Structure of calmodulin bound to the hydrophobic IQ domain of the cardiac Ca(v)1.2 calcium channel.
Ca2+-dependent inactivation (CDI) and facilitation (CDF) of the Ca(v)1.2 Ca2+ channel require calmodulin binding to a putative IQ motif in the carboxy-terminal tail of the pore-forming subunit. We present the 1.45 A crystal structure of Ca2+-calmodulin bound to a 21 residue peptide corresponding to the IQ domain of Ca(v)1.2. This structure shows that parallel binding of calmodulin to the IQ domain is governed by hydrophobic interactions. Mutations of residues I1672 and Q1673 in the peptide to alanines, which abolish CDI but not CDF in the channel, do not greatly alter the structure. Both lobes of Ca2+-saturated CaM bind to the IQ peptide but isoleucine 1672, thought to form an intramolecular interaction that drives CDI, is buried. These findings suggest that this structure could represent the conformation that calmodulin assumes in CDF.


Adaptive Neural Coordinated Control for Multiple Euler-Lagrange Systems With Periodic Event-Triggered Sampling.
This article addresses the event-triggered coordinated control problem for multiple Euler-Lagrange systems subject to parameter uncertainties and external disturbances. Based on the event-triggered technique, a distributed coordinated control scheme is first proposed, where the neural network-based estimation method is incorporated to compensate for parameter uncertainties. Then, an input-based continuous event-triggered (CET) mechanism is developed to schedule the triggering instants, which ensures that the control command is activated only when some specific events occur. After that, by analyzing the possible finite-time escape behavior of the triggering function, the real-time data sampling and event monitoring requirement in the CET strategy is tactfully ruled out, and the CET policy is further transformed into a periodic event-triggered (PET) one. In doing so, each agent only needs to monitor the triggering function at the preset periodic sampling instants, and accordingly, frequent control updating is further relieved. Besides, a parameter selection criterion is provided to specify the relationship between the control performance and the sampling period. Finally, a numerical example of attitude synchronization for multiple satellites is performed to show the effectiveness and superiority of the proposed coordinated control scheme.


[Pituitary apoplexy and empty sella].
Pituitary apoplexy (PA) is currently considered as one of the causes of empty sella (ES). However, in most reported cases the diagnosis of PA was based on anamnesis. A prospective study of three patients diagnosed during the PA episode was carried out. Periodical evaluations of hormone concentrations and cerebral computed tomography images were carried out. Initially, the three patients had a global anterior pituitary developed ES within 6 and 18 months. Surgical therapy was not undertaken in any case. Owing to the rarity of the disease definitive conclusions are difficult to obtain; however, the present study suggests that after an episode of PA global anterior pituitary failure develops, with subsequent ES. Early medical therapy with glucocorticoids can avoid surgical therapy.


Genetic variation in Labeo fimbriatus (Cypriniformes: Cyprinidae) populations as revealed by partial cytochrome b sequences of mitochondrial DNA.
Labeo fimbriatus, a medium sized carp is assessed as a commercially important aquaculture species in Indian subcontinent. In the present study, the genetic diversity and population structure of four Indian riverine populations of L. fimbriatus have been evaluated using partial cytochrome b sequences of mitochondrial DNA. Sequencing and analysis of this gene from 108 individuals defined 7 distinct haplotypes. Haplotype diversity (Hd) and nucleotide diversity (π) ranged from 0.067 to 0.405 and 0.00023 to 0.03231, respectively. The Mahanadi population had the highest π level. Analysis of molecular variance (AMOVA) indicated that 47.36% of genetic variation contained within population and 53.76% of genetic variation among groups. Pairwise FST analysis indicated that there was little or no genetic differentiation among populations (-0.0018 to 04572) from different geographical regions except Mahanadi population. The Mahanadi population can be considered as a separate stock from rest three riverine populations. Accordingly, the genetic information generated from this study can be implemented while taking decision in formulating base population for the sustainable selective breeding programs of this species.


Trends in premature mortality in the Islamic Republic of Iran: probability of dying between ages 30 and 70 years.
The burden of noncommunicable diseases (NCDs) is a major challenge facing the whole world. Around 15 million premature deaths due to NCDs occur in people aged 30-70 years annually. Mortality data based on death registration systems and population data were used to estimate proposed mortality statistics in the Islamic Republic of Iran. Various criteria and methods were used to assess the quality of mortality data. The probability of dying among those aged 30-70 years for all causes and for NCDs was calculated using the life table method. The mortality rate in the population aged 30-69 years was 343.12 (per 100 000 persons) in 2006 and decreased to 240.62 in 2016 in both sexes. The probability of dying due to NCDs was 21.36% in 2006 and declined to 14.95% in 2016 for both sexes. The number of premature deaths due to NCDs have decreased over the last decade. We predict that this reduction will continue and the country will meet the targets of the WHO NCD action plan by 2025 and also the targets of the Sustainable Development Goals for reducing premature deaths by 2030. However, the morbidity and burden of NCDs are still public health concerns in the country. Due to advancements in health care technologies and also the aging population, these concerns will impose greater costs on the health system. Hence, prevention programmes for NCDs should be an urgent priority for Iranian health policy.


Uniaxial magnetocrystalline anisotropy of metal/semiconductor interfaces: Fe/ZnSe(001).
A theoretical study of the magnetic moments and the in-plane magnetic anisotropy of an interface between a cubic ferromagnet and a cubic semiconductor, Fe/ZnSe(001), is presented. Theory confirms the observed, much debated, uniaxial anisotropy of the iron film. This result is important since the calculations are for perfect interfaces with squarelike environments, proving that the fourfolded symmetry of the interface Fe atoms is broken beyond the nearest neighboring semiconducting layer, effects that are usually assumed small. It is demonstrated how the uniaxial anisotropy is produced by the directional covalent bonds at the interface, even without atomic relaxations.


[Effects of testosterone on smooth muscle in the isolated rabbit corpus cavernosum penis].
It has been reported that there is no relationship between serum testosterone level and erectile function and that testosterone mainly acts on the brain and not on the penis. However, we have found that erectile dysfunction in some patients with low serum testosterone improved after androgen replacement therapy. We therefore studied the effects of testosterone on the contraction and relaxation of the corpus cavernosum penis. Four groups of rabbits were studied over a similar time span. The testosterone group were non-operated and received testosterone propionate 10 mg/day for 14 days before sacrifice. Two groups (castration+testosterone group and castration group) were castrated 28 days before sacrifice. The castration group received sesame oil for 14 days, and the castration+testosterone group received testosterone 10 mg/day for 14 days. Entire penis were removed immediately after death by desanguination and dissected to obtain corpus cavernosum strips. These strips were suspended under 1 g tension in a 20 ml organ bath containing Tyrode's solution. After equilibration for 2 hours, the addition of drugs was started. Changes in tension were monitored with an isometric transducer and recorded. The vasoactive drugs used were norepinephrine bitartrate, 1-phenylephrine hydrochloride, clonidine hydrochloride, acetylcholine chloride and vasoactive intestinal polypeptide. The contractility of the corpus cavernosum strips increased significantly in the testosterone group and the castration + testosterone group, but decreased significantly in the castration group as compared with the control after adding norepinephrine, phenylephrine and clonidine.(ABSTRACT TRUNCATED AT 250 WORDS)


Developments in treatment of primary irresectable rectal cancer.
Abstract The treatment options for primary irresectable rectal cancers are discussed. Assessment of tumour stage is the first step for an appropriate choice of treatment. Following a diagnosis of rectal cancer, a vast array of diagnostic procedures is available to determine its stage, and thereby its best treatment options. From the many (new) diagnostic options the merits and drawbacks are discussed. If a diagnosis of irresectability is made, further treatment options should include radiotherapy in most cases, some aspects of timing and application, i.e. intra-operative treatment are discussed. Chemotherapy options are manifold, the results are discussed and some new options are explored.


Secreted Factors from Adipose Tissue Reprogram Tumor Lipid Metabolism and Induce Motility by Modulating PPARα/ANGPTL4 and FAK.
Recent studies indicate that adipose tissue in obesity promotes breast cancer progression by secreting protumorigenic chemokines, growth factors, and fatty acids. However, the detailed mechanisms by which hypertrophic adipose tissue influences breast cancer cells are still not well understood. Here we show that co-culture with adipose tissue from high-fat diet induced obese C57BL/6 mice alters transcriptome profiles in triple-negative breast cancer (TNBC) cells, leading to upregulation of genes involved in inflammation and lipid metabolism, such as IL1B, PLIN2, and ANGPTL4. Similar results were obtained by treating TNBC cells with adipose tissue conditioned media (ACM) generated from fat tissue of obese female patients. Many of the upregulated genes were activated by PPAR nuclear receptors, as shown by pathway analyses and gene expression experiments using PPAR agonists and antagonists. Metabolic analysis revealed that TNBC cells cultivated with ACM had significantly higher levels of β-oxidation. Furthermore, ACM-treated TNBC cells displayed a pronounced aggressive cell phenotype, with enhanced wound healing, proliferation, and invasion capabilities. ACM-induced invasion was dependent on the PPAR-target ANGPTL4 and activated FAK signaling, as shown by ANGPTL4 depletion and FAK inhibition. Together, our data suggest that factors released by adipose tissue change PPAR-regulated gene expression and lipid metabolism and induce a more aggressive TNBC cell phenotype. These effects are, at least in parts, mediated by fatty acids provided by the adipose tissue. IMPLICATIONS: Adipose tissue provides factors for increased progression of TNBC cells, identifying PPAR- and FAK-signaling as potential novel targets for treatment of TNBC, especially in obese women.


Bone Marrow Micrometastases in Breast Cancer Patients: A Long-Term Follow-up Study.
In 125 early breast cancer patients who underwent multiple bone marrow aspirates, there was no significant difference in terms of disease-free and overall survival after a median follow-up of 163 months between the patients with or without micrometastasis at the time of primary surgery. However, when the time-dependent evolution of the bone marrow aspirates was taken into account, some evidence for a longer disease-free and overall survival was found for the patients with negative bone marrow.


