysozyme complex reveals that lysozyme causes the C terminus of the polymerase to flip out of the active site. Experiments in which carboxypeptidase A is used to probe the lysozyme-induced exposure of the C terminus reveal a large decrease in carboxypeptidase sensitivity following transcription initiation, suggesting that interactions with the 3'-end of the RNA help stabilize the active site in a functional (carboxypeptidase protected) conformation. Thus, the resistance of the EC to lysozyme appears to be due to the consecutive establishment of two sets of RNA:RNAP interactions. The first is made with the 3'-end of the RNA and helps stabilize a functional conformation of the active site, thereby suppressing the effects of lysozyme on KNTP. The second is made with a more upstream element of the RNA and keeps the EC from being destabilized by lysozyme binding.


The RuvAB branch migration complex can displace topoisomerase IV.quinolone.DNA ternary complexes.
Quinolone antimicrobial drugs target both DNA gyrase and topoisomerase IV (Topo IV) and convert these essential enzymes into cellular poisons. Topoisomerase poisoning results in the inhibition of DNA replication and the generation of double-strand breaks. Double-strand breaks are repaired by homologous recombination. Here, we have investigated the interaction between the RuvAB branch migration complex and the Topo IV.quinolone.DNA ternary complex. A strand-displacement assay is employed to assess the helicase activity of the RuvAB complex in vitro. RuvAB-catalyzed strand displacement requires both RuvA and RuvB proteins, and it is stimulated by a 3'-non-hybridized tail. Interestingly, Topo IV.quinolone.DNA ternary complexes do not inhibit the translocation of the RuvAB complex. In fact, Topo IV.quinolone.DNA ternary complexes are reversed and displaced from the DNA upon their collisions with the RuvAB complex. These results suggest that the RuvAB branch migration complex can actively remove quinolone-induced covalent topoisomerase.DNA complexes from DNA and complete the homologous recombination process in vivo.


Biocide susceptibility testing of bacteria: Development of a broth microdilution method.
Biocide susceptibility testing (BST) of bacteria lacks standardised methods. Based on a recently established broth macrodilution BST method, a broth microdilution method for BST was developed. To establish the respective protocol, four reference strains Staphylococcus aureus ATCC® 6538, Enterococcus hirae ATCC® 10541, Escherichia coli ATCC® 10536 and Pseudomonas aeruginosa ATCC® 15442 were investigated for their minimal inhibitory concentrations (MICs) towards quaternary ammonium compounds (benzalkonium chloride), cationic compounds (chlorhexidine), aldehydes (glutardialdehyde) and alcohols (isopropanol) using tryptic soy broth. All combinations of (i) inoculum preparation according to the German Veterinary Medical Society (DVG) or the Clinical and Laboratory Standards Institute (CLSI) with some modifications, (ii) use of 1st subculture (SC) and 2nd SC, (iii) direct colony suspension (DCS) with/without glass beads, and (iv) incubation at 37 °C for 24 h, 48 h, and 72 h were compared using seven independent replications. Overall, the reproducibility was high for all abovementioned strain/biocide/parameter combinations. In total, 86.9 % - 100 % of the results were within ± one dilution step of the mode value. The proposed method for a standardised BST protocol comprises (i) two different inoculum densities, (ii) the use of a fresh overnight culture (1st SC or 2nd SC), (iii) the preparation of the inoculum suspension by either of the two methods using DCS with or without glass beads, and (iv) the incubation at 37 °C for 24 h. This broth microdilution method will help to harmonize BST of bacterial pathogens in routine diagnostics.


Phylogeny, Macroevolutionary Trends and Historical Biogeography of Sloths: Insights From a Bayesian Morphological Clock Analysis.
Sloths, like other xenarthrans, are an extremely interesting group of mammals that, after a long history of evolution and diversification in South America, became established on islands in the Caribbean and later reached North America during the Great American Biotic Interchange. In all three regions, they were part of the impressive Pleistocene megafauna. Most taxa became extinct and only two small, distantly related tree-dwelling genera survived. Here, we incorporate several recently described genera of sloths into an assembled morphological data supermatrix and apply Bayesian inference, using phylogenetic and morphological clock methods, to 64 sloth genera. Thus, we investigate the evolution of the group in terms of the timing of divergence of different lineages and their diversity, morphological disparity and biogeographical history. The phylogeny obtained supports the existence of the commonly recognized clades for the group. Our results provide divergence time estimates for the major clades within Folivora that could not be dated with molecular methods. Lineage diversity shows an early increase, reaching a peak in the Early Miocene followed by a major drop at the end of the Santacrucian (Early Miocene). A second peak in the Late Miocene was also followed by a major drop at the end of the Huayquerian (Late Miocene). Both events show differential impact at the family level. After that, a slight Plio-Pleistocene decline was observed before the marked drop with the extinction at the end of the Pleistocene. Phenotypic evolutionary rates were high during the early history of the clade, mainly associated with Mylodontidae, but rapidly decreased to lower values around 25 Ma, whereas Megalonychidae had lower rates at the beginning followed by a steady increase, peaking during the Late Miocene and the Pliocene. Morphological disparity showed a similar trend, with an early increase, followed by a slowly increasing phase through the Late Oligocene and Early Miocene, and ending with another increase beginning at the middle of the Miocene. Biogeographic analysis showed southern South America as the most probable area of origin of the clade and the main region in which the early diversification events took place. Both Megatheriinae and Nothrotheriinae basal nodes were strongly correlated with Andean uplift events, whereas the early history of Mylodontidae is closely associated with southern South America and also shows an early occupation of the northern regions. Within Megalonychidae, our results show Choloepus as a descendant of an island dispersing ancestor and a probable re-ingression to South America by a clade that originated in Central or North America.


