[Enzyme labeling methods and it's specificities].
Enzyme labeled antigen for use in ELISA of Hapten (steroids, prostanoid, carbohydrate, nucleic acid, peptide, herbicide, insecticide and antibiotic) have usually been prepared by condensation of carboxy group of hapten with amino groups of lysine residue in enzyme. The horseradish peroxidase (HRP) is best suitable as labeling enzyme, therefore it is small molecular, and substrate turnover is much higher compared to the other enzymes. The mixed anhydride and carbodiimide methods have mainly been used the preparation of hapten conjugate BSA, but not satisfactory for enzyme labeling. The N-hydroxysuccinimide ester (NHS: active ester) method is satisfactory with respect to reproducibility and sensitivity. The sensitivity is related to the bridging phenomenon: One of the disadvantages of the homologous labels is that the antibody shows an affinity not only for the Hapten but also for the bridge which connects the Hapten to carrier protein. We have developed a sensitive bridge heterologous EIA for progesterone (P) using geometrical isomers of P-3 (E/Z) (O-carboxymethyl) oxime-N-hydroxysuccinimide esters [ef Ab of P-3 (E) CMO-BSA/P-3 (Z) CMO-HRP]3). The sensitivity of heterologous proved to be higher than a homologous EIA or a conventional RIA. It seem like that a 1:1 steroid-enzyme conjugate is suitable for obtaining a high sensitivity. The avidin-biotin (AB) system provides great versatility, since by conjugation with an appropriate label, the AB assay can be used with any chosen detector. Furthermore, IgG can be labels with biotin without significantly influencing their immunological activity.(ABSTRACT TRUNCATED AT 250 WORDS)


Prevalence of chronic post-thoracotomy pain in patients with traumatic multiple rib fractures in South Korea: a cross-sectional study.
Chronic post-thoracotomy pain is a debilitating condition after traumatic multiple rib fractures and surgery. We aimed to estimate the prevalence of chronic post-thoracotomy pain after traumatic multiple rib fractures in South Korea and explore factors associated with it. From October 2017 to June 2019, a cross-sectional survey of 100 adults, who had undergone thoracotomy due to traumatic fractures of two or more ribs 2 years to 3 months prior to the survey, was conducted in the regional trauma center in South Korea. In total, 80% and 65% patients reported any level and above moderate chronic pain, respectively. Quality of life was mostly below the normative value of the US general population. Forty-six percent patients had restrictive respiratory dysfunction, and 47% and 59% patients were classified as being at risk of above mild-level anxiety and depression, respectively. More than 70% of patients had a current opioid prescription. Multivariable logistic regression analysis showed weak evidence of association between acute, severe postoperative pain and chronic postsurgical pain (adjusted odds ratio 2.4, 95% confidence intervals 0.9 to 6.4). Collectively, chronic post-thoracotomy pain and associated incomplete recovery regarding respiratory, functional, and psychological outcomes were prevalent in patients with traumatic multiple rib fractures in South Korea.


Rest Redistribution Functions as a Free and Ad-Hoc Equivalent to Commonly used Velocity-Based Training Thresholds During Clean Pulls at Different Loads.
This study determined whether redistributing total rest time into shorter, but more frequent rest periods could maintain velocity and power output during 3 traditional sets of 6 clean pulls using 80% (TS80), 100% (TS100) and 120% (TS120) of power clean 1RM with 180 seconds of inter-set rest and during 3 "rest redistribution" protocols of 9 sets of 2 clean pulls using 80% (RR80), 100% (RR100) and 120% (RR120) of power clean 1RM with 45 seconds of inter-set rest. The total number of repetitions performed above 10 and 20% velocity loss thresholds, mean and peak velocity maintenance (the average of all 18 repetitions relative to the best repetition; MVM, PVM), and decline (the worst repetition relative to the best repetition; MVD, PVD) were calculated. For MVM, PVM, MVD, and PVD, there were small-to-moderate effect sizes in favour of RR80 and RR100, but large effects favouring RR120, compared to their respective TS protocols. The number of repetitions within a 20% velocity loss threshold was 17.7 ± 0.6 during RR and 16.5 ± 2.4 during TS (effect size 0.69); and the number of repetitions within a 10% velocity loss threshold was about 13.1 ± 3.7 during RR and 10.7 ± 3.6 during TS (effect size 0.66). Therefore, RR generally allowed for a better overall maintenance of velocity and power, especially at heavy loads. Coaches who wish to implement velocity-based training, but who do not wish to purchase or use the associated equipment, may consider rest-redistribution to encourage similar training stimuli.


[An adult patient of Reye's syndrome--the possible background mechanism of lesions in claustrum, striatum and limbic system and limbic dementia].
We reported a 35-year-old male patient with Reye's syndrome, who showed temporarily lesions of claustrum, striatum, hippocampus and amygdala on CT, MRI and PET scan. He was previously healthy and affected upper respiratory infection. After taking 4 tablets of aspirin (335 mg x 4), he developed severe headache and status epileptics. The cerebrospinal fluid showed normal cell count and protein. The serum GOT and GPT elevated to 499 IU/l and 221 IU/l respectively. The parainfluenza virus type I titer was 32 times on admission and increased up to 128 times two weeks later. In spite of the anticonvulsant, status epileptics lasted for about one month and he needed mechanical ventilation. On 13-18 days of illness, abnormal lesions appeared in bilateral claustrum and striatum on CT and MRI. On 49 days of illness, abnormal lesions appeared in bilateral hippocampus and amygdala. All these lesions changed into normal on MRI on 111 days of illness. The 18F-FDG PET study on 80 days of illness revealed high uptake on striatum, hippocampus and amygdala bilaterally and changed into normal on 130 days of illness. He has improved markedly but showed long-standing abnormal signs of limbic dementia. We suggested this patient could be suffered from post infectious encephalitis in limbic system after Reye's syndrome.


Biodiagnostics using oriented and aligned inorganic semiconductor nanotubes and nanowires.
The simplicity of synthesis of deterministically positioned inorganic semiconductor nanorods (NRs) and nanotubes (NTs) coupled with their chemical stability, high surface area, controllable optical properties and tunable surface functionality, have sparked worldwide research efforts towards biodiagnostic applications. Biosensors based on oriented and aligned one-dimensional (1-D) inorganic semiconductor nanostructures have demonstrated remarkable detection sensitivity, high throughput and label-free operability. In comparison to suspensions of nanoparticles and discrete randomly oriented nanowires, nanowire (NW) and nanotube arrays offer continuous charge transport pathways, a major advantage for all-electrical detection and in exploiting electrokinetic effects. We review highly sensitive biosensors based on oriented and aligned NTs/NRs/NWs employing conventional detection methods, inclusive of fluorescence, electrochemistry and electromechanical sensing as well as detection methods unique to nanowires such as field-effect transistors. Entirely new types of sensing applications such as the impaling of living cells to monitor cellular events in situ, and substrates with electrically controlled wetting for surface-assisted laser desorption and ionization are emerging to take advantage of the unique properties of nanowire arrays. Concurrently, we explain the semiconductor materials and architectures employed, and the functionalization procedures used to construct the biosensors. Aligned semiconductor array-based approaches are critically examined in relation to prevailing technologies to get a sense of the exclusive niches that nanotube/nanorod array biosensors inhabit. The versatility of the detection principles that nanowire/nanotube arrays are compatible with are enabling hybrid approaches where combinations of detection methods are used. Such advantages offset the complexity associated with changing the status quo with respect to the current state-of-the-art in biodiagnostic platforms and devices.


Implementation of Legionella Prevention Policy in Health Care Facilities: The United States Veterans Health Administration Experience.
The Veterans Health Administration requires implementation of Legionella prevention policy in potable water systems at Department of Veterans Affairs (VA) medical facilities across the United States and territories. The Veterans Health Administration Central Office program offices with expertise in engineering and clinical aspects of Legionella prevention policy have provided joint, structured on-site assistance to VA medical facilities for consultation on policy implementation. Site visits included review of facility documentation and data, discussions with staff, touring of buildings, and development of recommendations. Information obtained from on-site consultative assistance provided to VA medical facilities from December 2012 through January 2018 was reviewed to identify engineering and clinical challenges and lessons from implementation of Legionella prevention policy in VA health care buildings. Fifteen consultative site visits were conducted during this period regarding implementation of Legionella prevention and validation of effectiveness. It was found that implementation of Legionella prevention policy in potable water systems was complex and practices varied for each building. Common implementation challenges included capability of applying engineering controls, water stagnation, and assessment of health care association of Legionella cases. Process challenges included routine verification of actions, methods for assessing environmental validation data, and documentation of requirements. It was found that consistent and data-driven implementation of policy is crucial for an effective program. Guidance and standards documents in the community for Legionella prevention in building water systems are often general in nature, but implementation requires specific decisions and routine assessments and modifications to optimize outcomes. This real-world review of challenges and lessons from a large health care system with a detailed primary Legionella prevention policy informs future development of guidance and policy, both within and external to VA, and can provide insight to other health care facilities planning to implement practices for water safety.


A lipase with broad temperature range from an alkaliphilic gamma-proteobacterium isolated in Greenland.
A gamma-proteobacterium related to the genera Alteromonadales and Pseudomonadales, isolated from a cold and alkaline environment in Greenland, has been shown to produce a lipase active between 5 degrees C and 80 degrees C, with optimal activity at 55 degrees C and pH 8. PCR-based screening of genomic DNA from the isolated bacterium, followed by genome walking, resulted in two complete open reading frames, which were predicted to encode a lipase and its helper protein, a lipase foldase. The amino acid sequence derived for the lipase showed resemblance to lipases from Pseudomonas, Rhodoferax, Aeromonas and Vibrio. The two genes were cloned into different expression systems in E. coli with or without a putative secretion sequence, but despite the fact that both recombinant lipase and lipase foldase were observed on SDS-PAGE, no recombinant lipase activity was detected. Attempts to refold the recombinant lipase in vitro using a purified lipase foldase remained unsuccessful.


