Pain With Differing Insufflation Pressures During Robotic Sacrocolpopexy: A Randomized Controlled Trial.
To evaluate whether decreasing insufflation pressure reduces postoperative pain and opioid use in women undergoing robotic-assisted sacrocolpopexy. In a single-blinded randomized trial, women with pelvic organ prolapse underwent robotic-assisted sacrocolpopexy at either 12 mm Hg (experimental) or 15 mm Hg (standard) insufflation pressure. The primary outcome was pain rating on a visual analog scale (VAS) on postoperative day 1 within 24 hours of surgery. Secondary outcomes included VAS pain rating at outpatient follow-up, inpatient and outpatient use of opioids, operative time, and estimated blood loss. A margin of 15 mm was considered clinically different on the VAS, and at 80% power, a sample size of at least 64 participants was needed to show significance. From April 27, 2021, to May 17, 2022, 80 women were enrolled, with 41 in the experimental group and 39 in the standard group. All participants underwent surgery as planned and attended a 2-week postoperative follow-up. Participants in the experimental group had less pain on postoperative day 1 with median VAS of 17.0 mm (interquartile range 26.0) compared with 29.0 mm (interquartile range 32.0, P=.007) in the standard group. No differences were noted in the secondary outcomes of operative time, estimated blood loss, or length of stay. Participants in the experimental group were noted to use fewer opioids while an inpatient (P=.04) and outpatient (P=.02). In multivariable analyses, lower insufflation pressure and increasing age were negatively associated with postoperative VAS scores. Lowering insufflation pressure (12 mm Hg) during robotic-assisted sacrocolpopexy safely reduced postoperative pain and opioid use compared with standard pressure (15 mm Hg). ClinialTrials.gov, NCT04858438.


Managing the Increasing Burden of Atrial Fibrillation through Integrated Care in Primary Care: A Cost-Effectiveness Analysis.
Integrated care for patients with atrial fibrillation (AF) in primary care reduced mortality compared to usual care. We assessed the cost-effectiveness of this approach. Dutch primary care practices were randomised to provide integrated care for AF patients or usual care. A cost-effectiveness analysis was performed from a societal perspective with a 2-year time horizon to estimate incremental costs and Quality Adjusted Life Years (QALYs). A sensitivity analysis was performed, imputing missing questionnaires for a large group of usual care patients. 522 patients from 15 intervention practices were compared to 425 patients from 11 usual care practices. No effect on QALYs was seen, while mean costs indicated a cost reduction between €865 (95% percentile interval (PI) -€5730 to €3641) and €1343 (95% PI -€6534 to €3109) per patient per 2 years. The cost-effectiveness probability ranged between 36% and 54%. In the sensitivity analysis, this increased to 95%-99%. Results should be interpreted with caution due to missing information for a large proportion of usual care patients. The higher costs from extra primary care consultations were likely outweighed by cost reductions for other resources, yet this study doesn't give sufficient clarity on the cost-effectiveness of integrated AF care.


Synthesis and characterization of bio-compatible shape memory polymers with potential applications to endovascular embolization of intracranial aneurysms.
Intracranial aneurysms (ICAs) are focal dilations in the brain's arteries. When left untreated, ICAs can grow to the point of rupture, accounting for 50-80% of subarachnoid hemorrhage cases. Current treatments include surgical clipping and endovascular coil embolization to block circulation into the aneurysmal space for preventing aneurysm rupture. As for endovascular embolization, patients could experience aneurysm recurrence due to an incomplete coil filling or compaction over time. The use of shape memory polymers (SMPs) in place of conventional platinum coils could provide more control and predictability for mitigating these complications. This study was focused on characterization of an aliphatic urethane-based SMP to evaluate its potential as a novel biomaterial for endovascular embolization. Twelve compositions of the SMP were synthesized and their thermomechanical properties together with the shape recovery behavior were comprehensively investigated. Our results showed that the SMPs experienced a significant decrease in storage and loss moduli as heated above their glass transition temperatures (32.3-83.2 °C), and that all SMPs were thermally stable up to 265 °C. Moreover, the SMPs exhibited both composition-dependent stress relaxation and a decrease in elastic modulus during cyclic loading. The shape recovery time was less than 11 s for all SMP compositions, which is sufficiently short for shape changing during embolization procedures. Several candidate compositions were identified, which possess a glass transition temperature above body temperature (37 °C) and below the threshold of causing tissue damage (45 °C). They also exhibit high material strength and low stress relaxation behavior, suggesting their potential applicability to endovascular embolization of ICAs.


Pregnancy in Women with Adult Congenital Heart Disease.
Women with congenital heart disease are pursuing pregnancy in increasing numbers. Counseling about genetic transmission, medication management, maternal and fetal risks, and maternal longevity should be initiated well before pregnancy is considered. Although preconception medical and surgical optimization as well as coordinated multidisciplinary care throughout pregnancy decrease maternal and fetal risks, the rate of complications remains increased compared with the general population. Lesion-specific risk stratification and care throughout pregnancy further improve outcomes and decrease unnecessary interventions.


Radiographic appearance of nutrient canals in the region of the erupting permanent maxillary cuspid.
A retrospective radiographic search was made for nutrient canals situated immediately inferior to the incisal tip of the unerupted permanent maxillary cuspid. In this study, the structure was observed radiographically in 35.4% of the children between the ages of 6 and 10 years, with an apparently greater incidence among girls.


The impacts of adrenoleukodystrophy newborn screening on the evaluation of adrenal dysfunction in male children: An integrative literature review.
Adrenoleukodystrophy (ALD) is an x-linked genetic condition with a high risk of adrenal dysfunction recommended for newborn screening. This review aims to critically appraise and synthesize existing literature identifying the impacts of ALD newborn screening in the United States on the evaluation and treatment of adrenal dysfunction in male children. An integrative literature review was conducted using the Embase, PubMed, and CINAHL databases. English-language primary source studies published in the past decade and seminal studies were included. Twenty primary sources met the inclusion criteria, including five seminal studies. Three major themes emerged from the review: 1) prevention of adrenal crisis, 2) unexpected outcomes, and 3) ethical impacts. ALD screening increases disease identification. Serial adrenal evaluation prevents adrenal crisis and death; data is needed to establish predictive outcomes in ALD prognosis. Disease incidence and prognosis will become more apparent as states increasingly add ALD screening to their newborn panel. Clinicians need awareness of ALD newborn screening and state screening protocols. Families first learning of ALD through newborn screening results will require education, support, and timely referrals for appropriate care.


The SNMP/CD36 gene family in Diptera, Hymenoptera and Coleoptera: Drosophila melanogaster, D. pseudoobscura, Anopheles gambiae, Aedes aegypti, Apis mellifera, and Tribolium castaneum.
Sensory neuron membrane proteins (SNMPs) are membrane bound proteins initially identified in olfactory receptor neurons of Lepidoptera and are thought to play a role in odor detection; SNMPs belong to a larger gene family characterized by the human protein CD36. We have identified 12-14 candidate SNMP/CD36 homologs from each of the genomes of Drosophila melanogaster, D. pseudoobscura, Anopheles gambiae and Aedes aegypti (Diptera), eight candidate homologs from Apis mellifera (Hymenoptera), and 15 from Tribolium castaneum (Coleoptera). Analysis (sequence similarity and intron locations) suggests that the insect SNMP/CD36 genes fall into three major groups. Group 1 includes the previously characterized D. melanogaster emp (epithelial membrane protein). Group 2 includes the previously characterized D. melanogaster croquemort, ninaD, santa maria, and peste. Group 3 genes include the SNMPs, which fall into two subgroups referred to as SNMP1 and SNMP2. D. melanogaster SNMP1 (CG7000) shares both significant sequence similarity and five of its six intron insertion sites with the lepidopteran Bombyx mori SNMP1. The topological conservation of this gene family within the three major holometabolous lineages indicates that it predates the coleopteran and hymenoptera/dipera/lepidoptera split 300+ million years ago. The current state of knowledge of the characterized insect members of this gene family is discussed.