Interactions of an intact proteoglycan and its fragments with basic homopolypeptides in dilute aqueous solution.
The interactions between a proteoglycan and cationic polypeptides have been investigated by the use of circular-dichroism spectroscopy. The interaction produces an induced conformational change for poly(l-arginine) and poly(l-lysine), similar to the effects previously reported for mucopolysaccharide-polypeptide mixtures. For bovine nasal septum proteoglycan, the interactions are similar to those for chondroitin 4-sulphate, which comprises approximately 63% of the total polysaccharide. The results also suggest that the interactions produce a conformational change in the protein core. Similar studies for the Smith-degradation product show that the protein core can adopt a substantial alpha-helical content and is capable of interactions with poly-(l-arginine). The interactions for chondroitin sulphate ;doublets' are significantly different from those for the separated chains, indicating that the arrangement of the polysaccharide side chains in pairs (and larger groups) along the protein backbone contributes to the interaction properties of the intact proteoglycan.


Subpopulations of common acute lymphoblastic leukemia antigen-positive lymphoid cells in normal bone marrow identified by hematopoietic differentiation antigens.
Bone marrow samples from normal adults and children with nonhematologic malignancies not involving the marrow, acute lymphoblastic leukemia (ALL) in continued remission, and immune cytopenias were studied by two-color immunofluorescence (IF) and flow cytometry to characterize common acute lymphoblastic leukemia antigen (CALLA)-positive marrow lymphoid cells. Marrow was separated by Ficoll/Hypaque centrifugation followed by passage over a monoclonal antibody affinity column to remove myeloid cells prior to IF staining. A higher proportion of CALLA-positive cells was found in the pediatric marrows (mean, 33.7% +/- 6.3% SEM) than in the adult marrows (mean, 4.5% +/- 1.6% SEM). Two subpopulations of CALLA-positive cells identified by cell sorting to be of lymphoid morphology were found in both adult and pediatric marrows. A small subpopulation comprising 12.3% of the total CALLA-positive cells was characterized by a high intensity of CALLA, terminal deoxynucleotidyl transferase (TdT), and MY10 expression, but low B1, common leukocyte antigen, and peanut agglutinin receptor expression. The remainder of the CALLA-positive cells displayed low intensity of CALLA expression, positivity for the common leukocyte antigen, B1 and peanut agglutinin, and negative reaction with TdT and MY10. Both CALLA-positive subpopulations were positive for HLA-DR and the pan-B cell marker B4, but negative for cytoplasmic immunoglobulin, B2 and Leu 1. BrdU labelling studies showed that a similar proportion of cells in each subpopulation was in S phase. A slightly higher proportion of the strongly CALLA-positive cells possessed the morphologic features of high nuclear/cytoplasmic (N/C) ratio and prominent nucleoli. These studies suggest that a discrete maturation step occurs among CALLA-positive marrow lymphoid cells, resulting in the loss of TdT and MY10 expression, but gradual acquisition of the B cell marker B1 and the common leukocyte antigen. The presence of B4 antigen in nearly all CALLA-positive cells suggests that both subpopulations of normal CALLA-positive marrow cells are committed to the B cell lineage.


Vitamin D and cardiometabolic risk factors and diseases.
Obesity, type 2 diabetes, and cardiovascular disease (CVD) are the most common preventable causes of morbidity and mortality worldwide. Insulin resistance, which is a shared feature in these conditions, is also strongly linked to the development of polycystic ovary syndrome (PCOS), which is the most common endocrine disease in women of reproductive age and a major cause of infertility. Vitamin D deficiency has reached epidemic proportions worldwide, primarily due to the shift to sedentary, indoor lifestyles and sun avoidance behaviours to protect against skin cancer. In recent years, vitamin D deficiency has been implicated in the aetiology of type 2 diabetes, PCOS and CVD, and has been shown to be associated with their risk factors including obesity, insulin resistance, hypertension, as well as chronic low-grade inflammation. Treating vitamin D deficiency may offer a feasible and cost-effective means of reducing cardiometabolic risk factors at a population level in order to prevent the development of type 2 diabetes and CVD. However, not all intervention studies show that vitamin D supplementation alleviates these risk factors. Importantly, there is significant heterogeneity in existing studies with regards to doses and drug regimens used, populations studied (i.e. vitamin D deficient or sufficient), and the lengths of supplementation, and only few studies have directly examined the effect of vitamin D on insulin secretion and resistance with the use of clamp methods. Therefore, there is a need for well-designed large scale trials to clarify the role of vitamin D supplementation in the prevention of type 2 diabetes, PCOS, and CVD.


Associations between staff feelings toward patients and treatment outcome at psychiatric treatment homes.
This paper presents, as part of a national Swedish research project, a study of associations between staff feelings toward patients and treatment outcome at 23 small psychiatric inpatient units. The outcome was measured with a composite scale based on structured interviews. Staff feelings were reported on a feeling checklist. Few and scattered correlations were found between staff feelings and treatment outcome when the whole group of patients was analyzed together. More meaningful patterns were found when data for psychotic and borderline patients were analyzed separately. For psychotic patients, positive outcome was associated with low levels of negative feelings throughout treatment. For borderline patients, positive outcome was associated with negative feelings at the beginning of treatment, followed by strong positive feelings in the later part. Staff feelings were more strongly associated with outcome for borderline patients than for psychotic patients. Patients with different structural diagnoses need different kinds of staff "feeling milieus."


