Myelodysplastic syndrome and pregnancy: the Mayo Clinic experience.
Although the myelodysplastic syndrome (MDS) is most common in the elderly, younger patients, including women of child-bearing age, may be affected. The association of MDS with pregnancy appears to be very rare: fewer than 25 cases have been reported. We report the outcomes of seven pregnancies in four women seen at the Mayo clinic between 1983 and 2000. Three of the women were found to have MDS when an abnormal complete blood count was detected during routine prenatal care. The fourth patient had an apparently congenital MDS, and suffered three spontaneous abortions before undergoing premature menopause as a result of pelvic irradiation for vulvar cancer. We discuss some of the unique concerns regarding pregnant patients with MDS. As women give birth at older ages and as more young persons survive cancer, MDS and pregnancy are likely to be seen together with increasing frequency.


Induction of vascular injury by Pseudomonas aeruginosa cytotoxin in rabbit lungs is associated with the generation of different leukotrienes and hydroxyeicosatetraenoic acids.
Pseudomonas aeruginosa cytotoxin, a transmembrane pore-forming protein, causes an increase in pulmonary microvascular permeability with subsequent lung edema formation, possibly related to the induction of arachidonic acid (AA) lipoxygenase products. To investigate this, isolated rabbit lungs were perfused with cytotoxin-containing buffer (6.5 and 13 micrograms of toxin/ml). A severalfold increase in the capillary filtration coefficient was induced, both preceded and accompanied by a marked time- (15-60 min) and dose-dependent release of cysteinyl leukotrienes (LT), LTB4, and 5-, 12-, and 15-hydroxyeicosatetraenoic acids (HETEs) into the lung perfusate. In the bronchoalveolar lavage fluid, corresponding AA-derived products were detected; the total sum of HETEs surpassed that of cysteinyl LTs in this compartment. The lipoxygenase inhibitors AA861 (10 microM) and nordihydroguaiaretic acid (100 microM) and EGTA (5 mM) suppressed the intravascular and alveolar liberation of all 5-lipoxygenase-derived AA metabolites, paralleled by a marked reduction and retardation of microvascular permeability increase (AA861). It thus seems that Pseudomonas cytotoxin induces generation of LTs and HETEs in rabbit lungs that may contribute to the development of pulmonary microvascular injury evoked by this bacterial agent.


The problem of "chronic mastitis" with epitheliosis.
The incidence of breast cancer complicating chronic mastitis with epitheliosis has been reported to be as high as 45% and as low as 6%. At least part of this discrepancy appears to be due to difficulty in distinguishing between benign and malignant intraduct epithelial proliferation.A small series is presented here in which the incidence of invasive cancer after local excision of breast tissue showing chronic mastitis with epitheliosis was nil. It is concluded that it is necessary to follow up larger series of cases longer before it can be said that severe epitheliosis and borderline lesions should in all cases be treated by anything more radical than local excision.


Building community capacity for health promotion: a challenge for public health nurses.
The centennial celebration of public health nursing is a strong reminder of the tradition and practice of public health nursing's commitment to communities. Partnerships with communities give public health nurses fiduciary responsibility to be actively involved in public health reform to advance health promotion and health protection. Public health nurses must rise to the challenge to build community capacity through facilitating community participation, enhancing community health services, and coordinating public policy to achieve core public health responsibilities of assessment, policy, and assurance. This paper explicates strategies for building community capacity for health promotion.


Experimental vitamin C depletion and supplementation in young men. Nutrient interactions and dental health effects.
Biochemical indices of AA clearly showed that the young men in this study were brought into various states of AA depletion and repletion according to their dietary AA intakes. While previous studies have postulated that supplemental intakes of AA may adversely affect body status of vitamins B6 and B12, we found no changes in the B vitamin status of the young men receiving varying AA intakes. Moderate AA supplementation (605 mg/day) showed no antagonistic effect on markers of vitamins B6 and B12. Blood markers of fat-soluble vitamins A and E and iron status were not affected by AA intakes. The propensity of the gingiva to become inflamed or bleed on probing was reduced after normal (65 mg/day) AA intakes as compared to deficient (5 mg/day) intakes and upon supplementary (605 mg/day) AA intakes as compared to normal intakes. The results suggest that AA status may influence early stages of gingival inflammation and crevicular bleeding, and warrant further study of the relationship between AA and periodontal health.


Metabolic considerations of drugs in the treatment of allergic diseases.
The clinical management of allergic diseases involves a number of drugs, most of which are extensively metabolized. This review aims to analyze the metabolism and the clinical implications of altered metabolism for these drugs. The authors present an overview of current knowledge of the metabolism of: antihistamine drugs, glucocorticoids, inhaled β-2 bronchodilators, anticholinergics and other drugs used in allergic diseases, such as cromoglycate, omalizumab, montelukast and epinephrine. Polymorphic drug metabolism is relevant for chlorpheniramine, loratadine and montelukast. Inhibition of drug metabolism is relevant for loratadine, methylprednisolone, fluticasone, mometasone, triamcinolone or prednisolone. Polymorphic pre-systemic metabolism may be relevant to budesonide, fluticasone, beclomethasone, mometasone or salmeterol. The authors also discuss the current information on gene variations according to the 1,000 genomes catalog and other databases. Finally, the authors review the clinical implications of these variations with a particular regard to drugs used in the management of allergic diseases. Most drugs used in allergic diseases are extensively metabolized. Drug interaction or adverse reactions related to altered metabolism are relevant issues that should be considered in the management of allergic diseases. However, much additional research is required before defining pharmacogenomic biomarkers for the management of drugs used in allergic diseases.


Characterization of heterotrimeric collagen molecules in a sea-pen (Cnidaria, Octocorallia).
The collagen of a primitive invertebrate, the sea-pen Veretillum Cnidaria, Octocorallia), was studied with respect to its molecular-chain composition. The soft extracellular tissues (mesoglea) were solubilized by limited pepsin proteolysis and the collagen was isolated by selective precipitation at 0.7 M NaCl under acidic conditions. The pepsinized molecules were 260 nm in length, as demonstrated by electron microscope studies of rotary-shadowed molecules and of the segment-long-spacing crystallites obtained by dialysis against ATP. SDS/PAGE of the extract produced two main bands susceptible to bacterial collagenase, designated as the alpha 1 and alpha 2 chain, which were differentiated clearly by their CNBr cleavage products and the higher glycosylation rate of the alpha 2 chain. The latter finding corresponds with the high hydroxylysine content of the alpha 2 chain. The alpha 1/alpha 2 chain ratio observed in SDS/PAGE and the fact that only one peak was obtained by concanavalin-A affinity chromatography of a non-denatured 0.7 M NaCl extract demonstrate the alpha 1 [alpha 2]2 molecular structure of this collagen. These results contrast with data on the structure of other coelenterates (i.e. [alpha]3 for sea anemone collagen molecules and alpha 1 alpha 2 alpha 3 for jellyfish collagen molecules). They are discussed in relation to the evolution of collagen.


Writing manuscripts describing clinical trials: a guide for pharmacotherapeutic researchers.
Once researchers have completed a clinical trial and analyzed the data, they have a duty to make the results known to their peers by writing a manuscript suitable for publication in a biomedical journal. Before beginning any writing, those involved in the clinical drug trial first need to decide among themselves who is to be the first author and secondary authors, the readership they want to influence, and the most appropriate target journal to reach this readership. For content and formatting of the manuscript, writers need to carefully follow the instructions for authors as stipulated by the target journal. In general, a manuscript based on a clinical trial is presented sequentially in four sections: Introduction, Methods, Results, and Discussion (IMRAD). The introduction concisely presents background information about the topic that was researched in the clinical trial, provides the study hypothesis, and describes the study rationale, purpose, and objectives. The Methods section delineates the study design, subject/patient selection process, procedures, end points, and types of analysis conducted in the clinical trial to investigate the study hypothesis. The Results section presents the findings of the clinical trial, and the Discussion section interprets the meaning of these findings, assesses how the findings answer the study hypothesis, and compares the study data with findings reported in earlier studies. Writers should select a title for the clinical trial manuscript that is fewer than 10 words and which embodies the essence of the study findings clearly and specifically without being sensationalistic. Writers should create the abstract last; the abstract should provide an overview of the manuscript and stimulate readers' interest. Overall, following the above principles in writing a manuscript based on a clinical drug trial will make the actual writing easier and more enjoyable, as well as increase the possibility of the manuscript being accepted for publication.


Tryptophan emission from myosin subfragment 1: acrylamide and nucleotide effect monitored by decay-associated spectra.
The intrinsic emission due to the tryptophan residues of the heavy chain of myosin subfragment 1 can be divided into three classes, on the basis of spectra associated with lifetimes of 0.72, 4.5, and 8.8 ns. The percentage contribution of each component to the total emission is 9%, 45%, and 46%, respectively. Low concentrations of acrylamide quench the long component with a quenching constant of 14.9 +/- 2.9 M-1, while the intermediate and short components are unaffected. Upon addition of ATP the total intensity increases by 17%. The bulk of this increase is in the intermediate lifetime component. Quenching by acrylamide in the presence of ATP again quenches only the long lifetime component, indicating that the tryptophan residues affected by ATP binding are not accessible to the solvent.


[Oral health in care-dependent elderly: an inventory in a nursing home in the north of the Netherlands].
When people grow old and dependent on care, it usually becomes increasingly difficult to maintain oral health. The aim of this study was to assess what changes have taken place during the last ten years in oral health and the need for dental care among patients who were admitted to a nursing home between 2002 and 2012. Results revealed that the number of patients with remaining teeth increased significantly, from 7.9% to 28.7%, and that the number of patients with implants increased from 0.0% to 3.2%. More than 80% of the patients had moderate to poor oral health upon arrival. Moreover, almost half of the patients were revealed to be non-cooperative for evaluation and/or treatment, especially those who had remaining teeth. The expectation is that as a result of the increasing number of care-dependent elderly with remaining teeth in combination with poor oral health, the demand for dental care for care-dependent elderly in nursing homes will increase harply in the coming years.