The Epidemiologic and Clinical Findings of Patients with Buerger Disease.
Buerger disease is a nonatherosclerotic peripheral arterial disease, which is mostly observed in young male smokers. Buerger disease is characterized by the observation of peripheral arterial occlusion by angiography. The condition may be caused by microembolization in the small-sized arteries of the distal extremities. Buerger disease is diagnosed based on the Shionoya's clinical diagnostic criteria, which include: (1) a history of smoking, (2) onset before the age of 50 years, (3) the presence of infrapopliteal arterial occlusions, (4) either upper limb involvement or phlebitis migrans, and (5) the absence of atherosclerotic risk factors other than smoking. Several studies have reported that oral bacterial infections (periodontitis) could activate the onset of Buerger disease. In this study, we report the epidemiologic and clinical manifestations of patients with Buerger disease. Fifty-eight patients who were surgically treated between July 1989 and June 2014 at Tokyo Medical and Dental University Hospital were enrolled in this study. All of the patients clinically diagnosed with Buerger disease based on Shionoya's clinical diagnostic criteria. Fifty-five male and 3 female patients were treated. The mean age of the patients was 48 years (range, 21-73 years). All of the patients were either smokers or had a history of smoking. The mean Brinkman index score was 780 (range, 150-1,640). Their mean age at the onset of Buerger disease was 38 years (range, 21-50). The arterial lesions extended to the femoral arteries in 25% of cases, to the iliac arteries in 8% and to the abdominal aorta and/or visceral arteries in 6% of cases. Upper limb involvement, including cyanosis, paleness, and gangrene, was obvious in 84% of patients, and phlebitis migrans was recognized in 34%. The lower extremities symptoms involved intermittent claudication in 23% of the patients, rest pain in 13% of the patients, and ulceration or gangrene in 64% of the patients. Fifteen patients had undergone surgical arterial reconstruction, 4 patients had received endovascular therapy, 33 patients had undergone lumbar sympathectomy and 8 patients had undergone thoracic sympathectomy. Twenty percent of the patients needed minor limb amputations, and 4% required major limb amputations. In the patients who were examined for their oral conditions, periodontitis corresponding to grades B (moderate periodontitis), C (severe periodontitis), and D (edentulous patients) was revealed in 31%, 56%, and 13% of the patients, respectively. More than half of the Buerger disease patients in this study were suffering from severe periodontitis. It is possible that not only the cessation of smoking, but also the improvement of periodontal care could improve the clinical symptoms related to Buerger disease.


Effectiveness of Administering a Mixture of Lactic Acid Bacteria to Control Salmonella ser. Enteritidis Infections in Broilers.
Non-typhoidal Salmonella spp. cause persistent asymptomatic infections in poultry. The consumption of Salmonella-infected poultry products is associated with food poisoning. One of the pathogens that causes such infections is Salmonella ser. Enteritidis (SE). Therefore, alternative measures are required for better control of salmonellosis and to reduce potential antibiotic use. Here, the efficacy of a mixture of lactic acid bacteria (LAB), formulated based on competitive exclusion, was evaluated. The LAB mixture was administered to 1- to 20-day-old chickens using different schemes; the chickens were then inoculated with an SE strain, which was previously identified to be prevalent in broiler breeder farms. Even with short-term administration, the group treated with LAB exhibited lower SE isolation levels in the spleen and cecal content and greater weight gain than that in the control group. This protective efficacy of LAB was retained even after two weeks without LAB administration. According to the results of animal experiments and field tests, evidence of SE infection was absent after treatment of the animals with the LAB formulation used in this study. Thus, this LAB mixture can be used as a potential strategy for protecting poultry farms from Salmonella contamination. This will also help reduce potential antibiotic use.


Circular RNA circTMEM45A Acts as the Sponge of MicroRNA-665 to Promote Hepatocellular Carcinoma Progression.
Mounting evidences indicate that circular RNAs (circRNAs) play vital roles in the development and progression of various cancers. However, the detailed functions and underlying mechanisms of circRNAs in hepatocellular carcinoma (HCC) remain largely unknown. The expression profile of circRNAs was screened by circRNA microarrays. Quantitative real-time PCR was used to determine the level-10 circRNAs selected from the top five upregulated (hsa_circ_0001955, hsa_circ_0001535, hsa_circ_0061395, hsa_circ_0000502, and hsa_circ_0066659) and top five downregulated circRNAs (hsa_circ_0046366, hsa_circ_0003418, hsa_circ_0026134, hsa_circ_0005692, and hsa_circ_0014130). The effects of circTMEM45A in HCC cells were studied both in vitro (in a Cell Counting Kit-8 assay, apoptosis analysis, and cell cycle assays) and in vivo (by means of tumor xenografts in nude mice). Luciferase reporter, RNA immunoprecipitation (RIP), and rescued assays were used to confirm the interactions between circTMEM45A, miR-665, and insulin growth factor 2 (IGF2). We found that the level of circTMEM45A was significantly upregulated in HCC and was positively correlated with clinicopathological features and poor prognosis of patients with HCC. Functionally, circTMEM45A promoted cell mobility in vitro, as well as in vivo tumorigenesis. Mechanistically, circTMEM45A acted as a miR-65 sponge to relieve the repressive effect of miR-665 on its target IGF2. Moreover, circTMEM45A was upregulated in serum exosomes from HCC patients. circTMEM45A promotes HCC progression through the miR-665/IGF2 axis and may serve as a novel diagnostic marker and target for treatment of HCC patients.


Transforming acidic coiled-coil proteins (TACCs) in human cancer.
Fine-tuned regulation of the centrosome/microtubule dynamics during mitosis is essential for faithful cell division. Thus, it is not surprising that deregulations in this dynamic network can contribute to genomic instability and tumorigenesis. Indeed, centrosome loss or amplification, spindle multipolarity and aneuploidy are often found in a majority of human malignancies, suggesting that defects in centrosome and associated microtubules may be directly or indirectly linked to cancer. Therefore, future research to identify and characterize genes required for the normal centrosome function and microtubule dynamics may help us gain insight into the complexity of cancer, and further provide new avenues for prognostic, diagnostics and therapeutic interventions. Members of the transforming acidic coiled-coil proteins (TACCs) family are emerging as important players of centrosome and microtubule-associated functions. Growing evidence indicates that TACCs are involved in the progression of certain solid tumors. Here, we will discuss our current understanding of the biological function of TACCs, their relevance to human cancer and possible implications for cancer management.


Operative indications in fractures of the calcaneus: problems of reduction and fixation.
In fractures of the calcaneus the fundamental importance of complete restoration of the architectural structure of the bone is stressed. To this end, the technique of internal fixation calls for a special device. Three different types of plate are described and the indications for each discussed.


Carbohydrate and lipid metabolism in Turner syndrome: effect of therapy with growth hormone, oxandrolone, and a combination of both.
To evaluate the effects of growth-promoting therapy on carbohydrate metabolism in girls with Turner syndrome, we determined glucose and insulin concentrations during oral glucose tolerance tests (OGTTs) at baseline and after 5 days, 2 months, and 12 months of treatment with growth hormone (GH), oxandrolone, or a combination of GH and oxandrolone, or after the same intervals with no therapy. Before therapy, subjects had a significantly greater glucose response during OGTT than published normal control values. There were no significant changes in mean fasting glucose, cholesterol, or triglyceride concentrations in any of the treatment groups. The integrated glucose concentrations rose significantly over baseline values in the oxandrolone group at 2 and 12 months and in the combination group at 5 days. There were significant increases in the mean integrated insulin concentrations at 2 and 12 months for the group receiving oxandrolone alone and at all three times for the group receiving combination therapy. Thus oxandrolone, alone or in combination with GH, had significant effects on carbohydrate metabolism in subjects with Turner syndrome, whereas GH alone did not.


