A novel rice hull - microalgal biorefinery for the production of natural phenolic compounds comprising of rice hull acid pretreatment and a two-stage Botryococcus braunii cultivation process.
Recently, the rising demand of the industry for natural phenolic antioxidant compounds has turned to the study of microalgae as potential sources. Yet, more economic substrates for microalgal cultivation are sought to lower production costs. To this end, the present work deals with the utilization of rice hull hydrolysate (RHH) as substrate for microalgae Botryococcus braunii through a novel two-stage cultivation system. Initially, RHH was optimized to maximize the contained nutrients while minimizing its inhibitors content. The optimum point was reached under 121 °C, 60 min, 2% (v/v) H2SO4, 30% (w/v) loading. Next, B. braunii was successfully grown first heterotrophically in RHH (25%, v/v), obtaining high biomass production (6.67 g L-1) and then autotrophically to enhance phenolics accumulation. At the end, a high phenolic content of 7.44 ± 0.60 mg Gallic Acid Equivalents g-1 DW was achieved from the produced biomass, thus highlighting the potential of this novel biotechnological method.


Correction: Mechanosensitive caveolin-1 activation-induced PI3K/Akt/mTOR signaling pathway promotes breast cancer motility, invadopodia formation and metastasis in vivo.
[This corrects the article DOI: 10.18632/oncotarget.7583.].


Considerations and Recommendations for Care of Black Pregnant Patients During COVID-19.
Black pregnant patients experience perinatal morbidity and mortality rates greater than other ethnic groups. These health disparities exist primarily because of systemic racism, bias, and discriminatory acts within the health care system. The COVID-19 pandemic has reinforced health disparities experienced by all vulnerable populations in the United States, including black pregnant patients. This article highlights some of the factors that may impact the experience of black people as they navigate the COVID-19 pandemic and presents strategies that every provider can implement to minimize the detrimental effects of this devastating virus during pregnancy.


Anti-inflammatory effects of Bryophyllum pinnatum (Lam.) Oken ethanol extract in acute and chronic cutaneous inflammation.
Bryophyllum pinnatum (Lam.) Oken (Crassulaceae), popularly known in Brazil as "folha-da-fortuna", is a plant species used in folk medicine for the external and internal treatment of inflammation, infection, wound, burn, boil, ulcers and gastritis, and several other diseases. The present study aimed to perform the chemical characterization and the evaluation of the topical anti-inflammatory effect of the ethanol extract of Bryophyllum pinnatum leaves (EEBP) in acute and chronic mice ear edema models induced by different irritant agents. The EEBP chemical characterization was performed by HPLC-UV DAD. Ear edema on Swiss mice was induced by the topical application of Croton oil (single and multiple applications), arachidonic acid, phenol, capsaicin and ethyl phenylpropiolate (EPP). The topical anti-inflammatory effect of EEBP was evaluated by measuring the ear weight (acute inflammation models) and thickness (chronic inflammation model). Histopathological analyses of ear tissue samples sensitized with Croton oil (single and multiple applications) were also performed. The flavonoids rutin, quercetin, luteolin and luteolin7-O-β-d-glucoside were detected in EEBP. Topical application of EEBP significantly (P<0.001) inhibited the ear edema induced by Croton oil single application (inhibition of 57%), arachidonic acid (inhibition of 67%), phenol (inhibition of 80%), capsaicin (inhibition of 72%), EPP (inhibition of 75%) and Croton oil multiple application (55% after 9 days). Histopathological analyses confirmed the topical anti-inflammatory effect of EEBP since it was observed reduction of edema, epidermal hyperplasia, inflammatory cells infiltration and vasodilation. The results suggest that EEBP is effective as a topical anti-inflammatory agent in acute and chronic inflammatory processes possibly due to inhibition of arachidonic acid pathway, which justify the traditional use of Bryophyllum pinnatum as a remedy for skin disorders.


Experiences of breathlessness: a systematic review of the qualitative literature.
Breathlessness is one of the core symptoms in many advanced conditions. The subjective nature of the symptom has been acknowledged in many definitions, emphasizing that it can only be fully perceived and interpreted by the patients themselves. To review and assess the evidence on the psychosocial nature or experience of breathlessness. Relevant literature was identified through electronic and hand searches. Studies with qualitative enquiry or mixed method designs were included. The methodological quality of studies was assessed with a standard grading scale. Twenty-two studies were identified, 12 from the United Kingdom, 4 from the United States, 3 from Canada, 1 from Sweden, 1 from Iceland, and 1 from Finland. The nature of the studies determined the themes in which the studies were subsumed. Studies on COPD (19) outnumbered "all other conditions" (3), one of which had COPD and cancer patients and so these were analyzed separately. Within the COPD category most studies (17) considered the experience of breathlessness from the perspective of the patient, 1 study from the informal carer, and 1 from the professional carer. Most of the papers sought to understand the meaning of the symptom in the patient's daily life. The other papers demarcated separate areas of the experience of acute exacerbations and the patient's view on care. The studies explored the subjective component of breathlessness, as part of human experience and social life. The papers showed the influence of the meaning the symptom has for those affected on their ability to cope and on their management. Although the work in this area is still dominated by research on COPD, the totality of the evidence now shows breathlessness as an intractable symptom in other advanced conditions. Practice recommendations focused on the holistic approach as part of palliative and nursing care.


Systematic literature review of the performance characteristics of Chebyshev polynomials in machine learning applications for economic forecasting in low-income communities in sub-Saharan Africa.
Chebyshev polynomials have unique properties that place them in a class of functions that are highly efficient in the approximation of non-linear functions. Machine learning techniques are being applied to solve complex non-linear problems in the financial markets where there is a proliferation of financial products. The techniques for valuing diverse portfolios of these products can be time consuming and expensive. Formal research has been conducted to determine how machine learning can considerably reduce the computational effort without losing accuracy. The objective of this systematic literature review is to discover evidence of research on the optimal use of Chebyshev polynomials in machine learning and neural networks that may be used for the estimation of generalized financial outcomes of large clusters of small economic units in low-income communities in sub-Saharan Africa. Scopus, ProQuest, and Web of Science databases were queried with search criteria designed to recover peer-reviewed research articles that addressed this objective. Many articles discussing broader applications in engineering, computer science, and applied mathematics were found. Several articles provided insights into the challenges of forecasting stock price outcomes from unpredictable market activities, and in investment portfolio valuations. One article addressed specific environmental issues relating to energy, biology, and ecological situations, and presented encouraging results. While the literature search did not find any similar articles that address economic forecasting for low-income communities, the applications and techniques used in stock market forecasting and portfolio valuations can contribute to formative theory on sustainable development. There is currently no theoretical underpinning of sustainable development initiatives in developing countries. A framework for small business structures, data collection, and near real-time processing is proposed as a potential data-driven approach to guide policy decisions and private sector involvement. The online version contains supplementary material available at 10.1007/s43546-022-00328-w.


Progress in the retrograde approach for chronic total coronary artery occlusion: a case with successful angioplasty using CART and reverse-anchoring techniques 3 years after failed PCI via a retrograde approach.
After the introduction of the retrograde approach in percutaneous coronary intervention for chronic total occlusion (CTO), different kinds of strategies and techniques have been developed in order to achieve final success. However, it has not been fully demonstrated whether these strategies and techniques can really improve the final result. We observed one case, for which the initial attempt of the retrograde approach for a CTO lesion was unsuccessful despite the successful approach of a retrograde guidewire to the lesion, and with the second retrograde approach 3 years later being eventually successful by using various kinds of strategies and techniques. This case clearly demonstrates how the final success through the retrograde approach can be achieved by using a combination of the improved strategies and techniques for CTO lesions.


Effects of partial and total isovolemic exchange transfusion in fully conscious rats using pyridoxylated polyhemoglobin solution as a colloidal oxygen-delivering blood replacement fluid.
Stroma-free hemoglobin (SFHb) treated with pyridoxal 5'-phosphate (PP) was intermolecularly cross-linked with glutaraldehyde to give pyridoxylated polyhemoglobin (PP-PolyHb) solution (14.0 g/dl) with colloid osmotic pressure = 25 torr and a P50 = 20 torr. To evaluate PP-PolyHb as a blood substitute, fully conscious rats with chronic cannulations were subjected to blood replacement (30-100%) by a new continuous isovolemic exchange transfusion set up. Crystalline SFHb, PP-SFHb, PP-PolyHb, bovine serum albumin (BSA) and Ringer's solution were tested. Respiration, pulse and arterial blood pressure were more stable following transfusion with PP-PolyHb or PP-SFHb compared to BSA. By 7-8 days post-exchange, hematological changes returned to normal. Plasma retention of PP-PolyHb was 10-15 times longer than either crystalline SFHb or PP-SFHb for major blood exchanges. A T1/2 of 30 h was obtained for PP-PolyHb after total replacement. Long-term survival rates of 80, 63 and 50%, following replacement of 70, 85 and 100%, respectively, were significantly higher (p less than 0.05) than survival obtained for all other solutions tested. Superiority of PP-PolyHb over other fluids was clearly demonstrated.


Leveraging an epidemic-economic mathematical model to assess human responses to COVID-19 policies and disease progression.
It is imperative that resources are channelled towards programs that are efficient and cost effective in combating the spread of COVID-19, the disease caused by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). This study proposed and analyzed control strategies for that purpose. We developed a mathematical disease model within an optimal control framework that allows us to investigate the best approach for curbing COVID-19 epidemic. We address the following research question: what is the role of community compliance as a measure for COVID-19 control? Analyzing the impact of community compliance of recommended guidelines by health authorities-examples, social distancing, face mask use, and sanitizing-coupled with efforts by health authorities in areas of vaccine provision and effective quarantine-showed that the best intervention in addition to implementing vaccination programs and effective quarantine measures, is the active incorporation of individuals' collective behaviours, and that resources should also be directed towards community campaigns on the importance of face mask use, social distancing, and frequent sanitizing, and any other collective activities. We also demonstrated that collective behavioral response of individuals influences the disease dynamics; implying that recommended health policy should be contextualized.


Integrated nursing teams in primary care.
This article looks at different models of integrated nursing and more traditional models of community nursing in primary care, as well as examining models of change for implementing integrated nursing. The models of change used by those who have developed integrated nursing teams successfully will be useful for anyone embarking on a similar project.