Nucleotide sequence of the putative human tyrosinase pseudogene.
We have cloned and sequenced the putative human tyrosinase pseudogene, which shares more than 98% nucleotide homology with exon 4 and exon 5 of the human tyrosinase gene including their flanking introns. Because of such a high homology, both the tyrosinase gene and its pseudogene could be amplified from genomic DNA by polymerase chain reaction. The nucleotide sequences presented thus enable us to discriminate the tyrosinase gene from its related sequences and are invaluable for a gene diagnosis of oculocutaneous albinism.


[Progress in molecular genetics of epilepsy].
Epilepsy is a group of disorders characterized by recurrent seizures. The etiologies of idiopathic epilepsy commonly have a genetic basis. Gene mutations causing several of the inherited epilepsies have been mapped. In this review, the authors summarize the available information on the genetic basis of human epilepsies and epilepsy syndromes, emphasizing how genetic defects may correlate with the pathophysiological mechanisms of brain hyperexcitability and gene defects can lead to epilepsy by altering multiple and diverse aspects of neuronal function.


Health evaluation of pampas deer (Ozotoceros bezoarticus celer) at Campos del Tuyú Wildlife Reserve, Argentina.
Samples from 14 free-ranging pampas deer (Ozotoceros bezoarticus celer) were collected in 1995 and 1998, at Campos del Tuyú Wildlife Reserve, Buenos Aires, Argentina. Hematology, serum chemistries, minerals and metals, and fecal parasites were analyzed. In addition, fecal ova and parasites were evaluated seasonally during 1998-2000. Serology for infectious diseases included blue-tongue, brucellosis, bovine respiratory syncytial virus infection, bovine viral diarrhea/mucosal disease, infectious bovine rhinotracheitis, Johne's disease (paratuberculosis), foot and mouth disease (FMD), leptospirosis (eight serovars), epizootic hemorrhagic disease, and parainfluenza-3 (PI-3). Three (21%) pampas deer had antibodies to Leptospira spp. and six (43%) to PI-3 virus. Serologic results for all other infectious agents were negative. Domestic cattle (n = 27) included in this study for comparison had antibodies to Leptospira, infectious bovine rhinotracheitis virus, bovine viral diarrhea virus, and PI-3 virus (74-100% of tested animals) and one animal (4%) to Brucella sp. All cattle had antibodies to FMD virus attributable to vaccination. This study provides the first data on the health status of the southernmost sub-species of pampas deer.


Long-range ordering of turbulent stresses in two-dimensional flow.
Using filter-space techniques, we study the spatial structure of the turbulent stress that couples motion on different length scales in a quasi-two-dimensional laboratory flow. As the length scale increases, we observe the appearance of long-range, system-spanning spatial order of this stress, even though the flow field remains disordered. Suggestively, this ordering occurs only in the range of scales over which we find net inverse energy transfer to larger scales. However, we find that a field built from wave vectors with random phases also displays ordering, suggesting that at least some of the ordering we observe is purely kinematic. Our results help to clarify the role played by geometric alignment in the turbulent energy cascade and highlight the importance of the scale-dependent rate of strain in the energy-transfer process.


IDENTIFYING INDIVIDUAL STRESS SUSCEPTIBILITY USING GENOMIC AND IMMUNE BIOMARKERS.
Significant adverse impact of various forms of psychological stress on susceptibility to infection, altered wound healing, increased prevalence and severity of hypersensitivity diseases, and even increased mortality in cancer patients has been well described. Yet these observations are limited by often unpredictable individual responses to various stressful situations. These associations are further clouded by natural variability among diverse forms of and responses to chronic life stressors and associated comorbid conditions. This is particularly true for inflammatory diseases where gene/external environmental interactions are well-described. What is much less understood is gene-internal environmental (i.e., psychological) interactions that commonly affect disease activity and possible susceptibility. We have used selected single nucleotide polymorphisms of stress hormone and regulatory cytokine receptors to categorize both baseline and stress-associated immune parameters for the a priori classification of individuals with the most stress susceptible immune systems to identify those most responsive to a stress reduction/management-based intervention.


A Tutorial Review on Clinical Acoustic Markers in Speech Science.
The human voice changes with the progression of neurological disease and the onset of diseases that affect articulators, often decreasing the effectiveness of communication. These changes can be objectively measured using signal processing techniques that extract acoustic features. When measuring acoustic features, there are often several steps and assumptions that might be known to experts in acoustics and phonetics, but are less transparent for other disciplines (e.g., clinical medicine, speech pathology, engineering, and data science). This tutorial describes these signal processing techniques, explicitly outlines the underlying steps for accurate measurement, and discusses the implications of clinical acoustic markers. We establish a vocabulary using straightforward terms, provide visualizations to achieve common ground, and guide understanding for those outside the domains of acoustics and auditory signal processing. Where possible, we highlight the best practices for measuring clinical acoustic markers and suggest resources for obtaining and further understanding these measures.


Impact of vascular risk factors on clinical outcome in elderly patients with depression receiving electroconvulsive therapy.
Although electroconvulsive therapy (ECT) is a highly effective, safe, and well-tolerated antidepressant treatment for late-life depression (LLD), there is large variability in response rates across individuals. We hypothesized that these variations would be in part explained by the level of vascular risk in this population. We therefore compared response rates to ECT in patients with LLD presenting with or without vascular risk factors (VRF). 52 patients with LLD (age > 55) who received a course of ECT were separated into 2 groups according to the presence of VRF (n = 20) or not (n = 32). Framingham score (10-year risk for developing a coronary heart disease) was calculated for each patient. Our primary outcome was the number of responders to ECT in each group (defined as at least 50% decrease of the Montgomery-Åsberg Depression Rating Scale score following ECT course). Scores at the self-rated Beck Depression Inventory are also reported. Patients with VRF presented significant lower response rates to ECT (12 out of 20; 60%) than patients without VRF (30 out of 32; 94%; p = 0.004). A negative correlation was found between Framingham score and changes in depression scores pre/post ECT (r = -0.42; p = 0.0039). Our study was limited by sample size and retrospective design. Patients with LLD and VRF showed lower response rates to ECT than those without VRF. The more the VRF increased, the less the antidepressant effect of ECT was observed. Results are discussed in light of the role of apathy in clinical response to ECT.


[Predictive value of serum glycosylated hemoglobin for the onset of nonalcoholic fatty liver disease].
Objective: To discuss the affect of glycosylated hemoglobin (HbA1c) level for the onset of nonalcoholic fatty liver disease (NAFLD) in cohort population. Methods: An epidemiological survey of the relationship between HbA1c and NAFLD conducted in 2012 was based at cohort baseline, and three follow-up sessions conducted in 2013, 2014 and 2015. In total 2 811 subjects were included in the study after exclusion of NAFLD patients at baseline and those who lost their lives due to relocation, and death. The Cox proportional hazard model was used to analyze the relationship between glycosylated hemoglobin and other risk factors of NAFLD. Continuous variables were compared using the t-test or the Mann-Whitney test. χ (2)-test was used for the measurement of categorical data. Results: A total of 2 811 subjects with mean age of 59 (58.2±9.8) years old, including 1 664 males and 1 147 females. Age, waist circumference, body mass index, systolic blood pressure, γ-glutamyltransferase and fasting blood glucose level of HbA1c abnormal group were higher than normal group. The incidence of NAFLD in the abnormal HbA1c level group (25.4%) was higher than normal group (14.9 %), and diastolic blood pressure, high-density lipoprotein cholesterol was lower than normal group and the differences were statistically significant. During the three follow-up intervals, there were 440 new cases of NAFLD, consisting 285 males and 155 females with cumulative incidence of 15.7% (440/2 811). Multivariate Cox regression analysis showed that patients with elevated HbA1c had a higher risk of developing NAFLD (HR 1.796; 95% CI 1.335~2.418; P < 0.01), and the increased HbA1c level after adjustment for gender, age, and metabolic syndrome-related factors remained an independent risk factors for NAFLD (HR 1.580; 95.0% CI 1.161-2.152; P < 0.01). Conclusion: An elevated HbA1c levels have a positive predictive value for the onset of NAFLD.


Olfactory identification deficits in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy.
Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is an inherited angiopathy caused by mutations of the Notch 3 gene. Olfactory identification deficits are present in a number of neurodegenerative disorders. However, olfaction has not been investigated in CADASIL. The aim of the present study was to assess olfactory identification in CADASIL and to determine whether there is an association between olfactory identification and the frontotemporal lobe. Twenty-seven patients and 27 control subjects had an olfactory identification test and neuropsychological testing. Brain MRIs were obtained from 25 patients. Involvement of frontal white matter, anterior temporal white matter and the external capsule were measured. Olfactory identification scores were lower in CADASIL patients than in healthy comparison subjects. The Mini-Mental Status Examination (MMSE) and semantic Controlled Oral Word Association Test (COWAT) were also affected. In CADASIL patients, olfactory identification scores correlated with MMSE, COWAT scores and Scheltens' scores from frontal white matter. The tendency for an association between olfactory identification scores and Scheltens' scores from anterior temporal white matter was also observed. Our findings suggest that olfactory identification deficits may be a sensitive indicator of frontotemporal dysfunction in CADASIL.


Does increasing community and liquor licensees' awareness, police activity, and feedback reduce alcohol-related violent crime? A benefit-cost analysis.
Approximately half of all alcohol-related crime is violent crime associated with heavy episodic drinking. Multi-component interventions are highly acceptable to communities and may be effective in reducing alcohol-related crime generally, but their impact on alcohol-related violent crime has not been examined. This study evaluated the impact and benefit-cost of a multi-component intervention (increasing community and liquor licensees' awareness, police activity, and feedback) on crimes typically associated with alcohol-related violence. The intervention was tailored to weekends identified as historically problematic in 10 experimental communities in NSW, Australia, relative to 10 control ones. There was no effect on alcohol-related assaults and a small, but statistically significant and cost-beneficial, effect on alcohol-related sexual assaults: a 64% reduction in in the experimental relative to control communities, equivalent to five fewer alcohol-related sexual assaults, with a net social benefit estimated as AUD$3,938,218. The positive benefit-cost ratio was primarily a function of the value that communities placed on reducing alcohol-related harm: the intervention would need to be more than twice as effective for its economic benefits to be comparable to its costs. It is most likely that greater reductions in crimes associated with alcohol-related violence would be achieved by a combination of complementary legislative and community-based interventions.