Genome-wide analysis of glutamate receptor gene family in allopolyploid Brassica napus and its diploid progenitors.
Ionotropic glutamate receptors are ligand-gated nonselective cation channels that mediate neurotransmission in the central nervous system of animals. Plants possess homologous proteins called glutamate receptor-like channels (GLRs) which are involved in vital physiological processes including seed germination, long-distance signaling, chemotaxis, Ca2+ signaling etc. Till now, a comprehensive genome-wide analysis of the GLR gene family members in different economically important species of Brassica is missing. Considering the origin of allotetraploid Brassica napus from the hybridization between the diploid Brassica oleracea and Brassica rapa, we have identified 11, 27 and 65 GLR genes in B. oleracea, B. rapa and B. napus, respectively showing an expansion of this gene family in B. napus. Chromosomal locations revealed several tandemly duplicated GLR genes in all the three species. Moreover, the gene family expanded in B. napus after allopolyploidization. The phylogenetic analysis showed that the 103 GLRs are classified into three main groups. The exon-intron structures of these genes are not very conserved and showed wide variation in intron numbers. However, protein sequences are much conserved as shown by the presence of ten short amino acid sequence motifs. Predicted cis-acting elements in 1 kb promoters of GLR genes are mainly involved in light, stress and hormone responses. RNA-seq analysis showed that in B. oleracea and B. rapa, some GLRs are more tissue specific than others. In B. napus, some GLRs are downregulated under cold stress, while others are upregulated. In summary, this bioinformatic study of the GLR gene family of the three Brassica species provides evidence for the expansion of this gene family in B. napus and also provided useful information for in-depth studies of their biological functions in Brassica.


Solid-state NMR measurements of the kinetics of the interaction between phospholamban and Ca2+-ATPase in lipid bilayers.
Phospholamban (PLB) is a small transmembrane protein that regulates calcium transport across the sarcoplasmic reticulum (SR) of cardiac cells via a reversible inhibitory interaction with Ca2+-ATPase. In this work solid-state NMR methods have been used to investigate the dynamics of the inhibitory association between PLB and Ca2+-ATPase. Skeletal muscle Ca2+-ATPase was incorporated into phosphatidylcholine membranes together with a ten-fold excess of a null-cysteine mutant of PLB labelled with 13C at Leu-44 in the transmembrane domain ([alpha-13C-L44]AAA-PLB). In these membranes the PLB variant was found to partially inhibit Ca2+-ATPase by reducing the affinity of the enzyme for calcium. Cross-polarization magic angle spinning (CP-MAS) 13C NMR spectra of the membranes exhibited a signature peak from [alpha-13C-L44]AAA-PLB at 56 ppm. Changes in the intensity of the peak were observed at different temperatures, which was diagnostic of direct interaction between [alpha-13C-L44]AAA-PLB and Ca2+-ATPase. Measurements of dipolar couplings between the 13C label and neighbouring protons were analysed to show that the mean residency time for the association of AAA-PLB with Ca2+-ATPase was on the order of 2.5 ms at temperatures between 0 degrees C and 30 degrees C. This new NMR approach will be useful for examining how the association of the two proteins is affected by physiological stimuli such as kinases and the elevation of calcium concentration.


Diverse food in urban gardens in the promotion of food and nutrition security in Brazil: a review.
Food and nutrition security can be supported by an urban garden. The present study comprises a critical reflection on the difficulty of producing food in urban gardens in Brazil and shows the potential of food production and the obstacles to its expansion. In addition, issues related to the agroecological management of gardens are addressed and suggestions are made to improve the proposed public policies. Urban gardens are multifunctional and have social, economic and environmental impacts. They are strategically important for supporting low-income families and urban development. Through urban gardens, diverse foods and quality foods can be produced for self-consumption. This review highlights the importance of generating detailed information on urban gardens in Brazil to support policies aimed at this sector. Long-term and multidisciplinary studies are needed to evaluate the relationship between food production in urban gardens and household food and nutrition security. This approach revealed a lack of information on the amount of food produced by Brazilians in their gardens and consumed by the household. In addition, there is little information on the management of production. There is a gap relating to the impact of food produced in urban gardens and the prevalence of food and nutrition security. © 2019 Society of Chemical Industry.


Parasympathetic and sympathetic alterations of Mobitz type II heart block.
This study examined the effects of changes in parasympathetic and sympathetic tone on the cycle length at which Mobitz type II second degree atrioventricular (AV) block occurred. Four patients who had electrocardiographic evidence of type II AV block and confirmation of block in the His-Purkinje system during electrophysiologic study were evaluated. These patients received intravenous atropine (1.0 to 2.4 mg), propranolol (0.15 mg/kg body weight) or isoproterenol (1 and 2 micrograms/min) alone or in combination. In two of three patients receiving propranolol, the atrial pacing cycle length at which 1:1 His-Purkinje conduction occurred was prolonged relative to control (from 360 to 470 ms and 440 to 590 ms, respectively). In contrast, atropine in the presence of beta-adrenergic blockade shortened the cycle length at which 1:1 His-Purkinje conduction occurred in three of four patients receiving the drug (470 to 390, 630 to 570 and 590 to 560 ms, respectively). Isoproterenol also improved His-Purkinje conduction in the one patient receiving this drug. No agent affected the duration of the HV interval during spontaneous sinus rhythm or right atrial pacing. Thus, drugs that alter autonomic tone influence abnormal His-Purkinje conduction minimally during sinus rhythm but, importantly, may modulate the atrial pacing cycle length at which type II AV block occurs.


Medication counseling for the elderly: effects on knowledge and compliance after hospital discharge.
The findings from the instruments used in this study and the additional qualitative data of the personal interviews provide information helpful to the nurse's understanding of medication knowledge and compliance patterns in older persons. Investigations that study older persons over time are needed to identify how behaviors change. Such studies would also be helpful in identifying self-care behaviors learned over extended periods of time. It may also be helpful to investigate knowledge and compliance behaviors in the home setting, where the environment may be more conducive to learning. With the patient assuming more and more responsibility for self-care, it is imperative that professionals explore all opportunities to assist patients in acquiring the skills essential to promoting their own well-being.


Monoamine oxidase A genotype, childhood trauma, and subclinical atherosclerosis: a twin study.
A functional promoter polymorphism in the monoamine oxidase A (MAOA) gene has been implicated in neuropsychiatric disorders and also moderates the association between early-life stress and mental disorders, which often co-occur with cardiovascular disease. No study has examined the relationship between MAOA genotype, childhood trauma, and subclinical atherosclerosis. The objective of this investigation was to examine whether childhood trauma moderates the association between MAOA genotype and subclinical atherosclerosis. A sample including 289 middle-aged male twin pairs was studied. Subclinical atherosclerosis was assessed by brachial flow-mediated dilation (FMD) using ultrasound. Childhood trauma, before age 18 years, was measured with the Early Trauma Inventory and included physical, emotional, and sexual abuse as well as general trauma. Generalized estimating equation models were used to test the main and interactive effects of the MAOA genotype and each domain of childhood trauma on FMD, adjusting for known risk factors. General trauma was the most prevalent childhood trauma (28.4%), followed by physical abuse (25.0%), emotional abuse (19.4%), and sexual abuse (11.6%). MAOA genotype was not associated with any domain of childhood trauma. There was no significant evidence for a main effect for the MAOA genotype (β = .02, p = .82) or childhood trauma (.005 < β < .10, p > .54) FMD. However, a significant interaction was observed between MAOA genotype and physical (β interaction = .37, p = .026) or emotional abuse (β interaction = .43, p = .025) on subclinical atherosclerosis. Childhood trauma modulates the impact of MAOA variant on subclinical atherosclerosis, independent of traditional cardiovascular risk factors.


MiR-145 silencing promotes steroid-induced avascular necrosis of the femoral head repair via upregulating VEGF.
To investigate the role of miR-145 silencing in the expression of vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), B-cell lymphoma-2 (Bcl-2), BCL2-Associated X(bax) and caspase-3 in avascular necrosis of femoral head (ANFH). A total of 12 healthy wild-types (the control group) and 12 miR-145 knock-out (miR-145-/-) (the experimental group) adult New Zealand white rabbits were selected to construct ANFH model with a steroid. Four weeks later, immunohistochemistry, qRT-PCR and Western blot were performed to measure the VEGF, bFGF, Bcl-2, bax, caspase-3, β-catenin as well as c-Myc expression. Terminal-deoxynucleotidyl transferase mediated nick end labeling (TUNEL) staining analysis was used to detect the apoptosis of bone cells in each group. Compared with the control group, the expression of VEGF, bFGF, Bcl-2, β-catenin and c-Myc in the miR-145-/- group raised (p<0.05). Moreover, the expression level of bax and caspase-3 significantly decreased in the miR-145-/- group (p<0.05). TUNEL staining showed decreased apoptosis in the miR-145-/- group. MiR-145 silencing promotes bone repair of ANFH via upregulating VEGF, bFGF and inhibiting the bone cells apoptosis through Wnt/β-catenin pathway.