Single Nucleotide Polymorphism in the COL11A2 Gene Associated with Heat Pain Sensitivity in Knee Osteoarthritis.
Pain is one of the most prominent symptoms of osteoarthritis. However, there is often discordance between the pain experienced by individuals with osteoarthritis and the degree of articular pathology. This suggests that individual differences, including genetic variability in the central processing of nociceptive stimuli, may impact the presentation of osteoarthritis. Here, we show that the single nucleotide polymorphism rs16868943 in the collagen gene COL11A2 is significantly associated with lowered heat pain tolerance on the arm in participants with knee osteoarthritis (P = 1.21 × 10−6, P = 0.0053 after Bonferroni correction, beta = −3.42). A total of 161 knee osteoarthritis participants were included and evaluated for heat, punctate and pressure pain sensitivity of the affected knee and the ipsilateral arm. Each participant was genotyped for 4392 single nucleotide polymorphisms in genes implicated in pain perception, inflammation and mood and tested for association with pain sensitivity. The minor A allele of single nucleotide polymorphism rs16868943 was significantly associated with lower arm heat pain tolerance after correction for age, gender, race, and study site. This single nucleotide polymorphism was also nominally associated with other measures of heat pain sensitivity, including lowered knee heat pain tolerance (P = 1.14 × 10−5, P = 0.05 after Bonferroni correction), lowered arm heat pain threshold (P = 0.0039, uncorrected) and lowered knee heat pain threshold (P = 0.003, uncorrected). Addition of genotypes from 91 participants without knee pain produced a significant interaction between knee osteoarthritis status and the rs16868943 single nucleotide polymorphism in heat pain tolerance (P = 1.71 × 10−5), such that rs16868943 was not associated with heat pain tolerance in participants without knee pain (P = 0.12, beta = 1.3). This is the first study to show genetic association with heat pain tolerance in individuals with osteoarthritis. The association is specific to participants who have already developed knee osteoarthritis, suggesting that the COL11A2 gene, which has previously been associated with familial osteoarthritis, may play a role in pain sensitization after the development of osteoarthritis.


Reassessing the good judge of personality.
Are some people truly better able to accurately perceive the personality of others? Previous research suggests that the good judge may be of little practical importance and individual differences minimal. In four large samples we assessed whether expressive accuracy (the good target) is a necessary condition for perceptive accuracy (the good judge) to emerge. As predicted from Funder's (1995) realistic accuracy model, assessments of the good judge predicted increased impression accuracy in the context of judgments of the good target. In contrast, evaluative tendencies for judges did not evidence a similar interaction; the positivity of impressions did not reliably increase as a function of how positively targets tend to be viewed. The present results suggest the good judge does indeed exist-some individuals are much better able to detect and utilize valid cues from targets-but this is only strongly evident when perceiving a good target. (PsycINFO Database Record (c) 2019 APA, all rights reserved).


Curious Case of Acute Unilateral Deep Vein Thrombosis: May-Thurner Syndrome.
May-Thurner syndrome (MTS) or iliac vein compression syndrome is an uncommon cause of deep venous thrombosis (DVT) of the lower limb occurring, especially on the left side. It occurs due to compression of the left common iliac vein by the right common iliac artery and occurs predominantly in young females. The awareness of such a presentation is essential to guide therapy. We report one such unusual case of acute-onset DVT of the left lower limb due to MTS.


New science challenges old notion that mercury dental amalgam is safe.
Mercury dental amalgam has a long history of ostensibly safe use despite its continuous release of mercury vapor. Two key studies known as the Children's Amalgam Trials are widely cited as evidence of safety. However, four recent reanalyses of one of these trials now suggest harm, particularly to boys with common genetic variants. These and other studies suggest that susceptibility to mercury toxicity differs among individuals based on multiple genes, not all of which have been identified. These studies further suggest that the levels of exposure to mercury vapor from dental amalgams may be unsafe for certain subpopulations. Moreover, a simple comparison of typical exposures versus regulatory safety standards suggests that many people receive unsafe exposures. Chronic mercury toxicity is especially insidious because symptoms are variable and nonspecific, diagnostic tests are often misunderstood, and treatments are speculative at best. Throughout the world, efforts are underway to phase down or eliminate the use of mercury dental amalgam.


Plant alkaloid tetrandrine and its analog block CD28-costimulated activities of human peripheral blood T cells: potential immunosuppressants in transplantation immunology.
T lymphocyte activation mediated by CD28 costimulation plays a critical role in graft rejection. Plant alkaloid tetrandrine, purified from a Chinese antirheumatic herb, is a potent immunosuppressant. Here, we examined its effects on several CD28-costimulated T-cell activities. In addition, such effects were readily compared with the effects of three tetrandrine analogs. T lymphocytes were purified from whole blood by negative selection. The stimuli that mimic CD28 costimulation included both anti-CD3 + anti-CD28 monoclonal antibody and PMA+anti-CD28 monoclonal antibody. The determination of CD28-costimulated cell proliferation was performed by tritium uptake, cytokine production by ELISA, cell surface interleukin 2Ra and CD69 expression by flow cytometry, and mixed leukocyte reaction by tritium uptake. Drug cytotoxicity was determined by trypan blue exclusion, propidium iodide staining, and MTT colorimetric assays. Tetrandrine inhibited CD28-costimulated T-cell proliferation and cytokine production through a mechanism different from that of cyclosporine. In addition, tetrandrine down-regulated both T helper 1 and T helper 2 cytokine production in CD4+ and CD8+ T-cell subpopulations. By examining cytokine production and T-cell activation marker expression, we further demonstrated that, among tetrandrine and its analogs tested, dauricine was the most potent suppressor of CD28-costimulated T-cell activities. Furthermore, the different immunosuppressive activities of these compounds were not associated with their cytotoxic capacities. Finally, the unparalleled inhibitory potency of dauricine on both mixed leukocyte reaction and CD28-costimulated T-cell proliferation suggests that dauricine preferentially targeted CD28-costimulated T-cell activities. This is the first report to show that tetrandrine and its analogs potently inhibited both PMA+CD28-costimulated and CD3 + CD28-costimulated activation of human peripheral blood T cells. Based upon their structural similarity and different immunosuppressive potency, these in vitro data also provide very useful information for further identification and development of more potent and less toxic immunosuppressants to achieve transplantation success.