Prooxidant-antioxidant balance and cardiac function in patients with cardiovascular disease following cardiac surgery.
Cardiopulmonary bypass (CPB) is used during on-pump coronary artery bypass grafting (CABG) and heart valvular replacement surgery, and is associated with the induction of oxidative stress. The aim of the study was to assess the association between indices of cardiac function and prooxidant-antioxidant balance (PAB) values in patients undergoing valve replacement surgery and on-or off-pump CABG. Data were obtained from 44, 33, and 41 patients undergoing off-pump CABG, on-pump CABG, and valve replacement surgery, respectively. The PAB values were measured 24 h before and after the operative procedure, and at the time of discharge. Echocardiography was performed before surgery and before discharge. The changes in E/E', end-diastolic volume, end-systolic volume, left ventricular diastolic and systolic diameter were significantly related to baseline PAB values. In the valve replacement group, neither baseline nor changes in PAB values were associated with echocardiographic measurements. Also, neither off-pump nor on-pump CABG were significantly different in inducing oxidative stress (p = 0.596). When PAB values were measured in CABG patients, there was a significant difference in values between the three time points (p = 0.013). In the valve replacement group, PAB values were not significantly different between the preoperative and postoperative samples. The inverse association between the level of oxidative stress and cardiac function measurement may indicate that high levels of oxidative stress may be a predictor of the deterioration of cardiac function in CABG patients. However, in valvular heart disease patients the serum PAB value was not associated with changes in cardiac function. Levels of oxidative stress, as assessed by the PAB assay, were not significantly different for patients undergoing surgery with or without CPB.


CRISPR Gene Therapy: Applications, Limitations, and Implications for the Future.
A series of recent discoveries harnessing the adaptive immune system of prokaryotes to perform targeted genome editing is having a transformative influence across the biological sciences. The discovery of Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) and CRISPR-associated (Cas) proteins has expanded the applications of genetic research in thousands of laboratories across the globe and is redefining our approach to gene therapy. Traditional gene therapy has raised some concerns, as its reliance on viral vector delivery of therapeutic transgenes can cause both insertional oncogenesis and immunogenic toxicity. While viral vectors remain a key delivery vehicle, CRISPR technology provides a relatively simple and efficient alternative for site-specific gene editing, obliviating some concerns raised by traditional gene therapy. Although it has apparent advantages, CRISPR/Cas9 brings its own set of limitations which must be addressed for safe and efficient clinical translation. This review focuses on the evolution of gene therapy and the role of CRISPR in shifting the gene therapy paradigm. We review the emerging data of recent gene therapy trials and consider the best strategy to move forward with this powerful but still relatively new technology.


Role of transesophageal echocardiography in dissection of the aorta and evaluation of degenerative aortic disease.
The combination of different ultrasound techniques such as transthoracic, suprasternal, subcostal, and TEE has a high sensitivity and specificity in the diagnosis of aortic dissection. Limitations of this combined ultrasound technique are related to the visualization of the ascending part of the aortic arch, which, because of the interposition of the trachea, cannot be visualized completely. The beginning or end of a dissection in this part of the aorta may be misinterpreted. However, false-negative results are rare. False-positive results due to artifacts resulting from reverberations in an ectatic ascending aorta must be taken into account. The most important diagnostic goals in acute or chronic aortic dissection are (1) confirmation of the diagnosis by visualization of the intimal membrane; (2) the differentiation of true and false lumen, depending on visualization of spontaneous echocardiographic contrast, thrombus formation, slow or reduced reversed flow, systolic diameter reduction, and signs of entry jet into the false lumen; (3) detection of intimal tear, demonstrating communication by 2-D or color Doppler echocardiography; (4) determination of the extent of dissection with classification according to DeBakey types I, II, and III, or Stanford types A and B, with differentiation between communicating or noncommunicating dissection and antegrade or retrograde dissection limited to the descending aorta or expanding into the ascending aorta; (5) detection of wall motion abnormalities as a sign of preexisting coronary artery disease or myocardial ischemia due to ostium occlusion by an intimal flap, coronary artery rupture, or collapse of the true lumen during diastole; (6) detection and grading of aortic insufficiency; (7) detection of side branch involvement by suprasternal, subcostal, and abdominal sonography (which will provide information about the choice of the site for cannulation or catheterization of the femoral artery); and (8) detection of pericardial or pleural effusion and mediastinal hematoma as signs of an emergency situation (i.e., suspending rupture). Based on ultrasound diagnostic information, operation can be performed in all acute situations in patients with type A dissection without further investigation. The ability to act decisively in this setting is particularly important in patients with signs suggesting a dire prognosis (i.e., pericardial or pleural effusion or mediastinal hematoma). For follow-up studies, the combination of echocardiography with MR tomography is recommended. With TEE, entry tears can be detected with a higher sensitivity than with MR tomography. This capability may be important for the patient's prognosis. MR tomography, on the other hand, has a better spatial resolution showing the entire aorta, particularly the ascending aortic arch.


Detecting range expansions from genetic data.
We propose a method that uses genetic data to test for the occurrence of a recent range expansion and to infer the location of the origin of the expansion. We introduce a statistic ψ (the directionality index) that detects asymmetries in the 2D allele frequency spectrum of pairs of population. These asymmetries are caused by the series of founder events that happen during an expansion and they arise because low frequency alleles tend to be lost during founder events, thus creating clines in the frequencies of surviving low-frequency alleles. Using simulations, we show that ψ is more powerful for detecting range expansions than both FST and clines in heterozygosity. We also show how we can adapt our approach to more complicated scenarios such as expansions with multiple origins or barriers to migration and we illustrate the utility of ψ by applying it to a data set from modern humans.


Acute cytotoxic effects of ethanol on cultured mouse myocardial cells in a monolayer--enzymatic, chronotropic and ultrastructural studies.
The cytotoxicity of ethanol was investigated by detecting the leakage of lactate dehydrogenase (LDH) from three types of cultured mouse cells--non-proliferative but spontaneously and synchronously contracting atrial and ventricular myocardial cells in monolayer sheets, and also proliferative non-muscle fibroblast-like cells--over a 24-hr period (1, 3, 6 and 24 hr) after exposure to ethanol (12.5, 50, 200 and 500 mM). The beat rate and ultrastructure were also investigated. Only a 24-hr exposure to 500 mM ethanol markedly increased LDH leakage from all three types of cells, and it made 20-50% of these cells dead. The rate of spontaneous contractions of ventricular cells transiently increased after a 1-hr exposure to 200 mM ethanol and a 3-hr exposure to 500 mM ethanol compared with the control, though that of atrial cells did not show any significant change but tended rather to dose-dependently cease contracting. Atrial cells exposed to 500 mM ethanol never contracted, while ventricular cells ceased contracting only at 24 hr. After a 24-hr exposure to 500 mM ethanol some cells were necrosed ultrastructually, and the surviving cells contained giant mitochondria being bizarre in shape and many lipid droplets. Thus, ethanol induced cytotoxic effects terminating in death in cultured mouse heart-derived cells at a concentration of 500 mM. However, this concentration of ethanol did not induce any fatal effects within a 6-hr period, and neither did ethanol concentrations of less than 200 mM over a 24-hr period, as confirmed by the continuance of spontaneous contractions and ultrastructural observations.


ENKD1 is a centrosomal and ciliary microtubule-associated protein important for primary cilium content regulation.
Centrioles and cilia are conserved, microtubule-based structures critical for cell function and development. Their dysfunction causes cancer and developmental disorders. How microtubules are organized into ordered structures by microtubule-associated proteins (MAPs) and tubulin modifications is best understood during mitosis but is largely unexplored for the centrioles and the ciliary axoneme, which are composed of stable microtubules that maintain their length at a steady-state. In particular, we know little about the identity of the centriolar and ciliary MAPs and how they work together during the assembly and maintenance of the cilium and centriole. Here, we identified the Enkurin domain containing 1 (ENKD1) as a component of the centriole wall and the axoneme in mammalian cells and showed that it has extensive proximity interactions with these compartments and MAPs. Using in vitro and cellular assays, we found that ENKD1 is a new MAP that regulates microtubule organization and stability. Consistently, we observed an increase in tubulin polymerization and microtubule stability, as well as disrupted microtubule organization in ENKD1 overexpression. Cells depleted for ENKD1 were defective in ciliary length and content regulation and failed to respond to Hedgehog pathway activation. Together, our results advance our understanding of the functional and regulatory relationship between MAPs and the primary cilium.


Asphyxial homicide in two Scandinavian capitals.
In the Oslo and Copenhagen capital areas, 94 asphyxial homicides were committed in the 10-year period 1985-1994, accounting for 22% of all homicides in that period. Sixty-nine (73%) of the asphyxia victims were female. The most common method of asphyxiation was manual strangulation. Seventeen (18%) of the victims were below the age of 10, accounting for 59% of all homicides in that age group. Whereas 38% of the female victims were killed by their spouse, this was the case for only one male victim. The motive was not known in a great proportion of cases. Fifty-seven percent of the victims had been subjected to additional violence, and in this respect there was no difference between the sexes. In 12 of the cases the offender was female; in 9 such cases the victim was her offspring. More than half of the victims had no blood alcohol. When disregarding the victims less than 10 years of age, 33% of the male and 49% of the female victims had no blood alcohol. The crime scene was the victim's domicile among 72% of female and 52% of male victims. Forty-two percent of the female and 11% of the male victims above the age of 10 years were married or cohabitant.


Morphological volatility precedes ecological innovation in early echinoderms.
Origins of higher taxonomic groups entail dramatic and nearly simultaneous changes in morphology and ecological function, limiting our ability to disentangle the drivers of evolutionary diversification. Here we phylogenetically compare the anatomy and life habits of Cambrian-Ordovician echinoderms to test which facet better facilitates future success. Rates of morphological evolution are faster and involve more volatile trait changes, allowing morphological disparity to accrue faster and earlier in the Cambrian. However, persistent life-habit evolution throughout the early Palaeozoic, combined with iterative functional convergence within adaptive strategies, results in major expansion of ecospace and functional diversity. The interactions between tempo, divergence and convergence demonstrate not only that anatomical novelty precedes ecological success, but also that ecological innovation is constrained, even during a phylum's origin.