Tools to assess employment readiness for colorectal cancer survivors: A scoping review.
The ability to return to work and remain at work is an important recovery milestone after a cancer diagnosis. With the projected number of colorectal cancer patients of working age likely to increase, it is important to identify when a person is ready to resume work. There are many employment-related tools available to help people return to work after injury or illness; however, it is unknown which may be suitable for a person with colorectal cancer. To identify tools related to employment readiness in colorectal cancer survivors and to chart the relevant factors of employment assessed by these tools. Literature searches were performed in PubMed, CINAHL, Embase and Medline, the Cochrane library and PsycINFO using search terms around cancer, survivorship and employment to identify all peer-reviewed articles published in English up to June 2022. Thirty-five studies used a total of 77 tools focused on assessing employment issues experienced by people with cancer in general. Four tools were used with colorectal cancer survivors. None considered all relevant employment-related factors for colorectal cancer survivors. Tools used to identify return-to-work and remain-at-work were not specific to colorectal cancer. There are a range of existing tools that collate some, but not all, of the domains and outcome criteria required to meet the employment needs of colorectal cancer survivors. To optimize work outcomes for the working colorectal cancer population, a specified tool is warranted.


Description and validation of an improved method to feed solitary bees (Osmia spp.) known amounts of pesticides.
Pesticide exposure is an important driver of bee declines. Laboratory toxicity tests provide baseline information on the potential effects of pesticides on bees, but current risk assessment schemes rely on one species, the highly social honey bee, Apis mellifera, and there is uncertainty regarding the extent to which this species is a suitable surrogate for other pollinators. For this reason, Osmia cornuta and Osmia bicornis have been proposed as model solitary bee species in the EU risk assessment scheme. The use of solitary bees in risk assessment requires the development of new methodologies adjusted to the biology of these species. For example, oral dosing methods used with honey bees cannot be readily applied to solitary bees due to differences in feeding behaviour and social interactions. In this study, we describe the "petal method", a laboratory feeding method, and validate its use in acute and chronic exposure oral tests with Osmia spp. We conducted five experiments in which we compared the performance of several artificial flowers combining visual and olfactory cues against the petal method, or in which variations of the petal method were confronted. We then use the results of these experiments to optimize the feeding arenas and propose standardized methods for both acute and chronic exposure tests. The petal method provides high levels of feeding success, thus reducing the number of bees needed. It works with a wide variety of petal species and with both female and male Osmia spp., thus ensuring reproducibility across studies. To validate the use of the petal method in ecotoxicology tests, we assess the toxicity of a standard reference insecticide, dimethoate, in O. cornuta adults and determine LD50 values for this species. The petal method should facilitate the inclusion of solitary bees in risk assessment schemes therefore increasing the protection coverage of pesticide regulation.


Arachidonic acid and related methyl ester mediate protein kinase C activation in intact platelets through the arachidonate metabolism pathways.
Unlike unsaturated fatty acids, which almost fully activated purified brain protein kinase C in a phosphatidylserine- and Ca2(+)-free reaction, related methyl esters were poorly active in vitro. In contrast, methyl arachidonate was revealed to be as potent as arachidonic acid in activating protein kinase C in intact platelets. Arachidonic acid-mediated activation peaked at 20 s while methyl arachidonate-mediated activation plateaued at 2 min when both lipids were added at 50 microM. At concentrations higher than 0.3 mM, all tested unsaturated fatty acids and related methyl esters were weak activators of the enzyme, with the exception of linolenic acid and methyl linolenate which evoked strong enzyme activation. However, inhibitors of arachidonate metabolism blocked both arachidonic-acid and methyl-arachidonate-induced responses. At 5 microM arachidonic acid and methyl arachidonate, protein kinase C activation was due to a cyclooxygenase product(s) whereas at 50 microM the lipoxygenase pathway was mostly involved in the reaction. Therefore, arachidonic acid and its methyl ester activate protein kinase C in platelets mainly through action of their metabolites and eicosanoid synthesis. It is suggested that such indirect protein kinase C activation may account for the tumor-promoting activity of unsaturated fatty acids and related methyl esters.


Tourettism as clinical presentation of Huntington's disease with onset in childhood.
Infantile Huntington's disease (HD) shows a wide clinical heterogeneity. Here we describe the case of a child affected by HD who showed unusual neurological features consistent with tourettism. The absence of family history and persisting normal magnetic resonance imaging (MRI) results long after the onset of symptoms delayed the diagnosis of the disease. An MRI exam performed 26 months after disease onset disclosed bilateral atrophy in the putamen, suggesting HD. The diagnosis was confirmed by genetic analysis. The present report underlines the need to consider HD in childhood cases of unusual and even unfamiliar progressive movement disorders.


Acute myocardial infarction caused by coronary embolism from infective endocarditis.
Identifying an acute myocardial infarction caused by a non-atherosclerotic process can have consequences on the short- and long-term management of the disease. In the first case reported, a 39-year-old woman with a history of hypertension, diabetes, end-stage renal disease, deep vein thrombosis, and a recent hospitalization for staphylococcal bacteremia presented to the Emergency Department (ED) with acute onset of chest pain and shortness of breath. Her electrocardiogram (ECG) showed findings of an ST-segement elevation lateral wall acute myocardial infarction (AMI). The patient's condition worsened in the ED, and thrombolytic therapy was initiated. The patient subsequently had a coronary catheterization that illustrated an irregular mitral valve and abrupt occlusions in the left anterior descending artery, suggestive of coronary embolism from a mitral valve source. This patient was later treated with intravenous antibiotics and mitral valve replacement. In the second case reported, a 56-year-old man with a history of hypertension, diabetes, and end-stage renal disease presented to the ED with shortness of breath, fever, and chest pain. His ECG was significant for ST-segment elevation in the lateral leads, suggestive of an AMI. This patient had a history of positive blood cultures in a previous admission as well as an echocardiogram revealing an aortic valve vegetation. Given the high suspicion for an infective endocarditis causing an embolic event that in turn led to the myocardial infarction, thrombolytics were withheld in the ED and the patient was transported for coronary catheterization. The coronary angiogram demonstrated abrupt cutoffs at the distal left anterior descending artery and distal left posterior descending artery suggestive of an embolic occlusion of these vessels. He was subsequently treated with intravenous antibiotics and aortic valve replacement. These two cases illustrate the importance of broadening our differential in the causes of AMI. In these cases, the recognition of an embolic event from infective endocarditis as the cause of the acute coronary syndrome allowed physicians to direct their interventions to optimize the appropriate care for each patient.


