[Physiotherapy in patients after lung parenchyma resection].
Lung parenchyma resection is the treatment of choice for early-stage lung cancer. The surgery involves the loss of respiratory surface and consequently leads to reduction in exercise capacity. Proper rehabilitation is essential for restoring the function and good performance of the respiratory system. Rehabilitation should be an integral part of surgical treatment. It should be implemented early and maintained until full restoration of function and fitness. The paper discusses the physiotherapeutic procedure in patients after lung parenchyma resection. Under current guidelines, the recommended physiotherapeutic approach has been described as a multi-stage process. A preoperative exercise program can prepare the patient better for surgery and reduce the risk of some postoperative complications. Since there is a tendency to shorten the hospital stay, guidelines in preparation for surgery have been developed in the form of leaflets given to patients. In specifically described perioperative treatment we can see the physiotherapeutic procedures that the patient, after lung parenchyma resection, may undergo. Physiotherapy protocol was documented using a proposed patient's card that described the basic treatment and included additional space for comments, in case of complications etc. Post-hospital rehabilitation, described in accordance with current guidelines, complements the treatment after surgery as a whole. To achieve the goals of rehabilitation a team of closely cooperating specialists must emerge. It should include physicians, physiotherapists, nurses, psychologists and occupational therapists. Family support plays a significant role as well. Proper education for patients and informing them about the purposefulness of the treatment are very significant factors. Further analysis allowed the creation of an algorithm for physiotherapeutic care in patients without complications after lung cancer surgery.


INTERMEDIATE ENDEMICITY OF HEPATITIS A VIRUS INFECTION IN RURAL SETTLEMENT PROJECTS OF SOUTHWEST GOIÁS, BRAZIL.
Rural populations present an elevated risk of exposure to hepatitis A virus. The objective of this study was to estimate the prevalence and risk factors associated with hepatitis A virus infection among residents of rural settlement projects of southwest Goiás, Central Brazil. A total of 466 residents were interviewed and tested for the detection of anti- hepatitis A virus antibodies by ELISA. The global prevalence of anti- hepatitis A virus was 82.2%. In individuals aged 5-9 years and 10-19 years, the prevalence was 15% and 58.8%, respectively. Persons in the 10-19 age group, with a history of life in encampments, with more than five people per residence consuming well water, were predictors for exposure to hepatitis A virus. Our results suggest that the hepatitis A virus endemicity in rural settlements in southwest Goiás similar to that found in the urban population of the Midwest Region, confirming the implementation of universal hepatitis A vaccination in children.


Audience response system: effect on learning in family medicine residents.
The use of an electronic audience response system (ARS) that promotes active participation during lectures has been shown to improve retention rates of factual information in nonmedical settings. This study (1) tested the hypothesis that the use of an ARS during didactic lectures can improve learning outcomes by family medicine residents and (2) identified factors influencing ARS-assisted learning outcomes in family medicine residents. We conducted a prospective controlled crossover study of 24 family medicine residents, comparing quiz scores after didactic lectures delivered either as ordinary didactic lectures that contained no interactive component, lectures with an interactive component (asking questions to participants), or lectures with ARS. Post-lecture quiz scores (maximum score 7) were 4.25 +/- 0.28 (61% correct) with non-interactive lectures, 6.50 +/- 0.13 (n=22, 93% correct) following interactive lectures without ARS, and 6.70 +/- 0.13 (n=23, 96% correct) following ARS lectures. The difference in scores following ARS or interactive lectures versus non-interactive lectures was significant (P <.001). Mean quiz scores declined over 1 month in all three of the lecture groups but remained highest in the ARS group. Neither lecture factors (monthly sequence number) nor resident factors (crossover group, postgraduate training year, In-Training Examination score, or post-call status) contributed to these differences, although postcall residents performed worse in all lecture groups. Both audience interaction and ARS equipment were associated with improved learning outcomes following lectures to family medicine residents.


A pivotal role of calcineurin signaling in development and maturation of postnatal cerebellar granule cells.
Primary culture of postnatal cerebellar granule cells provides a model system that recapitulates many molecular events of developing granule cells in vivo. Depolarization of cultured granule cells increases intracellular Ca(2+) and activates Ca(2+)/calmodulin-dependent calcineurin (CaN) phosphatase. This Ca(2+) signaling mimics some of the signaling events for proliferation, migration, and differentiation of granule cells in vivo. We investigated the genome-wide expression profiles of depolarization- and CaN-regulated genes in cultured mouse granule cells and addressed their relevance to gene regulation in developing granule cells in vivo. Granule cells were cultured under a nondepolarization condition (5 mM KCl) and a depolarization condition (25 mM KCl) with and without the CaN inhibitor FK506. Gene expression profiles between depolarization and nondepolarization and between FK506 treatment and untreatment were analyzed by microarray techniques. Both depolarization and FK506 treatment influence expression levels of a large number of genes, most of which are overlapping, however, are conversely regulated by these two treatments. Importantly, many of the FK506-responsive genes are up- or down-regulated in parallel with gene expression in postnatal granule cells in vivo. The FK506-down-regulated genes are highly expressed in proliferating/premigratory granule cells and many of these genes encode cellular components involved in cell proliferation, migration, and differentiation. In contrast, the FK506-up-regulated genes are predominantly expressed in postmigratory granule cells, including many functional molecules implicated in synaptic transmission and modulation. This investigation demonstrates that the CaN signaling plays a pivotal role in development and synaptic organization of granule cells during the postnatal period.


HIV-associated Immune Complex Kidney Disease with C3-dominant Deposition Induced by HIV Infection after Treatment of IgA Nephropathy.
A 57-year-old man was diagnosed with IgA nephropathy. Hematuria and proteinuria were improved by tonsillectomy plus methylprednisolone pulse therapy. Lymphadenopathy, hypocomplementemia and pancytopenia were observed six years later, and urinalysis abnormalities recurred. A biopsy revealed mesangial proliferative glomerulonephritis with C3-dominant deposition. Human immunodeficiency virus (HIV) antibody demonstrated positive conversion. He was diagnosed with HIV-associated immune complex kidney disease (HIVICK). The hematuria, proteinuria and hypocomplementemia were improved by reducing the HIV viral load through antiretroviral therapy. When C3-dominant deposition is observed on a renal biopsy, HIVICK must be differentiated.


[Quo vadis, hypophysis? Some news and prospects].
Knowledge of hypophysis could hardly stagnate in a context of general progress in medical science as such. New knowledge in physiology, pathology and treatment of hypophysis diseases is vast and only some of it could be included in the article. New regulators of hypophysial secretion have been discovered. Among them are hypothalamic chemokines and the KISS-1 gene product--kisspeptin. Impulses coming to the hypophysis from the brain centres and the periphery need to be integrated. This is provided by a system of folliculo-stellate cells, paracrine mechanisms and hypophysial microcirculation. Are there stem cells in the hypophysis, too? It seems there are. It could be the above mentioned folliculo-stellate system cells, or the recently discovered SP (side population) cells. Massive injuries such as multiple traumas, severe burns and shock states provoke a double-phase response of the hypophysis. The acute phase is characterised by hypersecretion of most of hypophysial hormones and peripheral resistance to their actuation. In the subsequent chronic phase, however, the secretion of all hypophysial hormones is reduced, except for ACTH. Clinically relevant hypophysial adenomas affect approximately 1 per thousand of population. Two thirds of the above number are prolactinomas. Most prolactinomas can be cured without major difficulty, only those resistant to pharmacological treatment can become a problem. In such cases, Leksell gamma knife can play an important role. The treatment of acromegaly is far more difficult, though. We have developed our own acromegaly treatment method. We treat adenomas surgically, expose possible residua to Leksell gamma knife irradiation and apply pharmacological therapy until the effect of irradiation has been achieved. The therapeutic options are ordered in a cost sequence: cabergolin, somatostatin analogues, pegvisomant. Similar approach is applied to patients with central etiology Cushing's syndrome, the only difference being the fact that the pharmacological therapy preceding the effect of the gamma knife treatment uses ketoconazol and metyrapone. Like in the case of acromegaly, also in that of Cushing's disease, new drugs are developed which promise greater therapeutic advantages.


Huntingtin Is Required for Neural But Not Cardiac/Pancreatic Progenitor Differentiation of Mouse Embryonic Stem Cells In vitro.
Mutation in the huntingtin (HTT) gene causes Huntington's disease (HD). It is an autosomal dominant trinucleotide-repeat expansion disease in which CAG repeat sequence expands to >35. This results in the production of mutant HTT protein with an increased stretch of glutamines near the N-terminus. The wild type HTT gene encodes a 350 kD protein whose function remains elusive. Mutant HTT protein has been implicated in transcription, axonal transport, cytoskeletal structure/function, signal transduction, and autophagy. HD is characterized by the appearance of nuclear inclusions and degeneration of the striatum. Although HTT protein is expressed early in embryos, most patients develop symptoms in mid-life. It is also unclear why the ubiquitously expressed mutant HTT specifically causes striatal atrophy. Wild type Htt is essential for development as Htt knockout mice die at day E7.5. Increasing evidence suggests mutant Htt may alter neurogenesis and development of striatal neurons resulting in neuronal loss. Using a mouse embryonic stem cell model, we examined the role of Htt in neural differentiation. We found cells lacking Htt inefficient in generating neural stem cells. In contrast differentiation into progenitors of mesoderm and endoderm lineages was not affected. The data suggests Htt is essential for neural but not cardiac/pancreatic progenitor differentiation of embryonic stem cells in vitro.


Poultry science graduate students: challenges and opportunities.
"What are you going to do next?" is a common question often asked of a student who has recently graduated with either an MSc or PhD degree. We should not be surprised to hear the answer "I do not know yet." I have talked with many poultry science graduate students who usually start thinking about their future careers a few months before defending their thesis. I personally believe that nothing happens overnight in this world (excluding political-related issues), so we as graduate students need to have a comprehensible and pragmatic strategy when it comes to answering the question "What to do next?" This paper is not about how graduate students can find a job because there are numerous sources of information that are readily available elsewhere. One of the key messages of this paper is that networking is of paramount importance when it comes to moving in the right direction after graduation. Consequences of any decision made at this stage will often have a far-reaching unseen influence on us for many years into the future. I am also fully aware that there are many things over which we do not have any control, but as graduate students, are we doing our best to prepare ourselves for the real world?


Training for prescriptions vs. prescriptions for training: where are we now? Where should we be? How do we get there?
The proposal that state legislatures should grant prescription privileges to psychologists is examined critically, with particular attention to the proposal's implications for the future education and training of clinical psychologists. First, the current status of clinical psychology is described. Then, an alternative to the prescription privilege proposal is presented; this alternative prescribes a scientific approach to clinical psychology. Finally, a plan for achieving this alternative is outlined.