Teaching clinical reasoning to undergraduate medical students by illness script method: a randomized controlled trial.
The illness script method employs a theoretical outline (e.g., epidemiology, pathophysiology, signs and symptoms, diagnostic tests, interventions) to clarify how clinicians organized medical knowledge for clinical reasoning in the diagnosis domain. We hypothesized that an educational intervention based on the illness script method would improve medical students' clinical reasoning skills in the diagnosis domain. This study is a randomized controlled trial involving 100 fourth-year medical students in Shiraz Medical School, Iran. Fifty students were randomized to the intervention group, who were taught clinical reasoning skills based on the illness script method for three diseases during one clinical scenario. Another 50 students were randomized to the control group, who were taught the clinical presentation based on signs and symptoms of the same three diseases as the intervention group. The outcomes of interest were learner satisfaction with the intervention and posttest scores on both an internally developed knowledge test and a Script Concordance Test (SCT). Of the hundred participating fourth-year medical students, 47 (47%) were male, and 53 (53%) were female. On the knowledge test, there was no difference in pretest scores between the intervention and control group, which suggested a similar baseline knowledge in both groups; however, posttest scores in the intervention group were (15.74 ± 2.47 out of 20) statistically significantly higher than the control group (14.38 ± 2.59 out of 20, P = 0.009). On the SCT, the mean score for the intervention group (6.12 ± 1.95 out of 10) was significantly higher than the control group (4.54 ± 1.56 out of 10; P = 0.0001). Learner satisfaction data indicated that the intervention was well-received by students. Teaching with the illness script method was an effective way to improve students' clinical reasoning skills in the diagnosis domain suggested by posttest and SCT scores for specific clinical scenarios. Whether this approach translates to improved generalized clinical reasoning skills in real clinical settings merits further study.


The Torres Indigenous Hip Hop Project: evaluating the use of performing arts as a medium for sexual health promotion.
The Torres Indigenous Hip Hop Project (the Project) was conducted in the Torres and Northern Peninsula Area of Queensland during early 2010. This paper provides a critical analysis of project outcomes and identifies criteria that may form a suitable framework for the assessment of proposals for sexual health promotion using performing arts-based approaches in Aboriginal and Torres Strait Islander settings. A case study method was used. The first phase of analysis assessed whether project objectives were met using data collected during project planning and implementation. The second phase used these findings, augmented by interviews with key personnel, to respond to the question 'How could this be done better?'. The Project required significant human and organisational implementation support. The project was successful in facilitating event-specific community mobilisation. It raised awareness of sexual health disadvantage and engaged effectively with the target group. It laid important groundwork to progress school-based and community mechanisms to address regional youth disadvantage. Against these benefits are issues of opportunity cost and the need for ongoing resources to capitalise on the opportunities created. With substantial support and planning, such approaches can play an important role in engaging young people and bridging the gap between clinical interventions and improvements in health deriving from community-driven strategies. SO WHAT? This paper contributes to existing literature by identifying key elements of an effective approach to using performing arts in sexual health promotion in Aboriginal and Torres Strait Islander settings. It also provides guidance when consideration is being given to investment in resource-intensive health promotion initiatives.


New metal-organic polygons involving MM quadruple bonds: M8(O2CtBu)4(mu-SC4H2-3,4-{CO2}2)6 (M=Mo, W).
The reactions between M2(O2CtBu)4, where M=Mo or W, and thienyl-3,4-dicarboxylic acid (0.5-1.5 equiv) in toluene proceed via a series of detectable intermediates to the compounds M8(O2CtBu)4(mu-SC4H2-3,4-{CO2}2)6, which are isolated as air-sensitive yellow (M=Mo) or red (M=W) powders and show parent molecular ions in their mass spectra (MALDI). The structure of the molybdenum complex was determined by single-crystal X-ray crystallography and shown to contain an unusual M8 polygon involving four Mo2 quadruply bonded units linked via the agency of the six 3,4-thienylcarboxylate groups. The structure has crystallographically imposed S4 symmetry and may be described in terms of a highly distorted tetrahedron of Mo2 units or a bisphenoid in which two Mo2 units are linked by a thienyldicarboxylate such that intramolecular Mo2...O bonding is present, while the other thienylcarboxylate bridges merely serve to link these two [Mo2]...[Mo2] units together. The color of the compounds arises from intense M2 delta-to-thienyl pi transitions and, in THF, the complexes are redox-active and show four successive quasi-reversible oxidation waves. The [M8]+ radical cations, generated by one-electron oxidation with AgPF6, are shown to be valence-trapped (class II) by UV-vis-near-IR and electron paramagnetic resonance spectroscopy. These results are supported by the electronic structure calculations on model compounds M8(O2CH)4(mu-SC4H2-3,4-{CO}2)6 employing density functional theory that reveal only a small splitting of the M2 delta manifold via mixing with the 3,4-thienylcarboxylate pi system.


The characteristics of EEG power spectra changes after ACL rupture.
Reestablishing knee stability is the core of the treatment of ACL (Anterior Cruciate Ligament) injury. Some patients still have a feeling of instability of the knee after ACL injury treatment. This unstable feeling may be caused by central nervous system changes after ACL rupture. To identify the central changes after ACL rupture, EEG spectra were recorded to compare ACL patients and healthy controls when they were walking, jogging, and landing. There was a significant increase in delta, theta, alpha and beta band power during walking, jogging and landing in ACL patients. We also found an asymmetry phenomenon of EEG only in the ACL patients, mainly in the frontal area and central-parietal area. The asymmetry of beta band power extended to the frontal and the central area during jogging and landing task. There were significant differences in EEG power spectra between the ACL patients and healthy people. ACL patients showed high EEG band power activities and an asymmetry phenomenon. EEG power changes were affected by movements, the asymmetry extended when performing more complicated movements.


Closed intramedullary shortening of the femur.
Closed intramedullary shortening of the femur in the adult provides a method for leg length equalization that poses minimal operative risks, maximizes healing, and produces an excellent functional and cosmetic result. The etiology of anisomelia and any associated abnormalities must be carefully analyzed preoperatively. A series of 40 closed intramedullary shortenings of the femur were performed; shortening averaged 3.3 cm (range 2.0 to 5.0 cm). Three patients had significant complications: delayed union in one patient required renailing; two cases of symptomatic external rotation deformity required correction. The technique for the procedure is demanding in terms of experience and equipment. Otherwise, intramedullary femoral shortening is an excellent method for managing adult anisomelia.


The male external urethral sphincter is autonomically innervated.
The aim of the present study was to describe autonomic urethral sphincter (US) innervation using specific muscular and neuronal antibody markers and 3D reconstruction. We performed en-bloc removal of the entire pelvis of three male human fetuses between 18 and 40 weeks. Serial whole mount sections (5 μm intervals) were stained and investigated. The sections were stained with Masson's trichrome and Eosin Hematoxylin, and immunostained with: anti-SMA antibody for smooth muscle; anti-S100 antibody for all nerves; and anti-PMP22 antibody, anti-TH antibody, anti-CGRP antibody, anti-NOS antibody for somatic, adrenergic, sensory and nitrergic nerve fibers, respectively. The slides were digitized for 3D reconstruction to improve topographical understanding. An animated reconstruction of the autonomic innervation of the US was generated. The external and internal US are innervated by autonomic nerves of the inferior hypogastric plexus (IHP). These nerves are sympathetic (positive anti-TH antibody), sensory (positive anti-CGRP antibody), and nitrergic (positive anti-NOS antibody). Some autonomic fibers run within the neurovascular bundles, posterolaterally. Others run from the IHP to the posteromedial aspect of the prostate apex, above an through the rectourethral muscle. The external US is also innervated by somatic nerves (positive anti-PMP22 antibody) arising from the pudendal nerve, joining the midline but remaining below the rectourethral. This study provides anatomical evidence of an autonomic component in the innervation of the external US that travels in the neurovascular bundle. During radical prostatectomy, the rectourethral muscle and the neurovascular bundles are to be preserved, particularly during apical dissection.


Paradoxical cold conditions during the medieval climate anomaly in the Western Arctic.
In the Northern Hemisphere, most mountain glaciers experienced their largest extent in the last millennium during the Little Ice Age (1450 to 1850 CE, LIA), a period marked by colder hemispheric temperatures than the Medieval Climate Anomaly (950 to 1250 CE, MCA), a period which coincided with glacier retreat. Here, we present a new moraine chronology based on (36)Cl surface exposure dating from Lyngmarksbræen glacier, West Greenland. Consistent with other glaciers in the western Arctic, Lyngmarksbræen glacier experienced several advances during the last millennium, the first one at the end of the MCA, in ~1200 CE, was of similar amplitude to two other advances during the LIA. In the absence of any significant changes in accumulation records from South Greenland ice cores, we attribute this expansion to multi-decadal summer cooling likely driven by volcanic and/or solar forcing, and associated regional sea-ice feedbacks. Such regional multi-decadal cold conditions at the end of the MCA are neither resolved in temperature reconstructions from other parts of the Northern Hemisphere, nor captured in last millennium climate simulations.


Ovariectomy enhances renal cortical expression and function of cyclooxygenase-2.
Cyclooxygenase-2 (COX-2) inhibitors are used as analgesics in postmenopausal women, who develop edema and require a salt-restricted diet. This study was performed to determine the renal expression of COX-2 and on COX-2-dependent regulation of renal blood flow (RBF) in ovariectomized rats. Sprague-Dawley rats were divided into 4 groups: sham-operated rats fed a normal-salt diet (Sh+NS) or a low-salt diet (Sh+LS), and bilaterally ovariectomized rats fed a normal-salt diet (Ox+NS) or a low-salt diet (Ox+LS) (N= 6 in each group). Estrogen replacement therapy was performed on other ovariectomized rats. A renal clearance study was performed in anesthetized animals. Ovariectomy increased renal cortical COX-2 expression independently of dietary salt intake (Sh+NS <Ox+N; Sh+LS <Ox+LS). Inhibition of COX-2 by NS398 reduced the urinary excretion of 6-keto-prostaglandin F1alpha in all 4 groups, although the reduction was greater in the Ox+LS group than in the Ox+NS and Sh+LS groups, which in turn had a greater reduction than the Sh+NS group. RBF significantly decreased in every group except the Sh+NS group, but no effect on blood pressure, inulin clearance, or urinary sodium excretion was seen. The decrease in RBF was significantly greater in the Ox+LS group than in the Sh+LS and Ox+NS group. The decrease in RBF was dependent on cortical RBF in the Sh+LS and Ox+NS groups, and on both cortical and medullary RBF in the Ox+LS group. Estrogen replacement therapy reversed the ovariectomy-induced changes. Estrogen-dependent COX-2 expression plays an important role in the RBF regulation in female rats.