Safety of perioperative ketorolac administration in pediatric appendectomy.
Recent studies in adults undergoing gastrointestinal surgeries show an increased rate of complications with the use of ketorolac. This calls into question the safety of ketorolac in certain procedures. We sought to evaluate the impact of perioperative ketorolac administration on outcomes in pediatric appendectomy. The Pediatric Health Information System database was queried for patients aged 5-17 y with a primary diagnosis of appendicitis and a primary procedure of appendectomy during the period 2010-2014. Patients with procedures suggesting incidental appendectomy, those records with data quality issues, deaths, and extracorporeal membrane oxygenation were excluded. Variables recorded included age, sex, race, ethnicity, discharge year, complex chronic conditions, geographic region, intensive care unit admission, mechanical ventilation, and whether appendicitis was coded as complicated. The exposure variable was ketorolac administration on the day of or day after operation. The primary outcomes of interest were any surgical complications during the initial encounter, postoperative length of stay (LOS), total cost for the initial visit, any readmission to ambulatory, observation, or inpatient status within 30 d, and readmission with a diagnosis of peritoneal abscess or other postoperative infection or with transabdominal drainage performed. A total of 78,926 patients were included in the analysis cohort. Mean age was 11.4 y (standard deviation 3.3 y), the majority were males (61%), White (70%), and non-Hispanic (65%). Few had a complex chronic condition (3%) or required mechanical ventilation (2%) or an intensive care unit admission (1%). Patients with complicated appendicitis comprised 28% of the cohort. Most (73%) received ketorolac on postoperative day 0-1; those with complicated appendicitis were more likely to receive ketorolac. In all, 2.6% of the cohort had a surgical complication during the index visit, 4.3% were readmitted within 30 d, and 2% had a postoperative infection or transabdominal drainage (1% in the uncomplicated group and 5% in the complicated group). Median postoperative LOS was 1 d and mean cost was $9811 ± $9509. On bivariate analysis, ketorolac administration was associated with a decrease in same-visit surgical complications (P = 0.004) and cost ($459 decrease, P < 0.001) but was not associated with readmission, postoperative LOS, or postoperative infection. On multivariate analysis, ketorolac administration was associated with a significant decrease in any complication (adjusted odds ratio 0.89, 95% confidence interval 0.80-0.99) and cost (analysis of variance P < 0.001) but was not associated with readmission, postoperative LOS, or postoperative infection. Based on a large, contemporary data set from children's hospitals, ketorolac administration in the immediate postoperative period after appendectomy for appendicitis is common and was not associated with an increase in postoperative LOS, postoperative infection, or any-cause 30-d readmission. Ketorolac was, however, independently associated with a lower overall rate of postoperative complications and cost in this population.


Early antibiotic treatment in acute necrotising pancreatitis.
Despite improvements in surgical treatment and intensive care, mortality from severe acute pancreatitis remains high. We have carried out a randomised study of 60 consecutive patients with alcohol-induced necrotising pancreatitis to find out whether early antibiotic treatment can improve outcome. 30 patients were assigned cefuroxime (4.5 g/day intravenously) from admission. In the second group, no antibiotic treatment was given until clinical or microbiologically verified infection or after a secondary rise in C-reactive protein. The inclusion criteria were C-reactive protein concentration above 120 mg/L within 48 h of admission and low enhancement (< 30 Hounsfield units) on contrast-enhanced computed tomography. There were more infectious complications in the non-antibiotic than in the antibiotic group (mean per patient 1.8 vs 1.0, p = 0.01). The most common cause of sepsis was Staphylococcus epidermidis; positive cultures were obtained from pancreatic necrosis or the central venous line in 14 of 18 patients with suspected but blood-culture-negative sepsis. Mortality was higher in the non-antibiotic group (seven vs one in the antibiotic group; p = 0.03). Four of the eight patients who died had cultures from pancreatic necrosis positive for Staph epidermidis. We conclude that cefuroxime given early in necrotising pancreatitis is beneficial and may reduce mortality, probably by decreasing the frequency of sepsis.


Analysis of the causes of false negative cytology reports on breast cancer fine needle aspirates.
Forty-six (2.9%) false negative reports were recorded among adequate fine needle aspirates from 1609 consecutive histologically proven carcinomas, observed from 1991 to 1993. False negatives were more frequent among younger women (< 40 years = 7.1; 40-49 years = 4.0; 50-59 years = 3.6; 60-69 years = 1.7; > 69 years = 1.5%), lobular invasive subtypes (5.4%), and smaller tumours (pT1a = 4.2; pT1b = 7.6; pT1c = 1.9; pT2 = 2.1; pT3-4 = 1.5%). The latter findings is probably ascribable to better differentiation and less precise sampling of small non-palpable tumours. No significant association was found between the false negative rate and the sampler's or reader's skill and experience. The former finding may be ascribed to the wide use of sonography guided aspiration, even for palpable masses, and the latter to the fact that readers were highly experienced and undergo periodic quality control of individual performance. False negatives were reclassified at reviews as true false negatives, reading errors or inadequates in 27, 11, and eight cases, respectively. The observed findings suggest that in most cases cytological faults were due to the absence of cytological atypia in cells sampled from well differentiated tumours, rather than to misinterpretation or sampling from adjacent normal tissues.


ROS fine-tunes the function and fate of immune cells.
The redox state is essential to the process of cell life, which determines cell fate. As an important signaling molecule of the redox state, reactive oxygen species (ROS) are crucial for the homeostasis of immune cells and participate in the pathological processes of different diseases. We discuss the underlying mechanisms and possible signaling pathways of ROS to fine-tune the proliferation, differentiation, polarization and function of immune cells, including T cells, B cells, neutrophils, macrophages, myeloid-derived inhibitory cells (MDSCs) and dendritic cells (DCs). We further emphasize how excessive ROS lead to programmed immune cell death such as apoptosis, ferroptosis, pyroptosis, NETosis and necroptosis, providing valuable insights for future therapeutic strategies in human diseases.


Long noncoding RNA HULC in acute ischemic stroke: Association with disease risk, severity, and recurrence-free survival and relation with IL-6, ICAM1, miR-9, and miR-195.
This study aimed to evaluate the clinical role of long noncoding RNA (lncRNA) HULC in acute ischemic stroke (AIS). LncRNA HULC in plasma samples from 215 first episode AIS patients and 215 age/gender-matched non-AIS controls was detected by reverse transcriptional-quantitative polymerase chain reaction (RT-qPCR). Then, in AIS patients, interleukin-6 and intercellular adhesion molecule 1 (ICAM1), as well as microRNA (miR) target of lncRNA HUCL (miR-9 and miR-195), were detected by enzyme-linked immunosorbent assay and RT-qPCR, respectively. Disease severity was assessed by National Institution of Health stroke scale (NIHSS) score. AIS recurrence or death was recorded, and recurrence-free survival (RFS) was calculated. LncRNA HULC was increased in AIS patients compared to non-AIS controls (P < .001), and receiver operating characteristic curve showed that it was correlated with increased AIS risk (area under curve: 0.876, 95% confidence interval: 0.843-0.908). Meanwhile, lncRNA HULC was positively correlated with NIHSS score (P < .001, r = .456), interleukin-6 (P < .001, r = .275) and ICAM1 (P < .001, r = .383), whereas negatively correlated with miR-9 (P < .001, r = -.438) but not miR-195 (P = .205, r = -.087) in AIS patients. Additionally, miR-9 was negatively correlated with NIHSS score (P < .001, r = -.335), interleukin-6 (P = .001, r = -.231), and ICAM1 (P < .001, r = -.280), while miR-195 was only negatively associated with NIHSS score (P = .041, r = -.139) in AIS patients. Moreover, lncRNA HULC high expression predicted worse RFS (P = .013) in AIS patients. LncRNA HULC is correlated with higher AIS risk, increased disease severity and worse prognosis in AIS patients. Meanwhile, it associates with higher IL-6, elevated ICAM1, and lower miR-9 AIS patients.


Development of a tool to assess students' perceptions of respectful maternity care.
To develop and test a tool to measure Bachelor of Nursing students' perceptions towards respectful maternity care in Nepal, a lower-middle income country. A cross-sectional design was used. Phases of tool development included item generation, expert review for content validity testing, and psychometric testing. The draft tool had 42 items on a 5-point Likert response scale of 1 = strongly disagree to 5 = strongly agree. Psychometric testing included dimensionality, internal consistency, and test-retest reliability. A t-test assessed mean score differences between students who had witnessed or not witnessed disrespect and abuse. Two medical colleges in Chitwan, Nepal PARTICIPANTS: Undergraduate Bachelor of Nursing students (n = 171) undertaking their midwifery clinical practicum were invited to complete the online survey. Principal component analysis generated three factors: Respectful Care, Safety and Comfort, and Supportive Care and explained 37.44% of the variance. The 18-item tool demonstrated good internal reliability (Cronbach's alpha of 0.81). The mean total scale score was 71.23 (SD 7.47, range 52-88 out of 90). Pearson's correlation coefficient confirmed test-retest reliability at one week (r = 0.91, p <0.001). The magnitude of difference in mean scores between those who had witnessed or not witnessed disrespectful and abusive care was very small (η2 = 0.04). The new Student Perceptions of Respectful Maternity Care tool is the first valid and reliable measure of students' perceptions of respectful maternity care. Validation of the newly developed tool in other low- and middle-income countries is recommended. Measuring students' perceptions provides information to educators on how best to enhance students' understanding and provision of respectful care to women.