Peripheral NMDA and non-NMDA glutamate receptors contribute to nociceptive behaviors in the rat formalin test.
The present study demonstrates that local cutaneous administration of either the N-methyl-D-aspartate (NMDA) glutamate receptor antagonist MK-801 or the non-NMDA glutamate receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) significantly attenuates formalin-induced nociceptive behaviors. Specifically, pretreatment with either drug reduced the magnitude and time course of lifting and licking behavior in the late phase of formalin pain; however, flinching behavior was not affected. In contrast, post-treatment of formalin pain with either antagonist did not affect lifting and licking behavior, although flinching behavior was mildly attenuated. We hypothesize that these actions result from blocking of peripheral glutamate receptors located on unmyelinated axons at the dermal-epidermal junction. These data suggest that peripheral glutamate receptors on cutaneous axons can be manipulated to reduce certain aspects of pain of peripheral origin. This route of administration offers the advantage of avoiding the side effects of systemic administration.


[Management of aortic aneurysms in the endovascular era].
Abdominal aortic aneurysm is a disease seen in the elderly. Without intervention, an aneurysm can rupture which leads to death in most cases. Surgical resection was the gold standard treatment for many years but since two decades, endovascular repair has surged drastically. Less invasive and morbid than open repair, this technique has significantly evolved in the recent years. Nowadays the whole aorta can be treated with endovascular techniques in expert hands. This article presents an overview of different endovascular solutions and innovations in the management of aortic aneurysms.


Paraneoplastic recurrent hypoglycaemic seizures: an initial presentation of hepatoblastoma in an adolescent male-a rare entity.
Hepatoblastoma (HB) is a rare malignant tumour of the liver and usually occurs in the first three years of life. Hepatoblastoma in adolescents and young adults is extremely rare; nevertheless the prognosis is much worse than in childhood, because these kinds of tumours are usually diagnosed late. Characteristic imaging and histopathological and AFP levels help in the diagnosis of hepatoblastoma. Paraneoplastic features of hepatoblastoma are not uncommon at presentation and include erythrocytosis, thrombocytosis, hypocalcaemia, isosexual precocious puberty, and rarely hypoglycaemia. Even though hypoglycaemia is commonly seen in hepatocellular carcinoma, its association with hepatoblastoma is very rare. We present a case of 15-year-old male patient presenting with complaints of recurrent hypoglycaemic seizures ultimately leading to diagnosis of hepatoblastoma. Managed successfully with neoadjuvant chemotherapy, surgery and adjuvant chemotherapy with adriamycin and cisplatin based regimens. An extensive review of literature in the PubMed and MEDLINE did not reveal much data on paraneoplastic recurrent hypoglycaemic seizures as an initial presentation of hepatoblastomas in adolescents and young adults.


Microglial transcriptome analysis in the rNLS8 mouse model of TDP-43 proteinopathy reveals discrete expression profiles associated with neurodegenerative progression and recovery.
The microglial reaction is a hallmark of neurodegenerative conditions, and elements thereof may exert differential effects on disease progression, either worsening or ameliorating severity. In amyotrophic lateral sclerosis (ALS), a syndrome characterized by cytoplasmic aggregation of TDP-43 protein and atrophy of motor neurons in the cortex and spinal cord, the transcriptomic signatures of microglia during disease progression are incompletely understood. Here, we performed longitudinal RNAseq analysis of cortical and spinal cord microglia from rNLS8 mice, in which doxycycline-regulatable expression of human TDP-43 (hTDP-43) in the cytoplasm of neurons recapitulates many features of ALS. Transgene suppression in rNLS8 mice leads to functional, anatomical and electrophysiological resolution that is dependent on a microglial reaction that is concurrent with recovery rather than disease onset. We identified basal differences between the gene expression profiles of microglia dependent on localization in spinal cord or cortex. Microglia subjected to chronic hTDP-43 overexpression demonstrated transcriptomic changes in both locations. We noted strong upregulation of Apoe, Axl, Cd63, Clec7a, Csf1, Cst7, Igf1, Itgax, Lgals3, Lilrb4, Lpl and Spp1 during late disease and recovery. Importantly, we identified a distinct suite of differentially expressed genes associated with each phase of disease progression and recovery. Differentially expressed genes were associated with chemotaxis, phagocytosis, inflammation, and production of neuroprotective factors. These data provide new insights into the microglial reaction in TDP-43 proteinopathy. Genes differentially expressed during progression and recovery may provide insight into a unique instance in which the microglial reaction promotes functional recovery after neuronal insult.


Kinetics of geminate recombination of organic free radicals in viscous solvents.
The kinetics of geminate recombination of multiatomic organic free radicals in glycerol solutions have been investigated. Radicals were produced by ns laser flash photolysis under photoreduction of carbonyl compounds. An external moderate magnetic field decelerates geminate recombination leading to smaller cage effect values. The duration of geminate recombination is discussed.


Dementia risk in women higher in same-sex than opposite-sex twins.
Hormones may be one possible mechanism underlying sex differences in dementia incidence. We examined whether presumed differential prenatal hormone milieu is related to dementia risk by comparing dementia rates in same- and opposite-sex dizygotic twin pairs in male and female twins. The sample comprised 43,254 individuals from dizygotic twin pairs aged 60 and older from the Swedish Twin Registry. Survival analyses were conducted separately for females and males. Female twins from opposite-sex pairs had significantly lower dementia risk than female twins from same-sex pairs, but the differences emerged only after age 70 (hazard ratio = 0.64, P = 0.004). Results were not explained by postnatal risk factors for dementia, and no interaction between twin type and apolipoprotein E (APOE) ε4 was found. Male twins from same-sex versus opposite-sex pairs did not differ significantly. The results suggest that relatively masculine prenatal hormone milieus correlate with lower dementia risk in females.


Ginkgo biloba Extract Modulates the Retroperitoneal Fat Depot Proteome and Reduces Oxidative Stress in Diet-Induced Obese Rats.
The rapid increase in the number of individuals with obesity, over the past four decades, is triggered by a number of complex interactions among factors. Despite the plethora of treatments available, side effects are commonly observed and, in this context, herbal medicines have been employed as an alternative form of therapy. Ginkgo biloba extract (GbE) has been described as a promising new pharmacological approach to treat obesity. In order to better comprehend the mechanisms involved with this potential effect, the present study evaluated the effects of GbE treatment on diet-induced obese rats, focusing on the proteome and the oxidative stress defense system of visceral adipose tissue. After 14 days treatment, GbE significantly modulated 25 proteins. Retroperitoneal adipose tissue of treated animals exhibited higher amounts of proteins associated with adipogenesis (decorin), carbon metabolism and mitochondrial function (citrate synthase), and a concomitant reduction in adipocyte hypertrophy. In parallel, GbE down-regulated proteins involved in oxidative stress (peroxiredoxin) and the inflammatory response (complement C3, mast cell protease 1, and Ig gamma-2B chain C region). Moreover, also related to oxidative stress defense, GbE stimulated catalase activity, reduced malondialdehyde levels (lipid peroxidation indicator), and increased lactoylglutathione lyase levels. It was concluded that GbE acts as an antioxidant agent, and improved the proteome profile and oxidative stress response in the adipose tissue of diet-induced obese rats.


Heavy Metal Concentrations in the Groundwater of the Barcellona-Milazzo Plain (Italy): Contributions from Geogenic and Anthropogenic Sources.
We collected and analysed 58 samples of groundwater from wells in the Barcellona-Milazzo Plain, one of the most important coastal aquifers of Sicily (Italy), to determine major, minor, and trace element concentrations. In this area, geogenic and anthropogenic sources of heavy metals and other pollutants co-act, making the individuation of the main pollution sources difficult. Our work was aimed at the application of geostatistical criteria for discriminating between these pollution sources. We used probability plots for separating anomalous values from background concentrations, which were plotted on maps and related to possible sources of pollutants. Our results indicate that hydrothermal fluid circulation and the water⁻rock interaction of country rocks that host mineralized ore deposits generate a significant flux of heavy metals to groundwater, as well as anthropogenic sources like intense agriculture and industrial activities. In particular, NO₃, F, and Ni exceed the Maximum Admitted Concentrations (MACs) established by the WHO and Italian legislation for drinking-water. The spatial distributions of geogenic and anthropogenic sources were so deeply interlocked that their separation was not easy, also employing geostatistical tools. This complex scenario makes the implementation of human health risk mitigation actions difficult, since the flow of pollutants is in many cases controlled by simple water⁻rock interaction processes.


Health care of people in homelessness: a comparative study of mobile units in Portugal, United States and Brazil.
This paper describes and analyzes the legal and normative framework guiding the use of mobile units in Portugal, United States and Brazil, which seek to improve access and continuity of care for people in homelessness. We used a comparative analysis through literature and documentary review relating three categories: context (demographic, socio-economic and epidemiological), services system (access, coverage, organization, management and financing) and, specifically, mobile units (design, care and financing model). The analysis was based on the theory of convergence/divergence between health systems from the perspective of equity in health. Improving access, addressing psychoactive substances abuse, outreach and multidisciplinary work proved to be common to all three countries, with the potential to reduce inequities. Relationships with primary healthcare, use of vehicles and the type of financing are considered differently in the three countries, influencing the greater or lesser extent of equity in the analyzed proposals.


[Clinical characteristics and risk factors affecting outcomes of elderly patients with non-small cell lung cancer complicated by chronic obstructive pulmonary disease].
To investigate the clinical features, treatment strategy and risk factors affecting the prognosis of elderly patients with non-small cell lung cancer (NSCLC) complicated by chronic obstructive pulmonary disease (COPD). We retrospectively analyzed the data of elderly patietns (>60 years) with newly diagnosed NSCLC complicated by COPD at the Geriatric Institution of General Hospital of PLA between January, 2000 and June, 2015. The clinical data collected included history of smoking, pulmonary function test results, initial treatments, TNM stage, chief complaints, comorbidities and laboratory tests. The Cox proportional hazards regression model was used to explore the prognostic factors in these patients. A total of 200 NSCLC patients were reviewed, of which 107 (53.5%) patients had the co-morbidity of COPD as confirmed by spirometry using bronchodilator test. The median survival of the patients with NSCLC complicated by COPD was 45.8 months with 1-, 3-, 5-, and 10-year survival rates of 80.4%, 55.4%, 41.0% and 20.0%, respectively. Stratification analysis showed that patients with COPD Gold grades 1 and 2 had a significant longer median overall survival (51.7 and 43.1 months, respectively) than those with grade 3/4 (16.9 months; P=0.020 and 0.043, respectively). Univariate and multivariate analyses using Cox proportional hazards regression model showed that an older age, a higher Gold grade, advanced disease stage (stages III and IV), squamous cell carcinoma, nonsurgical initial treatment, coughing and an elevated serum CEA level were independent risk factors for shorter survival of the patients. Multiple prognostic factors can affect the outcomes of elderly patients with NSCLC complicated by COPD, and a higher COPD Gold grade that fails to respond to treatment within 3 months is the independent risk factor for survival of the patients.


