Survival benefit of exclusive use of in situ arterial conduits over combined use of arterial and vein grafts for multiple coronary artery bypass grafting.
The purpose of this study was to evaluate mortality after coronary artery bypass grafting (CABG) comparing the use of only in situ arterial grafts with the use of arterial and venous conduits. From April 1985 to March 1999, 1159 patients with multivessel disease underwent elective, isolated, primary, multiple CABG with at least one in situ arterial conduit. Patients who were on chronic dialysis, had active malignant disease, or had free arterial conduits were excluded. The long-term results were compared between 532 patients who had CABG using only in situ arterial conduits (group A; mean follow-up, 7.8 years) and 627 patients who underwent CABG using in situ arterial conduits and saphenous vein grafts (group B; mean follow-up, 10.3 years). Actuarial survival and freedom from cardiac death were determined by the Kaplan-Meier method. Propensity score was included in the Cox multivariable regression model for adjustment of selection bias. Survival at 10 years after surgery was 81.4% in group A and 76.9% in group B (P=0.11). Freedom from cardiac death at 10 years was 93.4% in group A and 90.4% in group B. Hazard ratio for cardiac death was significantly lower in group A (0.61; 95% confidence interval, 0.38 to 1.00; P=0.05). Our data suggest that the exclusive use of in situ arterial grafts in CABG achieves significantly better long-term survival compared with combined use of arterial and vein grafts.


Hypercapnia Impairs ENaC Cell Surface Stability by Promoting Phosphorylation, Polyubiquitination and Endocytosis of β-ENaC in a Human Alveolar Epithelial Cell Line.
Acute lung injury is associated with formation of pulmonary edema leading to impaired gas exchange. Patients with acute respiratory distress syndrome (ARDS) require mechanical ventilation to improve oxygenation; however, the use of relatively low tidal volumes (to minimize further injury of the lung) often leads to further accumulation of carbon dioxide (hypercapnia). Hypercapnia has been shown to impair alveolar fluid clearance (AFC), thereby causing retention of pulmonary edema, and may lead to worse outcomes; however, the underlying molecular mechanisms remain incompletely understood. AFC is critically dependent on the epithelial sodium channel (ENaC), which drives the vectorial transport of Na+ across the alveolar epithelium. Thus, in the current study, we investigated the mechanisms by which hypercapnia effects ENaC cell surface stability in alveolar epithelial cells (AECs). Elevated CO2 levels led to polyubiquitination of β-ENaC and subsequent endocytosis of the α/β-ENaC complex in AECs, which were prevented by silencing the E3 ubiquitin ligase, Nedd4-2. Hypercapnia-induced ubiquitination and cell surface retrieval of ENaC were critically dependent on phosphorylation of the Thr615 residue of β-ENaC, which was mediated by the extracellular signal-regulated kinase (ERK)1/2. Furthermore, activation of ERK1/2 led to subsequent activation of AMP-activated protein kinase (AMPK) and c-Jun N-terminal kinase (JNK)1/2 that in turn phosphorylated Nedd4-2 at the Thr899 residue. Importantly, mutation of Thr899 to Ala markedly inhibited the CO2-induced polyubiquitination of β-ENaC and restored cell surface stability of the ENaC complex, highlighting the critical role of Nedd4-2 phosphorylation status in targeting ENaC. Collectively, our data suggest that elevated CO2 levels promote activation of the ERK/AMPK/JNK axis in a human AEC line, in which ERK1/2 phosphorylates β-ENaC whereas JNK mediates phosphorylation of Nedd4-2, thereby facilitating the channel-ligase interaction. The hypercapnia-induced ENaC dysfunction may contribute to impaired alveolar edema clearance and thus, interfering with these molecular mechanisms may improve alveolar fluid balance and lead to better outcomes in patients with ARDS.


Impact of spatial distribution on the development of mutualism in microbes.
The evolution of mutualism is one of the long-standing puzzles in evolutionary biology. Why would an individual contribute to the group at the expense of its own fitness? Individual bacterial cells cooperate by secreting products that are beneficial for the community, but costly to produce. It has been shown that cooperation is critical for microbial communities, most notably in biofilms, however, the degree of cooperation strongly depends on the culturing conditions. Spatial community structure provides a solution how cooperation might develop and remain stable. This perspective paper discusses recent progresses on experiments that use microbes to understand the role of spatial distribution on the stability of intraspecific cooperation from an evolutionary point of view and also highlights the effect of mutualism on spatial segregation. Recent publications in this area will be highlighted, which suggest that while mechanisms that allow assortment help to maintain cooperative traits, strong mutualism actually promotes population intermixing. Microbes provide simple and suitable systems to examine the features that define population organization and mutualism.


[Assessment of the frequency of rare electrophoretic variants of blood proteins in children with congenital pathology].
The frequency of rare electrophoretic protein variants was studied in children with congenital anomalies. The stated frequency (1.07 X 10(-3] proved to be ten-fold higher than in the control group of newborns (1.09 X 10(-4). This difference was mainly due to rare variants of monomorphic proteins. The data obtained confirm the assumption of a functional importance of monomorphic protein loci.


Results in children with local and regional neuroblastoma managed with and without vincristine, cyclophosphamide, and imidazolecarboxamide. A report from the Children's Cancer Study Group.
Members of children's cancer study group designed Study CCG 351 to determine whether three drug chemotherapy improved the survival experience of children with localized neuroblastoma. Patients in stages I-III were treated with surgical removal of the primary tumor and those in stages II and III received radiation therapy to the tumor bed and chemotherapy. Treatment included cyclophosphamide, imidazolecarboxamide, and vincristine given in 5-day pulses each month for 12 courses. The results were compared to those from a previous study, CCG 011, for localized neuroblastoma, in which children were randomized between a treatment regimen that included cyclophosphamide and one with no chemotherapy. There were 133 evaluable patients, subdivided as follows: stages I-26, stages II-74, and stages III-33. The 3-year life-table survival rates by stage of 96, 89 and 50% were not significantly different from the patients in CCG 011 similarly staged who received either no chemotherapy or oral CPM. These data suggest that multiagent chemotherapy, as prescribed, did not improve the outlook for children with locally advanced but nonmetastatic neuroblastoma. The staging criteria employed showed a modest difference in outcome between patients in stages I and II, but a significant poorer survival for stage III as compared to either stage I or II.


Mortality, weight loss and quality of life of patients with morbid obesity: evaluation of the surgical and medical treatment after 2 years.
The surgical treatment for morbid obesity is becoming common in this country. Only a few papers reported the long-term results of the surgical approach for morbid obesity, mainly in terms of quality of life. To compare mortality rate, weight loss, improvement of both diabetes and hypertension, and quality of life of patients from the public healthcare in Cuiabá, MT, Brazil, who underwent either medical or surgical interventions after a minimum of 2 years. The population of this study was constituted by morbidly obese patients who initiated treatment between June 2002 and December 2006. The casuistic consisted of 89 patients submitted to medical therapy and 76 patients who underwent surgical procedures. The main variables were weight loss, improvement of hypertension and diabetes, quality of life, and mortality. The overall results showed that weight loss was significant in the two groups (P<0.001); however surgical patients showed a greater loss than the medical group (P = 0.05). The improvement of diabetes and hypertension was significantly greater in the surgical group (P<0.001), in which no cases of diabetes persisted. There was an increase in cases of hypertension among patients receiving medical attention. Mortality occurred in six cases (6.7%) of the medical group and in five cases (6.6%) of the surgical group (P = 0.97). The median grade of the quality of life score obtained by surgical patients (2.37 [range: -2.50 to 3.00]) was significantly greater (P<0.001) when compared to the medical group (1.25 [range: -1.50 to 3.00]). The surgical group presented better results regarding the weight loss, quality of life and improvement of hypertension and diabetes. There was no significant difference in mortality rate between the two groups after a minimum of 2 years.


Role of mitochondrial phospholipid hydroperoxide glutathione peroxidase (PHGPx) as an antiapoptotic factor.
Phospholipid hydroperoxide glutathione peroxidase (PHGPx) is a unique antioxidant enzyme that markedly reduces lipid hydroperoxide generated in biomembranes. Overexpression of mitochondrial PHGPx potentially suppresses the release of cytochrome c (cyt. c) from mitochondria and apoptosis. The hydroperoxide level in mitochondria was elevated in 2-deoxyglucose (2DG)-induced apoptosis, but not in apoptosis-resistant cells in which mitochondrial PHGPx was overexpressed. From studies of the overexpression of PHGPx, the generation of hydrogen peroxide and lipid hydroperoxide in mitochondria might be important triggers of apoptosis. In particular lipid hydroperoxide could be involved in the initiation of cyt. c liberation from mitochondria in 2DG-induced apoptosis since lipid hydroperoxide is a primary substrate for PHGPx. The release of cyt. c from mitochondria is an important proapoptotic signal in the mitochondrial death pathway. Several reports demonstrated the reactive oxgen species could be involved in cyt. c liberation, although its mechanism is still unknown. Cardiolipin (CL), which exclusively locates in the innermembrane of mitochondria, shows strong affinity for cyt. c is required for the adenine nucleotide translocator (ANT) that controls the opening and closing of the permeability transition pore. Association of cyt. c with CL is lost upon peroxidation. CL hydroperoxide (CLOOH), in contrast to CL, does not bind to cyt. c. Furthermore, CLOOH can open the permeability transion pore by the inactivation of ANT. These previous results suggest that mitochondrial PHGPx inhibits the release of cyt. c from mitochondria by the scavenging CLOOH and could prevent apoptosis.


[Capecitabine combined with TACE for advanced liver cancer].
To evaluate the clinical efficacy of capecitabine combined with transcatheter arterial chemoembolization (TACE) for advanced liver cancer. Forty-nine patients with liver cancer were retrospectively divided into two groups: Treatment group, on the basis of TACE, 23 patients received oral capecitabine at 2500 mg/m(2), twice-daily for 14 days followed by 7-day rest period and repeated in every three week intervals for more than two cycles. Control group, 26 patients received TACE only at 2-month intervals for at least two cycles. In capecitabine and TACE group: there were 1 CR, 14 PR, 5 SD and 3 PD; the overall response rate was 65.2%; the AFP and tumor reduction rates were 68.8% and 73.9%; the median survival time was 11.9 months. In the TACE only group: there were 0 CR, 7 PR, 12 SD and 7 PD; the overall response rate was 26.9%; the AFP and tumor reduction rates were 31.6 % and 30.8%; the median survival time was 8.3 months. The most common side-effects of capecitabine were hand-foot syndrome and diarrhea. Capecitabine combined with TACE is safe and effective for advanced liver cancer.