New Medical Device Acquisition During Pediatric Severe Sepsis Hospitalizations.
Severe sepsis is a significant cause of healthcare utilization and morbidity among pediatric patients. However, little is known about how commonly survivors acquire new medical devices during pediatric severe sepsis hospitalization. We sought to determine the rate of new device acquisition (specifically, tracheostomy placement, gastrostomy tube placement, vascular access devices, ostomy procedures, and amputation) among children surviving hospitalizations with severe sepsis. For contextualization, we compare this to rates of new device acquisition among three comparison cohorts: 1) survivors of all-cause pediatric hospitalizations; 2) matched survivors of nonsepsis infection hospitalizations; and 3) matched survivors of all-cause nonsepsis hospitalization with similar organ dysfunction. Observational cohort study. Nationwide Readmission Database (2016), including all-payer hospitalizations from 27 states. Eighteen-thousand two-hundred ten pediatric severe sepsis hospitalizations; 532,738 all-cause pediatric hospitalizations; 16,173 age- and sex-matched nonsepsis infection hospitalizations; 15,025 organ dysfunction matched all-cause nonsepsis hospitalizations; and all with live discharge. Among 18,210 pediatric severe sepsis hospitalizations, 1,024 (5.6%) underwent device placement. Specifically, 3.5% had new gastrostomy, 3.1% new tracheostomy, 0.6% new vascular access devices, 0.4% new ostomy procedures, and 0.1% amputations. One-hundred forty hospitalizations (0.8%) included two or more new devices. After applying the Nationwide Readmissions Database sampling weights, there were 55,624 pediatric severe sepsis hospitalizations and 1,585,194 all-cause nonsepsis hospitalizations with live discharge in 2016. Compared to all-cause pediatric hospitalizations, severe sepsis hospitalizations were eight-fold more likely to involve new device acquisition (6.4% vs 0.8%; p < 0.001). New device acquisition was also higher in severe sepsis hospitalizations compared with matched nonsepsis infection hospitalizations (5.1% vs 1.2%; p < 0.01) and matched all-cause hospitalizations with similar organ dysfunction (4.7% vs 2.8%; p < 0.001). In this nationwide, all-payer cohort of U.S. pediatric severe sepsis hospitalizations, one in 20 children surviving severe sepsis experienced new device acquisition. The procedure rate was nearly eight-fold higher than all-cause, nonsepsis pediatric hospitalizations, and four-fold higher than matched nonsepsis infection hospitalizations.


The role of oncovascular surgery in gynecologic oncology surgery.
Oncovascular surgery is a new term used to define tumor resection with simultaneous reconstruction of the great vessels when the tumor infiltrates or firmly adheres to such vessels. The benefit of oncovascular surgery has been widely described in patients with hepato-biliary-pancreatic cancers, retroperitoneal soft tissue sarcoma, and in other areas of gynecologic oncology, such as the lateral compartment of the pelvis, retroperitoneum, and hepato-biliary-pancreatic region, with an increase in complete resections and without increasing the morbidity and mortality rates. In the latter decades of the past century, several advances and accumulating scientific evidence led gynecologic oncologists to perform more thorough cytoreductive surgeries that included multivisceral resections. But to our knowledge, published studies on the frequency and relevance of vascular surgery in gynecological oncology are scarce. Gynecologic oncologists still do not receive formal training in vascular surgery and additionally, with the current reduction in experience with pelvic and para-aortic lymphadenectomy, as well as other types of radical abdominal and pelvic surgeries, trainees will encounter fewer vascular injuries and the opportunity to deal with a variety of management types required. Well-organized collaboration between each subspecialty with a multidisciplinary approach and adequate pre-operative planning are pivotal. The aim of this review is to pave the way towards the understanding that patients with suspicion of great vessels' infiltration or encasement by tumor require personalized and specialized treatment with the need to form an oncovascular surgery team, and that it is necessary for gynecologic oncology surgeons to take a step forward in surgical training.


Comparison of plastic vs. glass evacuated serum-separator (SST) blood-drawing tubes for common clinical chemistry determinations.
We evaluated a plastic evacuated blood-drawing tube containing an integral serum-separating barrier gel, by direct comparison with a glass counterpart. The plastic tube demonstrated no differences when compared for common clinical chemistry analytes with multiple types of instruments and systems. A total of 260 such different combinations were studied with emphasis on tests sensitive to drawing and handling indexes such as lactate dehydrogenase and potassium. A total of six separate blood drawings were tested with no significant differences noted in these tests. The total study included subjective evaluations of the plastic tube's use as a blood-drawing device and objective studies based on quantitative test results from normal and hospitalized patients and use of the primary sampling tubes (both plastic and glass) for 48-h storage.