A dark lens or a dark world? Conceptualising Justice Capital.
Perceptions of justice have been extensively researched within just world theory as both defensive coping mechanisms and as personal resources. This paper advocates for more programmatic efforts to be devoted to understanding perceptions of justice as rational reflections of individual access to justice. Justice Capital is conceptualised here as an individual difference based on status, microsystem authorities, effort-effect pipeline, voice, and society. These dimensions can overlap and operate on both personal and systemic levels. It is a form of capital to experience the effect of one's actions, to be treated fairly by authorities, to self-advocate, and to live in a society that has a higher justice baseline. Currently, just-world theory correlational research alternates between its positive and negative effects and between viewing belief in a just world as a predictor or as an outcome. For research to move forward productively in this field, researchers must articulate and investigate when self-evaluations of justice are rational reflections of participants' individual access to justice and connect research to existing injustices. This paper points to existing evidence of a Justice Capital interpretation and suggests how this construct can advance the theory into new directions of empirical research.


Long-Term Prognostic Impact of Estimated Glomerular Filtration Rate on Admission in Patients Hospitalized for Acute Heart Failure.
Although small-sample size studies have shown that basal alterations of estimated glomerular filtration rate (eGFR) are related to short- and mid-term higher mortality in acute heart failure (AHF), there is scarce information on the influence of an altered eGFR on long-term mortality and readmissions. Therefore, this multicenter study sought to investigate the relationship between eGFR on admission for AHF and both long-term mortality and readmissions in a large sample of patients. We retrospectively evaluated 4,595 patients consecutively discharged after admission for AHF at three tertiary-care hospitals from January 1, 2008, to January 1, 2020. To investigate the effect of eGFR on admission with long-term morbimortality, we stratified the patients according to four eGFR categories: <30 mL·min-1·1.73 m-2 (G4 and G5 patients, n = 534), 30-44 mL·min-1·1.73 m-2 (G3b patients, n = 882), 45-59 mL·min-1·1.73 m-2 (G3a patients, n = 1,080), and ≥60 mL·min-1·1.73 m-2 (G1 and G2 patients, n = 2,099). eGFR was calculated by the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation within the first 24 h following admission. At a median follow-up of 2.20 years, multivariate analyses revealed that compared to G1 and G2 patients, G4 and G5 patients exhibited a higher risk of all-cause (HR = 1.15, 95% CI: 01.02-1.30, p = 0.020) and cardiovascular (CV) (HR = 1.20, 95% CI: 1.04-1.39, p = 0.013) mortality. Similarly, multivariate analyses also showed that the lower the eGFR, the higher the risk of readmissions. In fact, compared to G1 and G2 patients, G4 and G5 patients displayed significantly increased incident rate ratios of total all-cause (28%), CV (26%), and HF-related (30%) readmissions. Data from this large study provide evidence that an eGFR below 30 mL·min-1·1.73 m-2 on admission could be an independent predictor for long-term mortality and readmissions in patients with AHF.


MRC European Carotid Surgery Trial: interim results for symptomatic patients with severe (70-99%) or with mild (0-29%) carotid stenosis. European Carotid Surgery Trialists' Collaborative Group.
The European Carotid Surgery Trial is a multicentre trial of carotid endarterectomy for patients who, after a carotid territory non-disabling ischaemic stroke, transient ischaemic attack, or retinal infarct, are found to have a stenotic lesion in the relevant (ipsilateral) carotid artery. Over the past 10 years 2518 patients have been randomised, and the mean follow-up is now almost 3 years among the 2200 thus far available for analysis of the incidence of strokes that lasted more than 7 days. For the patients with "moderate" (30-69%) stenosis on their prerandomisation angiogram the balance of surgical risk and eventual benefit remains uncertain, and full recruitment continues. For 374 patients with only "mild" (0-29%) stenosis there was little 3-year risk of ipsilateral ischaemic stroke, even in the absence of surgery, so any 3-year benefits of surgery were small, and were outweighed by its early risks. For 778 patients with "severe" (70-99%) stenosis, however, the risks of surgery were significantly outweighed by the later benefits: although 7.5% had a stroke (or died) within 30 days of surgery, during the next 3 years the risks of ipsilateral ischaemic stroke were (by life-table analysis) an extra 2.8% for surgery-allocated and 16.8% for control patients (a sixfold reduction, p less than 0.0001). There was also a small reduction in other strokes, and at 3 years the total risk of surgical death, surgical stroke, ipsilateral ischaemic stroke, or any other stroke was 12.3% for surgery and 21.9% for control (difference 9.6% SD 3.3, 2p less than 0.01). The main concern was to avoid disabling or fatal events, and, among severe stenosis patients, 3.7% had a disabling stroke (or died) within 30 days of surgery, an extra 1.1% surgery versus 8.4% control (p less than 0.0001) had a disabling or fatal ipsilateral ischaemic stroke by 3 years, and the total 3-year risk of any disabling or fatal stroke (or surgical death) was 6.0% surgery versus 11.0% control (overall difference 5.0% SD 2.3, 2p less than 0.05); but, for disabling or fatal stroke the control risks seemed to diminish after the first year, so delay of surgery by just a few months after clinical presentation might make this overall difference non-significant.


New technique for ultrasound imaging.
A new system of ultrasonic imaging has been developed which utilizes optical interferometry. This system has a broad frequency range, wide angular response, and good resolution. Operation of the system and the results of experimental imaging are described. Application of this technique to the evaluation of in vitro tissue specimens demonstrates its capability for characterization of ultrasonic tissue properties.


Praxis skills and executive function in children with neurofibromatosis type 1.
This study aimed at examining motor and ideomotor praxis skills in children with neurofibromatosis type 1 (NF1). The impact of executive dysfunction, frequently described in children with NF1, on the expression of praxis impairments was also studied. Eighteen children with NF1 were included and matched with 20 control children for age (7-14 years), sex, laterality, and parental education level. Both groups of children underwent an assessment based on cognitive models of apraxia including visuomotor tasks, executive tests, and everyday life questionnaires. The group of children with NF1 showed a trend to weaker performances on motor and ideomotor praxis than the control group, only on the finger use condition (ps < .05; with a moderate to large effect size), but not regarding manual use condition (ps > .08). Moreover, these praxis difficulties disappeared when executive dysfunctions (planning and inhibition) were controlled. These findings support the negative impact of executive dysfunctions on praxis skills in children with NF1. The identification of praxis and executive function disorders as well as their interaction is important for differentiating primary praxic disorder from a cognitive deficit that may be expressed in gesture. Clinically, this distinction is essential to optimize targeted and effective rehabilitative interventions.


Treatment planning dosimetric parameters for 192Ir seed at short distances: effects of air channels and neighboring seeds based on Monte Carlo study.
The dose distributions around two different arrangements of a single radioactive 192Ir seed in water, (1) with air channels at the ends, and (2) surrounded by two nonactive ("dummy") seeds on both longitudinal ends, were calculated using MCNP4C Monte Carlo simulations at distances up to 1 cm. The contributions from beta particles and electrons emitted by 192Ir were included in the calculations. The effects of (a) the air channels at the seed ends and (b) the interference effect of the dummy seeds on the dose distribution were quantified and compared. It was found that the dummy seeds do not cause significant dose reduction for radial distances beyond 0.05 cm from the seed center. It is decided to report the dose rate values and the dosimetric parameters in TG43 format for a single seed with air channels for use in treatment planning computer systems. The dose rate constant (at 1 cm) of 192Ir seed, lambda, is 1.108 cGyU(-1) h(-1). The values of radial dose function, g(r), are within 1% from the TG43 recommended polynomial fit, except for distances within 0.08 cm. The anisotropy function, F(r, theta), attains large values near the seed ends and shallow angles (up to 8), as well as many values greater than 2 at the 20 degrees polar angle. Treatment planning systems involving intravascular brachytherapy do not compromise the accuracy for dosimetry of multiple seed trains by summing single seed values in water.


Health students' expectations of the ideal educational environment: a qualitative research.
Educational environment is an important determinant of students' behavior and its elements are associated with academic achievement and course satisfaction. The aim of this study was to determine students' expectations of the ideal educational environment. This was a qualitative study with content analysis approach. Using a theoretical sampling method, we selected eight students from Health School of Hormozgan University of Medical Sciences, studying health education, public health, environmental health, occupational health and medical entomology. To collect data, semi-structured interviews were used and continued until reaching data saturation. Qualitative content analysis was used to analyze the data. Students' expectations of the ideal educational environment emerged in four main themes including school atmosphere, teaching, human aspects (with three subthemes including teachers, students, and school staff) and non-human aspects (with two subthemes including educational equipment and physical environment). Educational environment is a multidimensional issue and to achieve an ideal educational environment, educational planners should meet the students' expectations of the school atmosphere, teaching, teachers, students, school staff, educational equipment and physical environment.


Comparison of radicular symptoms caused by lumbar disc herniation and lumbar spinal stenosis in the elderly.
Comparative study using combined data from 2 prospective cohort studies. To expose the differences between the clinical characteristics of neurogenic claudication from magnetic resonance image-documented lumbar spinal stenosis (LSS) and lumbosacral radicular syndrome from acute, magnetic resonance image-documented, lumbar disc herniation (LDH). LSS and LDH are the common lumbar disorders that produce lower extremity pain. Though known factors such as pain induced by walking for LSS and the rapid onset of symptoms for LDH are useful for differentiating these disorders, exploration of differences in other factors has received limited study. This study included participants aged 60 yr or older from 2 previous studies. One examined walking limitations caused by LSS and the second the natural history of LDH in elderly adults. The clinical features of both groups were compared by calculating means, medians, and standard deviations for continuous variables, and frequencies for categorical variables. χ test was used to explore differences between LSS and LDH for categorical variables, and Student t test or Mann-Whitney test for continuous variables. Participants with LSS had more medical comorbidity, less intense leg pain, and less disability than those with LDH. Leg pain was more common in the anterior thigh, anterior knee and shin in LDH, and in the posterior knee in LSS. Trunk flexion was more impaired in LDH. Positive straight leg raising and femoral stretch signs were common in LDH, and rare in LSS. Abnormal Achilles reflexes were noted more frequently in LSS. In addition to established factors, greater leg pain intensity, greater disability, and pain in the anterior leg are more common in the elderly with LDH than in the elderly with LSS. Normal trunk flexion, absence of nerve root tension signs and abnormal Achilles reflexes are more common in LSS. 3.


