Alveolar iodine tampon packing after impacted third molar surgery improves oral health-related quality of life and postoperative sequela: a randomized study.
The aim of this study was to evaluate the effect of an iodine tampon on postoperative discomfort after surgical removal of a mandibular third molar. Patients were randomly assigned to two groups: one group received an alveolar iodine-containing tampon in the extraction socket (N = 44), and the other group used a disposable syringe (Monoject®) to rinse the wound (N = 43). Postoperative discomfort was assessed with the Oral Health Impact Profile-14 (OHIP-14) questionnaire, Pain Intensity Numerical Rating Scale (PI-NRS), and questions about self-care and discomfort. This study included 87 patients (52 women and 35 men) with an average age of 26.47 years (SD, 6.36). The mean OHIP-14 sum scores were significantly lower in the iodine tampon group compared with the Monoject® syringe group. Mean PI-NRS scores significantly differed between the iodine tampon group (3.33; SE, 0.27) and Monoject® syringe group (4.46; SE, 0.27) (F (1, 85) = 8.16, p < 0.01), with no interaction effect between time and PI-NRS (F (6, 510) = 1.26, p = 0.28). Patients in the iodine tampon group reported less postoperative discomfort. Insertion of an iodine-containing tampon in the postoperative socket reduced the pain and impact on oral health-related quality of life during the first postoperative week and positively influenced postoperative sequelae.


Ion balance, uptake, and transport processes in n(2)-fixing and nitrate- and urea-dependent soybean plants.
The objective of this study was to examine the influence of N(2) fixation and NO(3) (-)-N and urea-N assimilation on ion balance, uptake, and transport processes in soybean (Glycine max L. Merr.).Inoculated plants were grown in Perlite supplied daily with nutrient solutions which contained zero-N, 10 and 20 millimolar NO(3) (-)-N, and 10 and 20 millimolar urea-N, and they were sampled 41, 76, and 151 days after transplanting. Total uptake of inorganic cations and anions was determined by analysis of tissue for K(+), Ca(2+), Mg(2+), Na(+), total N from NO(3) (-), total S, H(2)PO(4) (-), and Cl(-). Differences in total inorganic cations (C) and inorganic anions (A) in plant tissue were used to estimate total carboxylate content.Internal OH(-) generation resulting from excess cation uptake (net H(+) excretion) by the roots accounted for more than 89% of the carboxylate accumulation in N(2)- and urea-fed plants, while OH(-) generation resulting from SO(4) (2-) reduction accounted for less than 11%. Shoots contained over 89% of the total plant carboxylate content. Malate balanced about 75% of the excess inorganic cationic charge of the xylem sap; allantoate and aspartate balanced most of the remaining charge. These results indicate that carboxylates (primarily malate) are synthesized in roots of N(2)- and urea-fed plants and transported to the shoots in the xylem to maintain charge balance. The high malate concentration resulted in the C/N weight ratio of xylem sap from N(2)-fed plants being >2.0, even though 83% of the N was transported as allantoin and allantoic acid which have a C/N ratio of 1.0. The data emphasize that C and N content of N compounds should not be the sole basis for calculating the C/N weight ratio of xylem sap.The C-to-A uptake ratio for plants supplied 10 millimolar NO(3) (-) ranged from 1.24 to 1.57 during development, indicating that internal OH(-) was generated both by excess cation uptake and by NO(3) (-) and SO(4) (2-) reduction. The C-to-A uptake ratio for 20 millimolar NO(3) (-) -fed plants ranged from 0.86 to 0.96 during development, indicating a small net OH(-) efflux from the roots for support of excess anion uptake. On a seasonal basis, only 15% of the OH(-) generated during NO(3) (-) and SO(4) (2-) reduction was associated with OH(-) efflux (excess anion uptake), while 85% was associated with carboxylate accumulation. The malate concentration in xylem sap from plants supplied 20 millimolar NO(3) (-) was only one-third that of N(2)- and urea-fed plants; however, it did balance 75% of the excess inorganic cationic charge. Potassium, recycling to accommodate excess anion uptake by 20 millimolar NO(3)-fed plants, was calculated to involve at most 17% of the total K(+) absorbed during the 41- to 76-day growth interval.


Mesostigmatid mites (Acari: Mesostigmata) on rainforest tree trunks: arboreal specialists, but substrate generalists?
Predatory mites (Acari: Mesostigmata) on tree trunks without significant epiphytic growth in a subtropical rainforest in Eastern Australia were assessed for habitat specificity (i.e. whether they are tree trunk specialists or occupying other habitats) and the influence of host tree and bark structure on their abundance, species richness and species composition. The trunks of nine tree species from eight plant families representing smooth, intermediate and rough bark textures were sampled using a knockdown insecticide spray. In total, 12 species or morphospecies of Mesostigmata (excluding Uropodina sensu stricto) were collected, most of which are undescribed. Comparison with collections from other habitats indicates that epicorticolous Mesostigmata are mainly represented by suspended soil dwellers (six species), secondarily by generalists (four species) and a bark specialist (one species). A typical ground-dwelling species was also found but was represented only by a single individual. In terms of abundance, 50.5% of individuals were suspended soil dwellers, 40.7% bark specialists, and 8.3% generalists. Host species and bark roughness had no significant effect on abundance or species richness. Furthermore, there was no clear effect on species composition. The distribution of the most frequently encountered species suggests that most mesostigmatid mites living on bark use many or most rainforest tree species, independent of bark roughness. These findings support the hypothesis that some epicorticolous Mesostigmata use tree trunks as 'highways' for dispersing between habitat patches, while others use it as a permanent habitat.


Effectiveness of modified periodontally accelerated osteogenic orthodontics in skeletal class II malocclusion treated by a camouflage approach.
Skeletal Class II malocclusion is a complex orofacial condition. Here, we translated the single clinical problem to a multidisciplinary approach that combined the periodontal surgery, biomaterial implantation, and orthodontics to treat this condition. This study aimed to explore the clinical effectiveness of modified periodontally accelerated osteogenic orthodontics (PAOO) in adult patients with skeletal Class II discrepancy via a camouflage orthodontic approach. This clinical trial has been registered in the Chinese Clinical Trial Registry (trial number: ChiCTR2100052638, trial URL: http://www.chictr.org.cn/showproj.aspx?proj=135827). A total of 26 adult female patients with similar skeletal Class II malocclusions and similar dental and skeletal discrepancies were enrolled. A total of 13 patients in the experimental group received modified PAOO characterized by vertical incisions in interradicular areas and random punching made by a piezoelectric device, whereas 13 patients in the control group received orthodontic treatment only. All patients underwent extraction of four premolars and orthodontic treatment with the sliding MBT straight-wire technique. Treatment courses were recorded and changes in dental and skeletal parameters were evaluated by cephalometric analysis and translated into upper digital cast for further measurements. The results showed that the durations of the alignment and leveling stage (4.51±1.53 mos versus 9.41±1.46 mos. P<0.01), space closing stage (13.56±2.57 mos versus 17.09±3.50 mos. P<0.05) and total treatment course (24.43±2.53 mos versus 31.16±4.17 mos. P<0.01) in the PAOO group were significantly shorter than in the control. The modified PAOO accelerated orthodontic tooth movement in adult extraction cases with skeletal Class II discrepancy and convex profile; the modified PAOO achieved dual goals of periodontal health and long-term stability of orthodontics. Ultimately, this multidisciplinary approach and the use of translational 3D measurements constitute powerful tools that can be used to solve complex clinical problems.


Nobody needs "relative tumour sizes" to compare tumour growth curves.
Tumour growth curve experiments play an important role in experimental oncology and established methods exist for their unbiased interpretation. However, many authors till introduce systemic biases to their data by using the so-called "relative tumour size" transformation, inspite of wide awarance about the limitations of this latter method. With this communication and by using a fictive exaggeration of the problems connected with the application of this transformation we would like to appeal to both authors and reviewers likewise to ban this potential source of misinterpretation from the oncological literature.


Method to measure the optical properties of small volumes of diffusive media.
The method consists of measuring the perturbation provoked by a small volume of the diffusive medium on light propagating through a medium of known optical properties. The absorption and the reduced scattering coefficients of the medium are retrieved from multidistance continuous-wave measurements of transmittance. The inversion procedure is based on the solution of the diffusion equation obtained with a perturbative approach. The method has been validated with Monte Carlo results. Examples of experimental results are reported.


Photosynthesis In Elodea canadensis Michx: Four-Carbon Acid Synthesis.
Experiments to determine the early labeled photosynthetic products in Elodea canadensis show that after 2 seconds of exposure to NaH(14)CO(3), 45% of the (14)C incorporated is located in malate and aspartate. Phosphoglyceric acid and sugars account for 27% of the label during similar exposures. Equivalent amounts of organic acids and C(3) cycle products are present after 8 seconds. Four-carbon acids remain relatively unchanged throughout the first 45 seconds of exposure, while sugars increase in a linear fashion. Enzyme assays indicate that ribulose diphosphate and phosphoenolpyruvate carboxylase enzymes are present in a ratio of approximately 2:1. It appears that E. canadensis is able to synthesize significant amounts of four-carbon acids via beta-carboxylation and this may play a role in maintaining a pH favorable for carboxylation in aquatic plants.


Medically serious versus non-serious suicide attempts: relationships of lethality and intent to clinical and interpersonal characteristics.
The study of near-fatal suicide attempts may provide insight into the minds of suicidal subjects. The aim of the study was to investigate the relationship of intent and lethality in medically serious and medically non-serious suicide attempts and to examine relationship of specific psychological and clinical variables with the subjective and objective components of suicide intent. The study group included 102 participants, 35 consecutive subjects hospitalized for a medically serious suicide attempt and 67 subjects who presented to the same tertiary medical center after a medically non-serious suicide attempt. All were interviewed with the SCID-I and completed the Suicide Intent Scale (SIS), the Lethality Rating Scale, and instruments measuring mental pain and communication difficulties. Patients who made medically serious suicide attempts had higher total SIS score and higher objective and subjective subscale scores. The objective component of the SIS was highly correlated with the lethality of the suicide attempt and communication difficulties; the subjective component was associated with mental pain variables. The interaction of mental pain and communication difficulties was predictive of the severity of the objective suicide intent. Relatively small number of patients with medically serious suicide attempt and the relatively large number of questionnaires which may to some extent have diminished informant reliability. Suicidal individuals with depression and hopelessness who cannot signal their pain to others are at high risk of committing a medically serious suicide attempts.


