Building Resilient Agricultural Communities: A Process for Addressing Mental Health Challenges in Agricultural Communities.
The impacts of stress on physical and mental health are increasingly salient, and understanding how occupational stress interacts with occupational health and safety will shape conditions and cultures for workers. The Upper Midwest Agricultural Safety and Health Center (UMASH) recognized a need to better understand occupational stressors and mental health outcomes in agriculture, and identify barriers to mental health care along with interventions to improve this system. UMASH hosted a one-day working forum that framed agricultural stress and poor mental health, and potential for interventions, for Minnesota farmers, agricultural workers, and their families. Building Resilient Agricultural Communities engaged a spectrum of stakeholders in agricultural work including: representatives of agricultural workers, farmers, health care, policy makers, and more. The forum further defined stressors and systemic barriers to health care for agricultural workers through presentations, panel discussion, that facilitated discussions and recommendations for intervention. Priority areas to focus outreach and engagement efforts, research, and screening are shared out, with reference to the continued outcomes and impact of this forum.


Entanglement Entropy in Two-Dimensional String Theory.
To understand an emergent spacetime is to understand the emergence of locality. Entanglement entropy is a powerful diagnostic of locality, because locality leads to a large amount of short distance entanglement. Two-dimensional string theory is among the very simplest instances of an emergent spatial dimension. We compute the entanglement entropy in the large-N matrix quantum mechanics dual to two-dimensional string theory in the semiclassical limit of weak string coupling. We isolate a logarithmically large, but finite, contribution that corresponds to the short distance entanglement of the tachyon field in the emergent spacetime. From the spacetime point of view, the entanglement is regulated by a nonperturbative "graininess" of space.


[Protective effects of yishen ruanjian power on renal interstitial fribrosis in chronic aristolochic acid induced nephropathy rat model].
To study the protective effects of Yishen Ruanjian Power (YRP) on renal interstitial fibrosis in rats with chronic aristolochic acid induced nephropathy (CAAN). Eighteen male SD rats were divided into 3 groups, 6 in each group. Water solution of Caulis Aristolochia Manshuriensis (CAM) Liquid Extract were given to the mice in the model group by gastrogavage to make CAAN animal model. For those in the TCM group, decocted water solution of YRP was given by gastrogavage after the mice being modeled with the above-mentioned method. Tap water was given by gastrogavage to the mice in the control group. Body weight, 24-hr urinary protein excretion and beta2 microglobulin (beta2-MG), and serum creatinine (r) were determined at the end of the 1st, 4th, 8th, 12th and 16th week. At the end of the 16th week, the rats were sacrificed and the pathological figure of their kidneys were observed by Masson staining. Transforming growth factor-beta1 (TGF-beta1), connective tissue growth factor (CTGF), plasminogen activator inhibitor-1 (PAI-1), tissue inhibitor of metalloproteinase-1 (TIMP-1) and type I collagen (Col I ) in kidney tissue were determined by RT-PCR and immunohistochemical method, respectively. At end of the 1st week, urinary protein excretion, urinary beta2-MG and SCr in the model group were significantly increased to the levels higher than those in the control group (P < 0.01 or 0.05). Relative area of interstitial fibrosis was significantly enlarged in the model group at the end of the 16th week (P<0.01), and at the same time, the mRNA and protein expression of TCF-beta1, CTGF, PAI-1, TIMP-1 and Col I in kidney tissue were significant up-regulated (P<0.01). After intervention with YRP, the above-mentioned up-regulated parameters, except 24-hr urinary protein excretion, were all significantly inhibited (P <0.01 or 0.05). YRP could inhibit the accumulation of extracellular matrix in renal interstitial tissue, so as to alleviate the renal interstitial fibrosis and improve the renal function.


[Epithelial and stromal cell culture of human endometrium and characterization].
Endometrium is a heterogeneous tissue, subject to many factors of which the actions and the regulations on the different cellular types were unknown. A medium with cortisol, cholera toxin, EGF, insulin and low concentration of horse serum is used for epithelial cell primary cultures (range 23-55 days, mean: 31.9 days). A medium with high concentration of fetal calf serum is used for stromal cell primary cultures (range 21-214 days, mean: 75 days). We have characterized by immunocytochemical studies all different cultures.


A clinically useful screen for attention-deficit/hyperactivity disorder in adult psychiatric outpatients.
Attention-deficit/hyperactivity disorder (ADHD) is a serious illness that is frequently underdiagnosed in adults. The goal of this report from the Rhode Island Methods to Improve Diagnostic Assessment and Services project was to determine if it was possible to identify 1 or 2 ADHD criteria that could serve as "gate" criteria to screen for the disorder. Psychiatric outpatients (N = 1,134) were evaluated using a semi-structured diagnostic interview for DSM-IV criteria of ADHD. We computed the sensitivity, specificity, and positive and negative predictive values of each of the 18 ADHD criteria to identify 1 or 2 criteria that could be used to screen for the disorder. We conducted a validation and cross-validation analysis by splitting the sample in half. In both the validation and cross-validation samples, a 2-item screen of difficulty sustaining attention and fidgetiness had a sensitivity of >90%. The negative predictive value of the 2-item screen was >95%. Clinicians can screen for ADHD in adults by inquiring about 2 features of the disorder (ie, difficulty sustaining attention and fidgetiness), the presence of which captures most patients with the disorder and the absence of which rules out the disorder.


15-Deoxyspergualin inhibits Akt kinase activation and phosphatidylcholine synthesis.
15-Deoxyspergualin (DSG) strongly inhibited growth of mouse EL-4 lymphoma cells in vitro and in vivo. It significantly prolonged the survival days of EL-4-transplanted mice. In vitro study revealed that its antiproliferative effect appeared only after 2 days of treatment. At that time, protein synthesis was significantly inhibited rather than DNA and RNA syntheses. Furthermore, DSG induced apoptosis without arresting the cell cycle. p70 S6 kinase (p70S6K), a key molecule in protein synthesis, was inhibited by 2 days of treatment of DSG. Akt, an upstream kinase of p70S6K, was also deactivated by 2 days of treatment of DSG. Hsp90 is reported to bind to and stabilize Akt kinase and also to bind to DSG. Yet DSG did not inhibit the binding of Hsp90 to Akt kinase. PI3-kinase, an activator of Akt, was not affected by DSG treatment. However, when we looked into phospholipid synthesis, we found that DSG inhibited phosphatidylcholine (PC) synthesis strongly rather than phosphatidylinositol even by 1 day of treatment. Moreover, DSG failed to inhibit Akt kinase activation and PC synthesis in DSG-less sensitive human K562 leukemia cells. These results demonstrate that DSG inhibits tumor cell growth through the inhibition of protein synthesis and induction of apoptosis, which is caused by the down-regulation of Akt kinase and p70S6K. It is also indicated that the down-regulation of Akt kinase by DSG should not depend on PI3-kinase and Hsp90. There might be possible involvement of PC in Akt kinase activity.


CD4(+) tumor infiltrating lymphocytes are prognostic and independent of R-IPI in patients with DLBCL receiving R-CHOP chemo-immunotherapy.
Despite the Revised International Prognostic Index's (R-IPI) undoubted utility in diffuse large B-cell lymphoma (DLBCL), significant clinical heterogeneity within R-IPI categories persists. Emerging evidence indicates that circulating host immunity is a robust and R-IPI independent prognosticator, most likely reflecting the immune status of the intratumoral microenvironment. We hypothesized that direct quantification of immunity within lymphomatous tissue would better permit stratification within R-IPI categories. We analyzed 122 newly diagnosed consecutive DLBCL patients treated with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) chemo-immunotherapy. Median follow-up was 4 years. As expected, the R-IPI was a significant predictor of outcome with 5-year overall survival (OS) 87% for very good, 87% for good, and 51% for poor-risk R-IPI scores (P < 0.001). Consistent with previous reports, systemic immunity also predicted outcome (86% OS for high lymphocyte to monocyte ratio [LMR], versus 63% with low LMR, P = 0.01). Multivariate analysis confirmed LMR as independently prognostic. Flow cytometry on fresh diagnostic lymphoma tissue, identified CD4(+) T-cell infiltration as the most significant predictor of outcome with ≥23% infiltration dividing the cohort into high and low risk groups with regard to event-free survival (EFS, P = 0.007) and OS (P = 0.003). EFS and OS were independent of the R-IPI and LMR. Importantly, within very good/good R-IPI patients, CD4(+) T-cells still distinguished patients with different 5 year OS (high 96% versus low 63%, P = 0.02). These results illustrate the importance of circulating and local intratumoral immunity in DLBCL treated with R-CHOP.


HIV/AIDS workplace policy addressing epidemic drivers through workplace programs.
HIV workplace policies have become an important tool in addressing the HIV Pandemic in Sub-Saharan Africa. In Zambia, the National AIDS Council has been advocating for establishing of HIV/AIDS workplace policies to interested companies, however no formal evaluation has been done to assess uptake and implementation. The study aimed to establish the existence of HIV/AIDS policies and programs in the private sector and to understand implementation factors and experiences in addressing HIV epidemic drivers through these programs. A mixed method assessment of the availability of policies was conducted in 128 randomly selected member companies of Zambia Federation of Employers in Lusaka. Categorized variables were analysed on Policy and programs using Stata version 12.0 for associations: Concurrently, 28 in-depth interviews were conducted on purposively sampled implementers. Qualitative results were analysed thematically before integrating them with qualitative findings. Policies were found in 47/128 (36.72%) workplaces and the private sector accounted for 34/47 (72.34%) of all workplaces with a policy. Programs were available in 56/128 (43.75%) workplaces. The availability of policy was 2.7 times more likely to occur with increased size of a workplace, P value = 0.0001, (P < 0.05). Management support was 0.253 times more likely to occur in workplaces with policy, P value = 0.013, (P < 0.05) compared to those without. Having a specific budget for programs was 0.23 times more likely to occur in workplaces with a policy (P < 0.05) than those without a policy. Implementation was hindered by reduced funding, lack of time, sensitisation and lack of monitoring/evaluation systems. HIV awareness (56/56, 100%) and HIV/AIDS/Stigma (47/56, 83.93%) were the most addressed epidemic drivers through programs while Mother to Child Transmission (30/56 53.57%) and Males having sex with males were the least addressed (18/56, 32.14%). HIV/AIDS policies exist in the private sector at a very low proportion but policy translation was very high suggesting that workplaces with polices are likely to implement programs. The eradication of HIV/AIDS by 2030, requires addressing epidemic drivers with a focus on marginalised populations, gender integration, a wellness and rights based approach within the context of the legal framework.


