Risk of malaria in visitors to the Kruger National Park, South Africa.
The risk of malaria to visitors to South Africa's nature reserves is unknown. Current recommendations for travelers are based on malaria incidence rates in local communities. These rates may well overestimate travelers' malaria risk and lead to unnecessary use of antimalarial prophylaxis with associated drug-related adverse events. This study investigated the incidence of malaria in visitors to South Africa's Kruger National Park (KNP). Postal questionnaires were sent to the cohort of visitors staying in the KNP during April 1996, 6 to 8 weeks after they returned to their homes. Nonrespondents received duplicate questionnaires 8 weeks later. Responses from 3267 groups, representing 11,107 visitors (56. 8%) allowed determination of the malaria attack rate in this group of travelers and assessment of associations between malaria risk and a number of factors, including type of accommodation used during the visit; duration of stay; use of chemoprophylaxis; and use of personal protection measures. All travelers indicating that they had suffered an episode of malaria following their visit were telephonically contacted and their health providers traced to determine the basis of diagnosis and clinical outcome. One clinically suspected and four confirmed cases of Plasmodium falciparum malaria among the visitors suggest a low attack rate of 4. 5 cases per 10,000 visitors during April, the highest risk month for malaria in South Africa. No association was found between malaria risk and accommodation type, duration of stay, use and type of chemoprophylaxis, and use and number of personal protection measures. These findings confirm the importance of careful assessment of local malaria risk before individualized advice is provided to travelers.


Elucidating the molecular bases of epigenetic inheritance in non-model invertebrates: the case of the root-knot nematode Meloidogyne incognita.
Root-knot nematodes of the genus Meloidogyne are biotrophic plant parasites that exhibit different life cycles and reproduction modes, ranging from classical amphimixis to obligatory mitotic parthenogenesis (apomixis), depending on the species. Meloidogyne incognita, an apomictic species, exhibits a worldwide distribution and a wide host range affecting more than 3000 plant species. Furthermore, evidences suggest that apomixis does not prevent M. incognita from adapting to its environment in contrast to what is expected from mitotic parthenogenesis that should theoretically produce clonal progenies. This raises questions about mechanisms of genome plasticity leading to genetic variation and adaptive evolution in apomictic animals. We reasoned that epigenetic mechanisms might in part be responsible for the generation of phenotypic variants that provide potential for rapid adaptation. We established therefore a pipeline to investigate the principal carriers of epigenetic information, DNA methylation and post-translational histone modifications. Even if M. incognita possesses the epigenetic machinery i.e., chromatin modifying enzymes, 5-methyl-cytosine and 5-hydroxy-methyl-cytosine content is absent or very weak. In contrast, we demonstrated that the canonical histone modifications are present and chromatin shows typical nucleosome structure. This work is the first characterization of carriers of epigenetic information in M. incognita and constitutes a preamble to further investigate if M. incognita development and its adaptation to plant hosts are under epigenetic control. Our pipeline should allow performing similar types of studies in any non-model organism.


Changing trends of hepatitis B seromarkers amongst Pakistani population: a laboratory-based review.
To study the changing trends of hepatitis B markers tested at Aga Khan University Hospital clinical laboratory according to the internationally recognised classification of hepatitis B profile. The retrospective study involved analysis of laboratory records of hepatitis B profiles of all patients collected from January 2001 to December 2008 at the Aga Khan University Hospital's clinical laboratory. Patients with complete profile tested were categorised according to the Centre for Diseases Control classification of hepatitis B profile. SPSS 16 was used for statistical analysis. A total of 185,825 patients had serological markers for hepatitis B tested. Mean-age of reactive hepatitis B surface antigen (HBsAg) patients was 30+/-12.5 years. HBsAg reactivity was significantly higher in males than females (34% vs 12%; p <0.0001). HBsAg showed a slight decline in the percentage reactivity during the 8-year study period, while a gradual increase in hepatitis B surface antibody (HBsAb) reactivity was observed. Of the total, 23% patients belonged to the 'susceptible to infection' category; 39% patients were classified as 'chronically-ill'; 12% patients were categorised as 'immune due to hepatitis B vaccination. 3% patients were classed as 'acutely infected'. Overall, samples received from Peshawar, Quetta and Larkana showed very high reactivity rates. The study substantiated the general perception that levels of HBsAg is showing a decreasing trend, while levels of HBsAb are increasing perhaps due to better vaccination of population.


Spontaneous intracranial hemorrhage in a patient with Middle East respiratory syndrome corona virus.
The Middle East respiratory syndrome corona virus (MERS-CoV) is a novel positive sense singlestranded ribonucleic acid virus of the genus Beta corona virus. This virus was first isolated from a patient who died from severe respiratory illness in June 2012 in Jeddah, Kingdom of Saudi Arabia. We describe an unusual case of a 42 year old healthcare worker who was admitted to our Intensive Care Unit (ICU)King Abdul-Aziz Medical City, with MERS-CoV and severe acute respiratory distress Syndrome and developed a sudden-onset diabetes insipidus and spontaneous massive intracranial hemorrhage with intra-ventricular extension and tonsillar herniation. Computed angiogram of the brain did not reveal any aneurysm or structural defects. She never had uncontrolled hypertension, or coagulopathy, nor she received antiplatelets. We are reporting a rare case of structural neurological damage associated with MERS-CoV infection.


[Morphological characteristic of wound healing process in patients with diabetic purulent-necrotic foot lesion treated with oxytocin].
Wound healing was studied in 90 patients with "diabetic foot" receiving complex treatment which included oxytocin (40 patients) or did not use it (50 patients). Intraarterial injection or local application of oxytocin resulted in significant differences of wound process characteristics as compared with those ones in control group. The necrobiotic and necrotic changes in the tissues of skin, subcutaneous adipose tissue and skeletal muscles, located within the purulent-necrotic foci, were less expressed. The number of sludged capillaries, as well as of arterioles and venules with the signs of microthrombosis, was significantly decreased. Simultaneously, the regenerative potential of endotheliocytes, fibroblasts and adventitial cells was increased, showing a significant stimulation of their DNA-synthesizing capacity. The histological findings obtained indicate that the introduction of oxytocin in complex treatment activates the processes of vasculogenesis, proliferation of endotheliocytes anf histiocytes, that, in turn, results in the effective clearance of the wound and optimal granulation tissue formation.


Dimensions of alcohol-related social and health consequences in survey research.
Dimensions of alcohol-related social and health consequences are approached from two different perspectives. First, classical approaches with factor analytic techniques are used to empirically determine the dimensionality of item batteries intended to measure harm. Second, a closer look is taken at theoretically underlying dimensions of social and health consequences and their association with alcohol consumption. Using as empirical material data from the US national survey of males aged 21-59 (N3) conducted in 1969, the following specific questions are discussed: (1) What are the underlying dimensions of alcohol-related social and health consequences? (2) How should the relation between alcohol consumption and consequences best be assessed (in terms of epidemiological traditions or social constructivist traditions)? (3) How can we best incorporate the time perspective into modeling the relationship between alcohol consumption and consequences? A first attempt is made to develop practical guidelines for future research on handling these problems.


Aquatic therapy for patients with rheumatic disease.
Aquatic therapy is justifiably a rapidly expanding, beneficial form of patient treatment. The goals established at the initial and subsequent evaluations usually are met as quickly and as sensibly as possible. Understanding the theory of water techniques is essential in implementing an aquatic therapy program. The success of the program, however, will always depend on the pleasure and benefits achieved by the patients. Remember, rheumatic patients most likely will need to modify their previous daily functioning. Patients need to be aware of the long-term ramifications of the disease process and understand how treatment and care may be altered during various stages of exacerbation and remission. Patient education is critical in ensuring individual responsibility for the changes that must be made when not supervised by a professional. Aquatic therapy is a step in molding a positive lifestyle change for the patient. The patient can be encouraged to be fitness oriented and, at the same time, exercise in a manner that is safe, effective, and biomechanically and physiologically sound. The environment, hopefully, also will be conductive to family and social interaction that ultimately encourages the compliance of long-term exercise programs.


Chromosomal-level reference genome of the incense tree Aquilaria sinensis.
Trees in the genus Aquilaria (Thymelaeaceae) are known as lign aloes, and are native to the forests of southeast Asia. Lign aloes produce agarwood as an antimicrobial defence. Agarwood has a long history of cultural and medicinal use, and is of considerable commercial value. However, due to habitat destruction and over collection, lign aloes are threatened in the wild. We present a chromosomal-level assembly for Aquilaria sinensis, a lign aloe endemic to China known as the incense tree, based on Illumina short-read, 10X Genomics linked-read, and Hi-C sequencing data. Our 783.8 Mbp A. sinensis genome assembly is of high physical contiguity, with a scaffold N50 of 87.6 Mbp, and high completeness, with a 95.8% BUSCO score for eudicotyledon genes. We include 17 transcriptomes from various plant tissues, providing a total of 35,965 gene models. We reveal the first complete set of genes involved in sesquiterpenoid production, plant defence, and agarwood production for the genus Aquilaria, including genes involved in the biosynthesis of sesquiterpenoids via the mevalonic acid (MVA), 1-deoxy-D-xylulose-5-phosphate (DXP), and methylerythritol phosphate (MEP) pathways. We perform a detailed repeat content analysis, revealing that transposable elements account for ~61% of the genome, with major contributions from gypsy-like and copia-like LTR retroelements. We also provide a comparative analysis of repeat content across sequenced species in the order Malvales. Our study reveals the first chromosomal-level genome assembly for a tree in the genus Aquilaria and provides an unprecedented opportunity to address a variety of applied, genomic and evolutionary questions in the Thymelaeaceae more widely.