Cholestatic effect of large bilirubin loads and cholestasis protection conferred by cholic acid co-infusion: a molecular and ultrastructural study.
Large intravenous bilirubin loads block biliary phospholipid secretion, produce canalicular membrane lesions and cause canalicular cholestasis. Cholic acid co-infusion forestalls these untoward effects. The aim of this study was first to determine whether bilirubin overload causes cholestasis through reducing the activity or the hepatic expression of the bile salt export pump (bsep) or Na-taurocholate co-transporting polypeptide (ntcp) and, secondly, whether cholic acid co-infusion forestalls cholestasis by upregulating bsep, ntcp or phosphoglycoprotein 3 (pgp3) expressions or activities. A further aim was to determine whether large bilirubin infusions also produce ultrastructural changes inside hepatocytes. The effects of intravenous infusion of 2 g bilirubin over 150 min on hepatic expression of bsep, ntcp and pgp3 were studied in bile acid-depleted and cholic acid co-infused pigs, and related to canalicular bile acid transport and bile secretion. Effects on hepatocyte ultrastructural morphology were analysed by electron microscopy. Bilirubin-induced cholestasis reflected marked diminution of bsep and pgp3 transport activities and not reduced hepatic expression of these transporters. Hepatocyte ultrastructural abnormalities were predominantly confined to the hepatocyte canalicular membrane in cholestatic livers. Cholic acid co-infusion with bilirubin conferred complete cholestasis protection through enhancing pgp3 and bsep transporter activities and not through upregulating their expression. Bilirubin infusion did not change ntcp expression. Bilirubin-induced cholestasis is due to markedly impaired activity of the membrane-embedded bsep transporter consequent upon ultrastructural injury to the canalicular membrane. Cholic acid co-infusion with bilirubin enhances bsep and pgp3 activities and confers protection against canalicular membrane injury and bilirubin-induced cholestasis.


Electron transfer photoredox catalysis: intramolecular radical addition to indoles and pyrroles.
The utilization of the photoredox catalyst, tris(2,2'-bipyridyl)ruthenium dichloride, and a household light bulb to effect radical cyclizations onto indoles and pyrroles at room temperature is reported. A reactive free radical intermediate is generated via the reduction of an activated C-Br bond by the single electron reductant, Ru(I), generated in a visible light induced photocatalytic cycle. This system represents an expansion of the application of photoredox catalysis in conventional free radical processes.


A system for accelerometer-based gesture classification using artificial neural networks.
A great many people suffer from neurological movement disorders that render typical hardware interface devices ineffective. A need exists for a universal interface device that can be trained to accept a wide range of inputs across varying types and severities of movement disorders. In this regard, this paper details the design, testing and optimization of an accelerometer-based gesture identification system. A Bluetooth-enabled IMU mounted on the wrist provides hand motion trajectory information to a local terminal. Several techniques are applied to decrease the intra-class variance and reduce classifier complexity including filtering, segmentation and temporal scaling. Datasets consisted of 520 training samples, 260 validation samples and a further 520 testing samples. A multi-layer feed forward artificial neural network (ML-FFNN) was used to classify the input space into 26 different classes. Initial system accuracy, using arbitrary hyperparameters was 77.69% with final optimized accuracy at 99.42%.


COVID-19 and thrombosis: Clinical features, mechanism of disease, and therapeutic implications.
COVID-19 is a viral respiratory illness caused by the SARS-CoV-2 infection. In addition to lung disease, clinical complications of COVID-19 include myocardial damage and ischemia-related vascular disease. Severe manifestations and poor prognosis in these patients are associated with a hypercoagulable state predisposing to thrombotic-related complications and eventually death. However, these clinical features can also occur in other forms of pneumonia, such as community-acquired pneumonia (CAP), which, is also complicated by vascular diseases and characterized by platelet activation. Platelets play a pivotal role in these settings as bacteria and viruses may induce activation via Toll-like receptors (TLRs) in CAP patients and different and multiple pathways, including ACE2-AngII axis and/or TLRs, in COVID-19 patients. Despite evidence confirming the implication of platelet activation in both settings, their contribution to the thrombotic process is still under investigation. Thus, in this review, we (1) compare the thrombotic features of SARS-CoV-2 infection and CAP, (2) analyze the putative mechanisms accounting for venous and arterial thrombosis in SARS-CoV-2 infection, and (3) discuss the potential anticoagulant armamentarium to counteract thrombosis.


Fatal Meningitis in a 14-Month-Old with Currarino Triad.
We report a case of a 14-month-old girl with undiagnosed Currarino triad presenting acutely with meningitis caused by enteric commensals. Head CT demonstrated a large pneumocephalus. A fistulous neurenteric tract through a presacral mass was present on spine MRI and abdominal CT. The patient had a history of constipation for the last three months. However, an underlying diagnosis of Currarino triad had not been suspected. In retrospect, a sickle-shaped sacral anomaly was present on a previous abdominal radiograph. The patient succumbed to complications of meningitis. The purpose of the case report is to highlight the potentially fatal complication of Currarino triad and sensitize radiologists to look actively for sacral anomalies on abdominal radiographs, especially of children with chronic constipation.


The cytokine-induced conformational switch of nuclear factor κB p65 is mediated by p65 phosphorylation.
The transcription factor NF-κB (nuclear factor κB) serves to up-regulate gene expression in response to precarious signals such as the pro-inflammatory cytokines TNF (tumour necrosis factor) and IL-1 (interleukin 1). In the present study we show that stimulation of cells with TNF or IL-1 results in a profound conformational switch of the NF-κB subunit p65, as revealed by limited proteolysis assays. We also describe the identification of a conformation-specific monoclonal antibody that preferentially immunoprecipitates the inducibly refolded p65 protein. The cytokine-triggered reconfiguration of p65 mainly occurs for p65 contained in the nuclear fraction. Phosphorylations serve as the central driving force for the inducible reconfiguration of p65. Accordingly, mutation of single phosphorylation sites in the C-terminal transactivation domain led to large conformational changes which result in strongly decreased ubiquitination and also in differential protein-protein interactions. Induced conformational changes of p65 thus increase the intramolecular flexibility and therefore expand and specify the repertoire of possible protein-protein interactions. Constitutively bound chaperones of the Hsp (heat-shock protein)/Hsc70 (heat-shock cognate protein, 73 kDa) family are not important for the cytokine-induced conformational switch, but rather control the fidelity of protein rearrangement. Accordingly, pharmacological inhibition of Hsp/Hsc70 interferes with p65-triggered gene expression.


Targeted, Stimuli-Responsive, and Theranostic 19F Magnetic Resonance Imaging Probes.
Unlike conventional 1H magnetic resonance imaging (MRI), 19F MRI features unambiguous detection of fluorine spins due to negligible background signals. Therefore, it is considered a promising noninvasive and selective imaging method for the diagnosis of cancers and other diseases. For 19F MRI, fluorine-rich molecules such as perfluorocarbons (PFC) have been formulated into nanoemulsions and used as its tracer agent. Along with advancements in other types of nanoparticles as targeted theranostics and stimuli-triggered probes and combined with the advantages of 19F MRI, PFC nanoemulsions are being empowered with these additional functionalities and becoming a promising theranostic platform. In this Review, we provide an overview of fluorine-based materials for sensitive 19F MRI of biological and pathological conditions. In particular, we describe designs and applications of recently reported stimuli-responsive and theranostic 19F MRI probes. Finally, challenges and future perspectives regarding the further development of 19F MRI probes for their clinical applications are described.


A case of severe visceral leishmaniasis resulting from travel to Greece.
Visceral leishmaniasis is rare in the developed world, particularly in immunocompetent hosts. It must be considered, however, in patients who are unwell, febrile and unresponsive to conventional antibiotics with a history of travel to areas where leishmaniasis is endemic. A case of more severe clinical manifestations than have been previously reported in Australia is presented here. The recent introduction of PCR technology for the detection of Leishmania in Australia has improved the diagnosis and management of leishmaniasis. Treatment with liposomal amphotericin B proved to be very effective in this severe case of visceral leishmaniasis.


High precision measurements of 17O/16O and 18O/16O ratios in H2O.
We have optimized the method of water fluorination using the solid reagent CoF3 to produce O2. This allows isotope ratio measurements by dual-inlet mass spectrometry with very high precision of 0.01 to 0.03/1000 for both delta17O and delta18O. Using this method, delta17O and delta18O of atmospheric O2 were determined as 12.08 and 23.88/1000 vs. VSMOW, respectively. Likewise, delta17O and delta18O of GISP were -13.12 and -24.73/1000, and for SLAP they were -29.48 and -55.11/1000 vs. VSMOW, respectively. Analysis of these data in a ln(delta17O + 1) vs. ln(delta18O + 1) plot yields a line with a regression coefficient (lambda) of 0.5279 +/- 0.0001 (R2 = 0.999999). We also determined the fractionation factors 17alpha and 18alpha in liquid-vapor equilibrium, and found that the ratio ln 17alpha/ln 18alpha is constant (0.529 +/- 0.001) over the temperature range 11.4 to 41.5 degrees C.


Stress-Induced Evolution of Heat Resistance and Resuscitation Speed in Escherichia coli O157:H7 ATCC 43888.
The development of resistance in foodborne pathogens to food preservation techniques is an issue of increasing concern, especially in minimally processed foods where safety relies on hurdle technology. In this context, mild heat can be used in combination with so-called nonthermal processes, such as high hydrostatic pressure (HHP), at lower individual intensities to better retain the quality of the food. However, mild stresses may increase the risk of (cross-)resistance development in the surviving population, which in turn might compromise food safety. In this investigation, we examined the evolution of Escherichia coli O157:H7 strain ATCC 43888 after recurrent exposure to progressively intensifying mild heat shocks (from 54.0°C to 60.0°C in 0.5°C increments) with intermittent resuscitation and growth of survivors. As such, mutant strains were obtained after 10 cycles of selection with ca. 106-fold higher heat resistance than that for the parental strain at 58.0°C, although this resistance did not extend to temperatures exceeding 60.0°C. Moreover, these mutant strains typically displayed cross-resistance against HHP shock and displayed signs of enhanced RpoS and RpoH activity. Interestingly, additional cycles of selection maintaining the intensity of the heat shock constant (58.5°C) selected for mutant strains in which resuscitation speed, rather than resistance, appeared to be increased. Therefore, it seems that resistance and resuscitation speed are rapidly evolvable traits in E. coli ATCC 43888 that can compromise food safety. In this investigation, we demonstrated that Escherichia coli O157:H7 ATCC 43888 rapidly acquires resistance to mild heat exposure, with this resistance yielding cross-protection to high hydrostatic pressure treatment. In addition, mutants of E. coli ATCC 43888 in which resuscitation speed, rather than resistance, appeared to be improved were selected. As such, both resistance and resuscitation speed seem to be rapidly evolvable traits that can compromise the control of foodborne pathogens in minimal processing strategies, which rely on the efficacy of combined mild preservation stresses for food safety.