Aminated polyethersulfone-silver nanoparticles (AgNPs-APES) composite membranes with controlled silver ion release for antibacterial and water treatment applications.
The present study reports the antibacterial disinfection properties of a series of silver nanoparticle (AgNP) immobilized membranes. Initially, polyethersulfone (PES) was functionalized through the introduction of amino groups to form aminated polyethersulfone (NH2-PES, APES). AgNPs were then coordinately immobilized on the surface of the APES composite membrane to form AgNPs-APES. The properties of the obtained membrane were examined by FT-IR, XPS, XRD, TGA, ICP-OES and SEM-EDAX analyses. These structural characterizations revealed that AgNPs ranging from 5 to 40 nm were immobilized on the surface of the polymer membrane. Antibacterial tests of the samples showed that the AgNPs-APES exhibited higher activity than the AgNPs-PES un-functionalized membrane. Generally, the AgNPs-APES 1 cm × 3 cm strip revealed a four times longer life than the un-functionalized AgNPs polymer membranes. The evaluation of the Ag(+) leaching properties of the obtained samples indicated that approximately 30% of the AgNPs could be retained, even after 12 days of operation. Further analysis indicated that silver ion release can be sustained for approximately 25 days. The present study provides a systematic and novel approach to synthesize water treatment membranes with controlled and improved silver (Ag(+)) release to enhance the lifetime of the membranes.


Mechanism of action of iodothyronine-5'-deiodinase.
Production of 3,3'-di-iodothyronine (3,3'-T2) from 3,3',5'-tri-iodothyronine (reverse T3, rT3) as catalysed by rat liver microsomal fraction was measured with a specific radioimmunoassay. The effect of the addition of 2-thiouracil and of varying concentrations of cofactor (dithiothreito) on the kinetic parameters of this reaction were studied. It was found that thiouracil is an uncompetitive inhibitor with respect to substrate and a competitive inhibitor with respect to cofactor. The effect of a decrease in the concentration of cofactor was similar to the effect of addition of thiouracil, i.e. a proportional decrease in Km and V. The results strongly suggest that enzymatic 5'-deiodination of iodothyronines follows a ping-pong mechanisms, which may be envisaged as a transiodination and the subsequent reduction of the iodo-enzyme complex by cofactor. The intermediate is probably a sulfenyl iodide form of the enzyme, which reacts with thiouracil to yield a mixed disulfide.


Effects of running the Boston marathon on plasma concentrations of large neutral amino acids.
Plasma large neutral amino acid concentrations were measured in thirty-seven subjects before and after completing the Boston Marathon. Concentrations of tyrosine, phenylalanine, and methionine increased, as did their "plasma ratios" (i.e., the ratio of each amino acid's concentration to the summed plasma concentrations of the other large neutral amino acids which compete with it for brain uptake). No changes were noted in the plasma concentrations of tryptophan, leucine, isoleucine, nor valine; however, the "plasma ratios" of acid patterns may influence neurotransmitter synthesis.


Isolation of three zebrafish dachshund homologues and their expression in sensory organs, the central nervous system and pectoral fin buds.
Drosophila dachshund (dac) interacts with sine oculis (so), eyes absent (eya) and eyeless (ey) to control compound eye development. We have cloned three zebrafish dac homologues, dachA, dachB and dachC, which are expressed widely, in distinct but overlapping patterns. Expression of all three is found in sensory organs, the central nervous system and pectoral fin buds. dachA is also expressed strongly in the somites and dachC in the neural crest and pronephros. These expression domains overlap extensively with those of zebrafish pax, eya and six family members, the homologues of Drosophila ey, eya and so, respectively. This is consistent with the proposal that Dach, Eya, Six and Pax family members may form networks, similar to that found in the fly eye, in the development of many vertebrate organs.


PNA Technology.
Peptide nucleic acids (PNA) are deoxyribonucleic acid (DNA) mimics with a pseudopeptide backbone. PNA is an extremely good structural mimic of DNA (or of ribonucleic acid [RNA]), and PNA oligomers are able to form very stable duplex structures with Watson-Crick complementary DNA and RNA (or PNA) oligomers, and they can also bind to targets in duplex DNA by helix invasion. Therefore, these molecules are of interest in many areas of chemistry, biology, and medicine, including drug discovery, genetic diagnostics, molecular recognition, and the origin of life. Recent progress in studies of PNA properties and applications is reviewed.


Mental health after first childbirth in women requesting a caesarean section; a retrospective register-based study.
Psychiatric illness before delivery increases the risk of giving birth by caesarean section on maternal request (CSMR) but little is known about these women's mental health after childbirth. In this study we aimed to compare the prevalence of psychiatric disorders five years before and after delivery in primiparae giving birth by CS on maternal request to all other primiparae giving birth, indifferent on their mode of delivery. The study population comprised all women born in Sweden 1973-1983 giving birth for the first time in 2002-2004. Psychiatric diagnoses, in- and outpatient care were retrieved from the National Patient Register in Sweden. The risk of psychiatric care after childbirth was estimated using CSMR, previous mental health and sociodemographic variables as covariates. Psychiatric disorders after childbirth were more common in women giving birth by CSMR compared to the other women (11.2% vs 5.5%, p < 0.001). CSMR increased the risk of psychiatric disorders after childbirth (aOR 1.5, 95% CI 1.2-1.9). The prevalence of psychiatric disorders had increased after compared to before childbirth (mean difference 0.02 ± 0.25, 95% CI 0.018-0.022, p < 0.001). Women giving birth by CSMR tended to be diagnosed in the inpatient care more often (54.9% vs. 45.8%, p = 0.056) and were more likely to have been diagnosed before childbirth as well (39.8% vs. 24.2%, p < 0.001). Women giving birth by CSMR more often suffer from psychiatric disorders both before and after delivery. This indicates that these women are a vulnerable group requiring special attention from obstetric- and general health-care providers. This vulnerability should be taken into account when deciding on mode of delivery.


Investigation of arsenic contamination in groundwater using hydride generation atomic absorption spectrometry.
The validated hydride generation atomic absorption spectrometry (HG-AAS) method has been used to investigate total arsenic in groundwater. Under optimal experimental conditions, the concentration of arsenic in groundwater can be analysed in the range of 0.5 to 50 µg/L, with a method detection limit of 0.15 µg/L. Its recovery in the field is from 96.3 to 99.8%, with high repeatability. The method was used to observe the total arsenic pollution in groundwater collected in Phu Tho Province, Vietnam. A total of 364 groundwater samples were analysed. The results showed that arsenic pollution was significant, with 15.93% of the samples higher than the maximum permissible level of arsenic. About 20.69% of the contaminated samples had a total arsenic ten times higher (100 µg/L) than the maximum permissible level of arsenic. The pollution source was also considered by comparing the arsenic level in the groundwater with arsenic in the surface water in the same areas. Thus, the use of the high-accuracy and sensitive method, HG-AAS, supplies valuable data on groundwater pollution for water resources management and environmental protection.


Chemohormone therapy of metastatic melanoma with megestrol acetate plus dacarbazine, carmustine, and cisplatin.
Chemotherapy with dacarbazine, carmustine, and cisplatin produces a modest objective response rate in melanoma. Megestrol acetate may ameliorate cachexia, abrogate drug resistance, and increase survival time in melanoma. Nineteen patients with metastatic melanoma (16 evaluable) treated with dacarbazine (220 mg/m2/day for 3 days, intravenously [IV]), cisplatin (25 mg/m2/day for 3 days IV) every 3 weeks, and carmustine (150 mg/m2 IV single dose every 6 weeks) together with megestrol acetate (160 mg/day by mouth continuously) starting 2 days before chemotherapy. This regimen was well tolerated and resulted in a mean net weight gain of 1.45 kg. A 47% objective response rate was observed in all patients, including visceral sites of response, with a 39+ week median duration of response and median survival time of 16.7+ months in all evaluable patients. In this small Phase II study, the authors showed that megestrol acetate may contribute to a high objective response rate and prolonged median survival when used with a chemotherapy regimen of dacarbazine, carmustine, and cisplatin.


A method for the production of an undisplaced reproducible tibial fracture in the rat.
Forty inbred hooded rats sustained a fracture of the left tibia and 2 animals had an additional fracture of the right tibia (44 fractures in 42 rats). Before the fracture, medullary nailing was done with a 0.8-mm stainless-steel wire. Forty-one of the 42 fractures were transverse, 7 of the 42 nails bent more than 15 degrees. Radiological union occurred within 3--4 weeks.


Multiple fibrous xanthomas of tendon sheath.
Fibrous xanthomas of the digital tendon sheath system are a common benign tumour. The varying recurrence rates cited in the literature have usually been attributed to inadequate surgical excision. However, Boyes (1964) has suggested "seeding" as a possible mechanism to explain persistence of the tumour. Our case of multiple fibrous xanthomas at different levels in a single digital sheath system is presented as an example of "seeding" along the tendon sheath.


Mitochondrial dysfunction characterized in human induced pluripotent stem cell disease models in MELAS syndrome: A brief summary.
Human induced pluripotent stem cells (hiPSCs) for MELAS syndrome (mitochondrial myopathy, encephalopathy, lactic acidosis, stroke-like episodes) may allow deeper understanding of how tissue-specific mitochondrial dysfunction result in multi-systemic disease. Here, we summarize how the m.3243G mtDNA mutation affects mitochondrial function in different tissues using iPSC and iPSC-differentiated cell type disease models and what significant findings have been replicated in the independent studies. Through this brief review and with a focus on mitochondrial dysfunction in iPSC-differentiated cell types, namely fibroblast, neuron, and retinal pigment epithelium cells, we aim to bring awareness of hiPSC as a robust mitochondrial disease model even if many unanswered questions remain.


A guide to tax-exempt bonds.
Nursing administrators are actively involved in hospital credit ratings. We review sources of funding for capital investments, bond rating agencies, and hospital bond ratings. The questions frequently asked of nursing are outlined as well as steps to prepare for a facility visit.