Stabilization of bacteriophage during freeze drying.
With preliminary clinical trials completed for the treatment of antibiotic resistant infections using bacteriophages, there is a need to develop pharmaceutically acceptable formulations. Lyophilization is an established technique for the storage of bacteriophage, but there is little consensus regarding drying cycles, additives and moisture content specific to phage. Here, the addition of sucrose or poly(ethylene glycol) 6000 yielded stable freeze-dried cakes only from high concentrations (0.5 M and 5%, respectively), with addition of bacteriophage otherwise causing collapse. Gelatin, which is added to storage media (a solution of salts), played no role in maintaining bacteriophage stability following lyophilization. A secondary drying cycle was most important for maintaining bacteriophage activity. The addition of high concentrations of PEG 6000 or sucrose generally caused a more rapid fall in bacteriophage stability, over the first 7-14 d, but thereafter residual activities for all phage formulations converged. There was no distinct change in the glass transition temperatures (T(g)) measured for the formulations containing the same additive. Imaging of cakes containing fluorescently labeled bacteriophage did not show gross aggregation or phase separation of bacteriophage during lyophilization. However, the moisture content of the cake did correlate with lytic activity, irrespective of the formulation, with a 4-6% moisture content proving optimal. We propose that residual moisture is followed during lyophilization of bacteriophage from minimal concentrations of bulking agent.


Brain-to-Brain Synchrony Tracks Real-World Dynamic Group Interactions in the Classroom.
The human brain has evolved for group living [1]. Yet we know so little about how it supports dynamic group interactions that the study of real-world social exchanges has been dubbed the "dark matter of social neuroscience" [2]. Recently, various studies have begun to approach this question by comparing brain responses of multiple individuals during a variety of (semi-naturalistic) tasks [3-15]. These experiments reveal how stimulus properties [13], individual differences [14], and contextual factors [15] may underpin similarities and differences in neural activity across people. However, most studies to date suffer from various limitations: they often lack direct face-to-face interaction between participants, are typically limited to dyads, do not investigate social dynamics across time, and, crucially, they rarely study social behavior under naturalistic circumstances. Here we extend such experimentation drastically, beyond dyads and beyond laboratory walls, to identify neural markers of group engagement during dynamic real-world group interactions. We used portable electroencephalogram (EEG) to simultaneously record brain activity from a class of 12 high school students over the course of a semester (11 classes) during regular classroom activities (Figures 1A-1C; Supplemental Experimental Procedures, section S1). A novel analysis technique to assess group-based neural coherence demonstrates that the extent to which brain activity is synchronized across students predicts both student class engagement and social dynamics. This suggests that brain-to-brain synchrony is a possible neural marker for dynamic social interactions, likely driven by shared attention mechanisms. This study validates a promising new method to investigate the neuroscience of group interactions in ecologically natural settings.


Longitudinal serological measures of common infection in the Avon Longitudinal Study of Parents and Children cohort.
Antibodies against pathogens provide information on exposure to infectious agents and are meaningful measures of past and present infection. Antibodies were measured in the plasma of children that are the offspring in a population-based birth cohort, the Avon Longitudinal Study of Parents and Children (ALSPAC). Plasma was collected during clinics at age 5, 7, 11 and 15 years. The antigens examined include: fungal ( Saccharomyces cerevisiae); protozoan ( Toxoplasma gondii and surface antigen 1 of T. gondii); herpes viruses (cytomegalovirus, Epstein-Barr virus, herpes simplex virus type 1); common colds (influenza virus subtypes H1N1 and H3N2); other antigens (measles); animal (feline herpes virus, Theiler's virus); bacteria ( Helicobacter pylori); dietary antigens (bovine casein alpha protein, bovine casein beta protein). Alongside the depth of data available within the ALSPAC cohort, this longitudinal resource will enable the investigation of the association between infections and a wide variety of outcomes.


Habituation Protocols Improve Behavioral and Physiological Responses of Beef Cattle Exposed to Students in an Animal Handling Class.
Our objective was to determine the impact of different habituation protocols on beef cattle behavior, physiology, and temperament in response to human handling. Beef heifers were exposed to three habituation strategies: (1) tactile stimulation (brushing) in the working chute for seven consecutive days (STI; n = 18); (2) passage through the working chute for seven consecutive days (CHU; n = 19) and; (3) no habituation (CON; n = 19). Individual heifer respiratory rate (RR; n/min), internal vaginal temperature (VAGT; °C), and blood cortisol were measured. Further, behavior parameters were observed to generate a behavior score, and heifer interaction with students and their behavioral responses were recorded. Habituation with STI and CHU resulted in improved numerical behavioral scores compared to CON, and greater (p ≤ 0.05) handling latencies. Vaginal temperature was decreased in STI compared to CHU and CONT (p ≤ 0.05). Cortisol concentration did not differ among treatments, but decreased (p ≤ 0.05) from the start of the experiment to 14 days after treatment initiation. Both habituation protocols showed benefits, but heifers that received the positive tactile stimulation in the chute had the greatest behavior improvements. Furthermore, these heifers responded more calmly during student-animal interactions in class, which is beneficial for the students' and animals' safety.


Cerivastatin gender effect: sub-analyses of results from a multinational, randomised, double-blind study. Cerivastatin Study Group.
We previously reported the results of a multicentre, randomised, double-blind, parallel-group study comparing the efficacy and safety of cerivastatin 0.4 mg/day and cerivastatin 0.2 mg/day in patients with primary hypercholesterolaemia. Exploratory analysis in this study suggested a gender difference in the 0.4 mg group: mean low-density lipoprotein cholesterol (LDL-C) decreased by 44.4 +/- 8.9% in women, compared with a mean decrease of 37.0 +/- 0.9% in men (p < 0.046). This paper reports the results of further sub-analyses from this study. Overall in the per-protocol (PP) population, 71.5% (n = 73) of women taking cerivastatin 0.4 mg had an LDL-C decrease of > 40%, compared with 38.0% (n = 76) of men taking the same dose. In the cerivastatin 0.2 mg PP population, 34% (n = 17) of women had an LDL-C decrease of > 40%, compared with 19% (n = 18) of men. Mean LDL-C/HDL-C ratio decreased by 43% from baseline to the end of the study in the cerivastatin 0.4 mg PP group: -41.3% in males vs. -48.3% in females. In the cerivastatin 0.2 mg group, the decrease in LDL-C/HDL-C ratio from baseline to endpoint did not markedly differ between genders: -37.0% for males vs. -37.3% for females. Categorial analysis of the LDL-C/HDL-C ratio found that 90% of PP patients taking cerivastatin 0.4 mg, and 84% of PP patients taking cerivastatin 0.2 mg, had a low CHD risk (defined as a LDL-C/HDL-C ratio < or = 3) after 8 weeks of treatment. The 6th and 95th percentiles of the distribution of LDL-C reduction from baseline revealed that 90% of PP patients taking cerivastatin 0.4 mg had an LDL-C reduction of between 22% and 56%. The mean LDL-C reduction for this 90% subset of patients was 40.1%. The same analysis for PP patients taking cerivastatin 0.2 mg found that 90% had an LDL-C reduction of between 13% and 49%. The mean LDL-C reduction in this 90% subset of patients was 31.5%. Of the patients taking cerivastatin 0.4 mg and valid for treatment according to National Cholesterol Education Program (NCEP) criteria, 71% (149/211) achieved NCEP targets for LDL-C at Week 16.


