Potential disease agents in domestic goats and relevance to bighorn sheep (Ovis canadensis) management.
Domestic goats are raised for meat, milk and hair production, in herds for rangeland weed control, and as pack animals. Domestic sheep, goats and wild bighorn sheep are all susceptible to a multifactorial pneumonia. We sampled 43 herd goats from 7 herds and 48 pack goats from 11 herds for viral and bacterial serology, parasitology, and Pasteurellaceae microbiology. The goats in this study were in generally good health, although most goats did harbor various pathogens and parasites including several bacteria, specifically Pasteurellaceae, which have been associated with pneumonia in free-ranging bighorn sheep. It is not known if domestic goats can transmit the Pasteurellaceae or other pathogens found in this study readily to wild bighorn sheep. However, due the possibility of transmission, domestic goats in areas in or near bighorn sheep habitat should be managed to minimize the risk of spreading disease agents to bighorn sheep.


[Hydrocephalus in premature infants].
In the light of personal observations from the years 1948-1974 the author discusses the incidence of hydrocephalus in premature babies. The material observed confirms the generally accepted view that the incidence of hydrocephalus is higher in premature babies than in full-term babies. The author analyzes the causes which may be responsible for this finding and concludes that noxious factors during early or late pregnancy are the main cause although perinatal injuries play also a significant role.


Axonal outgrowth, neuropeptides expression and receptors tyrosine kinase phosphorylation in 3D organotypic cultures of adult dorsal root ganglia.
Limited knowledge from mechanistic studies on adult sensory neuronal activity was generated, to some extent, in recapitulated adult in vivo 3D microenvironment. To fill this gap there is a real need to better characterize the adult dorsal root ganglia (aDRG) organotypic cultures to make these in vitro systems exploitable for different approaches, ranging from basic neurobiology to regenerative therapies, to address the sensory nervous system in adult stage. We conducted a direct head-to-head comparison of aDRG and embryonic DRG (eDRG) organotypic culture focusing on axonal growth, neuropeptides expression and receptors tyrosine kinase (RTK) activation associated with neuronal survival, proliferation and differentiation. To identify alterations related to culture conditions, these parameters were also addressed in retrieved aDRG and eDRG and compared with organotypic cultures. Under similar neurotrophic stimulation, aDRG organotypic cultures displayed lower axonal outgrowth rate supported by reduced expression of growth associated protein-43 and high levels of RhoA and glycogen synthase kinase 3 beta mRNA transcripts. In addition, differential alteration in sensory neuropeptides expression, namely calcitonin gene-related peptide and substance P, was detected and was mainly pronounced at gene expression levels. Among 39 different RTK, five receptors from three RTK families were emphasized: tropomyosin receptor kinase A (TrkA), epidermal growth factor receptors (EGFR, ErbB2 and ErbB3) and platelet-derived growth factor receptor (PDGFR). Of note, except for EGFR, the phosphorylation of these receptors was dependent on DRG developmental stage and/or culture condition. In addition, EGFR and PDGFR displayed alterations in their cellular expression pattern in cultured DRG. Overall we provided valuable information particularly important when addressing in vitro the molecular mechanisms associated with development, maturation and regeneration of the sensory nervous system.


Globus pallidus and motor initiation: the bilateral effects of unilateral quisqualic acid-induced lesion on reaction times in monkeys.
The results of many experimental studies have shown that the globus pallidus (GP) is involved in the control of motor activities, particularly during motor execution. Whether or not the GP is involved in the initiation phase is still a matter of controversy, however. This question was investigated in the present study in Papio papio monkeys after GP lesion using a simple reaction time (RT) task, focusing particularly on the initiation phase. The monkeys were trained to perform this task, which consisted of raising their hand as quickly as possible in response to a visual signal. The RT and its premotor and motor components were measured. In addition, the distribution of the RTs was analyzed in order to assess the number of long latency responses. After making unilateral GP cell lesions by locally injecting small amounts of the excitatory amino acid quisqualic acid, a bilateral increase was observed in RT. This lengthening involved both the premotor and the motor phases of the RT when the task was performed with the contralateral limb and only the premotor phase when it was performed with the ipsilateral one. A significant increase was observed in the percentage of long latency responses recorded in the contralateral limb after the GP lesion but not in the ipsilateral one. Increases in the RT and in the percentage of long latency responses are thought to constitute two indices of the akinesia observed in our task involving speed constraints, which suggests that the GP may participate in motor initiation. A complete recovery of the RT was observed within one month, whereas the increase in the percentage of long latency responses persisted. These two indices of akinesia seemed therefore to result from an impairment involving both motor and nonmotor processes. These data suggest that the GP may be involved in the control of postural adjustment, motivation, and/or the control of the initial isometric part of movements. The time course of the recovery from the deficits observed after GP lesion shows the existence of mechanisms which seem to have been operative particularly in the case of impairments affecting motor processes.


Characterizing neuropathies associated with monoclonal gammopathy of undetermined significance (MGUS): a framework consistent with classifying injuries according to fiber size.
Neuropathies associated with monoclonal gammopathy of undetermined significance (MGUS) occur frequently in the elderly. Data from 42 consecutive elderly patients with a MGUS-associated neuropathy - 12 patients with IgM MGUS, 25 patients with IgG MGUS, 5 patients with IgA MGUS - were evaluated prospectively using quantifiable clinical criteria and quantitative sensory testing. Results consistent with preferential injury to large fibers were found in patients with IgM isotypes (P <.005) but not in patients with IgG isotypes (P <.0005 to.0004). These findings support an immunologic origin for at least some MGUS-associated neuropathies and provide information important for the clinical evaluation of neuropathies in the elderly.


Differentiation between symptomatic Chiari I malformation and asymptomatic tonsilar ectopia by using cerebrospinal fluid flow imaging: initial estimate of imaging accuracy.
To determine the sensitivity and specificity of cerebrospinal fluid (CSF) flow imaging in distinguishing between patients with symptomatic Chiari I malformation and those with asymptomatic tonsilar ectopia by using a neurosurgeon's overall clinical determination as the reference standard. The institutional review board of the University of Wisconsin Hospital and Clinics approved our HIPAA-compliant retrospective study and granted a waiver for informed consent. Seventeen patients (five male, 12 female; aged 4-43 years) with tonsils extending more than 5 mm below the foramen magnum were classified by the neurosurgeon as symptomatic for Chiari I malformation or asymptomatic for tonsilar ectopia. The CSF flow images of the two groups were read independently in blinded fashion by four neuroradiologists. Reader agreement was calculated as percentage of readings in each patient that agreed with the neurosurgeon's classification. Sensitivity and specificity were respectively calculated as the percentage of abnormal readings in symptomatic patients and the percentage of normal readings in asymptomatic patients. Of 17 patients, nine were classified by the neurosurgeon as symptomatic Chiari I malformation and eight as asymptomatic tonsilar ectopia. Agreement between pairs of readers was 63%-44%. For sagittal and transverse images, reader sensitivity for finding abnormal flow in symptomatic Chiari I malformation patients averaged 76% and specificity for normal flow in patients with asymptomatic tonsilar ectopia averaged 62%. The number of positive readings in the symptomatic patient group was significantly greater than that in the asymptomatic group (P < .02). Readers detected an abnormal CSF flow pattern significantly more often in patients with symptomatic Chiari I malformation than in patients with asymptomatic tonsilar ectopia.


The role of scalene lymph node biopsy in advanced carcinoma of the cervix uteri.
Considerable controversy exists in the role of scalene lymph node biopsy in the pretreatment assessment of patients with carcinoma of the cervix uteri. Scalene lymph node biopsy was carried out on ten patients having advanced carcinoma of the cervix uteri with documented para-aortic nodal involvement. Metastatic carcinoma was found in the scalene lymph nodes in five of ten patients. These preliminary findings suggest that excision of scalene lymph nodes should be carried out prior to the institution of therapy in all patients with carcinoma of the cervix uteri which is metastatic to the para-aortic lymph nodes.


A new Drepanosticta species from Seram, Moluccas (Odonata: Platystictidae).
Drepanosticta seramensis sp. nov. (holotype ♂: Indonesia, Moluccas, Seram Island, 36 km SW of Wahai, S 2.9768, E 129.2269; 2-xii-1996; deposited in RMNH, Leiden), is described as new to science. It is closely related to D. moluccana Lieftinck, 1938 from Buru and D. amboinensis van Tol, 2007 from Ambon.


Insertion reactions of dicyclohexylcarbodiimide with aminoboranes, -boryls and -borylenes.
Insertion reactions of dicyclohexylcarbodiimide with aminoboranes and with aminoboryl and -borylene transition metal complexes have been examined as potential routes to new boron-containing ligand systems. Reactions with systems containing two-coordinate boron centres are found to be significantly more facile than those with three-coordinate substrates. Thus, reaction of (dicyclohexylamino)boron dichloride () with dicyclohexylcarbodiimide over 36 h at 50 degrees C generates the (structurally authenticated) guanidinate complex Cy(2)NC(NCy)(2)BCl(2) () via insertion into the BN bond. By contrast, the corresponding reaction with the cationic aminoborylene complex [CpFe(CO)(2)(BNCy(2))](+)[BAr(f)(4)](-) () proceeds rapidly at ca.-30 degrees C, via initial insertion into the FeB bond to give [CpFe(CO)(2)C(NCy)(2)BNCy(2)](+)[BAr(f)(4)](-) (). Consistent with related studies, a key factor in facilitating such insertion chemistry is thought to be the formation of an initial donor/acceptor complex between the diimide and the group 13 centre. Thus, DFT studies suggest that [CpFe(CO)(2)B(NCy(2))(CyNCNCy)](+)[BAr(f)(4)](-) is a potential intermediate in the reaction of with CyNCNCy, and that further reaction to give the observed product, , is strongly exergic (-183 kJ mol(-1)). By contrast, DFT calculations for the alternative isomer [CpFe(CO)(2)B(CyN)(2)CNCy(2)](+)[BAr(f)(4)](-) (), formed by BN insertion, suggest that it is 112 kJ mol(-1) less stable than . Such experimental and computational findings imply that under reaction conditions where a suitable isomerisation pathway is available, cationic complexes such as , which contain a four-membered boron-donor heterocycle are likely to be disfavoured with respect to alternative C-bound isomers.