Defining the safe working zones using the minimally invasive lateral retroperitoneal transpsoas approach: an anatomical study.
The lateral retroperitoneal transpsoas approach is being increasingly employed to treat various spinal disorders. The minimally invasive blunt retroperitoneal and transpsoas dissection poses a risk of injury to major nervous structures. The addition of electrophysiological monitoring potentially decreases the risk of injury to the lumbar plexus. With respect to the use of the direct transpsoas approach, however, there is sparse knowledge regarding the relationship between the retroperitoneum/psoas muscle and the lumbar plexus at each lumbar segment. The authors undertook this anatomical cadaveric dissection study to define the anatomical safe zones relative to the disc spaces for prevention of nerve injuries during the lateral retroperitoneal transpsoas approach. Twenty lumbar segments were dissected and studied. The relationship between the retroperitoneum, psoas muscle, and the lumbar plexus was analyzed. The area between the anterior and posterior edges of the vertebral body (VB) was divided into 4 equal zones. Radiopaque markers were placed in each disc space at the midpoint of Zone III (middle posterior quarter). At each segment, the psoas muscle, lumbar plexus, and nerve roots were dissected. The distribution of the lumbar plexus with reference to the markers at each lumbar segment was analyzed. All parts of the lumbar plexus, including nerve roots, were found within the substance of the psoas muscle dorsal to the posterior fourth of the VB (Zone IV). No Zone III marker was posterior to any part of the lumbar plexus with the exception of the genitofemoral nerve. The genitofemoral nerve travels obliquely in the substance of the psoas muscle from its origin to its innervations. It emerges superficially and anterior from the medial border of the psoas at the L3-4 level and courses along the anterior medial fourth of the L-4 and L-5 VBs (Zone I). The nerves of the plexus that originate at the upper lumbar segments emerge from the lateral border of the psoas major and cross obliquely into the retroperitoneum in front of the quadratus lumborum and the iliacus muscles to the iliac crest. With respect to prevention of direct nerve injury, the safe anatomical zones at the disc spaces from L1-2 to L3-4 are at the middle posterior quarter of the VB (midpoint of Zone III) and the safe anatomical zone at the L4-5 disc space is at the midpoint of the VB (Zone II-Zone III demarcation). There is risk of direct injury to the genitofemoral nerve in Zone II at the L2-3 space and in Zone I at the lower lumbar levels L3-4 and L4-5. There is also a potential risk of injury to the ilioinguinal, iliohypogastric, and lateral femoral cutaneous nerves in the retroperitoneal space where they travel obliquely, inferiorly, and anteriorly to the reach the iliac crest and the abdominal wall.


Hyperglycemia-Driven Inhibition of AMP-Activated Protein Kinase α2 Induces Diabetic Cardiomyopathy by Promoting Mitochondria-Associated Endoplasmic Reticulum Membranes In Vivo.
Fundc1 (FUN14 domain containing 1), an outer mitochondrial membrane protein, is important for mitophagy and mitochondria-associated endoplasmic reticulum membranes (MAMs). The roles of Fundc1 and MAMs in diabetic hearts remain unknown. The aims of this study, therefore, were to determine whether the diabetes mellitus-induced Fundc1 expression could increase MAM formation, and whether disruption of MAM formation improves diabetic cardiac function. Levels of FUNDC1 were examined in the hearts from diabetic patients and nondiabetic donors. Levels of Fundc1-induced MAMs and mitochondrial and heart function were examined in mouse neonatal cardiomyocytes exposed to high glucose (HG, 30 mmol/L d-glucose for 48 hours), and in streptozotocin-treated cardiac-specific Fundc1 knockout mice and cardiac-specific Fundc1 knockout diabetic Akita mice, as well. FUNDC1 levels were significantly elevated in cardiac tissues from diabetic patients in comparison with those from nondiabetic donors. In cultured mouse neonatal cardiomyocytes, HG conditions increased levels of Fundc1, the inositol 1,4,5-trisphosphate type 2 receptor (Ip3r2), and MAMs. Genetic downregulation of either Fundc1 or Ip3r2 inhibited MAM formation, reduced endoplasmic reticulum-mitochondrial Ca2+ flux, and improved mitochondrial function in HG-treated cardiomyocytes. Consistently, adenoviral overexpression of Fundc1 promoted MAM formation, mitochondrial Ca2+ increase, and mitochondrial dysfunction in cardiomyocytes exposed to normal glucose (5.5 mmol/L d-glucose). In comparison with nondiabetic controls, levels of Fundc1, Ip3r2, and MAMs were significantly increased in hearts from streptozotocin-treated mice and Akita mice. Furthermore, in comparison with control hearts, diabetes mellitus markedly increased coimmunoprecipitation of Fundc1 and Ip3r2. The binding of Fundc1 to Ip3r2 inhibits Ip3r2 ubiquitination and proteasome-mediated degradation. Cardiomyocyte-specific Fundc1 deletion ablated diabetes mellitus-induced MAM formation, prevented mitochondrial Ca2+ increase, mitochondrial fragmentation, and apoptosis with improved mitochondrial functional capacity and cardiac function. In mouse neonatal cardiomyocytes, HG suppressed AMP-activated protein kinase activity. Furthermore, in cardiomyocytes of Prkaa2 knockout mice, expression of Fundc1, MAM formation, and mitochondrial Ca2+ levels were significantly increased. Finally, adenoviral overexpression of a constitutively active mutant AMP-activated protein kinase ablated HG-induced MAM formation and mitochondrial dysfunction. We conclude that diabetes mellitus suppresses AMP-activated protein kinase, initiating Fundc1-mediated MAM formation, mitochondrial dysfunction, and cardiomyopathy, suggesting that AMP-activated protein kinase-induced Fundc1 suppression is a valid target to treat diabetic cardiomyopathy.


Auditory symmetry analysis.
The study of biological symmetry continues to be an important and active area of research, yet in the hearing sciences there are no established quantitative methods for measuring auditory asymmetries and dissimilarities in threshold tuning curves (i.e. audiograms). Using a paired design and adopting methods from the analysis of fluctuating asymmetry, we describe methods for auditory researchers interested in delineating auditory asymmetries and comparing tuning curves, behavioral or neural. We illustrate the methods using audiograms of the prothoracic T-cell interneuron in a nocturnal katydid (Neoconocephalus ensiger). The results show that 87-92 % of T-cells had right-minus-left threshold asymmetries no larger than expected from measurement error alone. Thus, apart from small random fluctuating asymmetries, T-cell pairs in N. ensiger showed no sensory bias and were bilaterally symmetrical from 5 to 100 kHz. The sensitivity of the methods for detecting tuning curve dissimilarities was confirmed in a sound lateralization paradigm by comparing the 'symmetry' (i.e. similarity) of T-cell tuning curves measured at 0 degrees stimulation with tuning curves measured at 90 degrees stimulation for the same T-cell. The results show that T-cell thresholds measured frontally (0 degrees ) were significantly higher than those measured laterally (90 degrees ), particularly for ultrasonic frequencies. Statistically, the directional shift (increase) in auditory thresholds was detected as a directional asymmetry in T-cell tuning, whose origin and functional significance to an insect behaving normally are discussed. The paper discusses practical considerations for detecting auditory asymmetries and tuning curve dissimilarities in general, and closes by questioning the relevance of auditory symmetry for sound localization in both vertebrates and insects.


Intracranial hemangiopericytomas: MR and CT features.
To describe the MR and CT imaging features of hemangiopericytoma and to identify the characteristics that might distinguish them from meningioma. We retrospectively reviewed the CT and MR findings in 34 pathologically proved cases of hemangiopericytoma. We evaluated the size, shape, and location of the tumor; the presence of hydrocephalus, edema, and mass effect; the type of dural attachment (broad-based or narrow-based) and bone changes (erosion, hyperostosis); and the tumor's density, signal, and contrast-enhancement characteristics. Thirty of 34 tumors were 4 cm or more in greatest dimension, 32 were lobular, and only seven were in the posterior fossa. Hydrocephalus was present in 18, edema in 30, and mass effect in 33. Twenty-three had broad-based dural attachment and 11 had narrow-based attachment. All 26 unenhanced CT scans showed hyperdense tumors; 19 were heterogeneous and seven homogeneous. All 27 contrast-enhanced CT scans showed enhancement; 17 were heterogeneous and 10 homogeneous. Bone erosion was present in 17 of 29 hemangiopericytomas imaged with CT. None had hyperostosis or tumor calcifications. On T1-weighted MR images, 13 of 17 tumors were isointense with cortical gray matter; on T2-weighted image, 10 of 17 were isointense. All 14 tumors imaged with contrast enhanced T1-weighted MR imaging showed enhancement, and 13 of these were heterogeneous; eight of the 14 had a "dural tail" sign. Intracranial hemangiopericytomas are multilobulated, extraaxial tumors, sometimes associated with narrow-based dural attachment and bone erosion. Unlike with meningiomas, hyperostosis and intratumoral calcification are not present.


Cystathionine beta synthase expression in mouse retina.
Abstract Purpose: Cystathionine β-synthase (CBS), a key enzyme in the transsulfuration metabolic pathway, converts homocysteine to cystathionine, which is converted to cysteine required for the synthesis of major retinal antioxidant glutathione (GSH). Enzyme activity assays suggest that CBS is present in human and pig retina, however recent studies reported that CBS is not expressed in mouse retina. We found this species difference puzzling. Given the plethora of studies using mouse retina as a model system, coupled with the importance of GSH in retina, we investigated CBS expression in mouse retina at the molecular and cell biological level. Wildtype (WT) mice or mice lacking the gene encoding CBS (cbs(-)(/)(-)) were used in these studies. RNA and protein were isolated from retinas and liver (positive control) for the analysis of cbs gene expression by RT-PCR and CBS protein expression by Western blotting, respectively. CBS was analyzed by immunofluorescence in retinal cryosections and primary retinal cells (ganglion, Müller, retinal pigment epithelial). CBS enzyme activity was measured in primary Müller cells. RT-PCR revealed robust cbs expression in WT liver, brain and retina. Western blotting detected CBS in retina, brain and liver of WT mice, but not in cbs(-)(/)(-) mice liver. In immunohistochemical studies, CBS was present abundantly in the ganglion cell layer of retina; it was detected also in primary isolations of Müller, RPE and ganglion cells. CBS activity was detected in Müller cells by fluorescent detection of H2S. We have compelling molecular evidence that CBS is expressed in mouse retina at the gene and protein level. Our immunofluorescence data suggest that it is present in several retinal cell types and the data from the enzyme activity assay suggest activity in Müller cells. These findings set the stage to investigate the role of CBS and the transsulfuration pathway in the generation of GSH in mouse retina.


Hook-up of GluA2, GRIP and liprin-alpha for cholinergic muscarinic receptor-dependent LTD in the hippocampus.
The molecular mechanism underlying muscarinic acetylcholine receptor-dependent LTD (mAChR-LTD) in the hippocampus is less studied. In a recent study, a novel mechanism is described. The induction of mAChR-LTD required the activation of protein tyrosine phosphatase (PTP), and the expression was mediated by AMPA receptor endocytosis via interactions between GluA2, GRIP and liprin-alpha. The hook-up of these proteins may result in the recruitment of leukocyte common antigen-related receptor (LAR), a PTP that is known to be involved in AMPA receptor trafficking. Interestingly, the similar molecular interaction cannot be applied to mGluR-LTD, despite the fact that the same G-protein involved in LTD is activated by both mAChR and mGluR. This discovery provides key molecular insights for cholinergic dependent cognitive function, and mAChR-LTD can serve as a useful cellular model for studying the roles of cholinergic mechanism in learning and memory.