Impact of GDP, spending on R&D, number of universities and scientific journals on research publications in pharmacological sciences in Middle East.
Research in pharmacological science is vital to support the health needs of human beings. Measuring the research output provides information that forms the basis of strategic decisions. This study aimed to investigate the impact of Gross Domestic Product (GDP), spending on Research and Development (R&D), number of universities and scientific journals on research documents (papers), citable documents, citations per document and H-index in pharmacological science among Middle East countries. All the 16 Middle East countries were included in the study. The information regarding GDP, spending on R&D, total number of universities and indexed scientific journals were collected. We recorded the total number of research documents, citable documents, citations per document and H-index in pharmacological science during the period 1996-2011. The main sources for information were World Bank, Web of Science, Journal Citation Reports (Thomson Reuters) and SCI-mago/Scopus. The mean per capita GDP of all the Middle East countries is 18125.49±5386.28 US$, spending on R&D 0.63±0.28% of GDP in US$, number of universities 36.56±11.33 and mean ISI indexed journal are 8.25±3.93. The number of research documents published in pharmacological science among the Middle East countries during the period 1996-2011 is 1344.44±499.34; citable documents 1286.37±476.34; citations per document 7.62± 0.84; and H-index is 30.68±6.32. There was a positive correlation between spending on R&D and citations per documents (r = 0.56, p = 0.02), H-Index (r = 0.56, p = 0.02); number of universities and research documents (r = 0.72, p = 0.002), citable documents (r = 0.72, p = 0.001); ISI indexed journals and research documents (r = 0.88, p = 0.0001), citable documents (r = 0.88, p = 0.0001), H-Index (r = 0.67, p = 0.004). However, there was no correlation between the GDP per capita and research outcome in pharmacological science. There is a positive association between spending on R&D, number of universities and indexed scientific journals on research outcome in pharmacological science in Middle East.


[The microscopic vasculitis in tongue].
This is the first report of 16 cases with microscopic vasculitis of the tongue in Chinese literatures. The clinical manifestations and histopathology of the disease were described. The treatment of promoting blood circulation to remove blood was used stasis. Probably the microscopic vasculitis plays an importment role in the glossodynia.


Primary Segmental Small Bowel Volvulus in an Adolescent Female.
Small bowel volvulus is a rare but important cause of abdominal pain and small bowel obstruction in children and adults. In the neonate, small bowel volvulus is a well-known complication of malrotation. Segmental small bowel volvulus is a lesser-known condition, which occurs in children and adults alike and can rapidly progress to bowel ischemia. Primary segmental small bowel volvulus occurs in the absence of rotational anomalies or other intraabdominal lesions and is rare in Europe and North America. Clinical presentation can be misleading, causing a delay in diagnosis and treatment, in which case the resection of necrotic bowel may become necessary. We report on a 14-year-old girl who presented with severe colicky abdominal pain but showed no other signs of peritoneal irritation or bowel obstruction. An emergency magnetic resonance imaging was highly suspicious for small bowel volvulus. Emergency laparotomy revealed a 115 cm segment of strangulated distal ileum with no underlying pathology. We performed a detorsion of the affected bowel segment. Despite the initial markedly ischemic appearance of the affected bowel segment, the patient achieved full recovery without resection of bowel becoming necessary.


Sphingosine 1-phosphate signalling and termination at lipid phosphate receptors.
Sphingosine 1-phosphate (S1P) is a polar lysophospholipid metabolite that is stored in platelets and released upon their activation. However, diverse stimuli such as growth factors, cytokines, G-protein coupled receptor (GPCR) agonists and antigens have been shown to increase sphingosine kinase activity and S1P formation in other cell types, such as smooth muscle. Indeed, S1P has been implicated in the regulation of several important cellular processes, such as proliferation, differentiation, apoptosis and migration in these cells. Over the past few years, there has been a major advance in our understanding of how S1P can act as an intercellular mediator by binding to a new class of G-protein coupled receptors to regulate cell function. This review focuses on the enzymatic regulation of S1P formation and degradation and its interaction with a novel tethered receptor complex containing the S1P receptor (S1P(1)) and the platelet-derived growth factor (PDGF) beta receptor. This tethered receptor complex enables coincident integrative signalling to p42/p44 MAPK. This is compared with a sequential model in which PDGF promotes S1P release, which in turn acts on S1P(1) to promote Rac signalling.


Coronavirus Disease 2019 in Pregnancy: The Experience at an Urban Safety Net Hospital.
Shortly after the identification of a novel coronavirus, the coronavirus disease 2019, or COVID-19, a global pandemic was declared. There have been conflicting data about the severity of COVID-19 disease course in pregnant women, with most US data suggesting an increase in severity and increased need for hospitalization and intubation in obstetric patients. In the general population, the disease is more common among racial and ethnic minority populations, and severity is increased with comorbid conditions and obesity. The purpose of this study is to characterize COVID-19 infection in pregnancy in a population of women getting prenatal care at an urban safety-net hospital. Beginning in April, 2020, all women were tested at admission for delivery, and additionally as an outpatient if presenting with COVID-19 symptoms. In three months, there were 208 discrete women tested and 23 (11.1%) who were positive for COVID-19. The incidence of COVID-19 was 5.1% in asymptomatic women being screened upon admission to the hospital. There was a high prevalence of obesity (68.2%) and other comorbid conditions (43.5%) in this population, and all patients were racial/ethnic minorities. Despite these risk factors, the patients uniformly had either mild or asymptomatic disease. No symptomatic patients required hospitalization for their infection. In this population of pregnant women at high risk for severe COVID-19 infection, only mild disease was observed.


[A case of unusual branching and aberrant course of the segmental vein (V2) in the upper lobe of the right lung].
Two right pulmonary veins emptying into the left atrium is the normal state. We describe a case observed at operation in which three pulmonary veins were present on the right side and emptied into the left atrium; a third vein arised from the dorsal part of the upper lobe and followed an abnormal extrapulmonary course. Right lower lobectomy and mediastinal lymph node dissection were carried out for a 73-year-old male with lung carcinoma. At operation, an aberrant branching vein arising from the upper lobe descended dorsally to the right main bronchus and emptied into the left atrium at the middle point between carina and inferior pulmonary vein. The intermediate bronchus lay between the anomalous vein and superior pulmonary vein. Conventional tomogram, CT scan and pulmonary angiogram showed that pulmonary arteries and bronchi were normal in their pattern of branching and distribution, and that the anomalous vein observed at operation was comprised of V2a and V2b according to the system of naming on Yamashita's. Infrequent variations of pulmonary veins are to be kept in mind to that operation may be performed in safety.


NFIX mutations affecting the DNA-binding domain cause a peculiar overgrowth syndrome (Malan syndrome): a new patients series.
The Nuclear Factor I-X (NFIX) is a member of the nuclear factor I (NFI) protein family and is deleted or mutated in a subset of patients with a peculiar overgrowth condition resembling Sotos Syndrome as well as in patients with Marshall-Smith syndrome. We identified three additional patients with this phenotype each carrying a different new mutation affecting the DNA-binding/dimerization domain of the NFIX protein. The present report further adds weight to the hypothesis that mutations in DNA-binding/dimerization domain are likely to cause haploinsufficiency of the NFIX protein and confirms that NFIX is the second gene that should be tested in individuals with overgrowth conditions resembling Sotos syndrome, previously tested negative for NSD1 mutations. We then propose to consider this overgrowth syndrome (namely Malan syndrome) and Marshall-Smith syndrome NFIX-related diseases.


Assessment of prevalence and characteristics of asthma-COPD overlap among patients with chronic airflow obstruction.
Given the paucity of research on asthma-chronic obstructive pulmonary disease (COPD) overlap (ACO) and the high prevalence of co-morbidities and healthcare utilization associated with it, the current study looked at the prevalence of ACO and its clinico-radiological phenotype in patients with chronic airflow obstruction. The study was conducted at a tertiary care hospital in North India. Patients over 40 with COPD or asthma were screened for inclusion in the ACO, asthma, and COPD groups. The ACO and COPD groups were further investigated. The clinical characteristics, lung functions, health-related quality of life, and radiological features of both groups were investigated and compared. ACO was discovered in 16.3% of patients with chronic airflow obstruction (asthma and COPD). The most commonly observed symptoms at presentation in the evaluated ACO patients (n=77) were shortness of breath, wheezing, cough, and expectoration (mean age at presentation: 57.9; mean duration of illness: 8.62 years). Exacerbation rates in ACO patients were significantly higher than in COPD patients (p<0.001). The ACO group had a significantly greater mean change in FEV1 post-bronchodilator in millilitres (ml) and percentage (379.61 ml and 37.72%) than the COPD group (p<0.001). The proportion of patients with emphysema was lower in the ACO group than in the COPD group (p<0.001). The ACO and COPD groups did not differ significantly in major airway wall thickness (p=0.3), but the COPD group had a significantly higher proportion of patients with vascular attenuation and distortion (p<0.001). Patients with COPD had a higher degree of hyperinflation, according to high resolution computed tomography (HRCT) indices. This study found that patients with ACO have a distinct phenotype in terms of clinical presentation and HRCT features. More research on the radiological features of ACO is required to identify the anatomical abnormalities involved in the disease's pathogenesis and to validate the radiological features of ACO.


How Taiwanese parents of children with autism spectrum disorder experience the process of obtaining a diagnosis: A descriptive phenomenological analysis.
An autism spectrum disorder can result in considerable stress and confusion for parents as they attempt to understand their child's problems and obtain a diagnosis. Few studies have explored the parental experience in the context of Chinese culture. The purpose of this study was to understand the experiences of parents in Taiwan of children diagnosed with autism spectrum disorder. In total, 15 parents, 1 father and 14 mothers, were recruited by purposive sampling. This qualitative study used semi-structured interviews and descriptive phenomenological analysis. The findings indicated that parents of children diagnosed with autism spectrum disorder underwent five coping experiences during the diagnostic process: (1) uncertainty and difficulty understanding their child's behaviour, which occurred during the pre-diagnosis phase; (2) obligation to obtain professional services; (3) anxious searching for a second opinion, which occurred during the diagnosis phase; (4) acceptance and fortitude and (5) further adjustment during the post-diagnosis phase. Our findings add to our understanding of how parents experience the diagnostic process, which could improve medical professionals' counselling and support for parents at the stage of obtaining a diagnosis for their children.


Voltage multiplication circuit for starting uv source gas discharge lamps.
Gas discharge lamps need a momentary high voltage to initiate their operation but normal operation only requires a much lower operating voltage. Circuit design parameters are presented, together with a practical arrangement, so that the HV trigger pulse may be derived in an economical manner from the normal operating power source.


