Anaesthetic and cardiorespiratory effects of a constant-rate infusion of alfaxalone in desflurane-anaesthetised sheep.
A prospective, randomised, blinded controlled study was performed to determine the anaesthetic and cardiorespiratory effects of a constant-rate infusion (CRI) of alfaxalone in 12 sheep anaesthetised with desflurane, and undergoing experimental orthopaedic surgery. Sheep were sedated with dexmedetomidine (4 μg/kg, intravenously) and butorphanol (0.3 mg/kg, intravenously). Anaesthesia was induced with alfaxalone (1 mg/kg/minute to effect, intravenously) and maintained with desflurane in oxygen and alfaxalone 0.07 mg/kg/minute or saline for 150 minutes (range 150-166 minutes). The anaesthetic induction dose of alfaxalone, the desflurane expiratory fraction required for anaesthetic maintenance, cardiorespiratory measurements and blood-gases were recorded at predetermined intervals. Quality of sedation, anaesthetic induction and recovery were assessed. The alfaxalone induction dose was 1.7 mg/kg (1.2 to 2.6 mg/kg). The desflurane expiratory fraction was lower (22 per cent) in sheep receiving alfaxalone CRI (P=0). Also, heart rate (P=0), cardiac index (P=0.002), stroke index (P=0) and contractility (P=0) were higher, and systemic vascular resistance (P=0.002) was lower. Although respiratory rate tended to be higher with alfaxalone, there was no difference in PCO2 between the groups. Recovery times were significantly longer in sheep given alfaxalone (25.4 v 9.5 minutes) but recovery quality was similar. Alfaxalone reduced requirements of desflurane and maintained similar cardiorespiratory function, but recovery time was more prolonged.


Technology Acceptance and Usability of the BrainFx SCREEN in Canadian Military Members and Veterans With Posttraumatic Stress Disorder and Mild Traumatic Brain Injury: Mixed Methods UTAUT Study.
Canadian Armed Forces service members (CAF-SMs) and veterans exhibit higher rates of injuries and illnesses, such as posttraumatic stress disorder (PTSD) and traumatic brain injury, which can cause and exacerbate cognitive dysfunction. Computerized neurocognitive assessment tools have demonstrated increased reliability and efficiency compared with traditional cognitive assessment tools. Without assessing the degree of technology acceptance and perceptions of usability to end users, it is difficult to determine whether a technology-based assessment will be used successfully in wider clinical practice. The Unified Theory of Acceptance and Use of Technology model is commonly used to address the technology acceptance and usability of applications in five domains. This study aims to determine the technology acceptance and usability of a neurocognitive assessment tool, which was titled BrainFx SCREEN, among CAF-SMs and veterans with PTSD by using the Unified Theory of Acceptance and Use of Technology model. This mixed methods embedded pilot study included CAF-SMs and veterans (N=21) aged 18-60 years with a diagnosis of PTSD who completed pre- and postquestionnaires on the same day the BrainFx SCREEN was used. A partial least squares structural equation model was used to analyze the questionnaire results. Qualitative data were assessed using thematic analysis. Facilitating conditions, which were the most notable predictors of behavioral intention, increased after using the BrainFx SCREEN, whereas effort expectancy decreased. Performance expectancy, effort expectancy, and social interaction were not factors that could predict behavioral intention. Participants who reported a previous mild traumatic brain injury were significantly more likely to report current symptoms of cognitive impairment. The BrainFx SCREEN is a feasible, usable, and accepted assessment tool for CAF-SMs and veterans who experience PTSD. As military health care systems integrate technological innovations to improve the services and care provided, research must continue to address the acceptability and use of these novel assessments and interventions.


Caiman crocodylus hemoglobin. Complete primary structures of alpha and beta chains; phylogenic and regulatory aspects.
In some reptiles, the hemoglobin oxygen affinity is lowered by CO2 and not by the usual phosphate cofactors. To understand the molecular mechanism of this regulation, Caiman crocodylus hemoglobin's primary structure has been determined. The alignment of the 141 residues of the alpha chain as well as the 146 of the beta chain were obtained by classical method of sequence analysis and are compared with some mammalian, avian, amphibian, and fish hemoglobin chains. Furthermore, from these sequences, it is possible to explain the non-interaction of phosphorylated cofactors with the caiman deoxyhemoglobin on the basis of mutations of the amino acids responsible for their fixation on the beta chain. Among these residues only lysine beta 82 is unchanged. In addition a site has been proposed for the fixation of HCO3- which involves ionic bonds with serine beta 1 and glutamic acid beta 144 (Perutz et al. (1981) Nature 291, 682-684) (1).


Mossy fiber sprouting induced by repeated electroconvulsive shock seizures.
The elicitation of repeated focal seizures (kindling) induces mossy fiber sprouting in the hippocampus of the rat. The present study investigated whether repeated generalized seizures also induce mossy fiber sprouting. Human psychiatric patients receive repeated generalized seizures during electroconvulsive therapy (ECT). Male Long-Evans rats received a course of eight electroconvulsive shock (ECS) seizures administered on a 48-h schedule over a course of 2 1/2 weeks. Control subjects received matched handling, but no stimulation. Fourteen days after the last ECS trial, all subjects were sacrificed and their brains subjected to Timm staining. Cell counts and area measures were also taken in the hilus. Significant sprouting, but not significant cell loss, was seen in the fascia dentata of the subjects that had received ECS.


Effect of the suture technique on postoperative pain, swelling and trismus after removal of lower third molars: A randomized clinical trial.
To evaluate the intensity of pain, swelling and trismus after the removal of impacted lower third molars comparing two different suture techniques of the triangular flap: the complete suture of the distal incision and relieving incision and the partial suture with only one suture knot for closure of the corner of the flap and the closure of the distal incision, without suturing the relieving incision. A prospective, randomized, cross-over clinical trial was conducted in 40 patients aged from 18 to 45 years who underwent surgical extraction of impacted lower third molars at the Department of Oral Surgery in the Odontological Hospital of the University of Barcelona during the year 2011. Patients were randomly divided in 2 groups. Two different techniques (hermetical closure and partial closure of the wound) were performed separated by a one month washout period in each patient. Postoperative pain, swelling and trismus were evaluated prior to the surgical procedure and also at 2 and 7 days postoperatively. No statistically significant differences were observed for pain (p<0.06), trismus (p<0.71) and swelling (p<0.05) between the test and the control group. However, the values of the three parameters related to the test group were lower than those for the control group. Partial closure of the flap without suturing the relieving incision after surgical extraction of lower third molars reduces operating time and it does not produce any postoperative complications compared with complete closure of the wound.


Neurological sequelae of cervical spine trauma.
It is estimated that there will be 5,000 new spinal cord injured patients each year. Prolonged survival has resulted from better understanding of the pathophysiology of cord damage, as well as from the advances in antibiotic and ventilatory therapy. Most well-motivated patients with lesions at or below C5 can attain a level of independence which obviates institutional care. Regional spinal injury centers have done much to increase the survival of and quality of life of cord injured patients. These realities make initial care of patients with acute traumatic lesions of the cervical spine of paramount importance. Neurologic function at both the nerve root and cord levels can be adversely affected by excessive motion of the unstable spine. Early evaluation of X-rays must therefore be carried out in an attempt to determine the stability of the spine.


Natural polyreactive IgA antibodies coat the intestinal microbiota.
Large quantities of immunoglobulin A (IgA) are constitutively secreted by intestinal plasma cells to coat and contain the commensal microbiota, yet the specificity of these antibodies remains elusive. Here we profiled the reactivities of single murine IgA plasma cells by cloning and characterizing large numbers of monoclonal antibodies. IgAs were not specific to individual bacterial taxa but rather polyreactive, with broad reactivity to a diverse, but defined, subset of microbiota. These antibodies arose at low frequencies among naïve B cells and were selected into the IgA repertoire upon recirculation in Peyer's patches. This selection process occurred independent of microbiota or dietary antigens. Furthermore, although some IgAs acquired somatic mutations, these did not substantially influence their reactivity. These findings reveal an endogenous mechanism driving homeostatic production of polyreactive IgAs with innate specificity to microbiota.


Maintaining an Effective Circle: Volunteer Experiences of Operational Aspects of Circles of Support and Accountability.
In Circles of Support and Accountability (CoSA), trained volunteers support an individual convicted for sexual offenses to reintegrate safely into the community. Developed in Canada, CoSA has been established in many jurisdictions with a growing number of volunteers; however, little is known about whether the training and support provided meets volunteer needs. Using a mixed-methods approach, the aim of the present research was to explore New Zealand CoSA volunteer experiences of the training and support they received and their perceptions about what contributed to the effective operation of a circle. In total, 18 volunteers took part in an interview and 23 volunteers completed a questionnaire. The findings found a mixed response to the training and support received, whereby some volunteers thought the training and support was adequate, whereas other felt the training support they received was inadequate. Findings also illustrate that adequate training, having access to a circle coordinator, selecting the right volunteers and core member, clear communication, and setting up boundaries were important factors in maintaining an effective circle. Findings are discussed in terms of implications for the training and support offered to current and future volunteers, as well as for maintaining the effectiveness of future circles.


Effects of animal and soy fats and proteins in the diet on fatty acid concentrations in the serum and skin of dogs.
Growing dogs were fed diets containing soy oil or poultry fat as the main fat source and soybean meal or meat meal as the main protein source to examine the effects of types of dietary fat and protein on fatty acid concentrations in serum and skin and on serum cholesterol concentrations. Dogs fed diets containing soy oil had higher serum linoleic acid concentrations and lower serum oleic acid, arachidonic acid, and cholesterol concentrations than dogs fed diets containing poultry fat. The type of dietary protein had marginal effects on fatty acid concentrations and did not affect serum cholesterol. Similar differences were found in cutaneous fatty acid concentrations, with soy oil-fed dogs having significantly (P < 0.05) higher linoleic acid and lower oleic acid concentrations in their skin than had poultry fat-fed dogs. This study suggested that dietary fat source influences serum and cutaneous fatty acid concentrations and serum cholesterol concentrations in dogs, irrespective of dietary protein source.