Color Match Between Composite Resin and Tooth Remnant in Class IV Restorations: A Case Series.
Rehydration of the tooth remnant and complete polymerization of the composite resin are aspects that should be considered in shade selection of composite resin. This article presents a case series of Class IV restorations performed to evaluate the color match between the composite resin and the tooth remnant. Thirteen Class IV restorations were performed in maxillary central incisors and evaluated according to the period following the restorative procedure: 10 minutes (baseline), 48 hours before and after finishing and polishing, and seven, 14, and 28 days. The color match of the restorations was evaluated by the ΔE values of the tooth remnant (TR) and the composite resin (CR) in each evaluation period using a spectrophotometer. The translucency, luminosity, and saturation were analyzed qualitatively in digital photographs of the restorations. The CR ΔE was statistically similar to the TR ΔE at 14 and 28 days ( p>0.05). The saturation and luminosity of most of the restorations remained unchanged, but there was a greater change in the translucency. The color match of the composite resin in Class IV restorations was observed after 14 days of clinical assessment in this case series.


Estimating deaths from foodborne disease in the UK for 11 key pathogens.
To estimate the number of deaths from foodborne disease in the UK from 11 key pathogens. Four different models were developed using data from a range of sources. These included enhanced surveillance, outbreaks, death certificates and hospital episode statistics data. For each model, median estimates were produced with 95% credible intervals (CrI). The results from the different models were compared. The estimates for foodborne deaths for each pathogen from the different models were consistent, with CrIs largely overlapping. Based on the preferred model for each pathogen, foodborne norovirus is estimated to cause 56 deaths per year (95% CrI 32 to 92), foodborne Salmonella 33 deaths (95% CrI 7 to 159), foodborne Listeria monocytogenes 26 deaths (95% CrI 24 to 28), foodborne Clostridium perfringens 25 deaths (95% CrI 1 to 163) and foodborne Campylobacter 21 deaths (95% CrI 8 to 47). The considerable overlap in the CrIs means it is not possible to make any firm conclusions on ranking. Most of these deaths occur in those aged over 75 years. Foodborne deaths from Shigella, Cryptosporidium, Giardia, adenovirus, astrovirus and rotavirus are all rare. We estimate that there are 180 deaths per year in the UK (95% CrI 113 to 359) caused by foodborne disease based on these 11 pathogens. While this is a small fraction of the estimated 2.4 million cases of foodborne illness per year it still illustrates the potential severity of these illnesses demonstrating the importance in continuing efforts to reduce these infections.


Randomised controlled trial of the READER method of critical appraisal in general practice.
To evaluate the READER model for critical reading by comparing it with a free appraisal, and to explore what factors influence different components of the model. A randomised controlled trial in which two groups of general practitioners assessed three papers from the general practice section of the BMJ. Northern Ireland. 243 general practitioners. Scores given using the READER model (Relevance, Education, Applicability, Discrimination, overall Evaluation) and scores given using a free appraisal for scientific quality and an overall total. The hierarchical order for the three papers was different for the two groups, according to the total scores. Participants using the READER method (intervention group) gave a significantly lower total score (P < or = 0.01) and a lower score for the scientific quality (P < or = 0.0001) for all three papers. Overall more than one in five (22%), and more men than women, read more than 5 articles a month (P < or = 0.05). Those who were trainers tended to read more articles (P < or = 0.05), and no trainers admitted to reading none. Overall, 58% (135/234) (68% (76/112) of the intervention group) believed that taking part in the exercise would encourage them to be more critical of published articles in the future (P < or = 0.01). Participants using the READER model gave a consistently lower overall score and applied a more appropriate appraisal to the methodology of the studies. The method was both accurate and repeatable. No intrinsic factors influenced the scores, so the model is appropriate for use by all general practitioners regardless of their seniority, location, teaching or training experience, and the number of articles they read regularly.


Tumor microenvironment: what can effusions teach us?
Malignant effusions, which are composed of malignant pleural and peritoneal fluid, are an unusual manifestation of cancer and frequently portend a poor prognosis. Neoplastic cells that disseminate into cavities containing effusions are highly metastatic and possess a strong autonomous proliferative drive while concurrently being stimulatory of exudative effusions. Most effusions will respond to transient therapeutic intervention, including the obliteration of potential space via pleurodesis. Cure, however, is rare, thus making effusions a biologically, biochemically, and clinically important topic of study. The local microenvironment that supports malignant growth, invasion, and dissemination of the solid primary tumor into the vasculature is composed of activated stroma that includes scaffolding consisting of materials that promote the tumor function, and vascular structures to provide conduits for travel and nutrient delivery. Less is understood about the tumor-cell microenvironment in malignant effusions. The fluid nature of such a microenvironment when compared with the solid primary tumor may have significant implications for disease dissemination and progression. Dissecting the signaling activity and components of such microenvironments will improve our understanding and ultimately our ability to provide better patient care.


Impaired activity of adherens junctions contributes to endothelial dilator dysfunction in ageing rat arteries.
Ageing-induced endothelial dysfunction contributes to organ dysfunction and progression of cardiovascular disease. VE-cadherin clustering at adherens junctions promotes protective endothelial functions, including endothelium-dependent dilatation. Ageing increased internalization and degradation of VE-cadherin, resulting in impaired activity of adherens junctions. Inhibition of VE-cadherin clustering at adherens junctions (function-blocking antibody; FBA) reduced endothelial dilatation in young arteries but did not affect the already impaired dilatation in old arteries. After junctional disruption with the FBA, dilatation was similar in young and old arteries. Src tyrosine kinase activity and tyrosine phosphorylation of VE-cadherin were increased in old arteries. Src inhibition increased VE-cadherin at adherens junctions and increased endothelial dilatation in old, but not young, arteries. Src inhibition did not increase dilatation in old arteries treated with the VE-cadherin FBA. Ageing impairs the activity of adherens junctions, which contributes to endothelial dilator dysfunction. Restoring the activity of adherens junctions could be of therapeutic benefit in vascular ageing. Endothelial dilator dysfunction contributes to pathological vascular ageing. Experiments assessed whether altered activity of endothelial adherens junctions (AJs) might contribute to this dysfunction. Aortas and tail arteries were isolated from young (3-4 months) and old (22-24 months) F344 rats. VE-cadherin immunofluorescent staining at endothelial AJs and AJ width were reduced in old compared to young arteries. A 140 kDa VE-cadherin species was present on the cell surface and in TTX-insoluble fractions, consistent with junctional localization. Levels of the 140 kDa VE-cadherin were decreased, whereas levels of a TTX-soluble 115 kDa VE-cadherin species were increased in old compared to young arteries. Acetylcholine caused endothelium-dependent dilatation that was decreased in old compared to young arteries. Disruption of VE-cadherin clustering at AJs (function-blocking antibody, FBA) inhibited dilatation to acetylcholine in young, but not old, arteries. After the FBA, there was no longer any difference in dilatation between old and young arteries. Src activity and tyrosine phosphorylation of VE-cadherin were increased in old compared to young arteries. In old arteries, Src inhibition (saracatinib) increased: (i) 140 kDa VE-cadherin in the TTX-insoluble fraction, (ii) VE-cadherin intensity at AJs, (iii) AJ width, and (iv) acetylcholine dilatation. In old arteries treated with the FBA, saracatinib no longer increased acetylcholine dilatation. Saracatinib did not affect dilatation in young arteries. Therefore, ageing impairs AJ activity, which appears to reflect Src-induced phosphorylation, internalization and degradation of VE-cadherin. Moreover, impaired AJ activity can account for the endothelial dilator dysfunction in old arteries. Restoring endothelial AJ activity may be a novel therapeutic approach to vascular ageing.


Trends in Drug Resistance of Acinetobacter baumannii over a 10-year Period: Nationwide Data from the China Surveillance of Antimicrobial Resistance Program.
Acinetobacter baumannii has emerged as an important pathogen causing a variety of infections. Using data from the China Surveillance of Antimicrobial Resistance Program conducted biennially, we investigated the secular changes in the resistance of 2917 isolates of A. baumannii from 2004 to 2014 to differ antimicrobial agents. Pathogen samples were collected from 17 to 20 hospitals located in the eastern, central, and western regions of China. Minimum inhibitory concentrations (MICs) were determined by a 2-fold agar dilution method, and antimicrobial susceptibility was established using the 2014 Clinical Laboratory Standards Institute-approved breakpoints. Isolates not susceptible to all the tested aminoglycosides, fluoroquinolones, β-lactams, β-lactam/β-lactam inhibitors and carbapenems were defined as extensively drug resistant. The rates of nonsusceptibility to common antimicrobial agents remained high (>65%) over the years with some fluctuations to certain agents. The prevalence of imipenem-resistant A. baumannii (IRAB) increased from 13.3% in 2004 to 70.5% in 2014 and that of extensively drug-resistant A. baumannii (XDRAB) increased from 11.1% in 2004 to 60.4% in 2014. The activity of tigecycline was stable with MIC90 ≤4 mg/L against A. baumannii from 2009 to 2014. Susceptibility to colistin remained high (97.0%) from 2009 to 2014. The prevalence of XDRAB increased in all the three surveillance regions over the years and was significantly higher in Intensive Care Unit (ICU) wards than non-ICU wards. This longitudinal multicenter surveillance program revealed the nationwide emergence of A. baumannii in China and showed a significant increase in prevalence from 2004 to 2014. High levels of bacterial resistance were detected among samples collected from clinical settings in China, with IRAB and XDRAB being especially prevalent. This study will help to guide empirical therapy and identify at-risk groups requiring more intense interventional infection control measures, while also helping to focus surveillance efforts.


Flow Cytometric Patterns of CD200 and CD1d Expression Distinguish CD10-Negative, CD5-Negative Mature B-Cell Lymphoproliferative Disorders.
The importance of distinguishing mature B-cell lymphoproliferative disorders (B-LPDs) is highlighted by the distinct treatments used for and varying prognoses seen in association with these different diseases. Immunophenotyping allows for accurate and efficient differentiation of many B-LPDs. Recently, we showed that CD200 is highly expressed in hairy cell leukemia (HCL) but not in marginal zone lymphoma (MZL), lymphoplasmacytic lymphoma (LPL), or hairy cell leukemia-variant (HCL-v). Here, we assessed the usefulness of a flow cytometric panel combining CD200 and CD1d with CD25, CD103, and CD11c to distinguish CD10-, CD5- B-LPDs. We analyzed the expression of CD200 and CD1d by flow cytometric analysis in 79 cases of CD10-, CD5- mature B-LPDs. Distinct patterns of CD200 and CD1d expression were seen in the examined B-LPDs. HCL showed bright positivity for CD200 along with positive staining for CD1d, whereas HCL-v showed low levels of expression for both markers. LPL demonstrated positive staining for CD200 in combination with dim to negative staining for CD1d. In contrast, MZL was commonly positive for CD1d and negative for CD200. Flow cytometric analysis of CD200 and CD1d, along with CD25, CD103, and CD11c, can aid in the diagnosis of CD10-, CD5- mature B-LPDs.


