Temperature-controlled organic carbon mineralization in lake sediments.
Peatlands, soils and the ocean floor are well-recognized as sites of organic carbon accumulation and represent important global carbon sinks. Although the annual burial of organic carbon in lakes and reservoirs exceeds that of ocean sediments, these inland waters are components of the global carbon cycle that receive only limited attention. Of the organic carbon that is being deposited onto the sediments, a certain proportion will be mineralized and the remainder will be buried over geological timescales. Here we assess the relationship between sediment organic carbon mineralization and temperature in a cross-system survey of boreal lakes in Sweden, and with input from a compilation of published data from a wide range of lakes that differ with respect to climate, productivity and organic carbon source. We find that the mineralization of organic carbon in lake sediments exhibits a strongly positive relationship with temperature, which suggests that warmer water temperatures lead to more mineralization and less organic carbon burial. Assuming that future organic carbon delivery to the lake sediments will be similar to that under present-day conditions, we estimate that temperature increases following the latest scenarios presented by the Intergovernmental Panel on Climate Change could result in a 4-27 per cent (0.9-6.4 Tg C yr(-1)) decrease in annual organic carbon burial in boreal lakes.


The formation of cerebrospinal fluid: nearly a hundred years of interpretations and misinterpretations.
The first scientific and experimental approaches to the study of cerebrospinal fluid (CSF) formation began almost a hundred years ago. Despite researchers being interested for so long, some aspects of CSF formation are still insufficiently understood. Today it is generally believed that CSF formation is an active energy consuming metabolic process which occurs mainly in brain ventricles, in choroid plexuses. CSF formation, together with CSF absorption and circulation, represents the so-called classic hypothesis of CSF hydrodynamics. In spite of the general acceptance of this hypothesis, there is a considerable series of experimental results that do not support the idea of the active nature of CSF formation and the idea that choroid plexuses inside the brain ventricles are the main places of formation. The main goal of this review is to summarize the present understanding of CSF formation and compare this understanding to contradictory experimental results that have been obtained so far. And finally, to try to offer a physiological explanation by which these contradictions could be avoided. We therefore analyzed the main methods that study CSF formation, which enabled such an understanding, and presented their shortcomings, which could also be a reason for the erroneous interpretation of the obtained results. A recent method of direct aqueductal determination of CSF formation is shown in more detail. On the one hand, it provides the possibility of direct insight into CSF formation, and on the other, it clearly indicates that there is no net CSF formation inside the brain ventricles. These results are contradictory to the classic hypothesis and, together with other mentioned contradictory results, strongly support a recently proposed new working hypothesis on the hydrodynamics of CSF. According to this new working hypothesis, CSF is permanently produced and absorbed in the whole CSF system as a consequence of filtration and reabsorption of water volume through the capillary walls into the surrounding brain tissue. The CSF exchange between the entire CSF system and the surrounding tissue depends on (patho)physiological conditions that predominate within those compartments.


The effect of grazing intensity on phosphorus spiralling in autotropic streams.
The effect of grazing on primary productivity and phosphorus cycling in autotrophic streams was studied using the snail Goniobasis clavaeformes. Snails were added to each of three replicate laboratory stream channels, receiving once-through flow of groundwater, in densities of 2.1, 3.0, and 4.2 g ash free dry mass (AFDM)/m2. A fourth channel received no snails and served as an ungrazed control.Presence of snail grazers resulted in a large reduction in aufwuchs biomass, primary productivity, and biotic phosphorus uptake; a modest reduction in fine particulate organic matter (FPOM); and an increase in the fraction of stream particulate organic matter (POM) exported as seston. Although primary production and aufwuchs biomass continued to decline with increasing snail density, phosphorus uptake increased. This increased phosphorus uptake is attributed to abiotic sorption to inorganic surfaces exposed as a result of efficient removal of aufwuchs at high snail densities. Although snail densities were chosen to bracket the density measured in a natural stream, the experimental densities may result in considerably higher grazing pressure on aufwuchs due to the absence of alternate food sources (e.g., coarse particulate organic matter) usually found in natural streams.Presence of snail grazers increased the spiralling length of phosphorus, primarily by reducing aufwuchs biomass and consequently reducing uptake of phosphorus from the water. Presence of snails also increased downstream transport velocity of phosphorus bound to organic particles. These results follow the patterns predicted in a previous theoretical analysis for mildly phosphorus-limited streams.


Potential role for matrix metalloproteinase-3 in gastric ulcer healing.
Matrix metalloproteinases (MMPs) are endopeptidases which perform important functions in extracellular matrix remodeling, cell proliferation, and inflammatory processes. Here, we compared MMP-3 levels with those of tissue inhibitor of metalloproteinases (TIMP)-1 and several inflammatory cytokines in gastric ulcer (GU) patients. This study enrolled 50 patients with GU and 6 with functional dyspepsia (FD). Samples of gastric mucosa from the antrum and the ulcer site were harvested from GU patients and of antral mucosa alone from FD patients during upper gastrointestinal endoscopy. Mucosal biopsy tissues were cultured for 24 h, and the culture supernatant was measured for levels of MMP-3, TIMP-1, IL-1beta, IL-6, and IL-8. All GU patients were positive for Helicobacter pylori, while all FD patients were negative. Antral levels of TIMP-1, IL-1beta, IL-6, and IL-8 were significantly higher in GU than FD patients. Further, MMP-3 levels were significantly higher in GU patients at the ulcer site than in the antrum, and had a significantly positive correlation with TIMP-1, IL-1beta, IL-6, and IL-8. MMP-3 levels were significantly higher at the ulcer site than in the antrum, suggesting that MMP-3 may perform an important function in gastric ulcer healing.


Intake levels and major food sources of energy and nutrients in the Taiwanese elderly.
The purpose of this article is to examine dietary intake levels and major food sources of energy and nutrients for the Taiwanese elderly in order to relate nutrient intakes to food choices and to provide suggestions for dietary improvement. The data were derived from the 24-hour recalls from 1,911 subjects (955 males and 956 females) aged 65 and above, who participated in the Elderly NAHSIT carried out from 1999 to 2000. The differences in food consumption patterns between the elderly and younger adults (aged 19 to 64) were also evaluated by comparison with data obtained from NAHSIT 1993-1996. The results revealed that cereals/roots, meat, other protein-rich foods and fats/oils contributed most to daily energy intake. The energy contributions from fats/oils, poultry, meat, other protein-rich foods, refreshments/snacks, alcoholic beverages, and miscellaneous food groups were lower in elderly diets compared with those of younger adults. Meat and cereals/roots were the major food sources of protein. The main carbohydrate-contributing food group was cereals/roots, while primary lipid sources were meat and fats/oils for the elderly. The food groups with a high contribution to vitamin intake were the following: vegetables for vitamin A; meat and cereals/roots for vitamin B1; dairy products, vegetables, cereals/roots and meat for vitamin B2; cereals/roots, seafood and meat for niacin; meat, vegetables and cereals/roots for vitamin B6; plant oils for vitamin E; and vegetables and fruit for vitamin C. The highest ranked food sources for minerals are listed as follows: dairy products, vegetables and seafood for calcium; dairy products and cereals/roots for phosphorous; vegetables and meat for iron; and vegetables, cereals/ roots, other protein-rich foods and seafood for magnesium. The elderly were found to consume more salt, dairy products and vegetables, but less poultry and meat than their younger counterparts. In summary, differences in consumption patterns between the elderly and younger adults was reflected in differences in common food sources of energy and specific nutrients. The dietary patterns of the elderly are in general "healthier" than that of younger adults except for higher salt intake among the elderly. Nonetheless, our elderly population needs to increase their intake of calcium, magnesium, vitamins E and B6, and dietary fiber, and decrease their consumption of salt. Promoting the ingestion of whole-grain and nut products may be a useful strategy to improve the nutritional status of the Taiwanese elderly, aiming at increasing the percentage of energy obtained from carbohydrates and the daily intake of vitamins E and B6, magnesium, and dietary fiber. Suitable strategies are also needed to improve the calcium status of Taiwanese elderly, particularly as a high proportion of them are either lactose intolerant or dislike dairy products.


HLA genotypic study of insulin-dependent diabetes the excess of DR3/DR4 heterozygotes allows rejection of the recessive hypothesis.
The genetics of insulin-dependent diabetes mellitus (IDDM) is currently an area of controversy, with some investigators proposing heterogeneity within the HLA region and even the existence of non-HLA-linked susceptibility genes, and others maintaining that a simple autosomal recessive gene linked to HLA with reduced penetrance is an adequate explanation. To resolve this latter question, we report here a simple method of testing whether a single HLA-linked susceptibility gene is inherited in a recessive fashion when it is associated with two different HLA alleles, as is the case for IDDM. It is shown that if the number of DR3/DR4 heterozygotes in a diabetic population exceeds the combined sum of DR3/3 and DR4/4 homozygotes in that same diabetic population, then a recessive mode of inheritance can be rejected. The advantages of the method are that it does not depend on ratios, as do relative risk calculations, nor does it depend on control data, but is based only on studies of the diabetics themselves. With data on 193 genotyped IDDM patients, we can clearly reject the recessive mode of inheritance, since the number of heterozygotes is 68 compared with a maximum of 22 homozygotes (P less than 10(-4)). Eight other published studies are in concordance with these results. Therefore, a nonparametric test, independent of the significance of any individual study, rejects equality of heterozygotes and homozygotes (P less than 0.002) and rejects the simple recessive mode of inheritance as a direct consequence. We conclude that more complex modes of inheritance of HLA-linked IDDM susceptibility, such as two different diabetogenic alleles or multiple loci, must be entertained. DIABETES 32:169-174, February 1983.


Evidence on the impact of sustained exposure to air pollution on life expectancy from China's Huai River policy.
This paper's findings suggest that an arbitrary Chinese policy that greatly increases total suspended particulates (TSPs) air pollution is causing the 500 million residents of Northern China to lose more than 2.5 billion life years of life expectancy. The quasi-experimental empirical approach is based on China's Huai River policy, which provided free winter heating via the provision of coal for boilers in cities north of the Huai River but denied heat to the south. Using a regression discontinuity design based on distance from the Huai River, we find that ambient concentrations of TSPs are about 184 μg/m(3) [95% confidence interval (CI): 61, 307] or 55% higher in the north. Further, the results indicate that life expectancies are about 5.5 y (95% CI: 0.8, 10.2) lower in the north owing to an increased incidence of cardiorespiratory mortality. More generally, the analysis suggests that long-term exposure to an additional 100 μg/m(3) of TSPs is associated with a reduction in life expectancy at birth of about 3.0 y (95% CI: 0.4, 5.6).