Estimation of salt intake assessed by 24-h urinary sodium level among adults speaking different dialects from the Chaoshan region of southern China.
Dietary salt intake may vary depending on different lifestyles. We aimed to estimate the different salt intakes and evaluate the knowledge and self-awareness about salt among people speaking the Teochew, Teochew-Hakka and Hakka dialects in the Chaoshan region of southern China. The study followed a cluster sampling of residents in Chaoshan region. General characteristics, lifestyles, health status as well as knowledge and self-awareness related to salt intake were investigated using a questionnaire. Anthropometric variables as well as Na and K excretion in a 24-h urine collection were measured. Chaoshan region of China. Four hundred fifteen adults who spoke only one of these three dialects. The salt intake of adults who spoke the Teochew, Teochew-Hakka and Hakka dialects was 7·19 (interquartile range (IQR) 5·29-10·17), 9·03 (IQR 6·62-11·54) and 10·12 (IQR 7·61-12·82) g/d, respectively, with significant differences between Teochew and Teochew-Hakka speakers and between Teochew and Hakka speakers (both P < 0·05). The Na:K ratio for adults who spoke the three dialects was 3·00 (IQR 2·00-4·11), 3·50 (IQR 2·64-4·82) and 4·52 (IQR 3·35-5·97), respectively, and differed significantly among the groups (all P < 0·05). Multiple linear regression analysis showed increased Na:K ratio associated with hypertension (β = 0·71, P = 0·043) in Hakka speakers. Knowledge and self-awareness about salt intake were poor in this population. Salt intake was closely related to lifestyles and was higher than the upper limit (5 g/d) recommended by the WHO in adults of Chaoshan, especially those speaking the Hakka dialect.


Surgical Proficiency of Obstetrics and Gynaecologic Residents in Nigeria.
The aim of residency training is to produce competent and professional experts in their areas of specialty. Surgical proficiency is required to be able to offer patients a genuine choice of treatment options and safety of procedures performed. We assessed self-reported level of proficiency for common major gynaecological surgeries among trainee gynaecologists. Pretested self- administered questionnaires were distributed to senior residents at the West African College of Surgeon's revision course in Obstetrics and Gynaecology. They were 42 respondents from 15 institutions in Nigeria; 66.7%were males. The mean number of years in residency was 5±1 years.The most commonly performed surgeries were salpingectomy, ovarian cystectomy, myomectomy where approximately 60%, 30% and 33% of residents had performed 10 or more of these surgeries respectively. The least performed surgeries were vaginal hysterectomy, fistula repair and laparoscopic surgeries because each of these surgeries had never been performed more than 60% of residents. These commonly performed surgeries were associated with self-reported average or more proficiency. Reported challenges to attaining surgical proficiency were trainer incapability (92.5%), theatre/hospital logistics (75%), inadequate cases (65%) and trainer unavailability (55%). Our findings suggest that majority of the senior residents of Obstetrics and Gynaecology assisted and performed insufficient number of gynaecological surgeries to attain proficiency in these procedures. A formal training curriculum needs to be utilized in the training of surgical residents.


Expression of the Pkd1 gene is momentously regulated by Sp1.
Autosomal dominant polycystic kidney disease (ADPKD) is a common human genetic disease that is caused by a mutation of a single gene inherited from either parent. Mutations in the Pkd1 gene result in the formation of multiple fluid-filled cysts in kidneys. In previous studies, the functional regulatory sequences of Pkd1 promoter region were detected by the use of comparative genome analysis. To investigate the transcriptional regulation of the Pkd1 gene, the Pkd1 promoter was isolated. This promoter contains three Sp1-binding sites. Two of the sites which are found in a 300 bp fragment (-127 to +157) were mutated. An electrophoretic mobility shift assay (EMSA) was performed to determine which transcription factors are bound to Pkd1. Based on studies using a luciferase assay, the Sp1-A site (the nearest Sp1 to the ATG start codon) is more important for activation of Pkd1. The result of EMSA showed that Sp1 transcription factor binds with Pkd1 promoter regions. Two of the Sp1 sites were found in a proximal promoter region of Pkd1 (-127 to +157). Sp1 sites affect an important role in the activation of the gene. Especially, the Sp1-A site is more important for expression of Pkd1.


EmDL: Extracting miRNA-Drug Interactions from Literature.
The microRNAs (miRNAs), regulators of post-transcriptional processes, have been found to affect the efficacy of drugs by regulating the biological processes in which the target proteins of drugs may be involved. For example, some drugs develop resistance when certain miRNAs are overexpressed. Therefore, identifying miRNAs that affect drug effects can help understand the mechanisms of drug actions and design more efficient drugs. Although some computational approaches have been developed to predict miRNA-drug associations, such associations rarely provide explicit information about which miRNAs and how they affect drug efficacy. On the other hand, there are rich information about which miRNAs affect the efficacy of which drugs in the literature. In this paper, we present a novel text mining approach, named as EmDL (Extracting miRNA-Drug interactions from Literature), to extract the relationships of miRNAs affecting drug efficacy from literature. Benchmarking on the drug-miRNA interactions manually extracted from MEDLINE and PubMed Central, EmDL outperforms traditional text mining approaches as well as other popular methods for predicting drug-miRNA associations. Specifically, EmDL can effectively identify the sentences that describe the relationships of miRNAs affecting drug effects. The drug-miRNA interactome presented here can help understand how miRNAs affect drug effects and provide insights into the mechanisms of drug actions. In addition, with the information about drug-miRNA interactions, more effective drugs or combinatorial strategies can be designed in the future. The data used here can be accessed at http://mtd.comp-sysbio.org/.


Clinical relevance of LINC00152 and its variants in western Chinese tuberculosis patients.
Recent studies indicate that the long intergenic non-coding RNA LINC00152 plays crucial roles in various human diseases. Here, we investigated whether levels of LINC00152 or its genetic variants correlate with the clinical features of tuberculosis (TB) in western Chinese patients. We genotyped the single nucleotide polymorphism LINC00152 rs80292941 in 476 TB patients and 475 healthy subjects using a custom-by-design 48-Plex SNPscan Kit, and measured relative levels of LINC00152 using RT-qPCR. We observed that LINC00152 levels were lower in TB patients than controls. Moreover, rs80292941 TT genotype carriers had the lowest LINC00152 levels among TB patients, and rs80292941 AA genotype carriers are more likely to suffer from hepatotoxicity induced by antituberculosis therapy [OR = 3.97, 95% = 1.53-10.13, p = 0.002]. Our findings strongly suggest that LINC00152 may promote TB progression and highlight rs80292941 single nucleotide polymorphism as a novel predisposition marker for antituberculosis drug-induced hepatotoxicity.


Automated in vivo 3D high-definition optical coherence tomography skin analysis system.
The in vivo assessment and visualization of skin structures can be performed through the use of high resolution optical coherence tomography imaging, also known as HD-OCT. However, the manual assessment of such images can be exhaustive and time consuming. In this paper, we present an analysis system to automatically identify and quantify the skin characteristics such as the topography of the surface of the skin and thickness of the epidermis in HD-OCT images. Comparison of this system with manual clinical measurements demonstrated its potential for automatic objective skin analysis and diseases diagnosis. To our knowledge, this is the first report of an automated system to process and analyse HD-OCT skin images.


N-(3-hydroxyhexanoyl)-l-homoserine lactone is the biologically relevant quormone that regulates the phz operon of Pseudomonas chlororaphis strain 30-84.
Phenazine production by Pseudomonas fluorescens 2-79 and P. chlororaphis isolates 30-84 and PCL1391 is regulated by quorum sensing through the activator PhzR and acyl-homoserine lactones (acyl-HSLs) synthesized by PhzI. PhzI from P. fluorescens 2-79 produces five acyl-HSLs that include four 3-hydroxy species. Of these, N-(3-hydroxyhexanoyl)-HSL is the biologically relevant ligand for PhzR. The quorum-sensing systems of P. chlororaphis strains 30-84 and PCL1391 have been reported to produce and respond to N-(hexanoyl)-HSL. These differences were of interest since PhzI and PhzR of strain 2-79 share almost 90% sequence identity with orthologs from strains 30-84 and PCL1391. In this study, as assessed by thin-layer chromatography, the three strains produce almost identical complements of acyl-HSLs. The major species produced by P. chlororaphis 30-84 were identified by mass spectrometry as 3-OH-acyl-HSLs with chain lengths of 6, 8, and 10 carbons. Heterologous bacteria expressing cloned phzI from strain 30-84 produced the four 3-OH acyl-HSLs in amounts similar to those seen for the wild type. Strain 30-84, but not strain 2-79, also produced N-(butanoyl)-HSL. A second acyl-HSL synthase of strain 30-84, CsaI, is responsible for the synthesis of this short-chain signal. Strain 30-84 accumulated N-(3-OH-hexanoyl)-HSL to the highest levels, more than 100-fold greater than that of N-(hexanoyl)-HSL. In titration assays, PhzR(30-84) responded to both N-(3-OH-hexanoyl)- and N-(hexanoyl)-HSL with equal sensitivities. However, only the 3-OH-hexanoyl signal is produced by strain 30-84 at levels high enough to activate PhzR. We conclude that strains 2-79, 30-84, and PCL1391 use N-(3-OH-hexanoyl)-HSL to activate PhzR.


μ-Opioid and 5-HT1A receptors in the dorsomedial hypothalamus interact for the regulation of panic-related defensive responses.
The dorsomedial hypothalamus (DMH) and the dorsal periaqueductal gray (DPAG) have been implicated in the genesis and regulation of panic-related defensive behaviors, such as escape. Previous results point to an interaction between serotonergic and opioidergic systems within the DPAG to inhibit escape, involving µ-opioid and 5-HT1A receptors (5-HT1AR). In the present study we explore this interaction in the DMH, using escape elicited by electrical stimulation of this area as a panic attack index. The obtained results show that intra-DMH administration of the non-selective opioid receptor antagonist naloxone (0.5 nmol) prevented the panicolytic-like effect of a local injection of serotonin (20 nmol). Pretreatment with the selective μ-opioid receptor (MOR) antagonist CTOP (1 nmol) blocked the panicolytic-like effect of the 5-HT1AR agonist 8-OHDPAT (8 nmol). Intra-DMH injection of the selective MOR agonist DAMGO (0.3 nmol) also inhibited escape behavior, and a previous injection of the 5-HT1AR antagonist WAY-100635 (0.37 nmol) counteracted this panicolytic-like effect. These results offer the first evidence that serotonergic and opioidergic systems work together within the DMH to inhibit panic-like behavior through an interaction between µ-opioid and 5-HT1A receptors, as previously described in the DPAG.