[Gastrointestinal stromal tumor (GIST): case report].
The authors report a case of a male patient in his forties with progressive abdominal pain associated with weight loss, dyspnea, and edema of the inferior limbs, culminating in a surgical acute abdomen. A segmental enterectomy containing a lesion of about 10 cm in diameter was performed. It was later confirmed, by means of immuno-histochemistry, as being a Gastrointestinal Stromal Tumor of high biological aggressiveness. Etiology, diagnosis, classification, prognosis and therapeutic with Imatinib Mesylate-STI-571 (Glivec®-Novartis) are hence discussed.


Oxidized low-density lipoprotein induces cytoskeletal disorganization in smooth muscle cells.
Vascular smooth muscle cells in atherosclerotic vessels proliferate and change from a contractile to a synthetic phenotype. To determine whether oxidized low-density lipoprotein (oxLDL) is involved in this transformation, we chronically incubated cultured smooth muscle cells with native and oxidized LDL. Western blot analysis detected a decrease in actin and myosin content in treated cells. This was dependent on the time and concentration of oxLDL employed. Confocal microscopic images of cells immunostained for smooth muscle-specific alpha-actin and myosin showed a normal, elongated alignment of myofilaments in cells after incubation with native LDL. Surprisingly, when the cells were treated with oxLDL, actin and myosin filaments underwent a striking process of disorganization and accumulation into ball-shaped aggregates. These changes were dependent on the duration and concentration of oxLDL employed. Our results demonstrate that oxLDL has the capacity to decrease the content of myofilaments in smooth muscle cells. The loss in myosin and actin protein may be associated with an unusual formation of large cellular aggregates that appear to be in the process of being expelled from the cell.


Resistant Hypertension, Time-Updated Blood Pressure Values and Renal Outcome in Type 2 Diabetes Mellitus.
Apparent treatment resistant hypertension (aTRH) is highly prevalent in patients with type 2 diabetes mellitus (T2D) and entails worse cardiovascular prognosis. The impact of aTRH and long-term achievement of recommended blood pressure (BP) values on renal outcome remains largely unknown. We assessed the role of aTRH and BP on the development of chronic kidney disease in patients with T2D and hypertension in real-life clinical practice. Clinical records from a total of 29 923 patients with T2D and hypertension, with normal baseline estimated glomerular filtration rate and regular visits during a 4-year follow-up, were retrieved and analyzed. The association between time-updated BP control (ie, 75% of visits with BP <140/90 mm Hg) and the occurrence of estimated glomerular filtration rate <60 and/or a reduction ≥30% from baseline was assessed. At baseline, 17% of patients had aTRH. Over the 4-year follow-up, 19% developed low estimated glomerular filtration rate and 12% an estimated glomerular filtration rate reduction ≥30% from baseline. Patients with aTRH showed an increased risk of developing both renal outcomes (adjusted odds ratio, 1.31 and 1.43; P<0.001 respectively), as compared with those with non-aTRH. No association was found between BP control and renal outcomes in non-aTRH, whereas in aTRH, BP control was associated with a 30% (P=0.036) greater risk of developing the renal end points. ATRH entails a worse renal prognosis in T2D with hypertension. BP control is not associated with a more-favorable renal outcome in aTRH. The relationship between time-updated BP and renal function seems to be J-shaped, with optimal systolic BP values between 120 and 140 mm Hg.


Effect of Inhaled Nitric Oxide on Survival Without Bronchopulmonary Dysplasia in Preterm Infants: A Randomized Clinical Trial.
Bronchopulmonary dysplasia (BPD) occurs in approximately 40% of infants born at younger than 30 weeks' gestation and is associated with adverse pulmonary and neurodevelopmental outcomes. To test whether administration of inhaled nitric oxide to preterm infants requiring positive pressure respiratory support on postnatal days 5 to 14 improves the rate of survival without BPD. This intent-to-treat study was a randomized clinical trial performed at 33 US and Canadian neonatal intensive care units. Participants included 451 neonates younger than 30 weeks' gestation with birth weight less than 1250 g receiving mechanical ventilation or positive pressure respiratory support on postnatal days 5 to 14. Enrollment spanned from December 23, 2009, to April 23, 2012, and neurodevelopmental outcome studies were completed by April 4, 2014. Placebo (nitrogen) or inhaled nitric oxide initiated at 20 ppm was decreased to 10 ppm between 72 and 96 hours after starting treatment and then to 5 ppm on day 10 or 11. Infants remained on the 5-ppm dose until completion of therapy (24 days). The primary outcome was the rate of survival without BPD at 36 weeks' postmenstrual age (PMA). Secondary outcomes included BPD severity, postnatal corticosteroid use, respiratory support, survival, and neurodevelopmental outcomes at 18 to 24 months' PMA. In total, 222 infants (52.3% male [n = 116]) received placebo, and 229 infants (50.2% male [n = 115]) received inhaled nitric oxide. Their mean (SD) gestation was 25.6 (1.5) vs 25.6 (1.4) weeks, and their mean (SD) birth weight was 750 (164) vs 724 (160) g. Survival without BPD at 36 weeks' PMA was similar between the placebo and inhaled nitric oxide groups (31.5% [n = 70] vs 34.9% [n = 80]) (odds ratio, 1.17; 95% CI, 0.79-1.73). Rates for severe BPD (26.6% [55 of 207] vs 20.5% [43 of 210]) and postnatal corticosteroid use for BPD (41.0% [91 of 222] vs 41.5% [95 of 229]) and the mean (SD) days of positive pressure respiratory support (55 [40] vs 54 [42]), oxygen therapy (88 [41] vs 91 [59]), and hospitalization (105 [37] vs 108 [54]) were equivalent between the 2 groups. No differences in the incidence of common morbidities were observed. Respiratory outcomes on discharge to home, at 1 year, and at age 18 to 24 months' PMA and neurodevelopmental assessments at 18 to 24 months' PMA did not differ between groups. Inhaled nitric oxide, initiated at 20 ppm on postnatal days 5 to 14 to high-risk preterm infants and continued for 24 days, appears to be safe but did not improve survival without BPD at 36 weeks' PMA or respiratory and neurodevelopmental outcomes at 18 to 24 months' PMA. clinicaltrials.gov Identifier: NCT00931632.


HMG-1 as regulatory trans-acting protein in the acute phase-induced expression of the rat liver haptoglobin gene.
Expression of the haptoglobin (Hp) gene is liver specific and acute phase (AP) responsive. It was previously shown that transcriptional induction process of the rat Hp gene during turpentine induced AP response has been mediated by the liver nucleoprotein p29 which was shown to be homologous to the HMG-1 chromatin-associated protein. The results presented in this report offered further evidence for the existence of structural and functional similarities between these two proteins implicating an involvement of HMG-1 in the regulation of the rat Hp gene transcription. By DNA binding assays we found the HMG-1 binding sites in the rat Hp gene cis-regulatory subelements A and C and revealed an increase in its DNA-binding after induction of AP response. In view of our previous and here shown data we assume that this increase could be a consequence of AP-induced release of HMG-1 from the chromatin and subsequent increase in its nuclear amount.


Metformin extends C. elegans lifespan through lysosomal pathway.
Metformin, a widely used first-line drug for treatment of type 2 diabetes (T2D), has been shown to extend lifespan and delay the onset of age-related diseases. However, its primary locus of action remains unclear. Using a pure in vitro reconstitution system, we demonstrate that metformin acts through the v-ATPase-Ragulator lysosomal pathway to coordinate mTORC1 and AMPK, two hubs governing metabolic programs. We further show in Caenorhabditis elegans that both v-ATPase-mediated TORC1 inhibition and v-ATPase-AXIN/LKB1-mediated AMPK activation contribute to the lifespan extension effect of metformin. Elucidating the molecular mechanism of metformin regulated healthspan extension will boost its therapeutic application in the treatment of human aging and age-related diseases.


Aging, encoding specificity, and memory change in the Double Memory Test.
Aged and young adults were tested by category cued recall after learning with category cues (CCR) or with item cues (ICR). CCR was about twice ICR for both aged and young adults. The aged recalled less than the young and did not benefit as much from greater encoding specificity and deeper processing in CCR. ICR and CCR were correlated, so that expected CCR can be predicted from ICR. The regression of CCR on ICR was linear for young adults, but was piecewise linear for the aged, showing that the relationship between ICR and CCR was not uniform for the aged adults. Lower than expected CCR by a subset of aged without clinical dementia may be a sign of preclinical dementia.


A framework to explore the knowledge structure of multidisciplinary research fields.
Understanding emerging areas of a multidisciplinary research field is crucial for researchers, policymakers and other stakeholders. For them a knowledge structure based on longitudinal bibliographic data can be an effective instrument. But with the vast amount of available online information it is often hard to understand the knowledge structure for data. In this paper, we present a novel approach for retrieving online bibliographic data and propose a framework for exploring knowledge structure. We also present several longitudinal analyses to interpret and visualize the last 20 years of published obesity research data.


Transposition of a gene encoding OXA-2 beta-lactamase.
A bla gene encoding OXA-2 beta-lactamase has been transposed from the Salmonella typhimurium R plasmid R1767. This transposable element which was designated Tn2410 encoded sulphonamide and mercury resistance in addition to the bla gene. It had a size of 18.5 kb and appeared to be flanked by small inverted repeats. Restriction enzyme analysis resulted in a detailed map of Tn2410, which showed a high degree of similarity with the published map of Tn2603, a transposon encoding OXA-1 beta-lactamase. The ampicillin and sulphonamide resistance genes on Tn2410 were mapped in a cluster on the region between the centre and the righ end of the map.