Comparative analysis of Corynebacterium glutamicum genomes: a new perspective for the industrial production of amino acids.
Corynebacterium glutamicum is a non-pathogenic bacterium widely used in industrial amino acid production and metabolic engineering research. Although the genome sequences of some C. glutamicum strains are available, comprehensive comparative genome analyses of these species have not been done. Six wild type C. glutamicum strains were sequenced using next-generation sequencing technology in our study. Together with 20 previously reported strains, we present a comprehensive comparative analysis of C. glutamicum genomes. By average nucleotide identity (ANI) analysis, we show that 10 strains, which were previously classified either in the genus Brevibacterium, or as some other species within the genus Corynebacterium, should be reclassified as members of the species C. glutamicum. C. glutamicum has an open pan-genome with 2359 core genes. An additional NAD+/NADP+ specific glutamate dehydrogenase (GDH) gene (gdh) was identified in the glutamate synthesis pathway of some C. glutamicum strains. For analyzing variations related to amino acid production, we have developed an efficient pipeline that includes three major steps: multi locus sequence typing (MLST), phylogenomic analysis based on single nucleotide polymorphisms (SNPs), and a thorough comparison of all genomic variation amongst ancestral or closely related wild type strains. This combined approach can provide new perspectives on the industrial use of C. glutamicum. This is the first comprehensive comparative analysis of C. glutamicum genomes at the pan-genomic level. Whole genome comparison provides definitive evidence for classifying the members of this species. Identifying an aditional gdh gene in some C. glutamicum strains may accelerate further research on glutamate synthesis. Our proposed pipeline can provide a clear perspective, including the presumed ancestor, the strain breeding trajectory, and the genomic variations necessary to increase amino acid production in C. glutamicum.


Comorbidity of depressive and anxiety disorders: challenges in diagnosis and assessment.
Comorbid anxiety is common in patients with depressive disorders. It complicates the clinical presentation of depressive disorders and can contribute to treatment resistance. Clinicians can assess the degree of overlap between depressive and anxiety symptoms either by measuring the severity of anxiety symptoms in individuals who meet diagnostic criteria for depression or by determining whether or not an individual with depression simultaneously meets criteria for an anxiety disorder. However, multiple factors in the Chinese clinical setting make it difficult to accurately assess patients with comorbid conditions. The resultant under-diagnosis of comorbid depression and anxiety - the most common type of comorbid psychiatric condition in China - seriously diminishes the effectiveness of treatments for common mental disorders in the country. We argue that the widespread use of valid and reliable dimensional assessment tools in Chinese clinical settings will help improve the diagnosis and treatment of the many individuals who have concurrent depressive and anxiety symptoms.


Effects on the contralateral eye after intravitreal bevacizumab and ranibizumab injections: a case report.
We report a case in which intravitreal bevacizumab and ranibizumab appeared to have effects in the contralateral, uninjected eye. An 83-year-old man with macular oedema from branch retinal vein occlusion (BRVO) in the right eye developed neovascular macular degeneration in the left eye. Intravitreal bevacizumab in the left eye improved macular oedema in the right eye temporarily before it recurred. Subsequently, intravitreal ranibizumab in the left eye also resulted in significant reduction of macular oedema in the right eye. Vision and macular oedema in the right eye improved. Bevacizumab and ranibizumab may have therapeutic effects in the uninjected eye, possibly because they may escape from the eye into the systemic circulation.


Preoperative Nutritional Status as an Adjunct Predictor of Major Postoperative Complications Following Anterior Cervical Discectomy and Fusion.
Retrospective analysis of the National Surgical Quality Improvement Program (NSQIP), a prospectively collected multicenter surgical outcomes database. To determine the effect of preoperative nutritional status, as measured by serum albumin concentration, on outcomes following anterior cervical discectomy and fusion (ACDF). Nutritional status has been shown to be an important predictor of postoperative recovery and outcomes. Serum albumin concentration is an established marker of overall nutrition and systemic disease, however, its correlation to outcomes following ACDF is unknown. ACDF cases from 2005 to 2010 were identified in the NSQIP and categorized by preoperative serum albumin: normal (≥3.5 g/dL), hypoalbuminemic (<3.5 g/dL), or not measured. Independent demographic and comorbidity variables were assessed, including American Society of Anesthesiologists (ASA) classification. Risk factors for major postoperative complications were identified, including preoperative hypoalbuminemia, and incorporated into a multivariable logistic regression model to determine the strength of preoperative hypoalbuminemia as an adjusted predictor of major postoperative complications. There were 3671 ACDF cases, of which 1382 (37.6%) had preoperative albumin measurements. Patients with albumin measurements were older and more likely to have higher ASA class, hypertension, and diabetes. Hypoalbuminemic patients had higher rates of having any major postoperative complication(s), specifically pulmonary complications, cardiac complications, and reoperation, relative to those with normal albumin (all P<0.01). These patients also had longer lengths of stay (5.0 vs. 1.9 d). With multivariable regression, preoperative hypoalbuminemia was a strong independent predictor of major postoperative complications, with an adjusted odds ratio of 3.37 (P=0.003). In this analysis of a prospective surgical outcomes database, preoperative serum hypoalbuminemia was an important adjunct predictor of major complications following ACDF. In high-risk patients with multiple medical comorbidities, we recommend that clinicians consider nutritional screening and optimization as part of preoperative risk assessment.


Plasma sulfate concentration and hyperhomocysteinemia in hemodialysis patients.
Severe hyperhomocysteinemia is common in hemodialysis patients, who also present a dramatic increase in plasma concentrations of sulfate, one of the main products of methionine and cysteine catabolism. The aim of this study was to verify the relationship between high plasma sulfate levels and cysteine or homocysteine concentrations in hemodialysis patients. Plasma sulfate, cysteine and homocysteine concentrations and some renal efficiency parameters were determined in 18 patients with end-stage renal failure, all undergoing 4h hemodialysis three times a week. The pattern of post-dialysis rises on plasma concentrations of sulfate, cysteine and homocysteine was established. Plasma sulfate, cysteine and homocysteine levels were significantly higher in patients than in normal controls. Plasma sulfate concentrations positively correlated with cysteinemia (p = 0.031; r = 0.482) which, in turn correlated with homocysteinemia (p = 0.042; r = 0.460). Sulfate levels also correlated with blood creatinine (p = 0.004; r = 0.630), nitrogen (p = 0.000; r = 0.899), protein (p = 0.014; r = 0.555), and albumin (p = 0.003; r = 0.642). Post-dialysis rises in sulfate and cysteine were detected some hours before homocysteine. The results suggest that high sulfate levels, due mainly to impaired renal function, are involved in the altered metabolism of homocysteine in hemodialysis patients.


IGFBP2 and IGFBP3 protein expressions in human breast cancer: association with hormonal factors and obesity.
The insulin-like growth factor (IGF) signaling system is involved in breast cancer initiation and progression. The prognostic relevance of tumor expression patterns of IGFI-related proteins remains poorly understood. This study associates the expression of selected IGF proteins with breast tumor and patient characteristics. IGFI, IGFI receptor, IGF-binding protein (IGFBP)2, and IGFBP3 expression was measured in 855 primary breast carcinomas by immunohistochemistry using tissue microarrays. We investigated the association of tumor and nodal stage, grade, hormone receptor status, HER2 gene amplification, menopausal status, body mass index, and survival with IGF protein expression. In contrast to IGFI, the expression of IGFI receptor, IGFBP2, and IGFBP3 was associated with estrogen receptor status. In addition, IGFBP3 was positively correlated with body mass index and premenopausal status. Importantly, IGFBP2 was an independent and positive predictor of overall survival (hazard ratio, 0.48; 95% confidence interval, 0.24-0.95; P = 0.04). There was a weak suggestion for IGFBP2 and overweight to modify each other's effect on survival. According to these results, which need confirmation in larger patient series, the prognostic relevance of IGFBP2 and IGFBP3 protein expressions in breast cancer may depend on the hormonal context and body weight.


On the effects of the dispersant Corexit 9500© during the degradation process of n-alkanes and PAHs in marine sediments.
In many coastal countries, oil spill contingency plans include several alternatives for removal of the spilled oil from the ocean. Frequently, these plans include dispersants. Because this process applies chemical substances that may add toxicity to oil that already contains toxic compounds, it is, at times, a controversial method to fight oil pollution. Additionally, local conditions may result in particular complications. We investigated the possible effects of the dispersant Corexit 9500© under conditions similar to those of subtropical oceans. We used fuel oil #6+ diesel as the test mixture. Under certain conditions, at least part of the dispersed oil may reach the sediment, particularly if the dispersant is applied in coastal waters. Nine experimental units were used in this experiment. Similar conditions of water temperature, salinity, air fluxes into the experimental units, and hydrocarbon concentrations in sediments were used. Two treatments and one control, each one with three replicates, were carried out. We concentrated our investigation on sediment, although measurements of water were also taken. Our results suggest that once the oil has penetrated the sediment, no significant differences exist between oil that contains dispersant and oil without dispersant. Noticeable degradation of aliphatic hydrocarbons occurred mainly in the low molecular weight aliphatic hydrocarbons and not in the others. Apparently, degradation of aromatics was easier than that of alkanes. However, some differences were noticed for the degradation of PAHs in the sediment, suggesting a faster degradation under particular conditions in aerobic environments such as under this experiment.


[Viral myc oncogene in the genome of transgenic mice and their progeny].
The fused gag-v-myc oncogene was microinjected into fertilized mouse eggs, which were then implanted into foster mothers. Approximately 26% of the offsprings from injected eggs carried v-myc sequences. 26 of 32 progeny animals were found to be transgenic and some progeny containing the amplified oncogene (about 40 copies per genome). In one F0 and one F1 mice 1.5-2 months after birth the development of tumors was observed: rhabdomyosarcoma and sebaceous carcinoma. In both the cases the tumors were highly differentiated. Because spontaneous tumors of these types are seldom observed in common lines of mice it seems probable that the tumors observed in this study may be associated with the presence of oncogene v-myc.


p53 immunohistochemical expression of Egyptian cervical carcinoma.
Data concerning the expression of p53 in cervical carcinoma, one of the leading cause of death in developing countries, are still confusing. This study was designed to identify p53 in Egyptian cervical carcinoma in an attempt to evaluate its prognostic significance. Eleven chronic cervicitis and 38 invasive carcinoma (31 squamous cell carcinoma (sqcc) and 7 adenocarcinoma, ranging from stage IB to IVB), were stained with the monoclonal antibody anti p53, DO7, using the microwave for antigen retrieval. No immunoreactivity was detected in chronic cervicitis, while nuclear p53 reactivity was detected in all carcinoma and in squamous intra-epithelial lesions (SIL) overlying 8 sqcc. P53 immunohistochemical (IHC) expression was more pronounced in early clinical stages (p=0.007) and in adenocarcinoma compared to sqcc (p=0.015). A positive correlation was present between p53 and heat shock protein 70 (hsp70) expressions (p=0.005). No correlation could be found between p53 expression and tumor infiltrating lymphocytes, the presence or absence of either schistosomiasis or HPV infections. It can be concluded, that in the Egyptian population, p53 immunoreactivity appears to be an early event in cervical neoplasm, and seems to play an important role together with other cell regulatory proteins in the process of carcinogenesis, which could be different between sqcc and adenocarcinoma.