Biotransformation of genotoxic agents in marine sponges. Mechanisms and modulation.
Marine sponges do not appear to suffer from neoplastic diseases, in spite of possible high exposures resulting from their nature as sessile bottom filter feeders which pump large volumes of sea water. The assessment of several parameters related to the biotransformation of mutagens/carcinogens showed that the metabolic machinery of sponge medulla cells is mainly oriented towards detoxification, with some differences depending on species (Geodia cydonium or Tethya aurantium). Glutathione (GSH) levels were unexpectedly high in these cells, especially in Geodia, in which the concentration of this tripeptide was more than twice that measured in liver preparations from untreated rats, at least when related to the protein content. The oxidoreductive enzyme activities involved in the glutathione cycle were balanced in such a way as to favour a high GSH: oxidized glutathione (GSSG) ratio. GSH S-transferase activity was conversely rather low, compared to that of rat liver, and the dehydrogenases involved in the hexose monophosphate shunt were high in Tethya but low in Geodia. The metabolism of mutagens was investigated by using the Salmonella typhimurium his- strains TA100, TA98 and YG1024. Sponge S12 fractions failed to activate aflatoxin B1, benzo[a]pyrene and the two heterocyclic amines 3-amino-1-methyl-5H-pyrido[4,3-b]indole and 2-amino-3,4-dimethyl-imidazo[4,5-f]quinoline. Although far less efficiently than untreated rat liver S12 fractions, Geodia and especially Tethya preparations weakly activated the three aromatic amines 2-acetyl-aminofluorene, 2-aminofluorene and 2-aminoanthracene. On the other hand, sponge S12 fractions were remarkably efficient in decreasing the mutagenic potency of the direct-acting mutagens 4-nitroquinoline 1-oxide and sodium dichromate.(ABSTRACT TRUNCATED AT 250 WORDS)


Kondo Resonance of a Co Atom Exchange Coupled to a Ferromagnetic Tip.
The Kondo effect of a Co atom on Cu(100) was investigated with a low-temperature scanning tunneling microscope using a monoatomically sharp nickel tip. Upon a tip-Co contact, the differential conductance spectra exhibit a spin-split asymmetric Kondo resonance. The computed ab initio value of the exchange coupling is too small to suppress the Kondo effect, but sufficiently large to produce the splitting observed. A quantitative analysis of the line shape using the numerical renormalization group technique indicates that the junction spin polarization is weak.


Arabidopsis TNL-WRKY domain receptor RRS1 contributes to temperature-conditioned RPS4 auto-immunity.
In plant effector-triggered immunity (ETI), intracellular nucleotide binding-leucine rich repeat (NLR) receptors are activated by specific pathogen effectors. The Arabidopsis TIR (Toll-Interleukin-1 receptor domain)-NLR (denoted TNL) gene pair, RPS4 and RRS1, confers resistance to Pseudomonas syringae pv tomato (Pst) strain DC3000 expressing the Type III-secreted effector, AvrRps4. Nuclear accumulation of AvrRps4, RPS4, and the TNL resistance regulator EDS1 is necessary for ETI. RRS1 possesses a C-terminal "WRKY" transcription factor DNA binding domain suggesting that important RPS4/RRS1 recognition and/or resistance signaling events occur at the nuclear chromatin. In Arabidopsis accession Ws-0, the RPS4(Ws) /RRS1(Ws) allelic pair governs resistance to Pst/AvrRps4 accompanied by host programed cell death (pcd). In accession Col-0, RPS4(Col) /RRS1(Col) effectively limits Pst/AvrRps4 growth without pcd. Constitutive expression of HA-StrepII tagged RPS4(Col) (in a 35S:RPS4-HS line) confers temperature-conditioned EDS1-dependent auto-immunity. Here we show that a high (28°C, non-permissive) to moderate (19°C, permissive) temperature shift of 35S:RPS4-HS plants can be used to follow defense-related transcriptional dynamics without a pathogen effector trigger. By comparing responses of 35S:RPS4-HS with 35S:RPS4-HS rrs1-11 and 35S:RPS4-HS eds1-2 mutants, we establish that RPS4(Col) auto-immunity depends entirely on EDS1 and partially on RRS1(Col) . Examination of gene expression microarray data over 24 h after temperature shift reveals a mainly quantitative RRS1(Col) contribution to up- or down-regulation of a small subset of RPS4(Col) -reprogramed, EDS1-dependent genes. We find significant over-representation of WRKY transcription factor binding W-box cis-elements within the promoters of these genes. Our data show that RRS1(Col) contributes to temperature-conditioned RPS4(Col) auto-immunity and are consistent with activated RPS4(Col) engaging RRS1(Col) for resistance signaling.


Optical control of focal epilepsy in vivo with caged γ-aminobutyric acid.
There is enormous clinical potential in exploiting the spatial and temporal resolution of optical techniques to modulate pathophysiological neuronal activity, especially intractable focal epilepsy. We have recently utilized a new ruthenium-based caged compound, ruthenium-bipyridine-triphenylphosphine-γ-aminobutyric acid (RuBi-GABA), which releases GABA when exposed to blue light, to rapidly terminate paroxysmal activity in vitro and in vivo. The convulsant 4-aminopyridine was used to induce interictal activity and seizures in rat neocortical slices and anesthetized rats. We examined the effect of blue light, generated by a small, light-emitting diode (LED), on the frequency and duration of ictal activity in the presence and absence of RuBi-GABA. Neither blue light alone, nor low concentrations of RuBi-GABA, affected interictal activity or baseline electrical activity in neocortical slices. However, brief, blue illumination of RuBi-GABA, using our LED, dramatically reduced extracellular spikes and bursts. More impressively, illumination of locally applied RuBi-GABA rapidly terminated in vivo seizures induced by topical application of 4-aminopyridine. The RuBi-GABA effect was blocked by the GABA(A) antagonist picrotoxin, but not duplicated by direct application of GABA. This is the first example of optical control of in vivo epilepsy, proving that there is sufficient cortical light penetration from an LED and diffusion of caged GABA to quickly terminate intense focal seizures. We are aware that many obstacles need to be overcome before this technique can be translated to patients, but at the moment, this represents a feasible method for harnessing optical techniques to fabricate an implantable device for the therapy of neocortical epilepsy.


Human nonpancreatic secreted phospholipase A2: interfacial parameters, substrate specificities, and competitive inhibitors.
The rate and equilibrium parameters for the interfacial catalysis by recombinant human nonpancreatic secreted phospholipase A2 were determined. Results show that the enzyme binds to anionic interfaces with considerably higher affinity than to zwitterionic interfaces. The extent of hydrolysis per enzyme on anionic vesicles in the processive scooting mode shows that the enzyme is fully catalytically active as a monomer. Among several secreted phospholipases A2 tested, the human nonpancreatic secreted enzyme is unique in its ability to undergo slow intervesicle exchange either by dissociation from the interface followed by binding to a different vesicle or by promoting the fusion of vesicles. The equilibrium dissociation constants for calcium, substrate analogs, reaction products, and several competitive inhibitors bound to the enzyme at the interface were determined by monitoring the ligand-conferred protection of the active site histidine residue from alkylation by phenacyl bromide. The interfacial Michaelis-Menten parameters were determined from the analysis of the entire reaction progress curve and also by monitoring the effect of competitive inhibitors on the initial rate of hydrolysis in the scooting mode. The interfacial Michaelis constant (KM*) for the substrate 1,2-dimyristoylglycero-sn-3-phosphomethanol was determined to be considerably above the maximal attainable mole fraction of unity for the substrate in the bilayer. Substrate specificity studies show that the enzyme does not significantly discriminate between phospholipids that differ in the type of polar head group or in the degree of unsaturation of the fatty acyl chains. Competitive inhibitors are described that display a high degree of selectivity for binding to the nonpancreatic versus pancreatic phospholipase A2. The kinetic properties of the human nonpancreatic secreted phospholipase A2 suggest that the enzyme has evolved to hydrolyze substrates at anionic interfaces and at high calcium concentrations.


Identification of Pea Gibberellins by Studying [C]GA(12)-Aldehyde Metabolism.
Experiments were designed to test the hypothesis that the labeled products recovered from plant tissue incubated with [(14)C]GA(12)-7-aldehyde ([(14)C]GA(12)ald) would serve as appropriate [(14)C]markers for the recovery of naturally-occurring gibberellins (GAs). The [(14)C]GA(12)ald (about 200 millicuries per millimole) was synthesized from pumpkin endosperm using [4,5-(14)C]mevalonic acid. It was added to the adaxial surface of isolated pea cotyledons at 22 days after flowering. Products recovered after 0.5 and 4.0 hour incubations yielded four major peaks which were separated by high performance liquid chromatography (HPLC). These products were purified by multiple-column HPLC using on-line radioactivity detection. They were then added as [(14)C]markers to two unlabeled pea extracts. In general, preparative HPLC followed by further HPLC purification resulted in a single UV-absorbing peak co-eluting with each [(14)C]marker. These [(14)C] and UV-absorbing peaks were shown to contain GA(53), GA(44), GA(20), GA(19), and GA(17) by GC-MS. The finding of GA(53) is novel; all others have previously been found in pea. Endogenous GAs of pea were thus readily detected using [(14)C]GA(12)ald metabolites as [(14)C]markers to recover naturally occurring GAs suggesting that the method may be applicable in detecting naturally occurring GAs in other species.


Metal-Organic Polyhedron with Four Fe(III) Centers Producing Enhanced T1 Magnetic Resonance Imaging Contrast in Tumors.
A metal-organic polyhedron (MOP) with four paramagnetic Fe(III) centers was studied as a magnetic resonance imaging (MRI) probe. The MOP was characterized in solution by using electron paramagnetic resonance (EPR), UV-visible (UV-vis) spectroscopies, Fourier-transform ion cyclotron resonance (FT-ICR) mass spectrometry, and in the solid state with single-crystal X-ray diffraction. Water proton T1 relaxation properties were examined in solution and showed significant enhancement in the presence of human serum albumin (HSA). The r1 relaxivities in the absence and presence of HSA were 8.7 mM-1 s-1 and 21 mM-1 s-1, respectively, per molecule (2.2 mM-1 s-1 and 5.3 mM-1 s-1 per Fe) at 4.7 T, 37 °C. In vivo studies of the iron MOP show strong contrast enhancement of the blood pool even at a low dose of 0.025 mmol/kg with prolonged residence in vasculature and clearance through the intestinal tract of mice. The MOP binds strongly to serum albumin and shows comparable accumulation in a murine tumor model as compared to a covalently linked Gd-HSA contrast agent.


A (-)-kolavenyl diphosphate synthase catalyzes the first step of salvinorin A biosynthesis in Salvia divinorum.
Salvia divinorum (Lamiaceae) is an annual herb used by indigenous cultures of Mexico for medicinal and ritual purposes. The biosynthesis of salvinorin A, its major bioactive neo-clerodane diterpenoid, remains virtually unknown. This investigation aimed to identify the enzyme that catalyzes the first reaction of salvinorin A biosynthesis, the formation of (-)-kolavenyl diphosphate [(-)-KPP], which is subsequently dephosphorylated to afford (-)-kolavenol. Peltate glandular trichomes were identified as the major and perhaps exclusive site of salvinorin accumulation in S. divinorum. The trichome-specific transcriptome was used to identify candidate diterpene synthases (diTPSs). In vitro and in planta characterization of a class II diTPS designated as SdKPS confirmed its activity as (-)-KPP synthase and its involvement in salvinorin A biosynthesis. Mutation of a phenylalanine into histidine in the active site of SdKPS completely converts the product from (-)-KPP into ent-copalyl diphosphate. Structural elements were identified that mediate the natural formation of the neo-clerodane backbone by this enzyme and suggest how SdKPS and other diTPSs may have evolved from ent-copalyl diphosphate synthase.