Differences in spike train variability in rat vasopressin and oxytocin neurons and their relationship to synaptic activity.
The firing pattern of magnocellular neurosecretory neurons is intimately related to hormone release, but the relative contribution of synaptic versus intrinsic factors to the temporal dispersion of spikes is unknown. In the present study, we examined the firing patterns of vasopressin (VP) and oxytocin (OT) supraoptic neurons in coronal slices from virgin female rats, with and without blockade of inhibitory and excitatory synaptic currents. Inhibitory postsynaptic currents (IPSCs) were twice as prevalent as their excitatory counterparts (EPSCs), and both were more prevalent in OT compared with VP neurons. Oxytocin neurons fired more slowly and irregularly than VP neurons near threshold. Blockade of Cl- currents (including tonic and synaptic currents) with picrotoxin reduced interspike interval (ISI) variability of continuously firing OT and VP neurons without altering input resistance or firing rate. Blockade of EPSCs did not affect firing pattern. Phasic bursting neurons (putative VP neurons) were inconsistently affected by broad synaptic blockade, suggesting that intrinsic factors may dominate the ISI distribution during this mode in the slice. Specific blockade of synaptic IPSCs with gabazine also reduced ISI variability, but only in OT neurons. In all cases, the effect of inhibitory blockade on firing pattern was independent of any consistent change in input resistance or firing rate. Since the great majority of IPSCs are randomly distributed, miniature events (mIPSCs) in the coronal slice, these findings imply that even mIPSCs can impart irregularity to the firing pattern of OT neurons in particular, and could be important in regulating spike patterning in vivo. For example, the increased firing variability that precedes bursting in OT neurons during lactation could be related to significant changes in synaptic activity.


Chronic second-by-second measures of L-glutamate in the central nervous system of freely moving rats.
l-glutamate (Glu) is the main excitatory neurotransmitter in the central nervous system (CNS) and is associated with motor behavior and sensory perception. While microdialysis methods have been used to record tonic levels of Glu, little is known about the more rapid changes in Glu signals that may be observed in awake rats. We have reported acute recording methods using enzyme-based microelectrode arrays (MEA) with fast response time and low detection levels of Glu in anesthetized animals with minimal interference. The current paper concerns modification of the MEA design to allow for reliable measures in the brain of conscious rats. In this study, we characterized the effects of chronic implantation of the MEA into the brains of rats. We were capable of measuring Glu levels for 7 days without loss of sensitivity. We performed studies of tail-pinch induced stress, which caused a robust biphasic increase in Glu. Histological data show chronic implantation of the MEAs caused minimal injury to the CNS. Taken together, our data show that chronic recordings of tonic and phasic Glu can be carried out in awake rats for up to 17 days in vivo allowing longer term studies of Glu regulation in behaving rats.


[Is there a risk of noise-induced hearing loss in automobile drivers and in automobile sport racing?].
Professional racing drivers are exposed to extreme noise pollution by their high-capacity cars. For the purpose of evaluating the emissive noise of racing-cars, noise-level measurements on race-courses were undertaken. As a result noise-levels up to 130 dB (A) for the outer noises and 125 dB (A) for the inner region of the car were measured. Moreover, eighteen professional racing drivers as well as eleven employees, working in the pit, underwent audiometric investigations. Only one of the racing drivers showed noise deafness. This result can be explained by the short periods of exposure to the noise, which is 150-180 hours every year, and the regular wearing of ear-plugs. The employees working in the pits, however, showed distinct hearing impairments, explained above all, by their activities at the motor-test blocks. Incidentally this paper also deals with the noise sources of vehicles and the origin of noise deafness. There is no risk of noise deafness for this group of persons.


Union Following Biological and Rigid Fixations of Distal Tibia Extra-articular Fractures.
Distal tibia fractures are among the most common bony injuries, with a significant rate of nonunion and delayed union. There are multiple methods for the management of distal tibia fractures. Among the plating methods, there are bridge plating and compression plating techniques. There is still a lack of evidence about whether one method has a higher rate of union than the other. The present study aimed to assess the union rate of extra-articular distal tibia fractures using biological fixation with bridge plating and rigid fixation with compression plating. This retrospective analysis was performed on 41 adult patients with distal tibia fractures. The subjects were divided into two groups based on the fixation method, namely bridge plating and compression plating. Baseline characteristics, fracture characteristics, and union status were analyzed and compared in this study. Baseline and fracture characteristics were similar between the groups. Only higher translation in any planes was noted in the bridge plating group (2.80±3.04 mm; P<0.001). As for union status, the rates of the union during 3 months and delayed/no union were similar between the two groups (P=0.18). During a 6-month follow-up, 92% and 93.8% of the patients achieved union in the bridge plating and compression plating groups, respectively. Rates of delayed union and nonunion are similar regarding extra-articular distal tibia fractures treated with either bridge plating or compression plating.


Nox isoforms in vascular pathophysiology: insights from transgenic and knockout mouse models.
Elevated reactive oxygen species (ROS) formation in the vascular wall is a key feature of cardiovascular diseases and a likely contributor to oxidative stress, endothelial dysfunction and vascular inflammation. The NADPH oxidases are a family of ROS generating enzymes, of which four members (Nox1, Nox2, Nox4 and Nox5) are expressed in blood vessels. Numerous studies have demonstrated that expression and activity of at least two isoforms of NADPH oxidase - Nox1 and Nox2 - are up-regulated in animal models of hypertension, diabetes and atherosclerosis. However, these observations are merely suggestive of a role for NADPH oxidases in vessel pathology and by no means establish cause and effect. Furthermore, questions surrounding the specificity of current pharmacological inhibitors of NADPH oxidase mean that findings obtained with these compounds must be viewed with caution. Here, we review the literature on studies utilising genetically-modified mouse strains to investigate the roles of NADPH oxidases in experimental models of vascular disease. While several studies on transgenic over-expressing or knockout mice support roles for Nox1- and/or Nox2-containing oxidases as sources of excessive vascular ROS production and causes of endothelial dysfunction in hypertension, atherosclerosis and diabetes, there are still no published reports on the effects of genetic modification of Nox4 or Nox5 in vascular or indeed any other contexts. Further understanding of the roles of specific isoforms of NADPH oxidase in vascular (patho)physiology should provide direction for future programs aimed at developing selective inhibitors of these enzymes as novel therapeutics in cardiovascular disease.


Effect of nano- and micro-scale topological features on alignment of muscle cells and commitment of myogenic differentiation.
Skeletal muscle injury can lead to severe motor deficits that adversely affect movement and quality of life. Current surgical treatments for skeletal muscle are hindered by the poor formation of organized myotube bundles at the wound site. Tissue-engineered skeletal muscle constructs to date have been unable to generate high degrees of myotube density and alignment. Generating a suitable in vitro tissue-engineered skeletal muscle construct requires the design of a scaffold that recapitulates the structural combination of nanoscale collagen fibrils and aligned microscale basal lamina tracks present in the native extracellular matrix (ECM). We hypothesized that a 3D aligned tubular porous scaffold containing aligned nanofibers inside the pores can mimic the native muscle tissue environment. We constructed a laminar section of the hypothesized scaffold with aligned chitosan-PCL nanofibers arranged co-axially with the aligned microscale chitosan scaffold bands to mimic the required myogenic environment. A 6-day study of C2C12 mouse myoblast cells cultured on this hybrid scaffold indicated that the nanofibers and scaffold bands in the scaffold played a synergetic role in directing cell orientation, interaction, migration and organization. Our results showed that aligned nanofibers mediated cell alignment and the aligned scaffold bands induced the formation of a more compact assembly of myotube cells as compared to various control substrates including chitosan films, nanofibers, and chitosan bands. The expression levels of both early and late-stage myogenic differentiation genes associated with myogenin and myosin heavy chain, respectively, were higher on the hybrid substrate than on control substrates. Our study suggests that the combination of nano and microscale topological features in the ECM can direct myogenic differentiation, and the hybrid material has the potential to improve the outcome of skeletal tissue engineering.


Activation of muscarinic acetylcholine receptors inhibits cell cycle progression of small cell lung carcinoma.
We previously reported that activation of muscarinic acetylcholine receptors (mAChR) of M3 subtype causes hydrolysis of phosphoinositides and inhibits voltage-gated Ca2+ channel activity in small cell lung carcinoma (SCLC) cells. We now report that mAChR activation causes exponentially growing SCLC cells to arrest in S and G2/M phases of the cell cycle, concomitant with a decrease in DNA synthesis. Cell cycle progression and DNA synthesis resume when mAChR are down-regulated. In serum-starved SCLC cells, mAChR activation inhibits DNA synthesis induced by serum, bombesin, insulin, or insulin-like growth factor-I. The finding that DNA synthesis is inhibited even when mAChR are activated after exposure of cells to growth factors indicates that decreased signal transduction by growth factor receptors is not the mechanism of mAChR-mediated growth inhibition. Our data suggest that mAChR activation disrupts a common event that is induced by different growth factors and is fundamental for cell cycle progression.


Environmental Enrichment in the 21st Century.
More than a quarter of a century has elapsed since the Animal Welfare Act mandated that research facilities develop and follow a plan to promote the psychological well-being of captive primates. Since passage of this law, considerable effort and resources have been directed to designing environmental enrichment strategies in an effort to improve animal welfare. These plans typically consist of environmental enrichment and socialization efforts. While environmental enhancement has undergone a great deal of improvement in the past 25 years, it should be viewed as a continual work in progress, which takes advantage of emergent and future technologies. In this review, we discuss the objectives of the environmental enhancement plan along with relevant outcome measures, as well as ongoing challenges, costs, and benefits. We then review various enrichment strategies and assess their efficacy in meeting goals and objectives. Finally, we look forward to consider what the future might hold for environmental enrichment of nonhuman primates used in research.


A Case Report of Refractory Postherpetic Neuralgia After Ramsay Hunt Syndrome Treated With Tympanic Nerve Neurectomy.
Ramsay Hunt syndrome is a facial nerve palsy that arises from herpes zoster infection. In rare cases, postherpetic neuralgia is a complication following Ramsay Hunt syndrome. Pain management to address postherpetic neuralgia includes facial nerve blocks, medications such as gabapentin, carbamazepine and botulinum toxin injections, and pulsed radiofrequency. Despite the reported benefits for patients with glossopharyngeal nerve pain, neurectomy as a treatment has rarely been described. A 45-year-old patient visited our ENT clinic for chronic right-sided facial, ear, and jaw pain that persisted for 9 years following the development of Ramsay Hunt syndrome. She trialed multiple medications including gabapentin, carbamazepine, and botulinum toxin injections with minimal relief to her symptoms. The patient underwent a diagnostic myringotomy with topical application of lidocaine to the tympanic nerve. This resulted in temporary relief of her pain until the effects of the lidocaine subsided. The patient was subsequently offered lysis of the right tympanic nerve for more definitive management. The patient experienced significant pain reduction after the right tympanic neurectomy procedure. Chronic postherpetic neuralgia following Ramsay Hunt syndrome can cause significant impairment in a patient's quality of life. For patients with ear pain refractory to conservative management, a tympanic neurectomy can be considered.