Prognostic significance of neutrophil lymphocyte ratio and platelet lymphocyte ratio in advanced gastric cancer patients treated with FOLFOX chemotherapy.
Several inflammatory response materials could be used for prediction of prognosis of cancer patients. The neutrophil lymphocyte ratio (NLR), and the platelet lymphocyte ratio (PLR) have been introduced for prognostic scoring system in various cancers. The objective of this study was to determine whether the NLR or the PLR would predict the clinical outcomes in advanced gastric cancer patients treated with oxaliplatin/ 5-fluorouracil (FOLFOX). The study population consisted of 174 advanced gastric cancer patients. Patients were treated with 85 mg/m2 of oxaliplatin as a 2-h infusion at day 1 plus 20 mg/m2 of leucovorin over 10 min, followed by 5-FU bolus 400 mg/m2 and 22-h continuous infusion of 600 mg/m2 at days 1-2. Treatment was repeated in 2-week intervals. The NLR and PLR were calculated from complete blood counts in laboratory test before and after first cycle of chemotherapy. NLR was a useful prognostic biomarker for predicting inferior overall survival (OS) (p = 0.005), but was not associated with progression free survival (PFS) (p = 0.461). The normalization of NLR after one cycle of chemotherapy was found to be in association with significant improvement in PFS (5.3 months vs. 2.4 months, p < 0.001), and OS (11.9 months vs. 4.6 months, p < 0.001). The normalization of PLR was also associated with longer PFS (5.6 months vs. 3.4 months, p = 0.006), and OS (16.9 months vs. 10.9 months, p = 0.002). In multivariate analysis, changes in NLR were associated with PFS (Hazard ratio (HR): 2.297, 95% confidence interval (CI): 1.429-3.693, p = 0.001). The NLR, (HR: 0.245, 95% CI: 0.092-0.633, p = 0.004), PLR (HR: 0.347, 95% CI: 0.142-0.847, p = 0.020), changes in NLR (HR: 2.468, 95% CI: 1.567-3.886, p < 0.001), and changes in PLR (HR: 1.473, 95% CI: 1.038-2.090, p = 0.030) were independent prognostic markers for OS. This study demonstrates that NLR, PLR, and changes in NLR or PLR are independent prognostic factor for OS in patients with advanced gastric cancer treated with chemotherapy. These specific factors may also help in identifying the patients, who are more sensitive to FOLFOX regimen.


Pediatric palliative care: a family-centered model for critical care.
Melanie's case and the associated concerns are not unique. Children with life-threatening conditions and their families and communities may benefit from a family-centered model of pediatric palliative care. Benefits from its implementation are not just at the end of life, but throughout the course of therapy. Compassion coupled with a holistic approach incorporating humane and family-centered care is essential in meeting physical, mental, and spiritual needs. An interdisciplinary and collaborative model of pediatric palliative care involves the work of many, including nurses, physicians, social workers, chaplains, child life specialists, pharmacists, ethicists, bereavement counselors, ancillary staff, volunteers, and families themselves. They must incorporate key elements of the model, including clinical services, education and training, support services, and research that address physical, mental, and spiritual needs of families, children, and communities faced with life-threatening conditions.


Adherence to a Mediterranean diet and its association with age-related macular degeneration. The Coimbra Eye Study-Report 4.
This study aimed to characterize the association of lifestyle and nutritional risk profiles with age-related macular degeneration (AMD) in two subpopulations with differing AMD prevalence. This case-control study (n = 1992) included 768 patients with AMD and 1224 age- and sex-matched participants without AMD with a single visit at a primary health care unit. Enrolled participants completed a validated lifestyle and food frequency questionnaire. A score to measure adherence to the Mediterranean diet (mediSCORE; Range, 0-9) was constructed from individual food intakes, which were further analyzed by conversion to nutrient consumption. Higher adherence to the Mediterranean diet (mediSCORE ≥6) was significantly associated with no AMD (odds ratio [OR] = 0.73; P = 0.009). The subpopulation with lower AMD prevalence presented significantly higher adherence to the Mediterranean diet in relation to all individual food groups that comprised the mediSCORE (P < 0.014) with the exception of cereals. Food group analysis showed significant associations between the increased consumption of vegetables (OR = 0.63; P < 0.001) and fruit and nuts (OR = 0.78; P = 0.010) with no AMD. Nutrient analysis revealed that an increased ingestion of water, fibers, total fat, monounsaturated and polyunsaturated fatty acids, linoleic acid, vitamins A and C, carotene, alpha-tocopherol, folate, magnesium, iron, and zinc were significantly associated with no AMD (P < 0.0013). Finally, regular physical activity was associated with no AMD (P = 0.003). High adherence to a Mediterranean diet and regular physical activity seem to be protective factors for AMD in a Portuguese population. The effect of the diet is likely driven by the increased consumption of vegetables, fruits, and nuts.


Merkel cell tumour of the eyelid and reconstruction with the Cutler-Beard technique: a clinicopathologic case report.
A case of Merkel cell tumour that developed on the left upper lid of a 76-year-old white man is reported. The diagnosis was ultrastructurally made by demonstrating characteristic light microscopic features of Merkel cell carcinoma; such as large, round nuclei and frequent mitoses. Immunohistochemically, the tumour cells were shown to possess simple epithelia-type keratin intermediate filaments. Merkel cell tumour probably develops from precursor cells which give rise to keratinocytes and Merkel cells, and nearly one out of 10 Merkel cell tumours occur in the eyelid and periocular region. They tend to be bulging lesions near the lid margin of elderly patients. The condition can be misdiagnosed as lymphoma, oat cell carcinoma, malignant melanoma, sweat gland tumours, neuroblastoma and Ewing's sarcoma, and frequently invades lymphatic vessels. Nearly one out of three Merkel cell tumours recur and two thirds cause regional lymph node metastases. Wide surgical resection and reconstructive procedures, should be followed by routine postoperative irradiation. This patient was treated with wide resection and the Cutler-Beard technique, then scheduled for radiotherapy.


Use of neuroimaging measurements of optic nerve sheath diameter to assess intracranial pressure in craniosynostosis.
This study aims to evaluate accuracy of optic nerve sheath diameter (ONSD) measurements obtained by magnetic resonance imaging (MRI) in patients with craniosynostosis (CS) for detection of high intracranial pressure (ICP) and to correlate MRI-derived ONSD measurements with those obtained by computed tomography (CT) scans in CS patients. A retrospective review was conducted on CS patients who had MRI- and age-matched controls with normal MRI. Diagnosis of intracranial hypertension was based on presence of papilledema, direct ICP monitoring, and/or lumbar puncture. The search also included patients with MRI and CT done within 30 days apart. ONSDs were measured 3 mm behind the globe on both modalities. The study identified 56 CS patients (mean age 3.8 ± 3.47 years) and 49 controls (mean age 3.7 ± 3.62 years). Mean ONSD in patients with high ICP was significantly higher than in patients without high ICP (P = 0.0001) and in controls (P < 0.0001). The optimal ONSD threshold for predicting raised ICP in patients >1 year old was 6 mm (71.4% sensitivity, 89.7% specificity). Nineteen patients with 38 single-eye MRI/CT pairs were identified. Substantial agreement between both modalities resulted (r = 0.959, 95% CI 0.923-0.978), and Bland and Altman Plot analysis showed that 95% of measurements fell within limits of agreement (1.96 SD; ± 0.6 mm). In CS patients, ONSD measured by MRI represent indirect non-invasive means of ICP assessment. Both MRI and CT measurements of ONSD gave comparable results, and the use of CT-derived ONSD measurements may give some idea about ICP in CS patients.


SOME ASPECTS OF HAEMOSTASIS AFTER OPEN-HEART SURGERY.
In two groups of patients undergoing extracorporeal circulation with hypothermia, changes were found in the coagulation mechanism which were probably due to the dosage of polybrene administered. The role of heparin and polybrene and the concept of activation of the coagulation mechanism in the production of bleeding after perfusion are discussed.


Does palliative chemotherapy provide a palliative effect on symptoms in late palliative stages? An interview study with oncologists.
The possible chemotherapy effects on symptoms in late stages of palliative chemotherapy are seldom registered in clinical practice or investigated as primary outcomes. The aim was therefore to study physicians' opinions and experiences about chemotherapy effects on symptoms. Thirty-five physicians (mainly oncologists) with variation as regards age, gender and experience were included in a qualitative study with semi-structured interviews. A qualitative content analysis was used for the 30-60 min long interviews. According to all the informants, symptoms were possible to control in successful cases but the chances reduce rapidly with the number of chemotherapy lines. Symptoms possible to control included various types of pain (bone pain, neuropathic cranial as well as meningeal nerve pain, colic pain, "liver" pain, headache and pain from cutaneous metastases); nausea and vomiting caused by obstruction; dyspnoea due to pleural effusions or bronchial obstructions. Also fatigue and B-symptoms were possible targets, as were diagnosis-specific symptom clusters (e.g., liver metastasis causing pain, nausea, tumour fever and night sweats; or head-neck cancers resulting in nerve pain, ulcerations, odour, dysphagia and impaired breathing). Some of the oncologists discussed whether the effects were related to chemotherapy treatment only or partly to premedication with steroids. Despite the claimed effects, the physicians did not keep record on symptoms, they did not evaluate them with validated instruments. Palliative chemotherapy has a substantial potential to reduce agonizing symptoms especially in first line treatments, but the effect is limited in late stages. The actual awareness of and knowledge about situations where the treatment has a reasonable potential, should be improved and symptoms should be monitored during treatment.


The butterfly design: coverage of a large sacral defect with two pedicled lumbar artery perforator flaps.
The treatment of sacral pressure sores in ambulatory patients presents a challenge to the reconstructive surgeon. We report the successful use of two pedicled lumbar artery perforator flaps to cover a sacral defect measuring 12 cm x 25 cm. Stable coverage was provided, with protective sensibility, acceptable contour and minimal donor-site morbidity, while additional functional loss of the gluteal muscle was avoided. The configuration of the flaps resembles a butterfly.


Gemfibrozil, a Lipid-Lowering Drug, Lowers Amyloid Plaque Pathology and Enhances Memory in a Mouse Model of Alzheimer's Disease via Peroxisome Proliferator-Activated Receptor α.
Deposition of extracellular senile plaques containing amyloid-β is one of the major neuropathological characteristics of Alzheimer's disease (AD). Therefore, targeting amyloid-β dyshomeostasis is an important therapeutic strategy for treatment of AD. In this study, we demonstrate that gemfibrozil, an FDA-approved drug for hyperlipidemia, can lower the amyloid plaque burden in the hippocampus and cortex of the 5XFAD model of AD. Additionally, gemfibrozil reduced microgliosis and astrogliosis associated with plaque in these mice. Administration of gemfibrozil also improved spatial learning and memory of the 5XFAD mice. Finally, we delineate that gemfibrozil requires the transcription factor peroxisome proliferator-activated receptor alpha (PPARα) to exhibit its amyloid lowering and memory enhancing effects in 5XFAD mice. These results highlight a new therapeutic property of gemfibrozil and suggest that this drug may be repurposed for treatment of AD.