Hydrolytically Stable TiIV-Hydrazone-Based Metallodrugs: Protein Interaction and Anticancer Potential.
In this work, three titanium(IV) [TiIV(L1-3)2] (1-3) complexes have been reported using three different tridentate dibasic ONO donor hydrazone ligands, pyridine-4-carboxylic acid (3-ethoxy-2-hydroxybenzylidene)-hydrazide (H2L1), furan-2-carboxylic acid (3-ethoxy-2-hydroxybenzylidene)-hydrazide (H2L2), and thiophene-2-carboxylic acid (3-ethoxy-2-hydroxybenzylidene)-hydrazide (H2L3) tethered with heterocyclic moieties. Elemental analysis, FT-IR, UV-vis, NMR, HR-ESI-MS, and single-crystal X-ray analysis have been used to characterize H2L1-3 and 1-3. In solid structures of 1-3, two ligand molecules with N2O4 donor sets give distorted octahedral geometries to the metal center. The aqueous stability of 1-3 was investigated and well correlated to their perceived pharmacological results. During the investigation, all three complexes were found to be hydrolytically stable in a 90% DMSO-d6/10% D2O (v/v) medium up to 48 h. Furthermore, the interaction of 1-3 with bovine serum albumin (BSA) was tested using fluorescence and absorption techniques. The complexes showed static quenching with a biomolecular quenching constant of Kq ∼ 1013 proposing a high affinity of complexes for BSA. Finally, the anticancer potential of 1-3 was tested against HeLa, A549, and NIH-3T3 cell lines. Among all, 1 with an IC50 value of 11.6 ± 1.1 μM against HeLa cells was found to be the most cytotoxic in the series. Furthermore, it has been found that the compounds induce an apoptotic mode of cell death, which is confirmed by the live cell confocal microscopy and flow cytometry techniques.


gamma-Aminobutyric acid (GABA) and hepatic encephalopathy: testing the validity of electroencephalographic evidence of the GABA hypothesis.
Some GABA-ergic drugs are known to produce electroencephalographic and behavioral signs of inhibition as well as alterations of the visual evoked potential (VEP) similar in shape and parameters to those in experimental fulminant hepatic failure. These findings, along with a number of biochemical findings, were considered to support the theory attributing hepatic encephalopathy to enhanced GABA-ergic transmission. The present review demonstrates that it is uncertain whether electrographic correlates of experimental encephalopathy can be attributed to faulty GABA-ergic mechanisms; nor it is clear whether drug-induced alterations of electrocortical potentials and those recorded in acute hepatic failure share a common pathogenesis. Special emphasis is put on findings with visual evoked potentials altered by drugs acting at GABA/benzodiazepine receptors to show the diversity of changes associated with the activity of the GABA system. Attention is called to the fact that brain GABA increase as a mechanism of hepatic encephalopathy was discussed without specifying the nature and anatomical location of allegedly impaired neural circuits utilizing the neurotransmitter.


Delineation of the arginine- and tetrahydrobiopterin-binding sites of neuronal nitric oxide synthase.
Nitric oxide synthase (EC 18.104.22.168) catalyses the conversion of arginine, NADPH and oxygen to nitric oxide and citrulline, using haem, (6R)-5,6,7,8-tetrahydro-l-biopterin (tetrahydrobiopterin), calmodulin, FAD and FMN as cofactors. The enzyme consists of a central calmodulin-binding sequence flanked on the N-terminal side by a haem-binding region that contains the arginine and tetrahydrobiopterin sites and on the C-terminal side by a region homologous with NADPH:cytochrome P-450 reductase. By using domain boundaries defined by limited proteolysis of full-length enzyme, recombinant haem-binding regions of rat brain neuronal nitric oxide synthase were expressed and purified. Two proteins were made in high yield: one, corresponding to residues 221-724, contained bound haem and tetrahydrobiopterin and was able to bind Nomega-nitro-l-arginine (nitroarginine) or arginine; the other, containing residues 350-724, contained bound haem but was unable to bind tetrahydrobiopterin, nitroarginine or arginine. These results showed that rat brain neuronal nitric oxide synthase contains a critical determinant for arginine/tetrahydrobiopterin binding between residues 221 and 350. Limited proteolysis with chymotrypsin of the former protein resulted in a new species with an N-terminal residue 275 that retained the ability to bind nitroarginine, further defining the critical region for arginine binding as being between 275 and 350. Comparison of the sequences of nitric oxide synthase and the tetrahydrobiopterin-requiring amino acid hydroxylases revealed a similarity in the region between residues 470 and 600, suggesting that this might represent the core region of the pterin-binding site. The stoichiometries of binding of substrate and cofactors to the recombinant domains were not more than 0.5 mol/mol of monomer, suggesting that there might be a single high-affinity site per dimer.


Ventriculoperitoneal shunt insertion in human immunodeficiency virus infected adults: a systematic review and meta-analysis.
Hydrocephalus is a common, life threatening complication of human immunodeficiency virus (HIV)-related central nervous system opportunistic infection which can be treated by insertion of a ventriculoperitoneal shunt (VPS). In HIV-infected patients there is concern that VPS might be associated with unacceptably high mortality. To identify prognostic indicators, we aimed to compare survival and clinical outcome following VPS placement between all studied causes of hydrocephalus in HIV infected patients. The following electronic databases were searched: The Cochrane Central Register of Controlled Trials, MEDLINE (PubMed), EMBASE, CINAHL Plus, LILACS, Research Registry, the metaRegister of Controlled Trials, ClinicalTrials.gov, African Journals Online, and the OpenGrey database. We included observational studies of HIV-infected patients treated with VPS which reported of survival or clinical outcome. Data was extracted using standardised proformas. Risk of bias was assessed using validated domain-based tools. Seven Hunderd twenty-three unique study records were screened. Nine observational studies were included. Three included a total of 75 patients with tuberculous meningitis (TBM) and six included a total of 49 patients with cryptococcal meningitis (CM). All of the CM and two of the TBM studies were of weak quality. One of the TBM studies was of moderate quality. One-month mortality ranged from 62.5-100% for CM and 33.3-61.9% for TBM. These pooled data were of low to very-low quality and was inadequate to support meta-analysis between aetiologies. Pooling of results from two studies with a total of 77 participants indicated that HIV-infected patients with TBM had higher risk of one-month mortality compared with HIV non-infected controls (odds ratio 3.03; 95% confidence-interval 1.13-8.12; p = 0.03). The evidence base is currently inadequate to inform prognostication in VPS insertion in HIV-infected patients. A population-based prospective cohort study is required to address this, in the first instance.


Pattern evoked potentials from the cat's retina.
We have studied electroretinograms (ERG) in the cat using phase-reversed sinusoidal gratings as a stimulus. Our purpose was to characterize response properties of this type of ERG. One basic question we addressed was whether the response to a grating stimulus is actually pattern specific. For the purpose of comparison, we used the same stimulus to investigate mass potentials from the lateral geniculate nucleus (LGN) and the visual cortex. The pattern ERG consists mainly of a vitreous negative after potential peaking shortly (120-200 ms) after reversal of the pattern. There is a notable absence in the pattern ERG of a b-wave that, however, can be elicited by a step increase of luminance over a uniform field. Pattern ERG amplitudes decrease monotonicaly with increasing spatial frequency and show no low-frequency attenuation when the pattern is phase reversed in square-wave fashion. This is markedly different than evoked potentials from the LGN and visual cortex that show band-pass characteristics. On the other hand, sinusoidal phase reversal reveals a clear attenuation of the pattern ERG amplitude at low spatial frequencies, whereas this type of stimulation produces very poor responses from LGN and visual cortex. The low spatial-frequency attenuation in the pattern ERG shows that the generating mechanism involves lateral interactions. There is thus a clear pattern-specific component in the pattern ERG. The pattern ERG has a surprisingly high contrast threshold relative to those estimated from cortical and LGN evoked potentials. Above threshold, pattern ERG response amplitude increases rapidly with contrast, but it often shows saturation at high contrast levels. These saturation points are generally high when contrast thresholds are high so that the rising portion of the contrast-response functions have fairly uniform slopes. Contrast-response curves from the LGN and cortical potentials are quite different from those for the retina in that amplitudes increase approximately linearly with log contrast over a 2-log-unit range (1 to 100%).


Ultrasound versus MRI: is there a difference in measurements of the fetal lateral ventricles?
To evaluate whether fetal brain lateral ventricle measurements differ between ultrasound (US) and MRI. We evaluated 115 fetuses with US and MRI performed within 24 h of each other. Ventricular measurements were performed in the axial plane at the level of the atria for both modalities and the right and left ventricles were evaluated separately. We compared mean measurements; mean differences, association with gestational age (GA), association with the presence of a brain anomaly, and agreement between MRI and US. The LV and RV were measured in 65 and 64 cases, respectively. LV and RV size estimates were significantly greater when measured by MRI compared with US (p < 0.001). Therefore, LV and RV were 0.87 mm and 0.89 mm larger in MRI versus US, respectively. Neither GA at measurement or presence/absence of a brain anomaly was significantly associated with differences in measurements. When comparing the agreement between the US and MRI measurements for ventriculomegaly; the kappa level of agreement for the LV and RV was 0.74 for each. MRI measurements of ventricles are significantly larger than the measurements by US by ∼1 mm. There is a good level of agreement when categorizing by normal, mild and severe ventriculomegaly.


The effects of the Balanced Budget Act of 1997 on home health and hospice in older adult cancer patients.
Home health and hospice services can constitute important elements in the continuum of care for older adults diagnosed with cancer. The Balanced Budget Act (BBA) of 1997 included provisions affecting those services. The first objective of this study is to assess the effect of the BBA of 1997 on home health and hospice service utilization in older cancer patients. The second objective is to estimate the effect of the BBA of 1997 on costs associated specifically with home health and hospice services and on total costs of care. The final objective is to evaluate the effect of the BBA of 1997 on mortality in these patients. Longitudinal analysis using the Surveillance, Epidemiology, and End Results-Medicare Database, covering a service area that includes 26% of the US population. Community-dwelling Medicare beneficiaries 65 years of age and older. Utilization rates of home health and hospice services; costs associated with those services, and total costs of care; and mortality. Home health utilization rates dropped substantially and hospice utilization rates increased after the BBA. Medicare costs for home health services declined as did total Medicare costs but hospice costs increased. There was no discernable effect on mortality rates. The BBA was successful in containing the costs of home health services and resulted in savings in overall costs of care for older cancer patients. Reduction in utilization of home health services did not seem to negatively affect outcomes. The BBA may have contributed to the trend of increasing use of hospice care.