A Pilot, Phase II, Observational, Case-Control, 1-Month Study on Asthenopia in Video Terminal Operators without Dry Eye: Contrast Sensitivity and Quality of Life before and after the Oral Consumption of a Fixed Combination of Zinc, L-Carnitine, Extract of Elderberry, Currant and Extract of Eleutherococcus.
The aims of the study were to investigate the ability and effectiveness of an oral intake of a fixed combination of zinc, L-carnitine, elderberry extract, black currant and Eleutherococcus extract in controlling the symptoms of eyestrain in videoterminal (VDT) users and to record its effects on contrast sensitivity. A single-center, phase II, observational, case-control, 1-month study in VDT workers without dry eye disease was carried out. Demographics and number of actual hours at VDT/day were taken into account. All subjects underwent a complete ophthalmic examination, including assessment of contrast sensitivity, and completed the computer vision symptom scale questionnaire at baseline and one month later. A total of 30 Caucasian subjects adhered to the required inclusion criteria and completed the study; 15 subjects were treated (T) and 15 were controls (C). All clinical data at baseline were similar in both groups (p > 0.05): after one month, all subjects had stable visual acuity, refractive defect and intraocular pressure (IOP); screen exposure time was unchanged. Regarding symptoms, at randomization, the groups had a similar score: 33.1 ± 3.3 in T and 32.8 ± 5.6 in C. One month later, the computer vision symptom scale (CVSS) questionnaire score decreased by -14.1 ± 3, 1 (p = 0.000) and -2.3 ± 1.8 (p = 0.568), respectively. Regarding contrast sensitivity, in group C the values of spatial frequencies remained unchanged, while they improved in almost all the cycles per degree stimuli in the treated group. Oral intake of a fixed combination of zinc, L-carnitine, elderberry extract, black currant and eleutherococcus extract can significantly improve contrast sensitivity and symptoms in VDT workers with no signs of dry eye disease.


Cross-cultural perspectives on pitch memory.
We examined effects of age and culture on children's memory for the pitch level of familiar music. Canadian 9- and 10-year-olds distinguished the original pitch level of familiar television theme songs from foils that were pitch-shifted by one semitone, whereas 5- to 8-year-olds failed to do so (Experiment 1). In contrast, Japanese 5- and 6-year-olds distinguished the pitch-shifted foils from the originals, performing significantly better than same-age Canadian children (Experiment 2). Moreover, Japanese 6-year-olds were more accurate than their 5-year-old counterparts. These findings challenge the prevailing view of enhanced pitch memory during early life. We consider factors that may account for Japanese children's superior performance such as their use of a pitch accent language (Japanese) rather than a stress accent language (English) and their experience with musical pitch labels.


Decrease of lethal infectious complications in the context of causes of death (COD) after hematopoietic cell transplantation: COD-2 and COD-1 study of the Infectious Diseases Working Party EBMT.
We previously analyzed trends in incidence and factors associated with lethal complications in ALL/AML/CML patients (causes of deaths; COD-1 study). The objective of this study was the analysis of incidence and specific causes of death after HCT, with focus on infectious deaths in two time periods, 1980-2001 (cohort-1) and 2002-2015 (cohort-2). All patients with HCT for lymphoma, plasma cell disorders, chronic leukemia (except CML), myelodysplastic/myeloproliferative disorders, registered in the EBMT-ProMISe-database were included (n = 232,618) (COD-2 study). Results were compared to those in the ALL/AML/CML COD-1 study. Mortality from bacterial, viral, fungal, and parasitic infections decreased in very early, early and intermediate phases. In the late phase, mortality from bacterial infections increased, while mortality from fungal, viral, or unknown infectious etiology did not change. This pattern was similar for allo- and auto-HCT in COD-1 and COD-2 studies, with a distinct and constant lower incidence of all types of infections at all phases, after auto-HCT. In conclusion, infections were the main cause of death before day +100, followed by relapse. Mortality from infectious deaths significantly decreased, except late phase. Post-transplant mortality has significantly decreased in all phases, from all causes after auto-HCT; it has decreased in all phases after allo-HCT except late phase.


Circulating irisin levels and muscle FNDC5 mRNA expression are independent of IL-15 levels in mice.
Interleukin-15 (IL-15) and irisin are exercise-induced myokines that exert favorable effects on energy expenditure and metabolism. IL-15 can induce PGC-1α expression, which in turn induces expression of irisin and its precursor, FNDC5. Therefore, the present study tested the hypothesis that increases in circulating irisin levels and muscle FNDC5 mRNA expression are dependent on IL-15. Circulating irisin levels and gastrocnemius muscle FNDC5 mRNA expression were examined following acute exercise in control and IL-15-deleted (IL-15 KO) mice, following injection of IL-15 into IL-15 KO mice, and in transgenic mice with elevated circulating IL-15 levels (IL-15 Tg mice). Circulating IL-15 levels and muscle PGC-1α and PPARδ mRNA expressions were determined as positive controls. No effect of IL-15 deletion on post-exercise serum irisin levels or muscle FNDC5 mRNA expression was detected. While serum IL-15 levels and muscle PGC-1α expression were elevated post-exercise in control mice, both serum irisin levels and muscle FNDC5 expression decreased shortly after exercise in both control and IL-15 KO mice. A single injection of recombinant IL-15 into IL-15 KO mice that significantly increased muscle PPARδ and PGC-1α mRNA expressions had no effect on circulating irisin release, but modestly induced muscle FNDC5 expression. Additionally, serum irisin and gastrocnemius muscle FNDC5 expression in IL-15 Tg mice were similar to those of control mice. Muscle FNDC5 mRNA expression and irisin release are not IL-15-dependent in mice.


Abstracts of the 2016 CSBBCS Annual Meeting: Résumés du congrés annuel 2016 de la SCCCSC.
Provides a collection of abstracts from the 2016 CSBBCS Annual Meeting. (PsycINFO Database Record


Low-gradient single-sided NMR sensor for one-shot profiling of human skin.
This paper describes a shimming approach useful to reduce the gradient strength of the magnetic field generated by single-sided sensors simultaneously maximizing its uniformity along the lateral directions of the magnet. In this way, the thickness of the excited sensitive volume can be increased without compromising the depth resolution of the sensor. By implementing this method on a standard U-shaped magnet, the gradient strength was reduced one order of magnitude. In the presence of a gradient of about 2 T/m, slices of 2mm could be profiled with a resolution that ranges from 25 μm at the center of the slice to 50 μm at the borders. This sensor is of particular advantage for applications, where the scanning range is of the order of the excited slice. In those cases, the full profile is measured in a single excitation experiment, eliminating the need for repositioning the excited slice across the depth range to complete the profile as occurs with standard high gradient sensors. Besides simplifying the experimental setup, the possibility to move from a point-by-point measurement to the simultaneous acquisition of the full profile led to the shortening of the experimental time. A further advantage of performing the experiment under a smaller static gradient is a reduction of the diffusion attenuation affecting the signal decay measured with a CPMG sequence, making it possible to measure the T(2) of samples with high diffusivity (comparable to the water diffusivity). The performance of the sensor in terms of resolution and sensitivity is first evaluated and compared with conventional singled-sided sensors of higher gradient strength using phantoms of known geometry and relaxation times. Then, the device is used to profile the structure of human skin in vivo. To understand the contrast between the different skin layers, the distribution of relaxation times T(2) and diffusion coefficients is spatially resolved along the depth direction.


Partial D, weak D types, and novel RHD alleles among 33,864 multiethnic patients: implications for anti-D alloimmunization and prevention.
The D antigen includes category D, partial D, and weak D types, which are important because anti-D alloimmunization can occur in some but not all persons that express a variant RHD allele. At present, there is little prospective information on the prevalence of D variants among obstetric patients and potential transfusion recipients. The RHD alleles were prospectively examined in a large patient population identified on the basis of a difference in anti-D reactivity between two reagents. Fifty-five discrepancies (0.96% of D-) were noted among 33,864 ethnically diverse patients over 18 months, of which 54 represented mutated RHD alleles. Seven obstetric patients were assigned D- status based on serology; only 1 patient had a partial RHD allele. Ten of 25 (36%) obstetric patients and 4 of 6 (67%) female potential transfusion recipients of childbearing age or younger were assigned D+ status, and they expressed a D variant known to permit anti-D alloimmunization. In total 20 RHD alleles were identified including category, DVa or DVa-like alleles (n = 7), DAR (n = 8), and four novel RHD alleles including two new DAU alleles. Given the complexity of D antigen expression, it is concluded that some clinically important D variants identified by standard serologic analysis phenotype as D+ and are potentially at risk for the development of anti-D.


Beyond sleep duration: Sleep timing is associated with BMI among Brazilian adults.
To examine the association of sleep duration and timing with BMI among adults. Also, to identify obesogenic and unhealthy behaviors (e.g.diet/sleep quality, physical activity, screen time, smoking) associated with short sleep duration and late bedtime. Participants (n=755) were part of exploratory, population-based research, with data collection in a virtual environment. For purposes of characterizing the population we considered short sleepers<7h/night, and the population bedtime median was used to stratify participants into early and late sleepers (before and after 23:08). Student's t-test and chi-square test were performed to assess differences in characteristics between groups. Linear regression analyses were conducted to determine the association of sleep duration, bedtime, and wake-up time with BMI. Quantile regression was estimated for the 25th, 50th, and 75th quantiles to identify the distributional correlations between BMI and sleep variables. Restricted cubic splines were also used to study the shape of the association between sleep-BMI. Analyses were adjusted for potential confounding variables. BMI decreased by 0.40Kg/m2 for each additional hour of sleep duration [95%CI=-0.68,-0.12,p=0.005] and increased by 0.37 kg/m2 for each additional hour of bedtime [95%CI=0.12,0.61,p=0.003]. The association between bedtime and BMI remained even after adjustment for sleep duration. These effects were higher and stronger with higher BMI values (p75th). Wake-up time did not show statistically significant associations. Because we found that beyond sleep duration, bedtime was significantly associated with BMI, our data reflect the pertinence of assessing sleep timing patterns in disentangling sleep-obesity association. Insights into the characteristics, obesogenic and unhealthy behaviors related to short and late sleep may support specific strategies to prevent and treat excess body adiposity and other negative health outcomes.


Preparation of influenza virus subviral particles lacking the HA1 subunit of hemagglutinin: unmasking of cross-reactive HA2 determinants.
Acid treatment of influenza A and B virus preparations followed by addition of dithiothreitol (DTT) and centrifugation through a sucrose cushion removes the HA1 subunit of hemagglutinin from virus. Rabbit sera made against these subviral particles and untreated virus were tested in a radioimmune precipitation assay using [35S]cysteine-labeled virus. Conditions of the assay permitted discrimination of discrete HA1- and HA2-specific antibody populations. It was found that (a) sera raised to intact influenza A virus preparations contained both HA1- and HA-2 specific antibodies, (b) sera made to subviral particles of influenza A virus contained HA2-specific antibody but had little or no detectable HA1-specific antibody. (c) the HA2-specific antibodies were partially cross-reactive with the HA2 of an influenza A virus of a different subtype, and (d) sera raised against two strains of untreated influenza B viruses contained antibodies which were cross-reactive with the HA2 as well as the NP of influenza A viruses.