A phase I/II trial to evaluate three-dimensional conformal radiation therapy confined to the region of the lumpectomy cavity for Stage I/II breast carcinoma: initial report of feasibility and reproducibility of Radiation Therapy Oncology Group (RTOG) Study 0319.
This prospective study (Radiation Therapy Oncology Group Study 0319) examines the use of three-dimensional conformal external beam radiation therapy to deliver accelerated partial breast irradiation. Reproducibility, as measured by technical feasibility, was the primary end point with the goal of demonstrating whether the technique is widely applicable in a multicenter setting before a Phase III trial is undertaken. This study was designed such that if fewer than 5 cases out of the first 42 patients evaluable were scored as unacceptable, the treatment would be considered reproducible. Patients received 38.5 Gy in 3.85 Gy/fraction delivered twice daily. The clinical target volume included the lumpectomy cavity plus a 10-15-mm margin bounded by 5 mm within the skin surface and the lung-chest wall interface. The planning target volume (PTV) included the clinical target volume plus a 10-mm margin. Treatment plans were judged as follows: (1) No variations (total coverage), 95% isodose surface covers 100% of the PTV and all specified critical normal tissue dose-volume histogram (DVH) limits met. (2) Minor variation (marginal coverage), 95% isodose surface covers between > or = 95% and <100% of the PTV. No portion of PTV receives <93% of prescription (isocenter) dose. All specified critical normal tissue DVH limits fall within 5% of the guidelines. (3) Major variation (miss), 95% isodose surface covers <95% of the PTV. Portion of PTV receives <93% of prescription isocenter dose. Any critical normal tissue DVH limit exceeds 5% of the specified value. A total of 58 patients were enrolled on this study between 8/15/03 and 4/30/04, 5 of whom were ineligible or did not receive protocol treatment. Two additional patients were excluded, one because the on-study form was not submitted, and the other because no treatment planning material was submitted. This primary end point analysis is based on the first 42 (out of 51) evaluable patients, which were accrued from 17 different institutions (31 centers were credentialed for case enrollment, but because of rapid accrual, not all centers were able to submit cases before trial closure). These 42 patients had the following characteristics: median age was 61 years; 48% had a maximum tumor dimension of <1 cm; 86% had invasive ductal carcinoma; 64% were postmenopausal; the location of tumor was upper outer for 40% and upper central for 21%; 79% had no chemotherapy, and 64% had no hormonal therapy. There were 4 cases with major variations (all 4 related to normal tissue DVHs exceeding 5% of the specified limit). A total of 32 cases with minor variations in treatment plans were detected (16 related to normal tissue DVHs exceeding the specified limits [by < or = 5%], 6 related to suboptimal coverage of the PTV, and 10 related to both). There were 6 cases with no variations. Of the 51 total evaluable patients, 1 additional major variation was noted (PTV receiving <93% of the prescription dose). An additional 5 cases with minor variations in treatment plans were detected (3 related to normal tissue DVHs exceeding the specified limits [by < or = 5%], 1 related to suboptimal coverage of the PTV, and 1 related to both). There were 3 more cases with no variations. Accelerated partial breast irradiation using three-dimensional conformal external beam radiation therapy was shown in this preliminary analysis of the first 42 evaluable patients to be technically feasible and reproducible in a multi-institutional trial using exceptionally strict dosimetric criteria.


Reporting standards for endovascular chemotherapy of head, neck and CNS tumors.
The goal of this article is to provide expert consensus recommendations for reporting standards, terminology and definitions when reporting on neurointerventional chemotherapy administration for head and neck tumors. These criteria may be used to design clinical trials, to provide definitions for patient stratification and to permit robust analysis of published data. This publication represents a consensus document by the Society for Neurointerventional Surgery. A PubMed search was conducted and included articles published in 2002-2011, with the search strategy designed to identify all studies of intra-arterial chemotherapy for tumors of neck and head. Articles were evaluated for evidence class, and recommendations were made using guidelines for evidence-based medicine proposed by a joint committee of the American Association of Neurological Surgeons and the Congress of Neurological Surgeons. Specifically, technical methods, outcome variables and reported complications were highlighted. Thirty-five publications were included in the review. While most studies represent class III evidence, there was sufficient concordance to justify level 2 recommendations regarding technical methods for administration of intra-arterial chemotherapy. The data also support level 2 recommendations regarding reporting of particular outcome variables subsumed within broad categories entitled 'Procedure-related', 'Disease control' and 'Survival'. The data support recommendations for the reporting of access site-related, neurologic, head and neck, ocular, hematologic and systemic complications, and also complications related to the percutaneous access site. Intra-arterial chemotherapy is a growing field in interventional neuroradiology. It is important to adopt uniform technical and reporting standards that will allow cross-publication comparisons and facilitate homogeneous practice standards. Published data support such standards, which are vital for the consistent evaluation of future published research.


Urinary fibrinogen derivative excretion and intraglomerular fibrin deposition in glomerulonephritis.
The relations between glomerular fibrin deposition, urinary excretion of fibrinogen derivatives (F.D.), and proteinuria were explored in 81 patients with glomerulonephritis. A positive correlation existed between proteinuria and F.D. excretion even when no fibrin could be detected in the glomerulus. In two patients with tubular proteinuria F.D. excretion was also raised, suggesting that tubular reabsorption or catabolism of F.D. or both normally occur.Disproportionately high titres of F.D. were observed when fibrin was deposited in an extracapillary site, but mesangial fibrin deposition was not accompanied by a higher excretion of F.D. than that observed in patients in whom intraglomerular fibrin was not detected. These observations suggest that the immunofluorescent findings on renal biopsies should be the major criteria on which a trial of anticoagulants in proliferative glomerulonephritis might be instituted and that measurement of urinary F.D. is likely to be of value in monitoring therapy in patients with extracapillary fibrin deposition.


Switching through symmetry breaking in coupled nonlinear micro-cavities.
We describe stable symmetry-breaking states in systems with two coupled nonlinear cavities, using coupled-mode theory and rigorous simulations. Above a threshold input level the symmetric state of the passive Kerr system becomes unstable, and we show how this phenomenon can be employed for switching and flip-flop purposes, using positive pulses only. A device with compact photonic crystal microcavities is proposed by which we numerically demonstrate the principle.


Determinants of health, health behaviours and demographic profile of patients attending an Australian university student-led osteopathy clinic.
Profiles of health professions practice can inform pre-professional education, provide evidence to assist with interprofessional practice, and inform policy development. An understanding of the profile of patients seeking osteopathy care is emerging. Current research suggests that musculoskeletal presentations predominate with approximately one-third of patients presenting with co-morbid diseases. There is little data on these presentations in Australian osteopathy practice. This study aimed to describe the patient demographics, clinical presentations, health behaviours and determinants of health, including health literacy, of those attending for care at an Australian student-led osteopathy clinic. A convenience sample design was utilised where consecutive patients presenting for their initial consultation were invited to complete a health information questionnaire during 2016-2017. The questionnaire explored a range of health behaviours and the patient's health status. Data from the clinical records were also extracted to establish the presenting complaint, duration of the complaint and pertinent demographics. Descriptive statistics were generated for each variable. Data were available for 1617 patients presenting for their initial consultation. The mean age of patients was 33.7 (±13.1) years with 55% (n = 887) identifying as female. Acute presentations predominated (n = 840, 52%), with presentations affecting the spine being the most common (57.8%). Most patients rated their health status as good to very good (75%). Approximately 7.5% of patients were identified as having low health literacy and 55.9% were currently suffering from one or more co-morbid presentations. The demographic profile and presenting complaints of patients presenting to a student-led osteopathy clinic are largely consistent with other Australian private practice profiles. The current work also identified co-morbid presentations, and positive and negative health behaviours. Osteopaths may play a role in the management of, or referral for, these presentations where health behaviours require change, or management of co-morbid conditions is beyond the scope of practice. The increasing volume of patient profile literature globally suggests that osteopaths can play a substantial role in the management of musculoskeletal complaints. Further, osteopathy may play a role in screening determinants of health, and engage in multidisciplinary care to ensure those patients with co-morbid conditions or adverse health behaviours are managed appropriately.


Prostate hyperplasia in a transgenic mouse with prostate-specific expression of prolactin.
Prolactin (PRL) is one of several polypeptide factors known to exert trophic effects on the prostate. We have previously reported a dramatic prostate enlargement with concurrent chronic hyperprolactinemia and elevated serum androgen levels in a PRL transgenic mouse (Mt-PRL) with ubiquitous expression of the transgene. To address the role of local PRL action in the prostate, a new transgenic mouse model (Pb-PRL) was generated using the prostate-specific rat probasin (Pb) minimal promoter to drive expression of the rat PRL gene. Pb-PRL transgenic males developed a significant enlargement of both the dorsolateral and ventral prostate lobes evident from 10 wk of age and increasing with age. Expression of the transgene was restricted to the prostate and detected from 4 wk of age. Low levels of transgenic rat PRL were detectable in the serum of adult Pb-PRL animals. Serum androgen levels were normal. The Pb-PRL prostate displayed significant stromal hyperplasia, ductal dilation, and focal areas of epithelial dysplasia. Quantitative analysis of prostatic tissue cellularity demonstrated a marked increase in the stromal to epithelial ratio in all lobes of Mt-PRL and Pb-PRL transgenic prostates compared with controls. Microdissections demonstrated an increased ductal morphogenesis in dorsolateral and ventral prostate lobes of Mt-PRL prostate vs. Pb-PRL and controls. In conclusion, this study indicates the ability of PRL to promote, directly or indirectly, ductal morphogenesis in the developing prostate and further to induce abnormal growth primarily of the stroma in the adult gland in a setting of normal androgen levels.