Optimizing vesicourethral anastomosis healing after robot-assisted laparoscopic radical prostatectomy: lessons learned from three techniques in 1900 patients.
Creation of an optimally apposed, tension-free, well-supported vesicourethral anastomosis remains the cornerstone for anastomotic healing after radical prostatectomy. We report the effect of three techniques of bladder neck reconstruction during robot-assisted radical prostatectomy on anastomotic leak, stricture formation, and continence recovery. Between January 2005 to September 2009, 1900 consecutive patients underwent robotic-assisted laparoscopic prostatectomy (RALP) by a single surgeon. Of these, the first 214 underwent vesicourethral conventional anastomosis (CA); the next 303 men underwent anterior reconstruction (AR) only; and last 1383 men underwent total anatomic restoration (TR). Data elements included patient age, body mass index, preoperative biopsy Gleason score and prostate-specific antigen level, prostate volume, total operative time, console time, time for performing vesicourethral anastomosis, estimated blood loss, tumor stage, and margin status on final pathologic findings. Primary end points were rates of clinically significant anastomotic leaks, bladder neck contractures, and time to return of continence. Chi-square and Fisher exact tests were used for analysis of categoric variables. The Cox proportional hazard model was used for both univariate and multivariate analysis. Clinically significant anastomotic leakage and bladder neck strictures were significantly fewer in the reconstructed groups (2.3% vs 1.0% vs 0.3% and 3.7% vs 1.3% vs 0.5% in the CA, AR, and TR groups, P < 0.01). Continence rates at 1, 6, 12, 26, and 52 weeks after RALP were also significantly better at all time points with AR and TR compared with CA alone (P < 0.001). TR of the continence mechanism optimizes vesicourethral anastomosis healing and hastens early continence return after RALP.


Resistance to thermal stress in corals without changes in symbiont composition.
Discovering how corals can adjust their thermal sensitivity in the context of global climate change is important in understanding the long-term persistence of coral reefs. In this study, we showed that short-term preconditioning to higher temperatures, 3°C below the experimentally determined bleaching threshold, for a period of 10 days provides thermal tolerance for the symbiosis stability between the scleractinian coral, Acropora millepora and Symbiodinium. Based on genotypic analysis, our results indicate that the acclimatization of this coral species to thermal stress does not come down to simple changes in Symbiodinium and/or the bacterial communities that associate with reef-building corals. This suggests that the physiological plasticity of the host and/or symbiotic components appears to play an important role in responding to ocean warming. The further study of host and symbiont physiology, both of Symbiodinium and prokaryotes, is of paramount importance in the context of global climate change, as mechanisms for rapid holobiont acclimatization will become increasingly important to the long-standing persistence of coral reefs.


Biomechanical studies on transverse olecranon and patellar fractures: a systematic review with the development of a new scoring method.
Several methods of transverse patellar and olecranon fixation have been described. This article compares biomechanical studies of various fixation methods using a newly developed scoring method. The databases PubMed, Web of Science, Science Direct, Google Scholar and Google were searched for relevant studies. Fixation hardware failure remains a problem. Various materials and fixation techniques have been tested to provide an improved fixation of transverse olecranon and patellar fractures. The difference in biomechanical testing setup between the studies makes it hard to compare different fixation techniques. The newly developed grading method was proved to be unbiased and reliable; however, extra specifications need to be added at some criteria when adopting the scoring method. Non-metallic constructs may provide an improvement to the currently used metallic tension band wiring technique; however, clinical research is required.


Significant dates in the history of forensic hypnosis.
Important dates in the history of forensic hypnosis are identified and their significance is briefly described. Trends regarding the use of forensic hypnosis are highlighted, as well as criticisms of various positions. The authors recommend that professionals who practice forensic hypnosis be thoroughly familiar with the significant precedents, problems, and pitfalls that have arisen concerning the use of hypnosis with memory in forensic settings.


Spherical Hole-Transporting Interfacial Layer Passivated Defect for Inverted NiOx-Based Planar Perovskite Solar Cells with High Efficiency of over 20.
In this study, we achieved a facile and low-cost (18-22 USD/g) synthesis of spiro[fluorene-9,9-phenanthren-10-one]-based interfacial layer materials (MSs; designated MS-PC, MS-PA, MS-OC, and MS-OA). Carbazoles and dimethylacridine substituents with an extended π-conjugation achieved through ortho- or para-orientations were used as donors at the spiro[fluorene-9,9'-phenanthren-10'-one] moiety. Highly efficient and stable inverted perovskite solar cells (PSCs) with the device architecture of ITO/NiOx/MSs/perovskite/PC61BM/BCP/Ag can be achieved to improve the surface morphology of NiOx when MSs are adopted as the interfacial layer. During a morphological study, the ortho-orientated donor of MS-OC and MS-OA has spherical structures indicated that the films were smooth and that the films of perovskite deposited on them had large grain size and uniformity. The photoluminescence properties of the perovskite layers on the NiOx/MSs were showed better hole-transporting capabilities than the bare NiOx. The dual-functional interfacial layer has shown defect passivation effect, it not only improved the surface morphology of NiOx but also enlarged the perovskite layer grain size. The best PSC device performance of the NiOx/MS-OC was characterized by 22.34 mA cm-2 short-circuit current density (Jsc), 1.128 V open-circuit voltage (Voc), and 80.8% fill factor (FF), resulting in 20.34% power conversion efficiency (PCE). The NiOx/MS-OC PSCs showed good long-term device stability, even retained the original PCE of 93.16% after 370 days under argon (25 °C). Owing to the superior perovskite morphologies of the NiOx/MSs, the resulting devices outperformed the bare NiOx-based PSCs.


Transcatheter Arterial Embolization Compared With Surgery for Uncontrolled Peptic Ulcer Bleeding: A Population-based Cohort Study.
To compare key outcomes after transcatheter arterial embolization (TAE) with conventional surgery for peptic ulcer bleeding when endoscopic intervention fails to achieve hemostasis. Mortality in peptic ulcer bleeding remains high, especially in patients who require surgical treatment. A population-based cohort study in Stockholm, Sweden, in 2000 to 2014, assessing the main outcome all-cause mortality and the secondary outcomes re-bleeding, re-intervention, length of hospitalization, and complications, was conducted. Data were taken from well-maintained registries and medical records. Multivariable Cox-regression provided hazard ratios (HRs) with 95% confidence intervals (CIs) adjusted for age, sex, ulcer history, comorbidity, and calendar period were considered. Included were 282 patients, 97 in the TAE group and 185 in the surgery group. Compared with the surgery group, the overall hazard of death was 34% decreased in the TAE group (adjusted HR 0.66, 95% CI 0.46-0.96). The corresponding HRs for mortality within 30 days, 90 days, 1 year, and 5 years were 0.70 (95% CI 0.37-1.35), 0.69 (95% CI 0.38-1.26), 0.88 (95% CI 0.53-1.47), and 0.67 (95% CI 0.45-1.00), respectively. The risk of re-bleeding was higher after TAE compared with surgery (HR 2.48, 95% CI 1.33-4.62). The median length of hospital stay was shorter in the TAE group-8 versus 16 days-acceleration factor 0.59 (95% CI 0.45-0.77) and the risk of complications was lower (8.3% vs 32.2%; P < 0.0001). This study indicates that TAE compares favorably with surgery regarding prognosis after refractory peptic ulcer bleeding, and the shorter length of hospital stay and fewer complications outweigh a higher risk of re-bleeding. TAE could be recommended as first-line treatment for these patients.


Magnitude of Nonalcoholic Fatty Liver Disease: Eastern Perspective.
Nonalcoholic fatty liver disease (NAFLD) is currently the most common chronic liver disease worldwide, affecting a quarter of the global adult population. Nonalcoholic steatohepatitis, the more active form of NAFLD with active hepatic necroinflammation and faster fibrosis progression, has become one of the leading indications for liver transplantation and an important cause of hepatocellular carcinoma in Western countries. Epidemiological studies suggest that NAFLD is almost equally prevalent in Asia as in the West, but severe liver complications appear to be less common. In this article, we review the epidemiology, clinical characteristics, risk factors and clinical outcomes of NAFLD in Asia. We highlight the issue of NAFLD in the nonobese population and discuss whether it is a unique phenomenon in Asia. Because of the rapidly changing epidemiology and natural history, future studies should continue to monitor the magnitude of NAFLD in Asia and define the best policy to control this new epidemic.


The ultrasonically activated scalpel versus bipolar diathermy for tonsillectomy: a prospective, randomized trial.
Among patients undergoing tonsillectomy, the ultrasonic scalpel has been reported to lead to less intraoperative blood loss than cold dissection, and less postoperative pain and faster recovery than monopolar electrocautery. However, the ultrasonic scalpel has not been compared with bipolar diathermy. The present study was a prospective, randomized, single-blind trial, comparing these two techniques with respect to postoperative pain. Twenty-one adults underwent tonsillectomy on one side using the ultrasonic scalpel, and on the other using bipolar diathermy. Pain scores were obtained on postoperative days 1, 2, 7 and week 3. There was no difference between the two treatments at any of the time points (P = 0.6047, 0.4018, 0.6047 and 0.5000, respectively). Inability to control bleeding with the ultrasonic scalpel resulted in the rescue use of an alternative technique of haemostasis in 14 cases. We conclude that the use of the ultrasonic scalpel in adult tonsillectomy is likely to be limited by its substantial costs and difficulties with haemostasis.