[Treatment for low-risk myelodysplastic syndromes].
Myelodysplastic syndromes (MDS) are clonal hematopoietic stem cell disorders characterized by cytopenia and leukemic transformation. Allogeneic hematopoietic stem cell transplantation is the only potential curative therapy for MDS; however, the first treatment option for transfusion-independent patients with low-risk MDS remains limited. Recently, lenalidomide has become available for patients with low-risk MDS and symptomatic anemia with del (5q) (5q-syndrome), darbepoetin (DA) for those with anemia without del (5q), and azacitidine for those with DA-resistant anemia or anemia with thrombocytopenia. DA may be the first treatment option for anemic patients with low-risk MDS because the incidence of 5q-syndrome is rare in Japan in contrast to western countries. It has been reported that primary or secondary failure of Erythropoiesis-stimulating agents (ESA) correlated with a higher risk of acute myeloid leukemia, and none of the leading second-line treatments significantly improved survival. In this review, I have described the treatment strategies in using such drugs and future perspectives for low-risk MDS.


Joint Resource Allocation of Spectrum Sensing and Energy Harvesting in an Energy-Harvesting-Based Cognitive Sensor Network.
The cognitive sensor (CS) can transmit data to the control center in the same spectrum that is licensed to the primary user (PU) when the absence of the PU is detected by spectrum sensing. However, the battery energy of the CS is limited due to its small size, deployment in atrocious environments and long-term working. In this paper, an energy-harvesting-based CS is described, which senses the PU together with collecting the radio frequency energy to supply data transmission. In order to improve the transmission performance of the CS, we have proposed the joint resource allocation of spectrum sensing and energy harvesting in the cases of a single energy-harvesting-based CS and an energy-harvesting-based cognitive sensor network (CSN), respectively. Based on the proposed frame structure, we have formulated the resource allocation as a class of joint optimization problems, which seek to maximize the transmission rate of the CS by jointly optimizing sensing time, harvesting time and the numbers of sensing nodes and harvesting nodes. Using the half searching method and the alternating direction optimization, we have achieved the sub-optimal solution by converting the joint optimization problem into several convex sub-optimization problems. The simulation results have indicated the predominance of the proposed energy-harvesting-based CS and CSN models.


Liuwei Dihuang soft capsules attenuates endothelial cell apoptosis to prevent atherosclerosis through GPR30-mediated regulation in ovariectomized ApoE-deficient mice.
Liuwei Dihuang (LWDH), a classical traditional Chinese medicine prescription, has been widely used to prevent and to treat various diseases with symptoms of 'Kidney-Yin' deficiency syndrome for over 1000 years in China. It is commonly used to treat functional decline associated with senile disease and menopausal syndrome, especially memory decline, insomnia, diabetes and osteoporosis. Modern experimental pharmacological studies indicated that the mechanism of LWDH treatment of menopausal syndrome may be associated with enhanced estrogenic effects. However, little attention has been paid to the potential impact of LWDH on atherosclerosis (AS) associated with female menopause. The aim of this study was to evaluate the preventive effects of LWDH intake on an animal model of female menopause AS and to explore the underlying molecular mechanism. ApoE-/- mice were randomly divided into 4 groups, with C57BN/L6 mice as the control group. All ApoE-/- mice were ovariectomized (Ovx) one week prior to oral administration and initiation of high-fat diet. C57BL/6 mice were given sham operation and maintained on normal diet. The three administered groups were given simvastatin (4mg/kg via i.g.) and LWDH (4.5, 9.0g/kg via i.g.) every day for 14 weeks. Atherosclerotic lesions in the aortic root were determined by oil red O staining and hematoxylin-eosin staining. α-Actin and CD68 in atherosclerotic lesions were detected by immunohistological assay. Serum lipids and homocysteine (Hcy) levels were measured in the 14th week. The cleaved caspase-3, C/EBP homologous protein (CHOP) and G protein coupled estrogen receptor 30 (GPR30) expressions in the aortic arch endothelium were determined by immunohistochemistry and Western blot. The inhibitory effect of LWDH-medicated (20%, 12h) on Hcy (20%, 24h)-induced apoptosis of human umbilical vein endothelial cells (HUVECs) was examined by flow cytometry and Hoechst 33258 staining. Intracellular ROS production, nitric oxide release, and endothelial NO synthase (eNOS) activity were measured with or without LWDH-medicated serum pretreatment. In addition, CHOP, glucose-regulated protein GPR30, 78 (Grp78), Bcl-2, Bax and cleaved caspase-3 were analyzed by Western blot. Finally, the influence of G15, a specific antagonist of GPR30, on the protective effect of LWDH on endothelial cells was investigated. In vivo administration of LWDH prevented plaque formation and reduced plasma lipid and Hcy levels. LWDH inhibited CHOP and cleaved caspase-3 expression in vivo and in vitro while maintaining GPR30 expression. In vitro study showed that Hcy-induced HUVECs apoptosis was weakened by LWDH-medicated serum pretreatment. Treatment with LWDH-medicated serum significantly upregulated NO release and eNOS activity in HUVECs. In addition, LWDH-medicated serum treatment optimized the balance between Bax and Bcl-2, and attenuated intracellular ROS production. G15 reversed the protective effect of LWDH on endothelial cells and the changes of apoptosis-related proteins. LWDH treatment can significantly reduce plaque formation in an animal model of menopausal AS. The mechanism may be inhibition of Hcy-induced endothelial cell apoptosis by modulating GPR30. Hence, LWDH can potentially be used to prevent AS-related vascular disease in menopausal women.


Facial palsy in Kawasaki disease: report of two cases.
Facial palsy is an unusual complication associated with Kawasaki disease, with only a few published case reports. We report two patients with typical Kawasaki disease and facial palsy. Both had coronary artery aneurysms and were treated with intravenous immunoglobulin. The facial palsy resolved completely over the next several months in both patients. Coronary artery aneurysms resolved completely in one patient, and the other has not regressed to normal till now. The incidence of coronary artery aneurysm appears to be higher in the handful of reported cases of Kawasaki disease with facial palsy.


Crystallization and preliminary X-ray crystallographic analysis of bacterial tRNA(Sec) in complex with seryl-tRNA synthetase.
Selenocysteine (Sec) is translationally incorporated into proteins in response to the UGA codon. The tRNA specific to Sec (tRNA(Sec)) is first ligated with serine by seryl-tRNA synthetase (SerRS). To elucidate the tertiary structure of bacterial tRNA(Sec) and its specific interaction with SerRS, the bacterial tRNA(Sec) from Aquifex aeolicus was crystallized as the heterologous complex with the archaeal SerRS from Methanopyrus kandleri. Although X-ray diffraction by crystals of tRNA(Sec) in complex with wild-type SerRS was rather poor (to 5.7 Å resolution), the resolution was improved by introducing point mutations targeting the crystal-packing interface. Heavy-atom labelling also contributed to resolution improvement. A 3.2 Å resolution diffraction data set for phase determination was obtained from a K(2)Pt(CN)(4)-soaked crystal.


An exploration of the link between adult attachment and problematic Facebook use.
Previous studies have reported on positive and negative psychological outcomes associated with the use of social networking sites (SNSs). Research efforts linking Facebook use with depression and low self-esteem have indicated that it might be the manner in which people engage with the site that makes its use problematic for some people. The aim of the current study was to test a theoretical model of problematic Facebook use, using adult attachment style as the predictor variable of interest. A cross-sectional design was employed wherein adult Facebook users (n = 717) completed measures of psychological distress, self-esteem, and adult attachment, in addition to measures of problematic Facebook use (i.e. social comparison, self-disclosures, impression management, & intrusive Facebook use). Data were analysed using hierarchical multiple regression and mediation analyses. The results of this study indicated that attachment anxiety was predictive of all facets of problematic Facebook use, and that attachment avoidance was predictive of impression management, and social consequences of intrusive Facebook use. Further analyses confirmed the mediating influences of psychological distress and self-esteem on these relationships. Users of Facebook with higher levels of attachment insecurity may be gravitating towards the site in order to fulfil their attachment needs. This tendency is likely to be particularly prevalent for those individuals with low self-esteem who are experiencing psychological distress.


Hydrostatic pressure induces profibrotic properties in hepatic stellate cells via the RhoA/ROCK signaling pathway.
Elevated interstitial fluid hydrostatic pressure is commonly observed in diseased livers. We herein examined the hypothesis that hydrostatic pressure induces hepatic stellate cells to acquire profibrotic properties under pathological conditions. Human hepatic stellate cells were exposed to 50 mmHg pressure for 24 h. Although we observed few changes of cell growth and morphology, PCR array data on the expression of fibrosis-associated genes suggested the acquisition of profibrotic properties. The exposure of hepatic stellate cells to 50 mmHg pressure for 24 h also significantly enhanced the expression of RhoA, ROCK1, α-SMA, TGF-β1 , p-MLC, and p-Smad2, and this was effectively attenuated by the ROCK inhibitor Y-27632. Our ex vivo experimental data suggest that elevated interstitial fluid hydrostatic pressure under pathological conditions may promote liver fibrosis by inducing acquisition of profibrotic properties of hepatic stellate cells through the RhoA/ROCK signaling pathway.


Cues of control modulate the ascription of object ownership.
Knowing whether an object is owned and by whom is essential to avoid costly conflicts. We hypothesize that everyday interactions around objects are influenced by a minimal sense of object ownership grounded on respect of possession. In particular, we hypothesize that tracking object ownership can be influenced by any cue that predicts the establishment of individual physical control over objects. To test this hypothesis we used an indirect method to determine whether visual cues of physical control like spatial proximity to an object, temporal priority in seeing it, and touching it influence this minimal sense of object ownership. In Experiment 1 participants were shown a neutral object located on a table, in the reaching space of one of two characters. In Experiment 2 one character was the first to find the object then another character appeared and saw the object. In Experiments 3 and 4, spatial proximity, temporal priority, and touch are pitted against each other to assess their relative weight. After having seen the scenes, participants were required to judge the sensibility of sentences in which ownership of the object was ascribed to one of the two characters. Responses were faster when the objects were located in the reaching space of the character to whom ownership was ascribed in the sentence and when ownership was ascribed to the character who was the first to find the object. When contrasting the relevant cues, results indicate that touch is stronger than temporal priority in modulating the ascription of object ownership. However, all these effects were also influenced by contextual social cues like the gender of both characters and participants, the presence of a third-party observer, and the co-presence of characters. Consistently with our hypothesis, results indicate that many different cues of physical control influence the ascription of ownership in daily social contexts.