Role of protein phosphatase 2A in calcium-dependent chloride secretion by human colonic epithelial cells.
EGF inhibits carbachol-induced chloride secretion by regulating a basolateral potassium channel via phosphatidylinositol 3-kinase (PI 3-kinase) and PKCepsilon activation. Although both EGF and carbachol cause tyrosine phosphorylation of p85 of PI 3-kinase, only EGF activates the enzyme. Serine phosphorylation of p85 is thought to suppress the lipid kinase of PI 3-kinase. Our present study examined whether the differential effects of carbachol and EGF on PI 3-kinase activity correspond to varying phosphorylation of p85, and the mechanisms and consequences. T(84) colonic epithelial cells were treated with either EGF or carbachol. Cell lysates were immunoprecipitated with p85 antibody and blotted with either phosphotyrosine or phosphoserine antibodies. Protein phosphatase (PP) 1 and 2A activities were also measured. Both tyrosine and serine residues of p85 were phosphorylated by carbachol, whereas EGF induced only tyrosine phosphorylation. Moreover, EGF abolished carbachol-induced serine phosphorylation of p85 and activated PP2A without affecting PP1. Carbachol did not affect either phosphatase. Calyculin A or okadaic acid pretreatment reversed the inhibitory action of EGF on carbachol-induced chloride secretion and restored serine phosphorylation of p85. Although carbachol recruits p85, it phosphorylates both serine and tyrosine residues so that the lipid kinase of PI 3-kinase is inhibited. EGF results in p85 tyrosine phosphorylation as well as dephosphorylation of serine residues via the activation of PP2A. This explains the differential induction of PI 3-kinase enzyme activity in response to EGF and/or carbachol and has functional implications. Our data provide further insights into negative signals that regulate chloride secretion and into the molecular basis of signaling diversification in the intestinal epithelium.


[Influence of social support on the quality of life of family caregivers while caring for people with dependence].
The objective of this study was to evaluate the Quality of Life (QOL) of family caregivers of handicapped people attended at home by Family Health Teams and the relationship with their social support. Sixty-six family caregivers were interviewed using the WHOQOL-bref for a QOL evaluation and Zarit Burden Interview for the burden. The Social Relations domain of the WHOQOL-bref received the second best score within the domains of the instrument. During multiple linear regressions analysis, female caregivers, with low burden scores and who had received help from someone to perform the care, obtained the highest scores. Similarly, caregivers with partners had higher mean scores in the overall global assessment for QOL and health than those without partners. The results provide evidence of the influence of social support regarding Quality of Life and the burden perceived by family caregivers.


Factors influencing patient pathways for receipt of cancer care at an NCI-designated comprehensive cancer center.
Within the field of oncology, increasing access to high quality care has been identified as a priority to reduce cancer disparities. Previous research reveals that the facilities where patients receive their cancer care have implications for cancer outcomes. However, there is little understanding of how patients decide where to seek cancer care. This study examined the factors that shape patients' pathways to seek their cancer care at a National Cancer Institute-designated comprehensive cancer center (NCI-CCC), and differences in these factors by race, income and education. In-depth interviews and survey questionnaires were administered to a random sample of 124 patients at one NCI-CCC in the Northeast US. In-depth interview data was first analyzed qualitatively to identify themes and patterns in patients' pathways to receive their cancer care at an NCI-CCC. Logistic Regression was used to examine if these pathways varied by patient race, income, and education. Two themes emerged: following the recommendation of a physician and following advice from social network members. Quantitative data analysis shows that patient pathways to care at an NCI-CCC varied by education and income. Patients with lower income and education most commonly sought their cancer care at an NCI-CCC due to the recommendation of a physician. Patients with higher income and education most commonly cited referral by a specialist physician or the advice of a social network member. There were no statistically significant differences in pathways to care by race. Our findings show that most patients relied on physician recommendations or advice from a social network member in deciding to seek their cancer care at an NCI-CCC. Due to the role of physicians in shaping patients' pathways to the NCI-CCC, initiatives that strengthen partnerships between NCI-CCCs and community physicians who serve underserved communities may improve access to NCI-CCCs.


Expression of Dp71 in Müller glial cells: a comparison with utrophin- and dystrophin-associated proteins.
The abnormal retinal electrophysiology observed in patients with Duchenne muscular dystrophy (DMD) has been attributed to an altered expression of C-terminal products of the dystrophin gene. It has been shown that Dp260 is expressed by photoreceptor cells, whereas Dp71 is present in glial cells. The present study was intended to identify all known members of the dystrophin superfamily and their associated proteins expressed in Müller glial cells (MGC). The expression of the proteins and of their messengers was studied in MGC cultures from 2-week-old rats, by polymerase chain reaction amplification, Western blot analysis, and immunocytochemistry. An immunocytochemical localization of the proteins was also performed on enzymatically dissociated Müller cells from adult rat retinas. MGCs expressed a spliced isoform of Dp71 called Dp71f, as well as utrophin, beta-dystroglycan, delta and gamma-sarcoglycans, and alpha1-syntrophin. In morphologically preserved differentiated Müller cells, Dp71f was localized in clusters, utrophin was diffusely distributed in the cytoplasm, and dystrophin-associated proteins (DAPs) were membrane-bound. Most of these proteins were preferentially expressed in the vitread portion of the cells. Dp71f and utrophin expression was restricted to MGCs, whereas all DAPs were also present in other retinal cell types. The exclusive localization of Dp71f and utrophin in MGCs suggests that these proteins, together with DAPs, play a specific role in these cells. Further knowledge of possible interactions of these proteins within a functional complex may provide new insights into the molecular basis of the electroretinogram phenotype in DMD.


The Role of Fatty Acid Metabolites in Vaginal Health and Disease: Application to Candidiasis.
Although the vast majority of women encounters at least one vaginal infection during their life, the amount of microbiome-related research performed in this area lags behind compared to alternative niches such as the intestinal tract. As a result, effective means of diagnosis and treatment, especially of recurrent infections, are limited. The role of the metabolome in vaginal health is largely elusive. It has been shown that lactate produced by the numerous lactobacilli present promotes health by limiting the chance of infection. Short chain fatty acids (SCFA) have been mainly linked to dysbiosis, although the causality of this relationship is still under debate. In this review, we aim to bring together information on the role of the vaginal metabolome and microbiome in infections caused by Candida. Vulvovaginal candidiasis affects near to 70% of all women at least once in their life with a significant proportion of women suffering from the recurrent variant. We assess the role of fatty acid metabolites, mainly SCFA and lactate, in onset of infection and virulence of the fungal pathogen. In addition, we pinpoint where lack of research limits our understanding of the molecular processes involved and restricts the possibility of developing novel treatment strategies.


Synthesis of 4-methyl-1,2,3-thiadiazole derivatives via Ugi reaction and their biological activities.
The Ugi reaction is a green and rapid one-pot reaction for lead derivation. To develop novel candidate pesticides with diverse biological activities, two series of 4-methyl-1,2,3-thiadiazole derivatives containing active substructures of 3-chloro-4-methylphenyl or 3-fluoro-4-methylphenyl, respectively, were rationally designed and synthesized via Ugi reaction according to the principle of combinations of bioactive substructures. All of the structures of newly synthesized compounds were confirmed by proton nuclear magnetic resonance and high-resolution mass spectrometry. Biological activities of the target compounds including fungicide activity, antivirus activity in vitro and in vivo, and systemic acquired resistance were evaluated systematically. The results indicated that derivatives containing 3-(trifluoromethyl)phenyl and 2-methylphenyl possessed a potential wide spectrum of fungicidal activity. Derivatives containing 3-(trifluoromethyl)phenyl and 4-hydroxyphenyl possessed good potential direct antivirus activities against tobacco mosaic virus (TMV) in vitro, and the replacement of Cl atom by F atom improved their direct inhibition activities against TMV in vitro. Derivatives containing phenyl, 2-(trifluoromethyl)phenyl, 3-(trifluoromethyl)phenyl, 3-nitrophenyl, 4-nitrophenyl, 2-methylphenyl, and 4-hydroxyphenyl possessed good potential bioactivities in vivo including protection, inactivation, curative, and induction activities against TMV. These studies indicate that the newly synthesized 4-methyl-1,2,3-thiadiazole derivatives possessed good potential bioactivities, and a combination of bioactive substructures via Ugi reaction was an effective way to find bioactive compounds for novel pesticide development.


The hand-held computer as a teaching tool for acid-base interpretation.
This paper presents an acid-base interpretation drill written for the Sharp PC-1211 and the Radio Shack TRS-80 PC-1 computers. The computer generates random numbers for PCO2 and HCO3(-) and calculates pH, then interprets the values according to a normal values key and a 13-item interpretation key. Next, the computer asks for the user's interpretation of the values, evaluates the user's interpretation, and informs him whether his answer is correct or incorrect. If it is incorrect, the user has the option of trying again or directing the computer to display the correct answer. The user is then given a chance to interpret a new set of acid-base values. I have found that this method of instruction enhances students' enthusiasm for learning and relieves the instructor of the tedious aspects of teaching acid-base interpretation.


Purification and characterization of the acetyl-CoA synthetase from Mycobacterium tuberculosis.
Acetyl-CoA (AcCoA) synthetase (Acs) catalyzes the conversion of acetate into AcCoA, which is involved in many catabolic and anabolic pathways. Although this enzyme has been studied for many years in many organisms, the properties of Mycobacterium tuberculosis Acs and the regulation of its activity remain unknown. Here, the putative acs gene of M. tuberculosis H37Rv (Mt-Acs) was expressed as a fusion protein with 6×His-tag on the C-terminus in Escherichia coli. The recombinant Mt-Acs protein was successfully purified and then its enzymatic characteristics were analyzed. The optimal pH and temperature, and the kinetic parameters of Mt-Acs were determined. To investigate whether Mt-Acs is regulated by lysine acetylation as reported for Salmonella enterica Acs, its mutant K617R was also generated. Determination of the enzymatic activity suggests that Lys-617 is critical for its function. We further demonstrated that Mt-Acs underwent auto-acetylation with acetate but not with AcCoA as the acetyl donor, which resulted in the decrease of its activity. CoA, the substrate for AcCoA formation, inhibited the auto-acetylation. Furthermore, the silent information regulator (Sir2) of M. tuberculosis (Mt-Sir2) could catalyze Mt-Acs deacetylation, which resulted in activation of Acs. These results may provide more insights into the physiological roles of Mt-Acs in M. tuberculosis central metabolism.