Establishment and validation of a novel nomogram for survival prediction of ovarian carcinosarcoma.
Ovarian carcinosarcoma (OCS) is a rare and aggressive histological type of ovarian cancer. Current prognostic methods for OCS are insufficient. This study was undertaken to establish and validate a novel nomogram for predicting the overall survival (OS) of OCS patients. We extracted 820 patients with OCS from the Surveillance, Epidemiology, and End Results (SEER) database and further randomly assigned them to a training set (n=574) and a validation set (n=246) at a ratio of 7-to-3. Univariate and multivariate regression analyses were utilized to verity independent prognostic factors, and a prognostic nomogram was constructed based on the results. The performance of the new model was compared with that of the AJCC staging system using the area under the receiver operating characteristic curve (AUC), net reclassification improvement (NRI), integrated discrimination improvement (IDI), calibration curve, and decision curve analysis (DCA). Cox regression analysis suggested that age, grade, tumor size, the American Joint Committee on Cancer (AJCC) stage, surgery, and chemotherapy were the independent prognostic factors. These factors were integrated into a prognostic nomogram to determine the 1-, 3-, and 5-year OS of OCS patients. The AUC, NRI, IDI, calibration curves, and DCA data demonstrated that our nomogram had better discriminative ability than the AJCC staging system alone. The calibration curves indicate that the nomogram was well-calibrated. The DCA verified the clinical applicability of the nomogram. Our current study is the first to establish and internally validate a novel nomogram for predicting the 1-, 3-, and 5-year OS probabilities of OCS patients. Our prognostic nomogram was of good performance and can be an accurate tool to predict individualized survival time of OCS in clinical work.


Survey of contagious caprine pleuropneumonia in goat herds in the Thrace region of Turkey.
Contagious caprine pleuropneumonia (CCPP) was detected for the first time on the European continent in the Thrace region of Turkey in 2002 following outbreaks of an unusually severe respiratory disease in goats. Mycoplasma capricolums ubspecies capripneumoniae (Mccp), the causative agent, was identified in many infected herds throughout the region by serological, bacteriological and molecular biological techniques. However, as no quantitative data on the prevalence and distribution of the disease have been gathered in the intervening years, the extent of infection is unknown. Consequently, in 2014, a random sample of 2,400 goats was drawn from a population of over 167,000 goats in the region by multistage sampling. Serum samples were collected and tested by a monoclonal antibodybased competitive enzyme-linked immunosorbent assay (cELISA). The overall prevalence of CCPP in Thrace was found to be just over 8%. The prevalence in the individual provinces was approximately 18%, 7%, 8% and 6% for Çanakkale, Edirne, K?rklareli and Tekirda?, respectively, while Istanbul province appeared to be CCPP-free. The results showed that CCPP has spread throughout the region and has become endemic, and may pose a potential risk to the neighbouring countries of Greece and Bulgaria. Mccp was regularly detected from lung samples of suspect goats until 2015 but since then there has been no further detection from clinical samples.


On the role of microkinetic network structure in the interplay between oxygen evolution reaction and catalyst dissolution.
Understanding the pathways of oxygen evolution reaction (OER) and the mechanisms of catalyst degradation is of essential importance for developing efficient and stable OER catalysts. Experimentally, a close coupling between OER and catalyst dissolution on metal oxides is reported. In this work, it is analysed how the microkinetic network structure of a generic electrocatalytic cycle, in which a common intermediate causes catalyst dissolution, governs the interplay between electrocatalytic activity and stability. Model discrimination is possible based on the analysis of incorporated microkinetic network structures and the comparison to experimental data. The derived concept is used to analyse the coupling of OER and catalyst dissolution on rutile and reactively sputtered Iridium oxides. For rutile Iridium oxide, the characteristic activity and stability behaviour can be well described by a mono-nuclear, adsorbate evolution mechanism and the chemical type of both competing dissolution and rate-determining OER-step. For the reactively sputtered Iridium oxide surface, experimentally observed characteristics can be captured by the assumption of an additional path via a low oxidation state intermediate, which explains the observed characteristic increase in OER over dissolution selectivity with potential by the competition between electrochemical re-oxidation and chemical dissolution.


CD20, CD3, and CD40 ligand microclusters segregate three-dimensionally in vivo at B-cell-T-cell immunological synapses after viral immunity in primate brain.
The clearance of virally infected cells from the brain is mediated by T cells that engage antigen-presenting cells to form supramolecular activation clusters at the immunological synapse. However, after clearance, the T cells persist at the infection site and remain activated locally. In the present work the long-term interactions of immune cells in brains of monkeys were imaged in situ 9 months after the viral inoculation. After viral immunity, the persistent infiltration of T cells and B cells was observed at the infection sites. T cells showed evidence of T-cell receptor signaling as a result of contacts with B cells. Three-dimensional analysis of B-cell-T-cell synapses showed clusters of CD3 in T cells and the segregation of CD20 in B cells, involving the recruitment of CD40 ligand at the interface. These results demonstrate that immunological synapses between B cells and T cells forming three-dimensional microclusters occur in vivo in the central nervous system and suggest that these interactions may be involved in the lymphocyte activation after viral immunity at the original infection site.


Biliary-colonic fistula: a case report and literature review.
We report the occurrence of common bile duct obstruction and biliary-colonic fistula after open cholecystectomy. Although it is a very unusual complication after cholecystectomy, biliary-colonic fistula should be part of the differential diagnosis for patients presenting with sepsis after open or laparoscopic cholecystectomy. After confirmation and characterization of the injury by endoscopic retrograde cholangiopancreatography and cholangiogram, assessment for undrained collections by computed tomography scan, control of sepsis and coagulopathy, and nutritional support, surgical repair was undertaken. The patient underwent fistula take-down between the common bile duct and the colon at the hepatic flexure, primary closure of the colon enterotomy, and a Roux-en-Y end-to-side hepaticojejunostomy at the confluence of the right and left hepatic ducts. Recovery was uneventful and the patient was doing well at the 6-month follow-up. Surgical repair should be undertaken by surgeons with extensive experience in hepatobiliary reconstruction.


Multicenter clinical evaluation of a novel transcription-mediated amplification assay for SARS-CoV-2 molecular testing.
The onset and spread of COVID-19 pandemic has forced clinical laboratories to rapidly expand testing capacity for SARS-CoV-2. This study evaluates the clinical performance of the TMA Procleix SARS-CoV-2 assay in comparison to the RT-PCR assay Allplex™ SARS-CoV-2 for the qualitative detection of SARS-CoV-2 RNA. Between November 2020 and February 2021, 610 upper-respiratory specimens received for routine SARS-CoV-2 molecular testing were prospectively collected and selected at the Hospital Universitari Vall d'Hebron and the Hospital Universitari Bellvitge in Barcelona, Spain. All samples were processed in parallel with the TMA and the RT-PCR assays, and results were compared. Discrepancies were retested by an additional RT-PCR method and the clinical history of these patients was reviewed. Overall, the level of concordance between both assays was 92.0% (κ, 0.772). Most discordant results (36/38, 94.7%) corresponded to samples testing positive with the TMA assay and negative with the RT-PCR method. Of these discrepant cases, most (28/36, 77.8%) were finally classified as confirmed or probable SARS-CoV-2 cases according to the discrepant analysis. In conclusion, the TMA Procleix SARS-CoV-2 assay performed well for the qualitative detection of SARS-CoV-2 RNA in a multisite clinical setting. This novel TMA assay demonstrated a greater sensitivity in comparison to RT-PCR methods for the molecular detection of SARS-CoV-2. This higher sensitivity but also the qualitative feature of this detection of SARS-CoV-2 should be considered when making testing algorithm decisions.


Deformable multi-modal registration using 3D-FAST conditioned mutual information.
Mutual information (MI) has been a preferred choice of similarity measure for multi-modal image registration, but the accuracy and robustness of MI are not satisfactory as MI only considers the global intensity correlation while ignoring local and structural information. To address this problem, we combine MI with local and structural information. We bring structural information extracted by a modified Accelerated Segment Test (FAST) algorithm into MI. Traditional FAST is transferred into 3 D for the first time, and the 3 D-FAST based structural information is added into MI as another channel, thereby incorporating spatial and geometric information with intensity information in the registration. The robustness and accuracy of the proposed method were demonstrated in three experiments. The average registration errors of our method were 1.17, 1.33 and 1.20 compared to 1.47, 1.63 and 1.40 of LMI in T1-T2, T1-PD and T2-PD registration respectively. In this paper, we use the structural similarity computed by 3 D-FAST as the conditional information to encode spatial and geometric cues into LMI. In all of these three experiments, our method shows to be more robust and accurate than common registration methods based on information theory.


The relationship of femoral intercondylar notch width to height, weight, and sex in patients with intact anterior cruciate ligaments.
Intercondylar notch width, femoral bicondylar width, height, and weight of patients with intact anterior cruciate ligaments were measured to determine whether intercondylar notch width was related to body size. A 45 degrees weight-bearing posteroanterior radiograph was obtained for 315 men and 163 women. Notch width and bicondylar width was measured at one-half notch height. Mean notch width for men was statistically significantly wider than for women (17.1 mm versus 14.7 mm, respectively; P<.01). There was no statistically significant correlation between height and notch width for men (r=-0.0019; P=.97) or women (r=0.1308; P=.10). No significant correlation existed between weight and notch width for men (r=-0.0311; P=.58) or women (r=0.0523; P=.51). Analysis of variance showed height and weight were not significant covariates in notch width for either men (P=.44) or women (P=.91). Women of the same height and weight as men had significantly narrower notches (P<.01). There was a statistically significant correlation between wider femoral bicondylar widths and higher weight for men (r=0.694; P<.01) and women (r=0.821; P<.01). Similarly, there was a statistically significant correlation between wider femoral bicondylar widths and increased height for men (r=0.670; P<.01) and women (r=0.785; P<.01). These data demonstrate height and weight are poor predictors of intercondylar notch width. Therefore, one cannot assume body size is a predictor of notch width. Furthermore, because mean notch width does not increase with increasing height and weight, the notch width index calculation cannot accurately reflect the size of the intercondylar notch.