Screening for dysfunction to promote multidisciplinary intervention by using the University of Washington Quality of Life Questionnaire.
To investigate the potential of the University of Washington Quality of Life Questionnaire (UW-QOL) in routine clinics as a quick screening tool for possible dysfunction in patients after treatment of head and neck cancer. Retrospective analysis. Regional Maxillofacial Unit, Aintree University Hospitals National Health Service Foundation Trust Liverpool, a National Health Service teaching hospital. Consecutive disease-free patients with oral or oropharyngeal squamous cell carcinoma, who had undergone primary surgery with or without adjuvant radiotherapy, for whom UW-QOL version 4 data from 2000 to May 2006 were available in our research database; and consecutive patients from previous studies (4 postal surveys of disease-free patients with oral or oropharyngeal squamous cell carcinoma, 1 clinic-based study that targeted speech and swallowing in patients with oropharyngeal disease, 1 that evaluated shoulder function in patients with various diagnoses, and 1 that recruited patients without cancer attending a general dental practice). Cutoff strategies for further evaluation/intervention derived from studies using the UW-QOL in parallel with 13 other established questionnaires. Effects of preferred cutoffs on trigger variation were assessed with the use of all available UW-QOL version 4 data (615 patients). Trigger rates for further intervention fell between 9% (recreation and speech) and 16% (swallowing). Eighty-one percent of patients with free-flap surgery and adjuvant therapy for T3 or T4 tumors met the trigger criteria at around 2 years, with 42% meeting the trigger on 3 or more domains. The fourth version of the UW-QOL is suitable for routine screening in clinical practice.


Long-term CO2 injection and its impact on near-surface soil microbiology.
Impacts of long-term CO2 exposure on environmental processes and microbial populations of near-surface soils are poorly understood. This near-surface long-term CO2 injection study demonstrated that soil microbiology and geochemistry is influenced more by seasonal parameters than elevated CO2 Soil samples were taken during a 3-year field experiment including sampling campaigns before, during and after 24 months of continuous CO2 injection. CO2 concentrations within CO2-injected plots increased up to 23% during the injection period. No CO2 impacts on geochemistry were detected over time. In addition, CO2-exposed samples did not show significant changes in microbial CO2 and CH4 turnover rates compared to reference samples. Likewise, no significant CO2-induced variations were detected for the abundance of Bacteria, Archaea (16S rDNA) and gene copy numbers of the mcrA gene, Crenarchaeota and amoA gene. The majority (75%-95%) of the bacterial sequences were assigned to five phyla: Firmicutes, Proteobacteria, Actinobacteria, Acidobacteria and Bacteroidetes The majority of the archaeal sequences (85%-100%) were assigned to the thaumarchaeotal cluster I.1b (soil group). Univariate and multivariate statistical as well as principal component analyses showed no significant CO2-induced variation. Instead, seasonal impacts especially temperature and precipitation were detected.


Characterization of mitochondrial DNA in citrus.
Characterization of mitochondrial DNA from leaves of four species of the genus Citrus by electron microscopy shows the presence of circular molecules with a great size dispersion and absence of discrete size classes. Restriction endonuclease patterns confirm the heterogeneity of the molecules.


Training and Capacity Building in LMIC for Research in Heart and Lung Diseases: The NHLBI-UnitedHealth Global Health Centers of Excellence Program.
Stemming the tide of noncommunicable diseases (NCDs) worldwide requires a multipronged approach. Although much attention has been paid to disease control measures, there is relatively little consideration of the importance of training the next generation of health-related researchers to play their important role in this global epidemic. The lack of support for early stage investigators in low- and middle-income countries interested in the global NCD field has resulted in inadequate funding opportunities for research, insufficient training in advanced research methodology and data analysis, lack of mentorship in manuscript and grant writing, and meager institutional support for developing, submitting, and administering research applications and awards. To address this unmet need, The National Heart, Lung, and Blood Institute-UnitedHealth Collaborating Centers of Excellence initiative created a Training Subcommittee that coordinated and developed an intensive, mentored health-related research experience for a number of early stage investigators from the 11 Centers of Excellence around the world. We describe the challenges faced by early stage investigators in low- and middle-income countries, the organization and scope of the Training Subcommittee, training activities, early outcomes of the early stage investigators (foreign and domestic) and training materials that have been developed by this program that are available to the public. By investing in the careers of individuals in a supportive global NCD network, we demonstrate the impact that an investment in training individuals from low- and middle-income countries can have on the preferred future of or current efforts to combat NCDs.


Delayed tranexamic acid after traumatic brain injury impedes learning and memory: Early tranexamic acid is favorable but not in sham animals.
Early but not late tranexamic acid (TXA) after TBI preserves blood-brain-barrier integrity, but it is unclear if and how dose timing affects cognitive recovery beyond hours postinjury. We hypothesized that early (1 hour post-TBI) but not late (24 hours post-TBI) TXA administration improves cognitive recovery for 14 days. CD1 male mice (n = 25) were randomized to severe TBI (injury [I], by controlled cortical impact) or sham craniotomy (S) followed by intravenous saline at 1 hour (placebo [P1]) or 30 mg/kg TXA at 1 hour (TXA1) or 24 hours (TXA24). Daily body weights, Garcia Neurological Test scores, brain/lung water content, and Morris water maze exercises quantifying swimming traffic in the platform quadrant (zone [Z] 1) and platform area (Z5) were recorded for up to 14 days. Among injured groups, I-TXA1 demonstrated fastest weight gain for 14 days and only I-TXA1 showed rapid (day 1) normalization of Garcia Neurological Test ( p = 0.01 vs. I-P1, I-TXA24). In cumulative spatial trials, compared with I-TXA1, I-TXA24 hindered learning (distance to Z5 and % time in Z1, p < 0.05). Compared with I-TXA1, I-TXA24 showed poorer memory with less Z5 time (0.51 vs. 0.16 seconds, p < 0.01) and Z5 crossing frequency. Unexpectedly, TXA in uninjured animals (S-TXA1) displayed faster weight gain but inferior learning and memory. Early TXA appears beneficial for cognitive and behavioral outcomes following TBI, although administration 24 hours postinjury consistently impairs cognitive recovery. Tranexamic acid in sham animals may lead to adverse effects on cognition.


[The current approach to the treatment of the patients with metastatic colorectal cancer].
Colorectal cancer is one of the most common malignant tumors. Despite the constant promotion of prevention remains around 20- 30% of cases dia-gnosed in the metastatic stage and approximately 50- 60% of patients developed the late dissemination. In 80- 90% of them we can find already unresectable metastases. Although surgical treatment is basic modality of therapy, with using mo-dern targeted therapy in combination with chemotherapy we can achieve longterm complete remission in the cases of advanced tumor and we can significantly prolonged the life of patients with this disease now. About 40- 50% patients in advanced stages who underwent metastasectomy survives 5-years and 10year survival rate is up to 25%. When administered systemic treatment median overall survival in these cases reaches around 24 months.


Photoemission Tomography of a One-Dimensional Row Structure of a Flat-Lying Picene Multilayer on Ag(110).
We applied photoemission tomography (PT) to a unique one-dimensional row structure of a picene multilayer realized on an anisotropic Ag(110) surface. Taking advantage of the simplified structure of the multilayer film, we successfully deconvoluted the photoelectron momentum maps of three frontier orbitals of picene. Thereafter, the clearly deconvoluted experimental momentum maps were compared to the Fourier transform simulation of the molecular orbitals of picene in detail, enabling not only the evaluation of the electronic structure of the picene in the multilayer but also the determination of the molecular orientation in the multilayer within a few degrees. In addition, the PT results indicated the orientation of the molecules in all layers to be flat-lying. The successful demonstration of PT of the multilayer molecular film marks an important step toward the wide-range utilization of the PT technique.


Molecular recognition theory and sense-antisense interaction: therapeutic applications in autoimmunity.
Perhaps behind only the understanding of the genetic code in importance is the comprehension of protein sequence and structure in its effect on modern scientific investigation. How proteins are structured and interact dictates a considerable amount of the body's processes in maintaining homeostasis. Unfortunately, in diseases of autoimmunity, these processes are directed against the body itself and most of the current clinical responses are severely lacking. This review addresses current therapeutics involved in the treatment of various autoimmune diseases and details potential future therapeutics designed with a more targeted approach. Detailed in this manuscript is the concept of utilizing peptides possessing an inverse hydropathy to the immunogenic region of proteins to generate anti-idiotypic (anti-Id) and anti-clonotypic T cell receptor (TCR) antibodies (Abs). Theoretically, the anti-Id Abs cross react with Id Abs and negate the powerful machinery of the adaptive immune response with little to no side effects. A series of studies by a number of groups have shown this to be an exciting and intriguing concept that will likely play a role in the future treatment of autoimmune diseases.


Histone deacetylase inhibitors promote apoptosis and senescence in human mesenchymal stem cells.
Histone deacetylase inhibitors (HDACi) have received a great amount of attention for their antitumoral properties. Suberoyl anilide hydroxamic acid (SAHA) and MS-275 are among the more promising HDACi for cancer treatments. Although these HDACi compounds exert low toxicity on normal cells, the therapies based on these molecules can cause side effects that can greatly impair the functions of the bone marrow microenvironment. This is a complex system that contains several types of stem cells, such as mesenchymal stem cells (MSCs). We conducted comparative studies on the effects of SAHA and MS-275 on human MSCs in order to ascertain if these compounds can impair the physiology of MSCs. Both SAHA and MS-275 induced an arrest in the cell cycle along with the induction of apoptotic pathways as evidenced by flow cytometry, annexin assay, detection of activated caspase 9, and molecular analysis of Bax/Bcl-2 expression. The MS-275 treatment induced an increase of senescent cells, whereas in cells treated with SAHA, we detected a reduction of senescent cells compared to the control. We hypothesize that SAHA preferentially transactivates apoptotic genes, thereby inducing a great majority of the damaged cells to die by programmed cell death rather than senescence. Following the HDACi treatment, we observed a decrease in the expression of some genes that are involved in the regulation of stem cell properties. This suggests that SAHA and MS-275 could also be involved in the impairment of the stemness characteristics of MSCs. The phenomena that were induced by HDACi treatment were associated with an upregulation of several cyclin kinase inhibitors. By contrast, the p53-p21 pathway is apparently not involved in these processes.