[Use of the Powell method to optimize the composition of HPLC mobile phase--the separation of ephedrine and pseudoephedrine].
The isomers ephedrine and pseudoephedrine are difficult to be separated by HPLC. In this paper, the Powell method was successfully introduced to optimize the composition of mobile phase in HPLC. On a mu Bondapak C18 column (8-10 microns, 3.9 mm x 30 cm), KH2PO4 solution methanol mobile phase system was optimized for separating ephedrine and pseudoephedrine by the Powell method. The optimized composition of the mobile phase was found as: 0.01 mol/L KH2PO4 -MeOH = 94: 6 (V/V). The Powell method was carried out in a process illustrated by tables and figures and 0.95 peak separation function was achieved.


Glutathione S-transferase pi Protects Serum Depletion-induced Cell Death by Inhibiting ASK1-MKK7-JNK Pathway in the 293 Cells.
Glutathione S-transferase pi (GSTpi) protects cells from death by altering intracellular oxidative stress. In order to understand the mechanism of GSTpi protection, a cell death model induced by serum depletion as the stress was established. Cotransfection of apoptosis signal-regulating kinase 1 (ASK1) and GSTpi cDNA was performed to elucidate the impact of GSTpi on ASK1 activity, as well as on its downstream signals, MKK7 and JNK, and to elucidate the potential protection of GSTpi on 293 cell death induced by serum depletion. The dominant negative mutant of JNK was used to explore if the blocking of the JNK pathway led to cell death inhibition. It was found that GSTpi had a dose-dependent inhibitory effect on activation induced by serum depletion, and also on inhibition both on MKK7 and JNK. Intracellular expression of GSTpi significantly inhibited serum depletion-induced cell death. Blocking the JNK pathway by transfection of a dominant negative form of JNK (JNK (APF)) brought about significant inhibition of cell death induced by serum depletion with an inhibiting rate as high as 15%. All the results suggest that the mechanism of GSTpi protection on serum depletion-induced cell death works through an ASK1-MKK7-JNK pathway.


Development and evaluation of a multiplex real-time polymerase chain reaction procedure to clinically type prevalent Salmonella enterica serovars.
A multiplex real-time polymerase chain reaction procedure was developed to identify the most prevalent clinical isolates of Salmonella enterica subsp. enterica. Genes from the rfb, fliC, fljB, and viaB groups that encode the O, H, and Vi antigens were used to design 15 primer pairs and TaqMan probes specific for the genes rfbJ, wzx, fliC, fljB, wcdB, the sdf-l sequence, and invA, which was used as an internal amplification control. The primers and probes were variously combined into six sets. The first round of reactions used two of these sets to detect Salmonella O:4, O:9, O:7, O:8, and O:3,10 serogroups. Once the serogroups were identified, the results of a second round of reactions that used primers and probes for the flagellar antigen l genes, 1,2; e,h; g,m; d; e,n,x; and z(10), and the Vi gene were used to identify individual serovars. The procedure was standardized using 18 Salmonella reference strains and other enterobacteria. The procedure's reliability and sensitivity was evaluated using 267 randomly chosen serotyped Salmonella clinical isolates. The procedure had a sensitivity of 95.5% and was 100% specific. Thus, our technique is a quick, sensitive, reliable, and specific means of identifying S. enterica serovars and can be used in conjunction with traditional serotyping. Other primer and probe combinations could be used to increase the number of identifiable serovars.


Chemical stability of the cardioprotective agent ICRF-187 in infusion fluids.
The chemical stability of the cardioprotective agent ICRF-187 in 0.9% sodium chloride and 5% dextrose infusion fluids has been investigated. The admixtures (concentration: 10 mg/mL and 1 mg/mL) were stored in glass bottles or polyvinyl chloride containers at 4 degrees C in the dark and at room temperature (20-22 degrees C) both protected from light and under normal room fluorescent light conditions in a day-night rhythm. Samples withdrawn immediately after preparation and after 6 hours, 1, 2, 3 and 6 days were analyzed using high performance liquid chromatography with ultraviolet detection. Samples were also inspected for visual changes and tested for changes in pH. Chemical stability of ICRF-187 was also investigated as a function of pH (range 1-12) at room temperature. It is concluded that ICRF-187 is slightly more stable in 5% dextrose than in 0.9% sodium chloride infusion fluids. The stability of the drug is not influenced by normal room fluorescent light nor by the type of container material used. Precipitation occurred in both 5% dextrose and 0.9% sodium chloride with a drug concentration of 10 mg/mL and storage in the refrigerator at 4 degrees C. The chemical stability of ICRF-187 in aqueous solution is mainly a function of pH. At pH 1, no decomposition is detected within 24 hours, at pH 7, 35% decomposition occurs in 21 hours, while at pH 12 it degrades completely within 20.5 hours.


The Impact of Stimulant Medications on Blood Pressure and Body Mass Index in Children with Attention Deficit Hyperactivity Disorder.
To describe changes in blood pressure (BP) and body mass index (BMI) associated with stimulant medication fills in children. Observational, retrospective matched cohort study of children 6-17.9 years initiating stimulant medication between 7/1/2010-6/30/2017 matched 1:3 by age, race, ethnicity, and sex to children with no stimulant use during this period. All BPs and BMIs recorded during ambulatory visits were identified. Generalized linear models were used to estimate differences in change in systolic BP (SBP), diastolic BP (DBP), and BMI over time. The 686 children with stimulant prescription fills and 2048 matched controls did not differ by baseline SBP or BMI. The matched control group (30.5% female, mean age 11.2 ± 3.4 years 79.7% white) was more likely to be publicly insured (35% vs. 21%, P < .01). After adjusting for baseline values, over a mean follow-up of 144 days change in SBP or DBP did not differ significantly between patients with stimulant medication fills and matched controls. Stimulant use was associated with a 4.7 percentile decrease in BMI percentile compared to matched controls (95% CI: 3.69, 5.71; P < .01). In a pediatric primary care cohort, stimulant prescription fills were associated with marked decreases in BMI but no significant changes in BP over time.


The μ-opioid receptor variant N190K is unresponsive to peptide agonists yet can be rescued by small-molecule drugs.
The μ-opioid receptor (MOR) plays an important role in modulating analgesia, feeding behavior, and a range of autonomic functions. In the current study, we investigated the degree to which 13 naturally occurring missense mutations affect the pharmacological properties of the human MOR. After expression of each receptor in human embryonic kidney 293 cells, signaling (Gα(i/o)-mediated) induced by peptide agonists was assessed using luciferase reporter gene assays. Multiple mutants (S66F, S147C, R260H, R265C, R265H, and S268P) show a significant reduction in agonist potency. At the N190K variant, agonist-mediated signaling was essentially absent. Enzyme-linked immunosorbent assay, microscopic analysis, and radioligand binding assays revealed that this mutant shows markedly reduced cell-surface expression, whereas all other receptor variants were expressed at normal levels. Surface expression of the N190K variant could be increased by incubation with the alkaloid agonist buprenorphine or with either naltrexone or naloxone, structurally related MOR antagonists. We were surprised to find that both putative antagonists, despite being inactive at the wild-type MOR, triggered a concentration-dependent increase in N190K receptor-mediated signaling. In contrast, peptidic ligands failed to promote expression or rescue function of the N190K mutant. Subsequent analysis of the N190K variant in an ethnically diverse cohort identified this isoform in a subgroup of African Americans. Taken together, our studies reveal that the N190K mutation leads to severe functional alterations and, in parallel, changes the response to established MOR ligands. The extent to which this mutation results in physiological abnormalities or affects drug sensitivity in selected populations (e.g., those with chronic pain or addiction) remains to be investigated.


"Why don't they just call the cops?": Reasons for differential police contact among women with abusive partners.
Incidents of domestic violence are frequently not reported to police (e.g., Johnson, 1990; Langan & Innes, 1986; Roy, 1977), and people commonly assume that women's reasons for not calling about violence by a current or former partner are intrapersonal (e.g., shame, embarrassment, love). However, few researchers have asked battered women themselves about the frequency of their police contacts and their reasons for not calling the police. In this study, participants were recruited from a battered women's shelter and asked about their experiences with the police over the prior 6 months. Two thirds of the sample had had contact with the police during that time, but most did not have as much contact with the police as they had needed. Women gave multiple reasons for not calling the police; these reasons frequently included situational barriers, such as being physically prevented from using the telephone and/or being threatened with more violence. Only 3% of the sample reported that shame, embarrassment, or love were their sole reasons for not calling the police. Underreporting was related to previous (negative) experience with the police, as well as to the level of violence experienced. The practical implications of these findings are discussed.


[Chemotherapy for liver metastasis of colorectal cancer].
In colorectal cancer, liver metastasis is the most common and most important prognostic factor. Although surgical resection is the first choice of treatment for liver metastasis of colorectal cancer, there are many cases we cannot choose the surgical treatment. The chemotherapy is very important in such cases. We examined 18 cases of unresectable liver metastases from colorectal cancer which were adapted a hepatic arterial infusion of 5-FU (HAI) with a weekly high-dose infusion method (WHF) as the first-line treatment, and then systemic chemotherapy of CPT-11 in combination with 5-FU as the second-line treatment. The response rate of this treatment is 72% (13/18) and the 1-, 2-, 3-year survival rates were 100% (16/16), 83% (10/12), and 50% (5/10), respectively. The combination chemotherapy of HAI with systemic chemotherapy using CPT-11 seemed to be an effective treatment method.