Autoimmune encephalitis with coexistent LGI1 and GABABR1 antibodies: case report.
Autoimmune encephalitis (AE) with multiple auto-antibodies is of great clinical significance because its complex clinical manifestations and atypical imaging increase the difficulty of diagnosis, differential diagnosis and treatment, which may aggravate the disease, increase the recurrence rate and mortality. The coexistence of anti-Leucinie-rich Glioma Inactivated 1 (LGI1) and anti-γ-aminobutyric acid-beta-receptor 1 (GABABR1) has not been published before. We herein present the case of a 60-year-old man with slow response, behavioral changes, psychosis and sleep disorders. Laboratory test included serum hyponatremia, positive serum LGI1 and GABABR1 antibodies using transfected cell-based assays. Electroencephalogram exhibited moderate diffusion abnormality. The patient responded well to steroid impulse treatment and sodium supplement therapy, and did not recur during the follow-up. Here we report the first AE characterized by positive LGI1 and GABABR1 antibodies, as well as summarizing AE with multiple auto-antibodies reported so far, hopefully to provide experience for clinical practice.


Healthcare worker protection against epidemic viral respiratory disease.
Lower respiratory infections are often caused or precipitated by viruses and are a leading cause of global morbidity and mortality. Mutations in these viral genomes can produce highly infectious strains that transmit across species and have the potential to initiate epidemic, or pandemic, human viral respiratory disease. Transmission between humans primarily occurs via the airborne route and is accelerated by our increasingly interconnected and globalised society. To this date, there have been four major human viral respiratory outbreaks in the 21st century. Healthcare workers (HCWs) are at particular risk during respiratory epidemics or pandemics. This is due to crowded working environments where social distancing, or wearing respiratory personal protective equipment for prolonged periods, might prove difficult, or performing medical procedures that increase exposure to virus-laden aerosols, or bodily fluids. This review aims to summarise the evidence and approaches to occupational risk and protection of HCWs during epidemic or pandemic respiratory viral disease.


Avascular necrosis of the hip: comparison of contrast-enhanced and nonenhanced MR imaging with histologic correlation. Work in progress.
In 15 hips with typical signs of avascular necrosis of the femoral head on plain radiographs and magnetic resonance (MR) images, gadolinium-enhanced spin-echo and fat-suppressed MR images were obtained and compared with nonenhanced T1- and T2-weighted images. Both enhanced and nonenhanced areas were consistently detected in the abnormal femoral heads. Enhanced areas showed a low signal intensity (SI) on T1-weighted MR images obtained before contrast material was administered and an intermediate to high SI on T2-weighted images. Nonenhanced areas showed an SI either identical (pattern 1) or hypointense (pattern 2) to that of fat on both sequences. Histologic correlation (six resected femoral heads) helped confirm that enhanced and nonenhanced areas corresponded respectively to viable and necrotic tissue. In most cases, SI analysis of nonenhanced T1- and T2-weighted images allows the differentiation of hypervascularized viable tissue from hypovascularized necrotic tissue of the sequestrum.


Hyaluronidase Inhibitor-Incorporated Cross-Linked Hyaluronic Acid Hydrogels for Subcutaneous Injection.
Hyaluronidase (HAase) inhibitor-incorporated hyaluronic acid (HA) hydrogel cross-linked with 1,4-butanediol diglycidyl ether (BDDE) was designed to reduce the toxicity risk induced by BDDE and its biodegradation rate in subcutaneous tissue. The formulation composition of hydrogel and its preparation method were optimized to have a high swelling ratio and drug content. Quercetin (QCT) and quetiapine (QTP), as an HAase inhibitor and model drug, respectively, were incorporated into the cross-linked hydrogel using the antisolvent precipitation method for extending their release after subcutaneous injection. The cross-linked HA (cHA)-based hydrogels displayed appropriate viscoelasticity and injectability for subcutaneous injection. The incorporation of QCT (as an HAase inhibitor) in the cHA hydrogel formulation resulted in slower in vitro and in vivo degradation profiles compared to the hydrogel without QCT. Single dosing of optimized hydrogel injected via a subcutaneous route in rats did not induce any acute toxicities in the blood chemistry and histological staining studies. In the pharmacokinetic study of rats following subcutaneous injection, the cHA hydrogel with QCT exhibited a lower maximum QTP concentration and longer half-life and mean residence time values compared to the hydrogel without QCT. All of these results support the designed HAase inhibitor-incorporated cHA hydrogel being a biocompatible subcutaneous injection formulation for sustained drug delivery.


[Crusted scabies in HIV/AIDS infected patients. Report of 15 cases].
Crusted (Norwegian) scabies is a rare disease that occurs in patients with compromised immune system like patients with HIV/AIDS. We report 15 cases of crusted scabies in patients with HIV/AIDS successfully treated with oral ivermectin. The mean age of the patients was 43.7±8.06 and the diagnosis was made at a median of 5 months. All patients were diagnosed with HIV/AIDS treatment with antiretroviral therapy. Patients were treated with repeated doses of oral ivermectin with different schemes with good tolerance and efficacy with full resolution and without recurrence. Ivermectin is the treatment of choice for crusted scabies; it is tolerable and accessible to the patient. Immunosuppressed patients are those with the highest risk of acquiring that disease; we highlight the importance of lesion scraping to perform a correct and early diagnosis.


Origins and complexes: the initiation of DNA replication.
Eukaryotic DNA is organized for replication as multiple replicons. DNA synthesis in each replicon is initiated at an origin of replication. In both budding yeast, Saccharomyces cerevisiae and fission yeast, Schizosaccharomyces pombe, origins contain specific sequences that are essential for initiation, although these differ significantly between the two yeasts with those of S. pombe being more complex then those of S. cerevisiae. However, it is not yet clear whether the replication origins of plants contain specific essential sequences or whether origin sites are determined by features of chromatin structure. In all eukaryotes there are several biochemical events that must take place before initiation can occur. These are the marking of the origins by the origin recognition complex (ORC), the loading onto the origins, in a series of steps, of origin activation factors including the MCM proteins, and the initial denaturation of the double helix to form a replication "bubble". Only then can the enzymes that actually initiate replication, primase and DNA polymerase-alpha, gain access to the template. In many cells this complex series of events occurs only once per cell cycle, ensuring that DNA is not re-replicated within one cycle. However, regulated re-replication of DNA within one cell cycle (DNA endoreduplication) is relatively common in plants, indicating that the "once-per-cycle" controls can be overridden.


Impact of Euro-Canadian agrarian practices: in search of sustainable import-substitution strategies to enhance food security in subarctic Ontario, Canada.
In Canada, food insecurity exists among Aboriginal (Inuit, Metis and First Nations) people living in remote northern communities, in part, because of their reliance on the industrialized, import-based food system. Local food production as a substitute to imports would be an adaptive response, but enhancement of food security via food localization requires reflection on previous failings of conventional agricultural strategies so that informed decisions can be made. In light of potential reintroduction of local food production in remote First Nations communities, we investigated the cultural, social and ecological effects of a 20th century, Euro-Canadian agrarian settlement on the food system of a subarctic First Nation; this will act as the first step in developing a more sustainable local food program and enhancing food security in this community. To investigate the socio-cultural impacts of the Euro-Canadian agrarian initiative on the food system of Fort Albany First Nation, purposive, semi-directive interviews were conducted with elders and other knowledgeable community members. Interview data were placed into themes using inductive analyses. To determine the biophysical impact of the agrarian initiative, soil samples were taken from one site within the cultivated area and from one site in an undisturbed forest area. Soil properties associated with agricultural use and productivity were assessed. To compare the means of a given soil property between the sites, one-tailed t-tests were employed. Vegetative analysis was conducted in both sites to assess disturbance. According to the interviewees, prior to the agrarian initiative, First Nation families harvested wild game and fish, and gathered berries as well as other forms of vegetation for sustenance. With the introduction of the residential school and agrarian initiative, traditional food practices were deemed inadequate, families were forced to work and live in the settlement (becoming less reliant on traditional foods), and yet little knowledge sharing of agricultural practices occurred. When the residential school and agrarian movement came to an end in the 1970s, First Nation community members were left to become reliant on an import food system. The mission's agrarian techniques resulted in overall degradation of soil quality and ecological integrity: compared the natural boreal forest, the cultivated area had been colonized by invasive species and had significantly lower soil levels of nitrogen, magnesium and organic carbon, and significantly higher levels of phosphorus and bulk density. Because the agrarian initiative was not a viable long-term approach to food security in Fort Albany, the people became more reliant on imported goods. Taking into account climate change, there exists an opportunity whereby fruits and vegetables, historically stunted-in-growth or outside the distributional range of subarctic Canada, could now grow in the north. Together, agroecosystem stewardship practices and community-based, autonomous food security programs have the potential to increase locally grown food availability in a sustainable manner.


Real-time CMR guidance for intracardiac and great vessel pressure mapping in patients with congenital heart disease using an MR conditional guidewire-results of 25 patients.
The aim of this study was to test a CE-certified MR-conditional guidewire to facilitate blood pressure measurement in cardiovascular magnetic resonance (CMR) using fluid-filled catheters in patients with congenital heart disease (CHD). The main purpose was to determine procedural success in a post market clinical follow-up (PMCF) for routine procedure in a diagnostic and interventional workflow. Real-time CMR provides high quality imaging without the risk of exposing the patient to X-rays, especially for patients with irregular heart anatomy and patients who are susceptible to radiation and iodinated contrast media. To date, the assessment of blood pressure gradients is not a common feature of CMR, as these gradients cannot be accurately evaluated in routine CMR. Twenty-five CHD patients who were planned for combined clinical CMR and diagnostic and/or interventional catheterization were enrolled in the trial. Prior to inclusion, a specific procedure for catheterization in CMR was defined, encompassing the assessment of pressure and pressure gradients in the heart and great vessels. By the use of an MR-conditional guidewire we successfully measured specific pressure and pressure gradients in up to 92% of cases with liquid-filled catheters which were guided exclusively under CMR guidance. There were no guidewire-related adverse events, and guidewire guidance and manipulation of catheters were successful. Using a MR-conditional guidewire assists in easily reaching targets in the heart and great vessels and makes the catheter itself visible, so that invasive blood pressure assessment by CMR guidance with liquid-filled catheters can be improved. Cardiovascular magnetic resonance (CMR); congenital heart disease (CHD); cardiac catheterization; magnetic resonance; pressure; guidewire.