Genetic differences in response properties of rostral ventromedial medulla neurons to the μ-opioid receptor agonist DAMGO in mouse inbred strains.
Opioid sensitivity varies among individuals. Although opioids can act partly in the rostral ventromedial medulla (RVM), which has a major role in pain perception, individual differences in the functions of the RVM in response to opioids have not been elucidated. Pain-related behavior among inbred mouse strains may reflect individual differences in sensitivity to pain. We therefore investigated the changes in action potentials of RVM neurons in response to opioid in different mouse strains. Two inbred strains of mice (A/J and CBA/J) were used. Their behavior to noxious stimuli was measured after intracerebroventricular injection of the μ-opioid receptor agonist, DAMGO. Using an in vivo extracellular recording technique, action potentials from single RVM neurons and their functional type (ON-like, OFF-like, or NEUTRAL-like cell) were identified. Evoked responses of the RVM neurons to noxious stimuli were recorded before and after DAMGO administration. The behavioral study showed that the dose-dependent antinociceptive effect in the A/J strain was significantly stronger than in the CBA/J strain. The electrophysiological study showed that the number of inhibitory OFF-like cells in A/J mice was significantly larger than in CBA/J mice (P<0.01), and that the evoked responses of neurons of A/J mice were inhibited significantly more than in CBA/J mice both for ON-like and OFF-like cells (P<0.01). The strain differences in the physiological properties of RVM neurons corresponded to the behavioral strain differences. Genetic differences may contribute to the interindividual variation seen in opioid-induced analgesia.


Chronic Migraine: Diagnosis and Management.
Migraine is the second leading cause of years lived with disability. Patients with chronic migraine (CM) face enormous barriers in accessing care and in receiving an accurate diagnosis and appropriate treatment. This article reviews the following: epidemiology, definition, pathophysiology, medication overuse, and acute and preventive treatment.


Delayed traumatic purulent pericarditis with cardiac tamponade - A rare case report.
Thoracic trauma often results in immediate or delayed hemorrhage. There are few cases of purulent pericarditis with pericardial tamponade reported in the literature. If a devastating complication develops several weeks following blunt thoracic trauma, the causal relationship with the thoracic trauma event is less evident. As such, accurate diagnosis and subsequent effective treatment implementation is likely to be delayed. Herein, we present the case of a 46-year-old male patient with delayed purulent pericarditis that led to cardiac tamponade 2 weeks after the initial trauma.


A family of conjugate gradient methods for large-scale nonlinear equations.
In this paper, we present a family of conjugate gradient projection methods for solving large-scale nonlinear equations. At each iteration, it needs low storage and the subproblem can be easily solved. Compared with the existing solution methods for solving the problem, its global convergence is established without the restriction of the Lipschitz continuity on the underlying mapping. Preliminary numerical results are reported to show the efficiency of the proposed method.


Branching Ratios of Aliphatic Amines + OH Gas-Phase Reactions: A Variational Transition-State Theory Study.
A theoretical study on the mechanism of the OH + aliphatic amines reactions is presented. Geometry optimization and frequencies calculations have been performed at the BHandHLYP/6-311++G(2d,2p) level of theory for all stationary points. Energy values have been improved by single-point calculations at the above geometries using CCSD(T) and the same basis set. All the possible hydrogen abstraction channels have been modeled, involving the rupture of C-H and N-H bonds. It was found that as the temperature decreases the contributions of the channels involving NH sites to the overall reaction also decrease, suggesting that for upper layers in the troposphere these channels become less important. Their percentage contributions to the overall reaction, at 298 K, were found to be about 20%, 2%, and 48% for methylamine, ethlylamine, and dimethylamine, respectively.


A systematic review of biomarkers in the diagnosis of infective endocarditis.
Timely diagnosis of bacterial infective endocarditis (IE) is crucial, as mortality remains high in this severe bacterial infection, currently without any distinct biological markers. Our goal was to evaluate potential diagnostic biomarkers by reviewing current literature. The MEDLINE, Embase and Scopus databases were searched for articles published from 1980 through June 2015 restricted to English, Norwegian, Danish and Swedish. Eighteen studies qualified, providing a review of the most promising candidates for future studies. Several studies are inconclusive, since they are characterized by using improper control groups. Patients with IE have bacteremia, and control groups should therefore be patients with bacteremia without IE. Based on current research, N-terminal-pro-B-type natriuretic peptide (NT-proBNP) alone or in combination with Cystatin C (Cys C), lipopolysaccharide-binding protein (LBP), troponins, aquaporin-9 (AQP9), S100 calcium binding protein A11 (S100A11), E-selectin (CD62E) and VCAM-1 (CD54) and interleukin-6 (IL-6) are potential biomarkers for future studies.


Associations of New-Onset Atrial Fibrillation With Risks of Cardiovascular Disease, Chronic Kidney Disease, and Mortality Among Patients With Type 2 Diabetes.
Atrial fibrillation (AF) frequently occurs in patients with type 2 diabetes (T2D); however, the longitudinal associations of new-onset AF with risks of adverse health outcomes in patients with T2D remain unclear. In this study, we aimed to determine the associations of new-onset AF with subsequent risks of atherosclerotic cardiovascular disease (ASCVD), heart failure, chronic kidney disease (CKD), and mortality among patients with T2D. We included 16,551 adults with T2D, who were free of cardiovascular disease (CVD) and CKD at recruitment from the UK Biobank study. Time-varying Cox regression models were used to assess the associations of incident AF with subsequent risks of incident ASCVD, heart failure, CKD, and mortality. Among the patients with T2D, 1,394 developed AF and 15,157 remained free of AF during the follow-up. Over median follow-up of 10.7-11.0 years, we documented 2,872 cases of ASCVD, 852 heart failure, and 1,548 CKD and 1,776 total death (409 CVD deaths). Among patients with T2D, those with incident AF had higher risk of ASCVD (hazard ratio [HR] 1.85; 95% CI 1.59-2.16), heart failure (HR 4.40; 95% CI 3.67-5.28), CKD (HR 1.68; 95% CI 1.41-2.01), all-cause mortality (HR 2.91; 95% CI 2.53-3.34), and CVD mortality (HR 3.75; 95% CI 2.93-4.80) compared with those without incident AF. Patients with T2D who developed AF had significantly increased risks of developing subsequent adverse cardiovascular events, CKD, and mortality. Our data underscore the importance of strategies of AF prevention to reduce macro- and microvascular complications in patients with T2D.


Bacterial expression and one-step purification of an isotope-labeled heterotrimeric G-protein alpha-subunit.
Heterologous expression systems are often employed to generate sufficient quantities of isotope-labeled proteins for high-resolution NMR studies. Recently, the interaction between the prodomain region of subtilisin and an active, mutant form of the mature enzyme has been exploited to develop a cleavable affinity tag fusion system for one-step generation and purification of full-length soluble proteins obtained by inducible prokaryotic expression. As a first step towards applying high-resolution NMR methods to study heterotrimeric G-protein alpha-subunit (G(alpha)) conformation and dynamics, the utility of this subtilisin prodomain fusion system for expressing and purifying an isotope-labeled G(alpha) chimera (approximately 40 kDa polypeptide) has been tested. The results show that a prodomain fused G(alpha) chimera can be expressed to levels approaching 6-8 mg/l in minimal media and that the processed, mature protein exhibits properties similar to those of G(alpha) isolated from natural sources. To assay for the functional integrity of the purified G(alpha) chimera at NMR concentrations and probe for changes in the structure and dynamics of G(alpha) that result from activation, 15N-HSQC spectra of the GDP/Mg2+ bound form of G(alpha) obtained in the absence and presence of aluminum fluoride, a well known activator of the GDP bound state, have been acquired. Comparisons of the 15N-HSQC spectra reveals a number of changes in chemical shifts of the 1HN, 15N crosspeaks that are discussed with respect to expected changes in the protein conformation associated with G(alpha) activation.