Tumor necrosis factor alpha as a marker of systemic and local inflammation in "healthy" smokers.
Tobacco smoking induces a local and systemic inflammatory reaction and also a decline in pulmonary function. There are some novel noninvasive methods to measure the degree of inflammatory bronchial reaction, including the exhaled breath condensate (EBC) in which several inflammatory markers can be measured, including tumor necrosis factor alpha (TNF-alpha). There is a clear clinical need to develop methods that allow early detection of smokers at risk of losing pulmonary function. THE AIMS OF THE PRESENT STUDY ARE: 1) to show that smokers show higher levels of TNF-alpha both in serum and EBC; 2) to analyze the possible influence of gender, age, and weight on this parameter; and 3) to determine a possible association between smoking and pulmonary function parameters and TNF-alpha levels. We have prospectively analyzed two cohorts of smokers and non-smokers subjects without any chronic or acute disease (within eight weeks of study initiation). We have performed pulmonary function tests with bronchodilators and also collected EBC and blood samples before smoking cessation. Statistical analysis was performed with SPSS 11.0 for Windows Statistical Package. The study has enrolled 17 patients (8 smokers), 50% of whom were females. Mean age was 38.59 years old (standard deviation, 7.4). The mean number of cigarettes smoked in the smoker group was 26.14 (11.29) cigarettes/day and the mean age when tobacco first began was 15.14 (2.04) years. We have not been able to show any significant differences in TNF-alpha levels according to age or weight. For the whole series we have not found any significant influence of gender in TNF-alpha levels, but after dividing the series in smokers and nonsmokers, we have shown higher levels of TNF-alpha in serum (5.59 [0.26] pg/mL vs 5.56 [0.37] pg/mL; nonsignificant [NS]) and EBC (4.94 [0.41] pg/mL vs 4.22 [0.36] pg/mL; p = 0.031) in male smokers. On the other hand, nonsmoking females showed slightly higher TNF-alpha levels in serum (5.70 [0.50] pg/mL vs 5.42 [0.29] pg/mL; NS) and EBC (4.54 [0.92] vs 4.11 [0.41 pg/mL]; NS). Smokers had higher TNF-alpha levels in EBC (4.46 [0.58] pg/mL vs 4.34 [0.62] pg/mL; NS), while serum TNF-alpha levels were slightly higher in nonsmokers (5.52 [0.56] pg/mL vs 5.50 [0.27] pg/mL; NS). We have not demonstrated any association between tobacco consumption and TNF-alpha levels. We have not shown any significant relation between pulmonary function and the studied parameters, with only a modest association between forced expiratory volume at one second and forced vital capacity and TNF-alpha levels in EBC. Smokers show higher TNF-alpha levels in EBC. Among smokers, males show higher levels of TNF in serum and EBC. We have not confirmed any significant influence of age or weight on TNF-alpha levels. These levels do not seem to be influenced either by the amount of tobacco or the time since habit began. We have shown a modest relation between pulmonary function and TNF-alpha levels in EBC.


[Preparation of organic-inorganic hybrid poly(ionic liquids) material and evaluation of the adsorption to dyes].
An organic-inorganic hybrid poly(ionic liquids) material was prepared by using allyl triethoxysilane and 1-vinyl-3-octyl imidazolium bromide ionic liquids via combining free radical polymerization with sol-gel process. The prepared hybrid poly(ionic liquids) material was characterized by infrared spectroscopy and scanning electron microscopy. The adsorption properties of the prepared material to common dyes such as tartrazine, sunset yellow, amaranth and allura red were investigated. The results showed that the prepared poly(ionic liquids) material had excellent adsorption properties to sunset yellow and allura red. The adsorption capacities were 29.20 and 86.17 mg/g, respectively. When the adsorption time was 5 min, the material showed a fast adsorption rate to allura red and sunset yellow, which were 87.5% and 72.8% of the balance adsorption capacities, respectively.


Contributing factors to sandblasters' silicosis: inadequate respiratory protection equipment and standards.
National concordance standards for respiratory protection during abrasive blasting have existed for more than 50 years; however, these standards have not kept pace with advances in blast equipment, have not provided realistic estimates of expected protection in the workplace, and have been misused by manufacturers and distributors of respiratory protective equipment who have assured, through sales literature, that the equipment is acceptable for conditions under which they have never been tested. This situation has contributed to exposure of sandblasters to hazardous levels of respirable free silica, and is reviewed here to prevent a continuation of the incompatibility of these and other standards for respiratory protection with the actual exposures to various noxious inhalants in the workplace.


Gastrointestinal cancers, ACE-2/TMPRSS2 expression and susceptibility to COVID-19.
Recent studies on the pathophysiology of COVID-19 are indicating that the Angiotensin convertase enzyme 2 (ACE-2) and transmembrane serine protease 2 (TMPRSS2) can act as a major component in the fusion of SARS-Cov-2 with target cells. It has also been observed that the expression of ACE-2 and TMPRSS2 can be altered in malignancies. Shedding light on this matter could be crucial since the COVID-19 pandemic interfered with many gastrointestinal cancer screening programs. Herein we discuss the possibility of severe forms of COVID-19 in patients with gastrointestinal cancers due to the gastrointestinal entry route of SARS-CoV-2 into the human body. The disruption of cancer screening programs caused by the current COVID-19 pandemic could therefore have massive negative health impact on patients affected by gastrointestinal malignancies.


Surface-exposed glycopeptidolipids of Mycobacterium smegmatis specifically inhibit the phagocytosis of mycobacteria by human macrophages. Identification of a novel family of glycopeptidolipids.
Phagocytosis by macrophages represents the early step of the mycobacterial infection. It is governed both by the nature of the host receptors used and the ligands exposed on the bacteria. The outermost molecules of the nonpathogenic Mycobacterium smegmatis were extracted by a mechanical treatment and found to specifically and dose dependently inhibit the phagocytosis of both M. smegmatis and the opportunistic pathogen M. kansasii by human macrophages derived from monocytes. The inhibitory activity was attributed to surface lipids because it is extracted by chloroform and reduced by alkaline hydrolysis but not by protease treatment. Fractionation of surface lipids by adsorption chromatography indicated that the major inhibitory compounds consisted of phospholipids and glycopeptidolipids (GPLs). Mass spectrometry and nuclear magnetic resonance spectroscopy analyses, combined with chemical degradation methods, demonstrated the existence of a novel family of GPLs that consists of a core composed of the long-chain tripeptidyl amino-alcohol with a di-O-acetyl-6-deoxytalosyl unit substituting the allo-threoninyl residue and a 2-succinyl-3,4-di-O-CH3-rhamnosyl unit linked to the alaninol end of the molecules. These compounds, as well as diglycosylated GPLs at the alaninol end and de-O-acylated GPLs, but not the non-serovar-specific di-O-acetylated GPLs, inhibited the phagocytosis of M. smegmatis and M. avium by human macrophages at a few nanomolar concentration without affecting the rate of zymosan internalization. At micromolar concentrations, the native GPLs also inhibit the uptake of both M. tuberculosis and M. kansasii. De-O-acylation experiments established the critical roles of both the succinyl and acetyl substituents. Collectively, these data provide evidence that surface-exposed mycobacterial glycoconjugates are efficient competitors of the interaction between macrophages and mycobacteria and, as such, could represent pharmacological tools for the control of mycobacterial infections.


Use of a computerised decision aid (DA) to inform the decision process on adjuvant chemotherapy in patients with stage II colorectal cancer: development and preliminary evaluation.
To develop a computerised decision aid (DA) to inform the decision process on adjuvant chemotherapy in patients with stage II colorectal cancer, and examine perceived usefulness, acceptability and areas for improvement of the DA. Mixed methods. Single outpatient oncology department in central London. Consecutive recruitment of 13 patients with stage II colorectal cancer, 12 of whom completed the study. Inclusion criteria were: age >18 years; complete resection for stage II adenocarcinoma of the colon or rectum; patients within 14-56 days after surgery; no contraindication to adjuvant chemotherapy; able to give written informed consent. Exclusion criterion: previous chemotherapy. Patient perceived usefulness (assessed by the PrepDM questionnaire) and acceptability of the DA. PrepDM scores, measuring the perceived usefulness of the DA in preparing the patient to communicate with their doctor and make a health decision, were above those reported in other patient groups. Patient acceptability scores were also high; however, interviews showed that there was evidence of a lack of understanding of key information among some patients, in particular their baseline risk of recurrence, the net benefit of combination chemotherapy and the rationale for having chemotherapy when cancer had apparently gone. Patients found the DA acceptable and useful in supporting their decision about whether or not to have adjuvant chemotherapy. Suggested improvements for the DA include: sequential presentation of treatment options (eg, no treatment vs 1 drug, 1 drug vs 2 drugs) to enhance patient understanding of the difference between combination and single therapy, diagrams to help patients understand the rationale for chemotherapy to prevent a recurrence and inbuilt checks on patient understanding of baseline risk of recurrence and net benefit of chemotherapy.


Cardiac Function in Children After Kidney Transplant.
Renal transplant improves echocardiographic markers of systolic and diastolic heart functions. The aim of this study was to evaluate the gradual changes in left and right ventricle functions in children and young adults before and after renal transplant. Thirty kidney recipients of median age 13 years (range, 5-19 years) were included the study. Tissue Dopplerimaging from the septal and lateral mitral annulus ofthe left ventricle and free wall of the right ventricle was performed. Right ventricle systolic excursion velocity and tricuspid annular plane systolic excursion were calculated. Systolic and diastolic heart functions-which gained just before transplant, were compared with posttransplant early- term (6 months to 1 year) and long-term (longer than 1 year) functions. Twelve patients received deceased-donor and 18 patients received living donor renal transplant. Follow-up after transplant was 44 ± 23 months. Left ventricle ejection fractions were normal. The left ventricle, right ventricle, and interventricular septalTei indices were significantly higher before transplant.The posttransplantation early- and late-term results of left ventricle,right ventricle, and interventricular septal Tei indices were similar. Tricuspid annular plane systolic excursion levels were abnormal in 11 patients (36%), and right ventricle systolic excursion velocities were abnormal in 7 patients (23%) before transplant. All tricuspid annular plane systolic excursion levels and 94% ofright ventricle systolic excursion velocities were normal, but left ventricle Tei indices were higher in 8 (26%) and right ventricle Tei indices were higher in 14 patients (46%) at late-term follow-up. The systolic and diastolic dysfunctions of both ventricles appear to be highly prevalent in pediatric renal transplant recipients, especially soon after transplant, and were shown to usually decrease with time. Improvements in right ventricle dysfunction are slower, even in optimally treated posttransplant patients.