A critical concentration of N-terminal pyroglutamylated amyloid beta drives the misfolding of Ab1-42 into more toxic aggregates.
A wide consensus based on robust experimental evidence indicates pyroglutamylated amyloid-β isoform (AβpE3-42) as one of the most neurotoxic peptides involved in the onset of Alzheimer's disease. Furthermore, AβpE3-42 co-oligomerized with excess of Aβ1-42, produces oligomers and aggregates that are structurally distinct and far more cytotoxic than those made from Aβ1-42 alone. Here, we investigate quantitatively the influence of AβpE3-42 on biophysical properties and biological activity of Aβ1-42. We tested different ratios of AβpE3-42/Aβ1-42 mixtures finding a correlation between the biological activity and the structural conformation and morphology of the analyzed mixtures. We find that a mixture containing 5% AβpE3-42, induces the highest disruption of intracellular calcium homeostasis and the highest neuronal toxicity. These data correlate to an high content of relaxed antiparallel β-sheet structure and the coexistence of a population of big spheroidal aggregates together with short fibrils. Our experiments provide also evidence that AβpE3-42 causes template-induced misfolding of Aβ1-42 at ratios below 33%. This means that there exists a critical concentration required to have seeding on Aβ1-42 aggregation, above this threshold, the seed effect is not possible anymore and AβpE3-42 controls the total aggregation kinetics.


S1P/S1P2 Signaling Axis Regulates Both NLRP3 Upregulation and NLRP3 Inflammasome Activation in Macrophages Primed with Lipopolysaccharide.
The activation of NLRP3 inflammasome is a key factor for various inflammatory diseases. Here, we provide experimental evidence supporting the regulatory role of sphingosine-1-phosphate (S1P) in NLRP3 inflammasome activation in mouse bone-marrow-derived macrophages (BMDMs), along with the S1P receptor subtype involved and underlying regulatory mechanisms. During the priming stage, S1P induced NLRP3 upregulation in BMDMs only when primed with lipopolysaccharide (LPS). In this event, S1P2, but not S1P1, was involved based on the attenuated NLRP3 upregulation with JTE013 (S1P2 antagonist) or S1P2 knockdown. During the activation stage, S1P induced NLRP3 inflammasome activation in LPS-primed BMDMs via caspase-1 activation, interleukin 1β maturation, apoptosis-associated speck-like protein containing a CARD (ASC) speck formation, and IL-1β secretion. Such NLRP3 inflammasome activation was blocked by either pharmacological inhibition or genetic knockdown of S1P2. NF-κB, PI3K/Akt, and ERK1/2 were identified as effector pathways underlying S1P/S1P2 signaling in the regulation of NLRP3 upregulation in LPS-primed BMDMs. Further, reactive oxygen species (ROS) production was dependent on the S1P/S1P2 signaling axis in these cells, and the ROS generated regulate NLRP3 inflammasome activation, but not NLRP3 priming. Collectively, our findings suggest that S1P promotes NLRP3 upregulation and NLRP3 inflammasome activation in LPS-primed BMDMs via S1P2 and subsequent effector pathways.


The personal meaning of eating disorder symptoms: an interpretative phenomenological analysis.
The current study aimed to explore the personal meaning of eating difficulties. Eight women with a variety of eating issues were interviewed. These conversations were then analysed using Interpretative Phenomenological Analysis to construct a framework for understanding the personal world of the interviewees. Three overarching themes identified in participants' accounts of their experiences are reported here: the experience of the eating difficulties as functional; negative effects of having eating difficulties; ambivalence towards the eating difficulties. These themes add to our knowledge of the potential role of personal experiences in the aetiology and maintenance of eating difficulties.


Segmentation of Glottal Images from High-Speed Videoendoscopy Optimized by Synchronous Acoustic Recordings.
Laryngeal high-speed videoendoscopy (LHSV) is an imaging technique offering novel visualization quality of the vibratory activity of the vocal folds. However, in most image analysis methods, the interaction of the medical personnel and access to ground truth annotations are required to achieve accurate detection of vocal folds edges. In our fully automatic method, we combine video and acoustic data that are synchronously recorded during the laryngeal endoscopy. We show that the image segmentation algorithm of the glottal area can be optimized by matching the Fourier spectra of the pre-processed video and the spectra of the acoustic recording during the phonation of sustained vowel /i:/. We verify our method on a set of LHSV recordings taken from subjects with normophonic voice and patients with voice disorders due to glottal insufficiency. We show that the computed geometric indices of the glottal area make it possible to discriminate between normal and pathologic voices. The median of the Open Quotient and Minimal Relative Glottal Area values for healthy subjects were 0.69 and 0.06, respectively, while for dysphonic subjects were 1 and 0.35, respectively. We also validate these results using independent phoniatrician experts.


A matrix isolation study of 2-isopropylidenecyclopentane-1,3-diyl (Berson-type diradical).
The photodenitrogenation of diazene 5 in an argon matrix at 10 K permitted the first observation of an IR spectrum of 2-isopropylidenecyclopentane-1,3-diyl 2 (a Berson-type diradical). A comparison of the IR spectrum with a vibrational simulation at the B3LYP/6-31G(d) level of theory revealed that the diradical 2 has a planar structure. The oxygen-trapping reaction of 2 produced regioselectively fused peroxide 6 in an oxygen-doped argon matrix at 10 K. Irradiation of the diradical 2 afforded enyne 8 in an argon matrix at 10 K.


The impact of deprescribing interventions on oral proton pump inhibitor utilisation in a Singapore tertiary hospital: A quality improvement initiative.
Proton pump inhibitors (PPIs) are effective treatments for upper gastrointestinal pathologies and short-term courses are well-tolerated. However, indiscriminate use of PPIs is undesirable due to its potential harms. We implemented a series of deprescribing interventions between 2016 and 2017 to curb PPI overutilisation in our institution. The aim of this study was to evaluate the effectiveness and safety of these interventions. An institutional PPI deprescribing guide was disseminated by email and educational roadshows were conducted to prescribers. Interrupted time series analysis was used to evaluate the effectiveness of the deprescribing interventions over a 7-year period from 2013 to 2019. To ascertain the safety of PPI deprescribing, we analysed the peptic ulcer disease incidence from 2015 to 2018 and conducted a retrospective chart review of 262 inpatients who were deprescribed PPIs. Following the first intervention, there was a significant decrease in mean oral PPI utilisation by 2,324.46 defined daily doses (DDD) per 1,000 prescriptions (95% confidence interval [CI] -3,542.66, -1,106.26) per month, followed by a month-to-month decrease of 302.61 DDD per 1,000 prescriptions per month thereafter (95% CI -473.95, -131.27). A second targeted educational intervention was only effective in sustaining the decline in the outpatient, but not in the inpatient setting. There were no significant changes in incidence of peptic ulcer disease. In the retrospective chart review, a majority (62.6%) of patients remained deprescribed at 6 months. We observed a sustained decrease in PPI utilisation in our institution for more than 12 months following our educational interventions. Cautious deprescribing of PPIs in eligible candidates was found to be safe with low recurrence rates of upper gastrointestinal events.


Carbachol- and elevated Ca(2+)-induced translocation of functionally active protein kinase C to the brush border of rabbit ileal Na+ absorbing cells.
Protein kinase C is involved in mediating the effects of elevated Ca2+ in ileal villus Na+ absorbing cells to inhibit NaCl absorption. The present studies were undertaken to understand the mechanism by which this occurs. The effects of carbachol and the calcium ionophore A23187, agents which elevate intracellular Ca2+ and inhibit NaCl absorption in ileal villus cells, were studied. Carbachol treatment of villus cells caused a rapid decrease in protein kinase C activity in cytosol, with an accompanying increase in microvillus membrane C kinase. Exposure of the villus cells to calcium ionophore also caused a quantitatively similar decrease in cytosol C kinase and increase in C kinase activity in the microvillus membrane. This increase caused by carbachol and Ca2+ ionophore was specific for the microvillus membrane. In fact, 30 s and 10 min after exposure of the cells to carbachol, basolateral membrane protein kinase C decreased, in a time-dependent manner; whereas 10 min of Ca2+ ionophore exposure did not alter basolateral C kinase. Exposure of villus cells to Ca2+ ionophore or carbachol caused similar increases in microvillus membrane diacylglycerol content. As judged by the ability to inhibit Na+/H+ exchange measured in ileal villus cell brush border membrane vesicles, the protein kinase C which translocated to the microvillus membrane was functionally significant. Inhibition of Na+/H+ exchange required ATP and was reversed by the protein kinase C antagonist H-7. In conclusion, the effect of carbachol and Ca2+ ionophore in regulation of ileal NaCl absorption is associated with an increase in microvillus membrane diacylglycerol content and functionally active protein kinase C. The effects of both carbachol and Ca2+ ionophore are different on brush border and basolateral membrane distribution of protein kinase C.


Synthesis of copolymers containing an active ester of methacrylic acid by RAFT: controlled molecular weight scaffolds for biofunctionalization.
We report the controlled radical copolymerization of N-(2-hydroxypropyl)methacrylamide (HPMA) with a monomer containing an active ester, N-methacryloyloxysuccinimide (NMS), by reversible addition fragmentation chain transfer (RAFT). The large difference in the reactivity ratios of HPMA and NMS resulted in significant variations in copolymer composition with increasing conversion during batch copolymerization. The use of a semi-batch copolymerization method, involving the gradual addition of the more reactive NMS, allowed uniformity of copolymer composition to be maintained during the polymerization. We synthesized polymers in a wide range of molecular weights (M(n) = 3000-50,000 Da) with low polydispersities (1.1-1.3). The effect of the ratio of monomer to chain transfer agent (CTA) on the molecular weight of the polymer was investigated. Given the numerous applications of poly(HPMA)-based conjugates in designing polymeric therapeutics, these controlled molecular weight activated polymers represent attractive scaffolds for biofunctionalization. As a demonstration, we attached a peptide to the activated polymer backbone to synthesize a potent controlled molecular weight polyvalent inhibitor of anthrax toxin.