Targeting the pyruvate dehydrogenase complex/pyruvate dehydrogenase kinase (PDC/PDK) axis to discover potent PDK inhibitors through structure-based virtual screening and pharmacological evaluation.
Proliferating cancer cells are characterized by the Warburg effect, a metabolic alteration in which ATP is generated from cytoplasmic glycolysis instead of oxidative phosphorylation. The pyruvate dehydrogenase complex/pyruvate dehydrogenase kinase (PDC/PDK) axis plays a crucial role in this effect and has been identified as a potential target for anticancer drug development. Herein, we present the discovery and pharmacological evaluation of potent PDK inhibitors targeting the PDK/PDC axis. We successfully identified 6 compounds from a small molecule library through a structure-based virtual screening campaign and evaluated their enzymatic inhibitory potencies for PDK1-4. Our results indicated that compound 1 exhibited submicromolar inhibitory activities against PDK1-3 (IC50 = 109.3, 135.8, and 458.7 nM, respectively), but is insensitive to PDK4 (IC50 = 8.67 μM). Furthermore, compound 1 inhibited the proliferation of A549 cells with an EC50 value of 10.7 μM. In addition, compound 1 induced cell apoptosis, arrested the cell cycle at the S phase, and reduced cell invasion and migration, while showing low in vivo toxicity at a high dose. Based on these observations, it can be concluded that compound 1 is a promising anti-PDK1-3 lead that merits further investigation.


[Current status of chronic filariasis in Jiangsu Province].
To understand the current status of chronic filariasis patients in Jiangsu Province so as to provide basic data for following-up care for them. The patients were followed up one by one according to history archives between June and July, 2018, and the clue investigation was also conducted. The base data of the patients was collected through a face-to-face questionnaire survey and analyzed. There were still 3 160 chronic filariasis patients in Jiangsu Province. Among them, the male accounted for 40.0%, and 91.8% of the patients were older adults aged 60 years or above. From the aspect of regional distribution, Suqian (24.2%), Huai'an (19.5%), Suzhou (17.3%), Xuzhou (11.2%), and Yancheng (9.8%) were the five top high prefectures. The patients with simple lymphatic inflammation or lymphadenitis, simple lymphedema or elephantiasis, simple chyluria, simple hydrocele of tunica vaginalis, and two symptoms or more accounted for 2.7%, 37.1%, 11.2%, 0.9%, and 48.1%, respectively. For the patients with lymphedema or elephantiasis, 97.8% of edema was seen in the lower limbs, and more than 90% of the edema stages were I-III. The number of current caring sites was 220, covering 2 091 patients. The average number of times of caring activities in this year was 3.2. The average cumulative time of caring activities among all the sites was 11.3 years. The number of chronic filariasis patients has been dramatically decreased, most of the patients are old and have long disease durations. The caring sites have not covered all the patients. In order to release the symptoms and improve the life quality of the patients, all the patients should be taken care of in Jiangsu Province.


A potential role for bat tail membranes in flight control.
Wind tunnel tests conducted on a model based on the long-eared bat Plecotus auritus indicated that the positioning of the tail membrane (uropatagium) can significantly influence flight control. Adjusting tail position by increasing the angle of the legs ventrally relative to the body has a two-fold effect; increasing leg-induced wing camber (i.e., locally increased camber of the inner wing surface) and increasing the angle of attack of the tail membrane. We also used our model to examine the effects of flying with and without a tail membrane. For the bat model with a tail membrane increasing leg angle increased the lift, drag and pitching moment (nose-down) produced. However, removing the tail membrane significantly reduced the change in pitching moment with increasing leg angle, but it had no significant effect on the level of lift produced. The drag on the model also significantly increased with the removal of the tail membrane. The tail membrane, therefore, is potentially important for controlling the level of pitching moment produced by bats and an aid to flight control, specifically improving agility and manoeuvrability. Although the tail of bats is different from that of birds, in that it is only divided from the wings by the legs, it nonetheless, may, in addition to its prey capturing function, fulfil a similar role in aiding flight control.


The Spectrum of Headache in Leptomeningeal Metastases: A Comprehensive Review with Clinical Management Guidelines.
Headaches are a common, oftentimes debilitating symptom in patients with leptomeningeal metastases. The third edition of the International Classification of Headache Disorders provides a useful diagnostic framework for headaches secondary to leptomeningeal metastases based on the temporal relationship of headache with disease onset, change in headache severity in correlation with leptomeningeal disease burden, and accompanying neurologic signs such as cranial nerve palsies and encephalopathy. However, headaches in patients with leptomeningeal metastases can be further defined by a wide range of varying cancer- and treatment-related pathophysiologies, each requiring a tailored approach. A thorough review of the literature and expert opinion on five observed headache sub-classifications in patients with leptomeningeal metastases is provided, with attention to necessary diagnostic testing, recommended first-line treatments, and prevention strategies.


Range of motion measurements diverge with increasing age for COL5A1 genotypes.
Increased and decreased joint range of motion (ROM) are modifiable risk factors for musculoskeletal soft-tissue injuries. Certain heritable disorders of connective tissue, which have a unifying symptom of joint hypermobility, are caused by mutations within the COL5A1 gene. Furthermore, the COL5A1 BstUI restriction fragment length polymorphism (RFLP) sequence variant is associated with ROM measurements in a mixed injured/uninjured cohort. The association between COL5A1 BstUI RFLP and sit and reach (SR) ROM in an apparently healthy and physically active cohort was investigated. The SR test was performed on 325 white subjects (204 males). Subjects were also genotyped for the BstUI RFLP (C/T) within the 3'-untranslated region of the COL5A1 gene. The COL5A1 BstUI RFLP genotype was associated with SR ROM in older (≥35 years) subjects (TT: 225 ± 96 mm, TC: 245 ± 100 mm, CC: 32 ± 108 mm, N=96, P=0.017). Age and COL5A1 BstUI genotype interacted significantly for SR ROM. Sex and COL5A1 genotype accounted for 22.8% of the variance in SR ROM in the older group. The COL5A1 BstUI RFLP is associated with SR ROM, particularly with increasing age and is an important contributing factor to ROM variation, particularly in older, apparently healthy and physically active individuals.


Simulation of the wastewater temperature in sewers with TEMPEST.
TEMPEST is a new interactive simulation program for the estimation of the wastewater temperature in sewers. Intuitive graphical user interfaces assist the user in managing data, performing calculations and plotting results. The program calculates the dynamics and longitudinal spatial profiles of the wastewater temperature in sewer lines. Interactions between wastewater, sewer air and surrounding soil are modeled in TEMPEST by mass balance equations, rate expressions found in the literature and a new empirical model of the airflow in the sewer. TEMPEST was developed as a tool which can be applied in practice, i.e., it requires as few input data as possible. These data include the upstream wastewater discharge and temperature, geometric and hydraulic parameters of the sewer, material properties of the sewer pipe and surrounding soil, ambient conditions, and estimates of the capacity of openings for air exchange between sewer and environment. Based on a case study it is shown how TEMPEST can be applied to estimate the decrease of the downstream wastewater temperature caused by heat recovery from the sewer. Because the efficiency of nitrification strongly depends on the wastewater temperature, this application is of practical relevance for situations in which the sewer ends at a nitrifying wastewater treatment plant.


Effect of low cholesterol, linoleic acid enriched diet on thrombotic tendency and plasma lipoproteins in patients with angina pectoris.
Eighteen patients with an established angina pectoris aged 46-74 years were investigated. These patients received a low cholesterol, linoleic acid enriched diet during a period of three months. Of these patients seventeen terminated the three months period. The adherence to the diet was assessed by determining the fatty acid pattern in cholesterol and triglycerides. Both were found to increase significantly and to the same extend. When comparing the values between the entry to the study and after three months of dietetic intervention we found a significant improvement in the fibrinogen level, haematocrit, the aggregation of platelets, the PAT I test according to Breddin and in the test according to Wu and Hoak. However, the fibrinolytic activity before occlusion of an arm was disminished. The changes in ADP -, collagen -, adrenalin and thrombin induced platelet aggregation were not uniform. We found a significant lowering of VLDL, LDL, phospholipids and total cholesterol. HDL did not change significantly. It seems that the diet had a favourable effect on several thrombotic and lipoprotein parameters in these patients.


NANOG as an adverse predictive marker in advanced non-small cell lung cancer treated with platinum-based chemotherapy.
NANOG is a master transcription factor that regulates stem cell pluripotency and cellular reprograming. Increased NANOG expression has been associated with poor survival in several human malignancies. However, the clinical significance of NANOG overexpression in lung cancer has been scarcely evaluated. The aim of this study was to investigate whether NANOG levels are associated with clinical outcomes of patients with non-small cell lung cancer (NSCLC) who were treated with platinum-based chemotherapy. NANOG levels were evaluated immunohistochemically using the histologic score (H-score) in tumor tissues from patients with advanced NSCLC who received platinum-based doublet treatment. We performed survival analyses according to the NANOG levels and evaluated the association between clinicopathological parameters and levels of NANOG. Multivariate analyses using 112 tumor specimens showed that high NANOG levels were independently associated with short progression-free survival (hazard ratio [HR] =3.09, 95% confidence interval [CI]: 2.01-4.76) and with short overall survival (HR =3.00, 95% CI: 1.98-4.54). Similar results were shown in the subgroup analyses for patients with adenocarcinoma and squamous cell carcinoma. NANOG expression was not associated with any clinicopathological parameter such as age, gender, smoking status, stage, differentiation, or histological subtypes. NANOG overexpression was associated with poor response and short overall survival in patients with advanced NSCLC who were treated with platinum-based chemotherapy, suggesting that NANOG could be a potential adverse predictive marker in this setting.


Registered nurses' experience of the withdrawal of treatment from the critically ill patient in an intensive care unit.
In this article the results of research undertaken to explore and describe the experience of Registered Nurses regarding the withdrawal of treatment from the critically ill patient in an Intensive Care Unit (ICU), are discussed. Withdrawal of treatment from a critically ill patient in an Intensive Care Unit (ICU) is a very traumatic experience for all those involved. The Registered Nurse has the most contact with all those who are involved throughout the process. This raises questions regarding how the nurse experiences the withdrawal of treatment, and about guidelines that can be developed to accompany the nurse during the process of treatment withdrawal. The study was qualitative, descriptive, exploratory, descriptive and contextual in nature. Data was gathered by means of phenomenological interviews conducted by the researcher. Trustworthiness was ensured through the implementation of Guba's model (in Krefting 1991: 214). The following themes were identified: 1. The relationships the nurse develops with individuals involved in the process of treatment withdrawal. 2. The inner moral conflict experienced by the nurse relating to the ethical aspects of withdrawal of treatment. The focus of this article is on the discussion of these experiences of the registered nurses. Based on the identified themes, guidelines were developed to accompany the nurse during the process of withdrawal of treatment.