Balance and fear of falling in Parkinson's disease.
To assess internal consistency and validity of measures of balance (Berg balance scale, BBS), postural changes (postural changes scale, PCS) and fear of falling (fear of fall measure, FFM) in 70 ambulant Parkinson's disease (PD) persons, these instruments were matched with performance-based balance and mobility tests, and other clinical, functional and quality of life PD-specific measures. The BBS, PCS and FFM showed a good internal consistency, moderate to good inter-correlation, and a significant correlation with measures of both disability (UPDRS-ADL, Schwab and England scale) and--to a lesser extent--impairment/severity of symptoms (UPDRS-ME, Hoehn and Yahr Scale). Tandem Romberg, Single-Limb Stance, Functional Reach, and the Timed Up & Go test correlated slightly better with BBS than with PCS and FFM. This study shows that problems of balance and postural control in PD patients result from complex interactions between motor impairment, functional abilities and fear of falling.


Making universal newborn hearing screening a success.
Following a long period of pilot study, Iaso maternity hospital established a universal newborn hearing screening program based on transiently evoked otoacoustic emissions (TEOAEs). The aim of this study is to present the improvement of outcome measures of this program, comparing the results of two groups of newborns screened successively. We analyzed data from two groups of full-term newborns screened at our setting. The first group included all newborns born and screened during the initial 3 years of application of the program and the second group included all newborns born and screened during the next 2 years. TEOAEs were performed during the first days after birth. All newborns who failed the initial test underwent repeat testing with TEOAEs before hospital discharge. Newborns with absence of otoacoustic emissions were referred to follow-up test after 1 month. Results were compared between the two groups. The first group included 22,195 newborns-examined during 3 years and the second group included 25,032 newborns-examined during 2 years, due to reduction of the rate of newborns who missed screening. Refer rate was 3.1% for the first group and 2.1% for the second group. "Missed to follow-up" rate was reduced from 72.2% in the first group to 58.2% in the second group. The rate of newborns who did not undergo screening and the rate of "missed to follow-up" newborns were reduced in time, due to various modifications of the protocol. Universal newborn hearing screening may be, thus, a feasible and cost effective method of identifying congenital hearing loss.


Brownian motion of aggregating nanoparticles studied by photon correlation spectroscopy and measurements of dynamic magnetic properties.
We have investigated colloidal stability of magnetic nanoparticle suspensions in different buffer systems and NaCl concentrations commonly used for biological applications. We have also investigated how conjugation of proteins to magnetic nanoparticles affects colloidal stability. Two different techniques, giving complementary information on the state of the particle system studied, have been used and compared. We have monitored the rotational Brownian motion of particles using measurements of dynamic magnetic susceptibility in the frequency domain. The results were processed using an algorithm that enables us to quantify changes of particle size distribution for particle suspensions subjected to various buffer conditions. The measurements were compared to results obtained for the translational Brownian motion of the same nanoparticles using photon correlation spectroscopy (PCS). We demonstrate that the complementarity of the two techniques enables more precise characterization of particles in suspension, particularly for suspensions of particles with a wide distribution in size and shape, or systems that are close to the onset of agglomeration.


Lack of asymmetrical distribution of receptor binding sites and of neurally active peptides within rat brain.
The high affinity binding of 5 tritiated (naloxone, spiroperidol, serotonin, quinuclidinylbenzilate, dihydroalprenolol) ligands to left and right frontal cortex, hippocampus and striatum has been compared in 8-week-old male rats. No lateralization of specific binding was observed between paired brain regions. Also, no regional asymmetry of protein content was found. No significant differences in met-enkephalin and substance P contents were found between paired striata, frontal cortex, and hippocampi. These data suggest that several neurotransmitter and neuromodulator indices are symmetrically distributed within the rat brain.


Sex differences in biopsychosocial correlates of binge eating disorder: a study of treatment-seeking obese adults in primary care setting.
Although community-based studies suggest equivalent levels of physical and psychological impairment by binge eating disorder (BED) in men and women, men with BED are still underrepresented in clinical studies. This study aimed to provide a comprehensive analysis of sex differences in biopsychosocial correlates of treatment-seeking obese patients with BED in primary care. One hundred-ninety obese adults (26% men) were recruited in primary care settings for a treatment study for obesity and BED. Very few significant sex differences were found in the developmental history and in current levels of eating disorder features, as well as psychosocial factors. Women reported significantly earlier age at onset of overweight and dieting and greater frequency of dieting. Men reported more frequent strenuous exercise. Men were more likely than women to meet criteria for metabolic syndrome; men were more likely to show clinically elevated levels of triglycerides, blood pressure, and fasting glucose levels. Despite few sex differences in behavioral and psychosocial factors, metabolic problems associated with obesity were more common among treatment-seeking obese men with BED than women. The findings highlight the importance of including men in clinical studies of BED and active screening of BED in obese men at primary care settings.


The N-terminal helix of Bcl-xL targets mitochondria.
Anti- and pro-apoptotic Bcl-2 family members regulate the mitochondrial phase of apoptotic cell death. The mitochondrial targeting mechanisms of Bcl-2 family proteins are tightly regulated. Known outer mitochondrial membrane targeting sequences include the C-terminal tail and central helical hairpin. Bcl-xL also localizes to the inner mitochondrial membrane, but these targeting sequences are unknown. Here we investigate the possibility that the N-terminus of Bcl-xL also contains mitochondrial targeting information. Amino acid residues 1-28 of Bcl-xL fused to EGFP are sufficient to target mitochondria. Although positive charges and helical propensity are required for targeting, similar to import sequences the N-terminus is not sufficient for efficient mitochondrial import.


The place of echography in percutaneous nephrostomy and nephrostolithotomy.
The advantages and limits of echography in the performance of percutaneous nephrostomy and nephrostolithotomy are described, based on our own cases.


Interval aeration improves degradation and humification by enhancing microbial interactions in the composting process.
Five full-scale food waste composts were conducted under different aeration frequencies (no aeration, aeration at different intervals, and continuous aeration) to reveal the optimal strategy and its microbial mechanisms. The highest degradation rate (77.2%) and humus content (29.3%) were observed in Treatment D with interval aeration (aeration 20 min, pause 10 min). Aeration influenced the degradation and humification rate by regulating microbial interactions. The microbial interactions peaked in Treatment D, with a 1.30-fold increase. In terms of the microbial community, Thermobifida was a key genus for improving positive cohesion, fulfilling three criteria (high abundance, high occurrence frequency, and significant differences between treatments). The aeration strategy employed in Treatment D not only increased relative abundance of Thermobifida (1.2 times higher) but also strengthened interaction between it and functional genera (34 nodes). Overall, interval aeration, featured by 20 min aeration and 10 min pause, could increase microbial interactions and improve composting efficiency.


Relationship of skin thickness to duration of diabetes, glycemic control, and diabetic complications in male IDDM patients.
Skin thickness is primarily determined by collagen content and is increased in insulin-dependent diabetes mellitus (IDDM). We measured skin thickness in 66 IDDM patients aged 24-38 yr and investigated whether it correlated with long-term glycemic control and the presence of certain diabetic complications. With univariate analysis, skin thickness was increased and significantly related to duration of diabetes (P less than .001), previous glycemic control (P less than .001), retinopathy (P less than .001), cheiroarthropathy (P less than .001), and vibration-perception threshold (P less than .05). There was a negative correlation between forced expiratory volume at 1 s (P less than .05) and vital capacity (P less than .05) with duration of diabetes. Neither skin thickness nor ankle arteriomedial wall calcification correlated with abnormal autonomic function tests. When corrected for duration of diabetes, there was a weak correlation between skin thickness and glycemic control (P less than .05) but no correlation with retinopathy, cheiroarthropathy, and vibration-perception threshold. This study confirms that there are widespread connective tissue changes in diabetes mellitus, although the biochemistry needs further elucidation.


Excellent performance supercapacitors with the compounding of Ni(OH)2 and ZIF-67 derived Co-C-N nanosheets as flexible electrode materials.
Owing to the advantages of high theoretical capacity, low cost, and excellent chemical stability, Ni(OH)2 is considered as a potential candidate for electrode materials of supercapacitors. However, its further applications are limited by its adverse surface chemical properties. In this paper, a composite material consisting of ZIF-67 derived Co-C-N nanosheets and Ni(OH)2 was synthesized facilely on carbon cloth in situ, and based on the collective advantages of the various components, excellent electrochemical performance could be achieved when used as a flexible electrode material of supercapacitors. In detail, the as-obtained sample Ni(OH)2/Co-C-N/CC exhibits an ultrahigh specific capacitance of 2100 F g-1 at a current density of 1 A g-1. Moreover, the further assembled asymmetric supercapacitor device exhibits a maximum energy density of 78.6 W h kg-1 at a power density of 749.4 W kg-1. Furthermore, the device also shows outstanding cycling stability with 90.2% capacitance retention after 5000 cycles of charge-discharge. Basically, the remarkable performance can be attributed to the well-developed structure, abundant active sites, complex beneficial components, and their intrinsic properties. Significantly, rational design can broaden the research directions of corresponding electrode materials.


Isolation of Histoplasma capsulatum from the air in the Aguas Buenas Caves, Aguas Buenas, Puerto Rico.
White mice were used to isolate H. capsulatum from the air in the Aguas Buenas Caves, Puerto Rico. Based on the infection of mice, the ten test sites yielded positive results for the presence of the fungus. Air currents through this cave are believed to be the most important factor responsible for the even distribution of H. capsulatum. Cultural differences concerning spore concentrations were observed. Age and sex of the exposed mice do not seem to play a role in acquiring histoplasmosis.


Thermo-optical switching enhanced with second harmonic generation in microring resonators.
We investigate the thermo-optic effects on second harmonic generation (SHG) in AlGaAs/AlO(x) microring (MR) waveguides. We show that SHG can be utilized to enhance the thermal sensitivity of MRs. This sensitivity makes this structure appropriate for thermal modulation and switching of optical signals or temperature sensing.