Effects of familial Alzheimer's disease mutations on the folding nucleation of the amyloid beta-protein.
The effect of single amino acid substitutions associated with the Italian (E22K), Arctic (E22G), Dutch (E22Q) and Iowa (D23N) familial forms of Alzheimer's disease and cerebral amyloid angiopathy on the structure of the 21-30 fragment of the Alzheimer amyloid beta-protein (Abeta) is investigated by replica-exchange molecular dynamics simulations. The 21-30 segment has been shown in our earlier work to adopt a bend structure in solution that may serve as the folding nucleation site for Abeta. Our simulations reveal that the 24-28 bend motif is retained in all E22 mutants, suggesting that mutations involving residue E22 may not affect the structure of the folding nucleation site of Abeta. Enhanced aggregation in Abeta with familial Alzheimer's disease substitutions may result from the depletion of the E22-K28 salt bridge, which destabilizes the bend structure. Alternately, the E22 mutations may affect longer-range interactions outside the 21-30 segment that can impact the aggregation of Abeta. Substituting at residue D23, on the other hand, leads to the formation of a turn rather than a bend motif, implying that in contrast to E22 mutants, the D23N mutant may affect monomer Abeta folding and subsequent aggregation. Our simulations suggest that the mechanisms by which E22 and D23 mutations affect the folding and aggregation of Abeta are fundamentally different.


The effect of hepatocyte growth factor on gut mucosal apoptosis and proliferation, and cellular mediators after severe trauma.
A severe burn injury is associated with an impairment of gut mucosal integrity and function, which is due to increases in small-bowel epithelial cell apoptosis and decreases in cell proliferation. Hepatocyte growth factor (HGF) was shown to improve regeneration in the liver, mesentery, and skin. The purpose of this study was to determine whether HGF can improve small-bowel homeostasis after injury and the cellular mechanisms by which these changes occur. Rats were pair-fed, underwent thermal trauma, and received saline (0.9% NaCl; n = 28) or HGF (200 microg/kg iv every 12 hours, n = 28). Small intestine and serum were taken at 1, 2, 5, and 7 days after injury. Measures were mucosal apoptosis, proliferation, villous morphology, and apoptotic and proliferative mediators, such as caspase-3 and caspase-7, Fas and Fas-ligand, Bcl-2, and Bax. In addition, serum cytokines were determined. Gut epithelial cell apoptosis was increased in the saline and HGF groups after the thermal injury. Despite an increase in serum tumor necrosis factor-alpha and interleukin-1beta, HGF did not affect small-bowel cell apoptosis, but it improved proliferation at days 1 and 2 after injury, which was associated with increased villous height and cell per villous, compared with saline controls, P < .05. Increased mucosal cell proliferation was associated with increased Bcl-2 in the HGF group, P < .05. HGF had no effect on apoptotic mediators, such as Fas, Fas-L, or caspase-3 and caspase-7. HGF improves small-bowel morphology after a severe burn by increasing mucosal Bcl-2 and, concomitantly, small-bowel epithelial cell proliferation.


Gut-associated lymphoid T cell suppression enhances bacterial translocation in alcohol and burn injury.
The mechanism of alcohol-mediated increased infection in burn patients remains unknown. With the use of a rat model of acute alcohol and burn injury, the present study ascertained whether acute alcohol exposure before thermal injury enhances gut bacterial translocation. On day 2 postinjury, we found a severalfold increase in gut bacterial translocation in rats receiving both alcohol and burn injury compared with the animals receiving either injury alone. Whereas there were no demonstrable changes in intestinal morphology in any group of animals, a significant increase in intestinal permeability was observed in ethanol- and burn-injured rats compared with the rats receiving either injury alone. We further examined the role of intestinal immune defense by determining the gut-associated lymphoid (Peyer's patches and mesenteric lymph nodes) T cell effector responses 2 days after alcohol and burn injury. Although there was a decrease in the proliferation and interferon-gamma by gut lymphoid T cells after burn injury alone; the suppression was maximum in the group of rats receiving both alcohol and burn injuries. Furthermore, the depletion of CD3(+) cells in healthy rats resulted in bacterial accumulation in mesenteric lymph nodes; such CD3(+) cell depletion in alcohol- and burn-injured rats furthered the spread of bacteria to spleen and circulation. In conclusion, our data suggest that the increased intestinal permeability and a suppression of intestinal immune defense in rats receiving alcohol and burn injury may cause an increase in bacterial translocation and their spread to extraintestinal sites.


Obstacles to remediating coping following traumatic brain injury.
Coping has been suggested as the final common pathway related to outcome after traumatic brain injury (TBI). Different types of coping have been related to either positive or negative psychosocial outcomes. As a result, a small set of studies have attempted to remediate coping through intervention, but the effectiveness of these studies has been modest. We propose that three primary factors are limiting our ability to effectively remediate coping following TBI through intervention TBI: 1) limited understanding of inter-patient variability following TBI; 2) limited understanding of the mechanisms underlying coping following TBI; and 3) reliance on self-report measures of coping. We discuss these obstacles in the context of a model of frontal lobe function, and in light of recent behavioural work on coping.


Paramedics assessing patients with complex comorbidities in community settings: results from the CARPE study.
The aim for this study was to provide information about how community paramedicine home visit programs best "navigate" their role delivering preventative care to frequent 9-1-1 users by describing demographic and clinical characteristics of their patients and comparing them to existing community care populations. Our study used secondary data from standardized assessment instruments used in the delivery of home care, community support services, and community paramedicine home visit programs in Ontario. Identical assessment items from each instrument enabled comparisons of demographic, clinical, and social characteristics of community-dwelling older adults using descriptive statistics and z-tests. Data were analyzed for 29,938 home care clients, 13,782 community support services clients, and 136 community paramedicine patients. Differences were observed in proportions of individuals living alone between community paramedicine patients versus home care clients and community support clients (47.8%, 33.8%, and 59.9% respectively). We found higher proportions of community paramedicine patients with multiple chronic disease (87%, compared to 63% and 42%) and mental health-related conditions (43.4%, compared to 26.2% and 18.8% for depression, as an example). When using existing community care populations as a reference group, it appears that patients seen in community paramedicine home visit programs are a distinct sub-group of the community-dwelling older adult population with more complex comorbidities, possibly exacerbated by mental illness and social isolation from living alone. Community paramedicine programs may serve as a sentinel support opportunity for patients whose health conditions are not being addressed through timely access to other existing care providers. ISRCTN 58273216.


Primary non-function in a deceased donor kidney transplant even with a Kidney Donor Risk Index less than 1.0: a case report.
Donations from deceased donors have been increasing since the introduction of expanded criteria for donor kidney selection. Several studies have shown that patients receiving deceased donor kidneys using these expanded criteria have improved survival compared to those remaining on the waiting list during hemodialysis. It is important, however, to consider that some of the kidneys classed as usable under the expanded criteria may in fact be unacceptable. To address this concern, preoperative biopsy and imaging of deceased donor kidneys are increasingly being used to assess candidate kidneys. We present the case of a 44-year-old female patient who underwent deceased donor kidney transplantation with negative complement-dependent cytotoxicity and flow cytometry crossmatch. Hours after graft reperfusion, given clinical evidence of primary nonfunction in the kidney, the patient underwent nephrectomy. Despite negative tests for blood type difference and crossmatch, and although the main artery and vein were well perfused, the kidney graft was never functional, and pathologic findings showed thrombotic microangiopathy and diffuse acute tubular necrosis. We conclude that further work on ideal criteria for identifying acceptable donor kidneys is needed.


Perception of initial moving target signals: support for a cumulative lateral inhibition theory.
The cumulative lateral inhibition (CLI) theory of the Fröhlich effect (perceptual mislocalization of the starting position of a moving target in the direction of movement) proposes that the target is difficult to see early in its trajectory because inhibitory feedback from later target views weakens initial target representations. In contrast, attention shift explanations contend that a phenomenal representation of the target is unavailable until attention has shifted to the vicinity of the target. Experiments 1-3 demonstrated that instructing naive undergraduate participants to accept different degrees of target clarity before making their response can alter the magnitude (and presence) of the Fröhlich effect. Experiments 2-4 showed that increasing movement distance by adding target presentations reduced the visibility of the target at early positions. These results are difficult to reconcile with an attention shift account.


Photosynthesis, Water Status and K+/Na+ Homeostasis of Buchoe dactyloides Responding to Salinity.
Soil salinization is one of the most serious abiotic stresses restricting plant growth. Buffalograss is a C4 perennial turfgrass and forage with an excellent resistance to harsh environments. To clarify the adaptative mechanisms of buffalograss in response to salinity, we investigated the effects of NaCl treatments on photosynthesis, water status and K+/Na+ homeostasis of this species, then analyzed the expression of key genes involved in these processes using the qRT-PCR method. The results showed that NaCl treatments up to 200 mM had no obvious effects on plant growth, photosynthesis and leaf hydrate status, and even substantially stimulated root activity. Furthermore, buffalograss could retain a large amount of Na+ in roots to restrict Na+ overaccumulation in shoots, and increase leaf K+ concentration to maintain a high K+/Na+ ratio under NaCl stresses. After 50 and 200 mM NaCl treatments, the expressions of several genes related to chlorophyll synthesis, photosynthetic electron transport and CO2 assimilation, as well as aquaporin genes (BdPIPs and BdTIPs) were upregulated. Notably, under NaCl treatments, the increased expression of BdSOS1, BdHKT1 and BdNHX1 in roots might have helped Na+ exclusion by root tips, retrieval from xylem sap and accumulation in root cells, respectively; the upregulation of BdHAK5 and BdSKOR in roots likely enhanced K+ uptake and long-distance transport from roots to shoots, respectively. This work finds that buffalograss possesses a strong ability to sustain high photosynthetic capacity, water balance and leaf K+/Na+ homeostasis under salt stress, and lays a foundation for elucidating the molecular mechanism underlying the salt tolerance of buffalograss.