Efficacy and tolerability of topical 1% cidofovir cream for the treatment of external anogenital warts in HIV-infected persons.
Treatment options for anogenital warts in patients with HIV-1 are unsatisfactory because they fail to eradicate latent human papillomavirus. To determine tolerability and efficacy of topical 1% cidofovir cream for the treatment of external anogenital warts in HIV-infected patients. A randomized, placebo-controlled, single-blind, crossover pilot study of either 1% cidofovir cream or placebo applied once daily 5 days a week for 2 weeks followed by 2 weeks of observation was performed. Six patients were randomized to 1% cidofovir cream and six to placebo. The latter patients eventually received 1% cidofovir cream. Thus, 12 treatment rounds of cidofovir were compared with six rounds of placebo. A reduction of more than 50% in the total wart area achieved by seven cidofovir treatments (58%), as compared with no placebo regimen (P = 0.02). Local reactions occurred in 10 of the 12 patients treated with cidofovir, as compared with 0 of the 6 subjects in the placebo group (P < 0.001). For the initial clearance of anogenital warts in HIV-infected patients, 1% cidofovir cream is significantly more effective than vehicle cream. Local mucosal erosion is a common side effect.


Self-reported changes in alcohol and tobacco use during COVID-19: findings from the eastern part of WHO European Region.
The COVID-19 pandemic might impact substance use behaviours around the globe. In this study, we investigate changes in alcohol and tobacco use in the second half of 2020 in countries of the eastern part of the WHO European Region. Self-reported changes in alcohol and tobacco use among 11 295 adults from 18 countries in the eastern part of the WHO European Region were collected between August 2020 and January 2021. The non-probabilistic sample was weighted for age, gender and education. For each country, proportions of respondents reporting a decrease, no change or increase in substance use over the past 3 months were examined, and multinomial regression models were used to test associations with age, gender and past-year alcohol use. In most countries, about half of the respondents indicating past-year alcohol or tobacco use reported no change in their substance use. Of those alcohol users who reported changes in their alcohol use, a larger proportion reported a decrease than an increase in most countries. The opposite was true for tobacco use. Women, young adults and past-year harmful alcohol users were identified as being more likely to change their substance use behaviour. We found diverging overall trends for alcohol and tobacco use in the second half of 2020. The patterns of change vary according to age, gender and past-year substance use. Individuals at risk to increase their substance use during the COVID-19 pandemic require most policy considerations.


Clinical experience with epoetin alfa in the management of hemoglobin levels in orthopedic surgery and cancer. Implications for use in gynecologic surgery.
Recombinant human erythropoietin (r-HuEPO, epoetin alfa) is used for treatment of anemia associated with chemotherapy for non-myeloid malignancies, chronic renal failure and zidovudine treatment in patients infected with the human immunodeficiency virus and for anemic patients undergoing elective, noncardiac, nonvascular surgery. Epoetin alfa has been shown to safely increase preoperative hemoglobin (Hb) levels in anemic patients undergoing elective noncardiac, nonvascular surgery and is more effective than preoperative autologous blood donation in reducing the need for perioperative blood transfusions in orthopedic surgery patients. Epoetin alfa was shown to significantly increase Hb levels and decrease transfusion requirements in gynecologic cancer patients undergoing chemotherapy. A once-weekly regimen of 40,000 IU per dose was effective in these patients. In addition to decreasing transfusion requirements and increasing Hb, epoetin alfa for relieving anemia-related fatigue and improving quality of life was demonstrated in clinical trials in anemic cancer patients receiving chemotherapy. With regard to quality of life in orthopedic surgery patients, a novel instrument to measure the effect of Hb management on postoperative recuperative power (i.e., vigor, functional ability) has been validated and may prove to be useful in optimizing rehabilitation and discharge planning. Extensive clinical experience with epoetin alfa in anemic patients undergoing major elective orthopedic surgery or those with gynecologic cancer provides a strong basis for its use in gynecologic surgery.


Patterns of work and retirement among pediatricians aged >or=50 years.
This study examined patterns of work and retirement among older pediatricians, including the determinants of part-time work and retirement, as well as extended participation in the pediatrician workforce. A mail survey regarding recent and expected workforce participation was distributed to American Academy of Pediatrics members who were aged >or=50 years. A total of 1158 (72%) responded, 1114 (70%) of whom were included in these analyses. Analyses examined levels of engagement in medicine, retirement plans, and differences between men and women and primary care pediatricians and pediatric subspecialists. Providing or planning to provide patient care past age 65 was reported by 45% of the respondents. Engaging in part-time work was increasingly more common with age and may represent a step toward retirement for many. In this sample, women were more likely to work part-time (32% vs 18% of men) and less likely to work past age 65 (26% vs 57% of men). When compared with primary care pediatricians, pediatric subspecialists worked more hours per week (59 vs 53) but spent a smaller percentage of their time on patient care (63% vs 82%). Part-time work and reduced work hours in anticipation of retirement are options that are used and desired by older pediatricians. Results of this study suggest that making provisions for gradual reduction in work hours or other forms of phasing out of the workforce could benefit the practice of pediatrics by extending the career length of the most experienced pediatricians.


The effects of a high dose, short course of interferon on hepatitis C.
To shorten the period of interferon (IFN) treatment for chronic hepatitis C, we investigated the clinical efficacy of a regimen using a higher dose and a shorter treatment period. Fifty chronic hepatitis C patients who were hepatitis C virus (HCV)-RNA positive and who were histologically diagnosed as having chronic hepatitis, took part in the study. Virus levels were measured before and 2 weeks after starting the treatment. We administered natural IFNalpha, 10 MU, i.m. daily for 2 consecutive weeks and then three times per week for the subsequent 14 weeks (total dose 560 MU). Patients who were HCV-RNA negative at the completion of the therapy and 6 months later, were evaluated as sustained responders (SR; 32%). Those who were not HCV-RNA negative at the two time points were evaluated as non-responders. Nucleotide and clone differences in the hypervariable region (HVR) and predictive factors for prognosis were also analysed. Low virus level and HCV-RNA genotype 2a/2b were the predictors for good prognosis, whereas the numbers of nucleotide differences and clone differences in HVR were not. Sustained responder patients became HCV-RNA negative 2 weeks after starting the treatment at a significantly higher rate, whereas no non-responder patients were HCV-RNA negative at that time. The SR rate (32%) was equivalent to those reported in previous 24 week treatment studies. This IFN therapy using a higher dose and a shorter period was useful.


The expression of alpha-, beta-, and gamma-synucleins in olfactory mucosa from patients with and without neurodegenerative diseases.
A family of homologous proteins known as alpha-, beta-, and gamma-synuclein are abundantly expressed in brain, especially in the presynaptic terminal of neurons. Although the precise function of these proteins remains unknown, alpha-synuclein has been implicated in synaptic plasticity associated with avian song learning as well as in the pathogenesis of Parkinson's disease (PD), dementia with LBs (DLB), some forms of Alzheimer's disease (AD), and multiple system atrophy (MSA). Since olfactory dysfunction is a common feature of these disorders and the olfactory receptor neurons (ORNs) of the olfactory epithelium (OE) regenerate throughout the lifespan, we used antibodies specific for alpha-, beta-, and gamma-synucleins to examine the olfactory mucosa of patients with PD, DLB, AD, MSA, and controls without a neurological disorder. Although antibodies to alpha- and beta-synucleins detected abnormal dystrophic neurites in the OE of patients with neurodegenerative disorders, similar pathology was also seen in the OE of controls. More significantly, we show here for the first time that alpha-, beta-, and gamma-synucleins are differentially expressed in cells of the OE and respiratory epithelium and that alpha-synuclein is the most abundant synuclein in the olfactory mucosa, where it is prominently expressed in ORNs. Moreover, alpha- and gamma-synucleins also were prominent in the OE basal cells, which include the progenitor cells of the ORNs in the OE. Thus, our data on synuclein expression within the OE may signify that synuclein plays a role in the regeneration and plasticity of ORNs in the adult human OE.


Feedback Control of Two-Component Regulatory Systems.
Two-component systems are a dominant form of bacterial signal transduction. The prototypical two-component system consists of a sensor that responds to a specific input(s) by modifying the output of a cognate regulator. Because the output of a two-component system is the amount of phosphorylated regulator, feedback mechanisms may alter the amount of regulator, and/or modify the ability of a sensor or other proteins to alter the phosphorylation state of the regulator. Two-component systems may display intrinsic feedback whereby the amount of phosphorylated regulator changes under constant inducing conditions and without the participation of additional proteins. Feedback control allows a two-component system to achieve particular steady-state levels, to reach a given steady state with distinct dynamics, to express coregulated genes in a given order, and to activate a regulator to different extents, depending on the signal acting on the sensor.


Diagnosis and Treatment of Obstructive Sleep Apnea Syndrome in Children.
Sleep is important for children pertaining to their physical and mental growth. Obstructive sleep apnea syndrome (OSAS) in children has been shown to have different effects as compared to OSAS in adults, including deficits in cognition and neuropsychological functions, hyperactivity, ADHD, behavior problems, aggressive behavior, learning problems and nocturnal enuresis. Hypertrophy of the adenoids and tonsils is a major cause of OSAS in children; therefore, adenotonsillectomy may decrease the effects of OSAS pertaining to physical and mental growth. It is important to accurately diagnose and appropriately treat OSAS in children to prevent OSAS in their adulthood.


Explorations in the "inner sanctum of the photosynthetic process," the water oxidizing system.
This article summarizes the present state of knowledge about the organization of the water oxidizing polypeptide complex of photosynthesis and the mechanism of its operation. Spectacular advances have been made in recent years, but many questions remain to be answered. Among them are those concerned with the organization and binding of the functional Mn, its specific role in the oxidant storage that precedes the formation of one oxygen from two water molecules, and its cooperation with other redox-active constituents. Much is still to be learned also about the function of the individual polypeptides and about the role of the cofactors Ca(2+) and Cl(-). Differences between the organization of the water oxidizing complexes in green plants and cyanobacteria suggest, furthermore, that in vivo their water oxidizing mechanisms must operate under different, still unrecognized constraints.