Soman induced changes in brain regional glucose use.
Soman, a potent central acetylcholine esterase inhibitor, has a greater impact on brain regional glucose use than other organophosphates, such as diisopropylfluorophosphate (DFP) or phospholinium iodide. At near-lethal doses soman induced explosive persistent seizures that were associated with a greater than fourfold increase of glucose use in many brain structures. Single near-lethal doses of soman lead to conspicuous neuronal damage and a marked reduction in brain activity, 1 to 3 days after exposure. When soman (2 X LD50) was given to TAB (an antidotal mixture of trimedoxime, atropine, and benactyzine ) pretreated rats, there was a greater than twofold reduction of glucose use in almost every brain region. We suggest that soman seizures are mediated via activation of muscarinic receptors; also, the substantia nigra has a key role in the initiation/propagation of seizures. Soman has in addition, a depressive effect on some brain components which appears not to involve muscarinic receptors. We suggest that the conspicuous pathology that follows a single, near-lethal dose of soman results from a depletion of energy flow along with an influx of Ca2+ which sets into motion a cascade of destructive reactions, such as activation of proteases.


Inner activation gate in S6 contributes to the state-dependent binding of cAMP in full-length HCN2 channel.
Recently, applications of the patch-clamp fluorometry (PCF) technique in studies of cyclic nucleotide-gated (CNG) and hyperpolarization-activated, cyclic nucleotide-regulated (HCN) channels have provided direct evidence for the long-held notion that ligands preferably bind to and stabilize these channels in an open state. This state-dependent ligand-channel interaction involves contributions from not only the ligand-binding domain but also other discrete structural elements within the channel protein. This insight led us to investigate whether the pore of the HCN channel plays a role in the ligand-whole channel interaction. We used three well-characterized HCN channel blockers to probe the ion-conducting passage. The PCF technique was used to simultaneously monitor channel activity and cAMP binding. Two ionic blockers, Cs(+) and Mg(2+), effectively block channel conductance but have no obvious effect on cAMP binding. Surprisingly, ZD7288, an open channel blocker specific for HCN channels, significantly reduces the activity-dependent increase in cAMP binding. Independent biochemical assays exclude any nonspecific interaction between ZD7288 and isolated cAMP-binding domain. Because ZD7228 interacts with the inner pore region, where the activation gate is presumably located, we did an alanine scanning of the intracellular end of S6, from T426 to A435. Mutations of three residues, T426, M430, and H434, which are located at regular intervals on the S6 α-helix, enhance cAMP binding. In contrast, mutations of two residues in close proximity, F431A and I432A, dampen the response. Our results demonstrate that movements of the structural elements near the activation gate directly affect ligand binding affinity, which is a simple mechanistic explanation that could be applied to the interpretation of ligand gating in general.


How to Evaluate a Tailor-made Social Work Intervention? Some Practice-Based Solutions with Single-Case Designs.
With the increased attention to the principles of evidence-based practice (EBP), social workers are challenged to adapt their daily interventions accordingly when treating clients. They usually work with individual clients, all with their own specificities. Single-Case Experimental Designs (SCEDs) can be used to inform a social worker about the effectiveness of an intervention at the individual client level. In everyday social work practice, however, it is difficult to meet methodological requirements of SCEDs to find causal explanations. A concern is that repeated measurements prior to an intervention are required in most situations. This study aims to provide researchers with alternatives to repeated measurement when using the logic of SCED to apply EBP in their everyday practice. In this study, we reviewed published single-case designs between January 1 and December 31, 2019, on types of SCEDs in the social domain, and how is dealt with baseline conditions. SCEDs and quasi-experimental alternatives are hardly published in situations when baseline data are not available. Four underused quasi-experimental strategies that can be employed when repeated measurement during baseline is not possible are as follows: retrospective baselines, theoretical inference, multiraters, and triangulation with qualitative data. The suggestions to work with single-case designs with quasi-experimental elements are meant to enable social workers to evaluate their interventions in a way that enhances mere narrative evaluations of the experiences of an intervention.


Radiation protection aspects of shallow land disposal of low and intermediate level liquid and solid radioactive waste at PINSTECH.
Operation of Pakistan Research Reactors 1 and 2, radioisotope production plants, and allied laboratories at the Pakistan Institute of Nuclear Science & Technology (PINSTECH) generates radioactive waste effluents of low and intermediate level. These waste materials are managed in a way to keep the human health and the environment free of radiation associated hazards. The prime practice has been of shallow ground or near-surface disposal type. Different measures and operational procedures at the institute, in step with the international norms for the management of low and intermediate level waste, have been adopted. To ensure the safe disposal practices and radiation safety of the workers and of the general public, radiological safety related routines are practiced with due concern. Some safety aspects of the prevailing practices are discussed in this presentation.


Posttraumatic Stress Symptoms and Alcohol-Related Outcomes Among Municipal Firefighters.
This study examined levels of posttraumatic stress symptoms (PTSS) and relationships between PTSS and alcohol-related outcomes in a near census of municipal firefighters. The study also assessed substance-use coping and drinking to cope as potential mediators of such outcomes. Firefighters (N = 740) completed measures that assessed PTSS, alcohol risk behaviors, alcohol problems, drinking motives, and coping with stress. Results showed that 32.4% of firefighters reported significant levels of PTSS using National Center for PTSD (2014) screening cutoff scores. Correlational analysis showed that PTSS was related to at-risk drinking (r = .18) and alcohol-related problems (r = .33), as well as use of maladaptive coping strategies (r = .58) and substance use coping (r = .40). Structural analyses comparing multiple alternative models suggested that a model that included substance use coping and drinking to cope as mediators of the association between PTSS and problem drinking provided the best fit to the data. Tests of multigroup invariance confirmed this model. Overall, PTSS were common in this population and they predicted maladaptive coping patterns and alcohol-related consequences. One implication of these findings is that fire departments might consider adding or enhancing screening and treatment options for PTS, alcohol misuse, or both.


Effect of Foam on Liquid Phase Mobility in Porous Media.
We investigate the validity of the assumption that foam in porous media reduces the mobility of gas phase only and does not impact the liquid-phase mobility. The foam is generated by simultaneous injection of nitrogen gas and a surfactant solution into sandstone cores and its strength is varied by changing surfactant type and concentration. We find, indeed, that the effect of foam on liquid-phase mobility is not pronounced and can be ignored. Our new experimental results and analyses resolve apparent discrepancies in the literature. Previously, some researchers erroneously applied relative permeability relationships measured at small to moderate capillary numbers to foam floods at large capillary number. Our results indicate that the water relative permeability in the absence of surfactant should be measured with the capillary pressure ranging up to values reached during the foam floods. This requires conducting a steady-state gas/water core flood with capillary numbers similar to that of foam floods or measuring the water relative-permeability curve using a centrifuge.


Overweight and obesity: The allies of prostate inflammation.
To the Editor, World Health Organization (WHO) defines infertility as the inability of a sexually active partner to achieve a clinically confirmed pregnancy after at least one year of intercourse without contraceptive protection on fertile days. As women are primarily responsible for the conception, childbirth, and postpartum, fertility problems have been related to fertile female capacity. However, men play an essential role, being responsible for about 50% of alterations in fertility due to dysfunctions in the male reproductive tract, including varicocele, hypogonadism, poorly descended testicles, testicular tumors, and even anti-sperm autoantibodies [...].


[Spatial distribution characteristics of metabolities in rhizome of Paris polyphylla var. yunnanensis: based on MALDI-MSI].
In this study, a method was established for in-situ visualization of metabolite distribution in the rhizome of Paris polyphylla var. yunnanensis. To be specific, through matrix-assisted laser desorption/ionization-mass spectrometry imaging(MALDI-MSI), the spatial locations of steroidal saponins, amino acids, organic acids, phytosterols, phytoecdysones, nucleosides, and esters in rhizome of the medicinal plant were directly analyzed, and six unknown compounds with differential distribution in rhizome tissues were identified. The specific procedure is as follows: preparation of rhizome tissue section, matrix screening and optimization, and MALDI-MSI analysis. The results showed that the steroidal saponins were mainly distributed in the central, amino acids in epidermis and cortex, low-molecular-weight organic acids in central epidermis, phytosterols in the epidermis and lateral cortex, the phytoecdysones in epidermis and cortex, nucleosides(uneven distribution) in epidermis and cortex, growth hormones around the epidermis and cortex, particularly outside the cortex, and esters in cortex with unobvious difference among different tissues. In this study, the spatial distribution of meta-bolites in the rhizome of P. polyphylla var. yunnanensis was characterized for the first time. The result can serve as a reference for identifying and extracting endogenous metabolites of P. polyphylla var. yunnanensis, exploring the synthesis and metabolism mechanisms of the metabolites, and evaluating the quality of medicinal materials.


Potentially fatal arrhythmias in two cases of adult Kawasaki disease.
Fatal arrhythmias in asymptomatic Kawasaki disease patients with normal left ventricular function have rarely been reported. In this study, we report the cases of two adult patients with largely unpredictable sudden cardiac arrest, despite almost-normal left ventricular function even after the diagnosis of presumed Kawasaki disease, as well as consider the mechanisms involved with reference to the literature.


Skin simulation for minor surgical procedures.
A simulated skin preparation is described which is made by bonding siliconized rubber to a latex foam base. This composite material, which simulates both the dermis/epidermis and subcutaneous fat, provides a realistic model which can be used to teach excision of skin lesions and a variety of suturing methods. We believe that this simulator is of value not only for surgeons in-training but also will allow general practitioners to improve their technical skills in performing minor surgical procedures.


[Preoperative hemodilution for the prevention of postoperative deep venous thrombosis and early infectious complications in colorectal resections].
The effectiveness of heparin DHE and preoperative haemodilution (M.N.H.) for prophylaxis against deep venous thrombosis (D.V.T.) and against early septic complications was investigated in a prospective controlled study on two comparable groups of patients who had undergone colorectal resections for malignant tumours. The results clearly suggested that there was no significant difference between heparin DHE and preoperative haemodilution for prophylactic effectiveness on D.V.T. yet, the percentage of postoperative septic early complications, that is insufficiency of anastomosis and abdominal wall infections, was much lower (p less than 0.001) in patients with moderate normovolaemic haemodilution (haematocrit = 30 per cent). While the number of cases reviewed was as low as 62, the point can be made that less postoperative septic complications occurred to patients with low haematocrit (30 per cent).