Highly prevalent at-risk sexual behaviours among out-of-school youths in urban Cameroon.
Cameroon has a high prevalence of out-of-school youths. Therefore, research relating to out-of-school youths and HIV/AIDS is imperative, since they might engage in high risk sexual behaviours. The current study investigated the highly prevalent at-risk sexual behaviours among out-of-school youths in urban Cameroon. A cross-sectional design was adopted using a self-administered questionnaire to collect data from a cluster sample of 405 out-of-school youths, aged 15-24 years. Statistics was calculated using SPSS version 20 at the level 0.05. By age less than 16 years, more females, 90.2% than males, 71.8% had experienced sex (p < 0.001); more females, 40.4% than males, 23.2% used condoms during first sex (p < 0.01); more males, 70.8% than females, 46.0% had multiple sequential sexual partners during the last one year prior to this study (p < 0.001); more males, 42.6% than females, 18.0% had multiple concurrent sexual partners during the study period (p < 0.01); more youths who did not belong to a well-defined social network, 80.8% had experienced sex than those who belonged, 55.8% (p < 0.001); more youths who did not belong to a well-defined social network had multiple sequential sexual partners, 46.7% than those who belonged, 32.3% (p < 0.01); more youths who belonged to a well-defined social network, 24.3% used condoms consistently than those who did not belong, 15.4% (p < 0.01). Sexual risk behaviours exist among out-of-school youths in urban Cameroon. There is need for campaigns and interventions to bring about sexual behaviour change especially among those with low socioeconomic status. Youths should be encouraged to join well-defined social networks.


Decreased expression of RASSF10 correlates with poor prognosis in patients with colorectal cancer.
Ras association domain protein 10 (RASSF10) was reported to act as a prognostic indicator in various types of cancer and it was proved to be tumor suppressor gene in colorectal cancer (CRC). The purpose of this study was to evaluate the prognostic significance of RASSF10 in CRC.Quantitative real-time polymerase chain reaction was used to detect the messenger RNA (mRNA) expression while enzyme-linked immunosorbent assay was taken to measure the protein expression of RASSF10 in tumor tissues and adjacent normal tissues from 102 patients with CRC. The relationship between RASSF10 expression level and clinical characteristics of CRC patients was analyzed by chi-squared test. In addition, the association between overall survival of CRC patients and RASSF10 expression was estimated by Kaplan-Meier analysis. Cox regression analysis was used to evaluate the prognostic value of RASSF10.The expression level of RASSF10 in tumor tissues was significantly lower than that in the normal tissues both at mRNA and protein levels. Moreover, the expression level was correlated with lymph-node-metastasis and tumor-node-metastasis stage. Kaplan-Meier analysis suggested that patients with high expression level of RASSF10 had a longer overall survival than those with low level (log-rank test, P < .001). Besides, RASSF10 might be a potential biomarker in the prognosis of CRC according to cox regression analysis.The down regulated of RASSF10 is found in CRC and it may be an ideal prognostic marker.


Vesicoanal, urethroanal, and urethrovesical reflexes initiated by lower urinary tract irritation in the rat.
Irritation of the urinary bladder causes activation of normally "silent" nociceptive primary afferent fibers. In the present study, it is reported that irritation of the urinary bladder or urethra with infusion of 0.5% acetic acid robustly activates motoneurons that innervate the striated muscle of the external anal sphincter via spinal reflex mechanisms. The activation of anal motoneurons following irritation of the bladder and urethra are termed vesicoanal and urethroanal reflexes, respectively. The reflexes can be mimicked by acute application of capsaicin to the bladder and urethra, and they show desensitization following prolonged topical application of capsaicin or following chronic systemic pretreatment with capsaicin. The reflexes can be demonstrated in chronic spinal cord-transected animals, indicating that the reflex pathways are organized within the spinal cord. The urethroanal reflex is also physiologically activated by urethral distension and/or increases in intraluminal pressure. In addition to activation of anal sphincter activity, slight distension, pressure increases, or instillation of 0.5% acetic acid into the urethra inhibited bladder contractions through activation of an inhibitory urethrovesical reflex. These reflexes are discussed in terms of clinical characteristics of urethritis and prostatitis. Anecdotally, it was discovered that the bladder can buffer acetic acid.


[Diagnosis of mosaic forms of karyotype anomalies in clinical cytogenetic research].
Mosaicism cases have been statistically analyzed with the aim to develop a general scheme of the cytogenetic study. Using the Bernoulli formula it is shown that when P = 0.95 and proportion of clones is 10:90% and more 29 cells should be initially analyzed. If all the cells are of the same chromosomal constitution (m = 0) the mosaicism is rejected. Mosaicism is highly probable when m = 4 and more among n = 29. When m = 1, 2 or 3 the number of cells should be increased to 44 in accordance with calculations by the formula: 1--Cnm.pm.(1--p)n-m = P.


Pregnancy outcomes, site of delivery, and community schisms in regions affected by the armed conflict in Chiapas, Mexico.
The Zapatista armed conflict began in the state of Chiapas, Mexico, in 1994, and overlaps pre-existing local disputes about land, religion, and other issues. Related disruptions in access to and utilization of health services have been alleged to have compromised local health status, particularly in vulnerable subgroups such as indigenous women and infants. The study objective was to measure maternal and perinatal mortality ratios and utilization of pregnancy-related health services in the region affected by the Zapatista conflict, and to describe associations between these primary outcome measures, socioeconomic and demographic factors, and factors associated with inter-party and intra-community conflict. A cross-sectional, population-based survey was conducted in 46 communities in three regions. The study subjects were 1227 women, 13-49 years old, who had been pregnant during the preceding 2 years (1999-2001). Principal outcome measures were maternal and perinatal mortality, and site of delivery. Secondary analyses explored associations between primary outcomes and socioeconomic, demographic, and conflict-related factors. Most births (87.1%) occurred at home. The crude observed maternal and perinatal mortality ratios were 607/100,000 and 23.5/1000 live births, respectively. Those who died had difficulty accessing emergency obstetrical care. Both home birth and mortality were associated with descriptors of intra-community conflict. Observed maternal and perinatal mortality ratios were substantially higher than those officially reported for Mexico or Chiapas. Reduction of high reproductive mortality ratios will require attention to socioeconomic and conflict-related problems, in addition to improved access to emergency obstetrical services.


PERN: an EU-Russia initiative for rhizosphere microbial resources.
Millions of microbial taxa inhabit the rhizosphere and could be used as biofertilizers, biopesticides, and/or for bioremediation. Only a fraction of these microbes have been described and/or are being utilized. Most are dispersed in collections, but coordination of their accessibility and availability is challenging. Here, we present the Pan-European Rhizosphere Resource Network (PERN), which is a transnational repository of microorganisms whose objectives are to facilitate access to rhizosphere resources and information and help users with technical and legal issues.


Clinical case reviews and poster sessions in multiple sclerosis spasticity: main outcomes and highlights.
Individuals with multiple sclerosis (MS) spasticity present with a range of symptoms and disability levels that are frequently challenging to manage. Summary : Clinical case reviews in treatment-resistant MS spasticity were presented in five country-specific sessions conducted in parallel at the MS Experts Summit. Attendees at the Norwegian session discussed early response to new treatments for severe spasticity and highlighted the importance of titrating THC:CBD oromucosal spray (Sativex®) when adding it to baclofen. The French group focussed on MS symptoms and patient characteristics that interact with spasticity and agreed on a list of minimum ratings for diagnosis of MS spasticity symptoms. Attendees at the Spanish session concurred that THC:CBD oromucosal spray is effective and well tolerated as add-on therapy in treatment-resistant MS spasticity, particularly for pain, spasms and gait disturbances. The Italian group discussed the use of add-on THC:CBD oromucosal spray and other possible combination therapies for treatment-resistant MS spasticity. Attendees at the German session highlighted the need to address trigger factors for MS spasticity to reduce the potential for impact on activities of daily living (ADL) and quality of life (QoL). Three innovative studies of MS spasticity from the poster session were selected for closer review. The MOVE 1 EU epidemiological study indicated that, across western Europe, patients with MS spasticity continue to have unmet management needs. A literature review demonstrated that symptomatic relief of MS spasticity in patients who respond to THC:CBD oromucosal spray translates into sustainable improvements in ADL and QoL. Enriched-design studies of medications targeting the endocannabinoid system require careful interpretation due to possible pharmacodynamic 'priming', i.e. carry-over effects of successful active treatment during the enrichment phase. Key Messages: Sharing experiences of clinical practice, including experience with the use of THC:CBD oromucosal spray, may be useful to overcome some of the challenges in the overall management of patients with moderate to severe treatment-resistant MS spasticity.


Validity and reliability of the short physical performance battery in two diverse older adult populations in Quebec and Brazil.
To assess the validity and reliability of the Short Physical Performance Battery (SPPB) in adults 65 to 74 years old, capable in all basic activities of daily living (ADL), in Quebec and Brazil. Participants were recruited in St. Bruno (Quebec) by local advertisements (n = 60) and in Santa Cruz (Brazil) by random sampling (n = 64). The SPPB includes tests of gait, balance, and lower-limb strength. Disability status was categorized as intact mobility, limited mobility, and difficulty in any of ADL. There was a graded decrease in mean SPPB scores with increasing limitation of lower limbs, disability, and poor health. Using the test-retest reliability the authors evaluated the intraclass correlation coefficient, which was high in both samples: .89 (95% CI: 0.83, 0.93) in St. Bruno and .83 in Santa Cruz (95% CI: 0.73, 0.89). This study provides evidence for the validity and reliability of SPPB in diverse populations.