A controlled clinical trial with pirfenidone in the treatment of pathological skin scarring caused by burns in pediatric patients.
Pathologic skin scarring reversion remains a big challenge for surgeons, as disfiguring scars have a dramatic influence on patient's quality of life. A controlled clinical trial was conducted to evaluate 8% pirfenidone (PFD) gel administered topically 3 times a day during 6 months to 33 pediatric patients with hypertrophic scars caused by burns. A total of 30 patients with hypertrophic scars with identical Vancouver Scar Scale values were treated with pressure therapy and included as controls. Improvements were evaluated by Vancouver Scar Scale and a Visual Analog Scale. Safety parameters were determined by the presence of adverse events and monitoring laboratory and hematology parameters. Patients treated with PFD during 6 months presented a continuous monthly statistically significant scar regression in comparison with the initial Vancouver measurement (P = <0.001). PFD group showed a higher improvement of all scar features as compared with control group treated with pressure therapy (P = <0.001). In the PFD group, 9 of 33 patients (27%) had their scores decreased in Vancouver classification by more than 55%, 22 patients (67%) had a 30% to 45% decrease, whereas 2 patients (6%) had a 30% decrease or less. Control group treated with pressure therapy showed a slight improvement in 16% of cases on an average. Patients did not show serious adverse effects or laboratory alterations throughout the study. Topical administration of 8% PFD gel 3 times a day is more effective and safe in the treatment of hypertrophic scars caused by burns in children, as compared with standard pressure therapy.


The reverse posterior interosseous artery flap: technical considerations in raising an easier and more reliable flap.
Major injuries of the hand with skin loss often require early flap cover, which should be versatile, simple in technique, and safe. The reverse posterior interosseus flap satisfies all of these requirements. Over the years, refinements in the technique of harvesting this flap have evolved to prevent venous congestion and flap necrosis. This study presents adaptations to avoid such complications and raise a successful flap. A total of 21 patients underwent this flap reconstruction between January 2008 and November 2010 for injuries around the wrist and hand. The average follow-up period was 6 months; 19 were male and 2 were female. The average age was 33 years (range, 9-70 y). In 17 patients, the flap reconstructions were done for posttraumatic injuries, in 2 after skin defects following tumor resection, and 1 each after defects resulting from release of first web contracture in multiple congenital contractures and burns. Average size of the flap was 51 cm(2) (range, 90- 30 cm(2)). The donor area was covered by a split skin graft. All flaps survived without major complications. Generally the flap matched the surrounding skin except for palmar defects. No patients reported donor skin graft color mismatch. The reverse posterior interosseous flap is a reliable and safe flap for soft tissue cover to the wrist, palm, dorsum of hand, first web space, and metacarpophalangeal joints. Thorough attention to the technical details, including performing a proximo-distal flap dissection with the deep fascia, avoiding dissection of the anastomotic arc between posterior and anterior interosseous artery, creating a broad pedicle with a cutaneous handle, and avoiding its tunneling for inset, will contribute to survival of the flap.


Biochemical components of seminal plasma and their correlation to the fresh seminal characteristics in Marwari stallions and Poitou jacks.
To investigate various biochemical components of seminal plasma in Marwari stallions and Poitou Jacks and to find out their correlation with that of the seminal characteristics. In this study, semen was collected from six Marwari stallions and six Poitou jacks aged from 4 to 6 years and with known fertility status. The semen collection from the stallions were collected during the breeding season, i.e., between the months of April and June. From the collected semen ejaculates, we estimated the values of some biochemical components, viz., total protein content, total lipid content, and enzymes such as glutamic pyruvic transaminase (GPT), glutamic oxaloacetic transaminase (GOT), alkaline phosphatase (ALP), acid phosphatase (ACP), and lactate dehydrogenase (LDH) as well as concentrations of glucose, cholesterol, total calcium (Ca), and phosphorus (P) and correlations among different seminal parameters were statistically examined using the Pearson correlation coefficient. In this study, we found positive correlations between semen volume as well as sperm concentration and GOT, GPT, ALP and ACP for both the group stallions. Significant correlation between motility and glucose, GOT and GPT could be an indication for their role metabolism and protection against free radicals to the spermatozoa. Based on the results, it is concluded that there is a positive correlation between some biochemical values such as glucose, Ca, ALP, and LDH and seminal parameters which play a key role in capacitation and onward movement of the spermatozoa.


Metformin Inhibits ROS Production by Human M2 Macrophages via the Activation of AMPK.
Metformin (1,1-dimethylbiguanide hydrochloride) is the most commonly used drug to treat type II diabetic patients. It is believed that this drug has several other beneficial effects, such as anti-inflammatory and anticancer effects. Here, we wanted to evaluate the effect of metformin on the production of reactive oxygen species (ROS) by human macrophages. Macrophages are generated in vivo from circulating monocytes depending on the local tissue environment. In vitro proinflammatory macrophages (M1) and anti-inflammatory macrophages (M2) can be generated by culturing monocytes in the presence of different cytokines, such as GM-CSF or M-CSF, respectively. We show that metformin selectively inhibited human monocyte differentiation into proinflammatory macrophages (M1) without inhibiting their differentiation into anti-inflammatory macrophages (M2). Moreover, we demonstrate that, in response to LPS, M2 macrophages produced ROS, which could be very harmful for nearby tissues, and metformin inhibited this process. Interestingly, metformin with LPS induced activation of the adenosine-monophosphate-activated protein kinase (AMPK) and pharmacological activation of AMPK by AICAR, a known AMPK activator, decreased ROS production, whereas the deletion of AMPK in mice dramatically enhanced ROS production in different types of immune cells. These results suggest that metformin exhibits anti-inflammatory effects by inhibiting the differentiation of human monocytes into M1 macrophages and by limiting ROS production by macrophages via the activation of AMPK.


VGLUT1 synapses and P-boutons on regenerating motoneurons after nerve crush.
Stretch-sensitive Ia afferent monosynaptic connections with motoneurons form the stretch reflex circuit. After nerve transection, Ia afferent synapses and stretch reflexes are permanently lost, even after regeneration and reinnervation of muscle by motor and sensory afferents is completed in the periphery. This loss greatly affects full recovery of motor function. However, after nerve crush, reflex muscle forces during stretch do recover after muscle reinnervation and reportedly exceed 140% baseline values. This difference might be explained by structural preservation after crush of Ia afferent synapses on regenerating motoneurons and decreased presynaptic inhibitory control. We tested these possibilities in rats after crushing the tibial nerve (TN), and using Vesicular GLUtamate Transporter 1 (VGLUT1) and the 65 kDa isoform of glutamic acid-decarboxylase (GAD65) as markers of, respectively, Ia afferent synapses and presynaptic inhibition (P-boutons) on retrogradely labeled motoneurons. We analyzed motoneurons during regeneration (21 days post crush) and after they reinnervate muscle (3 months). The results demonstrate a significant loss of VGLUT1 terminals on dendrites and cell bodies at both 21 days and 3 months post-crush. However, in both cellular compartments, the reductions were small compared to those observed after TN full transection. In addition, we found a significant decrease in the number of GAD65 P-boutons per VGLUT1 terminal and their coverage of VGLUT1 boutons. The results support the hypothesis that better preservation of Ia afferent synapses and a change in presynaptic inhibition could contribute to maintain or even increase the stretch reflex after nerve crush and by difference to nerve transection.


Leptin, adiponectin, leptin to adiponectin ratio and insulin resistance in depressive women.
Depressive disorder (DD) is associated with an increased risk of type 2 diabetes mellitus (DM2) and cardiovascular disease (CVD). It was suggested, that metabolic syndrome (MetS), cluster of metabolic and hormonal changes, such as insulin resistence (IR), abdominal obesity, dyslipidemia, arterial hypertension and elevated fasting glycaemia, could stand behind the connection. Recent findings have shown, that adipocytokines leptin and adiponectin might play a role in both depression and MetS. The aim of this pilot study was to observe the plasma concentrations of leptin, adiponectin, leptin-to-adiponectin ratio and indices of IR in women with depressive disorder. The plasma leptin, adiponectin, parameters of lipid and glucose homeostasis and indices of IR were investigated in a group of 38 women with DD. The results were compared with those of 38 healthy women of the control group, matched for age. Depressive women differed significantly from the controls in higher concentrations of plasma leptin (p <0.05), insulin (p <0.01), C-peptide (p <0.01), value of HOMA-IR (p <0.01), and the leptin-to-adiponectin ratio (p <0.05).The QUICKI index of insulin sensitivity was lower (p <0.01). HAM-D score of DD cases correlated negatively with adiponectin (r = - 0.3505; p < 0.05), independently of HOMA-IR. We have not found in DD group any differences between the drug free patients and those treated either with escitaloprame alone or in the combination with mirtazapine. The results of the pilot study presented support the hypothesis that at least part of DD cases has increased leptin serum levels and certain features of MetS. It could be the factor connecting depression with an increased risk of either DM2 or CVD.


Factors associated with early peritoneal dialysis catheter replacement in Veracruz, Mexico.
Catheter-related complications in patients on peritoneal dialysis lead to decreased effectiveness and discontinuation of the technique, conversion to haemodialysis, hospitalisation, and surgical interventions to replace the catheter. Determine risk factors for early catheter dysfunction that result in the need for replacement. We analysed 235 catheters placed by open surgery using an infra-umbilical midline incision. Possible risk factors included the following: age, sex, body mass index, body surface area, diabetes, polycystic kidney disease, previous surgery, time of surgical procedure, omentectomy, omentopexy, wound infection and postoperative incisional hernia. During the first year, 47 patients (20%) required a catheter replacement due to poor function. The most common complications were catheter migration and peritonitis (4.3% in both cases), followed by obstruction from omental wrapping (3.7%). Univariate analysis showed that patients with catheter dysfunction or requiring catheter replacement were younger, with a lower body mass index and body surface area (P<.05). There was a significant association of wound infection and post-operative incisional hernia with catheter replacement. Omentectomy was associated with a low incidence rate of catheter dysfunction/replacement in the univariate and logistical regression analyses (odds ratio: 0.275; 95% confidence interval: 0.101-0.751; P<.012). Our catheter placement technique offers a low complication rate and good results in the first year after surgery. Except for omentectomy, we did not discover any risk factors for catheter replacement in our study population. Omentectomy had a protective effect in terms of catheter replacement.


The toxoplasma Acto-MyoA motor complex is important but not essential for gliding motility and host cell invasion.
Apicomplexan parasites are thought to actively invade the host cell by gliding motility. This movement is powered by the parasite's own actomyosin system, and depends on the regulated polymerisation and depolymerisation of actin to generate the force for gliding and host cell penetration. Recent studies demonstrated that Toxoplasma gondii can invade the host cell in the absence of several core components of the invasion machinery, such as the motor protein myosin A (MyoA), the microneme proteins MIC2 and AMA1 and actin, indicating the presence of alternative invasion mechanisms. Here the roles of MyoA, MLC1, GAP45 and Act1, core components of the gliding machinery, are re-dissected in detail. Although important roles of these components for gliding motility and host cell invasion are verified, mutant parasites remain invasive and do not show a block of gliding motility, suggesting that other mechanisms must be in place to enable the parasite to move and invade the host cell. A novel, hypothetical model for parasite gliding motility and invasion is presented based on osmotic forces generated in the cytosol of the parasite that are converted into motility.