Pertinent cell population to characterize periodontal disease.
The purpose of this in situ study is to quantify the inflammatory cell subsets and the area fraction (AA%) occupied by collagen fibers in human healthy and diseased (four different stages) gingival connective tissue in order to establish a possible correlation between periodontal disease resulting in collagen breakdown and specific inflammatory cell subsets. Paraffin gingival tissue sections from eight healthy controls (group 0), 10 patients with gingivitis (group 1), 10 patients with moderate periodontitis (group 2) and 10 patients with severe periodontitis (group 3) were immunohistochemically investigated using antibodies against CD-45+, CD-3+, CD-8+, CD-20+, CD-68+, and EMA+ (plasma cells). The AA% occupied by gingival collagen fibers significantly decreased from 54.12% in group (0) to 38.58% in group (1), to 31.87% in group (2), and to 25.46% in group (3). In progressive lesions of periodontal disease, CD-3(+) and CD-8+ cell numbers were increased in early stages within the connective tissue, while CD-20+ cell numbers were increased only in late stages. On the other hand, EMA+, CD-68+ and CD-45+ cell numbers were progressively increased from group (0) to group (3). We demonstrated that CD-68+ monocyte/macrophages, CD-45+ leukocyte common antigen and notably EMA+ plasma cells are pertinently correlated with the severity of periodontal disease and related collagen breakdown.


Prediction Models based on miRNA-disease Relationship: Diagnostic Relevance to Multiple Diseases Including COVID-19.
Small, non-coding microRNAs, usually of 20-25 nucleotides, are known to regulate the post-transcriptional gene expression, which has a significant role in human biological processes, including immune-biogenesis, homeostasis and infection control as differential expression of such miRNAs is responsible for fine-tuning the organismic development. A search of bibliographic databases was carried out with a focused question on microRNA- Disease Prediction. A deductive qualitative content analysis approach was employed to assess the research's overall outcomes, review articles on prediction tools in miRNA-Diseases, and analyse the interventions. Diagnosis and therapeutics of diseases and miRNA prediction methods hold importance in identifying the regulatory mechanisms. Collections of efficient miRNA prediction methods to identify miRNA-mRNA-disease regulatory relationships have been presented through this review, consolidating the potential of miRNAs as a diagnostic and prognostic biomarker of multiple diseases, including COVID-19. The role of miRNA in the aetiology and pathogenesis of wide-range of pathologies, including viral, bacterial to chronic diseases such as cancer, is quite feasible through the modern tools in bioinformatics which has been elaborated focusing upon miRNA-disease prediction methods and their application potential establishing miRNAs as a robust and reliable biomarker in clinicomedical studies.


New paradigms in minimally-invasive vascular surgery.
Vascular surgery has been greatly evolved during the last decades and novel minimally invasive techniques have been introduced. Aim of this review is to briefly present all these advances and compare them with traditional repairs. The authors have extensively searched literature through the Pubmed and Embase databases. All articles published up to December 2021 referring to minimally invasive techniques used for treatment of peripheral artery disease, carotid disease, aortic aneurysms, and venous disease were evaluated. Minimally invasive techniques under investigation included endovascular and hybrid techniques, robot-assisted and laparoscopic approaches. Several minimally invasive techniques such as endovascular and hybrid approaches have been extensively used during the last two decades to treat vascular surgery patients offering them lower mortality and morbidity risks. Novel robot-assisted techniques have shown promising results in preclinical studies although further clinical evaluation is needed.


Laparoscopic management and its outcomes in cases with nonpalpable testis.
Diagnostic laparoscopy is the gold standard in the algorithm of nonpalpable testis. Testicular tissue is examined and treatment is planned accordingly. In this study we reviewed the place of diagnostic laparoscopy, and evaluated the results and effectiveness of laparoscopy in the diagnosis and management of nonpalpable testis. Children who had diagnostic laparoscopy for nonpalpable testes were included in the study. Physical examination results, ultrasonography (USG) reports, age at surgery, laparoscopic and inguinal exploration findings, surgical procedures, orchiopexy results, early and late-term complications were evaluated. Follow-up visits were performed at 3-month intervals for the first, at 6-month intervals for the 2. year, then at yearly intervals. Testicular size and location was evaluated by during control examination. Overall 58 boys, and 68 testes (26 left: 44.8%; 22 right: 37.9%, and 10 bilateral: 17.2%) were included in the study. Mean age at surgery was 5.5 years (10 months-17 years). Diagnostic value of USG was 15.7%. Diagnostic laparoscopy findings were as follows: Group 1: blind-ended vessels, n=7 (10.2%); Group 2: intraabdominal testes, n=8 (11.7%); Group 3: vas and vessels entering internal ring, n=53 (77.9%). Overall 43 testes underwent orchiopexy, which were normal (n=8) or hypoplastic (n=35). Mean follow-up period was 19 months (1-12 years), and on an average 7 visits were performed (5-14). On follow-up, 5 testes were normal-sized and located in the scrotum, while 4 testes were atrophic and underwent orchiectomy. Two testes were found in the inguinal canal and redo orchiopexy was performed. Control USG revealed reduced testicular blood supply and volume. Laparoscopic surgery is safe and effective in the management of nonpalpable testes. In the majority, routine use of diagnostic laparoscopy in the algorithma does not confer any additional contributions in many patients.


Redox-dependent DNA distortion in a SoxR protein-promoter complex studied using fluorescent probes.
The [2Fe-2S] transcriptional factor SoxR, a member of the MerR family, is regulated by the reversible oxidation and reduction of [2Fe-2S] clusters and functions as a sensor of oxidative stress in Escherichia coli. In the oxidized state, distortion of the target DNA promoter region initiates transcription by RNA polymerase, thereby activating transcription. The inactive reduced state of the protein has remained uncharacterized. Here, we directly observed redox-dependent conformational changes in the promoter DNA by site-specifically replacing selected adenine (A) and cytosine (C) bases in the promoter oligonucleotide with the fluorescent probes 2-aminopurine (2Ap) and pyrrolocytosine (pyrrolo-dC), respectively. Reduction of the [2Fe-2S] cluster in the SoxR-DNA complex dramatically weakened the fluorescence intensity of the 2Ap moieties incorporated into the central part of the DNA. In contrast, the fluorescence of 2Ap moieties incorporated at A in other regions and the fluorescence of pyrrolo-dC moieties in the central region of the DNA (C3 and C3') were only slightly decreased by the reduction. These results strongly suggest that the redox change causes a large conformational change within a region confined to the central A-T base pairs in the promoter region of the DNA.


Indirect and direct perceived behavioral control and the role of intention in the context of birth control behavior.
Unintended pregnancies can have negative consequences for both mother and child. The focus of this study was to utilize perceived behavioral control measures (PBC; part of the theory of planned behavior) to identify relevant behavioral determinants of birth control use. This study also tested associations between direct and indirect PBC measures and intention of birth control use and between intention and birth control use. The methods included a randomly selected sample of patients at a health care system in the Upper Midwest who were sent a self-administered survey, with 190 non-pregnant women returning completed surveys. Participants indicated a high level of control over using birth control, and a significant positive correlation was observed between direct and indirect PBC measures. Participants also reported high intentions to use birth control, and a significant positive correlation was observed between intention and PBC. Additionally, both PBC measures and intention were independently and significantly associated with behavior, and PBC remained significantly associated with behavior when intention was added into the model. In conclusion, compared to the previous literature, this study is unique in that it examines indirect PBC measures and also the important role that PBC plays with actual birth control behavior.


Investigation of the enteric pathogenic potential of oral Campylobacter concisus strains isolated from patients with inflammatory bowel disease.
Campylobacter concisus, a bacterium colonizing the human oral cavity, has been shown to be associated with inflammatory bowel disease (IBD). This study investigated if patients with IBD are colonized with specific oral C. concisus strains that have potential to cause enteric diseases. Seventy oral and enteric C. concisus isolates obtained from eight patients with IBD and six controls were examined for housekeeping genes by multilocus sequence typing (MLST), Caco2 cell invasion by gentamicin-protection-assay, protein analysis by mass spectrometry and SDS-PAGE, and morphology by scanning electron microscopy. The whole genome sequenced C. concisus strain 13826 which was isolated from an individual with bloody diarrhea was included in MLST analysis. MLST analysis showed that 87.5% of individuals whose C. concisus belonged to Cluster I had inflammatory enteric diseases (six IBD and one with bloody diarrhea), which was significantly higher than that in the remaining individuals (28.6%) (P<0.05). Enteric invasive C. concisus (EICC) oral strain was detected in 50% of patients with IBD and none of the controls. All EICC strains were in Cluster 1. The C. concisus strain colonizing intestinal tissues of patient No. 1 was closely related to the oral C. concisus strain from patient No. 6 and had gene recombination with the patient's own oral C. concisus. The oral and intestinal C. concisus strains of patient No. 3 were the same strain. Some individuals were colonized with multiple oral C. concisus strains that have undergone natural recombination. This study provides the first evidence that patients with IBD are colonized with specific oral C. concisus strains, with some being EICC strains. C. concisus colonizing intestinal tissues of patients with IBD at least in some instances results from an endogenous colonization of the patient's oral C. concisus and that C. concisus strains undergo natural recombination.


Preparation of α-amino acids by oxidative oxazoline-oxazinone rearrangement-hydrogenation (OOOH). Scope and limitations.
The range and scope of the oxidative oxazoline-oxazinone rearrangement-hydrogenation sequence (OOOH)--a short, direct asymmetric synthesis of α-amino acids from carboxylic acids--was explored. The highest yet reported diastereoselectivity for hydrogenation of the oxazinone C=N bond (d.r.=>80:1) is disclosed and rationalized with the aid of ab initio molecular calculations.


Association of GSTM1 and GSTT1 gene deletions with susceptibility to DNA damage in the pesticide-exposed workers of Punjab.
The main aim of this study was to evaluate genotoxic effects of pesticides in association with glutathione S-transferase (GST) polymorphism. To achieve this aim, DNA damage and the genotypes of the GSTM1 and GSTT1 genes were studied from blood lymphocytes of pesticide-exposed and unexposed (control) agricultural workers of the Punjab region of northwestern India. The blood samples were collected from 40 exposed and 27 unexposed subjects from the Kakrala and Sanour villages of Patiala district. DNA damage was evaluated by using an alkaline comet assay. The analysis of the comets was done through visual scoring and image analysis software (Tritek's CometScore). Damage Index (DI), Damage Frequency (DF) (calculated by visual scoring method), and % DNA in tail (measured by image analysis software) were considered for assessing DNA damage. The DNA extraction from blood cells was done using proteinase K and the phenol-chloroform method, and genotyping of GSTM1 and GSTT1 was done using multiplex PCR. It was found that all the pesticide-exposed subjects showed higher DI, DF, and % DNA in tail in comparison to the controls. The statistical comparison of DNA damage between the exposed group and unexposed group revealed highly significant differences (p < 0.05; Mann-Whitney U-test). In addition, the GSTT1 gene deletion and simultaneous deletions of GSTM1 and GSTT1 genes in increasing DNA damage were observed in the exposed group.