Detection of human papillomavirus gene sequences in cell lines derived from laryngeal tumors.
The role of Human Papillomaviruses (HPV) in laryngeal carcinomas has been studied with conflicting results. To evaluate the etiologic relationship between HPV infection and epithelial malignancy of the larynx we studied five laryngeal carcinoma cell lines obtained from patients undergoing surgery for laryngeal tumors. The paraffin embedded biopsy samples of the original tumor and different passages of the new established cell lines were investigated by PCR with consensus primers specific for HPV DNA. The findings indicate that HPV infection is associated with some larynx carcinomas. The positive association has been enhanced when a method of enrichment of epithelial cells from fresh tumor samples was used. All tumor cells enriched smears were positive for HPV DNA not only by PCR but also by in situ hybridization (ISH). Investigated by PCR, different passages of larynx tumor cell lines maintained expression of HPV DNA. At subsequent passages ISH gives constantly no signals suggesting a minimal amount of viral harbored sequences. In one cell line propagated more than 60 population doublings, the chromosomal frequency distribution shifted from modal number 46 at the 5(th) passage to 63 at the 60(th) passage. The mechanisms by which persistent HPV infection maintains continuous cell proliferation were discussed.


Intratendinous ganglion in the extensor digitorum communis.
We encountered a patient with intratendinous ganglion which developed in the extensor digitorum communis tendon. Although its developmental mechanism is unclear, synovitis is considered the cause. For treatment, it may be necessary to prepare for tendon transfer and tendon grafting in consideration of the risk of tendon injury.


A reappraisal of cryosurgery for eyelid basal cell carcinomas.
Liquid nitrogen spray freezing has been successfully applied for basal cell carcinomas in the eyelid region, but is not yet in general use. The reasons for this were analysed and the development of a more reliable, safer cryosurgical technique aimed for. New cryosurgical apparatus, contact probes with increased freezing power, and a special application technique were developed and clinically tested in a consecutive series of 221 patients with primary basal cell carcinomas of the lid region. Special efforts yielded follow up reports of 220 out of the 221 patients. Experimental measurements and clinical results demonstrated that this cryosurgical technique was at least as effective as spray freezing, with lower risks. The rate of recurrent tumours in patients followed up for 5 years or longer was 5.1% (surgeons first result) respectively 0.6% (result after optimised second cryosurgery). The figures were 6.8%, respectively max 2.7%, when including all patients, independent of follow up time. Traditional surgery and histopathology, still used at numerous places, resulted in higher recurrence rates despite extended loss of healthy eyelid tissues and should be abandoned. Micrographic surgery is considered mandatory to save more of the healthy structures and to obtain lower recurrence rates. Cost and time require worldwide restriction of micrographic surgery to selected cases. Updated cryosurgery provides a low cost option to micrographic surgery and results in preservation of eyelid structures and lacrimal pathways, tarsal plate, lid margin. It provides excellent cosmetic results. Thus, primary basal cell carcinomas in the eyelid region of suitable size and location should receive updated cryosurgery, and tumours beyond its range micrographic surgery.


Formation of Water-Channel by Propylene Glycol into Polymer for Porous Materials.
In this study, a porous membrane with a cellulose acetate (CA) matrix was fabricated using propylene glycol with a water pressure treatment without a metal salt as an additive. The water pressure treatment of the fabricated CA membrane with propylene glycol yielded nanopores. The nanopores were formed as the additives in the CA chains led to plasticization. The weakened chains of the parts where the plasticization occurred were broken by the water pressure, which generated the pores. Compared to the previous study with glycerin as an additive, the size of the hydration region was controlled by the number of hydrophilic functional groups. When water pressure was applied to the CA membrane containing propylene glycol as an additive, the hydration area was small, so it was effective to control the pore size and the number of nano pores than glycerin. In addition, the number of nanopores and pore size could be easily adjusted by the water pressure. The porosity of the membrane was increased owing to the trace amount of propylene glycol, confirmed by scanning electron microscopy (SEM) and porosimetry. The interaction between the CA and propylene glycol was verified by Fourier-transform infrared spectroscopy (FT-IR) and thermogravimetric analysis (TGA). Consequently, it was the optimum composition to generate pores at the CA/propylene glycol 1:0.2 ratio, and porosity of 69.7% and average pore diameter of 300 nm was confirmed. Since it is a membrane with high porosity and nano sized pores, it is expected to be applied in various fields.


Cloning and characterization of the human recombination activating gene 1 (RAG1) and RAG2 promoter regions.
Recombination activating gene 1 (RAG1) and RAG2 are the essential and tissue-specific components of V(D)J recombination. We have characterized the genomic organization of the human RAG locus, mapped the transcriptional initiation sites, and partially sequenced and performed functional reporter assays on the 5' flanking regions of human RAG1 and RAG2. Transcription initiation sites were mapped by rapid amplification of 5' cDNA ends, primer extension, and/or RNase protection in normal thymocytes, three pre-B cell lines, and a mature B cell line. A single promoter region was used for RAG1 transcription. In contrast, transcription of RAG2 initiates at two distinct regions of the genome. The 5'-flanking region of the human RAG2 gene is TATA-less; however, there is a GATAA consensus at position -34 with respect to the major transcriptional initiation site of RAG1. Promoter regions of human RAG1 and RAG2 are active in both lymphoid and nonlymphoid cell lines, suggesting that an outside regulatory element is probably involved in the tissue-specific transcriptional regulation of the RAG genes.


The impact of transrectal ultrasound on stage migration in a predominantly African-American population.
An important question left unanswered is whether transrectal ultrasound will result in earlier diagnosis in African Americans. Tumor registry data for 1985 and 1990 for a predominantly African-American population were reviewed to determine whether transrectal ultrasound influenced the stage at diagnosis of prostate cancer. Diagnosis by ultrasound increased from 0% to 60% of cases in those 5 years. Curable diseases (stages A and B) increased from 38% to 57% of cases. It is concluded that transrectal ultrasound can increase the diagnostic yield of potentially curable disease in a predominantly African-American population.


Plant-microbe networks in soil are weakened by century-long use of inorganic fertilizers.
Understanding the changes in plant-microbe interactions is critically important for predicting ecosystem functioning in response to human-induced environmental changes such as nitrogen (N) addition. In this study, the effects of a century-long fertilization treatment (> 150 years) on the networks between plants and soil microbial functional communities, detected by GeoChip, in grassland were determined in the Park Grass Experiment at Rothamsted Research, UK. Our results showed that plants and soil microbes have a consistent response to long-term fertilization-both richness and diversity of plants and soil microbes are significantly decreased, as well as microbial functional genes involved in soil carbon (C), nitrogen (N) and phosphorus (P) cycling. The network-based analyses showed that long-term fertilization decreased the complexity of networks between plant and microbial functional communities in terms of node numbers, connectivity, network density and the clustering coefficient. Similarly, within the soil microbial community, the strength of microbial associations was also weakened in response to long-term fertilization. Mantel path analysis showed that soil C and N contents were the main factors affecting the network between plants and microbes. Our results indicate that century-long fertilization weakens the plant-microbe networks, which is important in improving our understanding of grassland ecosystem functions and stability under long-term agriculture management.


Independent component analysis-based spatial filtering improves template-based SSVEP detection.
This study proposes a new algorithm to detect steady-state visual evoked potentials (SSVEPs) based on a template-matching approach combined with independent component analysis (ICA)-based spatial filtering. In recent studies, the effectiveness of the template-based SSVEP detection has been demonstrated in a high-speed brain-computer interface (BCI). Since SSVEPs can be considered as electroencephalogram (EEG) signals generated from underlying brain sources independent from other activities and artifacts, ICA has great potential to enhance the signal-to-noise ratio (SNR) of SSVEPs by separating them from artifacts. This study proposes to apply the ICA-based spatial filters to test data and individual templates obtained by averaging training trials, and then to use the correlation coefficients between the filtered data and templates as features for SSVEP classification. This study applied the proposed method to a 40-class SSVEP dataset to evaluate its classification accuracy against those obtained by conventional canonical correlation analysis (CCA)- and extended CCA-based methods. The study results showed that the ICA-based method outperformed the other methods in terms of the classification accuracy. Furthermore, its computational time was comparable to the CCA-based method, and was much shorter than that of the extended CCA-based method.


Novel methods to detect impacts within whole-body vibration time series data.
We present three candidate mathematical models for detecting impacts within time series accelerometer data in the context of whole-body vibration (WBV). In addition to WBV, data included recordings of erector spinae muscle activity and trunk posture collected during use of agricultural machines in a previous study. For each model, we evaluated associations between several mechanical and biomechanical variables at the time of predicted impact onset and the odds of subsequently observing a bilateral response of the erector spinae muscles. For all models, trunk posture at the time of impact onset was strongly associated with an observed bilateral muscle response; these associations were not observed when impacts were randomly assigned. Results provide a framework for describing the number and magnitudes of impacts that may help overcome ambiguities in current exposure metrics, such as the vibration dose value, and highlight the importance of considering posture in the evaluation of occupational WBV exposures. Practitioner summary: Common metrics of exposure to whole-body vibration do not quantify the number or magnitudes of impacts within time series accelerometer data. Three candidate impact detection methods are presented and evaluated using real-world data collected during use of agricultural machines. Results highlight the importance of considering posture when evaluating vibration exposure.


Regulation of in vitro diagnostics (IVDs) for use in clinical diagnostic laboratories: towards the light or dark in clinical laboratory testing?
A revised framework for the regulation of in vitro diagnostic devices (IVDs) came into force in Australia on July 1, 2010 that aims to 'ensure that public and personal health are adequately protected', but which instead may lead to adverse outcomes in clinical diagnosis and management. The regulatory process aims to regulate all IVDs, including those used by clinical diagnostic laboratories, which are already subject to scrutiny as part of the current laboratory accreditation process. The IVD regulatory process initiated in Australia is similar to that used in Canada, but different to that currently operating in the USA and Europe. However, it is feasible that other countries will in time adopt a similar regulatory framework, given that many countries are involved in the development process. In this opinion paper, the regulatory process for IVDs across several geographies are outlined, as are some benefits and weaknesses of the new regulatory process now applied to Australia, as potentially planned for other regions of the world.


Prevalence of Pediatric and Adolescent Balance Disorders: Analysis of a Mono-Institutional Series of 472 Patients.
(1) Background: To assess the prevalence and frequency distribution of balance disorders in children and adolescents to delineate the planning of a targeted clinical and instrumental diagnostic work-up; (2) Methods: Retrospective analysis of the clinical documentation of patients under 18 years suffering from balance disorders from 2010 to 2019. Detailed collection of clinical history, accurate clinical examination, including both nystagmus and vestibulospinal signs examinations, and specific instrumental testing were the basis of the diagnostic process. (3) Results: A total of 472 participants were included in the study. Vestibular loss (26.1%) was the most frequent cause of vertigo in children, followed by vestibular migraine (21.2%) and benign paroxysmal positional vertigo (10.2%). In 1.1% of patients, the cause of vertigo remained undefined; (4) Conclusions: The diagnostic process applied was effective in understanding the cause of balance disorders in most cases and prevents more complex and expensive investigations reserved for only a few selected cases.