Structure-guided design and synthesis of ATP-competitive N-acyl-substituted sulfamide d-alanine-d-alanine ligase inhibitors.
d-Alanine-d-alanine ligase (Ddl) catalyses the ATP-dependent formation of d-Ala-d-Ala, a critical component in bacterial cell wall biosynthesis and is a validated target for new antimicrobial agents. Here, we describe the structure-guided design, synthesis, and evaluation of ATP-competitive N-acyl-substituted sulfamides 27-36, 42, 46, 47 as inhibitors of Staphylococcus aureus Ddl (SaDdl). A crystal structure of SaDdl complexed with ATP and d-Ala-d-Ala (PDB: 7U9K) identified ATP-mimetic 8 as an initial scaffold for further inhibitor design. Evaluation of 8 in SaDdl enzyme inhibition assays revealed the ability to reduce enzyme activity to 72 ± 8 % (IC50 = 1.6 mM). The sulfamide linker of 8 was extended with 2-(4-methoxyphenyl)ethanol to give 29, to investigate further interactions with the d-Ala pocket of SaDdl, as predicted by molecular docking. This compound reduced enzyme activity to 89 ± 1 %, with replacement of the 4-methoxyphenyl group in 29 with alternative phenyl substituents (27, 28, 31-33, 35, 36) failing to significantly improve on this (80-89 % remaining enzyme activity). Exchanging these phenyl substituents with selected heterocycles (42, 46, 47) did improve activity, with the most active compound (42) reducing SaDdl activity to 70 ± 1 % (IC50 = 1.7 mM), which compares favourably to the FDA-approved inhibitor d-cycloserine (DCS) (IC50 = 0.1 mM). To the best of our knowledge, this is the first reported study of bisubstrate SaDdl inhibitors.


Culturally Competent Care: the awareness of self and others.
Today's healthcare environment is increasingly complex and provides significant challenges to nurses and patients alike. It is imperative that nurses strive to understand the diversity of their patients and coworkers to provide optimum care. One essential component of nursing practice is the ability to provide Culturally Competent Care (CCC). This article outlines several aspects of CCC and organizational efforts that support good nursing practice through staff education.


Mechanical stretching induces calcification and cartilage matrix metabolism, causing degeneration of the acetabular labrum.
The acetabular labrum plays an important role in joint lubrication, and damage to this structure leads to osteoarthritis. This study aimed to histologically classify the degree of degeneration of the acetabular labrum and to investigate the changes in gene expression induced by mechanical stretching. We obtained acetabular labrum cells from patients with hip osteoarthritis during total hip arthroplasty (n = 25). The labrum was stained with safranin O, and images were histologically evaluated using a new parameter, the red/blue (R/B) value. The samples were divided into the degenerated group (D group: n = 18) and the healthy group (H group: n = 7) in accordance with the Kellgren-Lawrence (KL) grade. The cultured acetabular labral cells were subjected to loaded uniaxial cyclic tensile strain (CTS). After CTS, changes in gene expression were examined in both groups. Spearman's correlation analysis revealed that the R/B value was significantly correlated with the KL grade and the Krenn score. The expression levels of genes related to cartilage metabolism, osteogenesis and angiogenesis significantly increased after CTS in the H group, while gene expression in the D group showed weaker changes after CTS than that in the H group compared to the nonstretched control group. The degree of labral degeneration could be classified histologically using the R/B value and the KL grade. Mechanical stretching caused changes in gene expression that support the pathological features of labral degeneration.


Simultaneous determination of amphetamine, methamphetamine, methylenedioxyamphetamine (MDA), methylenedioxymethamphetamine (MDMA), and methylenedioxyethylamphetamine (MDEA) enantiomers by GC-MS.
A method is described for the simultaneous determination of the ratio of l- and d-enantiomers of amphetamine, methamphetamine, 3,4-methylenedioxyamphetamine (MDA), 3,4-methylenedioxymethamphetamine (MDMA), and 3,4-methylenedioxyethylamphetamine (MDEA) in urine. The assay uses liquid-liquid extraction followed by derivatization with trifluoroacetyl-l-prolyl chloride (l-TPC) and analysis by gas chromatography-mass spectrometry. The assay was developed using prepared samples containing varying concentrations of each of the analytes over a range of percentages of each enantiomer. Results showed the method to provide accurate and reliable results in samples containing > or = 10 ng/mL amphetamine and methamphetamine and > or = 25 ng/mL MDA, MDMA, and MDEA. The assay was used to analyze urine samples from subjects of a controlled MDMA study. Results for each of the eight subjects showed a greater percentage of the l-enantiomer of MDMA initially, and the percentage increased with time postdose. Analysis of the metabolite MDA revealed that the proportion of d-enantiomer was initially greater than the l-enantiomer followed by a gradual increase in the proportion of l-enantiomer until it exceeded the amount of the d-enantiomer. In all cases, the l-MDA exceeded the d-MDA within the first 36 h postdose.


Bone flap elevation for intracranial EEG monitoring: technical note.
Intracranial electroencephalography (iEEG) provides invaluable information in determining seizure focus and spread due to its high spatial and temporal resolution, which are not afforded by noninvasive studies. Electrodes of various types (e.g., grid, strip, and depth electrodes) and configurations are often used for optimum coverage of suspected areas of seizure onset and propagation. Given the fixed intracranial volume and added mass effect from placement of cortical electrodes, brain edema and postoperative deficits can occur. The authors describe a simple, inexpensive, and highly effective technique of bone flap replacement using standard titanium plates to expand the intracranial volume and minimize risks of brain compression and intracranial hypertension. Rectangular titanium plates are bent and placed in a way that secures the bone flap in a slightly elevated position relative to the adjacent calvaria during iEEG monitoring. The authors evaluated the degree of bone flap elevation and amount of volume created using this technique in 3 iEEG cases. They then compared these results with the bone flap elevation and volume created using linear titanium plates, a method they had used previously. The use of rectangular plates produced on average 6.6 mm of bone flap elevation, compared with only 1.8 mm of bone flap elevation with the use of linear plates, resulting in a statistically significant 261% increase in bone flap elevation (p ≤ 0.001). The authors suggest that rectangular plates may provide stronger resistance to scalp tension after myocutaneous skin closure compared with the linear plates and that subsidence of the bone flap likely occurred with the use of linear plates. In summary, the described technique utilizing rectangular plates creates significantly increased bone flap elevation compared with a similar method using linear plates, and it may reduce the risk of neurological deficits related to intracranial electrode placement.


Topical tacrolimus may be effective in the treatment of oral and perineal Crohn's disease.
Crohn's disease of the mouth or perineum is more common in young people, and notably resistant to treatment. However, there is increasing evidence that topical therapy with tacrolimus (FK506) may be effective in skin diseases resistant to cyclosporin because of its high uptake in inflamed skin and subsequent reduction in keratinocyte chemokine production. Tacrolimus ointment was made up inhouse from the intravenous or oral formulation and suspended in appropriate vehicles for perioral or perianal administration at an initial concentration of 0.5 mg/g. This was administered open label to eight children (aged 5-18 years) with treatment resistant oral (three patients) and/or ulcerating perineal (six patients) Crohn's disease. Marked improvement was seen in 7/8 patients within six weeks and healing within 1-6 months. One child with gross perineal and colonic disease showed little response. Two of the responders showed rebound worsening when tacrolimus was stopped or the dosage reduced rapidly, and one of these eventually required proctectomy. Slower weaning of drug concentration has been successful in 6/8 patients, with four receiving intermittent treatment and two on regular reduced dosage (0.1-0.3 mg/g) with follow up times of six months to 3.5 years. Serum concentrations of tacrolimus were undetectable in all patients. Topical tacrolimus at low concentrations (0.5 mg/g) shows promise in the management of childhood perineal and oral Crohn's disease, with no evidence of significant systemic absorption. However, rapid weaning or abrupt cessation of therapy may cause rebound worsening of disease. Further controlled studies are required to assess the efficacy and safety of this treatment.


The screening of alpha- and beta-globin chain variants with isoelectric focusing.
A simple isoelectric focusing technique is presented for the screening of alpha- and beta-globin chain variants on polyacrylamide gel in the presence of 8 M urea. No detergent was used. Variants focused at discrete pH values, depending on the charge variation (-2, -1, 0, +1 or +2) introduced by the mutation. A linear relationship was evidenced between the charge variation and the shift of the apparent isoelectric point of the variants. The practical interest of this procedure is illustrated.


The evolution of the actin binding NET superfamily.
The Arabidopsis Networked (NET) superfamily are plant-specific actin binding proteins which specifically label different membrane compartments and identify specialized sites of interaction between actin and membranes unique to plants. There are 13 members of the superfamily in Arabidopsis, which group into four distinct clades or families. NET homologs are absent from the genomes of metazoa and fungi; furthermore, in plantae, NET sequences are also absent from the genome of mosses and more ancient extant plant clades. A single family of the NET proteins is found encoded in the club moss genome, an extant species of the earliest vascular plants. Gymnosperms have examples from families 4 and 3, with a hybrid form of NET1 and 2 which shows characteristics of both NET1 and NET2. In addition to NET3 and 4 families, the NET1 and pollen-expressed NET2 families are found only as independent sequences in Angiosperms. This is consistent with the divergence of reproductive actin. The four families are conserved across Monocots and Eudicots, with the numbers of members of each clade expanding at this point, due, in part, to regions of genome duplication. Since the emergence of the NET superfamily at the dawn of vascular plants, they have continued to develop and diversify in a manner which has mirrored the divergence and increasing complexity of land-plant species.


The steady state kinetic parameters and non-processivity of Escherichia coli deoxyribonucleic acid polymerase I.
A steady state kinetic study of Escherichia coli DNA polymerase I has been carried out using poly[d(A-T)] as the template-primer substrate. The results of substrate saturation and product inhibition kinetic studies suggest an altered Ordered Bi Bi mechanism for the enzyme. The Michaelis constants for polymer, d-atp, and dTTP are 5 nM (3'-OH ends), 1 muM, and 2 muM, respectively. The apparent equilibrium constant for the reaction, Keq equals [PPi]/[dNTP], was estimated as greater than or equal to 500. No quaternary complex of enzyme, template, and both deoxynucleoside triphosphates was detected. Single turnover experiments at 4 degrees indicated that the enzyme functions non-processively under the specified conditions, that is, dissociates after each catalytic step. The results at higher temperature were consistent with dissociation within 30 steps. Furthermore, at 4 degrees a burst of incorporation stoichiometric with the amount of enzyme was observed upon initiation of the reaction, indicating that the rate-limiting step in the steady state occurs after phosphodiester bond formation. There is a linear Arrhenius dependence of the initial reaction on temperature in the range 4-40 degrees, with an apparent Ea equals 17 kcal/mol. The rate equations appropriate for template-dependent polymerases which dissociate after each catalytic step have been derived.