Clinical effects of middle turbinate resection after endoscopic sinus surgery: a systematic review.
The middle turbinate (MT) is a structure that is often carefully preserved during endoscopic sinus surgery (ESS) in an effort to preserve nasal physiology and serve as an anatomic landmark. However, resection is performed in select cases because of involvement of the MT in the inflammatory process, obstruction, or instability. Therefore, significant controversy exists among surgeons regarding the indications for proceeding with MT resection in ESS. This study evaluates clinical outcomes of MT resection after ESS. An English language search of the PubMed and Ovid databases was conducted for publications examining clinical outcomes of MT resection after ESS performed for chronic rhinosinusitis. Two authors independently examined the articles to identify those meeting inclusion criteria. Any differences over which studies to include were resolved by discussion and consensus. Bias assessment was conducted using the Cochrane Collaboration bias tool for randomized controlled trials and the Newcastle-Ottawa bias tool for cohort and case-control studies. After initial screening, search results revealed 71 articles that warranted detailed evaluation. After applying inclusion criteria, 9 studies were selected. A total of 2123 patients were included among the studies. All studies were controlled. Within the limited available data, olfaction scores may be improved in the MT resection patients compared with MT preservation patients. No difference between the groups was noted for quality of life outcomes, nasal airway resistance, or rates of postoperative frontal sinusitis. In regard to postoperative endoscopic examinations, some studies note greater improvement in the MT resection group compared with the MT preservation group, while others were equivalent. Although some studies show outcome benefit in MT resection patients compared with MT preservation patients, several others show no difference. When MT resection was appropriately indicated, no studies showed detrimental effects compared with MT preservation in their designated outcomes. Additional more stringent studies are warranted.


A novel -2Fe-2S- ferredoxin from Pseudomonas putida mt2 promotes the reductive reactivation of catechol 2,3-dioxygenase.
Catechol 2,3-dioxygenase (XylE) is a component of the TOL plasmid-encoded pathway for the degradation of toluene and xylenes and catalyzes the dioxygenolytic cleavage of the aromatic ring. Purified XylE is oxygen-sensitive and unstable in vitro, particularly in the presence of substituted catechol substrates, but it is stabilized in vivo by another protein, XylT, encoded by the xylT gene located just upstream of xylE. In this study, we have purified to homogeneity the XylT product from a recombinant Escherichia coli strain containing a hyperexpressible xylT gene and characterized it as a novel [2Fe-2S] ferredoxin. It is the first example of a soluble ferredoxin with a net positive charge at neutral pH. The EPR signal of the iron sulfur cluster has rhombic symmetry as is the case for plant-type ferredoxins, but the XylT absorbance spectrum resembles more closely that of adrenodoxin. The midpoint redox potential was determined to be -373 +/- 6 mV, at pH 8. 5. XylT was unusually unstable for a [2Fe-2S] ferredoxin, with half-lives of 69 min at 25 degrees C in air and 70 min at 37 degrees C in argon. With photochemically reduced 5-deazaflavin for the controlled generation of reductant, it was demonstrated that XylT mediates the rapid reactivation of purified inactive catechol 2,3-dioxygenase in vitro. Inactivation of XylE by 4-methylcatechol resulted in oxidation of the active site iron to a high spin ferric state that was detectable by EPR. Spectroscopic evidence presented here demonstrates that XylT reactivates XylE through reduction of the iron atom in the active site of the enzyme. It is the first instance of a ferredoxin-mediated reactivation of an enzyme. The level of expression of XylT in Pseudomonas putida mt2 cells is low and the calculated XylT/XylE molar ratio is consistent with the proposal that XylE reactivation involves catalytic nonstoichiometric amounts of XylT.


Catechol: A minimal scaffold for non-peptide peptidomimetics of the i + 1 and i + 2 positions of the beta-turn of somatostatin.
The design, synthesis, and evaluation of a series of catechol-based non-peptide peptidomimetics of the peptide hormone somatostatin have been achieved. These ligands comprise the simplest known non-peptide mimetics of the i + 1 and i + 2 positions of the somatostatin beta-turn. Incorporation of an additional side chain to include the i position of the beta-turn induces a selective 9-fold affinity enhancement at the sst2 receptor.


Simulation of the expanding universe in hyperbolic metamaterials.
The particle horizon represents the boundary between observable and unobservable regions of the universe, which changes as the universe expands. Based on transformation optics, hyperbolic electromagnetic metamaterials can be utilized to simulate metrics with different signs due to their unique anisotropic properties. In this paper, we use hyperbolic metamaterials to visually depict the variation of the particle horizon under three models of an expanding universe (open, flat, and closed) by substituting one-dimensional time with one-dimensional space. The good agreement between theory and simulation confirms that hyperbolic metamaterials are excellent for simulating space-times, suggesting their potential as a new platform for cosmological analogies.


[Management of pediatric patients who underwent liver transplantation].
To evaluate the outcome of pediatric patients who underwent liver transplantation between Oct. 2002 and May 2005 in the Pediatric Hospital. Eight cases aged from 4 to 67 months who underwent liver transplantation were analyzed retrospectively. Four of the patients were boys and 4 girls, whose body weight at the time of liver transplantation was 6-19 kg. The underlying diseases were biliary atresia, congenital cholestasis, drug-induced cholestatic cirrhosis and cryptogenic cirrhosis. These patients had been followed up for blood routine examinations, liver and renal function, serum electrolytes and blood concentration of tacrolimus for 16 to 43 months after liver transplantation. Results of serological studies for viral etiology, liver biopsy, growth and mental development were also recorded. One-year survival rate was 75.0% with the longest survival time being 43 months after transplantation. One patient died from renal failure due to postoperative bleeding 24 hours after the surgery and another case died of variceal hemorrhage 8 months after transplantation. Posttransplantation complications included acute cellular rejection, viral infection and hypoalbuminemia. Viral infections included cytomegalovirus infection in 3 cases, Epstein-Barr virus infection in 1 and hepatitis B virus infection in 1. Surgical complications of portal vein thrombosis and stenosis of inferior vena cava and hepatic vein occurred in 2 cases respectively. Side effects of tacrolimus including hypertension, renal damage, liver damage and diarrhea were observed. Significant growth-retardation was not often seen. A self-reported high quality of life was common. Close follow-up and management of patients after liver transplantation may significantly increase the survival rate and improve quality of life in children with end-stage liver diseases.


Clarifying the anatomy of the superior sinus venosus defect.
We sought to clarify the variations in the anatomy of the superior cavoatrial junction and anomalously connected pulmonary veins in patients with superior sinus venosus defects using computed tomographic (CT) angiography. CT angiograms of 96 consecutive patients known to have superior sinus venosus defects were analysed. The median age of the patients was 34.5 years. In seven (7%) patients, the defect showed significant caudal extension, having a supero-inferior dimension greater than 25 mm. All patients had anomalous connection of the right superior pulmonary vein. The right middle and right inferior pulmonary vein were also connected anomalously in 88 (92%) and 17 (18%) patients, respectively. Anomalous connection of the right inferior pulmonary vein was more common in those with significant caudal extension of the defect (57% vs 15%, p=0.005). Among anomalously connected pulmonary veins, the right superior, middle, and inferior pulmonary veins were committed to the left atrium in 6, 17, and 11 patients, respectively. The superior caval vein over-rode the interatrial septum in 67 (70%) patients, with greater than 50% over-ride in 3 patients. Anomalous connection of the right-sided pulmonary veins is universal, but is not limited to the right upper lobe. Not all individuals have over-riding of superior caval vein. In a minority of patients, the defect has significant caudal extension, and anomalously connected pulmonary veins are committed to the left atrium. These findings have significant clinical and therapeutic implications.


Does being a coach benefit clinician-educators? A mixed methods study of faculty self-efficacy, job satisfaction and burnout.
Coaching is a growing clinician-educator role. Self-efficacy is a powerful faculty motivator that is associated positively with job satisfaction and negatively with burnout. This study examines self-efficacy, job satisfaction, and burnout in coaches and other clinician-educators. We conducted a mixed methods study using a quantitative survey followed by qualitative interviews of faculty at the University of California, San Francisco. Coaches (funded 20% full-time equivalents), faculty with other funded education positions ("funded"), and faculty without funded education positions ("unfunded") completed a 48-item survey addressing self-efficacy (teaching, professional development, and scholarship), job satisfaction, and burnout. Data were analyzed using analysis of variance followed by post-hoc tests and chi-square tests. To elaborate quantitative results, we conducted qualitative interviews of 15 faculty and analyzed data using framework analysis. 202 of 384 faculty (52.6%) responded to the survey; 187 complete surveys were analyzed. Teaching self-efficacy was similar across groups. Coaches and funded educators had significantly higher professional development self-efficacy and job satisfaction than unfunded educators. Burnout was more prevalent in coaches and unfunded educators. Qualitative analysis yielded three themes: sources of reward, academic identity, and strategies to mitigate burnout. Educator roles provide reward that enhances self-efficacy and job satisfaction but also generate competing demands. Coaches cited challenges in forming professional identities and working with struggling learners. The coaching role provides faculty with benefits similar to other funded educator roles, but the particular demands of the coach role may contribute to burnout.


Using a kinase-inducible bimolecular switch to control enzyme activity in living cells.
Molecular switches have been instrumental in the development of powerful and versatile genetic tools for directly probing biochemical processes, such as intracellular signaling, within their native contexts. A molecular switch can be broadly defined as a molecular system capable of existing in either of two states (e.g., conformations), which can be converted from one state to the other by a specific input stimulus. This protocol outlines a method for using a kinase-inducible bimolecular switch, along with live-cell fluorescence microscopy, to directly control and monitor the activity of a specific enzyme in living cells.


Managing Ridge Resorption After Tooth Extraction Using Partial Extraction Therapy.
Achieving successful long-term esthetic outcomes in implant dentistry requires that the height and width of the facial or buccal alveolar bone wall and, subsequently, the peri-implant tissues be maintained. Partial extraction therapy (PET) can be used to reduce the risk of facio-lingual collapse after tooth loss and improve the preservation of alveolar bone height and blood supply. This article demonstrates the use of PET for treatment of a hopeless tooth in the esthetic zone. After removal of the fractured maxillary central incisor, an implant was placed and restored with excellent esthetic, functional, and periodontal results.