Discovery of a potent tubulin polymerization inhibitor: synthesis and evaluation of water-soluble prodrugs of benzophenone analog.
Prodrugs have proven to be very useful in enhancing aqueous solubility of sparingly water-soluble drugs, thereby increasing in vivo efficacy without a need of special excipients. In vitro and in vivo evaluations of a number of amino acid prodrugs of 1, a previously identified potent tubulin polymerization inhibitor and cytotoxic against various cancer cell lines led to the discovery of 3·HCl (l-valine attached) which is highly efficacious in mouse xenografts bearing human cancer. Pharmacokinetic analysis in rats revealed that compound 1 was released immediately upon administration of 3·HCl intravenously, with rapid clearance of 3·HCl indicating the effective cleavage of prodrug. Compound 3·HCl (CKD-516) has now been progressed to phase 1 clinical trial.


Inappropriate iron intake in children on long-term parenteral nutrition: outcome after iron withdrawal.
Inappropriate parenteral iron intake in children on long-term parenteral nutrition can be responsible for iron overload. This study was carried out to monitor iron status changes when iron parenteral intake was stopped in case of iron overload. Seven children with serum ferritin concentrations above 800 ng/ml (6 with documented liver iron overload) were prospectively studied after total discontinuation of parenteral iron intake and without chelation therapy. Iron status was assessed, by means of ferritin and iron plasma concentrations, 8-15 months (T(1)) and 24-30 months (T(2)) after withdrawal of parenteral iron. Ferritin and iron concentrations declined at T(1), or T(2) in all but two children. At T(2) ferritin and iron concentrations were significantly lower (P < 0.05) than before iron parenteral discontinuation with a yearly reduction of 22 +/- 15% and 15 +/- 16%, respectively, for ferritin concentration and iron concentration. This fall in serum ferritin concentration is comparable to thalassemic subjects after bone marrow transplantation. The total withdrawal of parenteral iron intake improves iron status in children with iron overload. Nevertheless, iron overload related parenteral nutrition should be avoided by lowering iron intake in case of long-term total parenteral nutrition and by careful monitoring.


Comparison of human papillomavirus detection between freshly frozen tissue and paraffin embedded tissue of invasive cervical cancer.
Human Papillomavirus (HPV) detection results comparing paraffin embedded cervical tissue and other cervical specimens have been done with varying degrees of agreement. However, studies comparing freshly frozen specimens and paraffin embedded specimens of invasive cervical carcinomas are lacking. The aim of the study was to compare HPV detection using SPF10 broad-spectrum primers PCR followed by DEIA and genotyping by LiPA25 (version 1) between freshly frozen cervical tissue samples and paraffin embedded blocks of cervical tissue from the same patient. There were 171 pairs of paraffin embedded and freshly frozen samples analyzed from cervical carcinoma cases from Kampala, Uganda. 88.9% (95% CI: 83.2%-93.2%) of paraffin embedded samples were HPV positive compared with 90.1% (95% CI: 84.6%-94.1%) of freshly frozen samples, giving an overall agreement in HPV detection between fresh tissue and paraffin embedded tissue at 86.0% (95% CI: 79.8%-90.8%). Although the proportion of HPV positive cases in freshly frozen tissue was higher than those in paraffin blocks, the difference was not statistically significant (p > 0.05). In both types of tissues, single HPV infections were predominant, with HPV16 accounting for 47% of positive cases. Comparison in the overall agreement, taking into accounts not only positivity in general, but also HPV types, showed a 65% agreement (complete agreement of 59.7%, partial agreement of 5.3%) and complete disagreement of 35.0%. HPV detection in squamous cell carcinomas (SCC) and adenocarcinomas (ADC) was similar in fresh tissue or paraffin blocks (p ≥ 0.05).p16 immunostaining in samples that had at least one HPV negative results showed that 24 out of 25 cases had an over-expressed pattern. HPV DNA detection was lower among ADC as compared to SCC. However, such differences were minimized when additional p16 testing was added, suggesting that the technical issues may largely explain the HPV negative cases.


Structure-function analysis of ceTIR-1/hSARM1 explains the lack of Wallerian axonal degeneration in C. elegans.
Wallerian axonal degeneration (WD) does not occur in the nematode C. elegans, in contrast to other model animals. However, WD depends on the NADase activity of SARM1, a protein that is also expressed in C. elegans (ceSARM/ceTIR-1). We hypothesized that differences in SARM between species might exist and account for the divergence in WD. We first show that expression of the human (h)SARM1, but not ceTIR-1, in C. elegans neurons is sufficient to confer axon degeneration after nerve injury. Next, we determined the cryoelectron microscopy structure of ceTIR-1 and found that, unlike hSARM1, which exists as an auto-inhibited ring octamer, ceTIR-1 forms a readily active 9-mer. Enzymatically, the NADase activity of ceTIR-1 is substantially weaker (10-fold higher Km) than that of hSARM1, and even when fully active, it falls short of consuming all cellular NAD+. Our experiments provide insight into the molecular mechanisms and evolution of SARM orthologs and WD across species.


Response and survival predictors in a cohort of 319 patients with Waldenström macroglobulinemia treated with ibrutinib monotherapy.
Bruton tyrosine kinase (BTK) inhibitors are the only FDA-approved treatments for Waldenström macroglobulinemia (WM). Factors prognostic of survival and predictive of response to BTK inhibitors remained to be clarified. We evaluated 319 patients with WM to identify predictive and prognostic factors on ibrutinib monotherapy. Logistic and Cox proportional-hazard regression models were fitted for response and survival. Multiple imputation analyses were used to address bias associated with missing data. Major (partial response or better) and deep responses (very good partial response or better) were attained in 78% and 28% of patients. CXCR4 mutations were associated with lower odds of major (odds ratio [OR], 0.2; 95% confidence interval [CI], 0.1-0.5; P < .001) and deep response (OR, 0.3; 95% CI, 0.2-0.6; P = .001). CXCR4 mutations (hazard ratio [HR], 2.0; 95% CI, 1.2-3.4; P = .01) and platelet count 100 K/uL or less (HR, 2.5; 95% CI, 1.3-4.9; P = .007) were associated with worse progression-free survival (PFS). We proposed a scoring system using these 2 factors. The median PFS for patients with 0, 1, and 2 risk factors were not reached, 5 years and 3 years (P < .001). Patients with 2 risk factors had HR 2.2 (95% CI, 1.3-3.8; P = .004) compared with 1 factor, and patients with 1 factor had HR 2.3 (95% CI, 1.1-5.1; P = .03) compared with 0 factors. Age ≥65 years was the only factor associated with overall survival (HR, 3.2; 95% CI, 1.4-7.0; P = .005). Multiple imputation analyses did not alter our results. Our study confirms the predictive and prognostic value of CXCR4 mutations in patients with WM treated with ibrutinib monotherapy.


Biophysical factors affecting the distribution of demersal fish around the head of a Submarine Canyon off the Bonney Coast, South Australia.
We sampled the demersal fish community of the Bonney Canyon, South Australia at depths (100-1,500 m) and locations that are poorly known. Seventy-eight species of demersal fish were obtained from 12 depth-stratified trawls along, and to either side, of the central canyon axis. Distributional patterns in species richness and biomass were highly correlated. Three fish assemblage groupings, characterised by small suites of species with narrow depth distributions, were identified on the shelf, upper slope and mid slope. The assemblage groupings were largely explained by depth (ρw = 0.78). Compared to the depth gradient, canyon-related effects are weak or occur at spatial or temporal scales not sampled in this study. A conceptual physical model displayed features consistent with the depth zonational patterns in fish, and also indicated that canyon upwelling can occur. The depth zonation of the fish assemblage was associated with the depth distribution of water masses in the area. Notably, the mid-slope community (1,000 m) coincided with a layer of Antarctic Intermediate Water, the upper slope community (500 m) resided within the core of the Flinders Current, and the shelf community was located in a well-mixed layer of surface water (<450 m depth).


Toxocara-infestations in Austria: a study on the risk of infection of farmers, slaughterhouse staff, hunters and veterinarians.
A total of 585 persons from several occupational groups (farmers, slaughterhouse staff, hunters, veterinarians) exposed to Toxocara infestations and 50 persons of a control group were tested for the presence of specific antibodies to the Toxocara canis antigen using an enzyme-linked immunosorbent assay and a western blot. Farmers showed the highest seroprevalence (44%), followed by veterinarians (27%), slaughterhouse staff (25%) and hunters (17%), whereas only 2% of the individuals of the control group were seropositive. Thus, the risk to Toxocara infestation is 39, 18, 16 and 9 times higher for farmers, veterinarians, slaughterhouse staff (some workers were part-time farmers) and for hunters, respectively, when compared to the control group. The main source of infection in rural areas seems to be (roaming) farm cats and dogs that have not been dewormed. The results are discussed with a view to potential risk factors and preventive measures, in terms of veterinary and human medicine.


Interaction of DNA and purine nucleosides with cis-dichlorodiammineplatinum(II) and antimitotic activity of the complexes on meristematic root cells.
The appropriate experimental conditions for the preparation of complexes of cis-dichlorodiammineplatinum(II) with DNA and with purine nucleosides have been determined which leave negligible amounts of free drug in the solution. Important conformational changes of DNA upon binding to cis-Pt(NH3)2-Cl2 have been evidenced through viscosity, electric birefringence and thermal denaturation experiments. The antimitotic and antitumor activity of the drug was found to be totally inhibited by its binding to DNA and to the purine nucleosides. Enzymic degradation observations on the DNA-cis-Pt(NH3)2Cl2 complexes indicated an important inhibition of the degradation and the absence of release of free drug. The implications of the results in relation with the mode of binding of this compound to DNA, with the choice of carriers for drugs and the mechanism of action of lysosomotropic agents are discussed.


Serum acidosis prior to reperfusion facilitates hemodynamic recovery following liver transplantation.
Reperfusion is the most critical event during liver transplantation, and sustained leakage of acidic preservation solution from the liver graft contributes to marked hemodynamic instability. Recent laboratory studies with hepatocyte cultures have revealed that low pH may protect hepatocyte mitochondria against ischemia-reperfusion injury by inhibiting the mitochondrial permeability transition (MPT), the so-called "pH paradox." However, the clinical significance of this pH paradox theory remains largely unknown. In this study, we sought to determine whether there is an association between serum pH immediately prior to reperfusion and hemodynamic recovery after reperfusion and graft survival. We analyzed retrospective data from 527 patients who underwent Orthotopic liver transplantation between 2003 and 2008. All patients were allocated to one of two groups: pH ≤ 7.32 or pH > 7.32, as measured 5 min before reperfusion. Case-control matching was performed using the propensity score to adjust for background differences between the two groups. Data were analyzed using Student's t-test and the χ (2) test. There were 85 patients in the pH ≤ 7.32 group and 385 patients in the pH > 7.32 group. The recovery of mean arterial pressure after hepatic artery reperfusion was significantly faster in the pH ≤ 7.32 group (slope of recovery: 0.0004 % vs. 0.0002 %/min, p = 0.041). Other parameters studied, including vasopressor dosage after reperfusion, did not show any statistically significant difference between groups. Our findings suggest that less aggressive treatment of acidosis with a slower rate of normalization of serum pH (from low to normal) after reperfusion promotes faster hemodynamic stabilization. These findings provide evidence to support the concept of the pH paradox, and may also substantiate the argument against the usage of alkalizing agents before reperfusion unless acidosis becomes clinically significant.