Revisiting hematopoiesis: applications of the bulk and single-cell transcriptomics dissecting transcriptional heterogeneity in hematopoietic stem cells.
Hematopoietic system (HS) is one of the most unique, adaptive and comprehensive developmental systems on which various other body systems relies on. It consists of a central pool of multipotent hematopoietic stem cells (HSCs) differentiating into lymphoid and myeloid lineage by series of gradual loss of stemness potential. Thus, this highly coordinated phenomenon of blood cell renewal ensures robust immunity and limits autoimmunity. Any disease, chronic infection or stress interrupts HS homeostasis and breaks HSCs' dormancy, thereby activating HSCs to meet the peripheral demand for different immune cells via their expansion and differentiation into more lineage-restricted progenitors, primarily within the bone marrow (BM) in adult life. Therefore, a greater understanding of the overall regulatory landscape of HSC homeostasis and their perturbations is critical for dissecting protective immunity versus autoimmunity. Recent advancements in next-generation sequencing (NGS) viz genomic, transcriptomic, epigenomic and proteogenomic methods at bulk as well as single-cell levels have increased our apprehension for HSC working model. In this review, we discussed the recent findings and computational methods used to unravel the new HSC model revised over the classical model.


Evaluation of transport properties of biomembranes by means of Peusner network thermodynamics.
The R version of the Kedem-Katchalsky-Peusner (KKP) network equations is one of the basic research tools for membrane transport. For binary solutions of non-electrolytes containing a solvent and one solute, these equations include the Peusner resistance coefficients. The aim of the study was to assess the transport properties of biomembranes on the basis of the concentration characteristics of the coefficients: resistance, coupling, energy conversion efficiency and degraded and free energy fluxes. The subject of the study were polymer biomembranes used as a membrane dressing (Bioprocess) and used in hemodialysis (Nephrophan, Ultra-flo) with the coefficients of hydraulic permeability (Lp), reflection () and diffusion permeability () for aqueous glucose solutions. The research method was the R version of the KKP network equations for binary solutions of non-electrolytes. We developed a procedure for evaluation the transport properties of membranes. This procedure requires the calculation of the dependence of the following coefficients: Peusner resistance, Kedem-Caplan-Peusner coupling, Caplan-Peusner energy conversion efficiency, Peusner coupling, and the dissipated energy and free energy fluxes on the mean glucose concentration. Results show that the values of the Peusner resistance coefficients, the Kedem-Caplan-Peusner coupling, the Caplan-Peusner energy conversion efficiency, and the Peusner coupling depend on the mutual relationship between the coefficients Lp, ,  and C. In turn, the value of the dissipated energy and free energy fluxes it is also determined by the values of the volume and diffusion fluxes. The presented procedure for evaluation transport properties of membranes can be helpful in explaining the mechanisms of membrane transport and conducting energy analyzes of membrane processes. Therefore, this procedure can be used for selection of a suitable membrane for practical (eg., industrial or medical) applications.


[Cognitive neuro-imaging : phylogenesis and ontogenesis].
Brain imaging methods can visualize the anatomy and activity of children's brains, from the first year of life. These structures and activities are subsequently "recycled" by acquisitions such as reading and arithmetic. Evoked potential mapping of babies aged only a few months, with 64 or 128 electrodes, has a temporal precision of the millisecond order. Magneto-encephalography (MEG) is a costly method. Safe at the field strengths currently used (1.5 or 3 T), MRI requires anti-ferromagnetic precautions, noise protection (tunnel, helmet), and the presence of a parent in the child's field of view. Despite these efforts, movement artifacts remain more of a problem than with adult brain imaging. Brain organization in very young children includes cortical folds and their evolution with time in the premature brain; asymmetry and lateralization of language; the superior temporal sulcus; and anatomical asymmetries combined with early functional organization. The response to spoken language (two-three months), activation of the temporal region and left inferior frontal region (Broca)--as in adults, the asymmetry favoring the left hemisphere during temporal activation (planum). The temporal lobe is hierarchically organized: as in adults, the fastest responses are observed in the primary auditory cortex, decreasing gradually as one progresses to the planum temporal. Syllabes discrimination, regardless of the speaker, and a fusion of visual and auditory information with respect to speech. The newborn brain specializes in the vowels and consonants of the mother tongue, and early visual recognition, especially of faces. Evoked potentials to study the separation of a dorsal track and a classical ventral track in adults. Ventral = identification of objects regardless of their position and orientation; dorsal visual pathway = calculation of the position of objects, action planning, but also counting the number of objects. Evoked potentials at 3 months = brain = already capable of observing changes in the nature and number of a set of objects. We have observed at this early age a clear division between ventral (left temporal) processing of identity and dorsal (right parietal) processing of numbers of objects. The infant brain is already organized during the first months of life. My postulate is that these early cerebral biases provide a framework which constrains cultural learning. Cultural inventions such as reading or symbolic calculation invade the cortical circuits that have evolved in a different context but that can be partly recycled for new human-specific uses. Each cultural object occupies a particular brain niche, a circuit that is already organized but that has sufficient plasticity to be retrained.


Expression of RANKL and OPG mRNA in periodontal disease: possible involvement in bone destruction.
Periodontitis is a complex, multifactorial process affected by bacterial plaque-components and host defense mechanisms. Inflammation of the periodontitium may lead the destruction of the underlying ligament and alveolar bone. Receptor activator of NF-kappaB ligand (RANKL), a novel TNF receptor-related protein is an important factor for osteoclast differentiation and activation. Given osteolysis by osteoclast has been demonstrated in periodontitis, we hypothesized that RANKL expression may be associated with bone destruction in periodontitis. We used semi-quantitative RT-PCR to compare the gene expression of RANKL and osteoprogerin (OPG), a decoy receptor of RANKL, between moderate and advanced periodontitis, and healthy subjects. The level of RANKL mRNA was highest in advanced periodontitis. In contrast, the level of OPG mRNA in both advanced and moderate periodontitis was lower than that in the healthy group. It appears that the ratio of RANKL to OPG mRNA in periodontitis has increased. To determine the localization of RANKL gene transcripts in gingival tissue at the cellular level, in situ hybridization was performed using digoxigenin-labeled specific riboprobes. RANKL mRNA was expressed in inflammatory cells, mainly lymphocyte and macrophages. In addition, proliferating epithelium in the vicinity of inflammatory cells expressed high levels of RANKL mRNA. In short, our data suggest that up regulation of RANKL mRNA in both inflammatory cells and epithelium may be associated with the activation of osteoclastic bone destruction in periodontitis.


A Protocol for Remote Cognitive Training Developed for Use in Clinical Populations During the COVID-19 Pandemic.
Many traumatic brain injury (TBI) survivors face scheduling and transportation challenges when seeking therapeutic interventions. The COVID-19 pandemic created a shift in the use of at-home spaces for work, play, and research, inspiring the development of online therapeutic options. In the current study, we determined the feasibility of an at-home cognitive training tool (NeuroTrackerX) that uses anaglyph three-dimensional (3D) glasses and three-dimensional multiple object tracking (3D-MOT) software. We recruited 20 adults (10 female; mean age = 68.3 years, standard deviation [SD] = 6.75) as the at-home training group. We assessed cognitive health status for participants using a self-report questionnaire and the Mini-Mental State Examination (MMSE), and all participants were deemed cognitively healthy (MMSE >26). At-home participants loaned the necessary equipment (e.g., 3D glasses, computer equipment) from the research facilities and engaged in 10 training sessions over 5 weeks (two times per week). Participant recruitment, retention, adherence, and experience were used as markers of feasibility. For program validation, 20 participants (10 female; mean age = 63.39 years, SD = 12.22), who had previously completed at least eight sessions of the in-lab 3D-MOT program, were randomly selected as the control group. We assessed individual session scores, overall improvement, and learning rates between groups. Program feasibility is supported by high recruitment and retention, 90% participant adherence, and participants' ease of use of the program. Validation of the program is supported. Groups showed no differences in session scores (p > 0.05) and percentage improvement (p > 0.05) despite the differences in screen size and 3D technology. Participants in both groups showed significant improvements in task performance across the training sessions (p < 0.001). NeuroTrackerX provides a promising at-home option for cognitive training in cognitively healthy adults and may be a promising avenue as an at-home therapeutic for TBI survivors. This abstract was previously published on clinicaltrials.gov and can be found at: https://www.clinicaltrials.gov/ct2/show/NCT05278273.


Inhibition of spleen tyrosine kinase attenuates allergen-mediated airway constriction.
Spleen tyrosine kinase (SYK) is a key activator of signaling pathways downstream of multiple surface receptors implicated in asthma. SYK function has been extensively studied in mast cells downstream of the high-affinity IgE receptor, FcεR1. Preclinical studies have demonstrated a role for SYK in models of allergic inflammation, but a role in airway constriction has not been demonstrated. Here, we have used a potent and selective pharmacological inhibitor of SYK to determine the role of SYK in allergen-mediated inflammation and airway constriction in preclinical models. Attenuation of allergic airway responses was evaluated in a rat passive anaphylaxis model and rat and sheep inhaled allergen challenge models, as well as an ex vivo model of allergen-mediated airway constriction in rats and cynomolgus monkeys. Pharmacological inhibition of SYK dose-dependently blocked IgE-mediated tracheal plasma extravasation in rats. In a rat ovalbumin-sensitized airway challenge model, oral dosing with an SYK inhibitor led to a dose-dependent reduction in lung inflammatory cells. Ex vivo analysis of allergen-induced airway constriction in ovalbumin-sensitized brown Norway rats showed a complete attenuation with treatment of a SYK inhibitor, as well as a complete block of allergen-induced serotonin release. Similarly, allergen-mediated airway constriction was attenuated in ex vivo studies from nonhuman primate lungs. Intravenous administration of an SYK inhibitor attenuated both early- and late-phase allergen-induced increases in airway resistance in an Ascaris-sensitive sheep allergen challenge model. These data support a key role for SYK signaling in mediating allergic airway responses.


Rhinoplasty Refinements: Addressing the Deviated, Overprojected Nose.
Deprojection of an overprojected nose and correction of an infralobular deformity are very challenging for rhinoplasty surgeons because a systematic approach is needed to correct these problems. A deviated nose with a dorsal hump is a common deformity that is best treated using septal reconstruction and the component dorsal hump reduction technique using an open rhinoplasty approach. This article and its videos show how to correct a deviated nose with overprojection and a dorsal hump deformity.