Neuropsychological test performance in patients with dominantly inherited spinocerebellar ataxia: relationship to ataxia severity.
To determine whether the cognitive status of patients with dominantly inherited spinocerebellar ataxia (DSCA) might be related to neurologic severity, we administered a comprehensive neuropsychological test battery to 43 patients with DSCA, ranging in ataxia severity from mild to end-stage. As compared with the controls, the mildly ataxic patients scored normally or close to normal as a group on all of the neuropsychological tests. In contrast, approximately one-half of the moderately and all of the severely ataxic patients showed poor performance, independent of age, Hamilton Rating Scale for Depression score, or education, on the Wisconsin Card Sorting Test, suggesting impaired executive system function. In addition, a subgroup of these patients had a neuropsychological profile suggestive of mild generalized cognitive impairment. We conclude that DSCA is not a homogeneous group of disorders with respect to cognitive status and that the neurologic severity of the disorder is a major factor. Impaired executive system function could be explained by damage to olivopontocerebellar system control over cerebral cortical function or to damage to other neuronal systems (especially cholinergic) that degenerate in parallel with the olivopontocerebellar system.


Clinical value of mean platelet volume in predicting and diagnosing pre-eclampsia: a systematic review and meta-analysis.
Pre-eclampsia (PE) is a severe pregnancy complication. Thrombocytopenia and platelet dysfunction are common hematology disorders in PE. Previous studies considered mean platelet volume (MPV), a functional marker of platelets, as a potentially useful predictor for the diagnosis of PE. PubMed, China Biomedical Literature Database, Chinese National Knowledge Infrastructure, Embase, Wanfang, VIP, and Cochrane Library databases were searched to gather diagnostic trials evaluating the diagnosis of PE using MPV, from their inception to 13 March 2023. We also searched Google Scholar and Baidu. A total of 22 studies from 20 articles were found. The pooled diagnostic accuracy of the MPV for PE recognition was as follows: sensitivity (SEN) 0.676 [95% confidence interval (CI) (0.658-0.694)], specificity (SPE) 0.710 [95% CI (0.703-0.717)], and diagnostic odds ratio (DOR) 7.012 [95% CI (4.226-11.636)], and the SROC-AUC and Q* indices were 0.7889 and 0.7262, respectively. The pooled SEN, SPE, and DOR of the diagnostic accuracy of MPV for PE before 16 weeks of gestation were 0.707 [95% CI (0.670-0.743)], 0.639 [95% CI (0.611-0.667)], and 4.026 [95% CI (2.727-5.943)], and the SROC-AUC and Q* indices were 0.7278 and 0.6753, respectively. For the interval of truncation values between 9 and 10 fl, the SROC-AUC and Q* indices for MPV were 0.8856 and 0.8162, respectively. Available evidence suggests that MPV has a moderate predictive and diagnostic value for PE, particularly in diagnosing after 20 weeks of gestation. The diagnostic accuracy is higher when the MPV cut-off falls between 9 and 10 fl. The sensitivity of MPV alone in diagnosing PE is not high, and the combination of other markers for predictive diagnosis may better differentiate PE. https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42023425154, identifier: CRD42023425154.


Electrical and Optical Properties of Hydrogen Doped Aluminum-Doped Zinc Oxide Thin Films for Low Cost Applications.
Aluminum-doped zinc oxide (AZO) thin films were prepared on glass substrate using a magnetron sputtering system. In this work, a powder target was used as a source material for low cost applications, instead of a conventional sintered ceramic target. The effects of the hydrogen gas ratio on the electrical and optical properties of the AZO films. The hydrogen doped AZO (AZO:H) films had a hexagonal polycrystalline structure. A small amount of hydrogen gas deteriorated the electrical and optical properties of the AZO:H films. However, these properties improved, as the H2/(H2 + Ar) gas ratio increased. The AZO:H films grown at an H2/(H2+Ar) ratio of 10% showed good properties for low cost applications, such as a low resistivity of 1.35 x 10(-3) Ω-cm, high average transmittance of 83.1% in the visible range of light.


Convergence between parent report and direct assessment of language and attention in culturally and linguistically diverse children.
Parent report is commonly used to assess language and attention in children for research and clinical purposes. It is therefore important to understand the convergent validity of parent-report tools in comparison to direct assessments of language and attention. In particular, cultural and linguistic background may influence this convergence. In this study a group of six- to eight-year old children (N = 110) completed direct assessments of language and attention and their parents reported on the same areas. Convergence between assessment types was explored using correlations. Possible influences of ethnicity (Hispanic or non-Hispanic) and of parent report language (English or Spanish) were explored using hierarchical linear regression. Correlations between parent report and direct child assessments were significant for both language and attention, suggesting convergence between assessment types. Ethnicity and parent report language did not moderate the relationships between direct child assessments and parent report tools for either attention or language.


Behavioral activation is associated with post-disaster mental health: Secondary longitudinal analysis from a population-based study.
Interventions in post-disaster environments may be accelerated by identifying protective behavioral factors adding incremental value to models of psychopathology using longitudinal methods. One protective behavior applicable to post-disaster contexts is behavioral activation (BA). BA is defined here as a behavioral pattern involving presence of valued activity engagement. While relevant post-disaster, the incremental value of BA behaviors in predicting longitudinal post-disaster outcomes is not well understood. We hypothesized that higher baseline engagement in behaviors consistent with a BA framework would predict decreased posttraumatic stress disorder (PTSD) symptom severity, depression symptom severity, and sleep disturbance approximately 3, 6, and 12 months after hurricane survivors completed baseline measures. The current study is a secondary analysis from a randomized controlled trial of a disaster mental health digital intervention. Participants completed surveys at baseline and approximately 3, 6, and 12 months post-enrollment. Correlations and hierarchical regression analyses were calculated following data screening to predict PTSD symptom severity, depression symptom severity, and sleep disturbances. Controlling for alcohol use, prior trauma, displacement, and intervention condition, higher baseline BA consistently predicted less PTSD symptom severity, depression symptom severity, and sleep disturbances. Results suggest that post-disaster interventions should consider addressing BA. The study provides evidence that BA is potentially an important protective factor longitudinally predicting sleep disturbances and psychopathology after natural disasters.


Association between functionality assessment scales and the severity of dysphagia post-stroke.
The aim of this study was to investigate the association between the results of functionality scales and dysphagia severity determined from videofluoroscopy swallowing study (VSS) in post-stroke patients. A retrospective study of 109 VSS analysis of post-stroke patients. From the exams was collected information on the diagnosis of dysphagia severity and evaluated regarding the swallowing functionality in an independent way by two evaluators. A high number of discrete dysphagia was observed. In one third of dysphagic patients it was noticed the presence of tracheal aspiration. There was a significant association between the scores of Functional Oral Intake Scale and Dysphagia Outcome and Severity Scale in post-stroke patients which means when the swallowing is highly compromised, the level of intake by mouth will be smaller according to the evaluators' analysis (p < 0.001). There is an association between the scales and it can be used as evaluative benchmarks and in the management of clinical Speech Pathology intervention.


Synthesis, Characterization, and Efficient Catalytic Activities of a Nickel(II) Porphyrin: Remarkable Solvent and Substrate Effects on Participation of Multiple Active Oxidants.
A new nickel(II) porphyrin complex, [NiII (porp)] (1), has been synthesized and characterized by 1 H NMR, 13 C NMR and mass spectrometry analysis. This NiII porphyrin complex 1 quantitatively catalyzed the epoxidation reaction of a wide range of olefins with meta-chloroperoxybenzoic acid (m-CPBA) under mild conditions. Reactivity and Hammett studies, H218 O-exchange experiments, and the use of PPAA (peroxyphenylacetic acid) as a mechanistic probe suggested that participation of multiple active oxidants NiII -OOC(O)R 2, NiIV -Oxo 3, and NiIII -Oxo 4 within olefin epoxidation reactions by the nickel porphyrin complex is markedly affected by solvent polarity, concentration, and type of substrate. In aprotic solvent systems, such as toluene, CH2 Cl2 , and CH3 CN, multiple oxidants, NiII -(O)R 2, NiIV -Oxo 3, and NiIII -Oxo 4, operate simultaneously as the key active intermediates responsible for epoxidation reactions of easy-to-oxidize substrate cyclohexene, whereas NiIV -Oxo 3 and NiIII -Oxo 4 species become the common reactive oxidant for the difficult-to-oxidize substrate 1-octene. In a protic solvent system, a mixture of CH3 CN and H2 O (95:5), the NiII -OOC(O)R 2 undergoes heterolytic or homolytic O-O bond cleavage to afford NiIV -Oxo 3 and NiIII -Oxo 4 species by general acid catalysis prior to direct interaction between 2 and olefin, regardless of the type of substrate. In this case, only NiIV -Oxo 3 and NiIII -Oxo 4 species were the common reactive oxidant responsible for olefin epoxidation reactions.


Can statins reduce risk of lung cancer, especially among elderly people? A meta-analysis.
As the most common cause of cancer mortality throughout the world, lung cancer has drawn people's attention on how to reduce the risk with chemopreventive ways. Many epidemiological studies have shown inconsistent effects of statins on lung cancer, but some observational studies have showed that statins had protective effect on lung cancer among elderly people. So we preformed this meta-analysis to find whether statins were chemopreventive. We searched MEDLINE, EMBASE and Web of Science databases from inception to September, 2013. A total of 23 studies were selected, including 15 observational studies and 8 randomized controlled trials (RCTs). Both fixed and random-effects models were used to calculate pooled estimates in primary and sensitivity analyses. We used Q and I(2) statistics to assess statistical heterogeneity, and evaluated publication bias by Begg's test and Egger's test. No association between statins and lung cancer risk was identified either in the meta-analysis among RCTs [relative risk (RR): 0.95, 95% confidence interval (95% CI): 0.85-1.06] or observational studies (RR: 0.89, 95% CI: 0.77-1.04). We also selected 6 observational studies that all researched on elderly people. The result of meta-analysis showed that there was still no protective effect between statins and lung cancer among elderly people (RR: 1.03, 95% CI: 0.96-1.11). Our results did not support a protective effect of statins on the overall lung cancer risk and the lung cancer risk among elderly people. More well-designed RCTs are needed to enhance our understanding of the chemopreventive effect of statins on lung cancer.