Magnetic Filler Polymer Composites-Morphology Characterization and Experimental and Stochastic Finite Element Analyses of Mechanical Properties.
Polymer composites containing magnetic fillers are promising materials for a variety of applications, such as in energy storage and medical fields. To facilitate the engineering design of respective components, a comprehensive understanding of the mechanical behavior of such inhomogeneous and potentially highly anisotropic materials is important. Therefore, the authors created magnetic composites by compression molding. The epoxy polymer matrix was modified with a commercial-grade thickening agent. Isotropic magnetic particles were added as the functional filler. The microstructural morphology, especially the filler distribution, dispersion, and alignment, was characterized using microscopy techniques. The mechanical properties of the composites were experimentally characterized and studied by stochastic finite element analysis (SFEA). Modeling was conducted employing four cases to predict the elastic modulus: fully random distribution, randomly aligned distribution, a so-called "rough" interface contact, and a bonded interface contact. Results from experiments and SFEA modeling were compared and discussed.


Signal sequence and DNA-mediated expression of human lysosomal alpha-galactosidase A.
Twelve complementary DNA clones for human lysosomal alpha-galactosidase A were isolated from an Okayama-Berg library constructed from SV40-transformed human fibroblasts. The identity of these clones was confirmed by complete colinearity of the nucleotide-deduced amino acid sequence with that determined by direct chemical sequencing of human placental alpha-galactosidase A. Hybridization of the alpha-galactosidase A cDNA to genomic DNA from individuals with varying numbers of X chromosomes as well as from interspecies somatic-cell hybrids showed only a single locus in the genome at Xq 13.1-Xq 22. One cDNA clone (pcD-AG210) contained the complete coding sequence for both the signal peptide and mature alpha-galactosidase A. The signal peptide of 31 amino acids contains the expected hydrophobic domains consisting of Leu-Gly-Cys-Ala-Leu-Ala-Leu and Phe-Leu-Ala-Leu-Val and has Ala at the signal peptidase cleavage site. Twelve out of fifteen G residues flanking the 5' end of the cDNA in pcD-AG210 were removed and the truncated fragment was ligated into the original vector. This construct, pcD-AG502, encoded enzymatically active human alpha-galactosidase A in monkey COS cells.


A comparison of stream biological responses to discharge from wastewater treatment plants in high and low population density areas.
The ultimate purpose of this study was to identify broad relationships that may have relevance for the risk assessment of chemicals and materials that are discharged to receiving streams via municipal wastewater treatment plant (WWTP) effluents (e.g., consumer product ingredients). The effects of municipal wastewaters occurring in high population density (>500 persons per square mile, urban) and low population density (<500 persons per square mile, rural) environments were determined via analysis of biological, habitat, and water chemistry data collected both immediately upstream and downstream of 221 WWTPs in Ohio, USA. Several biological and chemistry indicators demonstrated poorer water quality in urban areas compared to rural areas. After considering the effect of river size, adverse effects downstream of WWTPs for both fish and macroinvertebrate communities were clearly identified for only urban areas. These data indicate that WWTP potency may be greater in urban areas compared to rural areas.


Case of a strangulated right paraduodenal fossa hernia in a malrotated gut.
We report an unusual case of a strangulated internal hernia resulting from a right paraduodenal fossa hernia (PDH) in the context of bowel malrotation. There are few documented cases of PDHs associated with a concomitant gut malrotation. Emergency laparotomy was performed based on clinical and radiological. Intraoperatively, the proximal jejunum was seen to enter a hernia sac formed by an aberrant duodenojejunal flexure located to the right of the aorta. This was presumed to be a strangulated internal hernia of the paraduodenal recess in a malrotated gut. The hernia neck was widened and the sac obliterated to allow reduction of the contents. On reduction and warming, the insulted small bowel appeared viable and returned to the abdominal cavity without resection.


Deaf identities in a multicultural setting: The Ugandan context.
Often located far apart from each other, deaf and hearing impaired persons face a multiplicity of challenges that evolve around isolation, neglect and the deprivation of essential social services that affect their welfare and survival. Although it is evident that the number of persons born with or acquire hearing impairments in later stages of their lives is increasing in many developing countries, there is limited research on this population. The main objective of this article is to explore the identities and experiences of living as a person who is deaf in Uganda. Using data from semi-structured interviews with 42 deaf persons (aged 19-41) and three focus group discussions, the study findings show that beneath the more pragmatic identities documented in the United States and European discourses there is a matrix of ambiguous, often competing and manifold forms in Uganda that are not necessarily based on the deaf and deaf constructions. The results further show that the country's cultural, religious and ethnic diversity is more of a restraint than an enabler to the aspirations of the deaf community. The study concludes that researchers and policy makers need to be cognisant of the unique issues underlying deaf epistemologies whilst implementing policy and programme initiatives that directly affect them. The upper case 'D' in the term deaf is a convention that has been used since the early 1970s to connote a 'socially constructed visual culture' or a linguistic, social and cultural minority group who use sign language as primary means of communication and identify with the deaf community, whereas the lower case 'd' in deaf refers to 'the audio logical condition of hearing impairment'. However, in this article the lower case has been used consistently.


The Reliability of a Single-Trial Measurement of Maximal Accumulated Oxygen Deficit Determined via Perceptually-Regulated Exercise.
Purpose: The aim of this study was to evaluate the reliability of a single-trial determination of maximal accumulated oxygen deficit (MAOD) achieved via the aid of perceptually-regulated incremental exercise. Methods: 14 trained male cyclists (age: 45 ± 8 yrs; height: 1.82 ± 0.06 m; mass: 79.7 ± 6.7 kg; V˙O2max: 4.09 ± 0.57 L·min-1) performed three trials of a submaximal incremental cycling test followed by a test to exhaustion at 116% of predicted V˙O2max. The intensity for each stage of the incremental test was regulated by participants to elicit perceived exertion levels of 9-15 on the Borg (6-20) scale. Linear regression was used to estimate V˙O2max at a perceived exertion level of 19. MAOD was calculated from the difference between predicted and actual oxygen demand in the test to exhaustion, reported in oxygen equivalents (O2 eq). A separate incremental test was used to measure V˙O2max directly. Results: Correlation coefficients between perceived exertion and V˙O2 across trials were strong (r ≥0.99), and there were no between-trial differences in predicted V˙O2max (4.03 ± 1.04, 3.76 ± 0.53, and 3.69 ± 0.64 L·min-1, respectively; p = .142) or MAOD (2.75 ± 2.28, 2.50 ± 1.53, and 2.93 ± 1.40 L O2 eq, respectively; p = .633). Nevertheless, the coefficients of variation for predicted V˙O2max (14.2%) and MAOD (142.8%) were poor. Conclusions: The prediction of V˙O2max from perceptually-regulated exercise displays a level of test-retest reliability which prevents its use as a means of evaluating MAOD reliably in a single-trial.


Monitoring of pre-competition dehydration- induced skeletal muscle damage and inflammation levels among elite wrestlers.
Weight loss practice before competitions is a common method in weight sports. The current study aimed to monitor Plasma Osmolarity (POsm), skeletal muscle damage and inflammation levels induced by pre-competition dehydration among elite wrestlers. Twenty-four male elite wrestlers participated in the study. A survey information form that assessed pre-competition weight loss practices were administered to the wrestlers. Additionally, Total Creatine Kinase (CK), Lactate Dehydrogenase (LDH), Aspartate Aminotransferase (AST), Alanine Aminotransferase (ALT), C-reactive Protein (C-RP) and POsm, analyses were evaluated by a specialist at the biochemical laboratory. POsm level for euhydration is ⩽ 290 mOsm/L. But if POsm level is > 290, then dehydration occurs. The wrestlers were divided into two groups according to POsm levels as weight loss and non-weight loss group. There were differences in the pre and post-test POsm levels of weight loss group. Similarly; it was identified that there were also statistically significant differences in terms of ALT, LDH and CK levels of weight loss group between pre and post-test. It was seen that POsm and levels of all indicators of skeletal muscle damage were higher than non-weight loss group. However, it was found that there were not any differences in terms of C-RP levels.


Steric control in the π-dimerization of oligothiophene radical cations annelated with bicyclo[2.2.2]octene units.
A Two series of oligothiophenes 2(nT) (n=4,5), annelated with bicyclo[2.2.2]octene (BCO) units at both ends, and quaterthiophenes 3 a-c, annelated with various numbers of BCO units at different positions, were newly synthesized to investigate the driving forces of π-dimerization and the structure-property relationships of the π-dimers of oligothiophene radical cations. Their radical-cation salts were prepared through chemical one-electron oxidation by using nitrosonium hexafluoroantimonate. From variable-temperature electron spin resonance and electronic absorption measurements, the π-dimerization capability was found to vary among the members of the 2(nT)(+)(·)SbF6(-) series and 3(+)(·)SbF6(-) series of compounds. To examine these results, density functional theory (DFT) calculations at the M06-2X/6-31G(d) level were conducted for the π-dimers. This level of theory was found to successfully reproduce the previously reported X-ray structure of (2(3T))2(2+) having a bent π-dimer structure with cis-cis conformations. The absorption bands obtained by time-dependent DFT calculations for the π-dimers were in reasonable agreement with the experimental spectra. The attractive and repulsive forces for the π-dimerization were divided into four factors: 1) SOMO-SOMO interactions, 2) van der Waals forces, 3) solvation, and 4) Coulomb repulsion, and the effects of each factor on the structural differences and chain-length dependence are discussed in detail.


Organization of the brain stem neural mechanisms for generation of respiratory rhythm--current problems.
The brain stem neural mechanism for central regulation of breathing is regarded as a complex neuronal mechanism consisting of several functional subsystems subserving different functions. One of its functions is the generation of the respiratory rhythm. Evidence indicates with certainty that the subsystem for respiratory rhythm-generating mechanisms is located in the medullary structure outside the DRG and VRG regions which have been postulated for many years as the hypothetical site generating respiratory rhythm. DRG and VRG are thought to be premotor neuron pools. Rhythmic activity originating in the medulla is dominant in terms of the spontaneity over other rhythmic activity in the pontine mechanisms as well as those in the spinal cord. Evidences for heterogeneity of functional properties of respiratory neurons in the brain stem are demonstrated. Possible functional differentiation among respiratory neurons is suggested. Neuronal mechanisms involving respiratory neurons identified as members of primary respiratory neuron populations or neuronal networks consisting of various types of respiratory neurons located in the lateral region of the bulbar reticular formation may play important roles in generation of respiratory rhythms. Precise neural processes within the neuronal mechanisms for respiratory rhythm generation are rather equivocal and remain to be determined by further investigation.