Hummingbirds arrest their kidneys at night: diel variation in glomerular filtration rate in Selasphorus platycercus.
Small nectarivorous vertebrates face a quandary. When feeding, they must eliminate prodigious quantities of water; however, when they are not feeding, they are susceptible to dehydration. We examined the role of the kidney in the resolution of this osmoregulatory dilemma. Broad-tailed hummingbirds (Selasphorus platycercus) displayed diurnal variation in glomerular filtration rate (GFR). During the morning, midday and evening, GFRs were 0.9+/-0.6, 1.8+/-0.4 and 2.3+/-0.5 ml h(-1), respectively. At midday, GFR increased linearly with increased water intake. During the evening, hummingbirds decreased renal fractional water reabsorption linearly with increased water intake. Broad-tailed hummingbirds appeared to cease GFR at night (-0.1+/-0.2 ml h(-1)) and decreased GFR in response to short-term ( approximately 1.5 h) water deprivation. GFR seems to be very responsive to water deprivation in hummingbirds. Although hummingbirds and other nectarivorous birds can consume astounding amounts of water, a phylogenetically explicit allometric analysis revealed that their diurnal GFRs are not different from the expectation based on body mass.


Accessory Genomes Drive Independent Spread of Carbapenem-Resistant Klebsiella pneumoniae Clonal Groups 258 and 307 in Houston, TX.
Carbapenem-resistant Klebsiella pneumoniae (CRKp) is an urgent public health threat. Worldwide dissemination of CRKp has been largely attributed to clonal group (CG) 258. However, recent evidence indicates the global emergence of a CRKp CG307 lineage. Houston, TX, is the first large city in the United States with detected cocirculation of both CRKp CG307 and CG258. We sought to characterize the genomic and clinical factors contributing to the parallel endemic spread of CG258 and CG307. CRKp isolates were collected as part of the prospective, Consortium on Resistance against Carbapenems in Klebsiella and other Enterobacterales 2 (CRACKLE-2) study. Hybrid short-read and long-read genome assemblies were generated from 119 CRKp isolates (95 originated from Houston hospitals). A comprehensive characterization of phylogenies, gene transfer, and plasmid content with pan-genome analysis was performed on all CRKp isolates. Plasmid mating experiments were performed with CG307 and CG258 isolates of interest. Dissection of the accessory genomes suggested independent evolution and limited horizontal gene transfer between CG307 and CG258 lineages. CG307 contained a diverse repertoire of mobile genetic elements, which were shared with other non-CG258 K. pneumoniae isolates. Three unique clades of Houston CG307 isolates clustered distinctly from other global CG307 isolates, indicating potential selective adaptation of particular CG307 lineages to their respective geographical niches. CG307 strains were often isolated from the urine of hospitalized patients, likely serving as important reservoirs for genes encoding carbapenemases and extended-spectrum β-lactamases. Our findings suggest parallel cocirculation of high-risk lineages with potentially divergent evolution. IMPORTANCE The prevalence of carbapenem-resistant Klebsiella pneumoniae (CRKp) infections in nosocomial settings remains a public health challenge. High-risk clones such as clonal group 258 (CG258) are particularly concerning due to their association with blaKPC carriage, which can severely complicate antimicrobial treatments. There is a recent emergence of clonal group 307 (CG307) worldwide with little understanding of how this successful clone has been able to adapt while cocirculating with CG258. We provide the first evidence of potentially divergent evolution between CG258 and CG307 with limited sharing of adaptive genes. Houston, TX, is home to the largest medical center in the world, with a large influx of domestic and international patients. Thus, our unique geographical setting, where two pandemic strains of CRKp are circulating, provides an indication of how differential accessory genome content can drive stable, endemic populations of CRKp. Pan-genomic analyses such as these can reveal unique signatures of successful CRKp dissemination, such as the CG307-associated plasmid (pCG307_HTX), and provide invaluable insights into the surveillance of local carbapenem-resistant Enterobacterales (CRE) epidemiology.


Wound healing revised: a novel reepithelialization mechanism revealed by in vitro and in silico models.
Wound healing is a complex process in which a tissue's individual cells have to be orchestrated in an efficient and robust way. We integrated multiplex protein analysis, immunohistochemical analysis, and whole-slide imaging into a novel medium-throughput platform for quantitatively capturing proliferation, differentiation, and migration in large numbers of organotypic skin cultures comprising epidermis and dermis. Using fluorescent time-lag staining, we were able to infer source and final destination of keratinocytes in the healing epidermis. This resulted in a novel extending shield reepithelialization mechanism, which we confirmed by computational multicellular modeling and perturbation of tongue extension. This work provides a consistent experimental and theoretical model for epidermal wound closure in 3D, negating the previously proposed concepts of epidermal tongue extension and highlighting the so far underestimated role of the surrounding tissue. Based on our findings, epidermal wound closure is a process in which cell behavior is orchestrated by a higher level of tissue control that 2D monolayer assays are not able to capture.


Therapeutic strategies targeting connexins.
The connexin family of channel-forming proteins is present in every tissue type in the human anatomy. Connexins are best known for forming clustered intercellular channels, structurally known as gap junctions, where they serve to exchange members of the metabolome between adjacent cells. In their single-membrane hemichannel form, connexins can act as conduits for the passage of small molecules in autocrine and paracrine signalling. Here, we review the roles of connexins in health and disease, focusing on the potential of connexins as therapeutic targets in acquired and inherited diseases as well as wound repair, while highlighting the associated clinical challenges.


Chromatin organization in the female mouse brain fluctuates across the oestrous cycle.
Male and female brains differ significantly in both health and disease, and yet the female brain has been understudied. Sex-hormone fluctuations make the female brain particularly dynamic and are likely to confer female-specific risks for neuropsychiatric disorders. The molecular mechanisms underlying the dynamic nature of the female brain structure and function are unknown. Here we show that neuronal chromatin organization in the female ventral hippocampus of mouse fluctuates with the oestrous cycle. We find chromatin organizational changes associated with the transcriptional activity of genes important for neuronal function and behaviour. We link these chromatin dynamics to variation in anxiety-related behaviour and brain structure. Our findings implicate an immediate-early gene product, Egr1, as part of the mechanism mediating oestrous cycle-dependent chromatin and transcriptional changes. This study reveals extreme, sex-specific dynamism of the neuronal epigenome, and establishes a foundation for the development of sex-specific treatments for disorders such as anxiety and depression.


Surgical tracheotomy performed with and without dual antiplatelet therapy.
Some patients who need dual antiplatelet therapy sometimes require tracheotomy. Aim of this study was to compare the rate of complications during and after surgical tracheotomy between patients requiring dual antiplatelet therapy and those without dual antiplatelet therapy. We retrospectively included 79 patients (62% men, mean age 64 ± 14 years) in the period 2007-2011. The following complications were analyzed: need for surgical revision within 24 hours after tracheotomy, need for bronchoscopy within 24 hour after tracheotomy, need for blood transfusion within 24 hours after tracheotomy, death attributed to tracheotomy and any complication attributed to tracheotomy. We compared patients where tracheotomy was performed while receiving dual antiplatelet therapy (n=27, 34%) to patients where tracheotomy was performed without dual antiplatelet therapy (n=52, 66%). Nonsignificant differences between the two groups were observed general characteristics. There were no statistically significant differences in complications after tracheotomy (surgical revision after tracheotomy p=0.63, bronchoscopy after tracheotomy p=0.74, blood transfusion after tracheotomy p=0.59, death attributed to tracheotomy p=1.00 and any complication attributed to tracheotomy p=1.00). The study shows that tracheotomy is safe in cardiac patients on dual antiplatelet therapy.


Performance of a PCR assay for detection of Pneumocystis carinii from respiratory specimens.
This study evaluates the performance of a PCR assay for the detection of Pneumocystis carinii from respiratory specimens that has been designed for use in the clinical microbiology laboratory. The test includes a simple method for nucleic acid extraction and amplification, a colorimetric probe hybridization technique for detection of amplicons, and an internal control to evaluate for the presence of inhibitors of amplification. Two hundred thirty-two clinical specimens (120 induced-sputum [IS] and 112 bronchoalveolar lavage [BAL] specimens) from 168 patients were tested by both immunofluorescent (direct fluorescent-antibody [DFA]) staining and PCR. Of the 112 BAL specimens, 17 were positive for P. carinii by DFA staining and PCR. An additional two specimens were DFA negative and PCR positive. For BAL specimens, the sensitivity and specificity of PCR compared to DFA were 100 and 98%, respectively. Eighteen IS specimens were positive for P. carinii by DFA, and 27 were positive by PCR. One of the 18 DFA-positive IS specimens was negative by PCR; this patient had just completed therapy for P. carinii pneumonia. Of the 10 specimens that were PCR positive and DFA negative, 4 were from patients who had a subsequent BAL specimen that was positive by DFA and PCR. For IS specimens, the sensitivity of DFA and PCR was 82 and 95%, respectively. The specificity of PCR for IS specimens was 94%. Due to the high sensitivity of PCR for the detection of P. carinii from IS specimens, a PCR-based diagnostic test may be a useful screening test and may alleviate the need for bronchoscopy in some patients.


Bacterial Membranes: Structure, Domains, and Function.
The bacterial cytoplasmic membrane is composed of roughly equal proportions of lipids and proteins. The main lipid components are phospholipids, which vary in acyl chain length, saturation, and branching and carry head groups that vary in size and charge. Phospholipid variants determine membrane properties such as fluidity and charge that in turn modulate interactions with membrane-associated proteins. We summarize recent advances in understanding bacterial membrane structure and function, focusing particularly on the possible existence and significance of specialized membrane domains. We review the role of membrane curvature as a spatial cue for recruitment and regulation of proteins involved in morphogenic functions, especially elongation and division. Finally, we examine the role of the membrane, especially regulation of synthesis and fluid properties, in the life cycle of cell wall-deficient L-form bacteria.