Cold stimulation is feasible and has limited aversiveness in healthy, pain-free dogs.
The study aimed to evaluate the applicability and repeatability of cold stimulation in dogs. 10 healthy Beagle dogs were used in a blinded cross-over experiment. Measurements were performed in triplicate at 4 skin locations. The probe was manually placed, and temperature decreased (32 to 10 °C) at different cooling rates (0.5, 1, and 5 °C second-1) and latency was measured (11 °C for 60 seconds). Stimulations were discontinued when avoidance reactions were detected. Thermal threshold or time-to-reaction were recorded. Experiments were performed 3 times per animal in weeks 1 (Exp1), 2 (Exp2), and 5 (Exp3). Feasibility of cold stimulation was scored (0-5). Data were analyzed with mixed logistic regression. No significant differences in number of avoidance reactions between cooling-rates were detected. Significantly more reactions (P < .001) were observed during Exp1 compared to Exp2 and Exp3. Thermal thresholds were 13 ± 2.6 °C, 17.7 ± 4 °C and 16.3 ± 4.6 °C for 5, 0.5 and 1 °C second-1, respectively. Latency to the reaction was determinable in 37% of measurements. The mean time-to-reaction was 13 ± 11 seconds. In 85% of measurements, a feasibility score of 0 (best feasibility) was assigned. The method is easily applicable and well tolerated, but habituation could not be excluded. Overall, the aversiveness of cold stimulation in healthy dogs is limited and it is not possible to recommend a specific protocol. In future studies, it needs to be determined if the aversiveness of cold stimulation is increased in diseased dogs.


An immunoluminometric assay for N-terminal pro-brain natriuretic peptide: development of a test for left ventricular dysfunction.
Measurement of plasma levels of brain natriuretic peptide (BNP) has been used to assess left ventricular dysfunction and prognosis. Levels of the N-terminus of the precursor of BNP (NT-proBNP) have been reported to be elevated to a greater extent than BNP in left ventricular dysfunction. We have devised a non-radioactive sensitive and specific assay for NT-proBNP based on a competitive ligand binding principle. The chemiluminescent label 4-(2-succinimidyloxycarbonylethyl)phenyl-10-methylacridinium 9-carboxylate fluorosulphonate was used to label peptides representing domains in the middle and C-terminal sections of NT-proBNP. Assay of the C-terminal section of NT-proBNP (amino acids 65-76) in patients with proven left ventricular dysfunction [left ventricular wall motion index median 0.9 (range 0.3-1.4)] revealed elevated values [median 639 (386-911) fmol/ml] compared with normal controls [left ventricular wall motion index of 2 in all, NT-proBNP median 159 (120-245) fmol/ml, P<0.001]. Measurement of the middle section of NT-proBNP (amino acids 37-49) was not a discriminating test. It is thus possible to derivatize small peptides with a methyl acridinium label and preserve immunodetection with specific antibodies. Such methodology may allow non-radioactive immunoluminometric assays to be devised.


Syme amputation for the treatment of fibular deficiency. An evaluation of long-term physical and psychological functional status.
Syme amputation is an accepted treatment for fibular deficiency. With improvement in limb-lengthening procedures, there has been renewed interest in limb salvage for these patients. The purpose of the present study was to evaluate the physical and psychological results in ten young adults who had had a Syme amputation for the treatment of fibular deficiency when they were children. The evaluation consisted of physical examination, prosthetic assessment, psychological testing, and physical performance testing of knee extension and flexion with use of a Cybex-II dynamometer. Five patients reported no difficulty with the involved limb since the Syme amputation, four had had minor secondary procedures (three medial distal femoral or proximal tibial hemiepiphyseodeses, one reconstruction with an autologous patellar ligament graft, one revision of the stump, and one tibial osteotomy) on the affected extremity, and one had mild instability of the knee that had been treated nonoperatively. All ten patients had an appropriate, functional Syme prosthesis, and none reported difficulty with walking or running. On psychological testing, this group generally did not differ from the norm with regard to occupational satisfaction, personal growth, relationships with family members and peers, and recreational behavior. The patients' overall assessment of self-reported quality of life and self-esteem was similar to that of normative adult samples. In general, these patients were leading active, productive lives and had always done so. On the basis of the results of this study, we concluded that young adults who have had a Syme amputation apparently are not limited in their ability to pursue and achieve personal goals. In order to justify recommending limb salvage rather than early Syme amputation for the treatment of fibular deficiency, the results of multistaged lengthening and reconstruction would have to match the functional, psychological, and cost-effective results for the patients whom we studied, who had had a Syme amputation.


Dietary arginine and lysine ratios in Large White toms. 2. Lack of interaction between arginine:lysine ratios and electrolyte balance.
The effect of dietary Arg:Lys ratios and dietary electrolyte balance (DEB) on growth and carcass parameters of Large White toms was evaluated in one experiment from 8 to 20 wk of age. Growth, feed conversion, and carcass composition were measured. All toms received a common basal diet from 0 to 8 wk of age. At 8 wk of age, 600 toms were randomly placed into 40 pens (15 toms per pen). The corn-soybean meal-based experimental diets were fed from 8 to 12, 12 to 16, and 16 to 20 wk of age and evaluated two Arg:Lys ratios (0.98 vs 1.22) and two DEB levels (148 vs 202 mEq/kg of diet) in a complete factorial arrangement. All experimental diets were pelleted. Composite samples of protein-contributing ingredients and complete experimental diets were analyzed for all amino acids, CP, DM, Cl, Na, and K. High and low average house temperature for the 8 to 20 wk period were 19 and 15 C, respectively. No interactions occurred between Arg:Lys ratios and DEB for any parameter measured except litter moisture. Increasing the Arg:Lys ratio improved 20-wk BW (P < or = 0.027) and 8 to 20 wk gain (P < or = 0.023). Feed:gain from 0 to 20 wk of age was decreased by increasing the Arg:Lys ratio (3.01 vs 2.94; P < or = 0.026) and by increasing the DEB (3.01 vs 2.95; P < or = 0.045). Dietary treatments did not affect mortality. Increasing DEB decreased cold carcass yield (P < or = 0.020). Total breast meat yield was increased (P < or = 0.076) by 1% in toms fed the diets containing the 1.22 Arg:Lys ratio vs toms fed diets containing the 0.98 Arg:Lys ratio. Toms responded favorably to increasing the Arg:Lys ratio for growth, feed conversion, and breast meat yield independent of DEB level.


Healthcare systems--an international review: an overview.
Based on the source of their funding, three main models of healthcare can be distinguished. The first is the Beveridge model, which is based on taxation and has many public providers. The second is the Bismarck 'mixed' model, funded by a premium-financed social insurance system and with a mixture of public and private providers. Finally, the 'Private Insurance model' is only in existence in the US. The present report explores the impact of these healthcare models on the access to, quality and cost of healthcare in selected European countries. Access is nearly 100% in countries with a public provider system, while in most of the 'mixed' countries, the difference from 100% is made up by supplementary private insurance. No differences are seen between public and mixed provider systems in terms of quality of care, despite the fact that the countries with the former model spend, in general, less of their Gross National Product on healthcare. The Private Insurance/private provider model of the US produces the highest costs, but is lowest in access and is close to lowest ranking in quality parameters.


Assembly of transcriptionally active 5S RNA gene chromatin in vitro.
We have studied the requirements for the in vitro assembly of transcriptionally active 5S RNA gene chromatin from cloned Xenopus laevis 5S plasmid DNA. Both plasmid DNA and DNA assembled into chromatin with Xenopus oocyte extracts are transcribed efficiently in vitro. Chromatin prepared by NaCl reconstitution with purified histones in the absence of any cellular factors, however, is transcriptionally inert. A transcriptionally active template is formed if plasmid DNA is incubated in an ovary extract prior to, but not after, NaCl reconstitution. The cellular component responsible for this effect is the 5S RNA transcription factor TFIIIA. Both chromatographically purified TFIIIA and TFIIIA derived from 7S RNP particles can complex with 5S DNA to yield an active chromatin template upon reconstitution with histones. This effect is specific for 5S RNA genes, since TFIIIA will not form an active template when incubated with a cloned Bombyx mori alanine tRNA gene.


Rotation and structure of FoF1-ATP synthase.
F(o)F(1)-ATP synthase is one of the most ubiquitous enzymes; it is found widely in the biological world, including the plasma membrane of bacteria, inner membrane of mitochondria and thylakoid membrane of chloroplasts. However, this enzyme has a unique mechanism of action: it is composed of two mechanical rotary motors, each driven by ATP hydrolysis or proton flux down the membrane potential of protons. The two molecular motors interconvert the chemical energy of ATP hydrolysis and proton electrochemical potential via the mechanical rotation of the rotary shaft. This unique energy transmission mechanism is not found in other biological systems. Although there are other similar man-made systems like hydroelectric generators, F(o)F(1)-ATP synthase operates on the nanometre scale and works with extremely high efficiency. Therefore, this enzyme has attracted significant attention in a wide variety of fields from bioenergetics and biophysics to chemistry, physics and nanoscience. This review summarizes the latest findings about the two motors of F(o)F(1)-ATP synthase as well as a brief historical background.


Effects of antihypertensive single-drug therapy on heart rate. Department of Veterans Affairs Cooperative Study Group on Antihypertensive Agents.
Heart rate increasingly is being recognized either as an independent risk factor for a wide variety of cardiovascular disorders or as a surrogate marker for them. We analyzed the changes in heart rate associated with antihypertensive therapy with six drugs and placebo from the VA Cooperative Study on Single-Drug Therapy. These results were published previously (American Journal of Hypertension 1998;11:597-601). This paper provides a summary of the earlier publication with the addition of three figures not previously published. Atenolol had the greatest effect on heart rate reduction, followed by clonidine and diltiazem-SR. Hydrochlorothiazide and captopril were associated with small reductions in heart rate over time, whereas prazosin increased heart rate. Patients whose blood pressure was controlled by placebo had a 3.1 beats/min reduction of heart rate at 2 years. When the baseline heart rate was 65 beats/min or less, all drugs increased the heart rate except for atenolol, which further reduced it. Although it is clear that each of the six drugs used in our study had a different effect on heart rate, we cannot state that drug-induced reduction in heart rate per se confers a decrease in cardiovascular risk.