Temporal relationship between awakening and seizure onset in nocturnal partial seizures.
Clinical awakening can be seen just before or after seizure onsets. In this study we determined the time between onset of seizures and awakening in patients with frontal lobe epilepsy (FLE) and temporal lobe epilepsy (TLE). Sixty-eight patients who underwent video-EEG monitoring with simultaneous PSG were retrospectively examined. TLE or FLE patients having seizures during sleep were included. Seizure onset and awakening onset were marked according to clinical and electrophysiological features. The duration between awakening and seizure onset was compared in patients with TLE and FLE. Twenty-five patients who had been diagnosed with TLE (17) or FLE (8) had a total of 75 seizures during sleep. All seizures except one, occurred during NREM sleep in both TLE and FLE patients. The seizure onsets were before awakening in 49 seizures (FLE: 20, TLE: 29) and the awakening preceded the seizure onsets in 12 seizures (FLE: 3, TLE: 9). The duration between seizure onset and the awakening was shorter in FLE, either in seizures with preceding awakening or not (p=0.014, p=0.015). Awakening was mostly seen after onset of seizures rather than before, especially in TLE. But in patients with FLE the duration between seizure onset and awakening was shorter. The localization of epileptic activity may play a role for the timing of awakening mechanisms during nocturnal partial seizures.


Intestinal absorption of arachidonic acid in experimental azotemia.
The effect of renal failure (RF) on intestinal absorption of dietary fatty acids is not known. We studied the intestinal absorption of arachidonic acid (AA) in rats with experimental short-term (2 weeks post-subtotal nephrectomy) and long-term (5-6 weeks post-subtotal nephrectomy) RF. The results were compared with those obtained in sham-operated animals on liberal food intake (NL) and in those pair-fed (PF) with the respective RF groups. In vivo perfusion and in vitro incubation experiments were performed at a wide range of AA concentrations. The rates of AA transport determined both in vivo and in vitro were significantly lower in the short-term RF group than those found in the NL controls and the PF animals who showed comparable values. In contrast animals with long-term RF exhibited an increased rate of AA transport as compared with the respective controls. The observed changes in the transport rates appeared to parallel directional changes in mucosal mass which was reduced in animals with short-term RF and restored in those with long-term RF.


Enhanced drought tolerance in transgenic Leymus chinensis plants with constitutively expressed wheat TaLEA3.
Leymus chinensis is an important grassland perennial grass. However, its drought tolerance requires to be improved. LEA (late embryogenesis abundant) genes are believed to confer resistance to drought and water deficiency. Using Agrobacterium-mediated transformation, a wheat LEA gene, TaLEA(3), was integrated into L. chinensis. The transgenic lines showed enhanced growth ability under drought stress during which transgenic lines had increased the relative water content, leaf water potential, relative average growth rate, but decreased the malondialdehyde content compared with the non-transgenic plant. Thus, transgenic breeding is an efficient approach to enhance drought tolerance in L. chinensis.


Synaptic vesicles interchange their membrane proteins with a large surface reservoir during recycling.
During recycling of synaptic vesicles (SVs), the retrieval machinery faces the challenge of recapturing SV proteins in a timely and precise manner. The significant dilution factor that would result from equilibration of vesicle proteins with the much larger cell surface would make recapture by diffusional encounter with the endocytic retrieval machinery unlikely. If SV proteins exchanged with counterparts residing at steady state on the cell surface, the dilution problem would be largely avoided. In this scenario, during electrical activity, endocytosis would be driven by the concentration of a pre-existing pool of SVs residing on the axonal or synaptic surface rather than the heavily diluted postfusion vesicular pool. Using both live cell imaging of endogenous synaptotagmin Ia (sytIa) as well as pHluorin-tagged sytIa and VAMP-2, we show here that synaptic vesicle proteins interchange with a large pool on the cell axonal surface whose concentration is approximately 10-fold lower than that in SVs.


Identification of the gene and the protein of RNA polymerase II subunit 9 (Rpb9) from the fission yeast Schizosacharomyces pombe.
Both the rpb9 gene and its cDNA encoding the subunit 9 of RNA polymerase II were cloned from the fission yeast Schizosaccharomyces pombe. From the DNA sequences, Rpb9 was predicted to consist of 113 amino acid residues with a molecular mass of 13,175. S. pombe Rpb9 is 47, 40 and 36% identical in amino acid sequence to the corresponding subunits from Saccharomyces cerevisiae, human and Drosophila melanogaster, respectively. Previously, we failed to detect Rpb9 in the purified RNA polymerase II by amino-terminal micro-sequencing of proteolytic fragments of subunits separated by SDS-gel electrophoresis. After Western blot analysis using antibodies raised against the protein product of the newly isolated rpb9 gene, we found that the purified RNA polymerase II contains Rpb9.


Characterization of UDP-N-acetylglucosamine:glycoprotein N-acetylglucosamine-1-phosphotransferase from Acanthamoeba castellanii.
The kinetic properties of UDP-N-acetylglucosamine:glycoprotein N-acetylglucosamine-1-phosphotransferase (GlcNAc-phosphotransferase) partially purified from the soil amoeba Acanthamoeba castellanii have been studied. The transferase phosphorylated the lysosomal enzymes uteroferrin and cathepsin D 3-90-fold better than nonlysosomal glycoproteins and 16-83-fold better than a Man9GlcNAc oligosaccharide. Deglycosylated uteroferrin was a potent competitive inhibitor of the phosphorylation of intact uteroferrin (Ki of 48 microM) but did not inhibit the phosphorylation of RNase B or the simple sugar alpha-methylmannoside. Deglycosylated RNase (RNase A) did not inhibit the phosphorylation of RNase B or uteroferrin. These results indicate that purified amoeba GlcNAc-phosphotransferase recognizes a protein domain present on lysosomal enzymes but absent in most nonlysosomal glycoproteins. The transferase also exhibited a marked preference for oligosaccharides containing mannose alpha 1,2-mannose sequences, but this cannot account for the high affinity binding to lysosomal enzymes. A. castellanii extracts do not contain detectable levels of N-acetylglucosamine-1-phosphodiester alpha-N-acetylglucosaminidase, the second enzyme in the biosynthetic pathway for the mannose 6-phosphate recognition marker. We conclude that A. castellanii does not utilize the phosphomannosyl sorting pathway despite expression of very high levels of GlcNAc-phosphotransferase.


Color response of tri-armed azo host colorimetric sensors and test kit for fluoride.
Five new chromogenic tripodal receptors (2a-e) containing electron withdrawing and donating groups appended to the azophenol moiety were synthesized, characterized, and their chromogenic behaviors toward various anions were investigated. These tripodal receptors showed a distinct color change only when treated with fluoride ions in CH(3)CN solution. Yet, other anions such as Cl(-), Br(-), I(-), NO(3)(-), ClO(4)(-), AcO(-), HSO(4)(-), and H(2)PO(4)(-) could not cause any color change. Thus, the receptors 2a-e can be used as a colorimetric chemosensor for the determination of fluoride ion. In addition, (1)H NMR experiments were carried out to explore the nature of interaction between tripodal receptors and fluoride. Finally, analytical application and the use of test strip of the receptor 2b to detect fluoride was also reported.


The diagnostic dilemma in a patient with neuroleptic malignant syndrome during the COVID-19 pandemic: A significant increase in acute phase reactants.
In some patients, neuroleptic malignant syndrome is accompanied significant high levels of erythrocyte sedimentation rate (ESR), C-reactive protein (CRP). Neuroleptic malignant syndrome (NMS) is an idiosyncratic life-threatening adverse reaction and usually triggered in response to antipsychotic drugs. In addition, leukocytosis and increased muscle enzymes levels (especially creatine phosphokinase) are observed in NMS. In addition, a transient increase in different types of acute phase reactants in NMS has been mentioned. This article describes a woman treated with haloperidol, perphenazine, escitalopram, and alprazolam because she developed catatonic symptoms after psychological stress. She suffered from NMS symptoms and had elevated CRP and ESR levels, among other signs and symptoms. Given the COVID-19 pandemic and reports of co-occurrence of catatonia and NMS and COVID-19 and elevated erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP), this patient was a diagnostic dilemma. After consultation with the consultation-liaison psychiatry units, she was managed adequately with electroconvulsive therapy and lorazepam.