[The natural history of peripheral arteriopathy].
An the content of atherosclerosis, knowledge of the natural history of peripheral arteriopathy of the lower limbs is of fundamental importance. The authors review the literature involved; in particular they examine the prevalence of peripheral arteriopathy, its incidence and multimodal course in time. It is very interesting to state the cardiovascular morbility and mortality owing to pathology of the coronary district as well as the cerebral one during the course of peripheral arteriopathy. The literature conclusions are not univocal; this matter is principally due to different approach methodologies. As far as arteriopathy of inferior limbs is concerned, the literature shows that we can have a worsening in the local picture for 25% of the cases involved, considering the worst hypothesis; amputation involves at the most 5% of the cases. The real problem in these patients is the presence of arteriosclerotic disease involving other different vascular districts.


Mothers' perceptions concerning oral health of children and adolescents with Down syndrome: a qualitative approach.
The aim of this qualitative study was to investigate the perceptions of a group of mothers of children and adolescents with Down syndrome (DS) concerning the overall health and oral health of their children. The information was collected interviewing in depth 19 mothers using an open-ended orientation form. To investigate the perceptions of the mothers was carried out a thematic content analysis. Two general themes were addressed: mothers' perceptions concerning the health of the child with DS and mothers' opinion on the impact of oral health on the life of the child with DS. According to the interviews, for the mothers, overall health and oral health entail specificities associated mainly with the absence of illness, the performance of daily activities, and feelings of well-being. Mothers tended to hold themselves accountable for their children's health status. Within the situations these women experience, many of the interviewees reported difficulties in caring for their children's oral health. Factors linked to financial constraints, time, and access to healthcare referral services hamper the search for specialised dental care for individuals with special needs.


Youth and adult public views of dairy calf housing options.
The objective of this study was to explore views on dairy calf housing options among American youth and adults. Youth views were of interest because they are future consumers, yet their influence on livestock production practices is often overlooked. Participants 5 to 17 yr of age (n = 463) and 18 yr or older (n = 1,310) completed an in-person survey at the Minnesota State Fair (St. Paul, MN) in summer 2018. The survey was administered via Qualtrics survey software (Qualtrics, Provo, UT) using iPads (Apple, Cupertino, CA) and, in addition to collecting demographics, presented 3 images of calf housing options (individual, pair, or group) and asked participants to select their preferred option and indicate their reasoning for selection (youth), or acceptance for each option and reasoning for selection (adult). The PROC SURVEYFREQ of SAS (9.4; SAS Institute Inc., Cary, NC) was used for descriptive analysis. Rao-Scott chi-square tests (PROC SURVEYFREQ, SAS 9.4) were used to investigate relationships between demographics and housing preference or acceptance. Content analysis identified recurring themes to describe qualitative reasoning underlying dairy calf housing preference or acceptance. The median age of youth participants was 11 yr, 61% were female, 82% were urban residents, and 63% did not have prior experience handling agricultural animals, but 83% had visited a farm in the past. Median age range of adult participants was 45 to 54 yr, 65% were female, 82% urban residents, 41% completed a bachelor's degree, and 81% did not have prior experience handling agricultural animals, but 63% had visited a farm in the past. Overall, group housing was overwhelmingly preferred by youth participants (80.1%), followed by pair (14.3%) and individual housing (5.6%). Youth who chose group housing most commonly cited reasons related to increased socialization (71.4%) and space allowance (58.5%). Housing preference of youth was not associated with age, gender, or prior visits to a farm. However, rural youth more frequently preferred individual housing compared with urban youth (13.6 ± 4.5% SE vs. 5.1 ± 1.3%, respectively). Similarly, adult participants were most accepting of group housing for dairy calves (75.8% of participants), with reasons focused on calves' ability to socialize and access to increased space allowance. Adult males, rural residents, and individuals with previous livestock handling experience more frequently accepted individual calf housing compared with females, urban residents, and individuals without previous livestock handling experience. These findings suggest that housing systems that enable greater degrees of behavioral freedom for calves may be more socially sustainable for the dairy sector.


Dissociation between acid secretion and mucosal blood flow after treatment of rats with reserpine.
The correlation between acid secretion and mucosal blood flow in the gastric mucosa after administration of reserpine to rats was determined in an attempt to define the etiology of reserpine-induced gastric erosions. Although gastric acid output was increased gradually by administration of reserpine, mucosal blood flow was not significantly affected. The increase in acid output induced by reserpine was completely prevented by pretreatment with atropine. Reserpine-induced increase in acid secretion may have been mediated by the vagus nerves, probably as a result of central and/or peripheral diminution in noradrenergic inhibitory mechanisms. The dissociation between mucosal blood flow and acid secretion, resulting in a relative ischemic state in the gastric mucosa, may have occurred in part from reduced cardiac function after treatment with reserpine. Vagal stimulation induced a parallel increase in both acid secretion and mucosal blood flow in control rats. 6-Hydroxydopamine-induced sympathectomy did not increase mucosal blood flow to a degree corresponding to the increase in acid output by vagal stimulation. In animals treated with 6-hydroxydopamine, gastric erosions occurred. We conclude that reserpine increases acid output but without a parallel increase in the mucosal blood flow and that the erosions which occur are probably due to the relative ischemic state of the gastric mucosa.


Dentifrice abrasivity. The use of laser light for determination of the abrasive properties of different silicas. An in vitro study.
The abrasive properties of five different silicon dioxides were investigated using laser reflexion. The substances were milled, amorphous silica gels of which four were commercially available dentifrice ingredients (Syloblanc) and one an experimental product. The abrasion process was carried out on acrylic plates in a brushing machine using two series of slurries of the substances, with and without sodium lauryl sulphate. Significant differences in abrasivity of the substances were observed. When sodium lauryl sulphate was included, the rate of abrasion decreased for the Syloblanc substances but increased for the experimental substance. The contrast was primarily explained by the capability of the different substances to form stable foams owing to their thickening properties. The investigation confirmed that silicon dioxides exhibit a wide range of abrasivity and proved that sodium lauryl sulphate influenced the abrasion process.


Manifestation of grain boundaries in the transport properties of p-sexiphenyl films.
Direct current conductivity of p-sexiphenyl films with 0.2-2.5 microm thickness deposited on glass substrates was investigated at temperatures between 10 and 300 K. The molecular dynamics simulations and quantum chemical calculations of the experimentally observed conductivity have shown that there exist at least three different states of the films effectively contributing to the observed features of the dc conductivity: conductivity caused by proper crystalline states, conductivity originated from amorphous-like inter-grain region and caused by grain's boundary. Comparison of the experimental data and theoretically calculated dependences shows that the main contribution to the observed dc conductivity gives grain boundaries between polycrystalline grains and amorphous-like background, though the latter possesses a relatively low part of the total volume.


Effect of nitrous oxide on halothane-induced hepatotoxicity in hypoxic, enzyme-induced rats.
The degree of hepatotoxicity induced by halothane in hypoxic (14% inspired oxygen), enzyme-induced (phenobarbitone treatment for 10 days), male Sprague-Dawley rats was assessed by histological examination and analysis of serum aspartate aminotransferase (Asp. AT) concentrations. There was a significant direct, linear relationship between dose of halothane and histology score (P = 2.96 X 10(-5), and Asp. AT concentration (P = 4.8 X 10(-5) ). The effect of administration of nitrous oxide before (70%) and during (86%) hypoxia was tested for in the presence and absence of 0.75% halothane. Nitrous oxide was found to produce no effect in the absence of halothane, but to potentiate the hepatotoxicity of 0.75% halothane (P = 0.0003 for Asp. AT and 0.0016 for histology scores). The possible mechanisms of this effect are discussed.


Psychiatrist-wife-mother: some aspects of role integration.
Throughout her professional life the woman who chooses to combine the roles of psychiatrist, wife, and mother may find them not only compatible but complementary. If she can adopt a philosophy of life that permits her to function in these roles, and if those around her support her activities, she can perform with relative ease and proficiency. Her lifestyle must of necessity differ from that of her male colleagues, but differing lifestyles among members of a profession vitalize the field. A broad perspective is desirable, especially in a profession that deals with the emotional and mental lives of people. Married women and mothers afford such a broadened perspective to the field of psychiatry.


Incidental findings on integrated PET/CT that do not accumulate 18F-FDG.
The purpose of this study was to report the prevalence of abnormalities that do not show increased 18F-FDG uptake on the CT component of integrated PET/CT in patients with non-small cell lung cancer. Images from all PET/CT studies performed consecutively between April and October 2003 on patients with non-small cell lung cancer were retrospectively reviewed. All abnormalities present on the CT component of the PET/CT scans that did not show abnormally increased 18F-FDG uptake were documented. Three hundred twenty-one patients with non-small cell lung cancer (179 men, 142 women; mean age, 67 years; age range, 38-91 years) underwent initial staging (198/321 [62%]) or restaging (123/321 [38%]) PET/CT imaging during the study period. In 263 (82%) of the patients, CT showed 1,231 abnormalities that were not 18F-FDG avid. The abnormalities were located in the thorax (n = 650), abdomen and pelvis (n = 444), head and neck (n = 69), and bony skeleton (n = 68). In total, 298 (24%) of the abnormalities that were not 18F-FDG avid were located outside the range of a standard thoracic CT scan. The clinical importance of these abnormalities was classified as major (n = 48 [4%]), moderate (n = 465 [38%]), or minor (n = 718 [58%]). Four (1%) of the patients had findings of major clinical importance that did not show increased 18F-FDG uptake and were previously unsuspected. Among patients with non-small cell lung cancer undergoing PET/CT, there is a high prevalence of CT abnormalities that do not show correlative 18F-FDG avidity but that may be clinically important.


Frailty and its influence on mortality and morbidity in COPD: A Systematic Review and Meta-Analysis.
Frailty increases vulnerability to adverse outcomes. Long-term conditions increase the risk of frailty. We searched PubMed, Web of Science, The Cochrane Library, EMBASE from inception to March 2022. Quality assessment was conducted using the NOS. Data was analysed in a pooled a random-effects meta-analysis. Our primary outcome was the impact of frailty on mortality in adults with Chronic Obstructive Pulmonary Disease (COPD) diagnosis according to the guidelines. Secondary outcomes were: frailty and association with readmissions, hospitalisations, exacerbation rates, and prevalence of frailty in COPD. We identified 25 studies, with 5882 participants. The median prevalence of frailty was 47% (IQR, 39.3-66.3%, range 6.4-72%). There was an association between COPD patients living with frailty and increased risk of mortality versus COPD patients without frailty (pooled OR, 4.21 (95% CI 2.99-5.93, I2 55%). A descriptive analysis of relationship between frailty and hospital readmission and all cause hospitalization showed positive associations. The relationship between frailty and the risk of exacerbation showed a pooled OR, 1.45 (95% CI 0.37-5.70, I2 80%). Frailty is significantly associated with higher mortality risk in COPD. Frailty is common in patients with COPD and its measurement should be considered in clinical practice to better characterise COPD.