[Rhubarb induced change of tumor necrosis factor-alpha level in guinea pig model of melanosis coli and its significance].
To study the induced change of tumor necrosis factor alpha (TNF-alpha) level in serum and colon tissue of guinea pig model with melanosis coli and its significance induced by rhubarb (RB). One hundred and twelve guinea pigs of clean grade were randomly divided into four groups: the 16 in the normal group (untreated) and the 3 RB groups (32 in each) treated with low (3 g/kg d), medium (6 g/kg d), and high (12 g/kg d) dose of rhubarb respectively, administered by gastrogavage for 60 successive days. All guinea pigs were sacrificed at the terminal of the experiment and their blood serum and colon tissue were taken for detecting TNF-alpha level and TNF-alpha mRNA expression qualitatively and quantitatively using ELISA and RT-PCR. Compared with the normal group, serum and colonic tissue levels of TNF-alpha and TNF-alpha mRNA expression in the RB groups were higher significantly (P<0.01), while no significant difference was found among the later three groups (P>0.05). RB could induce change of TNF-alpha level in serum and colon tissue of guinea pig with melanosis coli.


Partly conditional estimation of the effect of a time-dependent factor in the presence of dependent censoring.
We propose semiparametric methods for estimating the effect of a time-dependent covariate on treatment-free survival. The data structure of interest consists of a longitudinal sequence of measurements and a potentially censored survival time. The factor of interest is time-dependent. Treatment-free survival is of interest and is dependently censored by the receipt of treatment. Patients may be removed from consideration for treatment, temporarily or permanently. The proposed methods combine landmark analysis and partly conditional hazard regression. A set of calendar time cross-sections is specified, and survival time (from cross-section date) is modeled through weighted Cox regression. The assumed model for death is marginal in the sense that time-varying covariates are taken as fixed at each landmark, with the mortality hazard function implicitly averaging across future covariate trajectories. Dependent censoring is overcome by a variant of inverse probability of censoring weighting (IPCW). The proposed estimators are shown to be consistent and asymptotically normal, with consistent covariance estimators provided. Simulation studies reveal that the proposed estimation procedures are appropriate for practical use. We apply the proposed methods to pre-transplant mortality among end-stage liver disease (ESLD) patients.


Capacity to consent to or refuse treatment and/or research: theoretical considerations.
This article discusses theoretical dimensions of competency to consent to or refuse treatment and/or research. We will consider a number of issues. Our first subject is the nature of assessments of competency-their empirical, normative, and conceptual aspects. We then discuss how we should divide up the components of capacity-understanding, appreciation, reasoning, and evidencing a choice; how we should understand these different components; and whether all are indeed necessary. We discuss where to draw the line between capacity and incapacity on each of the four elements of capacity. We ask whether we should have a variable competency standard, either in general or in different contexts (e.g. treatment versus research). Finally we consider the role of mental illness in competency assessments.


Managing interdisciplinary health research--theoretical and practical aspects.
Interdisciplinary health research can offer valuable evidence for health care managers. However, there are specific challenges regarding the management of such projects. Based on 7 years of experience from a project in western Kenya, the authors point to the need for a sufficient time horizon, a high level of communication, equity between the disciplines and the identification of appropriate evaluation criteria as issues to be considered. The theoretical framework of Rosenfield was modified to comply with the complexities of field management.


Investigation of the Interaction between Hearing Function and Comorbidities in Adults Living with Human Immunodeficiency Virus.
Adults living with the human immunodeficiency virus (HIV) have a high prevalence of co-existing comorbidities. While research indicates that adults living with HIV are at risk of developing hearing impairment, limited research exists on the interaction between hearing function and comorbidities in this population. The objective of this study was to determine and compare the hearing function of a group of adults living with HIV and comorbidities and those without comorbidities. A sample of 132 adults living with HIV underwent a basic audiological test battery to assess their hearing function. Participants with comorbidities were 1.23 times more likely to develop hearing loss, with crude odds of 1.236 (95%CI 0.5467 to 2.795), while those with three comorbidities were 2.52 times more likely to develop hearing loss. Participants with hypertension were 93% more likely to develop hearing loss when compared to nonhypertensive participants (OR = 1.928; 95%CI: 0.7856 to 4.7345). There was only a marginal association between hypercholesterolemia and sensorineural hearing loss (SNHL), with no association between other comorbidities and the type of hearing loss. The current findings raise a need for prioritizing patients with comorbidities in audiological assessment and monitoring in resource-constrained contexts, where capacity versus demand challenges might prevent the provision of audiological services to all adults living with HIV. These findings also highlight the importance of preventive care in this population with regard to the burden of the disease, as it may lead to worse ear and hearing outcomes for affected individuals.


First pregnancies in jennies with vitrified donkey semen using a new warming method.
Sperm vitrification has been recently developed, but fertility trials have not been performed yet in equine species. In this study, a new warming technique for vitrified donkey semen was developed and the uterine inflammatory response and fertility were compared to conventional freezing. In Experiment 1, sperm was vitrified in straws and warmed in 3 ml of extender or in a water bath at: 37 °C/30 s; 43 °C/10 s; and 60 °C/5 s. Sperm motility, plasma and acrosome membranes and DNA integrity were compared between treatments. In Experiment 2, jennies were inseminated twice (500 × 106 sperm) in the uterine body either with vitrified or frozen semen (2 cycles/jenny). Pregnancy rates and the uterine inflammatory response (polymorphonuclear neutrophil concentration; PMN) were evaluated after artificial insemination (AI). No differences between warming in extender/water bath were found and 43 °C/10 s was better than lower temperatures in terms of total (53.8 ± 13.2%) and progressive sperm motility (41.4 ± 11.4%). No differences in PMN concentration (×103 PMN/ml) were found between vitrified (276.8 ± 171.6) or frozen (309.7 ± 250.7) semen after AI. However, PMN decreased faster (P < 0.05) using vitrified semen. Pregnancy rates were greater for vitrified (22%) than frozen semen (10%) but not statistically different. In conclusion, donkey sperm vitrified in straws could be directly warmed in a water bath at 43 °C/10 s, reducing the uterine inflammatory response obtained after AI and promoting positive pregnancy outcomes. These findings confirm the possibility to use vitrified semen as an alternative for AI in jennies.


Genetic identification of a gene involved in constitutive, high-affinity nitrate transport in higher plants.
Two mutations have been found in a gene (NRT2) of Arabidopsis thaliana that specifically impair constitutive, high-affinity nitrate uptake. These mutants were selected for resistance to 0.1 mM chlorate in the absence of nitrate. Progency from one of the backcrossed mutants showed no constitutive uptake of nitrate below 0.5 mM at pH 7.0 in liquid culture (that is, within 30 min of initial exposure to nitrate). All other uptake activities measured (high-affinity phosphate and sulfate uptake, inducible high-affinity nitrate uptake, and constitutive low-affinity nitrate uptake) were present or nearly normal in the backcrossed mutant. Electrophysiological analysis of individual root cells showed that the nrt2 mutant showed little response to 0.25 mM of nitrate, whereas NRT2 wild-type cells showed an initial depolarization followed by recovery. At 10 mM of nitrate both the mutant and wild-type cells displayed similar, strong electrical responses. These results indicate that NRT2 is a critical and perhaps necessary gene for constitutive, high-affinity nitrate uptake in Arabidopsis, but not for inducible, high-affinity nor constitutive, low-affinity nitrate uptake. Thus, these systems are genetically distinct.


Drug-related cues exacerbate decision making and increase craving in heroin addicts at different abstinence times.
Relapse is a persistent problem in the management of addiction. Drug-related cues are powerful instigators of relapse. Impulsive decision making may contribute to relapse through a poorly considered assessment of the consequences of drug use. Drug cues robustly increase subjective craving, which is frequently associated with relapse. The present study explored the effects of drug-related cues on decision making and craving in heroin addicts at different abstinence times: 1, 3, 12, and 24 months. The 75 male participants were given 5 min exposure to neutral and drug-associated cues while decision making performance, craving, blood pressure, heart rate, and emotional state pre- and post-exposure were assessed. The Iowa Gambling Task was used to evaluate decision making ability in heroin addicts. Drug-related cues exacerbated impulsive decision making and increased craving, heart rate, and systolic pressure in heroin addicts at all abstinence times. Drug-related cues aggravated decision making and increased craving in former heroin addicts who had been drug-free for 1-24 months, which might have significant clinical implications for the prevention of relapse.


Estimating the optimal interval between rounds of indoor residual spraying of insecticide using malaria incidence data from cohort studies.
Indoor residual spraying (IRS) reduces vector densities and malaria transmission, however, the most effective spraying intervals for IRS have not been well established. We estimated the optimal timing interval for IRS using a statistical approach. Six rounds of IRS were implemented in Tororo District, a historically high malaria transmission setting in Uganda, during the study period (3 rounds with bendiocarb active ingredient (Ficam®): December 2014 to December 2015, and 3 rounds with pirimiphos methyl active ingredient (Actellic 300®CS): June 2016 to July 2018). A generalized additive model was used to estimate the optimal timing interval for IRS based on the predicted malaria incidence. The model was fitted to clinical incidence data from a cohort of children aged 0.5-10 years from selected households observed throughout the study period. 494 children, 67% aged less than 5 years at enrolment were analysed. Six-months period incidence of malaria decreased from 2.96 per person-years at the baseline to 1.74 following the first round of IRS and then to 0.02 after 6 rounds of IRS. The optimal time interval for IRS differed between bendiocarb and pirimiphos methyl and by IRS round. To retain an optimum impact, bendiocarb would require respraying 17 (95% CI: 14.2-21.0) weeks after application whereas pirimiphos methyl could remain impactful for 40 (95% CI: 37.0-42.8) weeks, although in the final year this estimates 36 (95% CI: 32.7-37.7) weeks. However, we could not estimate from the data the optimal time after the second and third rounds of bendiocarb and after the second round of pirimiphos methyl. Neither the amount of rainfall nor the EIR nor the distribution of nets were found to be statistically significant for determining the time period between spray rounds. In our setting, the effect of the two IRS products was distinct. Statistically, pirimiphos methyl provided a longer window of protection than bendiocarb, although impact varied between different spray rounds and years which was not explained by rainfall or EIR or distribution of nets in our statistical approach. Understanding the effectiveness of IRS and how long it lasts can help for planning campaigns, but one should consider the financial cost and insecticide resistance. Monitoring the timing of spray campaigns using clinical incidence could be repeated in future programs to help determine the average period of protectivity of these products.