Current and future role of ultrafiltration in CRS.
Ultrafiltration has been used in patients with decompensated HF and volume overload refractory to diuretics. Criteria for the initiation of renal replacement therapy (RRT) in the ICU are oliguria, anuria, urea, creatinine, Na and K blood concentrations, pulmonary edema unresponsive to diuretics, uncompensated metabolic acidosis, temperature >40°C, uremic complication, and overdose with a dialyzable toxin. Moreover, the treatment of acute renal failure requires a different style and philosophy from renal replacement therapy for chronic renal failure. The degree and the location of renal lesion, the entity, the gravity of the concomitant acute or chronic cardiac damage, the weight of a trauma, surgical stress, or septic complication they determine a variability of clinical picture that can modify the prescription and the timing of RRT and the monitoring technology. In the presence of cardiac alterations due to a condition of chronic heart failure, all the acute events contribute to the progression of the cardiac insufficiency and the patient will always have as a result an ulterior reduction in the cardiac function. It derives the opportunity to put more precociously in action everything of it how much serves for a real cardioprotection. A valid hemodynamic monitoring is essential to reach the lowest possible value of pressure of left ventricular filling, without reduction in the cardiac output, increase in the cardiac frequency or the ulterior activation of the neurohormones. An early ultrafiltration allows a more easy control of the circulating mass but also an effective neurohormonal purification and of all the inflammation mediators.


Indorenate produces antidepressant-like actions in the rat forced swimming test via 5-HT1A receptors.
Indorenate has been proposed to possess antihypertensive, anorectic, stimulus control and anxiolytic-like actions. This compound has affinity mainly for the serotonergic(1A/1B) receptors, hence it could possess antidepressant-like activity. The general purpose of this study was to explore the possible antidepressant-like effects of the serotonergic compound indorenate in the forced swimming test (FST). In a first approach, a comparison of the actions of several doses of indorenate (2.5, 5.0, 10 mg/kg) with those of other 5-HT(1A) agonists, buspirone (5.0, 10.0 mg/kg) and 8-OH-DPAT (0.25, 0.50, 1.0 mg/kg), was performed in the FST. Secondly, in order to determine the serotonergic receptors that are participating in indorenate's action, different doses of serotonergic antagonists were administered. The compounds used were the 5-HT(1A/1B) and beta-adrenergic antagonist pindolol (2.5, 5.0 mg/kg), the 5-HT(1B)receptor antagonist GR 55562 (0.75, 1.5, 3.0 mg/kg), the 5-HT(1A) antagonist WAY 100635 (0.25, 0.5, 1.0 mg/kg) and the 5-HT(2) antagonist ketanserin (1.0, 2.0, 4.0 mg/kg). Indorenate (10 mg/kg), 8-OH-DPAT (1.0 mg/kg) and buspirone (5.0 and 10.0 mg/kg) reduced immobility behaviour in the FST, considered as an antidepressant-like effect. Both doses of pindolol (2.5 and 5.0 mg/kg) and WAY 100635 (0.5 and 1.0 mg/kg) antagonised the antidepressant-like effect of indorenate. Neither 5-HT(1B) (GR55562) nor 5-HT(2)(ketanserin) antagonists produced changes in the effect of indorenate in the FST. Indorenate produces antidepressant-like actions in the FST that are mediated by the stimulation of 5-HT(1A) receptors.


[Use of glucose and cellobiose by 3 strains of Fibrobacter succinogenes].
F succinogenes strains S85, 128 and 095 were compared with respect to their growth using glucose and/or cellobiose as the carbon and energy substrate(s) and their capacities to degrade cellulose. The growth rate of F succinogenes strain S85 was the same using glucose or cellobiose, whereas the growth rates of strains 128 and 095 were about thrice the rate when using cellobiose. Strain S85 could simultaneously use glucose and cellobiose, while strains 128 and 095 tended to use preferentially glucose then cellobiose in a mixture of the 2 sugars. Their capacities to degrade cellulose were equivalent.


Activated osteoclasts with CD51/61 expression in otosclerosis.
Stapes ankylosis is supposed to be a disease with variable histopathology caused by otosclerosis or pseudo-otosclerosis. Persistent measles virus infection of the otic capsule could induce reactivation of quiescent embryonic osteoclasts in otosclerosis. Presence of measles virus RNA was demonstrated in the footplates of otosclerotic patients by reverse-transcription polymerase chain reaction (RT-PCR). Histology of active otosclerosis is featured by the presence of numerous osteoclasts with unknown phenotype. Nucleic acid was extracted from stapes footplates of clinically otosclerotic patients (n = 261). Genomic RNA of measles virus was amplified by RT-PCR. Amplification results were correlated to postoperative histologic and CD51/61 specific immunohistologic findings. A parallel alcalic phosphatase activity assessment was performed to evaluate the metabolic activity of osteoclasts in each section. Among 261 stapes fixation cases, 175 otosclerotic stapes contained measles virus RNA. Histology for virus negative stapes (n = 86) represented nonotosclerotic, degenerative disorders. Histologically confirmed otosclerosis was featured by the presence of osteoclasts with renewed, embryonic phenotype. In otosclerosis, alcalic phosphatase activity was significantly higher compared with nonotosclerotic stapes ankylosis (P < .001). The presence of CD51/61 positive osteoclasts in otosclerotic bone containing viral sequences provides the basis for an inflammatory bone remodeling disorder. Otosclerosis is a disease caused by persistent measles virus infection and reactivation of resting embryonic osteoclasts in the otic capsule.


Structure and mechanisms of sodium-pumping KR2 rhodopsin.
Rhodopsins are the most universal biological light-energy transducers and abundant phototrophic mechanisms that evolved on Earth and have a remarkable diversity and potential for biotechnological applications. Recently, the first sodium-pumping rhodopsin KR2 from Krokinobacter eikastus was discovered and characterized. However, the existing structures of KR2 are contradictory, and the mechanism of Na+ pumping is not yet understood. Here, we present a structure of the cationic (non H+) light-driven pump at physiological pH in its pentameric form. We also present 13 atomic structures and functional data on the KR2 and its mutants, including potassium pumps, which show that oligomerization of the microbial rhodopsin is obligatory for its biological function. The studies reveal the structure of KR2 at nonphysiological low pH where it acts as a proton pump. The structure provides new insights into the mechanisms of microbial rhodopsins and opens the way to a rational design of novel cation pumps for optogenetics.


When a Peripartum Cardiomyopathy Patient Hides Various and Serious Risk Factors for Recurrent and Fatal Thromboembolic Events Even Under Well-Conducted Oral Anticoagulation.
Peripartum cardiomyopathy (PPCM) is a rare cause of heart failure that occurs during the final month of pregnancy through about five months after delivery, without any other known cause, and it increases the risk of thromboembolic events by many folds. A 38-year-old female with a history of peripartum dilated cardiomyopathy was admitted to our hospital, one month after a cesarean section, for severe breathlessness. Examination revealed signs of global heart failure and right deep vein thrombosis. Pulmonary CT angiography revealed pulmonary embolism of the right pulmonary artery. The patient was treated by oral anticoagulation with acenocoumarol with all international normalized ratio (INR) values within the target range (2-3). One month later, she was admitted to the emergency department with acute dyspnea and superior vena cava syndrome. Thoracic CT angiogram showed bilateral pulmonary emboli associated with an extensive deep vein thrombosis of both internal jugular veins, sigmoid sinuses, subclavian veins, innominate venous trunks, and the origin of the superior vena cava without any lesion suspected of malignancy. The thrombophilia screen performed six weeks after the suspension of vitamin K antagonists (VKAs) revealed severe deficiencies of protein C and protein S. In this report, we present the first case of recurrence of fatal thromboembolic events under well-conducted oral anticoagulation in a patient with PPCM associated with severe protein C and protein S deficiencies.


Quantitative exposure matrix for asphalt fume, total particulate matter, and respirable crystalline silica among roofing and asphalt manufacturing workers.
This paper summarizes available data on worker exposures to asphalt fume (soluble fraction), total particulate matter, and respirable crystalline silica (quartz) [hereinafter RCS] over a 30-year period in Owens Corning's asphalt production and roofing manufacturing plants. For the period 1977 through 2006, the air-monitoring database contains more than 1,400 personal samples for asphalt fume (soluble fraction), 2,400 personal samples for total particulate, and 1,300 personal samples for RCS. Unique process-job categories were identified for the asphalt production and roofing shingle manufacturing plants. Quantitative exposures were tabulated by agent, process-job, and calendar period to form an exposure matrix for use in subsequent epidemiologic studies of the respiratory health of these workers. Analysis of time trends in exposure data shows substantial and statistically significant exposure reductions for asphalt fume (soluble fraction), total particulate matter, and respirable crystalline silica at Owens Corning plants. Cumulative distribution plots for the most recent sampling period (2001-2006) show that 95% of the asphalt fume (soluble fraction) measurements were less than 0.25 mg/m3; 95% of the total particulate measurements were less than 2.2 mg/m3; and 95% of the RCS measurements were less than 0.05 mg/m3. Several recommendations are offered to improve the design of future monitoring efforts.


A novel modeling approach for finite element human body models with high computational efficiency and stability: application in pedestrian safety analysis.
The purpose of the current study was to develop and validate a finite element (FE) pedestrian model with high computational efficiency and stability using a novel modeling approach. Firstly, a novel modeling approach of using hollow structures (HS) to simulate the mechanical properties of soft tissues under impact loading was proposed and evaluated. Then, an FE pedestrian model was developed, employing this modeling approach based on the Total Human Model for Safety (THUMS) pedestrian model, named as THUMS-HS model. Finally, the biofidelity of the THUMS-HS model was validated against cadaver test data at both segment and full-body level. The results show that the proposed hollow structures can simulate the mechanical properties of soft tissues and the predictions of the THUMS-HS model show good agreement with the cadaver test data under impact loading. Simulations also prove that the THUMS-HS model has high computational efficiency and stability. The proposed modeling approach of using hollow structures to simulate the mechanical properties of soft tissues is plausible and the THUMS-HS model could be used as a valid, efficient and robust numerical tool for analysis of pedestrian safety in vehicle collisions.