Relationship between night shift work, eating habits and BMI among nurses in Lebanon.
The objective of this cross-sectional study was to evaluate the relationships between night shift work, eating habits and body mass index (BMI) among Lebanese nurses. A total of 307 nurses were randomly selected from five hospitals located in Beirut. Data about demographic and professional characteristics, anthropometric measures, dietary habits and intakes were collected through a validated questionnaire. To study the relationship between night shift work, eating habits and BMI, chi-square test, t-test and logistic regressions were used. The majority of nurses (78. 2%) had irregular meals timing with a significant decrease in the number of complete meals consumed during the day and an increase in the number of snacks consumed during night (p < 0. 05). The most consumed snacks during night shifts were sweets and potato chips. The findings highlighted that BMI and waist circumference significantly increased with the number of years of work (r = 0.175; p < 0.05) and the cumulative number of night shifts hours over the entire work history (r = 0.135/p < 0. 05). Night shift work is positively associated with abnormal eating patterns and BMI among Lebanese nurses. However the increase in BMI is not related to eating habits.


Assessing quality of life in people with HIV in Spain: psychometric testing of the Spanish version of WHOQOL-HIV-BREF.
The assessment of health-related quality of life (HRQoL) in people living with HIV (PLHIV) has become crucial to evidence-based practice. The goals of this study are to analyze the psychometric properties and evidence of the validity of the Spanish version of WHOQOL-HIV-BREF in a sample of PLHIV in Spain and to examine the more impaired HRQoL facets and dimensions and identify the PLHIV who show the most vulnerable profile. A total of 1462 PLHIV participated in an observational cross-sectional ex-post-facto study. Data were collected at 33 Spanish sites through an online survey. In addition to measuring HRQoL, the study used other tools to measure treatment adherence (CEAT-VIH 2.0 version), psychological well-being (GHQ-12) and HIV-related stigma (HSSS). Cronbach's alpha, first- and second-order confirmatory factor analysis (CFA), the Pearson coefficient and one-way ANOVA were used to evaluate reliability, construct validity and concurrent and known-group validity, respectively. Differences according to the socio-demographic and epidemiological profiles of participants were analyzed. First- and second-order CFAs confirmed a six-domain first-order structure of the Spanish version of WHOQOL-HIV-BREF and one second-order factor related to overall HRQoL with an acceptable fit to the data, although some minor changes would improve it. The six-domain structure showed an acceptable internal consistency (Cronbach's alpha ranged from .61 to .81). Significant moderate to large correlations between domains and overall HRQoL, adherence, psychological well-being and negative self-image were found. Significant differences were found according to participants' self-reported CD4+ cell count in several HRQoL facets and domains. Being female, heterosexual, having low socio-economic and educational statuses, having acquired HIV through an unsafe injection and living more years with HIV were related to poorer HRQoL. PLHIV older than 50 presented lower scores in 19 HRQoL facets. This study demonstrates that the Spanish version of the WHOQOL-HIV-BREF is a valid instrument. It also presents the most recent data about HRQoL in PLHIV in Spain with the largest sample to date.


Identification of ABCC3 and its isoforms as potential biomarker in hepatocellular carcinoma.
Liver diseases preceding the occurrence of hepatocellular carcinoma (HCC) play a crucial role in the progression and establishment of HCC, a malignancy ranked as the third deadliest cancer worldwide. Late diagnosis, alongside ineffective treatment, leads patients to a poor survival rate. This scenario argues for seeking novel alternatives for detecting liver alterations preceding the early occurrence of HCC. Experimental studies have reported that ABCC3 protein increases within HCC tumors but not in adjacent tissue. Therefore, we analyzed ABCC3 expression in public databases and investigated the presence of ABCC3 and its isoforms in plasma, urine and its release in extracellular vesicles (EVs) cargo from patients bearing cirrhosis and HCC. The UALCAN and GEPIA databases were used to analyze the expression of ABCC3 in HCC. The results were validated in a case-control study including 41 individuals bearing cirrhosis and HCC, and the levels of ABCC3 in plasma and urine samples, as well as EVs, were analyzed by ELISA and western blot. Our data showed that ABCC3 expression was higher in HCC tissues than in normal tissues and correlated with HCC grade and stage. ABCC3 protein levels were highly increased in both plasma and urine and correlated with liver disease progression and severity. The isoforms MRP3A and MRP3B of ABCC3 were significantly increased in both EVs and plasma/urine of patients bearing HCC. ABCC3 expression gradually increases in HCC tissues, and its protein levels are increased in both plasma and urine of patients with cirrhosis and HCC. MRP3A and MRP3B isoforms have the potential to be prognostic biomarkers of HCC.


Examining weight suppression as a predictor of eating disorder symptom trajectories in anorexia nervosa.
Research in individuals with bulimia nervosa has highlighted the clinical significance of weight suppression (WS), defined as the difference between one's highest and current weight. More recently, studies have suggested that WS also may play a role in symptom maintenance and weight gain during treatment in anorexia nervosa (AN) and that the influence of WS on AN outcomes may depend on an individual's body mass index (BMI). However, no study has investigated whether WS or the interaction between WS and BMI is associated with the longer-term course of eating pathology following treatment discharge in patients with AN. The current study examined a sample of females with AN (N = 180) who completed interviews and self-report questionnaires at discharge from intensive treatment and at 3, 6, and 12-months after discharge. Latent growth curve models tested whether WS, BMI, or the WS by BMI interaction significantly predicted the trajectory of eating disorder symptoms (i.e., Eating Disorder Examination global score, BMI, frequency of loss of control eating, frequency of purging) over the year following discharge. WS at discharge predicted change in BMI, and the interaction between WS and BMI predicted growth in eating disorder severity and purging frequency over time. Neither WS nor its interaction with BMI predicted growth in loss of control eating frequency. Results provide further support for the clinical significance of WS in AN symptom maintenance, but suggest that the influence of WS likely depends on an individual's BMI as well as the outcome being measured. © 2016 Wiley Periodicals, Inc.(Int J Eat Disord 2016; 49:753-763).


A simplified headspace biochemical oxygen demand test protocol based on oxygen measurements using a fiber optic probe.
Batch respirometric tests have many advantages over the conventional biochemical oxygen demand (BOD) method for analysis of wastewaters, including the use of nondiluted samples, a more rapid exertion of oxygen demand, and reduced sample preparation time. The headspace biochemical oxygen demand (HBOD) test can be used to obtain oxygen demands in 2 or 3 days that can predict 5-day biochemical oxygen demand (BOD5) results. The main disadvantage of the HBOD and other respirometric tests has been the lack of a simple and direct method to measure oxygen concentrations in the gas phase. The recent commercial production of a new type of fiber optic oxygen probe, however, provides a method to eliminate this disadvantage. This fiber optic probe, referred to here as the HBOD probe, was tested to see if it could be used in HBOD tests. Gas-phase oxygen measurements made with the HBOD probe took only a few seconds and were not significantly different from those made using a gas chromatograph (t test: n = 15, R2 = 0.9995, p < 0.001). In field tests using the HBOD probe procedure, the probe greatly reduced sample analysis time compared with previous HBOD and BOD protocols and produced more precise results than the BOD test for wastewater samples from two treatment plants (University Area Joint Authority [UAJA] Wastewater Treatment Plant in University Park, Pennsylvania, and The Pennsylvania State University [PSU] Wastewater Treatment Plant in University Park). Headspace biochemical oxygen demand measurements on UAJA primary clarifier effluent were 59.9 +/- 2.4% after 2 days (HBOD2) and 73.0 +/- 3.1% after 3 days (HBOD) of BOD, values, indicating that BOD5 values could be predicted by multiplying HBOD2 values by 1.67 +/- 0.07 or HBOD3 by 1.37 +/- 0.06. Similarly, tests using PSU wastewater samples could be used to provide BOD5 estimates by multiplying the HBOD2 by 1.24 +/- 0.04 or by multiplying the HBOD3 by 0.97 +/- 0.03. These results indicate that the HBOD fiber optic probe can be used to obtain reliable oxygen demands in batch respirometric tests such as the HBOD test.


A retrospective comparison of water births and conventional vaginal deliveries.
The aim of this study was to document the practice of water births and compare their outcome and safety with normal vaginal deliveries. A retrospective case-control study was conducted over a five year period from 1989 to 1994 at the Maternity Unit, Rochford Hospital, Southend, UK. Three hundred and one women electing for water births were compared with the same number of age and parity matched low risk women having conventional vaginal deliveries. Length of labour; analgesia requirements; apgar scores; maternal complications including perineal trauma, postpartum haemorrhages, infections; fetal and neonatal complications including shoulder dystocias; admissions to the Special Care Baby Unit, and infections were noted. Primigravidae having water births had shorter first and second stages of labour compared with controls (P<0.05 and P<0.005 respectively), reducing the total time spent in labour by 90 min (95% confidence interval 31 to 148). All women having water births had reduced analgesia requirements. No analgesia was required by 38% (95% confidence interval 23.5 to 36.3, P<0.0001) and 1.3% requested opiates compared to 56% of the controls (95% confidence interval 46. 3 to 58.1, P<0.0001). Primigravidae having water births had less perineal trauma (P<0.05). Overall the episiotomy rate was 5 times greater in the control group (95% confidence interval 15 to 26.2, P<0.0001), but more women having water births had perineal tears (95% confidence interval 6.6 to 22.6, P<0.001). There were twice as many third degree tears, post partum haemorrhages and admissions to the Special Care Baby Unit in the controls, although these differences were not significant. Apgar scores were comparable in both groups. There were no neonatal infections or neonatal deaths in the study. This study suffers from many of the methodological problems inherent in investigation of uncommon modes of delivery. However, we conclude that water births in low risk women delivered by experienced professionals are as safe as normal vaginal deliveries. Labouring and delivering in water is associated with a reduction in length of labour and perineal trauma for primigravidae, and a reduction in analgesia requirements for all women.


Absence of naloxone sensitivity in obese humans.
Studies in rodents suggest the possibility of an association between elevated endogenous opiate activity and overeating and obesity. One measure of elevated opiate activity is sensitivity to the opiate antagonist naloxone. Seven massively obese human subjects showed no subjective or physiological sensitivity to large intravenous doses of naloxone. This finding fails to support a relationship between elevated endorphin activity and human obesity.