Advancing understanding, diagnosis, and therapies for cutaneous lupus erythematosus within the broader context of systemic lupus erythematosus.
Cutaneous lupus erythematosus (CLE) is an autoimmune disease that can be associated with systemic lupus erythematosus (SLE) symptoms. The pathogenesis of both CLE and SLE is multifactorial, involving genetic susceptibility, environmental factors, and innate and adaptive immune responses. Despite the efficacy of current medications, many patients remain refractory, highlighting the necessity for new treatment options. Unfortunately, owing to challenges related in part to trial design and disease heterogeneity, only one new biologic in the last 50 years has been approved by the US Food and Drug Administration for the treatment of SLE. Thus, although SLE and CLE have a similar pathogenesis, patients with CLE who do not meet criteria for SLE cannot benefit from this advancement. This article discusses the recent trials and emphasizes the need to include patients with single-organ lupus, such as CLE, in SLE trials.


Structure characterization and antioxidant activity of a novel polysaccharide isolated from pulp tissues of Litchi chinensis.
A novel polysaccharide (LCP50S-2) with antioxidant activity was isolated from Litchi chinensis Sonn. The structure of LCP50S-2 was elucidated on the basis of physicochemical and instrumental analyses, and its average molecular weight was determined by gel permeation chromatography to be 2.19 × 10(2) kDa. The backbone of LCP50S-2 was composed of (1→3)-linked β-L-rhamnopyranosyl residues, (1→4)-linked α-D-xylopyranosyl residues, (1→4)-linked β-D-glucopyranosyl residues, and (1→4)-linked α-D-glucopyranosyl residues which branched at O-6. The two branches consisted of α-L-arabinopyranosyl residues and (1→6)-linked β-D-galactopyranosyl residues terminated with α-L-arabinopyranosyl residues, respectively. In the in vitro antioxidant assay, LCP50S-2 was found to possess DPPH radical-scavenging activity and hydroxyl radical-scavenging activity with IC(50) values of 220 and 266 μg/mL, respectively.


Force of cochlear implant electrode insertion performed by a robotic insertion tool: comparison of traditional versus Advance Off-Stylet techniques.
Robotic cochlear implant electrode array insertion offers substantial potential advantages, namely repeatability and minimization of insertion forces, leading to decreased intracochlear trauma. Using such a robotic insertion tool, we sought to analyze force profiles during deployment of stylet-containing electrode arrays using either traditional insertion, in which the stylet is withdrawn after complete insertion of the electrode, or Advance Off-Stylet (AOS) insertion, in which the stylet is withdrawn simultaneous with electrode array insertion. Prospective. Tertiary referral center. A robotic cochlear implant insertion tool coupled with a force-sensing carriage was used to perform electrode array insertions into an anatomically correct, three-dimensional scala tympani model during either straight insertion (n = 4) or AOS insertion (n = 4). Both insertion techniques begin with a 7-mm straight insertion during which forces were similar averaging approximately 0.006 N. For insertion from 7 to 17 mm, traditional insertion forces averaged 0.046 ± 0.027 N, with a peak of 0.093 N, and AOS insertion forces averaged 0.008 ± 0.006 N, with a peak of 0.034 N. Beyond 9.74 mm, the difference between traditional and AOS insertion forces was highly significant. With the use of a robotic insertion tool, which minimizes operator variability and maximizes repeatability, we have shown that cochlear implant electrode insertion via AOS is associated with lower average and maximum insertion forces compared with traditional insertion. These findings support the use of AOS over traditional, straight insertion.


[Factors associated with resistance to human immunodeficiency virus protease inhibitors].
To assess the risk factors associated with genotypic resistance to protease inhibitors (PI) in HIV-infected subjects with virologic failure despite highly active antiretroviral treatment (HAART). Retrospective chart review including 47 consecutive patients with virologic failure despite PI-based HAART who had undergone a genotypic HIV-1 testing. The prevalence of genotypic resistance to PI was determined and several demographic, clinical and laboratory variables were compared between patients with and without genotypic resistance to those drugs. The entire nucleotide sequence of the protease gene was obtained in 43 of the 47 patients; 18 of them had genotypic resistance to PI. Genotypic resistance to PI was associated with a previous therapy with suboptimal antiretroviral regimens (OR = 10.2; 95% CI, 1.05-245.1; P = 0.02), duration of antiretroviral therapy longer than 18 months (OR = 13.3; 95% CI, 1.23-340.85; P = 0.01), greater number of antiretroviral regimens and drugs before the virologic failure (p < 0.01) and presence of the 184V mutation in the reverse transcriptase gene (OR = 5.6; 95% CI, 1.2-29.2; P = 0.02). There was no relationship between PI resistance and the risk group, viral load or CD4 cell count. In the multivariate analysis, previous therapy with suboptimal antiretroviral regimens was the better predictor of PI resistance (OR = 11.1; 95% CI, 1.04-117.47; P = 0.046). Patients treated with suboptimal antiretroviral activity regimens before starting HAART can be at greater risk of developing genotypic resistance to protease inhibitors.


Usefulness of a partial median sternotomy for acute infectious endocarditis in patients with tracheostoma.
Infectious endocarditis patients occasionally need emergency cardiac surgery even if they have a tracheostoma. However, a median full-sternotomy approach carries increased risk for sternal infection and lethal mediastinitis in cardiac surgery for patients with tracheostomas. We successfully performed valve replacement procedures using a lower partial median sternotomy approach in 6 infectious endocarditis patients with tracheostomas. There were neither operative deaths nor complications related to wound infection in these cases. The partial sternotomy approach represents a safe alternative in cardiac surgery for acute infectious endocarditis patients with tracheostomas who need emergent surgery.


Antibiotic Prescribing and Antimicrobial Resistance from an Australian Perspective.
In Australia, the overuse or inappropriate prescribing of antimicrobials in health (human and animal) and agriculture is a concern that has increased over the years. This has given bacteria, fungi, parasites, and some viruses through exposure more opportunity to develop resistance. A process of artificial and natural selection, which favors microorganisms in developing the strongest natural defenses increasing prevalence of antimicrobial resistance (AMR). Appropriate use of antimicrobials can be lifesaving to humans and animals, but inappropriate use needs to be closely monitored and acted on to promote improved safety and quality of care. Inappropriate use includes prescribing antimicrobials when they are not necessary, prescribing the wrong type of antimicrobial and prescribing them for the incorrect duration. This short report reviews and summarizes some of the efforts used in Australia to control AMR and antibiotic prescribing.


Engineered nanoparticles enable deep proteomics studies at scale by leveraging tunable nano-bio interactions.
SignificanceDeep profiling of the plasma proteome at scale has been a challenge for traditional approaches. We achieve superior performance across the dimensions of precision, depth, and throughput using a panel of surface-functionalized superparamagnetic nanoparticles in comparison to conventional workflows for deep proteomics interrogation. Our automated workflow leverages competitive nanoparticle-protein binding equilibria that quantitatively compress the large dynamic range of proteomes to an accessible scale. Using machine learning, we dissect the contribution of individual physicochemical properties of nanoparticles to the composition of protein coronas. Our results suggest that nanoparticle functionalization can be tailored to protein sets. This work demonstrates the feasibility of deep, precise, unbiased plasma proteomics at a scale compatible with large-scale genomics enabling multiomic studies.


Analysis of variance to assess statistical significance of Laplacian estimation accuracy improvement due to novel variable inter-ring distances concentric ring electrodes.
Concentric ring electrodes have shown promise in non-invasive electrophysiological measurement demonstrating their superiority to conventional disc electrodes, in particular, in accuracy of Laplacian estimation. Recently, we have proposed novel variable inter-ring distances concentric ring electrodes. Analytic and finite element method modeling results for linearly increasing distances electrode configurations suggested they may decrease the truncation error resulting in more accurate Laplacian estimates compared to currently used constant inter-ring distances configurations. This study assesses statistical significance of Laplacian estimation accuracy improvement due to novel variable inter-ring distances concentric ring electrodes. Full factorial design of analysis of variance was used with one categorical and two numerical factors: the inter-ring distances, the electrode diameter, and the number of concentric rings in the electrode. The response variables were the Relative Error and the Maximum Error of Laplacian estimation computed using a finite element method model for each of the combinations of levels of three factors. Effects of the main factors and their interactions on Relative Error and Maximum Error were assessed and the obtained results suggest that all three factors have statistically significant effects in the model confirming the potential of using inter-ring distances as a means of improving accuracy of Laplacian estimation.


Multidirectional Instability: Natural History and Evaluation.
Multidirectional instability (MDI) represents a great challenge to the orthopedic surgeon. When treating these patients we must be aware that instability refers to a symptomatic situation, thus multidirectional instability is defined as symptomatic involuntary instability in two or more directions, and should be clearly differentiated from asymptomatic hyperlaxity. It may be associated with hyperlaxity, either congenital or acquired following repetitive stress, but also may be present without hyperlaxity, which is rare. We searched in the online data bases and reviewed the relevant published literature available. Many differences can be seen in the current literature when identifying these patients, unclear definitions and criteria to be included in this patient group are common. Understanding the complex shoulder biomechanics as well as being aware of the typical clinical features and the key examination signs, which we review in this article, is of paramount importance in order to identify and classify these patients, allowing the best treatment option to be offered to each patient.


Effect of a reduced fat and sugar maternal dietary intervention during lactation on the infant gut microbiome.
A growing body of literature has shown that maternal diet during pregnancy is associated with infant gut bacterial composition. However, whether maternal diet during lactation affects the exclusively breastfed infant gut microbiome remains understudied. This study sets out to determine whether a two-week of a reduced fat and sugar maternal dietary intervention during lactation is associated with changes in the infant gut microbiome composition and function. Stool samples were collected from four female and six male (n = 10) infants immediately before and after the intervention. Maternal baseline diet from healthy mothers aged 22-37 was assessed using 24-h dietary recall. During the 2-week dietary intervention, mothers were provided with meals and their dietary intake was calculated using FoodWorks 10 Software. Shotgun metagenomic sequencing was used to characterize the infant gut microbiome composition and function. In all but one participant, maternal fat and sugar intake during the intervention were significantly lower than at baseline. The functional capacity of the infant gut microbiome was significantly altered by the intervention, with increased levels of genes associated with 28 bacterial metabolic pathways involved in biosynthesis of vitamins (p = 0.003), amino acids (p = 0.005), carbohydrates (p = 0.01), and fatty acids and lipids (p = 0.01). Although the dietary intervention did not affect the bacterial composition of the infant gut microbiome, relative difference in maternal fiber intake was positively associated with increased abundance of genes involved in biosynthesis of storage compounds (p = 0.016), such as cyanophycin. Relative difference in maternal protein intake was negatively associated with Veillonella parvula (p = 0.006), while positively associated with Klebsiella michiganensis (p = 0.047). Relative difference in maternal sugar intake was positively associated with Lactobacillus paracasei (p = 0.022). Relative difference in maternal fat intake was positively associated with genes involved in the biosynthesis of storage compounds (p = 0.015), fatty acid and lipid (p = 0.039), and metabolic regulator (p = 0.038) metabolic pathways. This pilot study demonstrates that a short-term maternal dietary intervention during lactation can significantly alter the functional potential, but not bacterial taxonomy, of the breastfed infant gut microbiome. While the overall diet itself was not able to change the composition of the infant gut microbiome, changes in intakes of maternal protein and sugar during lactation were correlated with changes in the relative abundances of certain bacterial species.Clinical trial registration: Australian New Zealand Clinical Trials Registry (ACTRN12619000606189).