Assessing the Effectiveness of Fermented Banana Peel Extracts for the Biosorption and Removal of Cadmium to Mitigate Inflammation and Oxidative Stress.
This study identified 11 lactic acid bacteria (LAB) strains that exhibited tolerance to heavy metal cadmium concentrations above 50 ppm for 48 h. Among these strains, T126-1 and T40-1 displayed the highest tolerance, enduring cadmium concentrations up to 500 ppm while still inhibiting bacterial growth by 50%. Moreover, the fermentation of banana peel using LAB significantly enhanced the clearance rate of cadmium (p < 0.05) compared to nonfermented banana peel. Additionally, the LAB-fermented banana peel exhibited higher 1,1-diphenyl-2-picryl-hydrazyl (DPPH) and reduced power values. Strain T40-1 exhibited a significant improvement in its ability to chelate ferrous ions (p < 0.05). Regarding antibiotic resistance, both the T40-1 and TH3 strains demonstrated high resistance with a third-level inhibition rate against ampicillin and tetracycline. Cell viability tests revealed that incubation with the T40-1 and TH3 strains for a duration of 24 h did not result in any cellular damage. Moreover, these LAB strains effectively mitigated oxidative stress markers, such as reactive oxygen species (ROS), glutathione (GSH), and lactate dehydrogenase (LDH), caused by 2 ppm cadmium on cells. Furthermore, the LAB strains were able to reduce the inflammatory response, as evidenced by a decrease in interleukin-8 (IL-8) levels (p < 0.05). The use of Fourier transform infrared (FT-IR) spectroscopy analysis provided valuable insight into the interaction between metal ions and the organic functional groups present on the cell wall of fermented banana peel. In summary, this study highlights the potential of the LAB strains T40-1 and TH3 in terms of their tolerance to the cadmium, ability to enhance cadmium clearance rates, and their beneficial effects on oxidative stress, inflammation, and cell viability.


Hepatic lesions associated with iron accumulation in captive kori bustards (Ardeotis kori).
There are anecdotal reports of iron storage disease in captive kori bustards (Ardeotis kori), but detailed descriptions of this disease have not been reported. The goals of this retrospective, multi-institutional study were to (1) describe microscopic findings associated with iron accumulation in postmortem tissues of kori bustards and (2) use an adapted grading scale to score iron accumulation and associated hepatic lesions. Tissue sections from 19 adult captive kori bustards (age range 3-28 years; 12 males and 7 females) were evaluated histologically with hematoxylin and eosin, Masson's trichrome, and Prussian blue stains, and scored for iron accumulation. Hemochromatosis was diagnosed in cases with iron storage (in hepatocytes and/or Kupffer cells) and concurrent parenchymal damage (defined as having both necrosis and fibrosis). Hemosiderosis was diagnosed in animals with evidence of iron storage without necrosis or fibrosis. Ten of the 19 cases (age range 8-27 years; 7 males and 3 females) were diagnosed with hemochromatosis, including 6 with mild disease, 3 with moderate disease, and 1 with severe disease. Histologic evidence of iron accumulation was also identified in kidney, intestinal tract, adrenal gland, and spleen, but there were no associations between severity of iron accumulation in the liver and accumulation in other organs.


Valproate, lamotrigine, and insulin-mediated risks in women with epilepsy.
We recently reported the frequent occurrence of polycystic ovaries and hyperandrogenism associated with weight gain and hyperinsulinemia in women taking valproate for epilepsy. The purpose of this study was to evaluate the risks related to valproate-induced hyperinsulinemia and their reversibility after discontinuing the medication. Sixteen women with valproate-related polycystic ovaries or hyperandrogenism participated in the study. Vaginal ultrasonography was performed, and endocrine and lipid parameters were measured. Thereafter, lamotrigine was substituted for valproate and the patients were observed for 12 months. Twenty-four healthy age-matched women served as control subjects. Twelve women completed the 12-month follow-up. While still on valproate they had centripetal obesity with associated hyperinsulinemia and unfavorable serum lipid profiles. The body-mass index and fasting serum insulin and testosterone concentrations decreased during the first year after replacing valproate with lamotrigine whereas the HDL-cholesterol/total cholesterol ratios increased from 0.17 +/- 0.06 to 0.26 +/- 0.05. The total number of polycystic ovaries in these women decreased from 20 during valproate medication to 11 one year after replacing valproate with lamotrigine. Valproate induces a metabolic syndrome with centripetal obesity, hyperinsulinemia, lipid abnormalities, and polycystic ovaries/hyperandrogenism in women with epilepsy. These valproate-related risks can be reduced by substituting lamotrigine for valproate.


COMET: Cross-space Optimization-based Mutual learning network for super-resolution of CEST-MRI.
Chemical Exchange Saturation Transfer Magn-etic Resonance Imaging (CEST-MRI) is a promising approach for detecting tissue metabolic changes. However, due to the constraints of scan time and contrast-noise-ratio, CEST-MRI always exhibits low spatial resolution, hindering the clinical applications especially for detection of small lesions. Many super-resolution (SR) methods have shown good performance in medical images. However, when applied to CEST-MRI, these methods have two shortcomings that may limit their performance. Firstly, CEST-MRI has an additional frequency dimension, but the information along this dimension is not fully utilized. The second is that these SR methods mainly focus on improving the quality of the CEST-weighted images, while the accuracy of the quantitative maps is the most concerned aspect for CEST-MRI. To address these shortcomings, we propose a Cross-space Optimization-based Mutual learning nETwork (COMET) for SR of CEST-MRI. COMET incorporates novel spatio-frequency extraction modules and a mutual learning module to leverage and combine information from both spatial and frequency spaces, thereby enhancing the SR performance. Furthermore, we propose a novel CEST-based normalization loss to address the normalization-induced distribution problem and preserve the sharpness of quantitative maps, enabling more accurate CEST-MRI quantification. COMET is evaluated on an ischemia rat brain dataset and a human brain dataset. The results demonstrate COMET achieves 8-fold SR, providing accurate quantitative maps. Moreover, COMET outperforms all other state-of-the-art SR methods. Additionally, COMET exhibits its potential in prospective study.


Ascorbate deficiency influences the leaf cell wall glycoproteome in Arabidopsis thaliana.
The cell wall forms the first line of interaction between the plant and the external environment. Based on the observation that ascorbate-deficient vtc mutants of Arabidopsis thaliana have increased cell wall peroxidase activity, the cell wall glycoproteome of vtc2-2 was investigated. Glycoproteins were purified from fully expanded leaves by Concanavalin A affinity chromatography and analysed by liquid chromatography quadrupole time-of-flight mass spectrometry. This procedure identified 63 proteins with predicted glycosylation sites and cell wall localization. Of these, 11 proteins were differentially expressed between vtc2-2 and wild type. In particular, PRX33/34 were identified as contributing to increased peroxidase activity in response to ascorbate deficiency. This is the same peroxidase previously shown to contribute to hydrogen peroxide generation and pathogen resistance. Three fasciclin-like arabinogalactan proteins (FLA1, 2 and 8) had lower abundance in vtc2-2. Inspection of published microarray data shows that these also have lower gene expression in vtc1 and vtc2-1 and are decreased in expression by pathogen challenge and oxidative stresses. Ascorbate deficiency therefore impacts expression of cell wall proteins involved in pathogen responses and these presumably contribute to the increased resistance of vtc mutants to biotrophic pathogens.


Production of L2 lipase by Bacillus sp. strain L2: nutritional and physical factors.
A thermophilic bacterium, Bacillus sp. strain L2 was isolated from a hot spring in Perak, Malaysia. An extracellular lipase activity was detected through plate and broth assays at 70 degrees C after 28 h of incubation. The L2 lipase production was growth dependent as revealed by a number of factors affecting the secretion of extracelullar lipase. As for nutritional factors, casamino acids, trehalose, Ca(2+) and Tween 60 were found to be more effective for lipase production. The optimum physical condition for L2 lipase production was obtained at 70 degrees C after 28 h of cultivation time, at pH 7.0, 150 rpm of agitation rate and 1% of starting inoculum size. The activity staining of crude L2 lipase revealed a clearing zone at 39 kDa.


MiR-182-5p Knockdown Targeting PTEN Inhibits Cell Proliferation and Invasion of Breast Cancer Cells.
Breast cancer (BC) is one of the most common malignant tumors, affecting a significant number of women worldwide. MicroRNAs (miRNAs) have been reported to play important roles in tumorigenesis. The aim of this study was to determine the roles of miR-182-5p in BC progression. The expressions of miR-182-5p and phosphatase and tensin homolog deleted on chromosome 10 (PTEN) were measured in BC tissues and cells by quantitative real-time polymerase chain reaction or Western blot. Cell proliferation and invasion were detected by cell counting kit-8 assay and trans-well assay, respectively. The interaction between miR-182-5p and PTEN was probed by bioinformatics analysis, luciferase activity, and RNA immunoprecipitation. A murine xenograft model was established to investigate the role of miR-182-5p in BC progression in vivo. An abundance of miR-182-5p was noted in BC tissues and cells. High expression of miR-182-5p was associated with poor survival. Abrogation of miR-182-5p inhibited cell proliferation and invasion in BC cells. Interestingly, PTEN was indicated as a target of miR-182-5p, and its restoration reversed miR-182-5p-mediated promotion of proliferation and invasion of BC cells. Moreover, depletion of miR-182-5p suppressed tumor growth via up-regulating PTEN expression in the murine xenograft model. MiR-182-5p exhaustion blocked cell proliferation and invasion by regulating PTEN expression, providing a novel therapeutic avenue for treatment of BC.


Glial coverage of the small cell somata in the rat nucleus of tractus solitarius during postnatal development.
Astrocytes are thought to be active participants in synaptic plasticity in the developing nervous system. Previous studies suggested that axosomatic synapses decreased in number on the small cells of the rat caudal nucleus of tractus solitarius (cNTS) toward the end of the first postnatal week. Astrocytes might be involved in this phenomenon. We examined the morphological development of astrocytic processes around the small cell soma in the rat cNTS using light and electron microscopy. Glial fibrillary acidic protein (GFAP), glutamate-aspartate transporter (GLAST), and glutamate transporter-1 (GLT-1)-positive structures within the cNTS became more intensely stained as development proceeded. GLAST-positive structures encompassed calbindin-positive small cell somata after postnatal day 10. Electron microscopic observations indicated that astrocytic processes encompass the small cell soma, while the number of axosomatic synapses decreases as development proceeds. The timing for glial coverage of the small cell soma appears to be consistent with the decrease in axosomatic synapses on the small cells. These observations imply that astrocytes may participate actively in regulating the decrease of axosomatic synapses on small cells in the cNTS during postnatal development.