In vitro injury of porcine aortic endothelial cells by very-low-density lipoproteins from diabetic rat serum.
Primary cultures of porcine aortic endothelial cells were used to detect injurious agents in diabetic rat serum. Media containing normal or diabetic serum (streptozotocin-induced) were incubated with subconfluent primary cultures of endothelial cells. Cells exposed to 17% diabetic serum were severely contracted and permeable to trypan blue after 18 h. Cultures in normal serum contained significantly more protein (P less than 0.005) than cultures in diabetic serum after 1 day. When normal and diabetic serum were mixed in different proportions and added to cells at 17% total serum concentration, a 50% reduction from growth in normal serum occurred at a ratio of 1 part diabetic serum to 9 parts normal serum. The toxicity of diabetic serum was not altered by heat inactivation. Administration of insulin to diabetic rats reversed both cytotoxicity and elevated triglyceride levels. Serum triglyceride levels were inversely correlated with endothelial cell growth (r = -0.878, P less than 0.001). In vitro addition of up to 1 U/ml insulin to cultures in diabetic serum did not alter toxicity. Ultracentrifugal flotation of diabetic serum demonstrated the toxic substance to be entirely localized in the very-low-density lipoprotein fraction (d less than 1.006 g/ml). A pool of d greater than 1.006 fractions from diabetic serum supported growth equivalent to normal serum. Diabetic serum contains a substance localized in the very-low-density lipoprotein fraction that is severely toxic to aortic endothelial cells in vitro. Very-low-density lipoprotein injury of endothelial cells may play an important role in the development of arterial vascular disease in insulin-dependent diabetes.


Nanostructured Biomass Based Carbon Materials from Beer Lees for Hydrogen Storage.
The present work describes the preparation of carbon materials from beer lees and their hydrogen adsorption abilities. Activated carbons (ACs) from beer lees were prepared through chemical activation using potassium hydroxide as an activating agent. The low temperature nitrogen adsorption isotherm studies on prepared ACs were conducted at 77 K to determine their physical properties and adsorption energy distribution. The beer lees based carbons have energetically heterogeneous surfaces and high surface area ranging from 1927-2408 m2/g. ACs prepared in this study show the gravimetric hydrogen adsorption capacity of 2.43-2.92 wt% depending on their physical properties.


The importance of clinical experience for mental health nursing - part 2: relationships between undergraduate nursing students' attitudes, preparedness, and satisfaction.
Clinical experience is consistently emphasized in research findings as the primary influence in encouraging more positive attitudes to mental health nursing. The available research, however, presents two major limitations. First, it does not measure the specific factors that might contribute to a positive clinical experience. Second, it does not consider the relationship between clinical experience and attitudes towards people experiencing a mental illness or towards mental health nursing. This is the second of a two-part paper presenting findings from a statewide survey of undergraduate nursing students in Victoria. A pre-/post-test design was used to measure the impact of clinical experience on the following subscales: (i) attitudes towards people experiencing a mental illness; (ii) attitudes toward mental health nursing; and (iii) preparedness for mental health practice. Subscale (iv) satisfaction with clinical experience was also measured in the post-test phase. The findings demonstrated an improvement on all three subscales in the post-test phase and a high level of satisfaction with clinical experience. Furthermore, a relationship between all four subscales was evident.


microRNA control of cell-cell signaling during development and disease.
MicroRNAs (miRNAs) are critical post-transcriptional regulators that may collectively control a majority of animal genes. With thousands of miRNAs identified, a pressing challenge is now to understand their specific biological activities. Many predicted miRNA:target interactions only subtly alter gene activity. It has consequently not been trivial to deduce how miRNAs are relevant to phenotype, and by extension, relevant to disease. We note that the major signal transduction cascades that control animal development are highly dose-sensitive and frequently altered in human disorders. On this basis, we hypothesize that developmental cell signaling pathways represent prime candidates for mediating some of the major phenotypic consequences of miRNA deregulation, especially under gain-of-function conditions. This perspective reviews the evidence for miRNA targeting of the major signaling pathways, and discusses its implications for how aberrant miRNA activity might underlie human disease and cancer.


[Status of the hemostatic system in patients with chronic lung diseases].
Blood rheologic properties and homeostasis system were comprehensively examined in 23 patients with fibrous-cavernous pulmonary tuberculosis and 58 patients with various chronic nonspecific pulmonary diseases complicated by respiratory failure. The patients were found to have signs of erythrocyte edema, their more rapid depletion, lower resistance and higher aggregation which was accompanied by increased hematocrit and normal erythrocyte count. The thromboelastograms showed that all all phases of blood coagulation were shortened and fibrinolysis was deeply depressed. There was an increase in activated partial thromboplastin and thrombin time, a reduction in the values of the prothrombin indices and antithrombin III activity and higher heparin levels. The fibrinogen level was either normal or reduced despite an increase in other acute phase reactants, followed by the appearance of large amounts of blocked fibrinogen in the blood. Analysis of the findings enabled one to regard a combination of the above changes as signs of the latent DIC syndrome. Determination of fibrin and fibrinogen degradation products in a deep and long-term inhibition of fibrinolysis loses its diagnostic significance.


Phytochemistry, anti-inflammatory and analgesic activities of the aqueous leaf extract of Lagenaria breviflora (Cucurbitaceae) in laboratory animals.
The plant, and especially the fruit of Lagenaria breviflora is widely used in folklore medicine in West Africa as a herbal remedy for the treatment of human measles, digestive disorders, and as wound antiseptics (e.g. umbilical incision wound), while livestock farmers use it for Newcastle disease and coccidiosis treatment in various animal species, especially poultry. The purpose of this study was to contribute with new information on this plant leaves extract effect, as few studies have considered their effects. We collected fresh leaves of Lagenaria breviflora from the school farm of the University of Ibadan, Nigeria in May 2011. Dried leaves were ground and a 200g sample was used to prepare the extract. The grounded leaves material was allowed to shake in 1000mL distilled water for 48h, in an orbital shaker at room temperature of 24 degreeC. The obtained extract was filtered and concentrated to dryness under reduced pressure at 40 degreeC, and the thick solution was lyophilized, for a final extract yield of 12.6%. Standard phytochemical methods were used to test the presence of saponins, alkaloids, tannins, anthraquinones, cardiac glycosides, cyanogenetic glycosides and flavonoids. The anti-inflammatory activity of the aqueous leaf extract of the plant was assessed using carrageenan-induced paw edema and histamine-induced paw edema in rats. The analgesic effect was determined using the acetic acid writhing method as well as formalin test in mice. Our results showed that the extract at 100 and 200mg/ kg body weight significantly reduced the formation of the oedema induced by carrageenan and histamine. In the acetic acid-induced writhing model, the extract showed a good analgesic effect characterized by reduction in the number of writhes when compared to the control. The extract caused dose-dependent decrease of licking time and licking frequency in rats injected with 2.5% formalin, signifying its analgesic effect. These results were however less than those of indomethacin, the reference drug used in this study. Since the plant extract reduced significantly the formation of oedema induced by carrageenan and histamine, as well as reduced the number of writhes in acetic acid-induced writhing models and dose-dependent decrease of licking frequency in rats injected with 2.5% formalin, the results have validated the basis for the traditional use of Lagenaria breviflora against inflamed purulent wounds, swellings, and bruises seen in some infectious diseases such as New Castle disease.


Posterior Contraction Rates of the Phylogenetic Indian Buffet Processes.
By expressing prior distributions as general stochastic processes, nonparametric Bayesian methods provide a flexible way to incorporate prior knowledge and constrain the latent structure in statistical inference. The Indian buffet process (IBP) is such an example that can be used to define a prior distribution on infinite binary features, where the exchangeability among subjects is assumed. The phylogenetic Indian buffet process (pIBP), a derivative of IBP, enables the modeling of non-exchangeability among subjects through a stochastic process on a rooted tree, which is similar to that used in phylogenetics, to describe relationships among the subjects. In this paper, we study the theoretical properties of IBP and pIBP under a binary factor model. We establish the posterior contraction rates for both IBP and pIBP and substantiate the theoretical results through simulation studies. This is the first work addressing the frequentist property of the posterior behaviors of IBP and pIBP. We also demonstrated its practical usefulness by applying pIBP prior to a real data example arising in the field of cancer genomics where the exchangeability among subjects is violated.


Sarcomere shortening in pressure overload hypertrophy.
Sarcomere shortening during contraction was measured by using laser diffraction, in thin, rabbit right ventricular (RV) trabeculae from normal hearts (N) (n = 5) and from hearts subjected to RV pressure overload by pulmonary banding (H) (n = 5). Banding resulted in substantial RV hypertrophy after 2 wk. Hypertrophied preparations had the same resting muscle length (H = 3.15 +/- 0.29 mm) and resting sarcomere lengths (H = 2.16 +/- 0.005 micron) as the normal preparations (3.10 +/- 0.37 mm, 2.16 +/- 0.008 micron, respectively). Total tension at the peak of isometric twitches was the same as normal in the hypertrophied muscles (N = 8.06 +/- 1.20, H = 8.51 +/- 1.95 g/mm2). However, the amount of auxotonic sarcomere shortening was much less than normal in the hypertrophied preparations (N = 0.39 +/- 0.028, H = 0.19 +/- 0.034 micron; P less than 0.001). In isotonic contractions in which the ratio of muscle shortening to resting muscle length was the same in both the normal and hypertrophied muscles (ratio of 0.05 in both groups), the extent of sarcomere shortening relative to resting sarcomere length was less in the hypertrophied muscles than in the normal preparations (N = 0.14 +/- 0.01), H = 0.07 +/- 0.01; P less than 0.01). Series elasticity was the same as normal in the hypertrophied muscle P less than 0.05). Less auxotonic sarcomere shortening for a given level of isometric tension development and less isotonic sarcomere shortening per unit muscle shortening indicate that there is less than normal work per sarcomere during contraction in hypertrophied myocardium. These findings may have important implications for intracellular compensatory adaptation in pressure overload cardiac hypertrophy.