Self-assembly in mixed dialkyl chain cationic-nonionic surfactant mixtures: dihexadecyldimethyl ammonium bromide-monododecyl hexaethylene glycol (monododecyl dodecaethylene glycol) mixtures.
The self-assembly of dialkyl chain cationic surfactant dihexadecyldimethyl ammonium bromide, DHDAB, and nonionic surfactants monododecyl hexaethylene glycol, C(12)E(6), and monododecyl dodecaethylene glycol, C(12)E(12), mixtures has been studied using predominantly small-angle neutron scattering, SANS. The scattering data have been used to produce a detailed phase diagram for the two surfactant mixtures and to quantify the microstructure in the different regions of the phase diagram. For cationic-surfactant-rich compositions, the microstructure is in the form of bilamellar, blv, or multilamellar, mlv, vesicles at low surfactant concentrations and is in an L(beta) lamellar phase at higher surfactant concentrations. For nonionic-rich compositions, the microstructure is predominantly in the form of relatively small globular mixed surfactant micelles, L(1). At intermediate compositions, there is an extensive mixed (blv/mlv) L(beta)/L(1) region. Although broadly similar, in detail there are significant differences in the phase behavior of DHDAB/C(12)E(6) and DHDAB/C(12)E(12) as a result of the increasing curvature associated with C(12)E(12) aggregates compared to that of C 12E 6 aggregates. For the DHDAB/C(12)E(12) mixture, the mixed (blv/mlv) L(beta)/L(1) phase region is more extensive. Furthermore, C(12)E(12) has a greater impact upon the rigidity of the bilayer in the blv, mlv, and L(beta) regions than is the case for C(12)E(6). The general features of the phase behavior are also reminiscent of that observed in phospholipid/surfactant mixtures and other related systems.


Curative local excision for mucosal esophageal carcinoma.
We performed a curative local excision for mucosal esophageal carcinoma through a thoracotomy with the help of intraoperative endoscopy and Lugol's staining. The mucosa and submucosa containing the lesion is completely resected, with neither narrowing nor shortening of the esophagus left remaining.


Synthesis and pharmacological evaluation of [(3)H]HS665, a novel, highly selective radioligand for the kappa opioid receptor.
Herein we report the radiolabeling and pharmacological investigation of a novel radioligand, the N-cyclobutylmethyl substituted diphenethylamine [(3)H]HS665, designed to bind selectively to the kappa opioid peptide (KOP) receptor, a target of therapeutic interest for the treatment of a variety of human disorders (i.e., pain, affective disorders, drug addiction, and psychotic disorders). HS665 was prepared in tritium-labeled form by a dehalotritiated method resulting in a specific activity of 30.65 Ci/mmol. Radioligand binding studies were performed to establish binding properties of [(3)H]HS665 to the recombinant human KOP receptor in membranes from Chinese hamster ovary cells stably expressing human KOP receptors (CHOhKOP) and to the native neuronal KOP receptor in guinea pig brain membranes. Binding of [(3)H]HS665 was specific and saturable in both tissue preparations. A single population of high affinity binding sites was labeled by [(3)H]HS665 in membranes from CHOhKOP cells and guinea pig brain with similar equilibrium dissociation constants, Kd, 0.45 and 0.64 nM, respectively. Average receptor density of [(3)H]HS665 recognition sites were 5564 and 154 fmol/mg protein in CHOhKOP cells and guinea pig brain, respectively. This study shows that the new radioligand distinguishes and labels KOP receptors specifically in neuronal and cellular systems expressing KOP receptors, making this molecule a valuable tool in probing structural and functional mechanisms governing ligand-KOP receptor interactions in both a recombinant and native in vitro setting.


Direct adhesion between Cu foil and polytetrafluoroethylene without increasing surface roughness for high-frequency printed wiring boards.
Polytetrafluoroethylene (PTFE) serves as a suitable dielectric substrate for high-frequency printed wiring boards (PWBs) owing to its excellent properties at high frequency. However, to the best of our knowledge, no study has investigated the strong adhesion between PTFE and Cu foil with low surface roughness. Therefore, in this study, pure-PTFE comprising a weak boundary layer (WBL) on the surface and glass-cloth-containing PTFE (GC-PTFE), which did not contain a WBL, were subjected to heat-assisted plasma (HAP) treatment. Thereafter, we investigated the surface chemical bonding state, surface morphology, and adhesion properties of the as-prepared PTFE toward Cu foil with low surface roughness. As observed, oxygen-containing functional groups were generated on the HAP-treated PTFE, and the WBL in the as-received pure-PTFE was eliminated via HAP treatment. Moreover, the surface roughness of the HAP-treated PTFE did not increase compared to that of as-received PTFE. After performing thermal compression under atmospheric conditions, the adhesion strength of both HAP-treated pure-PTFE and GC-PTFE was ∼0.9 N mm-1. In addition, the adhesion strength of Cu/pure-PTFE and Cu/GC-PTFE increased after thermal compression under a reduced pressure, and the adhesion strength of 1 N mm-1 was obtained. Although the Cu foil was not roughened, Cu/PTFE realized strong adhesive strength. The developed method is advantageous because maintaining a low interface roughness is crucial for applying PTFE to manufacture high-frequency PWBs.


Imprinting and assisted reproductive technology.
In the past 25 years, the frequency of assisted reproductive technology (ART) births has increased rapidly to account for 1-2% of all births in many developed countries. ART procedures such as in vitro fertilization and intracytoplasmic sperm injection are generally considered to be safe, but recent studies suggest a small excess of birth defects and low-birth weight in ART children. In addition, several clinical studies have reported an increased frequency of ART conceptions among children with Beckwith-Wiedemann syndrome or Angelman syndrome caused by an imprinting defect. Although these studies require further confirmation, they are consistent with animal studies reporting disordered expression and epigenetic changes in imprinted genes following in vitro embryo culture. The absolute risk of an imprinting disorder after ART appears to be very small, but further data are required to determine whether the association between ART and human imprinting disorders reflects the effect of embryo culture (or some other aspect of ART) and/or a common mechanism for infertility and imprinting disorders. Retinoblastoma and neurodevelopmental defects have been only tentatively linked to ART, but in view of the role of epigenetic processes in the regulation of gene expression in development and cancer, further research is required into long-term health outcomes for ART children and the epigenetic consequences of ART protocols.


Human alkaline phosphatases. II. Metalloenzyme properties of the enzyme from human liver.
Human liver alkaline phosphatase is a metalloenzyme requiring Zn2 and Mg2 for full activity. Zn2 cannot be replaced by manganese, cobalt or calcium, whereas Mg2 can be replaced by manganese or calcium. The binding constants of the enzyme for different divalent cations were determined by the use of complexing agents. The enzyme is inhibited by a number of reducing and complexing agents such as 2-mercaptoethanol, cyanide, nitrilotriacetic acid and EDTA. From studies using these inhibitors it is suggested that there are different mechanisms of inhibition. Reversible inhibition occurs if the free Zn2 concentration is not significantly lower than 10(-12)M. Inhibition is irreversible at lower Zn2 concentrations. Evidence is given, that the human liver alkaline phosphatase possesses different zinc binding sites, which are responsible for the catalytic function and for the integrity of the enzyme structure.


The Metalloprotease, Mpr1, Engages AnnexinA2 to Promote the Transcytosis of Fungal Cells across the Blood-Brain Barrier.
Eukaryotic pathogens display multiple mechanisms for breaching the blood-brain barrier (BBB) and invading the central nervous system (CNS). Of the fungal spp., that cause disease in mammals, only some cross brain microvascular endothelial cells which constitute the BBB, and invade the brain. Cryptococcus neoformans, the leading cause of fungal meningoencephalitis, crosses the BBB directly by transcytosis or by co-opting monocytes. We previously determined that Mpr1, a secreted fungal metalloprotease, facilitates association of fungal cells to brain microvascular endothelial cells and we confirmed that the sole expression of CnMPR1 endowed S. cerevisiae with an ability to cross the BBB. Here, the gain of function conferred onto S. cerevisiae by CnMPR1 (i.e., Sc<CnMPR1> strain) was used to identify targets of Mpr1 that might reside on the surface of the BBB. Following biotin-labeling of BBB surface proteins, Sc<CnMPR1>-associated proteins were identified by LC-MS/MS. Of the 62 proteins identified several were cytoskeleton-endocytosis-associated including AnnexinA2 (AnxA2). Using an in vitro model of the human BBB where AnxA2 activity was blocked, we found that the lack of AnxA2 activity prevented the movement of S. cerevisiae across the BBB (i.e., transcytosis of Sc<CnMPR1> strain) but unexpectedly, TEM analysis revealed that AnxA2 was not required for the association or the internalization of Sc<CnMPR1>. Additionally, the co-localization of AnxA2 and Sc<CnMPR1> suggest that successful crossing of the BBB is dependent on an AxnA2-Mpr1-mediated interaction. Collectively the data suggest that AnxA2 plays a central role in fungal transcytosis in human brain microvascular endothelial cells. The movement and exocytosis of Sc<CnMPR1> is dependent on membrane trafficking events that involve AnxA2 but these events appear to be independent from the actions of AnxA2 at the host cell surface. We propose that Mpr1 activity promotes cytoskeleton remodeling in brain microvascular endothelial cells and thereby engages AnxA2 in order to facilitate fungal transcytosis of the BBB.


2-Chlorodeoxyadenosine as initial therapy for advanced low grade lymphomas.
In order to evaluate efficacy and safety of 2-chlorodeoxyadenosine (2-CdA) as primary therapy of low grade non Hodgkin's lymphoma, a phase II trial of 2-CdA was initiated in patients with previously untreated advanced low grade lymphoma. Fourteen previously untreated patients with stage III and IV low grade lymphoma were enrolled. Patients received 2-CdA 0.1 mg/kg/d by continuous infusion for 7 days every 28 days, for 1-6 cycles of therapy (median 3.5). Results showed one complete response and nine partial responses for an overall response rate of 75%. Until now there have only been three responding patients who have had progressive disease, with a median follow-up time of 18 months. The major toxicity was bone marrow suppression and nine patients stopped therapy prior to a planned six cycles because of prolonged cytopenias, primarily thrombocytopenia. Fifteen of 50 cycles of therapy were associated with neutropenic febrile episodes and there was one septic death secondary to Listeriosis. It seems from this small group of patients that 2-CdA is an active agent in previously untreated low grade lymphoma. Myelosuppression is cumulative and limits the number of cycles of therapy which can be given. Future exploration of different doses or schedules of this active agent is warranted.