Obesity-associated mouse adipose stem cell secretion of monocyte chemotactic protein-1.
Studies showed that monocyte chemotactic protein-1 (MCP-1) concentrations are increased in obesity. In our current study, we demonstrate that plasma MCP-1 level in leptin-deficient ob/ob mice is significantly higher than in lean mice. Furthermore, we determined that basal adipose tissue MCP-1 mRNA levels are significantly higher in ob/ob mice compared with lean mice. To determine the mechanisms underlying obesity-associated increases in plasma and adipose tissue MCP-1 levels, we determined adipose tissue cell type sources of MCP-1 production. Our data show that adipose tissue stem cells (CD34(+)), macrophages (F4/80(+)), and stromal vascular fraction (SVF) cells express significantly higher levels of MCP-1 compared with adipocytes under both basal and lipopolysaccharide (LPS)-stimulated conditions. Furthermore, basal and LPS-induced MCP-1 secretion levels were the same for both adipose F4/80(+) and CD34(+) cells, whereas adipose CD34(+) cells have twofold higher cell numbers (30% of total SVF cells) compared with F4/80(+) macrophages (15%). Our data also show that CD34(+) cells from visceral adipose tissue depots secrete significantly higher levels of MCP-1 ex vivo when compared with CD34(+) cells from subcutaneous adipose tissue depots. Taken together, our data suggest that adipose CD34(+) stem cells may play an important role in obesity-associated increases in plasma MCP-1 levels.


The influences of increased CO2 and water supply on growth, biomass allocation and water use efficiency of Sinapis alba L. grown under different wind speeds.
We examined how independent and interactive effects of CO2 concentrations, water supply and wind speed affect growth rates, biomass partitioning, water use efficiency, diffusive conductance and stomatal density of plants. To test the prediction that wind stress will be ameliorated by increased CO2 and/or by unrestricted water supply we grew Sinapis alba L. plants in controlled chambers under combinations of two levels of CO2 (350 ppmv, 700 ppmv), two water regimes and two wind speeds (0.3 ms-1, 3.7 ms-1). We harvested at ten different dates over a period of 60 days. A growth analysis was carried out to evaluate treatment effects on plant responses. Plants grown both in increased CO2 and in low wind conditions had significantly greater stem length, leaf area and dry weights of plant parts. Water supply significantly affected stem diameter, root weight and leaf area. CO2 enrichment significantly increased the rate of biomass accumulation and the relative ratio of biomass increase to leaf area expansion. High wind speed significantly reduced plant growth rates and the rate of leaf area expansion was reduced more than the rate of biomass accumulation. Regression analysis showed significant CO2 effects on the proportion of leaf and stem dry weight to total dry weight. A marked plant-age effect was dependent on water supply, wind speed and CO2 concentration. A reduced water supply significantly decreased the stomatal conductance, and water use efficiency significantly increased with a limited water supply, low wind and increased CO2. We found significant CO2 x wind effects for water diffusion resistance, adaxial number of stomata and water use efficiencies and significant wind x water effect for water use efficiency. In conclusion, wind stress was ameliorated by growing in unrestricted water but not by growing in increased CO2.


Expression of adhesion molecules in allergic lung diseases.
Endothelial adherence and migration of leukocytes into tissue is mediated by different sets of adhesion molecules. The expression of these sets might not only preselect the types of leukocytes that enter the inflammatory sites, but also activate these leukocytes, induce adherence to epithelial cells, and cause the release of cytokines. Atopic asthma, extrinsic allergic alveolitis, and sarcoidosis as examples of immunologic lung diseases were investigated for the expression of adhesion molecules. Bronchial biopsies in chronic obstructive lung disease (COPD) and resected lung tissue of juvenile emphysema were chosen for controls. Immunohistochemistry was done on sections from bronchial and transbronchial biopsies and on smears from bronchoalveolar lavage cells. In all three types of immune disorders, lymphocytes expressed the integrins alpha4/beta1 (VLA4) and ICAM3, whereas lymphocytes in COPD bronchitis and in emphysema controls were unreactive. Eosinophils in atopic asthma bronchitis in contrast to COPD bronchitis also expressed both VLA4 and ICAM3. The expression of VCAM1 on endothelial cells was only seen in atopic asthma and was related to disease activity. The expression of other adhesion molecules was nonspecific. Expression of VCAM1 on endothelial cells and its ligand VLA4 on lymphocytes and eosinophils seems to be a specific event in atopic asthma. Expression of VLA4 and ICAM3 on lymphocytes, however, might be a specific event in all three immune reactions.


Investigation of risk factors for postoperative seroma/hematoma after TAPP.
Seroma/hematoma formation is the most common postoperative complication after laparoscopic inguinal hernia repair. The occurrence of seroma/hematoma remains unclear. The aim of this study was to determine the risk factors for seroma/hematoma formation after transabdominal preperitoneal patch plasty (TAPP). The study enrolled 359 groin hernia patients treated by TAPP at Kumamoto Medical Center between 2014 and 2019. The primary outcome was risk factors for postoperative seroma/hematoma formation after TAPP. The secondary outcomes included recurrence of hernia, postoperative complications, and hospital stay. Among the 359 patients, the incidence rate of seroma/hematoma was 16% (n = 69 patients), and the recurrence rate was 0.3% (n = 1 patient, both sides). In total, there were 452 lesions. Japan Hernia Society (JHS) type II was present in 23% (n = 106) of the total cases but was significantly more common in the postoperative seroma/hematoma group (40%; P = 0.0082). Meanwhile, JHS type I-3 comprised 27% of the total JHS type I group but was significantly higher in the postoperative seroma/hematoma JHS type I group (40%; P = 0.016). Compared with JHS type I, the multivariable odds ratio for postoperative seroma/hematoma formation in JHS type II was 2.77 (95% CI 1.54-4.95). Compared with JHS grade 1/2, the multivariable odds ratio for postoperative seroma/hematoma formation in JHS grade 3 was 2.27 (95% CI 1.28-4.03). Internal inguinal hernia and hernia size ≥ 3 cm were considered risk factors for postoperative seroma/hematoma formation after TAPP.


Secondary anterior capsulotomy in pseudophakic eyes.
This report describes a 1-handed technique and a 2-handed technique anterior capsulotomy in pseudophakic eyes. Each technique was used in a case of proliferative vitreoretinopathy accompanying anterior capsule contraction that occurred following cataract and intraocular lens (IOL) implantation. A capsulorhexis forceps and a stab knife were inserted into the anterior chamber, and the capsule contraction alleviated without extracting the IOL in both cases. Secondary anterior capsulotomy contributed to both the surgeon's visibility during intraocular surgery, including the subsequent vitreous surgery, and the patient's postoperative visual acuity. The transparency of the pupil region was restored. While the 1-handed technique involves the risk of adversely affecting Zinn's zonule, the 2-handed technique does not place a burden on Zinn's zonule and is thought to considerably improve the surgeon's visibility in subsequent vitreoretinal surgery.


Pioneering study of outdoor sound propagation.
The Reflections series takes a look back on historical articles from The Journal of the Acoustical Society of America that have had a significant impact on the science and practice of acoustics.


Novel approach to complex pulmonary arteriovenous malformation embolization using detachable coils and Amplatzer vascular plugs.
We evaluated the feasibility of a modified embolization technique of pulmonary arteriovenous malformations (PAVM) using venous sac embolization with detachable coils combined with the feeding artery embolization with the Amplatzer vascular plug (AVP). We retrospectively studied technical and clinical success in the treatment of 11 complexe PAVMs. We recorded number and size of feeding arteries and draining vein, the last prior and post treatment in the follow up CT, size of PAVMs; and the number of devices needed to occlude each PAVM. 11 complexe PAVM were treated with detachable coils to venous sac embolization followed by AVP to embolize feeding arteries. In all but one case a complete occlusion of the PAVM was angiographically achieved. The mean number of feeding vessel was 2.64 ± 0.92 (2-5). The mean number of coils was 7.82 ± 5.09 (3-20 coils). CT-follow-up, that was possible in 8 patients, showed a significant reduction of the draining vein size. The mean diameter reduction of the draining vein was 62 ± 18% varying between 29% and 77%. In all but one case with the complexe angioarchitecture the reduction of draining vein size close to 70% was achieved. Our study implies that the venous sac embolization using the detachable coils followed by occlusion of the large feeding arteries using the AVP is a highly efficient method for the treatment of the complex PAVMs with large out-flow vessels and short feeding arteries.


Altered expression of melanocortin-1 receptor (MC1R) in a yellow-coloured wild raccoon dog (Nyctereutes procyonoides).
The melanocortin 1 receptor (MC1R) gene plays a key role in determining coat colour in mammals by controlling the proportion of eumelanin and pheomelanin granules. Wild raccoon dogs have a mixed coat colour, with black to brown and grey hairs. The study was performed to identify the cause of the variant yellow coat colour in a wild raccoon dog. A wild raccoon dog that showed coat colour change to yellow and four wild-type raccoon dogs that showed normal coat colour were included. To identify the cause of the variant yellow coat colour, we examined the sequence of the MC1R gene and its expression at the mRNA and protein levels. The coding region of the MC1R gene of this raccoon dog comprised 954 bp, the same as for wild-type raccoon dogs and domestic dogs. By comparing the gene with that in the wild-type raccoon dog, a 2 bp deletion was detected in the 5'-untranslated region, positioned 152 bp upstream of the start codon. However, there was no significant difference in the mRNA expression level. The yellow raccoon dog revealed a significantly decreased MC1R protein level compared with the wild-type raccoon dogs, indicating an increase in pheomelanin synthesis. These results suggest that the variant coat colour in the yellow raccoon dog was associated with decreased MC1R function.