'Don't push me aside, Doctor': Suicide attempters talk about their support needs, service delivery and suicide prevention in South Africa.
Few studies have explored the expressed support needs of suicide attempters in developing countries. Data, collected via in-depth interviews with suicide attempters admitted to a South African hospital, were analysed using thematic content analysis. Participants explicitly asked for integrated psycho-social services at a primary health care level and say they require assistance with alleviating psychiatric symptoms, establishing connectedness, interpersonal conflict and solving socio-economic problems. Findings highlight the importance for suicide prevention of (1) considering interpersonal and contextual socio-economic factors in addition to the psychiatric causes of suicidal behaviour; and (2) multilevel strategies, intersectoral collaboration and integrated person-centred primary health care.


Smooth muscle cell response to endothelial injury.
Electron microscopy and autoradiography with 3H-thymidine have been employed to study the cellular dynamic of intimal thickening occurring in the rabbit carotid artery after selective endothelial injury. The results obtained suggest that migration of SMC of the tunica media rather than proliferation is the key event in the development of the intimal thickening.


Patient and technician perspectives following the introduction of frontloaded visual field testing in glaucoma assessment.
Frontloaded visual field testing (twice per eye per session) is well-tolerated by patients and technicians, representing a viable strategy that can be implemented in routine clinical practice to capture enough clinical perimetry data for effective disease diagnosis, surveillance and management. To determine the experiences of patients and technicians following the implementation of frontloaded visual field testing (multiple tests per eye within the same session) in a glaucoma service. This was a retrospective, cross-sectional study. A written questionnaire was administered to patients (three questions) attending the glaucoma service at the Centre for Eye Health for glaucoma assessment and to their administering perimetry technicians (two questions). The questionnaire was administered after static automated perimetry (24-2 SITA-Faster on the Humphrey Field Analyzer) was performed twice for each eye (frontloaded) within the same session. Respondents were asked to provide a 1-5 Likert scale response to questions that targeted operational issues for frontloaded visual field testing. Responses were correlated against to demographic (age, gender, ethnicity) and clinical (diagnosis, refractive error, visual field indices, test duration) parameters. Approximately 90% of patient respondents agreed that frontloaded visual field testing was clearly explained to them, that they were comfortable during the test, and would prefer completing the tests at a single visit rather than returning to repeat the test. Most technician respondents were also able to keep their patients comfortable. 13% of technician respondents felt they ran late during the session, but on average, the total test duration for four visual field tests was 13 minutes, including breaks. There was no correlation found between demographic and clinical factors, and the responses. Frontloaded visual field testing was well-tolerated by patients and technicians. Strategies that may be helpful for other clinics to adopt this new paradigm are described.


Superior performance with sCMOS over EMCCD in super-resolution optical fluctuation imaging.
Super-resolution optical fluctuation imaging (SOFI) is a fast and low-cost live-cell optical nanoscopy for extracting subdiffraction information from the statistics of fluorescence intensity fluctuation. As SOFI is based on the fluctuation statistics, rather than the detection of single molecules, it poses unique requirements for imaging detectors, which still lack a systematic evaluation. Here, we analyze the influences of pixel sizes, frame rates, noise levels, and different gains in SOFI with simulations and experimental tests. Our analysis shows that the smaller pixel size and faster readout speed of scientific-grade complementary metal oxide semiconductor (sCMOS) enables SOFI to achieve high spatiotemporal resolution with a large field-of-view, which is especially beneficial for live-cell super-resolution imaging. Overall, as the performance of SOFI is relatively insensitive to the signal-to-noise ratio (SNR), the gain in pixel size and readout speed exceeds the loss in SNR, indicating sCMOS is superior to electron multiplying charge coupled device in context to SOFI in many cases. Super-resolution imaging of cellular microtubule structures with high-order SOFI is experimentally demonstrated at large field-of-view, taking advantage of the large pixel number and fast frame rate of sCMOS cameras.


Prevalence of gestational diabetes mellitus in Europe: A meta-analysis.
Estimates of the prevalence of gestational diabetes vary widely. It is important to have a clear understanding of the prevalence of this condition to be able to plan interventions and health care provision. This paper describes a meta-analysis of primary research data reporting the prevalence of gestational diabetes mellitus in the general pregnant population of developed countries in Europe. Four electronic databases were systematically searched in May 2016. English language articles reporting gestational diabetes mellitus prevalence using universal screening in general pregnant population samples from developed countries in Europe were included. All papers identified by the search were screened by one author, and then half screened independently by a second author and half by a third author. Data were extracted by one author. Values for the measures of interest were combined using a random effects model and analysis of the effects of moderator variables was carried out. A total of 3258 abstracts were screened, with 40 studies included in the review. Overall prevalence of gestational diabetes mellitus was 5.4% (3.8-7.8). Maternal age, year of data collection, country, area of Europe, week of gestation at testing, and diagnostic criteria were found to have a significant univariate effect on GDM prevalence, and area, week of gestation at testing and year of data collection remained statistically significant in multivariate analysis. Quality category was significant in multivariate but not univariate analysis. This meta-analysis shows prevalence of GDM that is at the upper end of previous estimates in Europe.


Conduct problems in adolescence: three domains of inhibition and effect of gender.
Behavioral and neuropsychological evidence has often shown that children with conduct disorder drawn from clinical populations show problems with impulsivity and are impaired in motor tasks of inhibitory control. We explored the relation between conduct problems and inhibitory deficits in a community sample. Three domains of inhibition were explored in 54 adolescents with conduct problems compared to 53 age, IQ, sex, school, and ethnicity matched controls in 2 geographical areas. Motor response inhibition was assessed using the Stop task, verbal inhibition using the Hayling Sentence Completion test, and cognitive interference inhibition using the Stroop task. Adolescents with conduct problems showed deficits in executive and inhibitory processes of the motor response inhibition task, but were unimpaired in cognitive or verbal inhibitory control. No sex differences were observed and impairments were independent of IQ or geographical location. Findings suggest that motor deficits, rather than higher cognitive forms of inhibitory control, are a specific deficit in children with conduct problems, that girls are as affected as boys, and that motor impulsiveness is a dimensional trait associated with conduct problems, as it is also observed in the community.


Interrupted vs. continued maintenance therapy in childhood acute leukemia.
A total of 313 patients with childhood acute leukemia received a combination of vincristine (2 mg/m2/week) and prednisone (60 mg/m2/day); 86% of 276 evaluable patients achieved a complete bone marrow remission in a median of 35 days. When a complete bone marrow remission was achieved, patients were randomized to one of three oral maintenance therapies: 6-mercaptopurine (6MP) (75 mg/m2/day), methotrexate (MTX) (25 mg/m2/twice weekly), or cyclophosphamide (CYC) (100 mg/m2/day). Patients receiving maintenance therapy were further randomized at 2 and 6 months after the start of maintenance either to continue or discontinue therapy. tthe median lengths of subsequent bone marrow remission for patients randomized at 2 months to continue vs. discontinue therapy were: 37 vs. 19 weeks for 6-MP patients; 25 vs. 14 weeks for MTX patients; and 29 vs. 13 weeks for CYC patients. The median lengths of subsequent marrow remissions for patients receiving maintenance therapy for 6 months and randomized to continue vs. discontinue were: 57 vs. 17 weeks for 6-MP patients; 60 vs. 40 weeks for MTX patients; and 23 vs. 10 weeks for CYC patients. Results indicate a significant advantage for continuing maintenance therapy at 2 and 6 months after the start of complete bone marrow remission.


N,N-diethylphenylacetamide in treated fabrics as a repellent against Aedes aegypti and Culex quinquefasciatus (Diptera: Culicidae).
The efficacy of fabrics impregnated with N,N-diethylphenylacetamide (DEPA), a new repellent, was studied in the laboratory and field against Aedes aegypti (L.) and Culex quinquefasciatus Say. DEPA-treated polyester cotton and cotton fabrics provided repellency for 30 and 36 d and had a half-life of 11 and 5 d, respectively. The repellent could not be applied at a rate of greater than 15% of fabric weight. DEPA-treated fabric patches were found to be a practical and novel approach and were effective for 90 d in the laboratory against Ae. aegypti and 77 d in the field against Cs. quinquefasciatus.


Synthesis, X-Ray Structure, Magnetic Properties, and a Study of Intra/Intermolecular Radical-Radical Interactions of a Triradical TEMPO Compound.
A novel triradical compound with a P=S core and three branches functionalized with 2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO) radicals is synthesized and characterized by IR, (1) H NMR, (31) P NMR, and EPR spectroscopy and MALDI-TOF mass spectrometry, and its chemical structure is confirmed by X-ray diffraction analysis. The triradical shows neither spin exchange interactions between its radical units nor detectable dipolar interactions. This is consistent with the separation between the radical units found in its X-ray diffraction structure, and discounts the existence of intramolecular interactions. This conclusion is confirmed by an EPR concentration study. The concentration at which intermolecular interactions start to appear is determined (5×10(-3) m) and this concentration should be taken into account as a higher concentration limit when studies on intramolecular radical-radical interactions in polyradicals with similar structure are required. SQUID magnetometry analysis of the compound shows antiferromagnetic interactions between the spin carriers of different molecules; that is, antiferromagnetic intermolecular interactions.