Antigen-chip technology for accessing global information about the state of the body.
Traditionally, immunologic diagnosis has been based on an attempt to correlate each disease with a specific immune reactivity, such as an antibody or a T-cell response to a single antigen specific for the disease entity. The state of the body, however, appears to be encoded by the immune system in collectives of reactivities and not by single reactivities. Here we describe our use of microarray technology and informatics to develop an antigen chip capable of detecting global patterns of antibodies binding to hundreds of antigens simultaneously. The patterns fashion diagnostic signatures.


A description of familial clustering of meningiomas in the Utah population.
Meningiomas are common intracranial tumors in adults, yet the genetics and cause of sporadic meningiomas are not well understood. Few familial clusters have been reported. The aim of this study was to investigate the familiality of meningiomas within the Utah Population Database. Meningioma cases reported in the Utah Cancer Registry were identified. Relative risk of their relatives was calculated. All possible cases were assessed with the Genealogical Index of Familiality (GIF), which measures average pairwise relatedness of all possible pairs using the Malecot coefficient of kinship. Clusters of cases descending from a common ancestor were identified. Eight hundred fifty-eight meningioma cases were reported. The relative risk of a first- or second-degree relative was 3.13 (95% CI: 1.67, 5.36) or 2.28 (1.30, 3.70), respectively. The GIF statistic demonstrated a clear excess of relationships for genetic distance <4 (closer than first cousins). We identified 920 pedigrees, including 2-21 meningioma cases. One hundred eighty-nine of these pedigrees, including 2-15 cases, had a significant excess (P < 0.05) of meningioma cases over what was expected. This Utah population-based analysis of meningiomas shows clear evidence of familial clustering and supports both a familial and a germline variant basis for meningioma. These clusters may allow identification of genes likely to contribute to tumorigenesis in high-risk pedigrees. These relative risk data provide the basis for further investigations of genetic contributions to meningioma. These data may contribute to developing a basis for determining screening criteria of higher-risk pedigrees for the presence of meningiomas.


Interaction between the muscle metaboreflex and the arterial baroreflex in control of arterial pressure and skeletal muscle blood flow.
The muscle metaboreflex and arterial baroreflex regulate arterial pressure through distinct mechanisms. During submaximal exercise muscle metaboreflex activation (MMA) elicits a pressor response virtually solely by increasing cardiac output (CO) while baroreceptor unloading increases mean arterial pressure (MAP) primarily through peripheral vasoconstriction. The interaction between the two reflexes when activated simultaneously has not been well established. We activated the muscle metaboreflex in chronically instrumented canines during dynamic exercise (via graded reductions in hindlimb blood flow; HLBF) followed by simultaneous baroreceptor unloading (via bilateral carotid occlusion; BCO). We hypothesized that simultaneous activation of both reflexes would result in an exacerbated pressor response owing to both an increase in CO and vasoconstriction. We observed that coactivation of muscle metaboreflex and arterial baroreflex resulted in additive interaction although the mechanisms for the pressor response were different. MMA increased MAP via increases in CO, heart rate (HR), and ventricular contractility whereas baroreflex unloading during MMA caused further increases in MAP via a large decrease in nonischemic vascular conductance (NIVC; conductance of all vascular beds except the hindlimb vasculature), indicating substantial peripheral vasoconstriction. Moreover, there was significant vasoconstriction within the ischemic muscle itself during coactivation of the two reflexes but the remaining vasculature vasoconstricted to a greater extent, thereby redirecting blood flow to the ischemic muscle. We conclude that baroreceptor unloading during MMA induces preferential peripheral vasoconstriction to improve blood flow to the ischemic active skeletal muscle.


Predictors of hospital acquired heel pressure ulcers.
The purpose of this study was to evaluate predictors of hospital acquired heel pressure ulcers. A prospective cohort study of hospitalized patients was conducted (N = 291). Subjects were enrolled by one team and followed by another team that was blind to initial assessment information. Initial assessment included demographics, Braden scale, and other variables found in the first study to be statistically significant. Ongoing evaluation involved heel assessment only. Univariate analysis yielded 15 statistically significant variables. Using multivariate logistic regression, subject's with a potential problem on the Braden Friction and Shear item (p = 0.01) and who were more frequently moist on the Braden Moisture item (p = 0.007) were more likely to develop heel ulcers (chi-square 30.52, df 3, p = 0.00001). Receiver Operator Characteristic (ROC) curves were plotted for the Braden scale and multiple other scoring systems. ROC curves were virtually identical using all new scoring systems as compared to the original Braden scale. No new scoring system was identified that led to a clinically significant improvement in sensitivity/specificity over the total Braden scale. While not perfect, the Braden scale may currently be the best predictive tool for heel pressure ulcer development.


Interleukin-17A promotes esophageal adenocarcinoma cell invasiveness through ROS-dependent, NF-κB-mediated MMP-2/9 activation.
Interleukin-17A (IL-17A), a pro-inflammatory cytokine secreted primarily by Th17 cells, has been proved to be involved in the microenvironment of certain inflammation-related tumors. However, the role of IL-17A in cancer development has always been controversial. In this study, we investigated the effect of IL-17A on the regulation of esophageal adenocarcinoma (EAC) cell invasiveness and related molecular mechanism. Surface IL-17 receptor (IL-17R) expression on human EAC cell line OE19 was examined using flow cytometry. The effect of IL-17A on cell proliferation was measured by MTT assay. Cell migration and invasive ability in vitro were assessed by wound-healing and Matrigel-coated Transwell invasion assay. Intracellular reactive oxygen species (ROS) levels were determined by flow cytometry and fluorescence microscope. The protein expression levels of MMP-2, MMP-9, NF-κB and p-IκB-α were detected by western blotting. Our results showed that IL-17A promoted migration and invasion of OE19 cells in a dose-dependent manner, however it had less effect on OE19 cell proliferation. Furthermore, IL-17A treatment significantly upregulated the expression of MMP-2 and MMP-9, stimulated intracellular ROS production, increased IκB-α phosphorylation and NF-κB nuclear translocation. Nevertheless, IL-17A-induced expression of MMP-2/9 and OE19 cell invasiveness were both inhibited by pretreatment with N-acetyl-L-cysteine (NAC, a ROS scavenger) or pyrrolidine dithiocarbamate (PDTC, a NF-κB inhibitor). In conclusion, these findings demonstrate that IL-17A can promote the migration and invasiveness of EAC cells through ROS/NF-κB/MMP-2/9 signaling pathway activation, indicating that IL-17A may be a potential therapeutic target for EAC.


Presynaptic Striatal Dopaminergic Function in Atypical Parkinsonism: A Metaanalysis of Imaging Studies.
Multiple-system atrophy (MSA), progressive supranuclear palsy (PSP), and corticobasal syndrome (CBS) have signs and symptoms overlapping those of Parkinson disease (PD), complicating their clinical diagnosis. Although presynaptic dopaminergic brain imaging with PET and SPECT is clinically widely used for patients with suspected PD, the benefit of functional imaging in atypical parkinsonism syndromes remains unclear. We compared striatal presynaptic dopaminergic function in MSA parkinsonism variant (MSA-P), MSA cerebellar variant (MSA-C), PSP, CBS, and PD using combined quantitative data from all published studies. Methods: The PubMed database was searched from inception to August 2018 for the terms "dopamine" OR "dopaminergic" AND "PET" OR "SPECT" OR "SPET" and keywords related to PD, MSA, PSP, and CBS. In total, 1,711 publications were identified. PET or SPECT studies comparing patients with atypical parkinsonism to another diagnostic group (PD, MSA, PSP, or CBS) were included. Tracers for dopamine transporter (DAT), aromatic amino acid decarboxylase (AADC), or vesicular monoamine type 2 were investigated. Tracer binding data were extracted from the original articles. Heterogeneity of the data was examined using I2 statistics, and a random-effects model was used to summarize data. Hedges g was used as an estimator of effect size in group comparisons. Results are reported according to PRISMA guidelines. Results: Thirty-five studies (29 DAT, 6 AADC, no vesicular monoamine type 2 studies) with 356 MSA-P patients, 204 PSP patients, 79 CBS patients, and 62 MSA-C patients were included in the metaanalysis. Caudate nucleus and putamen DAT function was clearly lower in PSP than in PD (caudate: 34.1% difference, g = -1.08, 95% confidence interval [CI] = -1.52 to -0.64; putamen: 18.2%, g = -0.86, 95% CI = -1.50 to -0.21) and MSA-P (striatum: 31.4%, g = -0.70, 95% CI = -1.21 to -0.19) and was clearly lower in MSA-P than in MSA-C (striatum: 46.0%, g = 1.46, 95% CI = 0.23 to 2.68). Although not significant because of limited data, aromatic l-AADC results paralleled the DAT findings. Conclusion: Striatal presynaptic DAT function is clearly lower in PSP patients than in PD and MSA-P patients and is clearly lower in MSA-P patients than in MSA-C patients.


Reproducibility of Doppler measures of ventricular function during maximal upright cycling.
Echocardiographic measures of ventricular function during exercise may prove useful in assessing myocardial health. This study examined test-retest reproducibility of measurements of Doppler mitral flow velocity (E-wave) and myocardial tissue Doppler imaging (E'-, S-waves) during a progressive maximal upright cycle test in 12 healthy lean adolescent males. Measurements were taken as subjects pedalled to exhaustion with 35 watt work increments in two separate trials. We observed no significant differences in mean values at rest, submaximal (70 watts) exercise, or maximal exercise for all three variables. Coefficients of variation at maximal exercise were 5.3%, 7.4%, and 8.1% for mitral E, tissue Doppler-S, and tissue Doppler-E', respectively. These findings indicated acceptable levels of reproducibility of Doppler ultrasound techniques for assessing ventricular systolic and diastolic functional response to maximal exercise in young lean male subjects.