[Percutaneous and intraluminal radiotherapy and radiochemotherapy in esophageal carcinoma].
Next to standard external beam radiation therapy, combined treatment schedules of percutaneous and endoluminal radiotherapy as well as simultaneous radiochemotherapy became important over the past ten years, especially for primarily inoperable, advanced carcinomas of the esophagus. Analyzing representative treatment protocols, the following conclusions are evident: the combination of external high-voltage therapy and endoluminal brachytherapy using high-dose afterloading techniques leads to intensified biologically effective tumor doses with increasing tumor control. The simultaneous application for radio- and chemotherapy with 5-fluorouracil, cisplatinum or mitomycin results in a longer median survival compared to irradiation alone, and it is comparable to results in historical controls with radical esophagectomy. Up to now, no reduction of distant metastases was seen after simultaneous radiochemotherapy regimen alone. There is some evidence, that intensified chemotherapy before or after radiochemotherapy might result in improved survival rates and decreased distant metastases.


Smartphone-based exercise intervention for chronic pain: PainReApp randomized clinical trial protocol.
To evaluate the effectiveness of PainReApp, an mHealth system, based on physical exercise recommendations for patients with chronic pain (low back pain, fibromyalgia and diabetic neuropathic pain) based on pain intensity, quality of life, anxiety and/or depression, and sleep quality. Single-blinded randomized controlled trial. One hundred patients from three different chronic conditions (low back pain, fibromyalgia and neuropathic diabetic pain) will be recruited and randomized into two groups to receive the intervention with a physical activity program guided by the PainReApp system (experimental group) or with the program information in paper format (control group). All patients will attend a first face-to-face session in which the smartphone application usage (experimental group) and exercise execution will be explained (both groups). Data will be collected at baseline, 4, 12 and 24 weeks. Nevertheless, the users of the application will have a daily registry of the exercise performed and the self-perceived difficulty. The primary outcomes of the trial will be the intensity of pain and quality of life. Anxiety and/or depression and sleep quality will be also assessed to evaluate the influence of the physical activity at multiple levels. Physical exercise is becoming one of the leading evidence-based interventions to treat chronic pain. It needs to be adapted to the necessities of each pain condition. One of the major problems is the low adherence to the proposed program. New strategies that empower the patients, such as the m-Health, are reliable and useful tools to ease this end. To the best of our knowledge, this is the first long-term randomized controlled trial researching the impact of an m-health system on chronic pain from different origin. The intervention is based on international physical exercise recommendations and can be performed without specific material, allowing the home-based practice. Australian and New Zealand Clinical Trials Registry (ACTRN12621000783820).


Efficacy of balance training on postural control in patients with rotator cuff disease: a randomized controlled study.
We evaluated the efficacy of adding balance training to a physical therapy program on postural control and health-related quality of life in patients with rotator cuff disease. Forty-two participants were randomly allocated to the control and intervention groups. Both groups received physical therapy (education, stretching, supervised strength training, and home exercise program) 3 days/week for 6 weeks. The intervention group was instructed to perform balance exercises at home. The primary outcomes were the stability index, the Fourier transformation (F5 and F6), the weight distribution index, and the fall index, as assessed by the posturography during eight conditions with different combinations of standing (solid surface, pillows, and different head positions) and vision (eyes open/closed). The secondary outcomes included the Western Ontario Rotator Cuff Index to assess the health-related quality of life, the Shoulder Pain and Disability Index, and the Numeric Pain Rating Scale. The adherence to in-person and home-based therapy was high (>83%). The intervention group significantly improved the stability index, F5, and F6 parameters but each in only one condition (P < 0.05). No significant improvement was found in the conditions for the other primary outcomes and in the health-related quality of life. (P > 0.05). We conclude that adding the balance training protocol to the physical therapy program does not improve postural control and health-related quality of life in patients with rotator cuff disease.


Arsenite oxidation-enhanced photocatalytic degradation of phenolic pollutants on platinized TiO2.
The effect of As(III) on the photocatalytic degradation of phenolic pollutants such as 4-chlorophenol (4-CP) and bisphenol A (BPA) in a suspension of platinized TiO2 (Pt/TiO2) was investigated. In the presence of As(III), the photocatalytic degradation of 4-CP and BPA was significantly enhanced, and the simultaneous oxidation of As(III) to As(V) was also achieved. This positive effect of As(III) on the degradation of phenolic pollutants is attributed to the adsorption of As(V) (generated from As(III) oxidation) on the surface of Pt/TiO2, which facilitates the production of free OH radicals ((•)OHf) that are more reactive than surface-bound OH radicals ((•)OHs) toward phenolic pollutants. The generation of (•)OHf was indirectly verified by using coumarin as an OH radical trapper and comparing the yields of coumarin--OH adduct (i.e., 7-hydroxycoumarin) formed in the absence and presence of As(V). In repeated cycles of 4-CP degradation, the degradation efficiency of 4-CP gradually decreased in the absence of As(III), whereas it was mostly maintained in the presence of As(III), which was either initially present or repeatedly injected at the beginning of each cycle. The positive effect of As(III) on 4-CP degradation was observed over a wide range of As(III) concentrations (up to mM levels) with Pt/TiO2. However, a high concentration of As(III) (hundreds of μM) inhibited the degradation of 4-CP with bare TiO2. Therefore, Pt/TiO2 can be proposed as a practical photocatalyst for the simultaneous oxidation of phenolic pollutants and As(III) in industrial wastewaters.


Production of compartmented cultures of rat sympathetic neurons.
The compartmented culture, in which primary neurons plated in a proximal compartment send their axons under silicone grease barriers and into left and right distal compartments, has enhanced the experimental capabilities of neuronal cultures. Treatments can be applied separately to cell bodies/proximal axons or distal axons, and cell bodies/proximal axons and distal axons can be separately harvested and analyzed. Distal axons can be axotomized, and the neurons can be studied while their axons regenerate. Construction of the culture dishes requires 3 h for 48 cultures, and preparing the neurons also requires 3 h. Compartmented cultures provide enough cellular material for biochemical analyses such as immunoblotting. The uses of compartmented cultures have included studies of neurotrophic factor retrograde signaling, axonal transport, and axonal protein and lipid biosynthesis. Here we focus on sympathetic neurons cultured from neonatal rats and provide protocols for the production and some of the uses of compartmented cultures.


Hhex Directly Represses BIM-Dependent Apoptosis to Promote NK Cell Development and Maintenance.
Hhex encodes a homeobox transcriptional regulator important for embryonic development and hematopoiesis. Hhex is highly expressed in NK cells, and its germline deletion results in significant defects in lymphoid development, including NK cells. To determine if Hhex is intrinsically required throughout NK cell development or for NK cell function, we generate mice that specifically lack Hhex in NK cells. NK cell frequency is dramatically reduced, while NK cell differentiation, IL-15 responsiveness, and function at the cellular level remain largely normal in the absence of Hhex. Increased IL-15 availability fails to fully reverse NK lymphopenia following conditional Hhex deletion, suggesting that Hhex regulates developmental pathways extrinsic to those dependent on IL-15. Gene expression and functional genetic approaches reveal that Hhex regulates NK cell survival by directly binding Bcl2l11 (Bim) and repressing expression of this key apoptotic mediator. These data implicate Hhex as a transcriptional regulator of NK cell homeostasis and immunity.


(Re)visualizing Black lesbian lives, (trans)masculinity, and township space in the documentary work of Zanele Muholi.
This article explores the politics of representing Black queer and trans subjectivities in the recent documentary film and photography of South African lesbian visual activist Zanele Muholi. While Muholi's work has been most often been positioned as an artistic response to the hate-crimes and violence perpetuated against Black lesbians in South African townships, most notably acts of sexual violence known increasingly as corrective rape, I argue that Muholi's documentary texts trouble the spatial, gendered, and highly racialized articulations that make up an increasingly global corrective rape discourse. The article considers how her visual texts foreground and (re)visualize Black queer and trans gender experiences that relocate, challenge, collaborate with, and at times, perform, masculinity as means to subvert heterosexist and racist constructions of township space and the Black gendered body.


Substrate binding is required for assembly of the active conformation of the catalytic site in Ntn amidotransferases: evidence from the 1.8 A crystal structure of the glutaminase domain of glucosamine 6-phosphate synthase.
Amidotransferases use the amide nitrogen of glutamine in a number of important biosynthetic reactions. They are composed of a glutaminase domain, which catalyzes the hydrolysis of glutamine to glutamate and ammonia, and a synthetase domain, catalyzing amination of the substrate. To gain insight into the mechanism of nitrogen transfer, we examined the structure of the glutaminase domain of glucosamine 6-phosphate synthase (GLMS). The crystal structures of the enzyme complexed with glutamate and with a competitive inhibitor, Glu-hydroxamate, have been determined to 1.8 A resolution. The protein fold has structural homology to other members of the superfamily of N-terminal nucleophile (Ntn) hydrolases, being a sandwich of antiparallel beta sheets surrounded by two layers of alpha helices. The structural homology between the glutaminase domain of GLMS and that of PRPP amidotransferase (the only other Ntn amidotransferase whose structure is known) indicates that they may have diverged from a common ancestor. Cys1 is the catalytic nucleophile in GLMS, and the nucleophilic character of its thiol group appears to be increased through general base activation by its own alpha-amino group. Cys1 can adopt two conformations, one active and one inactive; glutamine binding locks the residue in a predetermined conformation. We propose that when a nitrogen acceptor is present Cys1 is kept in the active conformation, explaining the phenomenon of substrate-induced activation of the enzyme, and that Arg26 is central in this coupling.


A social stress model of substance abuse.
The social stress model provides a framework for detecting protective factors that may contribute to adolescents' resiliency when confronted with compelling influences to engage in substance abuse. Parameters of the model were tested in 2 urban high school samples (N = 124) of Black (78%), White (16%), and Hispanic (6%) adolescents aged 12-14 years. Pretest and posttest measures, designed to detect the relative influence of stress, social networks, social competencies, and community resources on levels of students' usage, were completed at the beginning and end of the school year. The parameters of the model, estimated using LISREL7, indicated that the pathway from family characteristics to usage and from assertion to usage were significant. The paths from the remaining hypothesized variables were not significant. Implications for the design of prevention programs that facilitate youths' resiliency are discussed.