Urban Mind: Using Smartphone Technologies to Investigate the Impact of Nature on Mental Well-Being in Real Time.
Existing evidence on the beneficial effects of nature on mental health comes from studies using cross-sectional designs. We developed a smartphone-based tool (Urban Mind; www.urbanmind.info) to examine how exposure to natural features within the built environment affects mental well-being in real time. The tool was used to monitor 108 individuals who completed 3013 assessments over a 1-week period. Significant immediate and lagged associations with mental well-being were found for several natural features. These associations were stronger in people with higher trait impulsivity, a psychological measure of one's tendency to behave with little forethought or consideration of the consequences, which is indicative of a higher risk of developing mental-health issues. Our investigation suggests that the benefits of nature on mental well-being are time-lasting and interact with an individual's vulnerability to mental illness. These findings have potential implications from the perspectives of global mental health as well as urban planning and design.


SIZ1 small ubiquitin-like modifier E3 ligase facilitates basal thermotolerance in Arabidopsis independent of salicylic acid.
Small ubiquitin-like modifier (SUMO) conjugation/deconjugation to heat shock transcription factors regulates DNA binding of the peptides and activation of heat shock protein gene expression that modulates thermal adaptation in metazoans. SIZ1 is a SUMO E3 ligase that facilitates SUMO conjugation to substrate target proteins (sumoylation) in Arabidopsis (Arabidopsis thaliana). siz1 T-DNA insertional mutations (siz1-2 and siz1-3; Miura et al., 2005) cause basal, but not acquired, thermosensitivity that occurs in conjunction with hyperaccumulation of salicylic acid (SA). NahG encodes a salicylate hydroxylase, and expression in siz1-2 seedlings reduces endogenous SA accumulation to that of wild-type levels and further increases thermosensitivity. High temperature induces SUMO1/2 conjugation to peptides in wild type but to a substantially lesser degree in siz1 mutants. However, heat shock-induced expression of genes, including heat shock proteins, ascorbate peroxidase 1 and 2, is similar in siz1 and wild-type seedlings. Together, these results indicate that SIZ1 and, by inference, sumoylation facilitate basal thermotolerance through processes that are SA independent.


Chemopreventive agents: selenium.
The element selenium (Se) was recognized only 40 years ago as being essential in the nutrition of animals and humans. It is recognized as being an essential component of a number of enzymes, in which it is present as the amino acid selenocysteine. Se compounds have also been found to inhibit tumorigenesis in a variety of animal models, and recent studies indicate that supplemental Se in human diets may reduce cancer risk. The antitumorigenic activities have been associated with Se intakes that correct nutritionally deficient status in animals, as well as higher intakes that are substantially greater than those associated with maximal expression of the selenocysteine-containing enzymes. Therefore, it is proposed that while some cancer protection, particularly that involving antioxidant protection, involves selenoenzymes, specific Se metabolites, which are produced in significant amounts at relatively high Se intakes, also discharge antitumorigenic functions. According to this two-stage model of the roles of Se in cancer prevention, individuals with nutritionally adequate Se intakes may benefit from Se supplementation. Evidence for chemoprevention by Se and for the apparent mechanisms underlying these effects is reviewed to the end of facilitating the development of the potential of Se compounds as cancer chemopreventive agents.


Contraceptive methods women have ever used: United States, 1982-2010.
This report presents national estimates of the proportion of sexually experienced women aged 15-44 who have ever used various methods of contraception in the United States. Trends are shown since 1982, and results are shown by Hispanic origin and race, education, and religious affiliation. The number of methods ever used is also shown, along with reasons for stopping use of selected methods. Data for 2006-2010 were collected through in-person interviews with 22,682 women and men aged 15-44 in the household population of the United States. Interviews were conducted by female interviewers in the homes of sampled persons. This report is based primarily on the sample of 12,279 women interviewed in 2006-2010 from the National Survey of Family Growth (NSFG). Data from earlier NSFGs are presented to show trends in method choice since 1982. Virtually all women of reproductive age in 2006-2010 who had ever had sexual intercourse have used at least one contraceptive method at some point in their lifetime (99%, or 53 million women aged 15-44), including 88% who have used a highly effective, reversible method such as birth control pills, an injectable method, a contraceptive patch, or an intrauterine device. In 2006-2010, the most common methods that women or their partners had ever used were: the male condom (93%), the pill (82%), withdrawal (60%), and the injectable, Depo-Provera (23%). Method use varied by race and Hispanic origin, nativity among Hispanics, education, and religious affiliation, with significant proportions of women in all categories having used one or more of the most effective methods. The median number of methods ever used by women was about three, but nearly 30% have used five or more methods. Side effects were the most common reason for discontinuing use of the pill, Depo-Provera, and the patch among women who had ever discontinued using these methods due to dissatisfaction.


Examination of a newly developed mobile dry scrubber (DS) for coal mine dust control applications.
The Office of Mine Safety and Health Research of the U.S. National Institute for Occupational Safety and Health (NIOSH OMSHR) conducted laboratory testing of a self-tramming, remotely controlled mobile Dry Scrubber (DS) that J.H. Fletcher and Co. developed under a contract with NIOSH OMSHR to reduce the exposure of miners to airborne dust. The scrubber was found to average greater than 95 percent dust removal efficiency with disposable filters, and 88 and 90 percent, respectively, with optional washable filters in their prewash and post-wash test conditions. Although the washable filters can be reused, washing them generated personal and downstream respirable dust concentrations of 1.2 and 8.3 mg/m3, respectively, for a 10-min washing period. The scrubber's velocity-pressure-regulated variable-frequency-drive fan maintained relatively consistent airflow near the targeted 1.42 and 4.25 m3/s (3,000 and 9,000 ft3/min) airflow rates during most of the laboratory dust testing until reaching its maximum 60-Hz fan motor frequency or horsepower rating at 2,610 Pa (10.5 in. w.g.) of filter differential pressure and 3.97 m3/s (8,420 ft3/min) of scrubber airflow quantity. Laboratory sound level measurements of the scrubber showed that the outlet side of the scrubber was noisier, and the loaded filters increased sound levels compared with clean filters at the same airflow quantities. With loaded filters, the scrubber reached a 90 dB(A) sound level at 2.83 m3/s (6,000 ft3/min) of scrubber airflow, indicating that miners should not be overexposed in relation to MSHA's permissible exposure level - under Title 30 Code of Federal Regulations Part 62.101- of 90 dB(A) at or below this airflow quantity. The scrubber's washable filters were not used during field-testing because of their lower respirable dust removal efficiency and the airborne dust generated by filter washing. Field-testing the scrubber with disposable filters at two underground coal mine sections showed that it could clean a portion of the section return air and provide dust reduction of about 50 percent at the face area downstream of the continuous-miner operation.


Immunopathological effects of Agaricus blazei Murill polysaccharides against Schistosoma mansoni infection by Th1 and NK1 cells differentiation.
In this study, we examined the ability of A. blazei Murill polysaccharides (AB-PS) to activate the immune system in vivo and the protective activity exhibited against parasitic S. mansoni in the murine model. AB-PS treatment significantly reduced the worm and egg burden in infected BALB/c and C57BL/6 mice with dose- and time-dependent manners. Additionally, a dose- and time-dependent expression of IL-2, INF-γ, and TNF-α cytokines was also observed in both strains of mice treatments. Using T1/T2 doubly transgenic mice, we demonstrated that AB-PS-treated mice splenocytes initiated early differentiation of Th1 and NK1 cells, which was consistent with the reduction course of Schistosoma infection. Although AB-PS treatment enhanced the Th1 response, it did not suppress Th2 cell activity in treated mice. Histopathological data of the livers showed AB-PS treatment significantly attenuated the liver fibrosis induced by S. mansoni eggs. AB-PS augmented type-1 responses by inducing Th1 and NK1 cell differentiation to effectively decrease the infection rate of S. mansoni. Furthermore, AB-PS treatment may not only inhibit the schistosome infection, but also improving the pathological effects of granulomas formation. This study provides evidence for a novel therapeutic potential, by which A. blazei Murill may be used to treat or prevent schistosome infection.


Mechanical perturbations trigger endothelial nitric oxide synthase activity in human red blood cells.
Nitric oxide (NO), a vascular signaling molecule, is primarily produced by endothelial NO synthase. Recently, a functional endothelial NO synthase (eNOS) was described in red blood cells (RBC). The RBC-eNOS contributes to the intravascular NO pool and regulates physiological functions. However the regulatory mechanisms and clinical implications of RBC-eNOS are unknown. The present study investigated regulation and functions of RBC-eNOS under mechanical stimulation. This study shows that mechanical stimuli perturb RBC membrane, which triggers a signaling cascade to activate the eNOS. Extracellular NO level, estimated by the 4-Amino-5-Methylamino-2', 7'-Difluorofluorescein Diacetate probe, was significantly increased under mechanical stimuli. Immunostaining and western blot studies confirmed that the mechanical stimuli phosphorylate the serine 1177 moiety of RBC-eNOS, and activates the enzyme. The NO produced by activation of RBC-eNOS in vortexed RBCs promoted important endothelial functions such as migration and vascular sprouting. We also show that mechanical perturbation facilitates nitrosylation of RBC proteins via eNOS activation. The results of the study confirm that mechanical perturbations sensitize RBC-eNOS to produce NO, which ultimately defines physiological boundaries of RBC structure and functions. Therefore, we propose that mild physical perturbations before, after, or during storage can improve viability of RBCs in blood banks.