[Primary surgical treatment of lip-jaw-palate clefts in the year 2000. Report of the development of methods in the last 30 years and current status of surgical technique].
In this paper an attempt is made to survey the surgical treatment of cleft lip and palate regarding all classifications and all parts of the cleft. The most important developments up to 30 years ago to have been summarized in Millard's three-volume "Cleft Craft". Therefore, the author tries to analyze the present state-of-the-art cleft surgery. This part is certainly of a subjective nature due to the high rate of complexity in cleft malformations.


A new system to place single copies of genes, sites and lacZ fusions on the Escherichia coli chromosome.
To place a single-copy lacZ fusion on the E. coli chromosome, a method was developed based on in vivo homologous DNA recombination through P1 transduction. The fusions, initially constructed on plasmids, are crossed to lambdalacZ fusion vectors which are then lysogenized at the chromosomal lambda att site. The features of the new system are: (1) lambda lysogens carrying the fusion are made without regard for copy number; (2) P1 transduction from the lysogenic strain into an appropriate recipient generates the single-copy fusion; (3) The lacZ fusion has no prophage associated with it; (4) the lacZ fusion can be transferred by P1 transduction to other strains, simply by selecting for an antibiotic marker; (5) the system can be widely applied to construct single copies of any gene or site placed between bla and lacZ on the standard lacZ fusion plasmid vectors; and (6) the single-copy construct flanked by prophage att sites can be excised by site-specific recombination to generate non-replicating circular DNA of the clone or a cell cured of the construct.


Sign language, pantomime, and gestural processing in aphasic persons: a review.
Many aphasic individuals who fail to reacquire spoken language skills may retain the ability to acquire aspects of a manual communication system. This conclusion is reached after reviewing the results of studies of pantomime recognition and production, spontaneous gestural production, and manual language training in a wide range of aphasic subjects. Overall, the aphasic subjects appeared to be less impaired in their visuomotor processing than in their auditory-vocal processing. The results, however, are not definitive enough to resolve the long-standing debate as to whether or not a central symbolic deficit is present in aphasia.


Prevalence of Microorganisms of Public Health Significance in Ready-to-Eat Foods Sold in Developing Countries: Systematic Review and Meta-Analysis.
The issue of microbial quality and safety of ready-to-eat foods has become a public health concern that needs to be addressed to protect the consumer's health. Contamination of ready-to-eat foods by enteric pathogens such as Escherichia coli, Salmonella, and Staphylococcus aureus bacteria is associated with potential health risks and can cause foodborne outbreaks. Thus, the systematic review and meta-analysis aimed at determining the overall evidence on the prevalence of microorganisms of public health significance in ready-to-eat foods based on previous studies. The articles published from 2015 to 2020 were searched from multiple electronic databases such as PubMed, Google Scholar, MEDLINE, CINAHL, Science Direct, Web of Science, and the Directory of Open Access Journals. The JBI critical appraisal tool was applied to the included articles. To determine the heterogeneity among the included articles, I 2 statistics were used while publication bias was evaluated using the visual funnel plot. A Forest plot using the random effect model for meta-analysis was used to estimate the pooled prevalence of E. coli, Salmonella, and S. aureus in ready to eat foods. The pooled prevalence of E. coli, Salmonella, and S. aureus in ready to eat foods was 33.8% (95% CI: 19.9, 51.2; Q value = 67.080, I 2 = 89.56%), 26.0% (95% CI: 13.8, 43.6%; Q value = 83.67, I 2 = 91.63%), and 46.3% (95% CI: 24.8, 69.4%, I 2 = 94.9%), respectively. The findings show that contamination of ready-to-eat foods with pathogenic microorganisms continues to be a public health risk. Thus, effective food hygiene and safety systems are necessary to protect the health of the consumers and the public as a whole.


Faculty Learning and Professional Growth in the Sabbatical Leave.
The faculty sabbatical leave has been present in many institutions of higher education since its inception at Harvard University in 1880 but is relatively underexamined in the literature related to the outcomes not only to the institution but also to the faculty member. This study included interviews with 12 faculty members at one research university in the U.S. to better understand their perceptions of their sabbatical experiences in relation to the model of faculty professional growth. Findings underscored that faculty were agentic in their learning, the professional relationships they sought out to do this learning, as well as the commitments they made in this learning and growth, including that of their own work-life balance.


The clinical use of the Ohmeda Automated Anesthesia Record Keeper integrated in the Modulus II Anesthesia System. A preliminary report.
While performing his complex array of tasks, the anesthesiologist is also responsible for maintaining an anesthetic record. Up to now, this has been done by hand. The clinical use of automated anesthesia record keeping is presently evaluated. The anesthesia records generated by the Ohmeda Automated Anesthesia Record Keeper integrated in the Modulus II Anesthesia System is compared to hand written records. The differences between the two records of identical patients are quantified as erroneous or missing data. With the criteria adapted, we found significant and clinically relevant differences which stress the importance of automated record keeping.


HLA-DQB1, -DQA1, -DPB1, and -DPA1 genotyping and haplotype frequencies for a Hong Kong Chinese population of 1064 individuals.
HLA-DQB1, -DQA1, -DPB1, and -DPA1 genotyping and haplotype frequencies have been calculated from 1064 southern Chinese unrelated donors in a Hong Kong Bone Marrow Donor Registry. This is the first paper to report the distribution of DQB1-DQA1 and DPB1-DPA1 alleles in Hong Kong Chinese. Due to the Hardy-Weinberg equilibrium proportions (HWEP) deviation in DPB1 loci, this information may be of limited use for phylogenetic, comparative studies but will be useful for the permissible matching in HLA-DPB1 for Chinese patients awaiting haematopoietic stem cell transplantation in the near future due to the new recommendation of NMDP matching guidelines. The allele and haplotype data are available in the Allele Frequencies Net Database under the population name ''Hong Kong Chinese HKBMDR, DQ and DP'' and the identifier (AFND3667).


Numerical modeling of air-vented parallel plate ionization chambers for ultra-high dose rate applications.
Air-vented ionization chambers have been the secondary standard for radiation dosimetry since the origins of radiation metrology. However, the feasibility of their use in ultra-high dose rate pulsed beams has been a matter of discussion, as large losses are caused by ion recombinations and no suitable theoretical model is available for their correction. The theories developed by Boag and his contemporaries since the 1950s, which have provided the standard ion recombination correction factor in clinical dosimetry, do not provide an accurate description when used under the limit conditions of ultra-high dose rates (UHDRs). Moreover, the high-ion recombination effects of ionization chambers under extreme dose-rate applications are an obstacle to the development of adequate dosimetry standards. In this article, the charge carrier transport equations within a parallel plate ionization chamber (PPIC) have been solved numerically with a double aim. First, this numerical model provides a more accurate tool that can be used to evaluate ion recombination correction for established PPICs in pulsed ultra-high dose rate regimes. Second, studying the chamber behavior in detail allow as to explore the limits of new chamber designs in order to improve their performance under UHDRs. The model presented here has been tested by measuring the instantaneous current of one unit of a Roos chamber (i.e., the time-resolved current during and after the irradiation pulse under UHDR conditions) and comparing these results with the absolute value of the simulated current. The experimental data show consistent agreement with the results obtained using the numerical model. The experimental instantaneous current reveals effects such as the variation of the free electron fraction with the dose per pulse that are supported by the numerical model but cannot be explained in the framework of Boag's theory. Numerical solutions of the charge carrier released and transport in ionization chambers are able to estimate the effects observed when PPICs are irradiated with ultra-high dose rate beams and to provide new insight into processes related to recombination losses at UHDRs. These models can be reliably extended to include regions where current analytical solutions are not valid. An agreement of better than 5 % between the experimental and simulated effective free electron fraction is found. We were able to reproduce the instantaneous current from a Roos chamber. The discrepancies observed between the experimental data and the numerical simulations can be attributed to the uncertainty about the transport parameters involved in the calculation.


Nucleotide sequence of a regulatory region of the uidA gene in Escherichia coli K12.
Multiple regulatory events are involved in the expression of the uidA gene. A regulatory region of this gene has been located on a 460 base pair Sau3A-EcoRI fragment and its nucleotide sequence was determined by the dideoxy method using pEMBL plasmids. A preliminary analysis of this sequence revealed the presence of numerous palindromic structures with some overlaps.


Efficacy of sacral nerve stimulation for the treatment of fecal incontinence.
Sacral nerve stimulation has been shown to be an effective treatment for fecal incontinence and early studies reported success rates of 67% to 100%. However, "success" has been arbitrarily set at a 50% reduction in symptoms, and data are rarely reported with "intention to treat." This study aimed to assess the true efficacy of sacral nerve stimulation for fecal incontinence compared with the published literature. This prospective 5-year study was conducted to assess 50 patients with fecal incontinence treated with sacral nerve stimulation. All analyses were performed on an intention-to-treat basis. This study took place in a single tertiary referral colorectal department. Fifty consecutive patients with fecal incontinence refractory to conservative management were included in the study. The interventions performed were temporary evaluation with or without permanent sacral nerve stimulation. : Primary outcome measures were 1) attainment of continence, 2) reduction in fecal incontinence episodes, 3) improvement in Cleveland Clinic Fecal Incontinence scores, and 4) improvement in the ability to defer defecation. Thirteen patients (26%) did not respond at the temporary evaluation stage or were dissatisfied with the result. Ten further patients (20%) did not achieve a 50% reduction in symptoms following permanent implantation. The median follow-up was 17 months (range, 2-55), at which time 27 patients (54%) experienced a 50% or more reduction in symptoms, including 13 (26%) who achieved apparent continence. Median fecal incontinence episodes per fortnight reduced from 14 (range, 0-53) to 2 (range, 0-20; P < .0001). Median Cleveland Clinic Fecal Incontinence scores reduced from 15 (range, 3-20) to 8 (range, 0-17; P < .0001). The ability to defer defecation improved significantly (P < .0001). These results compare favorably with the published literature. Quality of life was not assessed. This study demonstrates that sacral nerve stimulation can be an effective treatment for patients with fecal incontinence; however, when analyzed by intention to treat, the symptoms of fecal incontinence continue in the majority (74%) of patients.