Application of Urine and Copro Antigen Assays after Primary Infection and Drug Treatment in an Experimental Opisthorchiasis Animal Model.
Infection by Opisthorchis viverrini causes significant health problems, including cholangiocarcinoma (CCA); thus control and elimination of this trematode is an important strategy for the reduction of CCA. Currently, urine and copro antigen detection is more sensitive than parasitological examination of the feces for the diagnosis of opisthorchiasis. Given limitations in human studies, we used an animal model to quantify the parasite antigen profiles in urine and feces in O. viverrine-infected hamsters, and postdrug treatment. The positive detections of O. viverrini antigen began from week 1 in urine and week 2 in feces after infection until week 28 of the study. The recoveries of O. viverrini worms were detected starting from week 1 and eggs of O. viverrini were detected in feces from week 3 after infection and remained detectable throughout the study period. There was a significant positive correlation of urine and copro antigen levels with the number of fecal egg counts (P < 0.01) and worm recovery (P < 0.01). In the drug-treatment experiment, treatment of infected hamsters with praziquantel significantly reduced worm burden, fecal egg output, and antigen in urine and feces compared with the untreated controls (P < 0.001). At 4 weeks posttreatment, the egg and worm reduction rates were 100% and 95.5%, respectively. The positive antigen detections in urine and feces corresponded with partial worm clearance from praziquantel treatment. This study demonstrated a direct link of urine and copro antigen tests with worms infecting the liver thereby reaffirming the reliability of urine and copro antigen assay in opisthorchiasis diagnosis.


[Effect of electroacupuncture and moxibustion preconditioning on blood endothelin and creatine kinase contents and myocardial HSP 70 expression in rabbits with myocardial ischemia-reperfusion injury].
To observe the effect of electroacupuncture (EA) and moxibustion (Moxi) preconditioning of bi- lateral "Neiguan" (PC 6) on plasma endothelin (ET) and serum creatine kinase (CK) contents and myocardial hot shock protein 70 (HSP 70) expression in myocardial ischemia-reperfusion injury (MIRI) rabbits, so as to revel their mechanisms underlying prevention of myocardial ischemia. A total of 72 New Zealand rabbits were randomly divided into sham operation, MIRI model, EA preconditioning and Moxi preconditioning groups (n = 18/group). Each group was further divided into 0 h, 24 h and 48 h (time-point) subgroups (n=6 in each subgroup). The MIRI model was established by occlusion of the anterior descending branch of the left coronary artery for 40 min and reperfusion for 60 min. The contents of plasma ET and serum CK were detected by ELISA, and myocardial HSP 70 expression was detected by immunohistochemistry. EA and Moxi preconditioning were respectively applied to bilateral PC 6 for 20 min, once daily for 5 days. Following MIRI, contents of plasma ET and serum CK contents were significantly increased at 0 h, 24 h and 48 h in comparison with the sham group (P<0.01, P<0.05), while myo- cardial HSP 70 expression at the 3 time-points was moderately increased (P>0.05). Compared with the model groups, plasma ET contents at both 24 h and 48 h in the EA preconditioning group and at 48 h in the Moxi preconditioning group, CK contents at both 24 h and 48 h only in the EA preconditioning group were significantly down-regulated (P<0.01, P<0.05). Myocardial HSP 70 expression levels in the EA and Moxi preconditioning groups were considerably up-regulated at the three time-points in comparison with the model group(P<0.05, P<0.01). Acupuncture and moxibustion pretreatment may suppress MIRI-induced increase of plasma ET and serum CK and up-regulate myocardial HSP 70 protein expression in MIRI rabbits, suggesting a preventive protection action on ischemic myocardium.


Diselenide Covalent Allosteric Inhibitors of Glutaminase with Strong In Vivo Anticancer Activity.
Allosteric glutaminase inhibitors demonstrate inhibition of glutamine-dependent cancer cells with low general drug toxicity, but have issues with efficacy in vivo. Here, we designed a series of diselenide compounds with 6 atoms in the middle, aiming to target the allosteric site of kidney type glutaminase (KGA) with a covalent linkage to strengthen the interaction. Proteomic analysis demonstrated that the diselenide compounds cross-linked with the Lys320 residue at the KGA allosteric site; this was confirmed by the KGA K320A mutant which showed essentially no binding to the diselenide. Further, structure-activity relationship (SAR) analysis demonstrated that growth inhibition correlated well with KGA inhibition and was enhanced by thioredoxin reductase (TrxR) inhibition. Interestingly, diselenide compounds showed no inhibition of glutamate dehydrogenase (GDH), indicating some enzyme selectivity. Importantly, the designed novel diselenides are glutaminase allosteric inhibitors that showed in vivo efficacy and survival in the xenograft animal model.


Plastome Evolution in Dolomiaea (Asteraceae, Cardueae) Using Phylogenomic and Comparative Analyses.
Dolomiaea is a medicinally important genus of Asteraceae endemic to alpine habitats of the Qinghai-Tibet Plateau (QTP) and adjacent areas. Despite significant medicinal value, genomic resources of Dolomiaea are still lacking, impeding our understanding of its evolutionary history. Here, we sequenced and annotated plastomes of four Dolomiaea species. All analyzed plastomes share the gene content and structure of most Asteraceae plastomes, indicating the conservation of plastome evolutionary history of Dolomiaea. Eight highly divergent regions (rps16-trnQ, trnC-petN, trnE-rpoB, trnT-trnL-trnF, psbE-petL, ndhF-rpl32-trnL, rps15-ycf1, and ycf1), along with a total of 51-61 simple sequence repeats (SSRs) were identified as valuable molecular markers for further species delimitation and population genetic studies. Phylogenetic analyses confirmed the evolutionary position of Dolomiaea as a clade within the subtribe Saussureinae, while revealing the discordance between the molecular phylogeny and morphological treatment. Our analysis also revealed that the plastid genes, rpoC2 and ycf1, which are rarely used in Asteraceae phylogenetic inference, exhibit great phylogenetic informativeness and promise in further phylogenetic studies of tribe Cardueae. Analysis for signatures of selection identified four genes that contain sites undergoing positive selection (atpA, ndhF, rbcL, and ycf4). These genes may play important roles in the adaptation of Dolomiaea to alpine environments. Our study constitutes the first investigation on the sequence and structural variation, phylogenetic utility and positive selection of plastomes of Dolomiaea, which will facilitate further studies of its taxonomy, evolution and conservation.


[Results of ligature of the upper testicular vein in idiopathic varicocele and subfertility].
The results of a total of 102 varicocele operations, 83 of which were performed because of subfertility and a desire to have children, are presented. In 3% of the cases a recidive operation was necessary because of persistent varicocele. 55 patients with limited fertility were subsequently examined for volume, density and form of sperm, total motility and propulsive motility. Whereas the volume of sperm and the total motility remained unchanged, the density and form of sperm and the propulsive motility had improved significantly 9 months after the operation. Among the men followed up the conception rate was 20%.


Effects of cigarette smoking and short-term smoking cessation on airway responsiveness to inhaled methacholine.
Threshold of airway responsiveness to methacholine aerosol was determined in 53 apparently healthy persons. In 18 nonallergic nonsmokers matched according to sex and age to 18 nonallergic smokers, the mean methacholine threshold of airway response (T), as measured using partial flow-volume curves, had a tendency to be greater in nonsmokers, but the difference was not significant for the group as a whole; it was, however, significant for a subset of 9 matched pairs with a cigarette consumption greater than 10 pack-years (mean T nonsmokers, 2.8 mg/ml; smokers, 0.3; p = 0.036). In 17 smokers who stopped smoking for 99 days in average, T was not significantly different for the group as a whole, although the majority of the smokers reported improvement of respiratory symptoms after cessation of smoking. The results of this study indicate that cigarette smoking is associated with increased airways responsiveness to inhaled methacholine and that this effect is dose related.


Cross-Links-Entanglements Integrated Networks Contributing to Highly Resilient, Soft, and Self-Adhesive Elastomers with Low Hysteresis for Green Wearable Electronics.
Green wearable electronics are attracting increasing attention to eliminate harmful byproducts generated by traditional devices. Although various degradable materials have been explored for green wearable electronics, the development of degradable elastomers with integrated characteristics of low modulus, self-adhesion, high resilient, and low hysteresis remains challenging. In this work, a degradable elastomer poly(1,8-octanediol-co-citrate-co-caprolactone) (POCL) is reported, in which a loosely cross-linked network contains plenty of entangled flexible chains. The coexistence of covalent cross-links and entanglements of long polymer chains endows the elastomer with good resilience and low hysteresis, in addition to low modulus and self-adhesion. Taking advantage of the unique mechanical properties, epidermal strain sensors based on the POCL elastomer were prepared, which exhibited good adhesion to human skin, high sensitivity, high response rate, and excellent fatigue resistance. We also fabricated stretchable electroluminescent devices using this degradable elastomer and demonstrated the recyclability of the nondegradable materials in the electronic device.


Identification of Biomarkers for Resistance to Fusarium oxysporum f. sp. cubense Infection and in Silico Studies in Musa paradisiaca Cultivar Puttabale through Proteomic Approach.
Panama wilt caused by Fusarium oxysporum f. sp. cubense (Foc) is one of the major disease constraints of banana production. Previously, we reported the disease resistance Musa paradisiaca cv. puttabale clones developed from Ethylmethanesulfonate and Foc culture filtrate against Foc inoculation. Here, the same resistant clones and susceptible clones were used for the study of protein accumulation against Foc inoculation by two-dimensional gel electrophoresis (2-DE), their expression pattern and an in silico approach. The present investigation revealed mass-spectrometry identified 16 proteins that were over accumulated and 5 proteins that were under accumulated as compared to the control. The polyphosphoinositide binding protein ssh2p (PBPssh2p) and Indoleacetic acid-induced-like (IAA) protein showed significant up-regulation and down-regulation. The docking of the pathogenesis-related protein (PR) with the fungal protein endopolygalacturonase (PG) exemplify the three ionic interactions and seven hydrophobic residues that tends to good interaction at the active site of PG with free energy of assembly dissociation (1.5 kcal/mol). The protein-ligand docking of the Peptide methionine sulfoxide reductase chloroplastic-like protein (PMSRc) with the ligand β-1,3 glucan showed minimum binding energy (-6.48 kcal/mol) and docking energy (-8.2 kcal/mol) with an interaction of nine amino-acid residues. These explorations accelerate the research in designing the host pathogen interaction studies for the better management of diseases.