An overview of statistical and regulatory issues in the planning, analysis, and interpretation of subgroup analyses in confirmatory clinical trials.
Whether confirmatory or exploratory in nature, the investigation of subgroups poses statistical and interpretational challenges, yet these investigations can have important consequences for product licensing, labeling, reimbursement, and prescribing decisions. This article provides a high-level, nontechnical summary of key statistical issues in the analysis of subgroups, with a focus on the regulatory context in which drug development and licensing decisions are made. References to specific aspects of regulatory processes are based on the system in Europe, though it is hoped that the principles outlined can be generally applied to other regulatory regions. This article challenges the common assumption that a clinical trial population should be assumed to be homogeneous, with homogeneous response to treatment, and asks whether commonly employed strategies for handling and identifying potential heterogeneity are sufficient. Investigations into subgroups are unavoidable, yet subgroup analyses suffer from fundamental complications and limitations of which those planning and interpreting clinical trials must be aware. Some areas for further methodological work and an improved methodological framework for the conduct of exploratory subgroup analyses are discussed. Above all, the need for an integrated scientific approach is highlighted.


Effects of phosphodiesterase inhibitors on interleukin-4 and interleukin-13 generation from human basophils.
The aim of the present study was to determine whether inhibition of cyclic nucleotide phosphodiesterase (PDE) modulates the stimulated generation of the cytokines, interleukin-4 (IL-4) and IL-13, from human basophils. This was addressed by evaluating the effects of both nonselective and selective inhibitors of PDEs on the generation of cytokines from basophils. The nonselective PDE inhibitors, isobutyl-methylxanthine (IBMX) and theophylline, attenuated the IgE-mediated generation of IL-4 and IL-13 and, also, the release of histamine from basophils. The effects of the isoform-selective inhibitors, 8-methoxymethyl-IBMX (PDE 1 inhibitor), siguazodan (PDE3 inhibitor), rolipram (PDE4 inhibitor), denbufylline (PDE4 inhibitor), Org 30029 (mixed PDE3 and 4 inhibitor) and zaprinast (PDE5 inhibitor), were studied. Of these selective compounds, only rolipram, denbufylline and Org 30029 inhibited the IgE-dependent generation of IL-4, IL-13 and histamine from basophils to a statistically significant (P<0.05) degree. The effects of isoform-selective inhibitors on basophils activated by IL-3 were evaluated. The IL-3-induced generation of IL-4, IL-13 and histamine was inhibited to a statistically significant (P<0.05) extent, only by compounds that act as inhibitors of PDE4. These data suggest that inhibition of PDE4 can regulate the generation of cytokines from human basophils.


Iterative method of baffle design for modified Ritchey-Chretien telescope.
We developed a baffle design method based on a combination of the results of optical design software and analytical relations formulated herein. The method finds the exact solution for baffle parameters of a modified Ritchey-Chretien telescope by iteratively solving the analytical relations using the actual ray coordinates of the telescope computed with the aid of optical design software. The baffle system so designed not only blocks the direct rays of stray light reaching the image plane but also provides minimum obscuration to imaging light. Based on the iterative method, we proposed a baffle design approach for a rectangular-image-format telescope.


The catalytic mechanism of alpha-amylases based upon enzyme crystal structures and model building calculations.
Based upon the known crystal structures of Taka-amylase A and the recently refined Porcine pancreatic alpha-amylase inhibitor complex a mechanism of catalysis in amylase active centers is proposed. The mechanism differs significantly from the well-known lysozyme model of catalysis. The hydrolysis is catalyzed by three carboxyl groups and its starts from a water nucleophilic attack and opening of the glucose ring in the catalytic center rather than from protonation of the glycosidic oxygen. The main supporting experimental observations are briefly discussed.


Acertannin attenuates LPS-induced inflammation by interrupting the binding of LPS to the TLR4/MD2 complex and activating Nrf2-mediated HO-1 activation.
Acertannin (ACTN) is a polyphenol known for its powerful anticancer and antioxidant effects. However, its anti-inflammatory effects have not been investigated at the molecular levels. Therefore, to evaluate anti-inflammatory effects of ACTN and its signaling pathway, the expression of proinflammatory markers was measured in lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages. Molecular docking predicted the binding site of ACTN to the TLR4/MD2 complex. Moreover, in LPS-microinjected zebrafish, we investigated whether ACTN reduces nitric oxide and reactive oxygen species (ROS) production. ACTN significantly attenuated LPS-induced proinflammatory cytokines and mediators by inhibiting nuclear factor-kappa B (NF-κB) activation. ACTN also reduced LPS-induced ROS production and activated nuclear factor E2-related factor 2 and heme oxygenase-1 (HO-1). In addition, zinc protoporphyrin, an HO-1 inhibitor, markedly abolished the anti-inflammatory and antioxidant effects of ACTN in LPS-stimulated zebrafish larvae. Moreover, molecular docking predictions verified that ACTN forms a conventional hydrogen bond with LYS91 in myeloid differentiation factor-2 (MD2) and interrupts LPS binding to the Toll-like receptor 4 (TLR4)/MD2 complex. In addition, ACTN forms many non-covalent bonds, such as π-π stacking, π-alkyl, unfavorable donor-donor, and van der Waals interactions, with the TLR4/MD2 complex. Furthermore, the binding of ACTN to the TLR4/MD2 complex inhibited the recruitment of intracellular adaptor proteins, including myeloid differentiation primary response 88 and interleukin-1 receptor-associated kinase 4, and consequently attenuated NF-κB-mediated inflammatory responses. The conclusion of this study is that ACTN is a potent anti-inflammatory agent in LPS-mediated inflammation, such as endotoxemia.


Is a normal computed tomography pulmonary angiography safe to rule out acute pulmonary embolism in patients with a likely clinical probability? A patient-level meta-analysis.
A normal computed tomography pulmonary angiography (CTPA) remains a controversial criterion for ruling out acute pulmonary embolism (PE) in patients with a likely clinical probability. We set out to determine the risk of VTE and fatal PE after a normal CTPA in this patient category and compare these risk to those after a normal pulmonary angiogram of 1.7 % (95 %CI 1.0-2.7 %) and 0.3 % (95 %CI 0.02-0.7 %). A patient-level meta-analysis from 4 prospective diagnostic management studies that sequentially applied the Wells rule, D-dimer tests and CTPA to consecutive patients with clinically suspected acute PE. The primary outcome was the 3-month VTE incidence after a normal CTPA. A total of 6,148 patients were included with an overall PE prevalence of 24 %. The 3-month VTE incidence in all 4,421 patients in whom PE was excluded at baseline was 1.2 % (95 %CI 0.48-2.6) and the risk of fatal PE was 0.11 % (95 %CI 0.02-0.70). In patients with a likely clinical probability the 3-month incidences of VTE and fatal PE were 2.0 % (95 %CI 1.0-4.1 %) and 0.48 % (95 %CI 0.20-1.1 %) after a normal CTPA. The 3-month incidence of VTE was 6.3 % (95 %CI 3.0-12) in patients with a Wells rule >6 points. In conclusion, this study suggests that a normal CTPA may be considered as a valid diagnostic criterion to rule out PE in the majority of patients with a likely clinical probability, although the risk of VTE is higher in subgroups such as patients with a Wells rule >6 points for which a closer follow-up should be considered.


Effects of Vitamin B6 Deficiency on the Composition and Functional Potential of T Cell Populations.
The immune system is critical in preventing infection and cancer, and malnutrition can weaken different aspects of the immune system to undermine immunity. Previous studies suggested that vitamin B6 deficiency could decrease serum antibody production with concomitant increase in IL4 expression. However, evidence on whether vitamin B6 deficiency would impair immune cell differentiation, cytokines secretion, and signal molecule expression involved in JAK/STAT signaling pathway to regulate immune response remains largely unknown. The aim of this study is to investigate the effects of vitamin B6 deficiency on the immune system through analysis of T lymphocyte differentiation, IL-2, IL-4, and INF-γ secretion, and SOCS-1 and T-bet gene transcription. We generated a vitamin B6-deficient mouse model via vitamin B6-depletion diet. The results showed that vitamin B6 deficiency retards growth, inhibits lymphocyte proliferation, and interferes with its differentiation. After ConA stimulation, vitamin B6 deficiency led to decrease in IL-2 and increase in IL-4 but had no influence on IFN-γ. Real-time PCR analysis showed that vitamin B6 deficiency downregulated T-bet and upregulated SOCS-1 transcription. This study suggested that vitamin B6 deficiency influenced the immunity in organisms. Meanwhile, the appropriate supplement of vitamin B6 could benefit immunity of the organism.


Hyperthermia and fibrinolytic therapy do not improve the beneficial effect of radioimmunotherapy following cytoreductive surgery in rats with peritoneal carcinomatosis of colorectal origin.
Cytoreductive surgery (CS) and heated intraperitoneal chemotherapy (HIPEC) are standard treatment for peritoneal carcinomatosis (PC) of colorectal cancer. Previously, we demonstrated that preclinical radioimmunotherapy (RIT) adjuvant to surgery in PC is a good alternative for HIPEC. Now we aimed to improve the effectiveness of RIT by combining it with whole-body hyperthermia (WBH) or fibrinolytic therapy. Rats were inoculated intraperitoneally with colon carcinoma cells. Animals underwent CS, CS + WBH (40 degrees C, 3 hours), CS + RIT (74 MBq 177Lu-labeled MG1), or CS + WBH + RIT. In the second experiment, rats underwent CS, CS + RIT, CS + recombinant tissue plasminogen activator (rtPA, twice daily, 3 days), or CS + RIT + rtPA. Median survival after CS and CS + WBH was 34 and 37 days. Median survival after CS + RIT or CS + RIT + WBH was 63 and 86 days (p < 0.0003, p < 0.0006 compared to CS + WBH). Median survival after CS and CS + rtPA was 50 and 42 days (p = 0.1). Median survival was 106 days after CS + RIT and 103 days after CS + RIT + rtPA (p < 0.0001 compared to CS + rtPA). No difference was found between CS + RIT and CS + RIT + rtPA (p = 0.83). The application of WBH or rtPA in combination with adjuvant RIT after CS for the treatment of PC of colonic was feasible but did not significantly potentiate the efficacy of RIT.


Spermidine biases the resolution of Holliday junctions by phage lambda integrase.
Holliday junctions are a central intermediate in diverse pathways of DNA repair and recombination. The isomerization of a junction determines the directionality of the recombination event. Previous studies have shown that the identity of the central sequence of the junction may favor one of the two isomers, in turn controlling the direction of the pathway. Here we demonstrate that, in the absence of DNA sequence-mediated isomer preference, polycations are the major contributor to biasing strand cleavage during junction resolution. In the case of wild-type phage lambda excision junctions, spermidine plays the dominant role in controlling the isomerization state of the junction and increases the rate of junction resolution. Spermidine also counteracts the sequence-imposed bias on resolution. The spermidine-induced bias is seen equally on supercoiled and linear excisive recombination junction intermediates, and thus is not just an artefact of in vitro recombination conditions. The contribution of spermidine requires the presence of accessory factors, and results in the repositioning of Int's core-binding domains on junctions, perhaps due to DNA-spermidine-protein interactions, or by influencing DNA conformation in the core region. Our results lead us to propose that spermidine together with accessory factors promotes the formation of the second junction isomer. We propose that this rearrangement triggers the activation of the second pair of Int active sites necessary to resolve Holliday junctions during phage lambda Int-mediated recombination.