Increased energy metabolism rescues glia-induced pathology in a Drosophila model of Huntington's disease.
Huntington's disease (HD) is a polyglutamine (polyQ) disease caused by an expanded CAG tract within the coding region of Huntingtin protein. Mutant Huntingtin (mHtt) is ubiquitously expressed, abundantly in neurons but also significantly in glial cells. Neuron-intrinsic mechanism and alterations in glia-to-neuron communication both contribute to the neuronal dysfunction and death in HD pathology. However, it remains to be determined the role of glial cells in HD pathogenesis. In recent years, development of Drosophila models facilitated the dissection of the cellular and molecular events in polyQ-related diseases. By using genetic approaches in Drosophila, we manipulated the expression levels of mitochondrial uncoupling proteins (UCPs) that regulate production of both ATP and reactive oxygen species in mitochondria. We discovered that enhanced levels of UCPs alleviated the HD phenotype when mHtt was selectively expressed in glia, including defects in locomotor behavior and early death of Drosophila. In contrast, UCPs failed to prevent the HD toxicity in neurons. Increased oxidative stress defense was found to rescue neuron but not glia-induced pathology. Evidence is now emerging that UCPs are fundamental to adapt the energy metabolism in order to meet the metabolic demand. Thus, we propose that UCPs are glioprotective by rescuing energy-dependent functions in glia that are challenged by mHtt. In support of this, increasing glucose entry in glia was found to alleviate glia-induced pathology. Altogether, our data emphasize the importance of energy metabolism in the glial alterations in HD and may lead to a new therapeutic avenue.


Clinical and immunoserological characteristics of the transition from primary to overlap antiphospholipid syndrome.
Antiphospholipid syndrome (APS) is a distinct clinical entity characterized by arterial and venous thromboembolic events, recurrent fetal loss and the presence of antiphospholipid antibodies in the patients' sera. In primary APS, there is no detectable underlying disease, while overlap APS is associated with clinical syndromes including systemic autoimmune diseases, infections, or malignancies. We carried out a retrospective analysis of serological and clinical manifestations as well as assessed outcome-measures in 165 patients with primary APS. Thrombotic manifestations and possible signs of autoimmune diseases were determined at the time of the diagnosis, followed by the analysis of recurrent thrombotic events and effects of therapy during the follow-up period. Among the 165 patients with primary APS at onset, 105 patients (63%) remained primary APS after a mean 5.2 years of follow-up. In 14% of the patients, subsequently APS became associated with various characteristics of undifferentiated connective tissue disease. Finally 23% of patients evolved into a definitive systemic autoimmune disease during a mean 9.75 years of follow-up. Recurrent thrombotic events were registered in 24% of patients. Our results suggest that primary APS may be considered as a potential early phase of a dynamic transition towards a well-defined systemic autoimmune disease.


The autophagy genes ATG8 and ATG1 affect morphogenesis and pathogenicity in Ustilago maydis.
Autophagy is a complex degradative process in which cytosolic material, including organelles, is randomly sequestered within double-membrane vesicles termed autophagosomes. In Saccharomyces cerevisiae, the autophagy genes ATG1 and ATG8 are crucial for autophagy induction and autophagosome assembly, respectively, and their deletion has an impact on the autophagic potential of the corresponding mutant strains. We were interested in the role of autophagy in the development and virulence of U. maydis. Using a reverse genetic approach, we showed that the U. maydis ATG8 orthologue, atg8, is associated with autophagy-dependent processes. Deletion of atg8 abolished autophagosome accumulation in the vacuoles of carbon-starved cells and drastically reduced the survival of U. maydisDeltaatg8 mutant strains during these conditions. In addition, atg8 deletion had an impact on the budding process during saprobic haploid growth. The infection of maize with compatible Deltaatg8 strains resulted in fewer galled plants, and fungal gall colonization was strongly reduced, as reflected by the very low hyphal density in these tissues. Deltaatg8 infections resulted in the formation of very few teliospores. To corroborate the role of autophagy in U. maydis development, we also deleted the ATG1 orthologue, atg1. Deletion of atg1 yielded phenotypes similar to the Deltaatg8 strains during saprobic growth, but of lower magnitude. The Deltaatg1 strains were only slightly less pathogenic than the wild-type and teliospore production was not affected. Surprisingly, atg1 deletion in the Deltaatg8 background exacerbated those phenotypes already observed in the Deltaatg8 and Deltaatg1 single-mutant strains, strongly suggesting an additive phenotype. In particular, the double mutant was completely suppressed for plant gall induction.


Current concepts of pemphigus with a deep insight into its molecular aspects.
Pemphigus vulgaris is an autoimmune bullous disease involving both the skin and mucosal areas, which is characterized by intraepithelial flaccid blisters and erosions. The pathogenesis of this disease is not yet completely established, but novel intuitions into its pathogenesis have recently been published. An unanswered question in its pathophysiology is the mechanism of acantholysis or loss of keratinocyte cell adhesion. Acantholysis seems to result from a communal action of autoantibodies against numerous keratinocyte self-antigens, of which desmogleins 1 and 3, desmocollins and nondesmosome components, such as the mitochondrion, might take part in the disease initiation. Lately, apoptosis was described as a possible underlying mechanism of acantholysis. Likewise, apoptolysis is assumed to be the association between suprabasal acantholytic and cell death pathways. Hence, the present review focuses on the current concepts in the pathogenesis of the pemphigus in a nutshell.


The human D-glucuronyl C5-epimerase gene is transcriptionally activated through the beta-catenin-TCF4 pathway.
Heparan sulphate (HS) is a ubiquitous constituent of the extracellular matrix that is required for the biological activity of circulating soluble and insoluble extracellular ligands. GLCE (D-glucuronyl C5-epimerase), an enzyme responsible for the epimerization of D-glucuronic acid into L-iduronic acid of HS, endows the nascent polysaccharide chain with the ability to bind to growth factors and cytokines. In order to examine the mechanism of regulation of GLCE expression, the functional organization of the human GLCE gene promoter has been investigated. Studies utilizing stepwise deleted and site-directed mutagenized promoter constructs have shed light on the functional relevance of two cis-acting binding elements for the beta-catenin-TCF4 complex (where TCF4 stands for T-cell factor 4) that are located in the enhancer region of the promoter. The ability of the putative binding sequences to bind the beta-catenin-TCF4 complex has been confirmed through electrophoretic mobility-shift and supershift analyses. We have found that, in a set of human colon carcinoma cell lines, the expression of GLCE correlates with the degree of activation of the beta-catenin-TCF4 transactivation complex. Furthermore, the ectopic expression of beta-catenin-TCF4 in cells that constitutively express low levels of the transactivation complex produces a significant increase of GLCE transcript level and, at the same time, enhances the rate of D-glucuronic acid epimerization in HS. The data obtained are consistent with the idea that the beta-catenin-TCF4 transactivation pathway plays a major role in modulating GLCE expression, thus contributing to the regulation of HS biosynthesis and its structural organization.


A qualitative inquiry into patients' perspectives on individualized priorities for treatment outcomes in inflammatory bowel diseases.
Patients with inflammatory bowel diseases (IBD) experience a variety of symptoms and limitations due to their condition. While many outcome measures are available to assess IBD symptom level and disease activity, individual patients' preferences are usually not accounted for. Individualized outcome measures allow individual patients to select and weigh outcomes based on their relative importance, and have been developed in other medical disciplines. In this study, we explored IBD patients' perspectives on different strategies to prioritize IBD-specific health outcomes. Existing individualized measures were modified for relevance to IBD patients. We performed six focus groups, in which patients were asked to rate and weigh these measures in a series of exercises and to discuss the pros and cons of five different prioritization methods (Likert scale, ranking, selecting outcomes, distribute points, and using a rotating disk) using a semi-structured approach. A thematic analysis revealed key themes in the data. Patients' thoughts could be grouped into four key themes with 2-4 subthemes each: (1) prioritizing outcomes; (2) differences between methods; (3) outcomes to include; and (4) practical use. Overall, it was challenging for many patients to prioritize outcomes. Among the different prioritization methods, the rotating disk was perceived as the most intuitive. Patients anticipated that this visualization would also help them communicate with their physician. In a series of focus groups, a visual rotating disk was found to be an intuitive and holistic way to elicit the relative importance of different outcomes for individual IBD patients.


[Rectal prolapse--laparoscopic resection and results].
postoperatively Seventeen females presenting rectal intussusception with a combined outlet obstruction underwent laparoscopic resection of the rectum (n = 4) or rectum and sigma (n = 13). Mean age was 61.5 +/- 9.7 years, mean duration of surgery took 117 +/- 30.4 minutes, realimentation started 3.5 +/- 1.3 days postoperatively and the mean stay in hospital lasted 11.8 +/- 2.9 days. In all patients an ano-rectal pressure-measurement and EMG were carried out. There was a significant lower resting-pressure of the anal sphincter in comparison to a normal collective of healthy patients with 67.8 +/- 21.6 cm H2O (p < 0.006). Postoperatively one severe complication with a generalized peritonitis and a resulting ARDS occurred. No perioperative mortality had to be remarked. Our results show that laparoscopic resection in patients with a rectal intussusception and outlet obstruction is safe. Wether rectal intussusception apart of rectal prolapse is an entity of its own, has to been shown in further investigations.


Adherence to physician recommendation to colorectal cancer screening colonoscopy among Hispanics.
Colorectal cancer (CRC) is the second most commonly diagnosed cancer among Hispanics in the United States (US), yet the use of CRC screening is low in this population. Physician recommendation has consistently shown to improve CRC screening. To identify the characteristics of Hispanic patients who adhere or do not adhere to their physician's recommendation to have a screening colonoscopy. A cross-sectional study featuring face-to-face interviews by culturally matched interviewers was conducted in primary healthcare clinics and community centers in New York City. Four hundred Hispanic men and women aged 50 or older, at average risk for CRC, were interviewed. Two hundred and eighty (70%) reported receipt of a physician's recommendation for screening colonoscopy and are included in this study. Dependent variable: self report of having had screening colonoscopy. sociodemographics, healthcare and health promotion factors. Of the 280 participants, 25% did not adhere to their physician's recommendation. Factors found to be associated with non-adherence were younger age, being born in the US, preference for completing interviews in English, higher acculturation, and greater reported fear of colonoscopy testing. The source of colonoscopy recommendation (whether it came from their usual healthcare provider or not, and whether it occurred in a community or academic healthcare facility) for CRC screening was not associated with adherence. This study indicates that potentially identifiable subgroups of Hispanics may be less likely to follow their physician recommendation to have a screening colonoscopy and thus may decrease their likelihood of an early diagnosis and prompt treatment. Raising physicians' awareness to such patients' characteristics could help them anticipate patients who may be less adherent and who may need additional encouragement to undergo screening colonoscopy.