Dietary intake of PUFAs and colorectal polyp risk.
Marine-derived n-3 (omega-3) PUFAs may reduce risk of developing colorectal cancer; however, few studies have investigated the association of n-3 PUFA intakes on colorectal polyp risk. The objective of this study was to examine the associations of dietary PUFA intake on risk of colorectal adenomatous and hyperplastic polyps. This was a colonoscopy-based case-control study that included 3166 polyp-free control subjects, 1597 adenomatous polyp cases, and 544 hyperplastic polyp cases. Dietary PUFA intake was calculated from food-frequency questionnaires and tested for association by using unconditional logistic regression. The urinary prostaglandin E(2) metabolite, which is a biomarker of prostaglandin E(2) production, was measured in 896 participants by using liquid chromatography and tandem mass spectrometry. n-6 PUFAs were not associated with adenomatous or hyperplastic polyps in either men or women. Marine-derived n-3 PUFAs were associated with reduced risk of colorectal adenomas in women only, with an adjusted OR of 0.67 (95% CI: 0.47, 0.97) for the highest quintile of intake compared with the lowest quintile of intake (P-trend = 0.01). Dietary intake of α-linolenic acid was associated with an increased risk of hyperplastic polyps in men (P-trend = 0.03), which was not seen in women. In women, but not in men, dietary intake of marine-derived n-3 PUFAs was negatively correlated with urinary prostaglandin E(2) production (r = -0.18; P = 0.002). Higher intakes of marine-derived n-3 PUFAs are associated with lower risk of adenomatous polyps in women, and the association may be mediated in part through a reduction in the production of prostaglandin E(2). This trial was registered at clinicaltrials.gov as NCT00625066.


Hypoxia--a key regulator of angiogenesis and inflammation in rheumatoid arthritis.
The importance of inflammation in rheumatoid arthritis (RA) is well understood. This knowledge has resulted in the development of anti-inflammatory therapies--either broadly acting (such as steroids) or more specific approaches (such as antibodies against TNF)--with biologic therapies (including TNF inhibitors) revolutionizing the treatment of RA. However, what is less well appreciated in RA are the links between inflammation, blood-vessel formation (angiogenesis) and cellular responses to changes in oxygen tension. Inadequate oxygenation, termed hypoxia, is thought to drive the increase in synovial angiogenesis that occurs in RA, through expression of hypoxia-inducible molecules, including vascular endothelial growth factor (VEGF). This process promotes further infiltration of inflammatory cells and production of inflammatory mediators, perpetuating synovitis. This Review highlights the molecular pathways activated by hypoxia, and how these pathways might interact with inflammatory signaling to promote and maintain synovitis in RA, with a particular focus on the response of macrophages to hypoxia in the context of RA. Successful treatment of RA, for example with anti-TNF antibodies, reduces levels of proangiogenic factors, including VEGF, and leads to normalization of the vasculature. These processes emphasise the close links between hypoxia, angiogenesis and inflammation in this disease and supports the concept that angiogenesis blockade could be of therapeutic benefit in RA.


A comparative analysis of recruitment methods used in a randomized trial of diabetes education interventions.
Recruitment methods heavily impact budget and outcomes in clinical trials. We conducted a post-hoc examination of the efficiency and cost of three different recruitment methods used in Journey for Control of Diabetes: the IDEA Study, a randomized controlled trial evaluating outcomes of group and individual diabetes education in New Mexico and Minnesota. Electronic databases were used to identify health plan members with diabetes and then one of the following three methods was used to recruit study participants: 1. Minnesota Method 1--Mail only (first half of recruitment period). Mailed invitations with return-response forms. 2. Minnesota Method 2--Mail and selective phone calls (second half of recruitment period). Mailed invitations with return-response forms and subsequent phone calls to nonresponders. 3. New Mexico Method 3--Mail and non-selective phone calls (full recruitment period): Mailed invitations with subsequent phone calls to all. The combined methods succeeded in meeting the recruitment goal of 623 subjects. There were 147 subjects recruited using Minnesota's Method 1, 190 using Minnesota's Method 2, and 286 using New Mexico's Method 3. Efficiency rates (percentage of invited patients who enrolled) were 4.2% for Method 1, 8.4% for Method 2, and 7.9% for Method 3. Calculated costs per enrolled subject were $71.58 (Method 1), $85.47 (Method 2), and $92.09 (Method 3). A mail-only method to assess study interest was relatively inexpensive but not efficient enough to sustain recruitment targets. Phone call follow-up after mailed invitations added to recruitment efficiency. Use of return-response forms with selective phone follow-up to non-responders was cost effective.


Assessment of pharmacists' views on biosimilar naming conventions.
As the date for the introduction of biosimilars in the United States approaches, questions remain regarding the naming, coding, and approval process for these agents that will need to be carefully considered. To (a) ascertain pharmacists' awareness of and comfort level with biosimilars and (b) determine the impact of identical or different nonproprietary names on pharmacists' confidence in substituting interchangeable biologics. The Academy of Managed Care Pharmacy, the American Pharmacists Association, and the American Society of Health-System Pharmacists fielded a survey to their membership or a partial segment of their membership. The survey consisted of 2 sections: (1) current processes for reporting biologics being dispensed and (2) familiarity and preferences regarding biosimilars. A substantial majority (70.1%) of respondents reported regularly using National Drug Code numbers as the identifier for biological products dispensed to patients; however, 10.4% of respondents reported using either the nonproprietary name or the Healthcare Common Procedure Coding System code as the identifier. When presented with 3 scenarios for naming conventions of interchangeable biosimilars and asked to rate their level of confidence (1 = not confident, 5 = very confident) to substitute, 74.6% of pharmacists indicated that they would be confident or very confident in substituting an interchangeable biosimilar with the reference product if both shared the same active ingredient or nonproprietary name of the reference biologic; 25.3% of pharmacists were confident in substituting when the nonproprietary name is not shared with the biologic; and 37.3% of pharmacists expressed confidence in substituting when the biologic and biosimilar product did not share the same nonproprietary name because of a prefix or suffix. The imminent entry of biosimilars into the U.S. market highlights the need to carefully evaluate current processes of identification, reporting, and recording of the biological products dispensed. The results of this survey indicate that the ultimate decision on the naming convention for biosimilars may influence dispensing pharmacists, with the majority of respondents being most comfortable with biosimilars having the same nonproprietary name as the reference biologic.


Recurrent candida prosthetic endocarditis over fifteen years managed with medical therapy and four valvular surgeries: a case report and review of literature.
Candida prosthetic endocarditis (CPE) is an uncommon disease involving less than 1 % of infective endocarditis patients and associated with high recurrence rate. Immunosuppresion, intravenous drug abuse, cardiac surgery and indwelling foreign bodies are the major risk factors for CPE. There are very few reported cases of CPE where more than one surgery was performed and there has generally been limited follow up on these cases. We report a case of a 35 year old woman who had mitral valve annuloplasty complicated by recurrent episodes of CPE leading to multiple mitral valve replacements (MVR). She underwent MVR surgeries a total of four times over an eighteen year period and had good functionality during most of this time while being on antifungal suppressive treatment. This is a unique case in terms of numbers of surgeries performed, the length of the follow up and the involvement of three different Candida species. Current guidelines for the treatment of candida endocarditis recommend surgical treatment followed by long term antifungal therapy although the cure rate by all treatments is low. However we feel that based on this one case it is reasonable to consider multiple redo valve replacement surgeries in conjunction with antifungal treatment for selected patients stable enough to tolerate the surgery.


Measuring the quality of depression care in a large integrated health system.
Guideline-based depression process measures provide a powerful way to monitor depression care and target areas needing improvement. To assess the adequacy of depression care in the Veterans Health Administration (VHA) using guideline-based process measures derived from administrative and centralized pharmacy records, and to identify patient and provider characteristics associated with adequate depression care. This is a cohort study of patients from 14 VHA hospitals in the Northeastern United States which relied on existing databases. Subject eligibility criteria: at least one depression diagnosis during 1999, neither schizophrenia nor bipolar disease, and at least one antidepressant prescribed in the VHA during the period of depression care profiling (June 1, 1999 through August 31, 1999). Depression care was evaluated with process measures defined from the 1997 VHA depression guidelines: antidepressant dosage and duration adequacy. We used multivariable regression to identify patient and provider characteristics predicting adequate care. There were 12,678 patients eligible for depression care profiling. Adequate dosage was identified in 90%; 45% of patients had adequate duration of antidepressants. Significant patient and provider characteristics predicting inadequate depression care were younger age (<65), black race, and treatment exclusively in primary care. Under-treatment of depression exists in the VHA, despite considerable mental health access and generous pharmacy benefits. Certain patient populations may be at higher risk for inadequate depression care. More work is needed to align current practice with best-practice guidelines and to identify optimal ways of using available data sources to monitor depression care quality.


Circulating Cell-Free DNA and Circulating Tumor Cells as Prognostic and Predictive Biomarkers in Advanced Non-Small Cell Lung Cancer Patients Treated with First-Line Chemotherapy.
Cell-free DNA (cfDNA) and circulating tumor cells (CTCs) are promising prognostic and predictive biomarkers in non-small cell lung cancer (NSCLC). In this study, we examined the prognostic role of cfDNA and CTCs, in separate and joint analyses, in NSCLC patients receiving first line chemotherapy. Seventy-three patients with advanced NSCLC were enrolled in this study. CfDNA and CTC were analyzed at baseline and after two cycles of chemotherapy. Plasma cfDNA quantification was performed by quantitative PCR (qPCR) whereas CTCs were isolated by the ScreenCell Cyto (ScreenCell, Paris, France) device and enumerated according to malignant features. Patients with baseline cfDNA higher than the median value (96.3 hTERT copy number) had a significantly worse overall survival (OS) and double the risk of death (hazard ratio (HR): 2.14; 95% confidence limits (CL) = 1.24-3.68; p-value = 0.006). Conversely, an inverse relationship between CTC median baseline number (6 CTC/3 mL of blood) and OS was observed. In addition, we found that in patients reporting stable disease (SD), the baseline cfDNA and CTCs were able to discriminate patients at high risk of poor survival. cfDNA demonstrated a more reliable biomarker than CTCs in the overall population. In the subgroup of SD patients, both biomarkers identified patients at high risk of poor prognosis who might deserve additional/alternative therapeutic interventions.