Calcium supplementation during sepsis exacerbates organ failure and mortality via calcium/calmodulin-dependent protein kinase kinase signaling.
Calcium plays an essential role in nearly all cellular processes. As such, cellular and systemic calcium concentrations are tightly regulated. During sepsis, derangements in such tight regulation frequently occur, and treating hypocalcemia with parenteral calcium administration remains the current practice guideline. We investigated whether calcium administration worsens mortality and organ dysfunction using an experimental murine model of sepsis and explored the mechanistic role of the family of calcium/calmodulin-dependent protein kinases in mediating these physiological effects. To highlight the biological relevance of these observations, we conducted a translational study of the association between calcium administration, organ dysfunction, and mortality among a cohort of critically ill septic ICU patients. Prospective, randomized controlled experimental murine study and observational clinical cohort analysis. University research laboratory and eight ICUs at a tertiary care center. A cohort of 870 septic ICU patients. C57Bl/6 and CaMKK mice. Mice underwent cecal ligation and puncture polymicrobial sepsis and were administered with calcium chloride (0.25 or 0.25 mg/kg) or normal saline. Administering calcium chloride to septic C57Bl/6 mice heightened systemic inflammation and vascular leak, exacerbated hepatic and renal dysfunction, and increased mortality. These events were significantly attenuated in CaMKK mice. In a risk-adjusted analysis of septic patients, calcium administration was associated with an increased risk of death, odds ratio 1.92 (95% CI, 1.00-3.68; p = 0.049), a significant increase in the risk of renal dysfunction, odds ratio 4.74 (95% CI, 2.48-9.08; p < 0.001), and a significant reduction in ventilator-free days, mean decrease 3.29 days (0.50-6.08 days; p = 0.02). Derangements in calcium homeostasis occur during sepsis that is sensitive to calcium administration. This altered calcium signaling, transduced by the calmodulin-dependent protein kinase kinase cascade, mediates heightened inflammation and vascular leak that culminates in elevated organ dysfunction and mortality. In the clinical management of septic patients, calcium supplementation provides no benefit and may impose harm.


While passing through.
Salaria Kea (O'Reilly) was one of 48 nurses who went to Spain with the medical units of the Abraham Lincoln Brigade, the American part of the International Brigades which fought with the Spanish people against Franco's forces. The Medical Bureau to Aid Spanish Democracy, in addition to organizing the ALB medical units, raised money to purchase and send to the Spanish Loyalists 70 ambulances and large quantities of medicines and medical supplies. Salaria Kea was the only black woman in the Abraham Lincoln Brigade. She was cited for courage and efficiency several times in Spanish Loyalist dispatches. These excerpts are from her unpublished memoirs. The entire memoirs will be published by the Institute of Social Medicine and Community Health's History Center.


Morbidity pattern of communicable diseases in an urban area of Uttar Pradesh.
The period prevalence rate of communicable diseases in Uttar Pradesh, India, in the present study was found to be 119.7 per thousand population. There were 1.08 communicable diseases per morbid person. The leading cause of morbidity was ascariasis (24.1 per 1000). The morbidity was significantly higher in young persons (below 14 years of age) and in those without spouse. The social class and educational status were found to have negative association with the morbidity. However, the sex did not show any influence on the morbidity.


Single versus bilateral external ventricular drainage for intraventricular fibrinolysis in severe ventricular haemorrhage.
Intraventricular fibrinolysis (IVF) through bilateral external ventricular drains (EVD) may provide better access of the thrombolytic agent to the intraventricular clot, potentially influencing clot clearance and outcome. Patients with spontaneous ganglionic intracerebral haemorrhage (ICH)<40 cm(3) and intraventricular haemorrhage (IVH) with acute hydrocephalus have been treated with IVF. The decision for placement of one or two EVDs has been left to the discretion of the treating physician. CT volumetry, the effects on cerebrospinal fluid (CSF) circulation and outcome at 3 months have been analysed for patients with one (group I, n = 13) or two EVDs (group II, n = 14). No difference was found in clot resolution between the two groups (clot half life 2.1 (SD 1.2) vs 2.4 (1.3) days). A separate analysis of the third and fourth ventricle clearance was similar (1.6 (0.6) versus 1.8 (0.8) days), indicating no difference in reconstitution of CSF circulation. A trend towards a longer EVD duration and higher infection rate was found in the bilateral EVD group. No difference was found in outcome at 3 months. Our results do not support the use of bilateral EVDs for IVF in patients with severe IVH.


Magnetic resonance imaging of bone marrow disorders of the knee.
Bone marrow abnormalities around the knee are encountered frequently when performing MR imaging. Some of these so-called abnormalities may represent normal variations of the bone marrow contents and have no clinical significance. On other occasions, MR imaging may be the only technique that demonstrates a bone marrow lesion. Edema, osteonecrosis, infection, and tumor are entities frequently detected and assessed with MR imaging. We now, perhaps for the first time, are able to visualize and assess directly the bone marrow and its disorders. Knowledge of normal anatomy, variants, and pathologic signs coupled with meticulous imaging techniques are of paramount importance for accurate interpretation of such MR images.


[Development of ICN's Code of Ethics].
Development of the ICN Code for Nurses (Ethical Concepts Applied to Nursing) was explored from the Finnish perspective. The article was mainly based on the archival sources of the Finnish Federation of Nurses and on the ICN publications. The 1953, 1965 and 1973 Codes were briefly discussed. It was observed that the Federation never explicitly integrated the Code for Nurses into its decision-making.


The morphology of prehatching embryos of Caecilia orientalis (Amphibia: Gymnophiona: Caeciliidae).
The state of development of advanced embryos of the direct-developing Ecuadorian caecilian Caecilia orientalis (Caeciliidae: Gymnophiona: Amphibia) was examined. Because it is established that development is correlated with reproductive modes in a number of features, we included comparison with taxa that represent the major reproductive modes and all of the modern normal tables and ossification sequences. The embryos of C. orientalis most closely resemble those of stage 47/48 Gegeneophis ramaswamii, an Indian caeciliid, and stage 47/48 Hypogeophis rostratus, a Seychellian caeciliid, both direct developers, in details of bone mineralization, chondrocranial degeneration, and vertebrogenesis. They are most like stage 45 H. rostratus in external features (gills, pigmentation, etc.). They are less similar to prehatchings of Ichthyophis kohtaoensis, an ichthyophiid with free-living larvae, and to fetuses of the viviparous caeciliid Dermophis mexicanus and the viviparous typhlonectid Typhlonectes compressicauda at comparable total lengths in both skeletal development and external features. The similarity of developmental features among the direct-developers suggests a correlation with mode of life history. A noteworthy feature is that C. orientalis has an armature of multiple rows of teeth on the lower jaw with tooth crowns that resemble the "fetal" teeth of viviparous taxa and that are covered with a layer of oral mucosal epithelium until full development and eruption, but the upper jaw bears a single row of widely spaced, elongate, slightly recurved teeth that resemble those of the adult.


Postoperative visual performance with a bifocal and trifocal diffractive intraocular lens during a 1-year follow-up.
To evaluate and compare the clinical outcomes with a diffractive bifocal and trifocal intraocular lens (IOL) during a 12-month follow-up. Prospective comparative study including 75 eyes of 38 patients (44-70y) undergoing uneventful cataract surgery. Each patient was randomly assigned to one type of IOL, bifocal (35 eyes) or trifocal (40 eyes). Visual, refractive, and contrast sensitivity changes were evaluated in a 12-month follow-up. The binocular defocus curve was also measured at 12mo postoperatively. No statistically significant differences between groups were found in postoperative uncorrected and corrected distance visual acuities (P≥0.276). Postoperative corrected near visual acuity (33 cm) was significantly better in the trifocal group during all follow-up (P≤0.004) as well as 6-month uncorrected near (P=0.008) and distance-corrected near visual acuities (P=0.016) (33/40 cm). Significantly better uncorrected intermediate and distance corrected-intermediate visual acuity were found during all follow-up in the trifocal group (P<0.001), which was consistent with differences among groups in binocular defocus curve. Differences among groups in contrast sensitivity were minimal, being only significant at 6 months for some low to medium spatial frequencies (P≤0.006). Bifocal and trifocal diffractive IOLs are able to provide an effective visual restoration which is maintained during a 12-month follow-up, with a clear benefit of the trifocal IOL for the intermediate vision.


IL-6-trans-signalling increases rapid-eye-movement sleep in rats.
Interleukin 6 (IL-6), a cytokine of the gp130-signalling-family, plays an important role in immediate immunological functions, in metabolism and in the central nervous system. IL-6-signalling is mediated by classic-signalling via the membrane bound IL-6 receptor or by IL-6-trans-signalling via the soluble IL-6 receptor. Whereas the receptor subunit gp130 is ubiquitously expressed within the body, IL-6 receptor expression is restricted to distinct cell populations. Within the brain parenchyma the IL-6 receptor is sparsely expressed, and therefore the brain is mostly dependent on IL-6-trans-signalling in its response to IL-6. Recently we have shown that IL-6-trans-signalling but not classic-signalling plays a pivotal role in the establishment and maintenance of chronic inflammation and cancer, whereas its role in sleep regulation has not been studied so far. We reasoned that the IL-6-trans-signalling mimetic Hyper-IL-6 which in contrast to IL-6 alone can activate almost all cells of the brain might have a profound effect on sleep regulation and performed sleep recordings with rats injected with recombinant Hyper-IL-6. In the present study, the i.c.v. administration of the designer cytokine Hyper-IL-6 into rats at dark onset increased the amount of rapid-eye-movement sleep (REM sleep) but did not affect non-rapid-eye-movement sleep (non-REM sleep). Our data define a new role of IL-6-trans-signalling in sleep regulation.


Pudendal afferents mapping in posterior sacral rhizotomies.
The effectiveness of pudendal afferents mapping in posterior sacral rhizotomies needs to be reviewed. To evaluate the effectiveness of pudendal afferents mapping for both the dorsal penile or clitoral nerve and the inferior anal nerve to decrease the risk of postoperative bowel and bladder dysfunction when the sacral nerve roots are candidates for rhizotomies. A retrospective review of 101 Asian children who underwent functional posterior rhizotomies with pudendal afferents mapping for spastic paresis was performed. Pudendal mapping was successful in 75 of 81 patients. The highest activity of afferent fibers of the dorsal penile or clitoral nerve was demonstrated at the S1 roots in 13.3%, at the S2 in 79.3%, and at the S3-5 in 7.3%. Considerable activity of the dorsal penile or clitoral nerve was recorded at 40% of the S1 roots, at 99.3% of the S2 roots, and at 52% of the S3-5 roots. The highest activity of afferent fibers of the inferior anal nerve was demonstrated at S2 roots in 42% and at S3-5 roots in 58%. Considerable activity of the inferior anal nerve was recorded at 10.7% of S1 roots, at 89.3% of S2 roots, and at 76.7% of S3-5 roots. The pathological S1 roots were divided into 3 to 4 rootlets, and the rootlets with significant afferent activity were preserved. None of the 75 patients experienced long-term bowel or bladder complications. Pudendal afferent mapping identified the sacral rootlets involved with genital and anal sensation. The preservation of such rootlets in sacral rhizotomies is considered to be important for minimizing postoperative bladder and bowel dysfunction.