HER2 assessment on core biopsy specimens using monoclonal antibody CB11 accurately determines HER2 status in breast carcinoma.
HER2 status is a prognostic factor in breast carcinoma and predicts response to trastuzumab therapy. Trastuzumab is effective in the neoadjuvant, adjuvant and advanced disease settings. Knowledge of HER2 status early in the diagnostic and therapeutic process is vital for treatment planning. HER2 analysis is usually carried out by immunohistochemistry or fluorescence in situ hybridization (FISH). The aim of this study was to establish whether HER2 immunohistochemistry using monoclonal antibody CB11 and carried out on the initial diagnostic core biopsy specimen accurately predicts HER2 amplification status. This is the largest study to date in which HER2 protein expression has been assessed by CB11 immunohistochemistry on the diagnostic core biopsy specimen and correlated with the result of FISH. Using FISH as the definitive HER2 status, we studied 568 invasive breast cancers using CB11 immunohistochemistry on core biopsy. This analysis had a sensitivity of 99.4%, specificity of 93.9%, false-positive frequency of 3.9% and false-negative frequency of 1.1%. These data are as good as those obtained from analysing resection specimens alone in UK national reference centres. CB11 immunohistochemistry accurately predicts HER2 amplification status and can be reliably carried out on core biopsy specimens of breast carcinoma.


NO(2) quantum yields from ultraviolet photodissociation of methyl and isopropyl nitrate.
Quantum yields, Phi(NO(2)), are reported for the NO(2) formation channel (RO + NO(2)) following photodissociation of methyl and isopropyl nitrate (CH(3)ONO(2) and C(3)H(7)ONO(2)) at the tropospherically relevant wavelengths of 308-320 nm. Measurements were made using ultra-violet (UV) laser absorption and cavity ring down spectroscopy (CRDS) detection of the NO(2) photoproducts. Analysis of CRDS data to obtain NO(2) quantum yields required account to be taken of the spatially inhomogeneous NO(2) distribution resulting from photolysis with a laser beam with a Gaussian intensity profile. Photodissociation quantum yields were measured to be unity (with <or=10% uncertainties (2SD)) for both methyl and isopropyl nitrate at wavelengths of 308, 315 and 320 nm in the presence of N(2) bath gas at pressures up to 700 Torr, and at a temperature of 294 K. An apparent decrease in the NO(2) yields, observed at bath gas pressures below 500 Torr, may result from photochemical formation of internally excited NO(2) which is not thermalized by collisions on the timescale of the measurement, or from diffusion of the photoproducts. Quantum yield values from the current work are in agreement with previously reported values at 308 and 248 nm photo-excitation wavelengths.


[Laparoscopy in penetrating abdominal injuries].
An experience with treatment of 138 patients with penetrating punctured-incised wounds of the abdominal cavity has shown advantages of laparoscopy in diagnostics of the character of injuries of internals. Laparoscopy used in cases with difficult diagnosis allowed to give up operative interventions in 53.8% of patients. High diagnostic value and relative safety of laparoscopy make it possible to widely use this method in wounds of the abdomen.


Summary of Future Developments.
Endometriosis is a chronic disease with the potential to cause devastating clinical manifestations such as infertility and chronic pelvic disease. Current treatment is limited to surgical intervention and pharmacologic therapy targeting estrogen and progesterone to suppress ectopic endometrial tissue proliferation. Undesired side effects and contraindications to the use of hormonal medications may reduce treatment options. As the pathogenesis of endometriosis continues to be investigated, new therapies will emerge. The identification of genes involved in the development of endometriosis may allow targeted therapy to prevent or cure disease. In addition, increasing knowledge of the inflammatory pathways that promote ectopic endometrial growth will permit the development of pharmacologic agents to manipulate these signaling pathways. Utilization of selective progesterone receptor modulators, aromatase inhibitors, and modern gonadotropin-releasing hormone antagonists provide more options to manage disease when traditional treatment fails. Individualized therapeutic strategies will soon be a reality as a greater understanding of endometriosis is obtained through the investigation of genomic studies, molecular pathways, and environmental influences.


Immune signatures predict prognosis in localized cancer.
The host immune response can impact cancer growth, prognosis, and response to therapy. In colorectal cancer, the presence of cells involved with T-cell-mediated adaptive immunity predicts survival better than the current staging method. We used the expression of genes recently associated with host immune responses (T(H1)-mediated adaptive immunity, inflammation, and immune suppression) to perform hierarchical clustering of multiple large cohorts of cancer specimens to determine if immune-related gene expression resulted in clinical significant groupings of tumors. Microarray data from prostate cancer (n = 79), breast cancer (n = 132), lung cancer (n = 84), glioblastoma multiforme (n = 120), and lymphoma (n = 127) were analyzed. Among adenocarcinomas, the T(H1)-mediated adaptive immunity genes were consistently associated with better prognosis, while genes associated with inflammation and immune suppression were variably associated with outcome. Specifically, increased expression of the T(H1)-mediated adaptive immunity genes was associated with good prognosis in breast cancer patients under 45 years of age (p = .04, hazard ratio [HR] = 0.42) and in prostate cancer patients (p = .03, HR = 0.36) but not in lung cancer patients (p = 0.45, HR = 1.37). In lymphoma, patients with increased expression of inflammation and immune suppression genes had better prognosis than those expressing the T(H1)-mediated adaptive immunity genes (p = .01, HR = 0.43) and in glioblastoma multiforme, the expression of inflammation genes conferred improved prognosis than those expressing immune suppression genes (p = 0.05, HR = 0.62). In aggregate, the gene expression signatures implicating specific components of the immune response hold prognostic import across solid tumors.


Single-case experimental designs: a systematic review of published research and current standards.
This article systematically reviews the research design and methodological characteristics of single-case experimental design (SCED) research published in peer-reviewed journals between 2000 and 2010. SCEDs provide researchers with a flexible and viable alternative to group designs with large sample sizes. However, methodological challenges have precluded widespread implementation and acceptance of the SCED as a viable complementary methodology to the predominant group design. This article includes a description of the research design, measurement, and analysis domains distinctive to the SCED; a discussion of the results within the framework of contemporary standards and guidelines in the field; and a presentation of updated benchmarks for key characteristics (e.g., baseline sampling, method of analysis), and overall, it provides researchers and reviewers with a resource for conducting and evaluating SCED research. The results of the systematic review of 409 studies suggest that recently published SCED research is largely in accordance with contemporary criteria for experimental quality. Analytic method emerged as an area of discord. Comparison of the findings of this review with historical estimates of the use of statistical analysis indicates an upward trend, but visual analysis remains the most common analytic method and also garners the most support among those entities providing SCED standards. Although consensus exists along key dimensions of single-case research design, and researchers appear to be practicing within these parameters, there remains a need for further evaluation of assessment and sampling techniques and data analytic methods.


Experience with rubber band ligation of hemorrhoids in northern Nigeria.
Treatment of hemorrhoids in Nigeria is usually done by the traditional open method that requires hospital admission; anesthesia and is associated with high morbidity. Rubber band ligation is a suitable alternative to open hemorrhoidectomy and has the potential to reduce the need for hospital admission. This was a prospective analysis of consecutive patients presenting with hemorrhoids that were suitable for surgical treatment to the Jos University Teaching Hospital and the Federal Medical Centre Gombe from January 2008 to December 2010 (24 months). A total of 232 rubber band ligations were performed on 40 patients whose ages ranged from 20 to 54 years with a mean age of 37.1 ± 12.2 years. There were 24 males and 16 females (M:F::2:3). Thirty-nine patients (97.5%) were cured of their symptoms following the procedure, and 1 patient (2.5%) had severe pain as complication of the treatment. Another patient had recurrence that was treated by repeat rubber band ligation. We conclude that rubber band ligation is a safe and reliable way for outpatient treatment of hemorrhoids in Nigeria.


Treatment of spontaneous leukemia in AKR mice with chemotherapy, immunotherapy, or interferon.
AKR mice are genetically destined to develop Gross (RNA) virus-induced lymphatic leukemia. Leukemic AKR mice treated with combination vincristine, cyclophosphamide (Cytoxan), and 1-(2-chloroethyl)-3-(trans-4-methylcyclohexyl)-1-nitrosourea sustained a 180% increase of life-span. Combination chemotherapy plus immunization with neuraminidase-treated allogeneic (Gross virus-induced) G2G leukemic cells intradermally resulted in 35% of animals surviving beyond 150 days without evidence of the disease. It is significant that allogeneic E2G leukemic cells as immunogen were as effective in prolonging the life-span of the immunized leukemic AKR mice as were syngeneic leukemic thymocytes. Virazole (1-beta-D-ribofuranosyl-1,2,4-triazole-3-carboxamide), an antiviral compound, alone showed no apparent antitumor effect. However, in experiments in which the clinically diagnosed leukemic AKR mice received a combination of cytoreductive therapy [vincristine plus prednisone or, more effectively, vincristine, Cytoxan plus 1-(2-chloroethyl)-3-(trans-4-methylcyclohexyl)-1-nitrosourea, followed by Virazole], there was a noticeable reduction of the viral titer, a delay in the reappearance of viable clonogenic cells, and an increase in the survival time for the leukemic AKR mice as compared to those receiving cytoreductive therapy alone. The effectiveness of purified mouse interferon in AKR mice was also examined. The decrease in the viral titer of animals that received interferon treatment was markedly greater than of those receiving a combination of cytoreductive therapy with Virazole or immunotherapy. The administration of mouse interferon had a direct effect on the appearance of the spontaneous leukemia in AKR mice. The median life-span of the control animals was 36 weeks, whereas 45% of the AKR mice treated with five doses of 5 X 10(4) units of interferon are still alive at 54 weeks of age. Thus, interferon not only reduces the Gross murine leukemia virus titer in the chronically infected AKR mice but also significantly delays the appearance of the primary lymphoma.


Fatty acids and postprandial inflammation.
Postprandial inflammation is an independent factor in evaluating food quality in addition to the well known parameters of nutritional value, caloric content and amount of carbohydrates, fats, proteins, minerals and vitamins. Among the latter, the quality and quantity of fatty acids in a meal is a major determinant of the magnitude of postprandial inflammation. Purpose of this review is to describe this exciting new area of research and its repercussions in the way we, the consumers, and the food industry evaluate the type and quantity of fat in food. A number of, by now classical, epidemiologic studies have documented a strong association between the type of fatty acids consumed and the incidence of cardiovascular diseases. Recently published reports suggest that the adverse effect of dietary fatty acids on cardiovascular health depends on their postprandial modification of innate immunity ending in the so-called 'postprandial metabolic inflammation'. The quantity of fat and its qualitative characteristics such as the percentage of saturated fatty acids and the ratio of n-3 to n-6 polyunsaturated fatty acids (PUFAs) in a meal have emerged as major determinants of the magnitude of postprandial inflammatory response. In this review, we will summarize all experimental evidence suggesting that the two families of PUFA appear to have antagonistic effects on postprandial inflammation, n-3 PUFA being anti-inflammatory while n-6 PUFA proinflammatory.