Contrast sonography, video densitometry and intervillous blood flow: a pilot project.
To examine the feasibility of constructing time-intensity (TI) curves from the intervillous space with an intravascular ultrasound contrast agent and computer assisted video densitometry. We sedated nine pregnant baboons, optimized the grey scale and color Doppler images of their placentas, and then fixed the transducers in place. For each injection of contrast, we recorded images on videotape without changing the ultrasound image processing functions. Video images were captured using a Macintosh personal computer equipped with a video-capture board using image analysis software (Image 1.4, W Rasband, NIH). For each injection, we sampled digitized images of a fixed region of interest at regular intervals. After computing the mean video density of each image, we used the sampling frequency to construct TI curves depicting any change over time as the contrast agents washed into and out of the intervillous space. Three of four agents tested produced changes in the video density of the placenta. TI curves were established using both grey scale and color Doppler signal augmentation. As expected, intra-arterial agents produced rapid accumulation and decay. Intravenous agents produced more protracted effects secondary to bolus dilution and transit through the right heart and pulmonary vascular bed. TI curves may be generated from the intervillous space with the use of a transpulmonary ultrasound contrast agent and video densitometry. If validated by further study, this may allow investigators to apply ultrasound and indicator-dilution theory to intervillous blood flow.


A comparison of clinicopathological features and prognosis in prostate cancer between atomic bomb survivors and control patients.
An atomic bomb (A-bomb) was dropped on Hiroshima on 6th August 1945. Although numerous studies have investigated cancer incidence and mortality among A-bomb survivors, only a small number have addressed urological cancer in these survivors. The aim of the present study was to investigate the clinicopathological features of prostate cancer (PCa) in A-bomb survivors. The clinicopathological features and prognosis of PCa were retrospectively reviewed in 212 survivors and 595 control patients between November 1996 and December 2010. The histopathological and clinical outcomes of surgical treatment of PCa were also evaluated in 69 survivors and 162 control patients. Despite the higher age at diagnosis compared with the control group (P=0.0031), survivors were more likely to have been diagnosed with PCa from a health check compared with the control group (P<0.0001). As a consequence, the survivors were found to exhibit metastasis significantly less frequently (199/212, 93.9%) compared with the control patients (521/595, 87.6%; P=0.0076). Prognosis in the two groups was examined, subsequent to a mean length of follow-up of 44 months. Overall survival (OS) and PCa-specific survival (CS) were similar between the two groups (OS, P=0.2196; CS, P=0.1017). A-bomb exposure was not found to be an independent predictor for prognosis by multivariate analysis (OS, P=0.7800; CS, P=0.8688). The clinicopathological features of patients who underwent a prostatectomy were similar except for the diagnosis opportunity between the two groups. Progression-free survival rates were similar between the two groups (P=0.5630). A-bomb exposure was not a significant and independent predictor for worsening of progression-free prognosis by multivariate analysis (P=0.3763). A-bomb exposure does not appear to exert deleterious effects on the biological aggressiveness of PCa and the prognosis of patients with PCa.


Novel Lactams as Cbl-b Inhibitors for Treating Cancer.
Provided herein are novel lactams as Cbl-b inhibitors, pharmaceutical compositions, use of such compounds in treating cancer, and processes for preparing such compounds.


Synchronization Dynamics in a Designed Open System.
We theoretically propose a unifying expression for synchronization dynamics between two-level constituents. Although synchronization phenomena require some substantial mediators, the distinct repercussions of their propagation delays remain obscure, especially in open systems. Our scheme directly incorporates the details of the constituents and mediators in an arbitrary environment. As one example, we demonstrate the synchronization dynamics of optical emitters on a dielectric microsphere. We reveal that the whispering gallery modes (WGMs) bridge the well-separated emitters and accelerate the synchronized fluorescence, known as superfluorescence. The emitters are found to overcome the significant and nonuniform retardation, and to build up their pronounced coherence by the WGMs, striking a balance between the roles of resonator and intermediary. Our work directly illustrates the dynamical aspects of many-body synchronizations and contributes to the exploration of research paradigms that consider designed open systems.


Defining the photochemical contribution to particulate matter in urban areas using time-series analysis.
The objective of this project is to demonstrate how the ambient air measurement record can be used to define the relationship between O3 (as a surrogate for photochemistry) and secondary particulate matter (PM) in urban air. The approach used is to develop a time-series transfer-function model describing the daily PM10 (PM with less than 10 microm aerodynamic diameter) concentration as a function of lagged PM and current and lagged O3, NO or NO2, CO, and SO2. Approximately 3 years of daily average PM10, daily maximum 8-hr average O3 and CO, daily 24-hr average SO2 and NO2, and daily 6:00 a.m.-9:00 a.m. average NO from the Aerometric Information Retrieval System (AIRS) air quality subsystem are used for this analysis. Urban areas modeled are Chicago, IL; Los Angeles, CA; Phoenix, AZ; Philadelphia, PA; Sacramento, CA; and Detroit, MI. Time-series analysis identified significant autocorrelation in the O3, PM10, NO, NO2, CO, and SO2 series. Cross correlations between PM10 (dependent variable) and gaseous pollutants (independent variables) show that all of the gases are significantly correlated with PM10 and that O3 is also significantly correlated lagged up to two previous days. Once a transfer-function model of current PM10 is defined for an urban location, the effect of an O3-control strategy on PM concentrations is estimated by calculating daily PM10 concentrations with reduced O3 concentrations. Forecasted summertime PM10 reductions resulting from a 5 percent decrease in ambient O3 range from 1.2 microg/m3 (3.03%) in Chicago to 3.9 microg/m3 (7.65%) in Phoenix.


Ultrastructural evidence for the formation of amyloid fibrils within cardiomyocytes in isolated atrial amyloid.
Isolated atrial amyloid (IAA) frequently affects elderly human hearts in which only the atria are involved by the deposits. Biochemical analysis has indicated that the major subunit protein of IAA is alpha-human atrial natriuretic peptide (alpha-ANP), which is synthesized by the atrial muscle cells. To define the exact location of the formation of IAA fibrils, right atria from 25 patients undergoing cardiac surgery have been examined by an immunohistochemistry and immunoelectron microscopy with anti-alpha-ANP, apolipoprotein E, amyloid P component, transthyretin, and cathepsin B antisera. Of 25 patients, 19 were involved with IAA deposits which reacted with anti-alpha-ANP, apolipoprotein E, amyloid P component antisera but not with anti-transthyretin antiserum. In 8 of them, amyloid fibrils were seen not only in the interstitium of the atrial myocardium but also in the dilated transverse tubules of the cardiomyocytes. In some cardiomyocytes, amyloid fibrils were also demonstrated within the organelles such as coated and uncoated secretory vesicles or lysosomes. These findings lead to the inescapable conclusion that the polymerization of amyloid fibrils in IAA occurs within the cytoplasm of cardiomyocytes under some conditions.


The p42/44 mitogen-activated protein kinase pathway couples photic input to circadian clock entrainment.
In mammals, the suprachiasmatic nuclei (SCN) of the hypothalamus function as the major biological clock. SCN-dependent rhythms of physiology and behavior are regulated by changes in the environmental light cycle. Currently, the second messenger signaling events that couple photic input to clock entrainment have yet to be well characterized. Recent work has revealed that photic stimulation during the night triggers rapid activation of the p42/44 mitogen activated protein kinase (MAPK) pathway in the SCN. The MAPK signal transduction pathway is a potent regulator of numerous classes of transcription factors and has been shown to play a role in certain forms of neuronal plasticity. These observations led us to examine the role of the MAPK pathway in clock entrainment. Here we report that pharmacological disruption of light-induced MAPK pathway activation in the SCN uncouples photic input from clock entrainment, as assessed by locomotor activity phase. In the absence of photic stimulation, transient disruption of MAPK signaling in the SCN did not alter clock-timing properties. We also report that signaling via the Ca(2+)/calmodulin kinase pathway functions upstream of the MAPK pathway, coupling light to activation of the MAPK pathway. Together these results delineate key intracellular signaling events that underlie light-induced clock entrainment.


Hemodynamics of anesthetized ventilated mouse models: aspects of anesthetics, fluid support, and strain.
This study evaluates the effects of anesthesia and fluid support on hemodynamic parameters of the mechanically ventilated mouse of four different strains. All experiments were performed at a similar surgical level of anesthesia, as indicated by the probing of the pedal withdrawal reflex. Three anesthetic regimens [fentanyl-fluanisone-midazolam (FFM), ketamine-medetomidine-atropine (KMA), and isoflurane (ISO)], four commonly used mouse strains (Swiss, CD-1, BalbC, and C57Bl6), and three different fluid support strategies (no fluid, 0.2 ml x h(-1) x 10 g(-1) of 6% polystarch solution, and 0.5 ml x h(-1) x 10 g(-1) saline) were studied. Mean arterial pressure (MAP) or heart rate (HR) was similar among the four strains of mice except a trend toward lower HR for the BalbC mice. In terms of MAP, KMA is the preferred anesthetic for the Swiss and CD-1 mice, whereas KMA or ISO are recommended for BalbC or C57Bl6 mice. In terms of HR, ISO is the preferred anesthetic for the Swiss, CD-1, and C57Bl6 strains. No differences in HR for the three anesthetics were observed for the BalbC strain. Compared with administration of no fluid, both saline and polystarch administration similarly increased MAP by 7 +/- 2, 10 +/- 2, and 11 +/- 2 mmHg at t = 1, 2, and 3 h, respectively, whereas fluid administration was without effect on HR. Saline supplementation resulted in an increased dry-to-wet ratio of the heart and both fluid regimens decreased total hemoglobin in the blood from 12.6 +/- 0.5 to 10.4 +/- 0.5 g/100 ml. Saline administration was associated with blood acidosis (pH 7.20 +/- 0.03) compared with the Haes (pH 7.29 +/- 0.02) or no-fluid group (pH 7.34 +/- 0.03), whereas PCO(2) was approximately 30 mmHg for all groups. We conclude that at similar surgical levels of anesthesia, the preferable type of anesthesia (ISO or KMA, but never FFM) depends on the strain used and whether MAP or HR is the focus of study. Additional fluid support is beneficial in terms of raising arterial blood pressure, although this is at the cost of changes in organ water content and increased anemia.