Receipt of A(H1N1)pdm09 vaccine by prisons and jails - United States, 2009-10 influenza season.
Approximately 2.3 million inmates were confined to U.S. prisons and jails on any given day in 2009. However, over the course of a year, approximately 10 million persons spend time in a correctional facility. To determine to what extent correctional facility populations were included in the national vaccine response to the influenza A (H1N1)pdm09 pandemic, staff members at the Emory University Preparedness and Emergency Response Research Center, aided by the National Commission on Correctional Health Care (NCCHC), conducted a survey to document whether jails and prisons received A(H1N1)pdm09 vaccine during the 2009-10 pandemic period. This report summarizes the results of that survey, which found that 55% of jails did not receive A(H1N1)pdm09 vaccine during the pandemic period, whereas only 14% of federal prisons and 11% of state prisons did not receive the vaccine. Greater inclusion of correctional facilities, especially smaller facilities, in pandemic preparedness planning might better protect correctional facility populations and the community as a whole in the event of future influenza pandemics.


Methods for Estimating Energy Expenditure in Critically Ill Adults.
Energy expenditure (EE) is the sum of metabolic activity within the body at a given time and comprises basal EE, diet-induced thermogenesis, and physical activity. In the intensive care unit, EE is most often assessed to determine a patient's caloric requirements. Energy expenditure also may be useful to understand disease states and the metabolic impact of interventions. Several methods for estimating EE are relevant for clinical use, including indirect calorimetry, predictive equations, exhaled carbon dioxide volume, and the Fick method. Indirect calorimetry is the preferred method for evaluating EE and is considered the gold standard for estimating EE in hospitalized patients. However, use of indirect calorimetry is not always practical or possible. Therefore, other methods of estimating EE must be considered. In this review, methods of evaluating EE in critically ill adults are examined and the benefits and limitations of each method are discussed, with practical considerations for use.


Surveying selected European feed and livestock production chains for features enabling the case-specific post-market monitoring of livestock for intake and potential health impacts of animal feeds derived from genetically modified crops.
This review, which has been prepared within the frame of the European Union (EU)-funded project MARLON, surveys the organisation and characteristics of specific livestock and feed production chains (conventional, organic, GM-free) within the EU, with an emphasis on controls, regulations, traceability, and common production practices. Furthermore, an overview of the origin of animal feed used in the EU as well as an examination of the use of genetically modified organisms (GMOs) in feed is provided. From the data, it shows that livestock is traceable at the herd or individual level, depending on the species. Husbandry practices can vary widely according to geography and animal species, whilst controls and checks are in place for notifiable diseases and general health symptoms (such as mortality, disease, productive performance). For feeds, it would be possible only to make coarse estimates, at best, for the amount of GM feed ingredients that an animal is exposed to. Labeling requirements are apparently correctly followed. Provided that confounding factors are taken into account, practices such as organic agriculture that explicitly involve the use of non-GM feeds could be used for comparison to those involving the use of GM feed.


Diffusion-limited patterning of molecules in nanofluidic channels.
Diffusion-limited patterning (DLP) is a new technique that enables patterning of labile molecular species in solution phase onto surfaces that are not easily accessible. This technique is self-aligning and is simple to implement for patterning multiple species. We demonstrated DLP by patterning alternating bands of fluorescently labeled and unlabeled streptavidin in biotin-functionalized nanofluidic channels with spatial resolution better than 1 microm. The methodology of DLP also enables experimental measurement of a unique parameter that relates molecular surface grafting density, concentration, diffusivity, and channel geometry.


A genome-wide screen for methyl methanesulfonate-sensitive mutants reveals genes required for S phase progression in the presence of DNA damage.
We performed a systematic screen of the set of approximately 5,000 viable Saccharomyces cerevisiae haploid gene deletion mutants and have identified 103 genes whose deletion causes sensitivity to the DNA-damaging agent methyl methanesulfonate (MMS). In total, 40 previously uncharacterized alkylation damage response genes were identified. Comparison with the set of genes known to be transcriptionally induced in response to MMS revealed surprisingly little overlap with those required for MMS resistance, indicating that transcriptional regulation plays little, if any, role in the response to MMS damage. Clustering of the MMS response genes on the basis of their cross-sensitivities to hydroxyurea, UV radiation, and ionizing radiation revealed a DNA damage core of genes required for responses to a broad range of DNA-damaging agents. Of particular significance, we identified a subset of genes that show a specific MMS response, displaying defects in S phase progression only in the presence of MMS. These genes may promote replication fork stability or processivity during encounters between replication forks and DNA damage.


Demographic Characteristics and Health Status of Transgender Adults in Select US Regions: Behavioral Risk Factor Surveillance System, 2014.
To describe the health status of the transgender population in the United States. We used 2014 Behavioral Risk Factor Surveillance System data that comprised a probability sample from 19 US states and Guam (n = 151 456). Bivariate analyses showed that, in comparison with cisgender individuals, transgender individuals had a higher prevalence of poor general health (odds ratio [OR] = 1.7; 95% confidence interval [CI] = 1.2, 2.4), more days per month of poor physical (b = 2.43; 95% CI = 0.61, 4.24; P < .01) and mental (b = 1.74; 95% CI = 0.28, 3.19; P = .02) health, and a higher prevalence of myocardial infarction (OR = 1.7; 95% CI = 1.1, 2.5). In addition, more transgender than cisgender people lacked health care coverage (OR = 1.8; 95% CI = 1.2, 2.7) and a health care provider (OR = 1.5; 95% CI = 1.0, 2.1), and they were less likely to have visited a dentist in the preceding year (OR = 0.7; 95% CI = 0.5, 1.0). However, transgender individuals did not differ from cisgender individuals with respect to prevalence of chronic diseases, cancers, or depressive disorders or in terms of health behaviors such as smoking, binge drinking, and always wearing a seatbelt. Our findings highlight areas of unmet needs in the transgender population.


Spinal muscular atrophy: experience in diagnosis and rehabilitation management of 60 patients.
Sixty patients with spinal muscular atrophy (SMA) are presented. Although the life span with Type I SMA (Werdnig-Hoffmann disease) may be short, children with the disease can be made more comfortable with appropriate medical care and parental support. Despite electrodiagnostic findings which are not always pathognomonic and muscle biopsies which can be difficult to interpret, the clinical presentation of these infants is so typical and the natural course of the disease so predictable that management can be telescopically designed. findings and muscle biopsies are more definitive. In these more benign forms of SMA, anticipatory medical management focuses on possible In SMA-II (Childhood) and SMA-III (Kugelberg-Welander), electrodiagnostic findings and muscle biopsies are more definitive. In these more benign forms of SMA, anticipatory medical management focuses on possible dislocating hips, scoliosis, pulmonary compromise, and sudden increase in weakness associated with intercurrent illness or prolonged immobilization due to fractures or surgery. Further considerations include maintenance of strength and endurance, independence in self-care, psychosocial, educational, and vocational endeavors. These more chronically affected children are eminently habilitable.


Well-designed internal electric field from nano-ferroelectrics promotes formic acid oxidation on Pd.
Pd-Based catalysts are considered the most efficient catalysts in direct formic acid fuel cells. However, the poisoning and dissolution of Pd in acidic systems limit its commercialization. Here, we propose an all-in-one solution for the anti-dissolution and anti-poisoning properties of palladium. A novel structured catalyst, Pd nanoparticles embedded in a carbon layer internally decorated with tourmaline nanoparticles (TNPs), is proposed for formic acid oxidation (FAO). The internal electric field strength of the catalysts is readily regulated by controlling the amount of TNPs. Remarkably, the prepared catalyst exhibits as high as 3.9 times mass activity (905 A g-1) compared with the commercial Pd/C catalyst. The significant improvement in the electrocatalytic performance of the catalyst is mainly due to the polarized electric field of TNPs causing charge transfer from Pd to tourmaline, which weakens the O-H bond of HCOOH and the bond between Pd and COad. Another advantage brought by the internal polarized electric field is that it facilitates water dissociation to produce OHad, thereby improving the anti-poisoning ability of the catalyst in acidic media. Moreover, the firmly anchored Pd nanoparticles can avoid dissolution and agglomeration during long-term use. 80.2% mass activity remained after the accelerated durability test.


[Infection of hepatitis C virus in patients with chronic renal failure undergoing hemodialysis therapy and staff members].
The prevalence of antibody to hepatitis C virus (anti-HCV) was determined in 564 patients and 145 staff members of nine hemodialysis (HD) units in Nagano Prefecture using an enzyme-linked immunosorbent assay based on the C 100 HCV antigen (the first generation anti-HCV assay). And also serum HBV markers were tested in these subjects. One hundred patients (18%) were anti-C100 HCV positive, indicating that this figure represents a much higher prevalence than that (0.9%) among general population in the same geographical area. Out of 141 patients without history of blood transfusion, 17 (12%) were positive for anti-C 100 HCV, suggesting that blood-transfusions-unrelated acquisition of HCV infection can occur. Anti-HCV prevalence correlated with both the blood units transfused and the duration of HD treatment. There was a significant difference in the prevalence of anti-C 100 HCV in individual dialysis units ranging from 0% to 53%. In the dialysis unit with prevalence of 53%, approximately half of the anti-HCV positive patients were found to have chronic liver disease. The prevalence of hepatitis B virus (HBV) markers among HD patients, on the other hand, was 36% (202/564). Fifty one (51%) of 100 anti-C 100 HCV positive patients and 151 (33%) of 464 anti-C 100 HCV negative patients were positive for HBV markers, with significant difference in HBV infection rate between the 2 groups. The prevalence of chronic liver disease, defined as abnormal serum transaminase levels for more than 6 months was significantly higher in anti-HCV positive patients than in anti-HCV negative ones (39% vs 10%, p less than 0.05), suggesting that HCV infection may contribute to chronic liver disease in HD patients. Among 145 staff members, only 3 (2%) were positive for anti-HCV, whereas 25 (17%) were positive for hepatitis B core antibody (anti-HBc), indicating prior HBV infection. With applying the second generation anti-HCV assay, which can detect antibodies to both capsid and nonstructural products of HCV gene, anti-HCV prevalence increased by two times in HD patients, but didn't change in HD staff members.(ABSTRACT TRUNCATED AT 400 WORDS)


Domain closure in adenylate kinase. Joints on either side of two helices close like neighboring fingers.
In large variants of adenylate kinase the AMP and ATP substrates are buried by a domain rotating by 90 degrees. Here conformational changes responsible for this domain closure are determined by an analysis of the open state of beef heart mitochondrial adenylate kinase and the closed state of Escherichia coli adenylate kinase. Although these two proteins have sequence differences, the principal structural changes responsible for the domain movements are large, and can clearly be distinguished from the effects of evolution. The mobile domain is linked to the rest of the protein by two helices packed together in an antiparallel fashion. During the closure, deformations take place in four localized regions, called joints, near the N and C termini of these helices. Three of these joints have simple motions that can be well approximated by rotations of three torsion angles, but the joint that makes contact with the ligand involves motion throughout an extended loop: i.e. two torsions on either side of a reverse turn change significantly. The main chain atoms of the joints have few packing constraints. The first pair of joints is responsible for approximately 30 degrees of the total rotation and the second pair for the remaining approximately 60 degrees. These movements carries along the regions between the joints, the two helices and the rest of the mobile domain, to a first approximation, as rigid bodies. This jointed domain closure mechanism is contrasted with the shear mechanisms found in other enzymes.