The selective VEGFR1-3 inhibitor axitinib (AG-013736) shows antitumor activity in human neuroblastoma xenografts.
Tumor angiogenesis in childhood neuroblastoma is an important prognostic factor suggesting a potential role for antiangiogenic agents in the treatment of high-risk disease. Within the KidsCancerKinome project, we evaluated the new oral selective pan-VEGFR tyrosine kinase inhibitor axitinib (AG-013736) against neuroblastoma cell lines and the subcutaneous and orthotopic xenograft model IGR-N91 derived from a primary bone marrow metastasis. Axitinib reduced cell proliferation in a dose-dependent manner with IC(50) doses between 274 and >10,000 nmol/l. Oral treatment with 30 mg/kg BID for 2 weeks in advanced tumors yielded significant tumor growth delay, with a median time to reach five times initial tumor volume of 11.4 days compared to controls (p = 0.0006) and resulted in significant reduction in bioluminescence. Simultaneous inhibition of VEGFR downstream effector mTOR using rapamycin 20 mg/kg q2d×5 did not statistically enhance tumor growth delay compared to single agent activities. Axitinib downregulated VEGFR-2 phosphorylation resulting in significantly decreased microvessel density (MVD) and overall surface fraction of tumor vessels (OSFV) in all xenografts as measured by CD34 immunohistochemical staining (mean MVD ± SD and OSFV at 14 days 21.27 ± 10.03 in treated tumors vs. 48.79 ± 17.27 in controls and 0.56% vs. 1.29%; p = 0.0006, respectively). We further explored the effects of axitinib on circulating mature endothelial cells (CECs) and endothelial progenitor cells (CEPs) measured by flow cytometry. While only transient modification was observed for CECs, CEP counts were significantly reduced during and up to 14 days after end of treatment. Axitinib has potent antiangiogenic properties that may warrant further evaluation in neuroblastoma.


Organocatalytic (3+3)-cycloaddition of ortho-substituted phenyl nitrones with aryl cyclopropane carbaldehydes: a facile access to enantioenriched 1,2-oxazinanes.
The first asymmetric (3+3)-cycloaddition of ortho-substituted phenyl nitrones with aryl cyclopropane carbaldehydes has been demonstrated by secondary amine catalysts. While the other ortho-substituents gave 1,2-oxazinanes, ortho-hydroxy ones provided a novel class of tetrahydrochromeno-1,2-oxazine cores via rare 1,3-aryl migration, followed by cyclization. An unusual type of asymmetric approach was also recognized.


Endoscopically guided nasojejunal tube placement in dogs for short-term postduodenal feeding.
To evaluate a method for endoscopically guided nasojejunal tube placement allowing short-term postduodenal feeding and chyme withdrawal in dogs. Pilot study. University teaching hospital. Three healthy Beagle dogs with jejunal nipple valve fistulas. After the dogs were anesthetized, an 8 Fr, 250-cm polyvinyl chloride catheter was advanced through a gastroscope into the jejunum. Correct jejunal placement was established using endoscopic visualization and confirmed by fluoroscopy and radiography. The proximal end of the tube was pulled out through 1 nostril and sutured to the skin of the forehead. Thereafter, jejunal feeding was administered for 4 days. Follow-up examinations included daily confirmation of the tube's position using radiography, physical examination, and blood analyses. Withdrawal of jejunal chyme was performed after jejunal and oral feeding. Fluoroscopic examination confirmed that endoscopic visualization alone allowed correct jejunal placement. During a 4-day postduodenal feeding period, repeated radiographic examination revealed stable positioning of the tubes within the jejunum with minor cranial displacement. The tubes were functional throughout the study without causing identifiable problems. Repeated physical examinations and blood analysis showed no abnormalities. We were able to administer the daily caloric requirements as a liquid diet. Jejunal chyme was successfully withdrawn via the tube. Endoscopically guided nasojejunal tube placement was shown to be a minimally invasive, well-tolerated method for short-term jejunal feeding in healthy dogs. This technique is a viable option for dogs requiring jejunal feeding but not laparotomy. The feasibility of chyme sampling is another unique application of the procedure.


Heavy metal removal potential of dried Salvinia biomass.
Investigations were carried out to evaluate heavy metal adsorption capacity of Salvinia. Batch experiments showed that dry plant biomass possess good potential to adsorb heavy metals such as Ni, Co, Cr, Fe, and Cd. The metal adsorption increased with increase in initial metal concentration. The data obtained fitted well with Freundlich equilibrium isotherm. Further characterization of plant biomass showed presence of both acidic and basic surface functionalities that might facilitate binding of metal ions. Fourier transform infrared (FTIR) spectra of plant biomass suggested involvement of carbonyl (C=O), carboxyl (-COO), and hydroxyl (-OH) groups in binding heavy metals to plant biomass. The studies establish S. natans as an effective biosorbent for removing heavy metals from wastewater and further emphasize biomass utilization in wastewater treatment technologies.


Disseminated spina ventosa.
Spina Ventosa is a rare condition. A rare case of disseminated tuberculosis of bones and skin without primary foci is presented. Gross sclerosis of the short bones of hand and leg were noted.


Methane activation by chromium oxide cations in the gas phase: a theoretical study.
Density Functional Theory, in its B3LYP formulation, was used to explore quantitative details of the potential energy hypersurfaces for the C-H bond activation reaction of methane by chromium dioxide cation. Both doublet ground and quartet excited states of the cation were considered, and all the minima and transition states localized along the paths leading to the formation of the experimentally observed products were characterized. All the calculated paths involve spin inversions that decrease the barrier heights of the involved transition states but do not play a significant role. Reaction pathways were also studied employing the nonhybrid BP86 functional, the reparametrized B3LYP* functional, and the CCSD(T) approach. Because other examples in the literature indicate that sequential ligation enhances the reactivity of bare transition metals cations, the state-selective reactivity of the chromium monoxide cation with respect to methane was also investigated and compared with that of the bare cation.


High-resolution MAS NMR analysis of PI3-SH3 amyloid fibrils: backbone conformation and implications for protofilament assembly and structure .
The SH3 domain of the PI3 kinase (PI3-SH3 or PI3K-SH3) readily aggregates into fibrils in vitro and has served as an important model system in the investigation of the molecular properties and mechanism of formation of amyloid fibrils. We describe the molecular conformation of PI3-SH3 in amyloid fibril form as revealed by magic-angle spinning (MAS) solid-state nuclear magnetic resonance (NMR) spectroscopy. The MAS NMR spectra of these fibrils display excellent resolution, with narrow (13)C and (15)N line widths, representing a high degree of structural order and the absence of extensive molecular motion for the majority of the polypeptide chain. We have identified the spin systems of 82 of the 86 residues in the protein and obtained sequential resonance assignments for 75 of them. Chemical shift analysis indicates that the protein subunits making up the fibril adopt a compact conformation consisting of four well-defined beta-sheet regions and four random-coil elements with varying degrees of local dynamics or disorder. The backbone conformation of PI3-SH3 in fibril form differs significantly from that of the native state of the protein, both in secondary structure and in the location of dynamic or disordered segments. The site-specific MAS NMR analysis of PI3-SH3 fibrils we report here is compared with previously published mechanistic and structural data, resulting in a detailed interpretation of the factors that mediate fibril formation by PI3-SH3 and allowing us to propose a possible model of the core structure of the fibrils. Our results confirm the structural similarities between PI3-SH3 fibrils and amyloid assemblies directly related to degenerative and infectious diseases.


Determination of lamotrigine, carbamazepine and carbamazepine epoxide in human serum by gas chromatography mass spectrometry.
A method for the identification and quantification of the antiepileptics lamotrigine, carbamazepine and carbamazepine epoxide (active metabolite) in human serum is described. In refractory epilepsy the combination of carbamazepine and lamotrigine was recently developed to a modern therapeutic concept. The goal of this paper is therapeutic drug monitoring (TDM) of these substances. Serum was extracted with a quick precipitation method using a modified commercial extraction-kit and analysed by gas chromatography mass spectrometry (GC-MS). A gas-chromatographic temperature-pressure programme was developed that allowed the determination of lamotrigine by gas chromatography mass spectrometry. A reference spectrum of pure lamotrigine is herewith published for the first time. A new mass spectra library was created to support the identification of the antiepileptics in human serum. In the Specified Ions Monitoring mode (SIM) a detection limit below the therapeutic range and recoveries above 90% were obtained. Comparison of results obtained by GC-MS or a commercially available high performance liquid chromatographic (HPLC) method (for lamotrigine) and a fluorescence polarisation immunoassay (FPIA) (for carbamazepine) from spiked serum samples showed disagreement of no more than 10% between the methods and demonstrated the accuracy of the new method. In addition, quantitative determinations of these antiepileptics in samples from patients under anticonvulsive therapy showed a strong linear correlation with r2 = 0.961 for carbamazepine and r2 = 0.964 for lamotrigine. Only two from a total of 46 results differed by more than 10%. Our method for quantifying lamotrigine in serum seems to be highly specific and capable of measuring lamotrigine in patients on single therapy, as well as on add-on therapy with carbamazepine or carbamazepine epoxide. No interference from other coadministered drugs was detected.


Successful use of cryocrit for monitoring response to therapeutic plasma exchange in type 1 cryoglobulinemia.
Waldenstrom macroglobulinemia (WM) is a clinical syndrome that is defined as lymphoplasmacytic lymphoma with bone marrow involvement and IgM monoclonal gammopathy of any level. In some instances WM can result in a type I cryoglobulinemia with very high cryocrits, which is unusual in type II and III cryoglobulinemia. We describe a case of an 80 year old male with WM, severe type I cryoglobulinemia, and an extremely elevated cryocrit (69%). Over the course of five weeks we performed nine therapeutic plasma exchanges (TPE), and after seven treatments his cryocrit had decreased to 6% with improvement in his symptoms. By monitoring his cryocrit throughout his TPE sessions, we were able to assess his response to treatment, determine the ideal length of treatment in addition to his symptomatic improvement. J. Clin. Apheresis 31:403-404, 2016. © 2015 Wiley Periodicals, Inc.