New leafhopper species of Jikradia from Mesoamerica with new records, revised key to species, distribution, origin, and checklist (Hemiptera: Cicadellidae: Coelidiinae: Teruliini).
The following four new species of leafhoppers are described and illustrated: Jikradia dentata n. sp. and J. trispinata n. sp. from Guatemala, J. variabilis n. sp. from Belize, and J. exilis n. sp. from Costa Rica. Jikradia basipendula Nielson and J. krameri Nielson are new records for Guatemala. Belize is a new record for the genus. A record of the first introduction of the genus in the Old World is reviewed. A revised key to the known species is provided with a review of its possible origin. A checklist of all known species is also given.


An in silico case study of idiopathic dilated cardiomyopathy via a multi-scale model of the cardiovascular system.
Mathematical modelling has been used to comprehend the pathology and the assessment of different treatment techniques such as heart failure and left ventricular assist device therapy in the cardiovascular field. In this study, an in-silico model of the heart is developed to understand the effects of idiopathic dilated cardiomyopathy (IDC) as a pathological scenario, with mechanisms described at the cellular, protein and organ levels. This model includes the right and left atria and ventricles, as well as the systemic and pulmonary arteries and veins. First, a multi-scale model of the whole heart is simulated for healthy conditions. Subsequently, the model is modified at its microscopic and macroscopic spatial scale to obtain the characteristics of IDC. The extracellular calcium concentration, the binding affinity of calcium binding proteins and the maximum and minimum elastances have been identified as key parameters across all relevant scales. The modified parameters cause a change in (a) intracellular calcium concentration characterising cellular properties, such as calcium channel currents or the action potential, (b) the proteins being involved in the sliding filament mechanism and the proportion of the attached crossbridges at the protein level, as well as (c) the pressure and volume values at the organ level. This model allows to obtain insight and understanding of the effects of the treatment techniques, from a physiological and biological point of view.


Dealing with trainees in difficulty.
Doctors are highly valued in every society as they are expected to serve humanity with dedication, commitment and motivation within professional boundaries. Those working within acute specialities are increasingly coming under public microscope. As the public expectations of a quality assured high quality services delivered by the doctors-- is increasing, so does the pressure on doctors to deliver these services. Our doctors in training are on the front line to deal with the initial assessment of acutely sick women and therefore may be exposed to stressful situations with little support. All doctors in training require support from their trainers and clinical supervisors but more support is needed for trainees who are struggling to cope with the pressure and are in difficulty. This paper examines underlying factors which need to be clearly understood before planning a remedial strategy for this group of doctors. They should be handled sensitively but pro actively.


Adjudin protects against cerebral ischemia reperfusion injury by inhibition of neuroinflammation and blood-brain barrier disruption.
Neuroinflammation mediated by activation of microglia and interruption of the blood-brain barrier (BBB) is an important factor that contributes to neuron death and infarct area diffusion in ischemia reperfusion injury. Finding novel molecules to regulate neuroinflammation is of significant clinical value. We have previously shown that adjudin, a small molecule compound known to possess antispermatogenic function, attenuates microglia activation by suppression of the NF-κB pathway. In this study we continued to explore whether adjudin could be neuroprotective by using the transient middle cerebral artery occlusion (tMCAO) model. Adjudin treatment after reperfusion significantly decreased the infarction volume and neuroscore compared to the vehicle group. Staining of CD11b showed that adjudin markedly inhibited microglial activation in both the cortex and the striatum, accompanied by a reduction in the expression and release of cytokines TNF-α, IL-1β and IL-6. Concomitantly, adjudin noticeably prevented BBB disruption after ischemia and reperfusion, as indicated by the reduction of IgG detection in the brain cortex and striatum versus the vehicle group. This finding was also corroborated by immunofluorescence staining and immunoblotting of tight junction-related proteins ZO-1, JAM-A and Occludin, where the reduction of these proteins could be attenuated by adjudin treatment. Moreover, adjudin obviously inhibited the elevated MMP-9 activity after stroke. Together these data demonstrate that adjudin protects against cerebral ischemia reperfusion injury, and we present an effective neuroinflammation modulator with clinical potential.