Pulmonary surfactant in birds: coping with surface tension in a tubular lung.
As birds have tubular lungs that do not contain alveoli, avian surfactant predominantly functions to maintain airflow in tubes rather than to prevent alveolar collapse. Consequently, we have evaluated structural, biochemical, and functional parameters of avian surfactant as a model for airway surfactant in the mammalian lung. Surfactant was isolated from duck, chicken, and pig lung lavage fluid by differential centrifugation. Electron microscopy revealed a uniform surfactant layer within the air capillaries of the bird lungs, and there was no tubular myelin in purified avian surfactants. Phosphatidylcholine molecular species of the various surfactants were measured by HPLC. Compared with pig surfactant, both bird surfactants were enriched in dipalmitoylphosphatidylcholine, the principle surface tension-lowering agent in surfactant, and depleted in palmitoylmyristoylphosphatidylcholine, the other disaturated phosphatidylcholine of mammalian surfactant. Surfactant protein (SP)-A was determined by immunoblot analysis, and SP-B and SP-C were determined by gel-filtration HPLC. Neither SP-A nor SP-C was detectable in either bird surfactant, but both preparations of surfactant contained SP-B. Surface tension function was determined using both the pulsating bubble surfactometer (PBS) and capillary surfactometer (CS). Under dynamic cycling conditions, where pig surfactant readily reached minimal surface tension values below 5 mN/m, neither avian surfactant reached values below 15 mN/m within 10 pulsations. However, maximal surface tension of avian surfactant was lower than that of porcine surfactant, and all surfactants were equally efficient in the CS. We conclude that a surfactant composed primarily of dipalmitoylphosphatidylcholine and SP-B is adequate to maintain patency of the air capillaries of the bird lung.


Repurposing Kinase Inhibitors as Antiviral Agents to Control Influenza A Virus Replication.
Influenza A virus (IAV) infection causes seasonal epidemics of contagious respiratory illness that causes substantial morbidity and some mortality. Regular vaccination is the principal strategy for controlling influenza virus, although vaccine efficacy is variable. IAV antiviral drugs are available; however, substantial drug resistance has developed to two of the four currently FDA-approved antiviral drugs. Thus, new therapeutic approaches are being sought to reduce the burden of influenza-related disease. A high-throughput screen using a human kinase inhibitor library was performed targeting an emerging IAV strain (H7N9) in A549 cells. The inhibitor library contained 273 structurally diverse, active cell permeable kinase inhibitors with known bioactivity and safety profiles, many of which are at advanced stages of clinical development. The current study shows that treatment of human A549 cells with kinase inhibitors dinaciclib, flavopiridol, or PIK-75 exhibits potent antiviral activity against H7N9 IAV as well as other IAV strains. Thus, targeting host kinases can provide a broad-spectrum therapeutic approach against IAV. These findings provide a path forward for repurposing existing kinase inhibitors safely as potential antivirals, particularly those that can be tested in vivo and ultimately for clinical use.


Effects of increased gamma-aminobutyric acid levels on GAD67 protein and mRNA levels in rat cerebral cortex.
Rats were injected with saline or the gamma-aminobutyric acid (GABA) transaminase inhibitor gamma-vinyl-GABA for 7 days and the effects on GABA content and glutamic acid decarboxylase (GAD) activity, and the protein and mRNA levels of the two forms of GAD (GAD67 and GAD65) in the cerebral cortex were studied. gamma-Vinyl-GABA induced a 2.3-fold increase in GABA content, whereas total GAD activity decreased by 30%. Quantitative immunoblotting showed that the decline in GAD activity was attributable to a 75-80% decrease in GAD67 levels, whereas the levels of GAD65 remained unchanged. RNA slot-blotting with a 32P-labeled GAD67 cDNA probe demonstrated that the change in GAD67 protein content was not associated with a change in GAD67 mRNA levels. Our results suggest that GABA specifically controls the level of GAD67 protein. This effect may be mediated by a decreased translation of the GAD67 mRNA and/or a change in the stability of the GAD67 protein.


Extranodal non-Hodgkin's lymphoma presenting as an abdominal wall mass. A case report and review of the literature.
Soft tissue lymphoma is a very rare clinical entity with varying presentation characteristics and atypical clinical and imaging features. The present report describes a patient who presented with a painless soft tissue mass on the posterolateral surface of the abdominal wall, simulating a neoplasm of mesenchymal origin. After complete surgical excision, the tumor was diagnosed as a diffuse large B-cell lymphoma. No B-symptoms were present and clinical staging did not reveal other sites of disease (stage I EA). The International Prognostic Index score was equal to 1 and classified the patient to the good risk group. Post-operatively the patient was treated with immuno-chemotherapy consisting of rituximab plus cyclophosphamide, epirubicin, vincristine and prednisolone and is currently free of disease for 10 months. The case is discussed with a brief review of the literature on the diagnosis, treatment and outcome of soft tissue lymphomas.


Transvaginal Natural Orifice Transluminal Endoscopic Hysterectomy and Apical Suspension of the Vaginal Cuff to the Uterosacral Ligament.
Transvaginal natural orifice transluminal endoscopic surgery (vNOTES) offers similar advantages of traditional vaginal surgery including no incisional pain as well as a better cosmetic outcome. Furthermore, vNOTES allows the surgeon to overcome the limited surgical space and lack of exposure when using the traditional vaginal instrumentation. Vaginal uterosacral ligament suspension subsequent to vaginal hysterectomy has the advantages of a mesh-free, minimally invasive approach for the treatment of pelvic organ prolapse. The objective of this video is to demonstrate a surgical technique and a few tips and tricks for vNOTES hysterectomy and uterosacral ligament suspension. Stepwise demonstration of the vNOTES technique for hysterectomy and vaginal apical suspension to the uterosacral ligament with narrated video footage. An academic tertiary referral center. The ethics committee ruled that approval was not required for this study. A 53-year-old woman. vNOTES hysterectomy and apical suspension to the uterosacral ligament. A 53-year-old woman (gravida 5, para 4) presented with Pelvic Organ Prolapse Quantification System stage III symptomatic uterine prolapse. The patient was selected to be operated on via a vaginal port. The video presents some tips and tricks to aid the surgeon to perform this surgery in a safe and timely manner using the vaginal GelPOINT system (Applied Medical, Rancho Santa Margarita, CA). vNOTES for repair of POP by uterosacral ligament suspension via a vaginal port is a feasible technique with promising cosmetic results. This technique allows the surgeon to expose the ureter well and lower the risk of ureteric injury. Additionally, this approach avoids mesh complications and should also decrease the risk of abdominal wound infection because of the absence of incisions on the abdomen.


The effect of enzyme predigestion on the quality of poultry by-product meal from whole turkey mortality.
Enzyme predigested poultry by-product meal made from onfarm, whole turkey mortality (E-TBM) was compared with soybean meal (SBM) and commercial poultry by-product meal (CPBM) in each of three experiments. In Experiment 1, young poults were fed diets containing 16, 20, or 24% CP with either SBM or E-TBM as protein sources. A separate group of poults was fed a nitrogen-free diet. The E-TBM was higher than SBM in protein, fat, lysine, methionine, and total sulfur amino acids. Diets containing E-TBM resulted in increased BW, feed consumption, and a higher protein efficiency ratio (PER) and net protein ratio (NPR) compared with diets containing SBM. In Experiment 2, feeding nonenzyme-treated turkey by-product (TBM) or E-TBM resulted in significantly improved BW and feed efficiency compared with CPBM but this may have been due to decreased protein in diets containing CPBM. Protein source did not affect feed intake, PER, NPR, or net protein utilization (NPU). In Experiment 3, the TMEn content of CPBM was lower than both TBM and E-TBM but lysine and methionine digestibilities were greater.


Genetic Diversity and Phylogeny of the Genus Euplotes (Protozoa, Ciliophora) Revealed by the Mitochondrial CO1 and Nuclear Ribosomal Genes.
Nuclear ribosomal and mitochondrial genes have been utilized individually or in combination to identify known species and discriminate closely related species. However, compared with metazoans, genetic diversity within the ciliate order Euplotida is poorly known. The aim of this study is to investigate how much nucleotide sequence divergence occurs within Euplotes. A total of 14 new gene sequences, comprising four SSU rDNA and 10 CO1 (including three species for the first time) were obtained. Phylogenetic analyses were carried out based on sequences of two DNA fragments from the same 27 isolates. We found that CO1 revealed a larger interspecific divergence than the SSU rRNA gene, thus demonstrating a higher resolution for separating congeners. Genetic distances differ significantly at the species level. Euplotes balteatus was revealed to have a large intraspecific variation at two loci, while E. vannus showed different levels of haplotype variability, which appeared as a polyphyletic cluster on the CO1 tree. These high genetic divergences suggest the presence of more cryptic species. By contrast, the CO1 gene showed low variability within E. raikovi, appearing as monophyletic clusters, which indicates that this species could be identified based on this gene. Conclusively, CO1 is a suitable marker for the study of genetic diversity within Euplotes, and increased taxon sampling gives an opportunity to screen relationships among members of this genus. Additionally, current data present no clear biogeographical pattern for Euplotes.