Chronic atrial fibrillation alters the functional properties of If in the human atrium.
Despite the evidence that the hyperpolarization-activated current (If) is highly modulated in human cardiomyopathies, no definite data exist in chronic atrial fibrillation (cAF). We investigated the expression, function, and modulation of If in human cAF. Right atrial samples were obtained from sinus rhythm (SR, n = 49) or cAF (duration >1 year, n = 31) patients undergoing corrective cardiac surgery. Among f-channel isoforms expressed in the human atrium (HCN1, 2 and 4), HCN4 mRNA levels measured by RT-PCR were significantly reduced. However, protein expression was preserved in cAF compared to SR (+85% for HCN4); concurrently, miR-1 expression was significantly reduced. In patch-clamped atrial myocytes, current-specific conductance (gf) was significantly increased in cAF at voltages around the threshold for If activation (-60 to -80 mV); accordingly, a 10-mV rightward shift of the activation curve occurred (P < 0.01). β-Adrenergic and 5-HT4 receptor stimulation exerted similar effects on If in cAF and SR cells, while the ANP-mediated effect was significantly reduced (P < 0.02), suggesting downregulation of natriuretic peptide signaling. In human cAF modifications in transcriptional and posttranscriptional mechanisms of HCN channels occur, associated with a slight yet significant gain-of-function of If , which may contribute to enhanced atrial ectopy.


Future practice profiles of Canadian medical trainees.
To investigate the future practice profiles of Canadian medical trainees. Data were extracted from the 2004 National Physician Survey, a questionnaire distributed to medical students, residents and physicians across Canada. Data were categorized by level of training and chi-square comparative analyses were done. The majority of trainees (about 64%) expressed plans to practice in the location in which they were training, with approximately 12% planning on practicing in another country. Family medicine (FM) residents were more likely to express wishes to practice in their location of training when compared to medical students and specialty residents. The location of training directly affects the future practice plans of Canadian medical trainees. Retaining specialist physicians may represent a challenge in the future.


Two-color interferometer for study of dense low-ionized plasma on the target in high-power pulse linear accelerator.
A two-color infrared interferometer has been developed for the investigation of high-density weakly ionized tantalum plasma in x-ray complexes based on linear induction accelerators (1.6 kA electron beam current, 4.6 MeV energy, and 100 ns pulse duration). Simultaneous probing at two different wavelengths makes it possible to independently measure the density of neutral and electron components. The interferometer uses wavelength values of 1.064 µm (Nd:YAG laser) and 10.6 µm (CO2 laser). To attenuate the effect of sample beam refraction in inhomogeneous plasma, the interferometer used a refraction suppression scheme composed of spherical mirrors focusing the object beam into the region occupied by the plasma. In addition, the power of the sample beam transmitted through the plasma was controlled in order to analyze whether there was a distortion of the interference pattern because of strong sample beam refraction and absorption in the plasma cloud. To calibrate the initial phase shift of the probe radiation, a movable mirror mounted on a piezoelectric element and oscillating according to a harmonic law with amplitude greater than the laser wavelengths was used. In initial experiments, the parameters of target plasma registered by this interferometer are as follows: the linear density of neutrals reached 1.5 · 1017 cm-2, and the degree of ionization was of the order of 10-2. The target plasma expansion velocity is determined as ∼6 km/s.


Association of IL-6 C-174G (rs 1800795) single nucleotide polymorphism with type 2 diabetes mellitus in Pakistani population.
To determine the association of interleukin-6 C-174G single nucleotide polymorphism with type 2 diabetes mellitus and metabolic parameters. This case-control study was conducted from June 2012 to December 2013 at the Military Hospital Rawalpindi, the Centre for Research in Experimental and Applied Medicine, Army Medical College, Rawalpindi, and the Institute of Biomedical and Genetic Engineering, Islamabad, Pakistan. Two cohorts of subjects were genotyped for the single nucleotide polymorphism. One cohort comprised type 2 diabetics and other included healthy subjects. In these groups, serum interleukin-6, serum insulin, blood sugar fasting, lipid profile, body mass index and insulin resistance was determined and correlated with genotypes. Of the 789 participants, 539(68.3%) were in the study group and 250(31.7%) in the control group. Serum interleukin-6 was significantly higher in diabetics than healthy controls (p<0.0001). The frequency of GG, GC and CC was 267(49.5%), 235(43.6%) and 37(6.9%) in diabetic patients and 128(51.2%), 74(29.6%) and 48(19.2%) in healthy controls, respectively. Interleukin-6 C-174G single nucleotide polymorphism was significantly associated with diabetes [odds ratio = 3.22 (95% confidence interval: 2.04-5.1; p<0.0001). Genotypes were within Hardy-Weinberg equilibrium. Interleukin-6 C-174G single nucleotide polymorphism was significantly associated with serum interleukin-6 in the order of GC>GG>CC but was not associated with body mass index, insulin resistance, serum insulin and dyslipidaemia in diabetic patients (p>0.05 each). Interleukin-6 C-174G single nucleotide polymorphism was a risk factor in type 2 diabetes and contributed to higher serum interleukin-6 levels among the participants.


Crystal structure of the complex between calyculin A and the catalytic subunit of protein phosphatase 1.
The crystal structure of the catalytic subunit of the protein phosphatase 1 (PP1), PP1 gamma, in complex with a marine toxin, calyculin A, was determined at 2.0 A resolution. The metal binding site contains the phosphate group of calyculin A and forms a tight network via the hydrophilic interactions between PP1 and calyculin A. Calyculin A is located in two of the three grooves, namely, in the hydrophobic groove and the acidic groove on the molecular surface. This is the first observation to note that the inhibitor adopts not a pseudocyclic conformation but an extended conformation in order to form a complex with the protein. The amino acid terminus of calyculin A contributes, in a limited manner, to the binding to PP1 gamma, which is consistent with findings from the studies of dose-inhibition analysis.


Fibroepithelial ureteral polyps and urolithiasis.
Fibroepithelial polyps are the most common benign tumor of the ureter. Most of the literature regarding their cause ascribes it to chronic infection. These publications, however, show that the majority of such cases never were associated with a documented urinary tract infection. Fibroepithelial polyps appear with equal frequency in male and female subjects and are found in all age groups including children, in contrast to what would have been expected with an infectious cause. Four histologically confirmed cases of fibroepithelial polyps were associated with chronic inflammation of the upper urinary tract related to the presence of calculi and/or Double J ureteral stents. All patients were managed successfully by endoscopic means, preserving renal function. Fibroepithelial ureteral polyps may be associated with urolithiasis, which serves as a source of chronic inflammation. A review of the literature is presented and supports these observations.


Propranolol can inhibit the development of hypertension in SHR.
The ability of propranolol, a beta-adrenergic blocking agent, to decrease blood pressure and inhibit the development of hypertension was assessed in spontaneously hypertensive rats (SHR). Oral propranolol was administered via drinking water to SHR and age matched normotensive control (WKY) groups beginning at conception, birth, three, six, or nine weeks of age. Controls for all groups were given tap water. Propranolol treatment was withdrawn from all groups at twelve weeks of age. A comparison of developmental parameters such as water consumption, weight gain and survival showed no differences between SHR and WKY or between SHR with propranolol vs WKY with propranolol. Systolic blood pressures and heart rates were monitored non-invasively from seven to sixteen weeks of age. There was a variable reduction in SHR blood pressures during propranolol treatments starting at 6 weeks of age or earlier, but when propranolol treatment was withdrawn, SHR blood pressures increased as did SHR without propranolol treatment. In SHR offspring who were exposed to propranolol through fetal and neonatal development and whose sires and dams were pretreated with propranolol, the development of high blood pressure was inhibited. Blood pressures indicated that this group did not develop hypertension for up to four weeks after propranolol was withdrawn even though heart rate returned to normal. Based upon these findings, a critical period during SHR development was defined during which development of hypertension can be inhibited by propranolol.


The dawn of algometry: Paolo Mantegazza's research on pain.
By the 1860s, Paolo Mantegazza was a professor of general pathology at the University of Pavia, where he had graduated in medicine in 1854. There, he founded Italy's first laboratory of experimental pathology and did his first research on pain, the subject of various communications presented to the Istituto Lombardo in Milan. In 1880, Mantegazza published Physiology of Pain, one of the several "physiologies" (of pleasure, of love, of hatred, of woman) that he wrote during his career. In this book, a testament to his scientific versatility, experimental observations supplemented his insights into hygienism and anthropology. This research on pain also led to a dispute between Mantegazza and Cesare Lombroso, which was the start of the two scientists' estrangement.


Mechanical testing of hydrogels in cartilage tissue engineering: beyond the compressive modulus.
Injuries to articular cartilage result in significant pain to patients and high medical costs. Unfortunately, cartilage repair strategies have been notoriously unreliable and/or complex. Biomaterial-based tissue-engineering strategies offer great promise, including the use of hydrogels to regenerate articular cartilage. Mechanical integrity is arguably the most important functional outcome of engineered cartilage, although mechanical testing of hydrogel-based constructs to date has focused primarily on deformation rather than failure properties. In addition to deformation testing, as the field of cartilage tissue engineering matures, this community will benefit from the addition of mechanical failure testing to outcome analyses, given the crucial clinical importance of the success of engineered constructs. However, there is a tremendous disparity in the methods used to evaluate mechanical failure of hydrogels and articular cartilage. In an effort to bridge the gap in mechanical testing methods of articular cartilage and hydrogels in cartilage regeneration, this review classifies the different toughness measurements for each. The urgency for identifying the common ground between these two disparate fields is high, as mechanical failure is ready to stand alongside stiffness as a functional design requirement. In comparing toughness measurement methods between hydrogels and cartilage, we recommend that the best option for evaluating mechanical failure of hydrogel-based constructs for cartilage tissue engineering may be tensile testing based on the single edge notch test, in part because specimen preparation is more straightforward and a related American Society for Testing and Materials (ASTM) standard can be adopted in a fracture mechanics context.