Treatment of chronic uremic patients with protein-poor diet and oral supply of essential amino acids. II. Clinical results of long-term treatment.
Twenty-six uremic patients - serum urea nitrogen (SUN) 110 MG/100 ml plus or minus 22.8 (mean plus or minus SD), serum cretinine (S-Creat) 13.2 mg/100 ml plus or minus 2.27, ratio SUN/S-Creat 8.6 plus or minus 2.26, and endogenous creatinine clearance (Ccr) 3.86 plus or minus 1.41 ml/min - were treated for three months or longer with an unselected protein-poor (16-20 g protein/day) diet with oral supply of the essential amino acids including histidine in high doses as coated tablets. The amino acids were instituted after an initial diet only period (mean 0.4 months). The average treatment time was 8.4 months (range 2.7-33.6). An improvement of the general condition was obtained, persisting for several months. SUN and SUN/S-Creat decreased on the diet alone, continued to decrease after one month, and increased slightly again after three months of treatment, but did not reach the initial levels for several months in spite of an almost doubled nitrogen intake. S-Creat increased after six months indicating a further deterioration of the renal function. In patients with initially low serum total protein (smaller than 6.5 g/100 ml, 9 patients), albumin (smaller than 3.5 g/100 ml, 10 patients), and total iron-binding capacity (smaller than 260 mug/100 ml, 11 patients) the values increased after one month on amino acids and were thereafter stable. No signs of bleeding tendency, progressive muscle atrophy, or progressive peripheral neuropathy were observed. - Five patients died due to cardiovascular maladies. A further 13 patients were withdrawn for medical reasons (overhydration, 4 patients; hypertension, 1 patient; nausea and vomiting, 7 patients; and pericarditis, 1 patient). - The renal function improved in one patient. Four patients received home dialysis training, three a kidney transplant. - The results indicate that it is possible to keep severely uremic patients free from uremic symptoms, counteract protein depletion, and even improve the nutritional status during long-term treatment with an unselected protein-poor diet supplementd with essential amino acids.


Compressibility of M3C60 Fullerene Superconductors: Relation Between Tc and Lattice Parameter.
X-ray diffraction and diamond anvil techniques were used to measure the isothermal compressibility of K(3)C(60) and Rb(3)C(60), the superconducting, binary alkali-metal intercalation compounds of solid buckminsterfullerene. These results, combined with the pressure dependence of the superconducting onset temperature T(c) measured by other groups, establish a universal first-order relation between T(c) and the lattice parameter a over a broad range, between 13.9 and 14.5 angstroms. A small secondorder intercalate-specific effect was observed that appears to rule out the participation of intercalate-fullerene optic modes in the pairing interaction.


Application of PCR and DNA probes in the characterisation of trypanosomes in the blood of cattle in farms in Morogoro, Tanzania.
Polymerase chain reaction (PCR) and deoxyribonucleic acid (DNA) probes were used to characterise trypanosomes from cattle in Morogoro region of Tanzania. Blood samples collected from 390 beef and dairy cattle in selected farms in Morogoro region were examined for presence of trypanosomes using the buffy coat technique (BCT) and blood smears (BSs). Fifty-two animals were found infected: 40 with Trypanosoma congolense, 10 with T. vivax and two with both T. congolense and T. vivax. DNA extracted from all the parasitologically positive and 62 randomly selected parasitologically negative samples were subjected to PCR amplification using primers specific for different trypanosome species. Using a set of seven specific-pairs of primers on the parasitologically positive samples, we detected only T. congolense, either the Savannah- or the Kilifi-type, as single or mixed infections. With the PCR, trypanosome DNA could be detected in 27 (43%) out of 62 samples that were parasitologically negative. DNA hybridisation using probes specific for Savannah- or Kilifi-types T. congolense, or T. vivax, confirmed the presence of these parasites in cattle kept on some farms in Morogoro region of Tanzania. From these studies, it is clear that there is a need to undertake molecular epidemiological studies to determine the distribution of trypanosome species and subspecies, and to assess the economic impact of these parasites in the productivity of livestock in Tanzania. In particular, it would be desirable to verify the assumed association between the different presentations of trypanosomosis on one hand and genotypes of T. congolense on the other.


The Glitter of Carbon Nanostructures in Hybrid/Composite Hydrogels for Medicinal Use.
In recent years, we have witnessed to fast developments in the medicinal field of hydrogels containing various forms of integrated nanostructured carbon that adds interesting mechanical, thermal, and electronic properties. Besides key advances in tissue engineering (especially for conductive tissue, such as for the brain and the heart), there has been innovation also in the area of drug delivery on-demand, with engineered hydrogels capable of repeated response to light, thermal, or electric stimuli. This mini-review focusses on the most promising developments as applied to the gelation of protein/ peptide (including self-assembling amino acids and low-molecular-weight gelators), polysaccharide, and/or synthetic polymer components in medicine. The emerging field of graphene-only hydrogels is also briefly discussed, to give the reader a full flavor of the rising new paradigms in medicine that are made possible through the integration of nanostructured carbon (e.g., carbon nanotubes, nanohorns, nanodiamonds, fullerene, etc.). Nanocarbons are offering great opportunities to bring on a revolution in therapy that the modern medicinal chemist needs to master, to realise their full potential into powerful therapeutic solutions for the patient.


Albumin infusion in patients undergoing large-volume paracentesis: a meta-analysis of randomized trials.
Albumin infusion reduces the incidence of postparacentesis circulatory dysfunction among patients with cirrhosis and tense ascites, as compared with no treatment. Treatment alternatives to albumin, such as artificial colloids and vasoconstrictors, have been widely investigated. The aim of this meta-analysis was to determine whether morbidity and mortality differ between patients receiving albumin versus alternative treatments. The meta-analysis included randomized trials evaluating albumin infusion in patients with tense ascites. Primary endpoints were postparacentesis circulatory dysfunction, hyponatremia, and mortality. Eligible trials were sought by multiple methods, including computer searches of bibliographic and abstract databases and the Cochrane Library. Results were quantitatively combined under a fixed-effects model. Seventeen trials with 1,225 total patients were included. There was no evidence of heterogeneity or publication bias. Compared with alternative treatments, albumin reduced the incidence of postparacentesis circulatory dysfunction (odds ratio [OR], 0.39; 95% confidence interval [CI], 0.27-0.55). Significant reductions in that complication by albumin were also shown in subgroup analyses versus each of the other volume expanders tested (e.g., dextran, gelatin, hydroxyethyl starch, and hypertonic saline). The occurrence of hyponatremia was also decreased by albumin, compared with alternative treatments (OR, 0.58; 95% CI, 0.39-0.87). In addition, mortality was lower in patients receiving albumin than alternative treatments (OR, 0.64; 95% CI, 0.41-0.98). This meta-analysis provides evidence that albumin reduces morbidity and mortality among patients with tense ascites undergoing large-volume paracentesis, as compared with alternative treatments investigated thus far.


Cytoskeleton-based forecasting of stem cell lineage fates.
Stem cells that adopt distinct lineages cannot be distinguished based on traditional cell shape. This study reports that higher-order variations in cell shape and cytoskeletal organization that occur within hours of stimulation forecast the lineage commitment fates of human mesenchymal stem cells (hMSCs). The unique approach captures numerous early (24 h), quantitative features of actin fluororeporter shapes, intensities, textures, and spatial distributions (collectively termed morphometric descriptors). The large number of descriptors are reduced into "combinations" through which distinct subpopulations of cells featuring unique combinations are identified. We demonstrate that hMSCs cultured on fibronectin-treated glass substrates under environments permissive to bone lineage induction could be readily discerned within the first 24 h from those cultured in basal- or fat-inductive conditions by such cytoskeletal feature groupings. We extend the utility of this approach to forecast osteogenic stem cell lineage fates across a series of synthetic polymeric materials of diverse physicochemical properties. Within the first 24 h following stem cell seeding, we could successfully "profile" the substrate responsiveness prospectively in terms of the degree of bone versus nonbone predisposition. The morphometric methodology also provided insights into how substrates may modulate the pace of osteogenic lineage specification. Cells on glass substrates deficient in fibronectin showed a similar divergence of lineage fates, but delayed beyond 48 h. In summary, this high-content imaging and single cell modeling approach offers a framework to elucidate and manipulate determinants of stem cell behaviors, as well as to screen stem cell lineage modulating materials and environments.


Port-site metastases after open laparoscopy: a study in 173 patients with advanced ovarian carcinoma.
Open laparoscopy was used to diagnose advanced ovarian cancer. Patients with a pelvic mass and an omental cake and/or large-volume ascites were selected for open laparoscopy. One hundred and seventy-three patients with stage III or IV ovarian carcinoma underwent diagnostic open laparoscopy. Seventy-one patients underwent complete excision of port sites at the time of debulking surgery. Thirty (17%) patients developed port-site metastases. However, only 8 (5%) of these port-site metastases were clinically diagnosed, while 22 out of 71 (31%) with complete port-site excision were diagnosed on pathologic examination. There was no significant relationship between the development of port-site metastases and median time to primary chemotherapy or surgery, the presence of ascites, or stage IV disease. All port-site metastases disappeared during primary therapy, and none of the patients developed a second relapse in one of their port sites. We observed a high rate of port-site metastases after laparoscopy in patients with advanced ovarian carcinoma. However, prognosis was not worse in this group of patients. Laparoscopy is a convenient technique to diagnose advanced ovarian carcinoma, to exclude other primary tumors, and to refer patients to a tertiary center.


Point mutations in Staphylococcus aureus PBP 2 gene affect penicillin-binding kinetics and are associated with resistance.
In Staphylococcus aureus, penicillin-binding protein 2 (PBP 2) has been implicated in non-PBP 2a-mediated methicillin resistance. The PBP 2 gene (pbpB) was cloned from an expression library of a methicillin-susceptible strain of S. aureus (209P), and its entire sequence was compared with that of the pbpB gene from strains BB255, BB255R, and CDC6. Point mutations that resulted in amino acid substitutions near the conserved penicillin-binding motifs were detected in BB255R and CDC6, two low-level methicillin-resistant strains. Penicillin binding to PBP 2 in both BB255R and CDC6 is altered, and kinetic analysis indicated that altered binding of PBP 2 by penicillin was due to both lower binding affinity and more rapid release of bound drug. These structural and biochemical changes may contribute to the strains' resistance to beta-lactam antibiotics.


Sex and gender analysis improves science and engineering.
The goal of sex and gender analysis is to promote rigorous, reproducible and responsible science. Incorporating sex and gender analysis into experimental design has enabled advancements across many disciplines, such as improved treatment of heart disease and insights into the societal impact of algorithmic bias. Here we discuss the potential for sex and gender analysis to foster scientific discovery, improve experimental efficiency and enable social equality. We provide a roadmap for sex and gender analysis across scientific disciplines and call on researchers, funding agencies, peer-reviewed journals and universities to coordinate efforts to implement robust methods of sex and gender analysis.