Orexin A upregulates the protein expression of OX1R and enhances the proliferation of SGC-7901 gastric cancer cells through the ERK signaling pathway.
Orexins are hypothalamic peptides that regulate food intake, wakefulness, the reward system and energy metabolism. Recent studies have demonstrated the ability of orexins to promote a robust apoptosis and subsequent inhibition of cell growth in various types of cancer cells. The present study was conducted to investigate the effects of orexin A on the survival of human gastric cancer cells, SGC‑7901, and the possible mechanisms. SGC‑7901 cells were exposed to various concentrations of orexin A in vitro in the presence or absence of the orexin receptor 1 (OX1R) antagonist (SB334867), extracellular signal‑regulated kinases 1 and 2 (ERK1/2) antagonist (U0126) or a combination of the two antagonists. The amount of cell proliferation, viability and apoptosis, caspase‑8 and caspases‑9 activities, OX1R protein expression and ERK1/2 protein levels were determined. The expression of OX1R in SGC‑7901 cells was observed. Orexin A (10-10 to 10-6 M) stimulated SGC‑7901 cell proliferation and viability, reduced the pro‑apoptotic activity of caspase‑9 and protected the cells from apoptosis in a dose‑dependent manner. Additionally, ERK1/2 phosphorylation was stimulated by orexin A (10-10 to 10-6 M). However, the OX1R antagonist SB334867 (10-6 M), ERK1/2 antagonist U0126 (30 µM) or the combination of antagonists blocked the effects of orexin A to a certain extent. These results suggest that stimulation of OX1R induces the growth of SGC‑7901 gastric cancer cells through activation of ERK1/2 signaling pathway. These findings add a new dimension to the biological activities of orexin, which may have important implications in health and disease, in particular gastric cancer.


Mortality from chronic obstructive pulmonary disease and pleural mesothelioma in an area contaminated by natural fiber (fluoro-edenite).
The purpose of the present study was to investigate the association between mortality from chronic obstructive pulmonary disease (COPD) and exposure to fluoro-edenite, a newly discovered amphibolic fiber found in Biancavilla (Sicily), a municipality on the slope of the Etna volcano, where a high mortality from malignant mesothelioma had been previously observed. Thirty-six municipalities located in the volcanic area of mount Etna were selected for study. An ecological regression model was applied with mortality from COPD as the dependent variable, mortality from mesothelioma as a proxy for exposure to fluoro-edenite, and lung cancer mortality, an urban-rural index, a deprivation index and an aging index as the predictors of COPD mortality. For each municipality, risk classes were determined for the continuous variables with the use of a finite mixture model. A significant association was found between COPD mortality and pleural neoplasm mortality among the women in this study. The association was less consistent for the men. Despite the limitations of this ecological study, the results cohere with the results of toxicologic and observational studies and suggest an etiologic role for fluoro-edenite in nonmalignant respiratory diseases.


Effect of aldose reductase inhibitor on corneal epithelial barrier function in galactose-fed dogs.
The effect of concomitant administration of galactose and the aldose reductase inhibitor(ARI) Epalrestat (Kinedak) on corneal barrier function was examined in dogs. Six-month-old male beagles were rendered aphakic in one eye and then divided into four groups as follows: 1) a control group fed on 30% cellulose, 2) a galactosemic group fed on 30% galactose, 3) a 30% galactose-fed group treated with low dose (20 mg/kg) ARI and 4) a 30% galactose-fed group treated with high dose (50 mg/kg) ARI. Forty-one months after the start of these diets, corneal autofluorescence and the corneal barrier function were measured in each dog using anterior fluorophotometry (FL-500). When barrier function was analyzed in non-operated eyes, fluorescence data were significantly higher in the galactosemic group compared to the control group. In non-operated eyes, fluorescent data in high-dose ARI treated group were significantly lower than those in the galactosemic group. However, in operated eyes, no significant difference was observed between the galactosemic group and the ARI treated groups. Similar trends were observed when corneal autofluorescence of each group was compared. Long-term galactose feeding appeared to damage corneal epithelial barrier function. This damage was not observed in the high-dose ARI treated group suggesting that this damage may be linked to the polyol pathway.


Potential ecological footprints of active pharmaceutical ingredients: an examination of risk factors in low-, middle- and high-income countries.
Active pharmaceutical ingredients (APIs) can enter the natural environment during manufacture, use and/or disposal, and consequently public concern about their potential adverse impacts in the environment is growing. Despite the bulk of the human population living in Asia and Africa (mostly in low- or middle-income countries), limited work relating to research, development and regulations on APIs in the environment have so far been conducted in these regions. Also, the API manufacturing sector is gradually shifting to countries with lower production costs. This paper focuses mainly on APIs for human consumption and highlights key differences between the low-, middle- and high-income countries, covering factors such as population and demographics, manufacture, prescriptions, treatment, disposal and reuse of waste and wastewater. The striking differences in populations (both human and animal), urbanization, sewer connectivity and other factors have revealed that the environmental compartments receiving the bulk of API residues differ markedly between low- and high-income countries. High sewer connectivity in developed countries allows capture and treatment of the waste stream (point-source). However, in many low- or middle-income countries, sewerage connectivity is generally low and in some areas waste is collected predominantly in septic systems. Consequently, the diffuse-source impact, such as on groundwater from leaking septic systems or on land due to disposal of raw sewage or septage, may be of greater concern. A screening level assessment of potential burdens of APIs in urban and rural environments of countries representing low- and middle-income as well as high-income has been made. Implications for ecological risks of APIs used by humans in lower income countries are discussed.


[Clinical effect of human lymphoblastoid interferon in patients with multiple myeloma].
Five patients with multiple myeloma were treated with human lymphoblastoid interferon (HLBI). HLBI, 3 X 10(6) IU/day, was administered daily for more than two weeks by intramuscular injection. Out of four evaluable patients, a minor response was obtained in 3 patients. In these responders, one patient developed pleural effusion due to the infiltration of myeloma cells during the administration of HLBI, and drug resistance was observed in another patient during the re-administration of HLBI. Therefore, out of six evaluable courses, a minor response was obtained in 3 courses of HLBI treatment. No severe side effects were observed. Thrombocytopenia, general malaise, liver dysfunction and anorexia were the main reasons for discontinuation of HLBI administration. On the basis of the preliminary study, it is concluded that HLBI is worth trying in the management of refractory multiple myeloma.


Sympathetic activity, assessed by power spectral analysis of heart rate variability, in white-coat, masked and sustained hypertension versus true normotension.
To assess, in a population-based approach, sympathetic nervous system activity by the use of power spectral analysis of heart rate variability, in normotension, white-coat hypertension, masked hypertension and sustained hypertension. The electrocardiographic RR interval was registered in the supine and standing positions and the low-frequency and high-frequency components of its variability were quantified. Cut-off values of 140/90 mmHg for conventional blood pressure and 135/85 mmHg for daytime ambulatory blood pressure were used to define the four blood pressure groups. After exclusion of patients with diabetes, myocardial infarction or treated hypertension, 1485 subjects with complete data remained for the analysis in the supine position. Age averaged 39 +/- 14 years; 54% were women. Conventional and ambulatory blood pressure averaged, respectively, 122 +/- 16/79 +/- 11 mmHg and 124 +/- 12/77 +/- 8 mmHg. After adjusting for demographic, anthropometric and lifestyle characteristics, the low-frequency to high-frequency ratio (geometric mean) averaged 0.81 in normotension and was significantly higher in white-coat hypertension (1.11; P < 0.001), based on a higher low-frequency component and a lower high-frequency component (P < 0.01). This ratio was not significantly different between normotension, masked hypertension (0.97) and sustained hypertension (0.93). The adjusted standing-to-supine ratio of the high-frequency component (geometric mean) was significantly higher in sustained hypertension (0.50) than in normotension (0.39; P < 0.01), but not in white-coat (0.40) and masked hypertension (0.45). The findings at rest are compatible with increased sympathetic activity and decreased parasympathetic modulation in white-coat hypertension, with normal autonomic cardiac regulation in masked and sustained hypertension. In addition, sustained hypertension is characterized by a blunted decrease of the high-frequency component on standing.


Profilin: at the crossroads of signal transduction and the actin cytoskeleton.
Despite its small size, profilin is an amazingly diverse and sophisticated protein whose precise role in cells continues to elude the understanding of researchers 15 years after its discovery. Its ubiquity, abundance and necessity for life in more evolved organisms certainly speaks for its extreme importance in cell function. So far, three ligands for profilin have been well-characterized in vitro: actin monomers, membrane polyphosphoinositides and poly-L-proline. In the years following its discovery, profilin's role in vivo progressed from that of a simple actin-binding protein which inhibits actin polymerization, to one which, as an important regulator of the cytoskeleton, can even promote actin polymerization under the appropriate circumstances. In addition, interactions with components of the phosphatidylinositol cycle and the RAS pathway in yeast implicate profilin as an important link through which the actin cytoskeleton is able to communicate with major signaling pathways.


[Hydatid cyst of the spine and spinal cord. Study of 24 cases].
In this retrospective study, we report our experience of severe hydatid disease located to the spine and the adjacent spinal cord observed in 24 cases between 1970 and 1994. In our series the sex ratio was predominant for males, and the mean age was 29 years. Clinically, the patients presented predominantly with a motor deficit. The diagnosis was assessed on radiological and biological investigations and was confirmed preoperatively. Hydatid serology was positive in 7 out of the ten cases explored. On standard X rays, the bone lesions were frequent: lysis in 10 cases, vertebral deformation in 3 cases, costal invasion in 5 cases, and paravertebral collection in 2 cases. These lesions were predominantly located at the thoracic level. Myelography confirmed a complete blockade in 8 out of 11 cases. When possible, the CT scan confirmed the bone lesion in all of the 10 cases explored, with an intrathecal cyst in 7 cases and a paravertebral collection in 8 cases. Magnetic resonance imaging was possible in one case only. Medical antihelminthic treatment was indicated as the sole treatment in one inoperable case. All the other patients were operated on, and the adjunctive specific medical treatment was associated in 5 cases. Using a posterior approach in 20 cases, the operative technique consisted in a complete removal (if possible) of the invaded bone and soft tissue, thus achieving a complete relief of the spinal cord compression. Complementary bone fixation was indicated in 2 cases. During the postoperative follow-up, two patients died from infection and trophic ulceration, 11 patients improved and 8 patients remained unchanged. In 5 cases, a reoperation was indicated and performed from 2 to 4 times. Three patients were lost for follow-up. The severity of this affection is confirmed in the literature. A complete recovery is quite exceptional. The best treatment remains an active nationwide prevention of the disease.