[Surgical treatment of rhythm disorders with simultaneous correction of heart valve defects].
Twenty-five patients (14 males and 11 females aged 11 to 45 years) with rhythm disorders and valvular defects were operated on. Supraventricular paroxysmal tachycardia was the most common of rhythm disorders occurring in 15 cases, with Ebstein's anomaly in 11, mitral valve incompetence in 2, combined mitral defects in 1 and aortic stenosis in 1 of those. Atrial fibrillation was recorded in 7 patients, with Ebstein's anomaly in 2, mitral stenosis in 2, mitral incompetence in 2 and mitral prolapse in 1 of those. Nodal tachycardia was found in 1 patients with Ebstein's anomaly and in 1 patient with mitral valve incompetence. Left-ventricular tachycardia was diagnosed in a female patient with mitral prolapse. The operations were simultaneous and comprised two steps; they were performed under extracorporeal circulation and drug- and cold-induced cardioplegia, with the elimination (surgical interruption) of accessory conduction pathways or removal of arrhythmogenic areas as the first step, and reconstructive surgery on heart valves as the second step.


The functional effects of physical exercise training in frail older people : a systematic review.
This systematic review describes the effect of exercise training on physical performance in frail older people. Randomized controlled trials were identified from searches in PubMed, EMBASE and CENTRAL from January 1995 through August 2007. Two reviewers independently screened the trials for eligibility, rated their quality, and extracted data. Randomized controlled trials that examined the effects on performance-based measures of physical function among frail older adults were included. The systematic search identified 20 studies, examining 23 different exercise programmes. The methodological quality score (0-9) of the trials ranged from 2 to 7 points. Sixteen of the studies were scored as high quality. There was a large variety in the studies concerning sample size, degree of frailty, types of interventions and types of assessments. The majority of the programmes were facility-based, group-exercise programmes that were performed three times a week for 45-60 minutes. The intervention programmes comprised resistance training (n = 9), Tai Chi training (n = 2), or multi-component training (n = 12). Six of the total selected 20 studies did not find a beneficial exercise effect on functional performance. This systematic review suggests that older adults with different levels of abilities can improve their functional performance by regular exercise training. To determine the most appropriate design of the exercise programme (type, intensity, frequency and duration of exercise) for functional improvement or prevention of loss of function, more high-quality trials are needed in which different training protocols are compared.


Eating behaviour, body image, and self-esteem of adolescent girls in Malaysia.
This cross-sectional study was undertaken with 489 secondary school girls, ages 15-17 years, to examine disordered eating behaviours of adolescent girls in Malaysia and to estimate associations with body weight, body-size discrepancy, and self-esteem. Dietary restraint, binge eating, body image, and self-esteem were assessed using the Restrained Eating scale of the Dutch Eating Behaviour Questionnaire, the Binge Scale Questionnaire, the Contour Drawing Rating Scale, and the Rosenberg Self-Esteem Scale, respectively. Pearson correlations estimated associations between variables. There were 3.1% underweight, 9.8% at risk of being overweight, and 8.6% overweight girls. A total of 87.3% were dissatisfied with their own body size. Dietary restraint and binge eating were reported by 36.0% and 35.4%, respectively. Body Mass Index (r = .34, p < .01) and body-size dissatisfaction (r = .24, p < .01) were significantly associated with dietary restraint and binge eating, but self-esteem (r = -.20, p < .001) was significantly associated only with binge eating.


Awareness of undergraduate dental students, interns, and freshly graduated dentists about oral manifestation associated with COVID-19.
There is growing evidence supporting the presence of oral manifestations associated with COVID-19. The study investigates the knowledge of dental undergraduates and recently graduated dentists concerning oral presentations related to COVID-19. A cross-sectional descriptive study in Saudi Arabia comprised 305 individuals, including undergraduate dental students, interns, and freshly graduated dentists. Data were collected using a questionnaire disseminated to approximately 500 subjects via WhatsApp groups and other applications. The questionnaire was tested in a pilot study for validity, edited, and validated by 2 supervisors at the College of Dentistry, Qassim University, Buraydah, Saudi Arabia. The questionnaire consisted of questions regarding sociodemographic attributes, the level of expertise of dental practitioners, and their knowledge and perspectives regarding COVID-19 and the implementation of oral lesions interrelated to it. The data was subjected to analysis through the utilization of descriptive statistics and chi-square tests, employing the statistical software SPSS (version 24). About 43.9% of subjects stated that COVID-19 causes oral symptoms. Respondents most frequently reported COVID-19-related dry mouth. Oral ulcers, Candida infection, Hyperpigmentation, tongue coating, atrophy, Petechiae, Herpes, white lesions, Gingivitis, and Periodontitis are further symptoms. COVID-19's oral manifestation was unknown to 41.0% of subjects, and 37.7% of respondents lacked knowledge regarding the most impacted locations of oral manifestations. Oral signs and COVID-19 symptoms are debated and significantly associated with higher educational levels. The dental students and freshly graduated dentists in this study have proper knowledge of COVID-19 and its symptoms. Also, most dental students and newly graduated dentists recognize the potential correlation between COVID-19 and oral manifestations with an average to excellent knowledge of the types and sites commonly affected. The level of awareness was associated with higher educational levels.


The geometry of nonmetal hydrides and the ligand radius of hydrogen.
The aim of this paper was to investigate why the geometries of nonmetal hydrides are often not in accordance with the VSEPR model. From a consideration of interligand distances in a variety of BX(4), CX(4), and NX(4) molecules where X is a ligand or a lone pair and in which there are at least two H ligands we have shown that the hydrogen ligands are essentially close-packed. For each of the central atoms we have obtained a value for the ligand radius of hydrogen. These radii decrease with decreasing negative charge and increasing positive charge of the hydrogen ligand as the electronegativity of the central atom increases, as has been found previously for other ligands such as F and Cl. We show that ligand-ligand intractions are an important factor in determining bond angles in hydrides and that the ligand close-packing (LCP) model gives a better explanation of bond angles than the VSEPR model according to which bond angles depend on the electronegativity of the ligand rather than on its size. For example, although the very small angles in PH(3) and SH(2) are not in accord with the VSEPR model, they are consistent with the LCP model in that they are a consequence of the small size of hydrogen ligands which are pushed together by the lone pairs until they are almost close-packed.


Silencing effect of CpG island hypermethylation and histone modifications on O6-methylguanine-DNA methyltransferase (MGMT) gene expression in human cancer.
O6-methylguanine-DNA methyltransferase (MGMT) repairs the cytotoxic and mutagenic O6-alkylguanine produced by alkylating agents such as chemotherapeutic agents and mutagens. Recent studies have shown that in a subset of tumors, MGMT expression is inversely linked to hypermethylation of the CpG island in the promoter region; however, how the epigenetic silencing mechanism works, as it relates to hypermethylation, was still unclear. To understand the mechanism, we examined the detailed methylation status of the whole island with bisulfite-sequencing in 19 MGMT non-expressed cancer cell lines. We found two highly methylated regions in the island. One was upstream of exon 1, including minimal promoter, and the other was downstream, including enhancer. Reporter gene assay showed that methylation of both the upstream and downstream regions suppressed luciferase activity drastically. Chromatin immunoprecipitation assay revealed that histone H3 lysine 9 was hypermethylated throughout the island in the MGMT negative line, whereas acetylation on H3 and H4 and methylation on H3 lysine 4 were at significantly high levels outside the minimal promoter in the MGMT-expressed line. Furthermore, MeCP2 preferentially bound to the CpG-methylated island in the MGMT negative line. Given these results, we propose a model for gene silencing of MGMT that is dependent on the epigenetic state in cancer.


A new method for kidney perfusion in situ: application to dynamics of autoregulation.
A procedure for in situ perfusion of kidney was developed in which renal resistance does not rise with continued perfusion at a constant rate and renal blood flow (RBF) can be changed as a step function. The kidney of dogs anesthetized with pentobarbital-chloralose was perfused by a pulsatile syringe pump via an extracorporeal circuit placed between the femoral artery and the renal artery. The perfusion pressure and pulse rate can be adjusted to match those of the dog. Following a step change in RBF from the control level, the dynamics of the autoregulatory response was studied by determining the time course of the alteration in renal perfusion pressure as RBF was maintained at the new constant level. An increase in RBF led to a time-dependent renal vasoconstriction (increase in renal resistance), and a decrease in RBF caused a time-dependent renal vasodilation (decrease in renal resistance). The time course of the response of renal resistance to step changes in RBF can be described by monoexponential functions. The time constant obtained for resistance changes after both an increase and a decrease in RBF was 37.5 +/- 2.8 (SD) s. During the period of step recovery from changes in RBF in either direction, the time constant of the renal resistance response was 53.4 +/- 3.2 s. These values are useful for the analysis of the mechanism of renal autoregulation as well as the modeling of circulatory and hormonal control. The results also indicate that this new procedure for renal perfusion in situ is well suited for studying renal hemodynamics and other functions.


Reflections on tissue engineering and trauma therapy.
Although all of Trauma Care has remarkably improved during the latter half of the last century the treatment of burn injury has substantially out paced other areas and serves as an excellent example illustrating the improvements taking place in the treatment of injured patients. Although Trauma treatment lagged behind the rest of medicine in mid-century today it rests solidly on the cutting edge of advancing therapeutic knowledge and practice in areas of metabolism, immunology, infection control, critical care, tissue engineering and the delivery of clinical care. It is important to understand what has happened to allow the treatment of injury to be so effective. The bench mark therapeutic moves that have had major effects allowing the present highly effective treatment are: immediate tailored fluid resuscitation, preventive (prophylactic) and topical antibiotics, metabolically designed nutritional therapy and most important early definitive repair of the injury. All must be delivered early after trauma if they are to be optimally effective in preventing the complications of injury that are devastating if encountered. Unfortunately, all problems are not solved by todays treatment of injury, improved as it is. These problems are largely related to an inexact understanding: of the physiologic changes of aging, of the exact pathophysiologic events in inhalation injury and multisystem organ failure and of the technology required to replace those body parts damaged by the injury itself that lead to death or to healing with loss of function. There will be major improvements in the understanding and ability to effectively deal with the problems of aging and inhalation injury through basic and clinical research but perhaps the major improvement in injury treatment will come through the ability to replace worn out, defective or damaged body parts through technologies that resemble regeneration. Here the concepts of Tissue Engineering have much to contribute and it is worth exploring the donation of Tissue Engineering to dermal replacement following burn injury to serve as an example of what types of additions to treatment Tissue Engineering can make.