Repeatedly evolved host-specific ectosymbioses between sulfur-oxidizing bacteria and amphipods living in a cave ecosystem.
Ectosymbioses between invertebrates and sulfur-oxidizing bacteria are widespread in sulfidic marine environments and have evolved independently in several invertebrate phyla. The first example from a freshwater habitat, involving Niphargus ictus amphipods and filamentous Thiothrix ectosymbionts, was recently reported from the sulfide-rich Frasassi caves in Italy. Subsequently, two new Niphargus species, N. frasassianus and N. montanarius, were discovered within Frasassi and found to co-occur with N. ictus. Using a variety of microscopic and molecular techniques, we found that all three Frasassi-dwelling Niphargus species harbor Thiothrix ectosymbionts, which belong to three distinct phylogenetic clades (named T1, T2, and T3). T1 and T3 Thiothrix dominate the N. frasassianus ectosymbiont community, whereas T2 and T3 are prevalent on N. ictus and N. montanarius. Relative distribution patterns of the three ectosymbionts are host species-specific and consistent over different sampling locations and collection years. Free-living counterparts of T1-T3 are rare or absent in Frasassi cave microbial mats, suggesting that ectosymbiont transmission among Niphargus occurs primarily through inter- or intraspecific inoculations. Phylogenetic analyses indicate that the Niphargus-Thiothrix association has evolved independently at least two times. While ectosymbioses with T1 and T2 may have been established within Frasassi, T3 ectosymbionts seem to have been introduced to the cave system by Niphargus.


Prevalence and persistence of sleep disordered breathing symptoms in young children: a 6-year population-based cohort study.
To describe the prevalence, persistence, and characteristics associated with sleep disordered breathing (SDB) symptoms in a population-based cohort followed from 6 months to 6.75 years. Avon Longitudinal Study of Parents and Children (ALSPAC). England, 1991-1999. 12,447 children in ALSPAC with parental report of apnea, snoring, or mouth-breathing frequency on any one of 7 questionnaires. Symptom prevalence rates-assessed as "Always" and "Habitually"-are reported at 0.5, 1.5, 2.5, 3.5, 4.75, 5.75, and 6.75 years of age. The proportion of children in whom symptoms develop, persist or abate between observation points is reported. Exploratory multivariate analyses identified SDB risk factors at 1.5, 4.75, and 6.75 years. The prevalence of apnea ("Always") is 1%-2% at all ages assessed. In contrast, snoring "Always" ranges from 3.6% to 7.7%, and snoring "Habitually" ranges from 9.6% to 21.2%, with a notable increase from 1.5- 2.5 years. At 6 years old, 25% are habitual mouth-breathers. The "Always" and "Habitual" incidence of each symptom between time points is 1%-5% and 5%-10%, respectively. In multivariate analyses of combined symptoms, socioeconomic factors have stronger, more persistent effects upon increased SDB risk than gestational age, gender, or race (aside from 1.5 years); adenoidectomy decreases risk by 40%-50%. This is the first natural history study of the primary symptoms of SDB across a key 6-year period in the development of SDB symptoms. Snoring rates are higher and spike earlier than previously reported. Symptoms are dynamic, suggesting the need for early and continued vigilance in early childhood.


Vacuum-assisted breast biopsy under ultrasonographic guidance: analysis of a 10-year experience.
To determine the indications and the diagnostic accuracy of vacuum-assisted breast biopsy (VABB) under ultrasonographic (US) guidance based on a 10-year period of clinical use. This was a retrospective analysis of 2,920 breast lesions in 2,477 consecutive patients who underwent US-guided VABB between February 2002 and December 2011. The proportions of each indication for VABB were analyzed as well as the trend of its use over divided time periods. Histopathological diagnosis and the malignancy rate of the lesions with VABB were analyzed. A comparison of the pathological diagnosis of VABB and the gold standard diagnosis revealed the false negative rate, the underestimation rate, and the agreement rate. Palpable lesions (44.4%), low-suspicion lesions (15.7%), high-risk lesions (12.4%), and calcifications (10.3%) were the most common indications for US-guided VABB. The malignancy rate of lesions submitted to VABB was 5.4%. The false negative rate was only 0.1%, while the underestimation rate of high-risk lesions and ductal carcinoma in situ was 3.1% and 13.8%, respectively, with a 98.7% agreement rate. Among 1,512 therapeutic VABB cases, 84.9% showed no residual or recurrent lesions on long term follow-up US for more than a year. Complications occurred in 1% of the patients without need for surgical intervention. US-guided VABB is an accurate and safe method that can help decision-making in the diagnostic process and can be an alternative for excisional surgery in some therapeutic circumstances.


Spatial stratification of various Lyme disease spirochetes in a Central European site.
To determine whether the genospecies composition of Lyme disease spirochetes is spatially stratified, we collected questing Ixodes ricinus ticks in neighboring plots where rodents, birds, and lizards were present as reservoir host and compared the prevalence of various genospecies. The overall prevalence of spirochetes in questing ticks varied across the study site. Borrelia lusitaniae appeared to infect adult ticks in one plot at the same frequency as did Borrelia afzelii in the other plots. The relative density of questing nymphal and adult ticks varied profoundly. Where lizards were exceedingly abundant, these vertebrates seemed to constitute the dominant host for nymphal ticks, contributing the majority of infected adult ticks. Because lizards support solely B. lusitaniae and appear to exclude other genospecies, their narrow genospecies association results in predominance of B. lusitaniae in sites where lizards are abundant, while limiting its spread to the host's habitat range. To the extent that Central European B. lusitaniae strains are nonpathogenic, the presence of numerous lizards should locally decrease risk of infection for people. Evaluation of regional risk of infection by Lyme disease spirochetes should take the spatial effect of hosts into consideration, which stratify the distribution of specifically infected ticks on a small scale.


18F-fluoride PET/CT for detection of sacroiliitis in ankylosing spondylitis.
The aim of this study was to evaluate the performance of (18)F-fluoride-PET/CT (PET/CT) for the diagnosis of sacroiliac joint (SIJ) arthritis in patients with active ankylosing spondylitis (AS). Included in the study were 15 patients with AS according to the modified New York criteria (AS group) and with active disease and 13 patients with mechanical low back pain (MLBP; control group) who were investigated with whole-body (18)F-fluoride PET/CT. The ratio of the uptake in the SIJ and that in the sacrum (SIJ/S) was calculated for every joint. The mean SIJ/S ratio of 30 quantified joints in the AS group was 1.66 (range 1.10-3.07) with PET/CT, and the mean SIJ/S ratio of 26 quantified joints in the MLBP group was 1.12 (range 0.71-1.52). The area under the receiver operating characteristic curve for SIJ arthritis was 0.84. With plain radiography as a the gold standard and taking an SIJ/S ratio of >1.3 as the threshold, the sensitivity, specificity and accuracy on a per patient basis were 80%, 77% and 79%, respectively. On a per SIJ basis, the greatest sensitivity (94%) was found in grade 3 sacroiliitis (n = 16). Our results suggest that quantitative (18)F-fluoride PET/CT may play a role in the diagnosis of sacroiliitis in active AS and is an alternative to conventional bone scintigraphy in times of molybdenum shortage.


Enlargement of Axo-Somatic Contacts Formed by GAD-Immunoreactive Axon Terminals onto Layer V Pyramidal Neurons in the Medial Prefrontal Cortex of Adolescent Female Mice Is Associated with Suppression of Food Restriction-Evoked Hyperactivity and Resilience to Activity-Based Anorexia.
Many, but not all, adolescent female mice that are exposed to a running wheel while food restricted (FR) become excessive wheel runners, choosing to run even during the hours of food availability, to the point of death. This phenomenon is called activity-based anorexia (ABA). We used electron microscopic immunocytochemistry to ask whether individual differences in ABA resilience may correlate with the lengths of axo-somatic contacts made by GABAergic axon terminals onto layer 5 pyramidal neurons (L5P) in the prefrontal cortex. Contact lengths were, on average, 40% greater for the ABA-induced mice, relative to controls. Correspondingly, the proportion of L5P perikaryal plasma membrane contacted by GABAergic terminals was 45% greater for the ABA mice. Contact lengths in the anterior cingulate cortex correlated negatively and strongly with the overall wheel activity after FR (R = -0.87, P < 0.01), whereas those in the prelimbic cortex correlated negatively with wheel running specifically during the hours of food availability of the FR days (R = -0.84, P < 0.05). These negative correlations support the idea that increases in the glutamic acid decarboxylase (GAD) terminal contact lengths onto L5P contribute toward ABA resilience through suppression of wheel running, a behavior that is intrinsically rewarding and helpful for foraging but maladaptive within a cage.


The basic keratin 10-binding domain of the virulence-associated pneumococcal serine-rich protein PsrP adopts a novel MSCRAMM fold.
Streptococcus pneumoniae is a major human pathogen, and a leading cause of disease and death worldwide. Pneumococcal invasive disease is triggered by initial asymptomatic colonization of the human upper respiratory tract. The pneumococcal serine-rich repeat protein (PsrP) is a lung-specific virulence factor whose functional binding region (BR) binds to keratin-10 (KRT10) and promotes pneumococcal biofilm formation through self-oligomerization. We present the crystal structure of the KRT10-binding domain of PsrP (BR187-385) determined to 2.0 Å resolution. BR187-385 adopts a novel variant of the DEv-IgG fold, typical for microbial surface components recognizing adhesive matrix molecules adhesins, despite very low sequence identity. An extended β-sheet on one side of the compressed, two-sided barrel presents a basic groove that possibly binds to the acidic helical rod domain of KRT10. Our study also demonstrates the importance of the other side of the barrel, formed by extensive well-ordered loops and stabilized by short β-strands, for interaction with KRT10.


Efficient mouse transgenesis using Gateway-compatible ROSA26 locus targeting vectors and F1 hybrid ES cells.
The ability to rapidly and efficiently generate reliable Cre/loxP conditional transgenic mice would greatly complement global high-throughput gene targeting initiatives aimed at identifying gene function in the mouse. We report here the generation of Cre/loxP conditional ROSA26-targeted ES cells within 3-4 weeks by using Gateway cloning to build the target vectors. The cDNA of the gene of interest can be expressed either directly by the ROSA26 promoter providing a moderate level of expression or by a CAGG promoter placed in the ROSA26 locus providing higher transgene expression. Utilization of F1 hybrid ES cells with exceptional developmental potential allows the production of germ line transmitting, fully or highly ES cell-derived mice by aggregation of cells with diploid embryos. The presented streamlined procedures accelerate the examination of phenotypical consequences of transgene expression. It also provides a unique tool for comparing the biological activity of polymorphic or splice variants of a gene, or products of different genes functioning in the same or parallel pathways in an overlapping manner.