Selective separation and purification of two lipases from chromobacterium viscosum using AOT reversed micelles.
Selective separation and purification of two lipases form Chromobacterium viscosum were carried out by liquid-liquid extraction using a reversed micellar system. Optimum parameters for extraction were determined using a 250 mM AOT micellar solution in isooctane. Complete separation of the two lipases was achieved at pH 6.0 with a 50mM potassium phosphate buffer solution containing 50 mM KCI. By adding 2.5% by volume of ethanol to the lipase-loaded micellar solution, 85% of the extracted lipase could be recovered in a new aqueous phase, 50 mM K(2)HPO(4) with 50 mM KCl, at pH 9.0. Lipase A was purified 2.6-fold with a recovery of 86%, and lipase B by 1.5-fold with a recovery of 76%.


Armodafinil for excessive daytime sleepiness.
Armodafinil is the (R)-enantiomer of the wakepromoting compound modafinil (racemic), with a considerably longer half-life of 10-15 hours. Armodafinil (developed by Cephalon, Frazer, PA, USA) was approved in June 2007 for the treatment of excessive sleepiness associated with narcolepsy, obstructive sleep apnea syndrome and shift work disorder, and the indications are the same as those for modafinil. Like modafinil, the mechanisms of action of armodafinil are not fully characterized and are under debate. Clinical trials in these sleep disorders demonstrated an enhanced efficacy for wake promotion (wake sustained for a longer time period using doses lower than those of modafinil). The safety profile is consistent with that of modafinil, and armodafinil is well tolerated by the patients. Like modafinil, armodafinil is classified as a non-narcotic Schedule IV compound. Many patients with excessive sleepiness may prefer the longer duration of effect and may have better compliance (with low doses) with armodafinil. The commercial challenge to armodafinil may come from generic modafinil, which may become available in 2012, as well as from classical amphetamine and amphetamine-like compounds (for the treatment of narcolepsy).


Mild venom-induced consumption coagulopathy associated with thrombotic microangiopathy following a juvenile Russell's viper (Daboia russelii) envenoming: A case report.
Russell's viper envenoming causes venom-induced consumption coagulopathy (VICC) within hours of a bite, which is associated with thrombotic microangiopathy (TMA) and acute kidney injury (AKI) in a proportion of cases. We report a juvenile Russell's viper bite in which a patient developed mild VICC after the usual 24-h observation period, which was subsequently associated with severe AKI due to TMA. This shows the clinical importance of detecting and treating mild VICC, which may be delayed or not detected with bedside clotting tests.


Revisiting Terminology and Characteristics of Stem Cells.
The majority of populations of differentiated cells are subject to renewal. Progenitor cells (cells-predecessors) and differentiated cells, having started the differentiation pathway or having finished it, can divide a limited number of times and are not capable of ensuring tissue regeneration during the whole period of ontogenesis. Renewal of tissues over such a long period is impossible without the participation of a specialized system which is responsible for regeneration. The given system is represented by pluripotent stem cells. Pluripotent stem cells, which conduct regeneration of all body tissues during ontogeny, are formed during implementation of the development program of the fertilized ovum, along with the formation of tissues and organs of the new organism. Being a separate direction of differentiation of embryonic cells, pluripotent stem cells are not embryonic cells. The immune system takes part in the formation of tissue-specific receptors among pluripotent stem cells. The latter remain pluripotent until the formation of tissue-specific receptors in them, and become committed (tissue-specific stem cells) after the formation of such receptors. Committed stem cells (tissue-specific stem cells) that migrate through the extracellular matrix replenish the progenitor cells of all tissues. Mesenchymal stem cells are the precursors of fibroblasts, and they only create conditions in the extracellular matrix for the migration and differentiation of committed (tissue-specific) stem cells in the places of cell death.


Comparative analysis on resistance profiling along tapered semiconductor nanowires: multi-tip technique versus transmission line method.
The detection of doping dependent values like contact- and path resistances along nanowires (NWs) still proves to be rather challenging compared to planar structures. Unfortunately, the usually used and well established TLM (transmission line measurement) setup exhibits some drawbacks. Complex preliminary preparation steps and the necessity of ohmic contacts limit the investigation to certain semiconductor materials. The simultaneous determination of contact- and path resistances with an unknown distribution makes an analysis on complex structures like tapered nanowires very challenging. Our approach is the utilization of a multi-tip scanning tunneling microscope (MT-STM) as a four point prober, which allows the investigation of freestanding nanowires with an increased spatial resolution. Here, the used measurement setup allows a local separation of current injection and potential measurement and thus a highly precise determination of path resistances. Tapered p-doped GaAs-NWs were used to compare both techniques. Whereas the evaluation of the axial doping profile by MT-STM was rather simple, correction factors had to be introduced for the TLM measurement to calculate the specific resistances and transfer length. By comparing the results of both methods for the very same NW-sample, the precision and accuracy of MT-STM measurements was demonstrated. We found an agreement, which allows the conclusion that both methods exhibit advantages; however the MT-STM was determined as the more precise setup, which enables additional characterization capabilities, such as surface, temperature or light dependent measurements.


Survey of undergraduates' perceptions of experiential learning in the MPharm programme: The TELL Project.
To determine the perception of undergraduate pharmacy students of their experiential learning (EL) placements both in the community and hospital settings. A cross-sectional survey was conducted utilizing a six-item online survey consisting of one open-ended and five closed-ended questions, the latter utilising five-point Likert-type scales ranging from strongly disagree (1) to strongly agree (5). All undergraduate pharmacy students from the School of Pharmacy (N=496) were included in the study. Survey questions assessed students' perceptions on the effectiveness of the EL, tutors and placements sites, and organisation and structure of the EL. Thematic content analysis was performed on the open-ended comments, where relevant themes were generated. From the 139 responses (response rate: 28%), 121 responses were analysed, and of these, 72.5% already had part-time jobs in community pharmacies. Close to 85% felt that their part-time work should contribute to EL hours, which is currently not recognised by the university. Respondents were positive about the effectiveness of EL in developing their professionalism and communication (M=3.84, SD=1.05), clinical (M=3.42, SD=1.22), and technical skills (M=3.32, SD=1.25) Respondents provided favourable feedback about their experience in the hospital as it gave them a real-world exposure to the role of a hospital pharmacist. Community placements were not viewed favourably and this was mainly attributed to the poor experience with tutors whom they felt used them as an extra pair of hands. This was thought to impede their learning experience. They also felt that hospital placements were of insufficient duration, reported by 72.5% of respondents. Respondents also felt they should be sent to other sites such as primary care for placements. Tutor-training is key to ensure tutors are aware of the responsibilities and expectations. Similarly, quality assurance measures should be adopted to ensure tutors and placement sites are capable of providing students with an effective placement experience. While placement durations are a concern, the focus should be on the quality of the placement experience, and ensuring there is structure and flexibility. Content changes are also needed to include emerging placement sites such as primary care to prepare students for evolving pharmacist roles in the changing healthcare system.


[Occupational Health Nurses' Role in the Occupational Health Surveillance of Exposure to Toxics: Toluene as a Case Study].
Toluene, an aromatic hydrocarbon present in various products, is primarily absorbed through the respiratory tract and can affect different body organs. Occupational health nurses play a key role in detecting acute and chronic exposures. They are also responsible for collecting and processing samples for biomonitoring. However, information on the collection and handling requirements, as well as nursing interventions, is scarce and heterogeneous. We reviewed the existing literature linking toluene and occupational health nursing, identified sample collection and processing requirements, as well as signs and symptoms of exposure, and related them to diagnoses and nursing interventions. We conducted a literature search using the PICO strategy, without limitations on document type, date, or language, in PubMed, Web of Science, and Scopus databases. Signs and symptoms were classified according to the system and nursing test performed during the health examination, identifying possible diagnoses and nursing interventions. We found no studies linking toluene and occupational health nursing. Seven out of 60 identified documents were selected, which provided information on sample collection requirements. Signs and symptoms were identified based on nursing tests and related to diagnoses and nursing interventions. The presence of occupational health nursing in studies on toluene is scarce. Sample collection criteria are heterogeneous and limited. There were no studies relating signs and symptoms of toluene exposure to diagnoses and nursing interventions. Further studies on occupational toxicology are needed from a nursing perspective.


Quantum persistence: a random-walk scenario.
In this paper we extend the concept of persistence, well defined for classical stochastic dynamics, to the context of quantum dynamics. We demonstrate the idea via quantum random walk and a successive measurement scheme, where persistence is defined as the time during which a given site remains unvisited by the walker. We also investigated the behavior of related quantities, e.g., the first-passage time and the succession probability (newly defined), etc. The study reveals power-law scaling behavior of these quantities with new exponents. Comparable features of the classical and the quantum walks are discussed.


Review of the genus Ceratotarsonemus De Leon, 1956 (Acari: Prostigmata: Tarsonemidae), with description of a new species from the Amazon Forest.
The genus Ceratotarsonemus De Leon (Acari: Prostigmata: Tarsonemidae) is reviewed here, with the addition of an updated key for the genus. Ceratotarsonemus amazonicus, sp. nov., found in the Brazilian Amazon rainforest, is described. Phase contrast (PC), differential interference contrast (DIC), low temperature scanning electron microscopy (LT-SEM) and confocal microscopy (CLSM) micrographs are provided. Biological and ecological aspects about the role of this species in its ecosystem are also discussed.


Influence of ICRF-159 or ICRF-186 on cytotoxicity of daunorubicin and doxorubicin.
It has been shown that ICRF-159 [1,2-bis(3,5-dioxopiperazine-1-yl)propane] and its more water soluble d-enantiomer, ICRF-186, antagonize the toxicity of daunorubicin and the cardiac toxicity of daunorubicin and doxorubicin and potentiate the antitumor effect of both substances in experimental animals. In particular, the antagonism against general toxicity was observed in combination with daunorubicin but not with doxorubicin. In this study, we evaluated the activity of ICRF-159 and ICRF-186 on the colony inhibition test of HeLa cells in vitro in combination with daunorubicin or doxorubicin. ICRF-159 and ICRF-186 similarly antagonize the cytotoxicity of daunorubicin but not of doxorubicin. There were no differences between ICRF-159 and ICRF-186, dissolved in DMSO and in physiological solution, respectively. The different activity of ICRF-159 and ICRF-186 against daunorubicin and doxorubicin is not explained by a different uptake of the anthracyclines by HeLa cells in vitro. In the present paper we report findings from our in vitro colony forming assay with HeLa cells, which has been used to evaluate the cytotoxicity of ICRF-159 and ICRF-186 in the presence of daunorubicin and doxorubicin.