The utility of local smoke evacuation in reducing surgical smoke exposure in spine surgery: a prospective self-controlled study.
Exposure to surgical smoke remains a potential occupational health concern to spine operating room personnel. Using a smoke evacuator (local exhaust ventilation) is currently regarded as a primary means of protection, yet few studies have evaluated its utility in actual surgeries. To examine the utility of two common types of local smoke evacuators, a para incisional evacuator and a smoke evacuation pencil, in reducing surgical smoke exposure in spine surgery. A prospective self-controlled study. After the pre-estimation of sample size, 51 consecutive spine surgeries (25 and 26 patients using the para incisional smoke evacuator and the smoke evacuation pencil, respectively) were enrolled between February 2018 and March 2019. Two outcome measures were used to evaluate the level of surgical smoke exposure, which was defined as the concentration of ultrafine smoke particles in the air (number of particles per cm3, ppc) around the operating table: (a) the average smoke level was the arithmetic mean of all measurements recorded during the surgery; and (b) the peak smoke level was the highest measurement recorded. Consecutive surgeries that involved bilateral symmetrical surgical exposure of the spine via a posterior midline incision were evaluated. Cauterized smoke was evacuated by two smoke evacuators: a "para incisional evacuator," which used a flat broad suction pad positioned immediately adjacent to the incision (25 patients), and a "surgical smoke evacuation pencil" which is an incorporated part of the electrocautery (26 patients). The level of smoke exposure was measured separately when surgically exposing the two sides of the spine: starting with one side (determined randomly) with the smoke evacuator being turned on and, then, the other side with the smoke evacuator off. The results were compared between the two sides. The para incisional smoke evacuator significantly reduced the average smoke level by an average of 59.7% (287 [interquartile range {IQR}: 126, 526] vs. 1,177 [IQR: 395, 2,702], p<.001). The surgical smoke evacuation pencil also reduced the average smoke level by an average of 44.1% (917 [IQR: 448, 1936] vs. 1,605 [IQR: 775, 4,280], p<.001). Both evacuators significantly reduced peak smoke levels as well. This study provides evidence supporting the utility of local smoke evacuation in reducing surgical smoke exposure in spine surgery. Such technology may help to improve the occupational health protection for spine operating room workers.


Induction of thromboxane A2 synthesizing enzymes in DMSO-induced granulocytic differentiation of HL-60 cells.
Human leukemia (HL)-60 cells were differentiated by several agents, and prostaglandins (PGs) and thromboxane (TX) synthesizing activity increased in response to the differentiation of the cells. We examined the expression of messenger RNA (mRNA) for TX-synthesizing enzymes, cyclooxygenase (COX)-1, COX-2 and TXA(2) synthase, in dimethyl sulfoxide (DMSO)-differentiated HL-60 cells by reverse transcriptase polymerase chain reaction (RT-PCR), and A23187-stimulated TXB(2) production, a stable metabolite of TXA(2), by radioimmunoassay (RIA). A23187-stimulated TXB(2) production, and mRNA abundance for COX-2, were not detected in non-treated HL-60 cells. TXA(2) synthase mRNA were barely detected in non-treated HL-60 cells. DMSO-induced HL-60 cells gained induction of TXB(2) synthesis and mRNA for COX-2 and TXA(2) synthase during granulocytic differentiation. COX-1 mRNA was constitutively expressed. A23187-stimulated TXB(2) production in DMSO-treated cells was inhibited by NS-398, a specific COX-2 inhibitor. These results demonstrated that TXB(2) production in granulocytic HL-60 cells was regulated at both the enzyme level of COX-2 and TXA(2) synthase.


Effects on walking of simultaneous upper/lower limb abobotulinumtoxina injections in patients with stroke or brain injury with spastic hemiparesis.
To compare walking speed in patients with spastic hemiparesis who received abobotulinumtoxinA either in the lower limb or simultaneously in both the lower and upper limbs. Post hoc analysis from a phase 3 study of abobotulinumtoxinA (Dysport®, NCT01251367). Adult patients with spastic hemiparesis causing gait dysfunction. Comfortable barefoot walking speed over 10 m was evaluated in patients receiving lower limb vs lower and upper limb injections over ≤4 treatment cycles; 1,000 U or 1,500 U in lower limb for cycle 1/2; optional upper limb injections from cycle 3 (500 U: upper limb, 1,000 U: lower limb). Mean (standard deviation; SD) lower limb cycle 3/4 doses were lower in the lower plus upper limb group vs lower limb only (1,000 U (SD 50), 1,000 U (SD 50) vs 1,380 U (SD 210), 1,360 U (SD 220). Baseline comfortable barefoot walking speed was similar between groups. Changes at cycle 3 week 4, in m/s, were: lower and upper limb: +0.063 (SD 0.131); lower limb only: +0.078 (SD 0.114), and cycle 4 week 4: lower and upper limb: +0.086 (SD 0.166); lower limb only: +0.086 (SD 0.123). Simultaneous lower and upper limb abobotulinumtoxinA treatment does not hamper improvement in walking speed compared with lower limb treatment alone. Thus, physicians may split the 1,500 U abobotulinumtoxinA dose as needed to best treat patients with spastic paresis.


Hodgkin lymphoma with unusual intrasinusoidal pattern of infiltration.
In spite of recent great advances in our understanding of both Hodgkin lymphoma (HL) and anaplastic large cell lymphoma (ALCL), occasionally there are CD30-positive large cell hematopoietic neoplasms, in which the morphologic and phenotypic features overlap to such an extent that they cannot easily be classified. We report a histologically unusual case of HL that mimicked ALCL, but had phenotypical characteristics of HL. The neoplastic cells resembling Reed-Sternberg cells or Hodgkin cells were mainly situated within sinusoidal spaces, which are characteristically seen in ALCL. However, they showed unequivocal expression of both CD30 and CD15, and no aberrant antigen expression to suggest ALCL (BSAP+, EMA-, LCA-, CD43-, CD2-, CD3-, CD4-, CD45RO-, ALK-, granzymeB-), with negative TCR gene rearrangement and no expression of EBV. HL with intrasinusoidal pattern has rarely been described, but we suggest that, although cases of HL with such a striking sinusoidal pattern are rare, nevertheless do exist. Since the identification of sinusoidal infiltration by CD30-positive neoplastic cells may lead to a mistaken view of ALCL, wide panel of antibodies should be used to confirm the diagnosis.


Cytokine-Coding Oncolytic Adenovirus TILT-123 Is Safe, Selective, and Effective as a Single Agent and in Combination with Immune Checkpoint Inhibitor Anti-PD-1.
Oncolytic viruses provide a biologically multi-faceted treatment option for patients who cannot be cured with currently available treatment options. We constructed an oncolytic adenovirus, TILT-123, to support T-cell therapies and immune checkpoint inhibitors in solid tumors. Adenoviruses are immunogenic by nature, are easy to produce in large quantities, and can carry relatively large transgenes. They are the most commonly used gene therapy vectors and are well tolerated in patients. TILT-123 expresses two potent cytokines, tumor necrosis factor alpha and interleukin-2, to stimulate especially the T-cell compartment in the tumor microenvironment. Before entering clinical studies, the safety and biodistribution of TILT-123 was studied in Syrian hamsters and in mice. The results show that TILT-123 is safe in animals as monotherapy and in combination with an immune checkpoint inhibitor anti-PD-1. The virus treatment induces acute changes in circulating immune cell compartments, but the levels return to normal by the middle of the treatment period. The virus is rapidly cleared from healthy tissues, and it does not cause damage to vital organs. The results support the initiation of a phase 1 dose-escalation trial, where melanoma patients receiving a tumor-infiltrating lymphocyte therapy are treated with TILT-123 (NCT04217473).


Intravenous proton pump inhibitors in the critical care setting.
Two well-controlled trials were carried out to investigate the effectiveness of intravenous proton pump inhibitors (PPIs) to reduce peptic ulcer rebleeding after successful hemostasis. The results demonstrated that the PPI reduced the rate of rebleeding significantly. The recent availability of the first intravenous PPI formulation in the United States, intravenous pantoprazole, represents an alternative to intravenous histamine-2 receptor antagonists. The results of 16 randomized, controlled trials involving a total of >3,800 patients (1,892 receiving PPIs and 1,911 controls) suggest that bolus administration plus continuous infusion of PPIs is a more effective pharmacotherapy than bolus infusion alone in decreasing both rebleeding and the need for surgery. Optimal effect is achieved with an intravenous 80-mg bolus, followed by continuous infusion of 8 mg/hr for 3 days, after which therapy may be continued with an oral PPI. Intermittent bolus administration yielded a minimal benefit. A difference in mortality rates has not yet been demonstrated.


Maribavir: a novel antiviral agent with activity against cytomegalovirus.
To review the pharmacology, pharmacokinetics, efficacy, and safety of maribavir, a novel antiviral agent in the benzimidazole drug class. Articles were identified through searches of MEDLINE (January 1998-July 2008). Abstracts from recent scientific meetings and the manufacturer were also included. All English-language in vitro and in vivo studies and abstracts evaluating maribavir were reviewed and considered for inclusion. All human studies were included. Maribavir has significant activity against both human cytomegalovirus (CMV) and Epstein-Barr virus, but not other herpesviruses. Unlike ganciclovir, which needs to be phosphorylated by UL 97 kinase to become an active inhibitor of DNA polymerase, maribavir directly inhibits UL 97 kinase. UL 97 kinase is an early viral gene product involved in viral DNA elongation, DNA packaging, and egress or shedding of capsids from viral nuclei. Maribavir has also been found to be effective against ganciclovir-resistant CMV strains. Maribavir differs from current CMV antiviral agents in its adverse event profile. Maribavir is not associated with nephrotoxicity or hematologic toxicities, but has been associated with taste disturbances. In February 2007, maribavir was granted Food and Drug Administration orphan drug status for prevention of CMV viremia and diseases in at-risk populations. Maribavir Phase 2 trials in stem-cell transplant recipients have been completed, and there are ongoing Phase 3 trials in stem-cell and organ transplant recipients. Maribavir may be an option for treatment of ganciclovir-resistant CMV infections. Its bioavailability is greater than that of oral ganciclovir, but less than that of valganciclovir. No differences in pharmacokinetics were seen in renally impaired patients, although dialysis-dependent patients were not evaluated. Maribavir is not associated with hematologic toxicities; however, the high prevalence of taste disturbances may limit its tolerability.