Revisiting the effects of omitting aspirin in combined antithrombotic therapies for atrial fibrillation and acute coronary syndromes or percutaneous coronary interventions: meta-analysis of pooled data from the PIONEER AF-PCI, RE-DUAL PCI, and AUGUSTUS trials.
Recently, three randomized trials reported that dual antithrombotic treatments (DATs) including non-vitamin K antagonist oral anticoagulants (NOACs) and a P2Y12 inhibitor without aspirin were associated with significantly less bleeding than vitamin K antagonist (VKA)-based triple antithrombotic therapy (TAT) in atrial fibrillation (AF) patients with acute coronary syndrome (ACS) or undergoing percutaneous coronary intervention (PCI). We conducted an analysis of pooled data from these trials. A meta-analysis of the PIONEER AF-PCI, RE-DUAL PCI, and AUGUSTUS trials considering major bleeding [International Society on Thrombosis and Haemostasis (ISTH) and Thrombolysis in Myocardial Infarction], clinically relevant non-major bleeding, all-cause/cardiovascular death, stroke, myocardial infarction (MI), and stent thrombosis. Treatment effect is reported as odds ratio (OR) and 95% confidence interval. Among 9463 patients (53% with ACS), DAT regimens were associated with significantly less bleeding than TAT (OR 0.598, 0.491 -0.727; P < 0.001 for ISTH major bleeding), as were NOAC-based vs. VKA-based regimens (OR 0.577, 0.477 -0.698; P < 0.001). Stroke and mortality rates were similar, but there was statistically non-significant trend towards greater risk of MI (OR 1.211, 0.955 -1.535; P = 0.115) and significantly higher risk for stent thrombosis (OR 1.672, 1.022 -2.733, P = 0.041) with DAT vs. TAT (but not NOAC- vs. VKA-based regimens). This was mainly driven by Dabigatran 110 mg; the trends were lower with full-dose NOAC or Rivaroxaban 15 mg-based DATs. Our findings support the use of full-dose NOAC (Apixaban 5 mg, Dabigatran 150 mg) or Rivaroxaban 15 mg-based treatments in most AF patients with ACS or undergoing PCI. Notwithstanding the better safety of DAT, an initial course of NOAC-based TAT may be desirable in most AF patients.


Dermatology on YouTube - an update and analysis of new trends.
Because YouTube is one of the most popular search engines, it is an instrumental tool to stay up to date on the most relevant dermatology trends and content in order to better direct patients and improve health outcomes. Twelve select terms (i.e. Dermatology, Sun protection, Skin cancer awareness, Skin cancer, Skin condition, Sun safety, Tanning, Melanoma, Basal cell carcinoma, Squamous cell carcinoma, Skin cancer treatment, Skin cancer prevention) were searched on YouTube. Overall, the results included 240 videos with over 160 million views. Educational content was most prevalent at 35% of the total search results. Of the total videos, 42% were uploaded by or featured a medical health professional (MD, DO, PhD, RN, ND), with 28% involving a board-certified dermatologist. Trends in content type have changed: educational and personal videos have increased, while advocacy and advertising have decreased. Most search terms are moving in a positive, informative direction, specifically the term "tanning." Other search terms such as "skin condition" and "skin cancer treatment" should be more closely monitored for misleading and perhaps harmful information. Therefore, dermatologists and other medical personnel should keep pace with relevant and popular dermatology content on YouTube in order to understand, advise, market, educate, and address patients' questions and concerns.


Intussusception in an Infant With SARS-CoV-2 Infection: A Case Report and a Review of the Literature.
Coronavirus disease 2019 (COVID-19) is caused by acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Even if predominantly considered a respiratory pathogen, it could be associated with gastrointestinal involvement, generally in mild forms. Recent reports highlight the association between SARS-CoV-2 and intussusception in infants. A case of intussusception is hereby described in a previously healthy infant in whom the diagnosis of SARS-CoV-2 was made after the analysis of bronchoalveolar lavage and intraoperative specimens following surgical procedures. Accordingly, a review of infant cases with intussusception and SARS-CoV-2 infection is also reported.


Photodynamic laser therapy. A bladder cancer protocol.
This data, along with data from other research studies, indicate that PDT is a promising new treatment for noninvasive bladder cancer. In the current study at Veterans Administration Medical Center, three of the four patients who received Thiotepa have had recurrences of their bladder tumors or positive urine cytology. The three patients who received PDT have not experienced any recurrences or positive urine cytology. Since we have been involved in this trial, we have developed some recommendations that other institutions may want to follow. The tip of the laser fiber is very bright. To decrease eye strain and fatigue, a lens cap with a green eye shield should be used on the cytoscope. All staff should wear green-colored safety eye glasses. This will protect their eyes from constant exposure to the intense incandescent radiation, and if the fiber should break, it would protect their eyes from the bright red color. With all the extra equipment such as ultrasound, power meters, light sources, and anesthesia equipment, it is important to avoid tripping over extension cords. The cords should be covered. Also, it is important not to bump into the equipment, which can happen because the OR is dark. At this time, the laser technician is the only person authorized at our medical center to operate the argon-pumped tunable dye laser. In the future, if more research programs are started or therapy is approved for other uses, additional personnel will be trained.


Prediction of alcohol use disorder using personality disorder traits: a twin study.
The DSM-IV personality disorders (PDs) are comorbid with alcohol use disorder (AUD) and with each other. It remains unclear which PD criteria are most likely to drive onset and recurrence of AUD and which are merely confounded with those criteria. We determine which individual PD criteria predict AUD and the degree of underlying genetic and/or environmental aetiology. A prospective observational twin study. Norway 1999-2011. A total of 2528 and 2275 Norwegian adult twins in waves 1 and 2 variable-selection analyses, and 2785 in biometric analyses. DSM-IV PDs and their 80 criteria were assessed using a structured personal interview, and AUD using the World Health Organization's Composite International Diagnostic Interview. In a variable-selection analysis, two PD criteria were associated with AUD even after taking all the other criteria into account: criterion 8 of antisocial PD (childhood conduct disorder) and criterion 4 of borderline PD (self-damaging impulsive behaviours). Adjusting for each other, their respective odds ratios were 3.4 [confidence interval (CI) = 2.1-5.4] and 5.0 (CI = 3.3-7.7). Endorsement strength of the criteria was associated with AUD in a dose-response manner and they explained 5.5% of variation in AUD risk-more than the full diagnoses of antisocial and borderline PDs together (0.5%). The association between borderline criterion 4 and AUD 10 years later derived mainly from their overlapping genetic factors, whereas the association between antisocial criterion 8 and AUD 10 years later was due to both genetic and non-genetic factors. Conduct disorder and self-harming impulsivity are the foremost risk traits for alcohol use disorder among the 80 personality disorder criteria of DSM-IV, predicting alcohol use disorder more effectively than personality disorder diagnoses. The twin-study analysis suggested that conduct disorder represents a joint genetic and developmental risk for alcohol use disorder and that impulsivity is a genetic risk.


Expression Profiles of Differentially Expressed Circular RNAs and circRNA-miRNA-mRNA Regulatory Networks in SH-SY5Y Cells Infected with Coxsackievirus B5.
Coxsackievirus B5 (CVB5) is the causative agent of hand, foot, and mouth disease (HFMD) that can cause neurological complications and fatalities. Circular RNA (circRNA) has been shown to play an important role in regulating pathogenic processes. However, the functions of circRNA in response to CVB5 infection remain unclear. In our research, RNA-seq was employed to analyze the expression profiles of circRNAs in SH-SY5Y cells with or without CVB5 infection. Out of 5,665 circRNAs identified to be expressed in SH-SY5Y cells, 163 circRNAs were found to be differentially expressed significantly. Moreover, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses showed that the differentially expressed circRNAs were mainly involved in ubiquitin-mediated proteolysis and signaling pathways during CVB5 infection. Additionally, RT-qPCR was used to validate the RNA-seq data, and a circRNA-miRNA-mRNA interaction network was constructed based on two circRNAs, such as hsa_circ_0008378 and novel_circ_0014617, which were associated with the regulation of innate immune response in host cells. Additionally, we confirmed the two circRANs up-regulated the key factors in the IFN-I signaling pathway, hampering viral replication. Our data provide a new perspective that facilitates further understanding of the virus-host mechanism.


Force microscopy imaging of individual protein molecules with sub-pico Newton force sensitivity.
The capability of atomic force microscopes (AFM) to generate atomic or nanoscale resolution images of surfaces has deeply transformed the study of materials. However, high resolution imaging of biological systems has proved more difficult than obtaining atomic resolution images of crystalline surfaces. In many cases, the forces exerted by the tip on the molecules (1-10 nN) either displace them laterally or break the noncovalent bonds that hold the biomolecules together. Here, we apply a force microscope concept based on the simultaneous excitation of the first two flexural modes of the cantilever. The coupling of the modes generated by the tip-molecule forces enables imaging under the application of forces ( approximately 35 pN) which are smaller than those needed to break noncovalent bonds. With this instrument we have resolved the intramolecular structure of antibodies in monomer and pentameric forms. Furthermore, the instrument has a force sensitivity of 0.2 pN which enables the identification of compositional changes along the protein fragments.


Chimeric agents derived from the functionalized amino acid, lacosamide, and the α-aminoamide, safinamide: evaluation of their inhibitory actions on voltage-gated sodium channels, and antiseizure and antinociception activities and comparison with lacosamide and safinamide.
The functionalized amino acid, lacosamide ((R)-2), and the α-aminoamide, safinamide ((S)-3), are neurological agents that have been extensively investigated and have displayed potent anticonvulsant activities in seizure models. Both compounds have been reported to modulate voltage-gated sodium channel activity. We have prepared a series of chimeric compounds, (R)-7-(R)-10, by merging key structural units in these two clinical agents, and then compared their activities with (R)-2 and (S)-3. Compounds were assessed for their ability to alter sodium channel kinetics for inactivation, frequency (use)-dependence, and steady-state activation and fast inactivation. We report that chimeric compounds (R)-7-(R)-10 in catecholamine A-differentiated (CAD) cells and embryonic rat cortical neurons robustly enhanced sodium channel inactivation at concentrations far lower than those required for (R)-2 and (S)-3, and that (R)-9 and (R)-10, unlike (R)-2 and (S)-3, produce sodium channel frequency (use)-dependence at low micromolar concentrations. We further show that (R)-7-(R)-10 displayed excellent anticonvulsant activities and pain-attenuating properties in the animal formalin model. Of these compounds, only (R)-7 reversed mechanical hypersensitivity in the tibial-nerve injury model for neuropathic pain in rats.


[The effect of hydrocortisone and insulin on ribonucleic acid synthesis in the nuclei and cytoplasm of sexually mature male rat liver cells].
Prolonged administration to male sexually-mature rats weighing 180-200 g of hydrocortisone, protamine-zinc-insulin enhanced considerably the synthesis of DNA-like RNA, precursor of ribosomal RNA in the nuclei and ribosomal RNA in the cytoplasm of the liver; this increase was even more pronounced after the administration of both hormones. The data obtained were in favour of the participation of DNA-like RNA, precursor of ribosomal RNA of the nuclei and ribosomal RNA of the cytoplasm of the liver of male sexually-mature rats in the synthesis of transaminases of their liver.


An uncommon dermatophyte infection: two cases of cutaneous infection with Trichophyton verrucosum.
Zoophilic dermatophytes can cause highly inflammatory cutaneous infections. Cattle represent the largest reservoir for the zoophilic dermatophyte Trichophyton verrucosum. Effective vaccination programmes have contributed to a low rate of livestock infection in central and northern Europe, and T. verrucosum infection is relatively more common in southern Europe and in Arabic countries. Transmission to humans typically results from direct contact with infected livestock. It may also be transmitted from person to person. We report two cases of T. verrucosum skin infections in Irish farmers. In both cases, effective treatment was delayed due to misdiagnosis of the condition as a bacterial infection in the primary care setting. Both cases responded rapidly to treatment with oral terbinafine. Culture of T. verrucosum can take 3 weeks or longer to grow, therefore a high index of clinical suspicion is necessary, and skin scrapings for potassium hydroxide microscopy and culture are essential for accurate diagnosis.