Effect of Selected Cooking Ingredients for Nixtamalization on the Reduction of Fusarium Mycotoxins in Maize and Sorghum.
Although previous studies have reported the use of nixtamalization for mycotoxins reduction in maize, the efficacy of calcium hydroxide and other nixtamalization cooking ingredients for mycotoxin reduction/decontamination in sorghum and other cereals still need to be determined. The current study investigated the effect of five nixtamalization cooking ingredients (wood ashes, calcium hydroxide, sodium hydroxide, potassium hydroxide, and calcium chloride) on the reduction of Fusarium mycotoxins in artificially contaminated maize and sorghum using liquid chromatography-tandem mass spectrometry. All tested cooking ingredients effectively reduced levels of mycotoxins in the contaminated samples with reduction initiated immediately after the washing step. Except for the calcium chloride nixtamal, levels of fumonisin B1, B2, and B3 in the processed sorghum nixtamal samples were below the limit of detection. Meanwhile, the lowest pH values were obtained from the maize (4.84; 4.99), as well as sorghum (4.83; 4.81) nejayote and nixtamal samples obtained via calcium chloride treatment. Overall, the results revealed that the tested cooking ingredients were effective in reducing the target mycotoxins. In addition, it pointed out the potential of calcium chloride, though with reduced effectiveness, as a possible greener alternative cooking ingredient (ecological nixtamalization) when there are environmental concerns caused by alkaline nejayote.


Computational Modeling of PI3K/AKT and MAPK Signaling Pathways in Melanoma Cancer.
Malignant melanoma is an aggressive tumor of the skin and seems to be resistant to current therapeutic approaches. Melanocytic transformation is thought to occur by sequential accumulation of genetic and molecular alterations able to activate the Ras/Raf/MEK/ERK (MAPK) and/or the PI3K/AKT (AKT) signalling pathways. Specifically, mutations of B-RAF activate MAPK pathway resulting in cell cycle progression and apoptosis prevention. According to these findings, MAPK and AKT pathways may represent promising therapeutic targets for an otherwise devastating disease. Here we show a computational model able to simulate the main biochemical and metabolic interactions in the PI3K/AKT and MAPK pathways potentially involved in melanoma development. Overall, this computational approach may accelerate the drug discovery process and encourages the identification of novel pathway activators with consequent development of novel antioncogenic compounds to overcome tumor cell resistance to conventional therapeutic agents. The source code of the various versions of the model are available as S1 Archive.


Epilepsy and schizophrenia.
Slater's work on the schizophrenia-like psychoses of epilepsy is re-examined in the light of subsequent developments in psychiatry and neurology. Simple causal links of the sort he postulated between epilepsies and psychoses appear increasingly tenuous, despite indications that some psychotic symptoms and some localised structural changes are linked. A resumption of the study of electrophysiological similarities between schizophrenia and limbic epilepsy may offer a useful alternative programme for research.


Characterization of miRNA-regulated networks, hubs of signaling, and biomarkers in obstruction-induced bladder dysfunction.
Bladder outlet obstruction (BOO) induces significant organ remodeling, leading to lower urinary tract symptoms accompanied by urodynamic changes in bladder function. Here, we report mRNA and miRNA transcriptome sequencing of bladder samples from human patients with different urodynamically defined states of BOO. Patients' miRNA and mRNA expression profiles correlated with urodynamic findings. Validation of RNA sequencing results in an independent patient cohort identified combinations of 3 mRNAs (NRXN3, BMP7, UPK1A) and 3 miRNAs (miR-103a-3p, miR-10a-5p, miR-199a-3p) sufficient to discriminate between bladder functional states. All BOO patients shared cytokine and immune response pathways, TGF-β and NO signaling pathways, and hypertrophic PI3K/AKT signaling pathways. AP-1 and NFkB were dominant transcription factors, and TNF-α was the top upstream regulator. Integrated miRNA-mRNA expression analysis identified pathways and molecules targeted by differentially expressed miRNAs. Molecular changes in BOO suggest an increasing involvement of miRNAs in the control of bladder function from the overactive to underactive/acontractile states.


Male mating constraints affect mutual mate choice: prudent male courting and sperm-limited females.
Costs of sperm production may lead to prudence in male sperm allocation and also to male mate choice. Here, we develop a life history-based mutual mate choice model that takes into account the lost-opportunity costs for males from time out in sperm recovery and lets mate competition be determined by the prevailing mate choice strategies. We assume that high mating rate may potentially lead to sperm depletion in males, and that as a result, female reproduction may be limited by the availability of sperm. Increasing variation in male quality leads, in general, to increased selective mate choice by females, and vice versa. Lower-quality males may, however, gain access to more fecund higher-quality females by lowering their courting rate, thus increasing their sperm reserves. When faced with strong male competition for mates, low-quality males become less choosy, which leads to assortative mating for quality and an increased mating rate across all males. With assortative mating, the frequency of antagonistic interactions (sexual conflict) is reduced, allowing males to lower the time spent replenishing sperm reserves in order to increase mating rate. This in turn leads to lower sperm levels at mating and therefore could lead to negative effects on female fitness via sperm limitation.


Distinguishing Causation From Correlation in the Use of Correlates of Protection to Evaluate and Develop Influenza Vaccines.
There is increasing attention to the need to identify new immune markers for the evaluation of existing and new influenza vaccines. Immune markers that could predict individual protection against infection and disease, commonly called correlates of protection (CoPs), play an important role in vaccine development and licensing. Here, we discuss the epidemiologic considerations when evaluating immune markers as potential CoPs for influenza vaccines and emphasize the distinction between correlation and causation. While an immune marker that correlates well with protection from infection can be used as a predictor of vaccine efficacy, it should be distinguished from an immune marker that plays a mechanistic role in conferring protection against a clinical endpoint-the latter might be a more reliable predictor of vaccine efficacy and a more appropriate target for rational vaccine design. To clearly distinguish mechanistic and nonmechanistic CoPs, we suggest using the term "correlates of protection" for nonmechanistic CoPs, and ''mediators of protection'' for mechanistic CoPs. Furthermore, because the interactions among and relative importance of correlates or mediators of protection can vary according to age or prior vaccine experience, the effect sizes and thresholds for protective effects for CoPs could also vary in different segments of the population.