Recent Advances in Phenylketonuria: A Review.
This article highlights the significance of inborn errors of metabolism and focuses specifically on phenylketonuria (PKU), a well-known inheritance disorder caused by the deficiency or absence of phenylalanine hydroxylase (PAH). This review discusses associated mutations in the PAH gene and their impact on phenylalanine metabolism. A total of 40 articles were analyzed between 2019 and 2023, covering diagnostic innovations, advancements in treatment and management strategies, and the long-term implications of PKU. This study emphasizes the importance of early diagnosis and highlights the ongoing need for advancements in screening methods and treatment approaches to optimize patient outcomes in PKU patients. This review provides valuable insights for healthcare professionals involved in the care of children with PKU and contributes to the enhancement of clinical practice in this field.


Lymphoplasmacytic lymphoma. Report of a case with three monoclonal proteins derived from a single neoplastic clone.
The unique case of a 60-year-old patient with a non-Hodgkin's B-cell lymphoma of the lymphoplasmacytic type and three associated monoclonal proteins, is described. The patient also exhibited various autoimmune phenomena that were consistent with the diagnoses of Sjögren's syndrome and autoimmune thyroiditis. The evolution from production of a single monoclonal protein (IgM-kappa) to three monoclonal proteins (IgG-kappa, IgA-kappa, and IgM-kappa) suggested that the lymphoplasmacytic cells were at different stages of terminal differentiation within a single neoplastic clone. The chronic antigenic stress imposed on the immune system by the autoimmune disorder may have played a role in the development of lymphoma and in the heavy chain immunoglobulin switching that occurred during the patients' clinical course.


Senile-Onset Subacute Sclerosing Panencephalitis, Presenting With Peculiar Findings.
Subacute sclerosing panencephalitis (SSPE) is a well-known childhood disease; however, the adult onset of SSPE cases are also widely recognized where the oldest case reported is 52 years old. We report a 61-year-old woman patient presenting with atypical clinical and EEG features, diagnosed with SSPE. Measles and SSPE have decreased dramatically owing to worldwide immunization programs; however, there are still reasons to consider SSPE in differential diagnosis even in patients presenting with atypical clinical findings and older ages. First, there is a generation who missed the immunization era, constituting a latent disease pool. Second, antivaccination movements have led to a decline in MMR (measles, mumps, rubella) vaccination worldwide, leading to measles outbreaks and potential future SSPE cases. Third, most of the vaccination programs start measles immunization at the age of 12 months, leading to a shift in the incidence below the age of 1 year, when the risk of developing SSPE in adult life is higher. Finally, disruption in vaccination programs, in which fast disease transmission due to close contact living, unhygienic conditions of refugee camps, and limited access to health care in displaced populations have also led to measles outbreaks. In conclusion, we believe that neurologists for adults should consider SSPE in differential diagnosis, even in older patients with atypical presentations.


[Efficient Pharmaceutical Formulation Designs and Their Development Using Mathematical and Statistical Analysis].
With the aim of directly predicting the functionality and mechanism of pharmaceutical excipients, we investigated an analysis method based on available surface area (S(t)), which is the surface area of a drug in direct contact with the external solvent during dissolution. First, to study the effect of lubricant concentration on the dissolution rate of acetaminophen (APAP), the dissolution behaviors as well as the change over time in S(t) of APAP tablets were examined. In the dissolution tests, a retarded dissolution of APAP was not observed with new lubricant triglycerin full behenate (TR-FB), whereas magnesium stearate (Mg-St) retarded the dissolution. The S(t) profiles for APAP with Mg-St at>0.5% showed downward curvature indicating a gradual decrease in surface area over time. Conversely, with TR-FB, even when its concentration was increased, the S(t) profile for APAP had a maximum value. The differences between Mg-St and TR-FB could be explained by the differences in extensibility deriving from their morphology. Next, we evaluated the effect of disintegtant concentration using five disintegrants. When disintegrant was added to ethenzamide tablet formulation, an increase in the dissolution rate and S(t) dependent on disintegrant concentration was observed, according to the type of disintegrant. It was found that the water absorption ability of disintegrants had strong correlations with the parameters of S(t). Taken together, this study demonstrates that analysis of S(t) can directly provide useful information, especially about the functionality of pharmaceutical excipients.


Nonmedical prescription opioid use among victimized women on probation and parole.
Nonmedical prescription opioid use (NPOU) is a major public health concern and few studies have described this phenomenon among victimized women involved in the criminal justice system. This study will describe the relationship between victimization, psychological distress, health status and NPOU among the vulnerable population of victimized women on probation and parole. A sample of 406 women on probation and parole responded to items assessing victimization history, self-reported health status, physical pain, psychological distress, and post-traumatic stress disorder. Multiple logistic regression analysis was utilized to differentiate NPOUs versus nonusers. Overall, 169 (41.6%) women reported lifetime NPOU, and 20% reported use in the past year. Compared to women who did not report NPOU, NPOUs were more likely to be White, have poorer general health, and more severe psychological distress across nine symptom domains. In multiple logistic regression models, each year of age reduced the odds of NPOU by 4%; White women were twice as likely as women of other races to report NPOU; each unit increase in the measure for physical pain was associated with a 30% increase in the odds of NPOU; and participants who met diagnostic criteria for PTSD were 60% more likely to report NPOU compared to individuals who did not. Victimized women on probation and parole report high rates of NPOU and comorbid mental and physical health problems. The criminal justice system should routinely screen for NPOU, as well as untreated or poorly managed physical pain and psychological distress, which may increase risk of NPOU.


Role of the Terrestrial Biosphere in Atmospheric Chemistry and Climate.
The terrestrial biosphere-atmosphere interface provides a key chemical, biological, and physical lower boundary for the atmosphere. The presence of vegetation itself modifies the physical boundary, or the biogeophysical aspects of the system, by controlling important climate drivers such as soil moisture, light environment, and temperature. The leaf surface area of the terrestrial biosphere provides additional surface area for emissions, and it can be up to 55% of the total Earth's surface area during the boreal summer. Vegetation also influences the biogeochemical aspects of the system by emitting a broad suite of reactive trace gases such as biogenic volatile organic compound (BVOC) emissions and climate-relevant primary biological aerosol particles (PBAP). Many of these emissions are a function of meteorological and climatological conditions at the surface, including temperature, light environment, soil moisture, and winds. Once emitted, they can be processed in the troposphere through a suite of chemical reactions. BVOC can contribute to the formation of ozone and secondary organic aerosols (SOA), and PBAP can rupture to form smaller particles with climatic relevance. These emissions and subsequent aerosol products can influence atmospheric processes that affect the surface climate, such as the attenuation of radiation, the formation of greenhouse gases such as ozone that can feedback to surface air temperature, and the alteration of clouds and subsequent precipitation. These atmospheric changes can then feedback to the land surface and emissions themselves, creating positive or negative feedback loops that can dampen or amplify the emission response. For the dominant BVOC isoprene, the feedback response to temperature can be positive or negative depending on ambient temperatures that drive isoprene emissions. The feedback response to soil moisture and precipitation can be positive, negative, or uncoupled depending on the moisture content of the soil and the total atmospheric aerosol loading. For light, the isoprene response can be positive or negative depending on the role of diffuse light. Overall, these feedbacks highlight the dynamical response of the biosphere to changing atmospheric conditions across a range of time scales, from minutes for trace gases and aerosols, to months for phenological changes, to years for land cover and land use change. The dynamic aspect of this system requires us to understand, simulate, and predict the complex feedbacks between the biosphere and atmosphere and understand their role in the simulation and understanding of climate and global change. From the observational perspective, these feedbacks are challenging to identify in observations, and predictive modeling tools provide a crucial link for understanding how these feedbacks will change under warming climate scenarios.


Characterization of C-type particles produced by a tissue culture-adapted murine myeloma.
C-type particles produced by a tissue culture-adapted BALB/c myeloma were characterized. It was determined that although the particles were morphologically and antigenically similar to murine leukemia and sarcoma virus, the size of their RNA was different, they lacked RNA-dependent DNA polymerase, they were unstable in NET buffer, sucrose and citrate but were stable in glycerol and Earle balanced salt solution, and they behaved differently from oncornaviruses when treated with ether and detergent.


The pattern of dreams of a sample of Nigerians.
In order to highlight the pattern of dreams, the psychosocial factors associated with it, and the meaning attributed to dream contents, 431 Nigerians were interviewed, consisting of undergraduates and government workers. While 6.9% could not recall ever having had a dream experience, over one-third of subjects had had at least three dream experiences in the previous three months. The most important factors associated with increase in frequency of dreams were conditions involving a high degree of expectation, emotional disturbance and happiness. About one-half of subjects claimed their dreams were predictive of what would happen in real life, while 61% claimed that their dreams related to what they were thinking about. The more highly educated and younger subjects dreamt significantly more frequently. Although life events and GHQ-12 scores were not significantly associated with frequency of dreams, those who reported recurrent disturbing dreams had significantly higher GHQ-12 scores. Relating the dream reports to life experiences, we were able to discern the following themes: expectation of positive material rewards; sexual themes; religious themes; sickness and death themes; disappointment and general guilt themes; and abstract manifest contents. Guilt themes were the least frequent. The social and clinical implications of the findings are discussed.


Protective action of a herbal preparation Liv-52 against beryllium toxicity in rats.
An Ayurvedic medicine, Liv-52 has been studied as a prophylactic against beryllium induced toxicity in rats. Administration of beryllium per se caused severe degenerative and necrotic changes in liver, kidney, lungs and spleen. Its administration reduced glycogen content, activity of alkaline phosphatase and adenosine triphosphatase in these organs. On the contrary, activities of acid phosphatase and glucose-6-phosphatase were increased significantly. In Liv-52 primed rats significant recoupment was observed in all the parameters.


[Signet-ring-cell adenoma of the thyroid: description of a case and review of the literature].
An occasional finding of a signet-ring cell type adenoma, occurring in a 81-year-old man, suffering from inoperable pharyngo-laryngeal carcinoma, is described. Multinodular thyroid parenchyma was excided in performing tracheostomy and histologically examined. On the basis of extensive morphological, histochemical and immunohistochemical observations and of reviewed literature, an unifying morphogenetic interpretation of the signet-ring cell transformation is proposed, with special reference to the pathogenesis of this cytotype and the significance of the cytostructural and cytometabolic characteristics. Problems related to the differential diagnosis and clinicopathological correlation are also discussed.