Scatter dose for wedged fields.
The behaviour of scatter dose in 4 and 8 MV wedged x-ray beams has been studied by calculating scatter-to-primary dose ratios (SPR) and comparing these with SPR for non-wedged beams. On the central axis the SPR for wedged and non-wedged beams differ only by a few per cent, a difference which increases slightly with wedge angle and field size. In other points within the field the differences are larger but generally less than 3% of the total dose on the central axis at the same depth. The product rule for points that do not lie in a principal plane is valid within the same limits as for non-wedged beams.


Pediatric Psoriasis: From New Insights into Pathogenesis to Updates on Treatment.
Psoriasis is a chronic inflammatory systemic disease primarily affecting the skin, but which often involves considerable comorbidities as well. One-third of psoriasis cases start during childhood. In pediatric psoriasis, an association with several medical comorbidities is also indicated. Furthermore, because of its chronic nature and frequent relapses, psoriatic patients tend to require long-term treatment and experience negative impacts on their quality of life. Considering the different clinical characteristics of pediatric psoriasis, it has recently been presented that the pathogenesis of pediatric psoriasis is distinct from adult psoriasis. Treatment for pediatric psoriasis usually involves the same methods as for adults. However, most treatments in pediatric psoriasis are used off-label and research in this regard is still lacking. Targeted therapies involving newly developed biologics are also increasingly being applied to psoriasis in children. This review summarizes the clinical characteristics of pediatric psoriasis and focuses mainly on the updated concepts of pathogenesis and treatments in pediatric psoriasis. This was undertaken to widen the understanding of these relevant aspects and to provide better management of pediatric psoriasis by clinicians.


[Factors associated with the lifestyle of military police officers].
The scope of this investigation was to analyze the association between lifestyle and socio-demographic and occupational characteristics among military police officers (MPs). This involved a cross-sectional epidemiological study. The sample consisted of 288 MPs within the Police Force of Recife, Pernambuco. The data were collected by means of a semi-structured questionnaire. For the data analysis, IT tools were used (STATA-10.0 and SPSS- 15.0 for Windows) and descriptive statistics procedures, chi-square analysis and regression associations (p < 0.05). Among the lifestyle results, 12% said that they smoked, 10% were classified as cases of suspected excess consumption of alcoholic beverages, 73% were considered to be insufficiently active and 40% admitted they were involved in frequent or occasional conflicts. Age of 39 years or over (RP = 1.39), lower education level (RP = 1.68), the lowest economic level (RP = 1.49) and being in the profession for 18 years or more (RP = 1.49) were associated with lifestyles with greater risk to health (with two or more unhealthy factors). Therefore, promotion and prevention measures should be adopted in order to attempt to reduce the health vulnerabilities of these workers.


Reduced metabolism in brain "control networks" following cocaine-cues exposure in female cocaine abusers.
Gender differences in vulnerability for cocaine addiction have been reported. Though the mechanisms are not understood, here we hypothesize that gender differences in reactivity to conditioned-cues, which contributes to relapse, are involved. To test this we compared brain metabolism (using PET and ¹⁸FDG) between female (n = 10) and male (n = 16) active cocaine abusers when they watched a neutral video (nature scenes) versus a cocaine-cues video. Self-reports of craving increased with the cocaine-cue video but responses did not differ between genders. In contrast, changes in whole brain metabolism with cocaine-cues differed by gender (p<0.05); females significantly decreased metabolism (-8.6%±10) whereas males tended to increase it (+5.5%±18). SPM analysis (Cocaine-cues vs Neutral) in females revealed decreases in frontal, cingulate and parietal cortices, thalamus and midbrain (p<0.001) whereas males showed increases in right inferior frontal gyrus (BA 44/45) (only at p<0.005). The gender-cue interaction showed greater decrements with Cocaine-cues in females than males (p<0.001) in frontal (BA 8, 9, 10), anterior cingulate (BA 24, 32), posterior cingulate (BA 23, 31), inferior parietal (BA 40) and thalamus (dorsomedial nucleus). Females showed greater brain reactivity to cocaine-cues than males but no differences in craving, suggesting that there may be gender differences in response to cues that are not linked with craving but could affect subsequent drug use. Specifically deactivation of brain regions from "control networks" (prefrontal, cingulate, inferior parietal, thalamus) in females could increase their vulnerability to relapse since it would interfere with executive function (cognitive inhibition). This highlights the importance of gender tailored interventions for cocaine addiction.


Evaluation of the effects of strabismus surgery on corneal backward light scattering.
Investigation of the effects of conventional strabismus surgeries on corneal densitometry (CD). Patients who had strabismus surgery between May 2022 and July 2022 were included in the study. CD software with a Pentacam device was used to determine corneal backward light scattering. CD data were analysed preoperatively and 1 month postoperatively. Patients were classified as those who had single muscle and two-muscle surgery. The study included 33 eyes of 28 patients. The mean age of the patients was 20.51 ± 8.22 (5-35) years. Of the eyes, 19 underwent single muscle recession surgery. Two-muscle surgeries (recession and resection combination) were performed in 14 eyes. In the 1st month postoperative, the mean CD value decreased statistically significantly only in the total cornea apical 0-2 mm zone among the layers examined (p = 0.039). There was no significant change in the other layers (p > 0.05 for all). Single-muscle and two-muscle surgery groups were similar in the amount of CD reduction, except for one layer. CD did not change in most of the corneal layers examined in the first month postoperatively. Single muscle and two-muscle horizontal rectus surgeries did not impair corneal clarity in the postoperative 1st month.


Preoperative or postoperative therapy for stage II or III rectal cancer: an updated practice guideline.
Uncertainty remains regarding the optimal therapy for patients with stage II or III rectal cancer. Systematic reviews and practice guidelines on preoperative and postoperative therapy for rectal cancer were published by the Gastrointestinal Cancer Disease Site Group in 2003 and 2000, respectively. The systematic reviews were updated and revised and new recommendations for preoperative and postoperative therapy were developed based on the updated body of evidence. The following research questions were addressed: After appropriate preoperative staging tests, should patients with resectable clinical stage II or III rectal cancer be offered preoperative radiotherapy (with or without chemotherapy)? What is the role of postoperative radiotherapy and/or chemotherapy for patients with resected stage II or III rectal cancer who have not received preoperative radiotherapy, in terms of improving survival and delaying local recurrence? The MEDLINE, EMBASE and Cochrane Library databases, as well as meeting proceedings from the American Society of Clinical Oncology, were searched for reports of randomised controlled trials and meta-analyses comparing preoperative or postoperative therapy with surgery alone or other preoperative or postoperative therapy for stage II or III rectal cancer. The draft practice guideline and systematic reviews were distributed through a mailed survey to 129 health care providers in Ontario for review. Systematic reviews on preoperative and postoperative therapy for rectal cancer were developed. On the basis of the evidence contained in these reviews, the Gastrointestinal Cancer Disease Site Group drafted recommendations. Of the 33 practitioners who responded to the mailed survey, 97% agreed with the draft recommendations as stated, 88% agreed that the report should be approved as a practice guideline and 94% indicated that they were likely to use the guideline in their own practice. Preoperative chemoradiotherapy is preferred, compared with standard fractionation preoperative radiotherapy alone, to decrease local recurrence. Preoperative chemoradiotherapy is also preferred, compared with a postoperative approach, to decrease local recurrence and adverse effects. For patients with relative contraindications to chemotherapy in the preoperative period, an acceptable alternative is preoperative radiotherapy alone followed by surgery. Patients with resected stage II or III rectal cancer who have not received preoperative radiotherapy should be offered postoperative therapy with concurrent chemoradiotherapy plus fluoropyrimidine-based chemotherapy.


Interleukin 2 receptor signaling regulates the perforin gene through signal transducer and activator of transcription (Stat)5 activation of two enhancers.
Optimal T cell differentiation into effector cells with specialized functions requires the participation of cytokine receptor signals. In T helper cells, this process is controlled by chromatin changes and distal and proximal regulatory elements as well as specific transcription factors. Analogous events during cytotoxic T lymphocyte (CTL) differentiation remain to be identified. This process is known, however, to be crucially regulated by interleukin (IL)-2 receptor (R) signals. It is accompanied by the induction of perforin expression via a mechanism that does not entail proximal regulatory elements. In this report, transgenically expressed human perforin gene locus DNAs demonstrate that IL-2R signals target two IL-2-dependent enhancers approximately 15 and 1 kilobase upstream of the promoter. The most distal enhancer may also respond to TCR signals. In transient transfections, both enhancers required two identically spaced Stat-like elements for their activation, which was abolished by expression of a dominant negative signal transducer and activator of transcription (Stat)5 molecule, whereas a constitutively active Stat5 molecule bypassed the requirement for IL-2R signals. These results provide a molecular explanation for the activation of the perforin gene during CTL differentiation and complement the analysis of animals deficient in the activation of the IL-2R Stat signaling pathway by establishing perforin as a target gene.


Animal Orientation Affects Brain Biomechanical Responses to Blast-Wave Exposure.
In this study, we investigated how animal orientation within a shock tube influences the biomechanical responses of the brain and cerebral vasculature of a rat when exposed to a blast wave. Using three-dimensional finite element (FE) models, we computed the biomechanical responses when the rat was exposed to the same blast-wave overpressure (100 kPa) in a prone (P), vertical (V), or head-only (HO) orientation. We validated our model by comparing the model-predicted and the experimentally measured brain pressures at the lateral ventricle. For all three orientations, the maximum difference between the predicted and measured pressures was 11%. Animal orientation markedly influenced the predicted peak pressure at the anterior position along the midsagittal plane of the brain (P = 187 kPa; V = 119 kPa; and HO = 142 kPa). However, the relative differences in the predicted peak pressure between the orientations decreased at the medial (21%) and posterior (7%) positions. In contrast to the pressure, the peak strain in the prone orientation relative to the other orientations at the anterior, medial, and posterior positions was 40-88% lower. Similarly, at these positions, the cerebral vasculature strain in the prone orientation was lower than the strain in the other orientations. These results show that animal orientation in a shock tube influences the biomechanical responses of the brain and the cerebral vasculature of the rat, strongly suggesting that a direct comparison of changes in brain tissue observed from animals exposed at different orientations can lead to incorrect conclusions.