Inherited liver diseases affecting the adult.
A variety of different inherited disorders may cause liver disease in adults. Recent advances in molecular genetics have improved our understanding of these diseases, such as the isolation and characterization of the genes responsible for Wilson disease, alpha1-antitrypsin deficiency, and cystic fibrosis. A candidate gene responsible for hereditary hemochromatosis has also recently been cloned. These scientific advances have important implications in the diagnosis, treatment, and screening of patients with genetic diseases and their families. We review the most common inherited liver diseases affecting adults, with emphasis on the clinical implications of recent molecular advances.


Personal and professional influences on health visitors' family focused practice for maternal mental illness: a cross sectional study.
Family focused practice (FFP) is an approach that recognises the inter-related needs of family members and recommends a continuum of activities to support families. While it is recognised that health visitors play a key role in supporting families when mothers have mental illness, there is limited understanding of health visitor's family focused practice (FFP) in this context and its relationships with factors, such as, workload, training, skill and knowledge, and personal and professional experience. This paper examined the effect of health visitors' interaction with the family, and personal and professional experience on their family focused practice. A cross sectional questionnaire (Family Focused Mental Health Practice Questionnaire) was distributed to 488 health visitors within community practice in Northern Ireland, with 230 choosing to take part. Independent t-tests and one-way analysis of variance were used to compare family focused practice scores. Results found that health visitors who had face to face contact with partners and children (t(221) = 2.61, p = .01), and those that directly supported the partner (t(221) = 2.61, p = 0.01) had a significantly higher mean score of FFP, than those that did not. However, frequency of visits (daily, weekly, monthly or yearly) had no effect on family focused practice scores. Training also had a significant effect on family focused practice scores (F(2,221) = 4.841, p = 0.029). Analysis of variance revealed that personal experience of mental illness had a significant effect on scores (M = 97.58, p = 0.009), however variables such as, age, parental status, time since registration, and being in a specialist position had no effect. In order for family focused practice to be effective, the quality, and content of visits and contact with family should be addressed, as opposed to a focus on the quantity of visits. However, in order for this to occur health visitors need to have appropriate support in their own right, with manageable caseloads and resources.


[Current status of lung preservation for organ transplantation].
This paper gives a survey of the development and the present state of the preservation of isolated lungs intended for transplantation. Hypothermal perfusion with a colloid-containing electrolyte solution, supplemented with certain additives, without ventilation of the preserved lung is obviously a technique that is ready to be used in practice. The present priorities in experimental research are: elaboration of a standardized preservation technique, of which the expenditure can be justified in a clinical transplantation program, and establishment of parameters for the control of its efficiency.


Efficacy of Cangrelor as Bridging Therapy Post PCI.
Dual antiplatelet therapy (DAPT) remains the cornerstone management for the prevention of acute stent thrombosis after percutaneous intervention (PCI). Situations mandating early interruption of DAPT carry a high risk of ischemic complications. Perioperative bridge therapy using Cangrelor, an intravenous P2Y2 inhibitor, may offer a potential solution. Unfortunately, evidence for its use in non-cardiac procedures is limited. Our protocol demonstrates successful off-label use of IV Cangrelor bridge therapy in a non-cardiac surgery patient. We describe a case of a 77-year old male; triple therapy with Aspirin, Apixaban, and Ticagrelor for recent drug-eluting stent placement required immediate surgical resection of stage I colonic adenocarcinoma. Cangrelor bridge therapy was utilized both preoperatively and postoperatively without ischemic or bleeding complications. The patient tolerated exploratory laparoscopic colectomy with minimal bleeding and good post-op recovery. Minimizing the interruption of DAPT therapy in high-risk patients is achievable. However, careful planning with a team-based approach involving surgeons, cardiologists and pharmacists, along with close clinical follow-up and vigilant management of anti-platelet therapy is recommended.


A survey of the complaints entering the medical council organization of tehran in three time periods: the years ending on 20 march 1992, 20 march 1997 and 20 march 2002.
One of the most important occupational tensions a physician encounters in his/her practice is the complaints lodged against him/her by the patients. The purpose of this study is examining the complaints against physicians and dentists entering the Medical Council Organization of Tehran in the years ending on 20 March 1992, 20 March 1997 and 20 March 2002 from the viewpoint of number, dispersion and inducing factors. The present study was performed as a descriptive and retrospective one with the aid of a questionnaire containing concerned data. Filling in the questionnaire or studying the file was accomplished by a trustee expert of the Medical Council Organization and the data obtained were analyzed after classification. During a 3-year period, 832 complaints were lodged against physicians and dentists. The complaints against physicians in the years ending on 20 March 1997 and 20 March 2002 were 70% more than that in the year ending on 20 March 1992. 83.1% of the physicians and dentists of Tehran that were sued had not been convicted until the date of the performance of the study, on the basis of the contents of the files, and had no malpractice from the vantage point of the Medical Council Organization. The most common causes of complaints from the viewpoint of complainers were therapeutic errors (38%), neglect (30.2%), financial affairs (25.4%) and the physicians' lack of skill (17.7%). On the basis of this study, with the increase of the doctor's practice track record and experience more than 15-20 years, the number of the complaints decreases and most of the complaints are against the middle-aged doctors/dentists with 10-20 years of experience. Most physicians and dentists of Tehran having been sued have not committed any wrong from the vantage point of the Medical Council Organization experts and a large part of the complaints are a consequence of doctor-patient inconvenient interactions. A behavior based on professional commitment of the physician/dentist vis-à-vis the patient can hinder a major part of complaints.