Baltimore pediatric ocular trauma study: Health disparities and outcomes in pediatric and adolescent open globe trauma.
Purpose Children represent approximately one-third of patients with serious ocular injuries. Our study evaluates associations between race and socioeconomic status in presentation and outcomes of pediatric and adolescent traumatic open globe injuries. Methods We conducted a retrospective chart review of traumatic open globe injuries in pediatric and adolescent patients presenting to Johns Hopkins Hospital and University of Maryland Medical Center between 2006 and 2020. Variables assessed included age, gender, parent-identified race, median household income, mechanism of injury, initial and final visual acuity (VA), and length of follow-up. Results Eighty patients ranging from 4 months to 17.7 years (mean 9.3 years) presented with traumatic open globe injury. Identifications were 28 White (35%), 38 Black (48%), and 5 Hispanic (6%). Initial presenting and final VA, pediatric ocular trauma score (POTS), and length of follow-up did not differ significantly among race, gender, or income. Black patients had higher rates of blunt trauma (odds ratio (OR) 3.81; 95% confidence interval (CI) 0.95-15.24, p = 0.07), uveal prolapse (OR 3.58; 95% CI 1.03-12.43; p = 0.049), and enucleation (OR 10.55; 95% CI 1.26-88.31). Hispanic patients presented at a younger age of 2.8 years mean age vs. 9.9 years (p = 0.004) for others. Conclusion Visual outcomes following traumatic open globe injury were independent of race, gender, or income. However, blunt trauma, uveal prolapse, and enucleation rates were higher in Black patients, and ocular trauma occurred at a younger age in Hispanic patients.


Evaluation of 3H-histamine incorporation into human peripheral blood leukocytes.
We have examined the use of 3H-histamine for evaluating in vitro basophil responses. Incubation of 3H-histamine for 4 h with basophil-enriched mononuclear fractions containing autologous plasma, resulted in the best incorporation of the label. Even so, less than 3% of the added label was actually recovered and other leukocytes also bound or incorporated 3H-histamine. Labeled mononuclear preparations failed to release 3H-histamine when challenged with zymosan-activated serum or anti-IgE, but endogenous histamine released under the same experimental conditions could be determined fluorometrically. The calcium ionophore, A23187, however, did cause a dose-dependent release of 3H-histamine. We conclude that 3H-histamine is not preferentially incorporated into basophil granules, and that this technique cannot be used for assessing allergen and/or IgE-mediated basophil responses.


Peyronie's disease: surgical experience and presentation of a proximal approach.
A total of 29 patients underwent 32 operations for correction of penile curvature. Of these patients 22 underwent placement of a semirigid prosthesis and 94 per cent of those available for followup were able to resume coitus. Of the 8 patients who underwent operative correction of penile curvature and who maintained potency only 3 (38 per cent) were able to resume intercourse. Vascular compromise and/or skin slough after degloving of the penile skin was noted in 3 patients. A proximal approach to penile reconstruction is presented.


Treatment of melanoma and nonmelanoma skin cancer.
The incidence of skin cancer is increasing in Caucasian populations worldwide. Treatment approaches for Nonmelanoma skin cancer (NMSC) are predominantly curative and surgery can be regarded as standard of care. Nevertheless, novel and less invasive topical therapy modalities like photodynamic therapy or local immune modifiers are in progress. In contrast to NMSC, the mortality of melanoma has not changed considerably over the last years and decades. Melanoma survival mainly depends on primary tumor thickness underlining the importance of primary and secondary prevention by avoidance or early detection of the disease. The chance to cure melanoma patients is steadily decreasing with tumor stage. As the prognosis in distant metastatic disease is still poor, except for single situations therapy approaches are palliative and accompanied by an optimal supportive care of the patients concerned. Albeit removal of localized metastases is currently the most effective approach in metastatic melanoma, chemo- and chemoimmunotherapy has to be regarded as standard treatment in most of the cases. Novel and promising therapeutic options accrue from growing insights in tumor biology and immunology. Not only in melanoma, development and application of targeted therapies currently attract the most attention in the treatment of advanced tumors. First clinical experiences with those antiproliferative, antiangiogenic and proapoptotic agents reveal only moderate antitumoral activity in melanoma, so that future efforts aim at defining more effective combination strategies using chemo-, targeted and vaccination therapy approaches.


Somatic DNA Hypomethylation in H. pylori-Associated High-Risk Gastritis and Gastric Cancer: Enhanced Somatic Hypomethylation Associates with Advanced Stage Cancer.
Helicobacter pylori-related high-risk gastritis (HRG) is a severe risk factor for gastric cancer (GC). The link between HRG and long-term risk for GC may involve genetic and epigenetic alterations underlying a field defect, i.e. a region of the mucosa prone to cancer development. Global DNA hypomethylation is a pervasive alteration in GC that associates with chromosomal instability and poor prognosis. The aim of this study was to determine the chronology of this alteration along the progression of HRG to GC, to test the hypothesis that it occurs early in the chronology of this pathway and plays a mechanistic role in the long-term cancer risk. We comparatively measured the genomic methylation level in gastric biopsies from 94 GC patients and 16 of their cancer-free relatives, 38 HRG patients, and 17 GERD patients, using a quantitative enzymatic method. GC biopsies were hypomethylated compared to their matching non-tumor mucosa (P=9.4 × 10(-12)), irrespective of the tumor location or patients' country of origin. Genome-wide hypomethylation was also found in gastric mucosa of GC (P=1.5 × 10(-5)) and HRG (P=0.004) patients compared with healthy donors and GC relatives, regardless of the biopsy location within the stomach or previous H. pylori eradication therapy. An enhanced hypomethylation, distinguished by a bi-slope distribution of the differences in methylation between tumor and normal tissues, associated with a more invasive (P=0.005) and advanced stage (P=0.017) type of GC. Universal DNA demethylation in normal gastric mucosa in GC patients appears sporadic rather than familial. Genomic hypomethylation in HRG possibly contributes to a field defect for cancerization that is not reversed by bacterial eradication. Enhanced somatic hypomethylation may stratify GC for prognostic purposes.


Dynamic bone loading exercises for postmenopausal women: effect on the density of the distal radius.
A set of dynamic bone loading exercises for the distal forearm, designed for high rates of loading, within physiologic range, and diversity of strain regime, was applied to a group of postmenopausal osteoporotic women. The effect of five months of three weekly sessions, 50 minutes each, on the bone status was studied by measuring the bone density at the distal radius by the Compton scattering technique. A group of 14 women who participated in the program and an inactive group of 26 women were examined one year prior to the study, at its beginning and at its end. During the year preceding the exercise program the mean bone density in both groups decreased significantly. During the exercise period the bone density of the exercise group increased by 3.8% while that of the control group continued to decline. This study demonstrates that an appropriate physical activity regime may be effective as a prophylactic treatment for postmenopausal bone loss.


Network structure embracing mutualism-antagonism continuums increases community robustness.
Theory predicts that contrasting properties of mutualistic and antagonistic networks differentially promote community resilience to species loss. However, the outcome of most ecological interactions falls within a continuum between mutualism and antagonism, and we ignore the extent to which this interactions' continuum might influence community stability. Using a large data set of interactions, we compared co-extinction cascades that either consider or ignore the mix of beneficial and detrimental actions that parrots exert on plants. When the antagonism-mutualism continuum was considered, a combination of the properties that separately enhance community stability in ecological networks emerged. This combination of properties led to an overall increase of the parrot community robustness to face plant species loss. Our results highlight that the conditional outcomes of interactions can influence the structure of ecological networks, thus affecting our predictions of community stability against eventual changes.


Observations of periwound skin protection in venous ulcers: a comparison of treatments.
The objective of this study was to examine the effectiveness of 2 products on venous ulcer periwound skin. This was a descriptive comparative study. An outpatient wound care clinic in a rural Midwestern area of the United States. Participants included a retrospective group of 50 patients and a prospective group of 28 patients. The intervention compared the experimental product (Remedy Nutrashield; Medline Industries, Mundelein, Illinois) versus Cavilon Moisturizing Lotion (3M, St Paul, Minnesota). The mean outcome measures were a decrease in periwound and ulcer size. For the periwound size, the estimated rates of change were as follows: 0.092 (SE, 0.021) cm/d and -0.026 (SE, 0.014) cm/d for products B and A groups, respectively. The decrease for the experimental group was significantly greater than the attenuated decrease for the retrospective cases (t297 = -2.57, P = .01), and the decrease for product B group was also significantly different from zero (t76 = -4.34, P < .0001). For the ulcer size model, the estimated rates of change were -0.272 (SE, 0.102) cm/d and -0.130 (SE, 0.067) cm/d for the experimental and retrospective groups, respectively. The rate for the experimental group was significantly less than zero (t76 = -2.67, P = .009), but there was no significant difference between prospective and retrospective cases in the rates of reduction in ulcer size (t308 = -1.16, P = .25). The results of this study illustrate how the integrity of the periwound skin may be an important determinant in decreasing periwound and ulcer size.


Sexual dimorphism in Drosophila melanogaster survival of Beauveria bassiana infection depends on core immune signaling.
In many animal species, females and males differ in physiology, lifespan, and immune function. The magnitude and direction of the sexual dimorphism in immune function varies greatly and the genetic and mechanistic bases for this dimorphism are often unknown. Here we show that Drosophila melanogaster females are more likely than males to die from infection with several strains of the fungal entomopathogen Beauveria bassiana. The sexual dimorphism is not exclusively due to barrier defenses and persists when flies are inoculated by injection as well as by surface exposure. Loss of function mutations of Toll pathway genes remove the dimorphism in survivorship. Surprisingly, loss of function mutation of relish, a gene in the Imd pathway, also removes the dimorphism, but the dimorphism persists in flies carrying other Imd pathway mutations. The robust sexual dimorphism in D. melanogaster survival to B. bassiana presents opportunities to further dissect its mechanistic details, with applications for biological control of insect vectors of human disease and insect crop pests.


Decreased cerebral activation during CPT performance: structural and functional deficits in schizophrenic patients.
Voxel-based morphometry (VBM) allows the output of structural data in a Statistical Parametric Map of the brain in the same way that the SPM can do with functional data. Using functional magnetic resonance (fMR), we studied brain activation in 14 patients with schizophrenia and 14 matched normal controls. We found significant hypoactivation in patients in several regions, especially in the right hemisphere, in the dorsolateral frontal and temporal regions and in the inferior parietal. Subcortically, we found strong hypoactivity in the thalamus. The optimized VBM method revealed gray matter (GM) abnormalities in the bilateral supramarginal gyrus and cingulate cortex, and in the right inferior temporal regions. Three regions involved in attentional processes showed both structural and functional deficits: the thalamus, the anterior cingulate and the inferior parietal. The results suggest that these regions may be involved in the attentional deficit in schizophrenia.