Leaded gasoline abuse: the role of tetraethyl lead.
Volatile substance abuse is practised worldwide however reports of the abuse of leaded gasoline have been limited to northern Canada, southwestern USA and the Australian Outback. Chronic, heavy abuse of leaded gasoline results in an encephalopathy, cerebellar and corticospinal symptoms and signs, dementia, mental status alterations, and persistent organic psychosis. Much of this is due to the hydrocarbons of gasoline while the tetraethyl lead contributes to the altered mental status and is responsible for the persistent psychosis. Lead chelation therapy is not rational and has not been shown to benefit these patients.


A one-dimensional silver(I) coordination polymer based on 5-methyl-1,3,4-thiadiazol-2-amine and pyridine-2,3-dicarboxylate.
The bifunctional pyridine-2,3-dicarboxylic acid (H2pdc) ligand has one N atom and four O atoms, which could bind more than one AgI centre with diverse binding modes. A novel infinite one-dimensional AgI coordination polymer, namely catena-poly[[silver(I)-(μ2-pyridine-2,3-dicarboxylato-κ2N:O3)-silver(I)-tris(μ2-5-methyl-1,3,4-thiodiazol-2-amine-κ2N:N')] monohydrate ethanol monosolvate], {[Ag2(C7H3NO4)(C3H5N3S)3]·H2O·C2H5OH}n, has been synthesized using H2pdc and 5-methyl-1,3,4-thiadiazol-2-amine (tda), and characterized by single-crystal X-ray diffraction. One AgI atom is located in a four-coordinated AgN4 tetrahedral geometry and the other AgI atom is in a tetrahedral AgN3O geometry. A dinuclear AgI cluster formed by three tda ligands with a paddelwheel configuration is bridged by the dianionic pdc2- ligand into a one-dimensional coordination polymer. Interchain N-H...O hydrogen bonds extend the one-dimensional chains into an undulating two-dimensional sheet. The sheets are further packed into a three-dimensional supramolecular framework by interchain N-H...O hydrogen bonds.


Alternate Strategies to Induce Dynamically Modulated Transient Transcription Machineries.
Emulating native transient transcription machineries modulating temporal gene expression by synthetic circuits is a major challenge in the area of systems chemistry. Three different methods to operate transient transcription machineries and to modulate the gated transcription processes of target RNAs are introduced. One method involves the design of a reaction module consisting of transcription templates being triggered by promoter fuel strands transcribing target RNAs and in parallel generating functional DNAzymes in the transcription templates, modulating the dissipative depletion of the active templates and the transient operation of transcription circuits. The second approach involves the application of a reaction module consisting of two transcription templates being activated by a common fuel promoter strand. While one transcription template triggers the transcription of the target RNA, the second transcription template transcribes the anti-fuel strand, displacing the promoter strand associated with the transcription templates, leading to the depletion of the transcription templates and to the dynamic transient modulation of the transcription process. The third strategy involves the assembly of a reaction module consisting of a reaction template triggered by a fuel promoter strand transcribing the target RNA. The concomitant nickase-stimulated depletion of the promoter strand guides the transient modulation of the transcription process. Via integration of two parallel fuel-triggered transcription templates in the three transcription reaction modules and application of template-specific blocker units, the parallel and gated transiently modulated transcription of two different RNA aptamers is demonstrated. The nickase-stimulated transiently modulated transcription reaction module is applied as a functional circuit guiding the dynamic expression of gated, transiently operating, catalytic DNAzymes.


Stereoselective synthesis of structurally simplified cephalostatin analogues by multiple Heck reactions and their biological evaluation.
The stereoselective synthesis of structurally simplified heptacyclic cephalostatin analogues 2, 3, 18-21, 31, 32 and 33 by multiple Heck reactions is described. The key step of the synthesis is a selective Heck reaction of hydrindene 7 with 12 and 25, respectively at the vinyl bromide moiety followed by the introduction of a second molecule of 7 and a twofold intramolecular Heck reaction. The obtained bissteroidal heptacyclic compounds 2 and 3, in which the central octahydrophenazine moiety of 1 is replaced by a benzene ring, contain an unusual cis-annulation of the two newly generated rings. The cytotoxicity of some of the derivatives was determined on human lung cancer cell line A 549 in HTFCA tests (Human tumor colony forming ability). They show a rather high activity with an ED(50) in the micro molar range.


Severity of hypothyroidism is inversely associated with impaired quality of life in patients referred to an endocrine clinic.
We investigated the association between health-related quality of life (HRQL) and the severity of hypothyroidism at diagnosis in patients referred to a secondary hospital clinic. Sixty-seven adult patients referred from primary care were enrolled. All patients had newly diagnosed hypothyroidism due to autoimmune thyroiditis and were treated with levothyroxine (LT4). The dose was adjusted according to thyroid function tests aiming at a normal plasma thyrotropin. Patients were stratified according to the severity of hypothyroidism in two different ways: the conventional approach (subclinical or overt hypothyroidism) and a novel approach according to the change (decrease or increase) in plasma level of free triiodothyronine index (FT3I) following LT4 treatment. The ThyPRO-39 questionnaire was used for measurement of HRQL at referral to the Endocrine Outpatient Clinic (higher score corresponds to worse HRQL). Free thyroxine index (FT4I) at diagnosis correlated positively with the scores on the Hypothyroid Symptoms and Tiredness scales (p = 0.018 for both). In accordance, patients with subclinical hypothyroidism (n = 36) scored higher on Hypothyroid Symptoms (p = 0.029) than patients with overt hypothyroidism (n = 31). The difference in HRQL was more pronounced if patients were stratified according to the dynamics in FT3I following LT4 treatment. Thus, patients who showed a decrease in FT3I following treatment (n = 24) scored significantly worse for Anxiety (p = 0.032) and Emotional Susceptibility (p = 0.035) than patients with an increase in FT3I (n = 43). Patients referred to an endocrine clinic with mild hypothyroidism had an impaired HRQL, compared to patients with more severe hypothyroidism. The most likely explanation of this finding is a lower threshold for seeking medical consultation and secondary care referral if HRQL is deteriorated. The dynamics in plasma FT3I following treatment may be more sensitive for such a discrimination in HRQL than a stratification according to the thyroid function tests at diagnosis.


Enhancing the response to parenteral nutrition in critical care.
Parenteral nutrition (PN) is an essential component in the support of critically ill patients with gastrointestinal dysfunction. Although PN cannot fully reverse hypermetabolism and accelerated skeletal muscle breakdown observed during periods of critical illness, it can prevent the adverse effects associated with malnutrition. The use of PN is not without complications, so care must be taken to ensure successful clinical outcomes with this complex therapy. Strategies have been developed by practitioners to promote safe practices with implementation of PN therapy and optimize a patient's response to PN. Identification of appropriate patient populations, strict glucose control, and manipulation of macro- and micronutrients are techniques being used to augment a patient's response to PN administration. This article will review the novel methods used to enhance benefits received from PN during critical illness.


Cardiac substrate uptake and metabolism in obesity and type-2 diabetes: role of sarcolemmal substrate transporters.
Cardiovascular disease is the primary cause of death in obesity and type-2 diabetes mellitus (T2DM). Alterations in substrate metabolism are believed to be involved in the development of both cardiac dysfunction and insulin resistance in these conditions. Under physiological circumstances the heart utilizes predominantly long-chain fatty acids (LCFAs) (60-70%), with the remainder covered by carbohydrates, i.e., glucose (20%) and lactate (10%). The cellular uptake of both LCFA and glucose is regulated by the sarcolemmal amount of specific transport proteins, i.e., fatty acid translocase (FAT)/CD36 and GLUT4, respectively. These transport proteins are not only present at the sarcolemma, but also in intracellular storage compartments. Both an increased workload and the hormone insulin induce translocation of FAT/CD36 and GLUT4 to the sarcolemma. In this review, recent findings on the insulin and contraction signalling pathways involved in substrate uptake and utilization by cardiac myocytes under physiological conditions are discussed. New insights in alterations in substrate uptake and utilization during insulin resistance and its progression towards T2DM suggest a pivotal role for substrate transporters. During the development of obesity towards T2DM alterations in cardiac lipid homeostasis were found to precede alterations in glucose homeostasis. In the early stages of T2DM, relocation of FAT/CD36 to the sarcolemma is associated with the myocardial accumulation of triacylglycerols (TAGs) eventually leading to an impaired insulin-stimulated GLUT4-translocation. These novel insights may result in new strategies for the prevention of development of cardiac dysfunction and insulin resistance in obesity and T2DM.


Key health themes and reporting of numerical cigarette-waterpipe equivalence in online news articles reporting on waterpipe tobacco smoking: a content analysis.
There is anecdotal evidence that health messages interpreted from waterpipe tobacco smoking (WTS) research are inconsistent, such as comparing the health effects of one WTS session with that of 100 cigarettes. This study aimed to identify key health themes about WTS discussed by online news media, and how numerical cigarette-waterpipe equivalence (CWE) was being interpreted. We identified 1065 online news articles published between March 2011 and September 2012 using the 'Google Alerts' service. We screened for health themes, assessed statements mentioning CWE and reported differences between countries. We used logistic regression to identify factors associated with articles incorrectly reporting a CWE equal to or greater than 100 cigarettes, in the absence of any comparative parameter ('CWE ≥100 cigarettes'). Commonly mentioned health themes were the presence of tobacco (67%) and being as bad as cigarettes (49%), and we report on differences between countries. While 10.8% of all news articles contained at least one positive health theme, 22.9% contained a statement about a CWE. Most of these (18.6% total) were incorrectly a CWE ≥100 cigarettes, a quarter of which were made by healthcare professionals/organisations. Compared with the Middle East, articles from the USA and the UK were the most significant predictors to contain a CWE ≥100 cigarettes statement. Those wishing to write or publish information related to WTS may wish to avoid comparing WTS to cigarettes using numerical values as this is a major source of confusion. Future research is needed to address the impact of the media on the attitudes, initiation and cessation rates of waterpipe smokers.