Associations between adiposity, hormones, and gains in height, whole-body height-adjusted bone size, and size-adjusted bone mineral content in 8- to 11-year-old children.
We examined fat-independent associations of hormones with height and whole-body bone size and mineral content in 633 school children. IGF-1 and osteocalcin predict growth in height, while fat, osteocalcin, and in girls also, IGF-1 predict growth in bone size. Leptin and ghrelin are inversely associated with bone size in girls. Obesity causes larger bone size and bone mass, but the role of hormones in this up-regulation of bone in obesity is not well elucidated. We examined longitudinal associations between baseline body fat mass (FM), and fat-independent fasting levels of ghrelin, adiponectin, leptin, insulin, insulin-like growth factor-I (IGF-1), osteocalcin, and intact parathyroid hormone, and subsequent changes in height and in whole-body height-adjusted bone area "BAheight" and size-adjusted bone mineral content "BMCsize" in 8- to 11-year-olds. Analyses were carried out separately for boys (n = 325) and girls (n = 308) including data from baseline, 3 and 6 months from OPUS School Meal Study. In both sexes: gain in BAheight was positively associated with baseline FM (≥2.05 cm(2)/kg, both p ≤ 0.003). Furthermore, gain in height was positively associated with baseline IGF-1 (≥0.02 cm/ng/ml, p = 0.001) and osteocalcin (≥0.13 cm/ng/ml, p ≤ 0.009); and gain in BAheight was positively associated with baseline osteocalcin (≥0.35 cm(2)/ng/ml, p ≤ 0.019). In girls only, gain in BAheight was also positively associated with baseline IGF-1 (0.06 cm(2)/ng/ml, p = 0.017) and inversely associated with both baseline ghrelin (-0.01 cm(2)/pg/ml, p = 0.001) and leptin (-1.21 cm(2)/μg/ml, p = 0.005). In boys, gain in BMCsize was positively associated with osteocalcin (0.18 g/ng/ml, p = 0.030). This large longitudinal study suggests that in 8- to 11-year-old children, IGF-1 and osteocalcin predict growth in height, while FM, osteocalcin, and in girls also, IGF-1 predict growth in BAheight. Fat-independent inverse associations of leptin and ghrelin with BAheight in girls' are contrary to proposed growth-stimulating effects of leptin. Osteocalcin in boys predicts gain in BMCsize.


Nanoparticle eluting-angioplasty balloons to treat cardiovascular diseases.
Nanoparticles (NPs) can be used to locally deliver anti-restenosis drugs when they are infused directly to the injured arteries after intervention procedures such as angioplasty. However, the efficacy of transferring NPs via infusion to the arterial wall is limited, at least partially, due to poor NP retention on the inner artery wall. To improve NP retention, angioplasty balloons coated with drug-loaded NPs were fabricated via either layer-by-layer (LbL) electrostatic coating or acrylic-based hydrogel (AAH) coating techniques. Three types of NPs, namely poly (lactide-co-glycolide) (PLGA), biodegradable photo-luminescent PLGA and urethane doped polyester were studied. The transfer efficacy of NPs from various coatings to the arterial wall were further evaluated to find the optimal coating conditions. The ex vivo NP transfer studies showed significantly more NPs being transferred to the rat arterial wall after the angioplasty procedure by the AAH coating (95% transfer efficiency) compared to that of the LbL technique (60%) and dip coating (20%) under flow conditions (10 dyn/cm2). Our results suggest that the AAH coating of drug-loaded NPs on the angioplasty balloon could potentially provide superior retention of drug-loaded NPs onto the arterial wall for a better local delivery of drug-loaded NPs to effectively treat arterial diseases.


Effectiveness of blood transfusions and risk factors for mortality in children aged from 1 month to 4 years at the Bon Marché Hospital, Bunia, Democratic Republic of the Congo.
To assess the effectiveness of blood transfusions in a hospital of north-eastern Democratic Republic of the Congo. Prospective study of children admitted for severe anaemia. During admission, data were collected on clinical condition and haemoglobin levels, before and after blood transfusion. A linear regression model was built to explore factors associated with haemoglobin level after transfusion. Risk factors for mortality were explored through multivariate logistic regression. Haemoglobin level (Hb) was below 4 g/dl in 35% (230/657), between 4 and 6 g/dl in 58% (348/657) and at least 6 g/dl in another 6% (43/657) of the transfused children. A transfusion of 15 ml/kg of whole blood increased the Hb from 4.4 to 7.8 g/dl. Haemoglobin level after transfusion was associated with baseline Hb, quantity of delivered blood and history of previous transfusions. Overall case-fatality rate was 5.6% (37/657). Risk factors for deaths were co-morbidities such as chest infection, meningitis or malnutrition, Hb ≥ 6 g/dl, impaired consciousness or jugular venous distention on admission, and provenance. Transfusion was a frequent practice, the use of which could clearly have been rationalised. While indications should be restricted, quantities of transfused blood should be adapted to needs.


Base deficit does not predict mortality when secondary to hyperchloremic acidosis.
Base deficit has been established as a predictor of mortality and endpoint of resuscitation. We hypothesized that in a significant subset of surgical intensive care patients, base deficit is secondary to hyperchloremic acidosis, and that these patients experience lower mortality than those patients whose base deficits are secondary to other causes. Seventy-five consecutive surgical intensive care patients with base deficits greater than 2.0 were prospectively studied. The etiology of the patients' base deficits was determined by admission laboratory data. Patients were divided into those with hyperchloremic acidosis, and those with acidosis from other causes. Mortality within these groups was compared by Fisher's exact test. Thirty-seven patients (49.3%) had hyperchloremic acidosis. Thirty-three patients (46.7%) had lactic acidosis. Three patients (4%) had base deficits secondary to ketosis, and two patients (2.6%) had base deficits secondary to uremia. There were no significant differences in age, APACHE II scores, or volumes of resuscitation between the hyperchloremic group and the remaining patients. There were four deaths (10.8%) in the hyperchloremic group and thirteen deaths (34.2%) in the remaining patients (P = 0.03). Hyperchloremic acidosis resulted from resuscitation with lactated Ringer's solution in 18 (48.6%) of the hyperchloremic patients. Hyperchloremic acidosis is a common etiology of base deficit in the surgical intensive care unit. It is associated with lower mortality than base deficit secondary to other causes. Moreover, it is frequently induced following resuscitation with lactated Ringer's solution. Failure to properly diagnose this subset of acidotic patients may result in inappropriate clinical interventions due to the erroneous presumption of ongoing tissue hypoxia.


[Antitumor activity of extracts of Ganoderma lucidum and their protective effects on damaged HL-7702 cells induced by radiotherapy and chemotherapy].
To study the inhibitory effect of Ganoderma lucidum, the extract of chloroform, the extract of ethyl acetate and the remains after two-time extraction on BEL-7402 and MGC-803 cells and their protective effects on HL-7702 cells pre-and post-exposed to cisplatin (DDP) and various doses of 60Co gamma irradiation. The antitumor activity and protective effects on damaged HL-7702 cells induced by radiotherapy and chemotherapy of ganoderma lucidum were determined by MTT technique. The anticancer activity of the extract of chloroform Ganoderma lucidum was the best: at the concentration of 0.125 mg x mL(-1), the inhibitory rate was over 50%. To the HL-7702 cells damaged by DDP, four kinds of extracts didn't exert restoring effect, but the pretreatment with the extract of chloroform reduced the damaged degree significantly. To the 60Co gamma irradiated HL-7702 cells, only the extract of chloroform exerted restoring effect to some extent when exposed to middle or high dose of irradiation. The pre-administration of four kinds of extracts reduced the damaged degree by radiation. The extract of chloroform exerts notable antitumor effects on cancer cells and protective effects on damaged normal cells induced by radiotherapy and chemotherapy.


Progressive ratio as a measure of reward strength.
Four rats were trained to press a lever on a ratio schedule of reinforcement in which the number of lever presses required on each consecutive run increased by a fixed increment. Both concentration and volume of the reward were varied. Relationships were obtained between reward and deprivation variables and the size of the final completed ratio run.


The rise and fall of the world's first fat tax.
In 2011, Denmark introduced the world's first tax on saturated fat, but only 15 months later the fat tax was abolished. The aim of this article is to investigate the political processes surrounding the implementation and rapid abolition of the fat tax. Our findings suggest that industry and trade associations were heavily involved in the political process of formulating the fat tax. Industry representatives used certain tactics to oppose the fat tax: threatening lawsuits, predicting welfare losses, casting doubt on evidence, diverting focus and requesting postponement. After the fat tax was implemented, the food industry continued their opposition through intensified lobbyism and juridical actions at EU level. However, other factors seem to have contributed to the fall of the fat tax. The tax received criticism for being poorly designed and gradually lost popularity among health professionals, politicians and the public. In the end, the fat tax was abolished for financial reasons. This study demonstrates how politicians considered the fat tax as a funding source rather than a public health initiative, which resulted in significant shortcomings. Furthermore, we demonstrate that the massive influence by industry stakeholders was not balanced with inputs from public health professionals, who should assume a more proactive role in policy-making.


SBML qualitative models: a model representation format and infrastructure to foster interactions between qualitative modelling formalisms and tools.
Qualitative frameworks, especially those based on the logical discrete formalism, are increasingly used to model regulatory and signalling networks. A major advantage of these frameworks is that they do not require precise quantitative data, and that they are well-suited for studies of large networks. While numerous groups have developed specific computational tools that provide original methods to analyse qualitative models, a standard format to exchange qualitative models has been missing. We present the Systems Biology Markup Language (SBML) Qualitative Models Package ("qual"), an extension of the SBML Level 3 standard designed for computer representation of qualitative models of biological networks. We demonstrate the interoperability of models via SBML qual through the analysis of a specific signalling network by three independent software tools. Furthermore, the collective effort to define the SBML qual format paved the way for the development of LogicalModel, an open-source model library, which will facilitate the adoption of the format as well as the collaborative development of algorithms to analyse qualitative models. SBML qual allows the exchange of qualitative models among a number of complementary software tools. SBML qual has the potential to promote collaborative work on the development of novel computational approaches, as well as on the specification and the analysis of comprehensive qualitative models of regulatory and signalling networks.