Survival in HIV-infected patients who have received zidovudine: comparison of combination therapy with sequential monotherapy and continued zidovudine monotherapy. Multicenter AIDS Cohort Study Group.
Among patients who begin receiving zidovudine during intermediate-stage human immunodeficiency virus (HIV) infection, it is unclear whether changing to combination therapy (adding didanosine or zalcitabine) or sequential monotherapy (changing to didanosine or zalcitabine) significantly improves survival. To determine, among patients who began receiving zidovudine during intermediate-stage HIV infection, the differential effects of changing to combination therapy (zidovudine with didanosine or zalcitabine) or sequential monotherapy (with didanosine or zalcitabine) or continuing zidovudine monotherapy. 1077 HIV-seropositive men in the Multicenter AIDS (acquired immunodeficiency syndrome) Cohort Study who began receiving zidovudine before an AIDS-defining illness developed. University-affiliated clinics in Baltimore, Chicago, Los Angeles, and Pittsburgh. Longitudinal cohort study, Treatment groups and important prognostic variables were modeled as time-dependent covariates in Cox proportional hazards models. Progression to AIDS and death. Compared with patients receiving continued zidovudine monotherapy, patients receiving combination therapy had a 45% improvement in survival (relative risk, 0.55 [95% Cl, 0.41 to 0.74; P < 0.001]) and patients who changed to sequential monotherapy had a 32% improvement in survival (relative risk, 0.68 [Cl, 0.52 to 0.89; P = 0.005]). In the landmark analyses, the median prolongation of survival associated with changing therapy was, at best, 3 to 6 months. Survival curves converged at 3.5 years for the 50 cells/mm3 disease-stage landmark, at 4.4 years for the 100 cells/mm3 landmark and at 4.9 years for the 150 cells/mm3 landmark. Mortality within these periods was 100%, regardless of treatment group or landmark. For patients who began receiving zidovudine during intermediate-stage disease, changing to either combination therapy or sequential monotherapy was associated with a statistically significant survival benefit compared with continuation of zidovudine monotherapy. The absolute increase in survival was modest, however, and long-term survival remained poor. Simultaneous time-dependent adjustment for changes in therapy and in important prognostic variables is necessary to derive relatively unbiased estimates of treatment effects in observational studies of HIV infection.


Prodrug enzymes and their applications in image-guided therapy of cancer: tracking prodrug enzymes to minimize collateral damage.
Many cytotoxic therapies are available to kill cancer cells. Unfortunately, these also inflict significant damage on normal cells. Identifying highly effective cancer treatments that have minimal or no side effects continues to be a major challenge. One of the strategies to minimize damage to normal tissue is to deliver an activating enzyme that localizes only in the tumor and converts a nontoxic prodrug to a cytotoxic agent locally in the tumor. Such strategies have been previously tested but with limited success due in large part to the uncertainty in the delivery and distribution of the enzyme. Imaging the delivery of the enzyme to optimize timing of the prodrug administration to achieve image-guided prodrug therapy would be of immense benefit for this strategy. Here, we have reviewed advances in the incorporation of image guidance in the applications of prodrug enzymes in cancer treatment. These advances demonstrate the feasibility of using clinically translatable imaging in these prodrug enzyme strategies.


Retrospective analysis of long-term outcomes of 64 patients treated by endopyelotomy in two low-volume hospitals: good and durable results.
Endopyelotomy is an option for the management of ureteropelvic junction (UPJ) obstruction, but long-term outcome data are lacking. The purpose of this study was to evaluate the long-term outcome of endopyelotomy. We retrospectively collected data from all endopyelotomies performed in two low-volume hospitals in Finland between 1987 and 2007. The diagnosis was based primarily on urography results. We also conducted a patient survey during the fall of 2007 for the subjective outcome of the operation. There were 18, 17, and 29 patients with a mean follow-up time 152.2, 67.1, and 77.6 months treated by percutaneous antegrade endopyelotomy, Acucise endopyelotomy, and retrograde endopyelotomy, respectively. Reoperation for recurrent UPJ obstruction was required for 0, 1 (6%) and 5 (17%) of the patients, the radiographic outcome of the operation was better in 17 (94%), 13 (76%), and 18 (62%) of the patients, and 0, 2 (12%), and 5 (17%) of the patients experienced no relief in pain after percutaneous antegrade endopyelotomy, Acucise endopyelotomy, and retrograde endopyelotomy, respectively. Complications necessitating intervention were recorded for 7 (38.9%), 4 (23.5%), and 4 (13.8%) patients after antegrade endopyelotomy, Acucise endopyelotomy, and retrograde endopyelotomy, respectively. According to the patient survey, 15 (100%), 11 (73%), and 19 (86%) of the respondents were satisfied with the results of the operation after antegrade endopyelotomy, Acucise endopyelotomy, and retrograde endopyelotomy, respectively. The patients were mainly monitored by radiologic examinations, not by renography. Endopyelotomy offers good and durable results in the long-term. Complications were common, however, and laparoscopic pyeloplasty may be a recommended option for management of primary UPJ obstruction.


Surgical treatment for severe slipping of the upper femoral epiphysis.
We have used a modified technique of cervical osteotomy to treat a consecutive series of 23 patients with chronic slip of the upper femoral epiphysis. It has been successful in correcting both moderate and severe deformities with a low incidence of avascular necrosis, comparable to that seen after subtrochanteric osteotomies. We describe the operative details and discuss the features which make cervical osteotomy technically superior to intertrochanteric and subtrochanteric procedures.


Engineering Enhanced Pore Sizes Using FhuA Δ1-160 from E. coli Outer Membrane as Template.
Biological membranes are the perfect example of a molecular filter using membrane channels to control the permeability of small water-soluble molecules. To allow filtering of larger hydrophilic molecules we started from the known mutant channel FhuA Δ1-160 in which the cork domain closing the channel had been removed. Here we further expand the pore diameter by copying the amino acid sequence of two β-strands in a stepwise manner increasing the total number of β-strands from 22 to 34. The pore size of the respective expanded channel protein was characterized by single-channel conductance. Insertion of additional β-strands increased the pore conductance but also induced more ion current flickering on the millisecond scale. Further, polymer exclusion measurements were performed by analyzing single-channel conductance in the presence of differently sized polyethylene glycol of known polymer random coil radii. The conclusion from channel conductance of small channel penetrating polymers versus larger excluded ones suggested an increase in pore radii from 1.6 nm for FhuA Δ1-160 up to a maximum of about 2.7 nm for +8 β insertion. Integration of more β-strand caused instability of the channel and exclusion of smaller sized polymer. FhuA Δ1-160 + 10 β and FhuA Δ1-160 + 12 β effective radius decreased to 1.4 and 1.3 nm, respectively, showing the limitations of this approach.


Reliability and applicability of movement disorder rating scales in the elderly.
Geriatric research clinicians were readily trained to use three scales initially developed for rating neuroleptic-induced movement disorders in mixed-age patients: the Abnormal Involuntary Movements Scale (AIMS), Simpson Extra Pyramidal Side Effect Scale (SEPSE), and Barnes Akathisia Scale (BAS). Interrater reliability, calculated by intraclass correlation coefficients, ranged from 0.79 to 0.93. Of elderly psychiatric inpatients tested, 97% were able to complete the examination, despite significant psychiatric, cognitive, and physical disabilities. AIMS, SEPSE, and BAS are reliable instruments for assessment of movement disorders in the elderly, representing an important first step in standardized evaluation of dyskinesia, parkinsonism, and akathisia in elderly psychiatric populations.


The response of common carp (Cyprinus carpio) to insonified bubble curtains.
Acoustic bubble curtains have been marketed as relatively low cost and easily maintained behavioural deterrents for fisheries management. Their energy efficiency can be improved by reducing air flow and exploiting bubble resonance. In a series of three flume experiments, we: (1) investigated the reactions of carp to a low air flow bubble curtain, (2) compared the effectiveness of resonant versus non-resonant insonified bubble curtains (for the same volume flux of gas injected through the nozzles) to deter passage, and determined the stimuli responsible for eliciting deterrence, and (3) included the effect of visual cues generated by the bubble curtain. This study showed that bubble curtains with a higher proportion of resonant bubbles deterred carp relatively better. Passage rejection was likely influenced by multiple cues at distances within a body length of the fish- specifically the rate of change in both particle motion and flow velocity caused by rising bubbles. All acoustic bubble curtains were less effective in the presence of daylight, suggesting that vision plays an important role at mediating carp reactions. We discuss the importance of ascertaining the bubble size distribution, in addition to the gas flow rate and aperture size, when characterising acoustically active bubble curtains.


Statistical difficulties of detecting interactions and moderator effects.
Although interaction effects are frequently found in experimental studies, field researchers report considerable difficulty in finding theorized moderator effects. Previous discussions of this discrepancy have considered responsible factors including differences in measurement error and use of nonlinear scales. In this article we demonstrate that the differential efficiency of experimental and field tests of interactions is also attributable to the differential residual variances of such interactions once the component main effects have been partialed out. We derive an expression for this residual variance in terms of the joint distribution of the component variables and explore how properties of the distribution affect the efficiency of tests of moderator effects. We show that tests of interactions in field studies will often have less than 20% of the efficiency of optimal experimental tests, and we discuss implications for the design of field studies.


Diaphragm dysfunction on admission to the intensive care unit. Prevalence, risk factors, and prognostic impact-a prospective study.
Diaphragmatic insults occurring during intensive care unit (ICU) stays have become the focus of intense research. However, diaphragmatic abnormalities at the initial phase of critical illness remain poorly documented in humans. To determine the incidence, risk factors, and prognostic impact of diaphragmatic impairment on ICU admission. Prospective, 6-month, observational cohort study in two ICUs. Mechanically ventilated patients were studied within 24 hours after intubation (Day 1) and 48 hours later (Day 3). Seventeen anesthetized intubated control anesthesia patients were also studied. The diaphragm was assessed by twitch tracheal pressure in response to bilateral anterior magnetic phrenic nerve stimulation (Ptr,stim). Eighty-five consecutive patients aged 62 (54-75) (median [interquartile range]) were evaluated (medical admission, 79%; Simplified Acute Physiology Score II, 54 [44-68]). On Day 1, Ptr,stim was 8.2 (5.9-12.3) cm H2O and 64% of patients had Ptr,stim less than 11 cm H2O. Independent predictors of low Ptr,stim were sepsis (linear regression coefficient, -3.74; standard error, 1.16; P = 0.002) and Simplified Acute Physiology Score II (linear regression coefficient, -0.07; standard error, 1.69; P = 0.03). Compared with nonsurvivors, ICU survivors had higher Ptr,stim (9.7 [6.3-13.8] vs. 7.3 [5.5-9.7] cm H2O; P = 0.004). This was also true for hospital survivors versus nonsurvivors (9.7 [6.3-13.5] vs. 7.8 [5.5-10.1] cm H2O; P = 0.004). Day 1 and Day 3 Ptr,stim were similar. A reduced capacity of the diaphragm to produce inspiratory pressure (diaphragm dysfunction) is frequent on ICU admission. It is associated with sepsis and disease severity, suggesting that it may represent another form of organ failure. It is associated with a poor prognosis. Clinical trial registered with www.clinicaltrials.gov (NCT 00786526).