Pheomelanogenesis is promoted at a weakly acidic pH.
The diversity of pigmentation in the skin, hair, and eyes of humans has been largely attributed to the diversity of pH in melanosomes with an acidic pH being proposed to suppress melanin production, especially eumelanogenesis. We previously showed that an acidic pH greatly suppresses the late stage of eumelanogenesis after the dopachrome stage. The oxidation of tyrosine by tyrosinase in the presence of cysteine forms cysteinyldopa isomers, which are further oxidized to give rise to pheomelanin via benzothiazine intermediates. However, how those steps are controlled by pH has not been characterized. We therefore examined whether pheomelanin synthesis is chemically promoted at an acidic pH. We found that pheomelanin production either from dopa or tyrosine in the presence of cysteine by tyrosinase was greatest at pH values of 5.8-6.3, while eumelanin production was suppressed at pH 5.8. This suggests that mixed melanogenesis is chemically shifted to more pheomelanic states at a weakly acidic pH.


Perioperative Multimodal Analgesia for Adults Undergoing Surgery of the Spine-A Systematic Review and Meta-Analysis of Three or More Modalities.
Multimodal analgesia is a strategy that can be used to improve pain management in the perioperative period for patients undergoing surgery of the spine. However, no review evidence is available on the quantitative models of multimodal analgesia within this clinical setting. We conducted a systematic review and meta-analysis to examine the effects of maximal (≥3 analgesic agents) multimodal analgesic medication for patients undergoing surgery of the spine. We included randomized controlled trials that had evaluated the use of ≥3 multimodal analgesia components (maximal multimodal analgesia) in patients undergoing spinal surgery. We excluded patients who had received neuraxial or regional analgesia. The control group consisted of placebo, standard care (any therapeutic modality including ≤2 analgesic components). The primary outcomes were the postoperative pain scores at rest evaluated at 24 and 48 hours. We searched MEDLINE via OvidSP, EMBASE via OvidSP, and the Cochrane Library (Cochrane Database of Systematic Reviews and CENTRAL). We used the Cochrane standard methods. We identified consistently improved analgesic endpoints across all predetermined primary and secondary outcomes. A total of 11 eligible studies had evaluated the primary outcome of pain at rest at 24 hours. The patients who had received maximal multimodal analgesia were identified to have had lower pain scores with an average mean difference of -1.03 (P < 0.00001). The length of hospital stay was shorter for the patients who had received multimodal analgesia (mean difference, -0.55; P < 0.00001). Perioperative maximal multimodal analgesia consistently improved the visual analog scale scores for an adult population in the immediate postoperative period, with a moderate quality of evidence. We found a significant decrease in the hospital length of stay for patients who had received maximal multimodal analgesia with a high level of evidence and no statistical heterogeneity.


Validation of Bengali version of Edmonton Symptom Assessment Scale-Revised (ESAS-r Bengali): A multidimensional symptom assessment tool for patients with advanced incurable diseases receiving palliative care.
Routine symptom assessment represents the cornerstone of symptom management of patients with advanced incurable diseases in palliative care. At present, there is no validated tool to assess symptoms among the Bengali-speaking population with incurable diseases. The aim of the study is to translate, culturally adapt, and validate the Edmonton Symptom Assessment Scale (Revised) into Bengali language. The study was conducted in two phases. Forward and backward translations of the English version of the Edmonton Symptom Assessment Scale (Revised) into Bengali were conducted by four independent translators. After obtaining reviews from an expert committee, pre-testing and cognitive debriefing the Bengali version of the tool was finalized. The final validation was conducted among 110 patients admitted to the Palliative Medicine Department of Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh. Validity (content, face, and construct validity) and reliability (internal consistency) were assessed in the final validation phase. All participants responded to all items. Seventy percent of the participants completely understood all questions but 30% had difficulty with three questions. The expert committee expressed their satisfaction regarding the face and content validity of the questionnaire. The Bengali version also had high reliability (α = 0.862). Principal component analysis with the distribution of varimax rotation of Edmonton Symptom Assessment Scale (Revised) Bengali ranged from 0.41 to 0.83. After the translation and cross-cultural adaptation, the Bengali version of the Edmonton Symptom Assessment Scale (Revised) achieved good levels of validity and reliability. It can be used as a symptom assessment tool for Bengali speaking population receiving palliative care.


New trends in cometary chemistry.
This paper presents some of the implications of new comet observations for cometary chemistry: recent observations of bright comets, space missions, and especially the first results of the Deep Impact experiment. Topics which are discussed are the molecular complexity of cometary material, the evidence for molecular diversity from the infrared observations by Deep Impact, possible relations between cometary nuclei and carbonaceous chondrites, the sites of ices in cometary nuclei, the problem of interpretation of the spin temperatures observed in cometary molecules.


Handsewn vs. stapled anastomoses in colon and rectal surgery: a meta-analysis.
Trials comparing handsewn with stapled anastomoses in colon and rectal surgery have not found statistical differences. Despite this, authors have differed in their conclusions as to which technique is superior. To help determine whether differences in patient outcomes are present, a meta-analysis of all trials was performed. A meta-analysis of all randomized, controlled trials assessing handsewn and stapled colon and rectal anastomoses was done using a fixed-effects model. Outcome variables were mortality, technical problems, leak rates, wound infections, strictures, and cancer recurrence. Outcomes were assessed for all anastomoses involving the colon and for the subset of colorectal anastomoses. Thirteen distinct trials met the inclusion criteria. Intraoperative technical problems were more likely to occur with stapled than with handsewn anastomoses for all anastomoses (P < 0.0001) and for colorectal anastomoses (P < 0.001). Strictures were also more common following stapled anastomoses (P = 0.015 for all anastomoses; P = 0.028 for colorectal anastomoses). All other outcome measures, including mortality, clinical and radiologic leak rates, and local cancer recurrence rates showed no difference between groups. Although intraoperative technical problems and postoperative strictures were more common with stapled anastomoses, other outcome measures showed no difference between groups. Thus, both techniques are effective, and the choice may be based on personal preference.


Belt lipectomy: procedure and outcomes.
Belt lipectomy includes the traditional abdominoplasty or panniculectomy with excision extended laterally around the entire trunk. This technique yields a lateral thigh and buttock lift, and when combined with liposuction is used to improve contour of the thighs. The focus of this paper is to describe current surgery for body contouring of the entire trunk and our experience at University of Iowa Hospitals and Clinics (UIHC) with 32 belt lipectomies.


[The value of the excursion of diaphragm tested by ultrosonography to predict weaning from mechanical ventilation in ICU patients].
Objective: To evaluate the excursion of the diaphragm and analyze the value in predicting weaning from mechanical ventilation in intensive care unit patients. Methods: The patients with mechanical ventilation (>48 hours) in ICU at Hebei Forth Medical University Hospital from June 2014 to December were classified into a success group or a failure group according to the weaning outcome. T-piece spontaneous breathing (SBT), airway occlusion pressure at 0.1 sec (P(0.1)) and maximal inspiratory pressure (MIP), rapid shallow breathing index (RSBI) and P(0.1)/MIP were measured or calculated. During the period of the 1st hour SBT, the excursion of diaphragm was measured with ultrasonography. The predictive value of each parameter to weaning was evaluated with ROC curve. Results: A total of 98 patients were enrolled in this study, including 74 successfully weaning and 24 failed. There were significant differences between two groups(success group and failure group) in P(0.1)[(2.00±2.00)cmH(2)O (1 cmH(2)O=0.098 kPa) vs (3.00±2.75)cmH(2)O, P<0.05], RSBI (39.14±16.81 vs 52.00±19.18, P<0.05), left diaphragmatic excursion [(1.12±0.97)cm vs (0.69±1.00)cm, P<0.001], right diaphragmatic excursion(1.87±0.75)cm vs (1.17±0.76)cm, P<0.001] and mean value of left and right diaphragmatic excursion [(1.57±0.52)cm vs (0.83±0.53)cm, and P<0.001]. The ventilation time [2.00(2.00-4.00)d vs 4.00(2.00-5.00)d], ICU hospital lengths of stay [4.50(3.00-7.25)d vs 8.50(6.25-15.25)d] and total hospital lengths of stay[20.00(15.00-25.25)d vs 25.00(20.25-37.25)d] were also statistically significant in success group and failure group respectively (all P<0.05). The cutoff value of diaphragmatic excursion for predicting successful extubation was determined to be 1.14 cm by ROC curve analysis. The sensitivity of diaphragmatic excursion to predict successful weaning was 89.2% and the specificity was 75.0%, the AUC(ROC) was 0.849. Conclusion: As an early predictor of diaphragmatic dysfunction, diaphragmatic excursion is probably superior to the traditional parameters in predicting weaning from ventilator in ICU patients.


Risk Factors for Mortality in Asian Children Admitted to the Paediatric Intensive Care Unit after Haematopoietic Stem Cell Transplantation.
This study aimed to investigate the risk factors associated with mortality in haematopoietic stem cell transplant (HSCT) patients admitted to our paediatric intensive care unit (PICU) over an 8-year period. A retrospective chart review was conducted of all HSCT patients requiring PICU admission at our centre (a tertiary care university hospital in Singapore) from January 2002 to December 2010. Chief outcome measures were survival at the time of PICU discharge and survival at 6 months after initial PICU admission. Ninety-eight patients underwent HSCT during this period; 18 patients (18%) required 24 PICU admissions post-HSCT. The overall survival to PICU discharge was 62.5%. Of those who survived discharge from the PICU, 33% died within 6 months of discharge. Non-survivors to PICU discharge had a higher incidence of sepsis (89% vs 33%, P = 0.013) and organ failure as compared to survivors (cardiovascular failure 100% vs 20%, P = 0.0003; respiratory failure 89% vs 20%, P = 0.002; and renal failure 44% vs 7%, P = 0.047). Mortality rates were higher in patients requiring mechanical ventilation (70% vs 14%, P = 0.010) and inotropic support (70% vs 14%, P = 0.010). Mortality in all patients with renal failure requiring haemodialysis (n = 4) was 100%. Presence of 3 or more organ failures was associated with 80% mortality (P = 0.003). Sepsis, multiple organ failure and the need for mechanical ventilation, inotropes and especially haemodialysis were associated with increased risk of mortality in our cohort of HSCT patients.