Protrudin binds atlastins and endoplasmic reticulum-shaping proteins and regulates network formation.
Hereditary spastic paraplegias are inherited neurological disorders characterized by progressive lower-limb spasticity and weakness. Although more than 50 genetic loci are known [spastic gait (SPG)1 to -57], over half of hereditary spastic paraplegia cases are caused by pathogenic mutations in four genes encoding proteins that function in tubular endoplasmic reticulum (ER) network formation: atlastin-1 (SPG3A), spastin (SPG4), reticulon 2 (SPG12), and receptor expression-enhancing protein 1 (SPG31). Here, we show that the SPG33 protein protrudin contains hydrophobic, intramembrane hairpin domains, interacts with tubular ER proteins, and functions in ER morphogenesis by regulating the sheet-to-tubule balance and possibly the density of tubule interconnections. Protrudin also interacts with KIF5 and harbors a Rab-binding domain, a noncanonical FYVE (Fab-1, YGL023, Vps27, and EEA1) domain, and a two phenylalanines in an acidic tract (FFAT) domain and, thus, may also function in the distribution of ER tubules via ER contacts with the plasma membrane or other organelles.


Duodenal neuroendocrine neoplasms on enhanced CT: establishing a diagnostic model with duodenal gastrointestinal stromal tumors in the non-ampullary area and analyzing the value of predicting prognosis.
To identify CT features and establish a diagnostic model for distinguishing non-ampullary duodenal neuroendocrine neoplasms (dNENs) from non-ampullary duodenal gastrointestinal stromal tumors (dGISTs) and to analyze overall survival outcomes of all dNENs patients. This retrospective study included 98 patients with pathologically confirmed dNENs (n = 44) and dGISTs (n = 54). Clinical data and CT characteristics were collected. Univariate analyses and binary logistic regression analyses were performed to identify independent factors and establish a diagnostic model between non-ampullary dNENs (n = 22) and dGISTs (n = 54). The ROC curve was created to determine diagnostic ability. Cox proportional hazards models were created and Kaplan-Meier survival analyses were performed for survival analysis of dNENs (n = 44). Three CT features were identified as independent predictors of non-ampullary dNENs, including intraluminal growth pattern (OR 0.450; 95% CI 0.206-0.983), absence of intratumoral vessels (OR 0.207; 95% CI 0.053-0.807) and unenhanced lesion > 40.76 HU (OR 5.720; 95% CI 1.575-20.774). The AUC was 0.866 (95% CI 0.765-0.968), with a sensitivity of 90.91% (95% CI 70.8-98.9%), specificity of 77.78% (95% CI 64.4-88.0%), and total accuracy rate of 81.58%. Lymph node metastases (HR: 21.60), obstructive biliary and/or pancreatic duct dilation (HR: 5.82) and portal lesion enhancement ≤ 99.79 HU (HR: 3.02) were independent prognostic factors related to poor outcomes. We established a diagnostic model to differentiate non-ampullary dNENs from dGISTs. Besides, we found that imaging features on enhanced CT can predict OS of patients with dNENs.


Family medicine residents' barriers to conducting scholarly work.
To identify family medicine residents' barriers to conducting high-quality research for the mandatory family medicine resident scholarly project, as well as to determine possible strategies to encourage research activity among family medicine residents. Descriptive study using an online survey. Department of Family Medicine at the University of Ottawa in Ontario. A total of 54 first- and second-year residents. Family medicine residents' involvement in research activities, perceived quality of their mandatory scholarly project, intentions for publication and presentation, and attitudes toward potential barriers to and facilitators of conducting high-quality research. Of the 54 residents, 20 (37%) reported that their project was of high quality, 6 (11%) intended to publish their findings, and 2 (4%) intended to present their findings. Respondents indicated that the main barriers to conducting high-quality research were lack of time, interest, and scholarly skills. The proposed solutions to increase participation in scholarly work were to allow full research days to be used in half-day increments and to offer a journal club where residents could learn scholarly activities. Family medicine residents found several factors to be considerable barriers to completing the required family medicine resident scholarly project. This indicates that there is a need to change the current approach to developing scholarly skills in family medicine. Greater allotment of and flexibility in protected research time and more sessions focused on developing scholarly skills might facilitate scholarly activity among family medicine residents.


Palliative care in rural areas - collaboration between district nurses and doctors: an interview study.
Palliative care requires major nursing interventions as well as medical interventions; thus, both district nurses and doctors are vital to the palliative team. Sparsely populated rural areas are characterised by large geographic distances with the nurses and doctors located far away from each other. If collaboration does not work, this can create challenges for district nurses when managing patients' symptoms. The aim of this study was to describe district nurses' experiences of collaborating with doctors-in-charge during palliative home care in sparsely populated rural areas. Semi-structured interviews were conducted with 10 district nurses. Inductive content analysis was used to analyse the data. The experiences of the district nurses are described under the overarching theme of Experiences of acting as the patient's advocate, which is divided into two categories: Feeling secure in oneself and the other person and Feeling alone when collaboration breaks down. Consensus and coherence, or lack thereof, between district nurses and doctors affect how collaboration is experienced. Positive experiences are generated when the district nurse and the doctor share a holistic approach, while collaboration is experienced as dysfunctional when the doctor's decisions are not consistent with what the nurse judges to be beneficial to the patient. An understanding of how collaboration across long distances is experienced in rural areas is necessary to enhance collaboration.


Longitudinal data for interdisciplinary ageing research. Design of the Linnaeus Database.
To allow for interdisciplinary research on the relations between socioeconomic conditions and health in the ageing population, a new anonymized longitudinal database - the Linnaeus Database - has been developed at the Centre for Population Studies at Umeå University. This paper presents the database and its research potential. Using the Swedish personal numbers the researchers have, in collaboration with Statistics Sweden and the National Board for Health and Welfare, linked individual records from Swedish register data on death causes, hospitalization and various socioeconomic conditions with two databases - Betula and VIP (Västerbottens Intervention Programme) - previously developed by the researchers at Umeå University. Whereas Betula includes rich information about e.g. cognitive functions, VIP contains information about e.g. lifestyle and health indicators. The Linnaeus Database includes annually updated socioeconomic information from Statistics Sweden registers for all registered residents of Sweden for the period 1990 to 2006, in total 12,066,478. The information from the Betula includes 4,500 participants from the city of Umeå and VIP includes data for almost 90,000 participants. Both datasets include cross-sectional as well as longitudinal information. Due to the coverage and rich information, the Linnaeus Database allows for a variety of longitudinal studies on the relations between, for instance, socioeconomic conditions, health, lifestyle, cognition, family networks, migration and working conditions in ageing cohorts. By joining various datasets developed in different disciplinary traditions new possibilities for interdisciplinary research on ageing emerge.


Baited-boats: an innovative way to control riverine tsetse, vectors of sleeping sickness in West Africa.
Human African Trypanosomiasis (HAT) is an important neglected tropical disease caused by Trypanosoma spp. parasites transmitted by species of tsetse fly (Glossina spp). The most important vectors of HAT are riverine tsetse and these can be controlled by attracting them to stationary baits such as insecticide-impregnated traps or targets deployed along the banks of rivers. However, the geographical nature of some riverine habitats, particularly mangroves but also extensive lake and river networks, makes deployment of baits difficult and limits their efficacy. It is known that tsetse are attracted by the movement of their hosts. Our hypothesis was that mounting a target on canoes typically used in Africa ('pirogues') would produce an effective means of attracting-and-killing riverine tsetse in extensive wetland habitats. In Folonzo, southern Burkina Faso, studies were made of the numbers of tsetse attracted to a target (75 × 50 cm) of blue cloth and netting mounted on a pirogue moving along a river, versus the same target placed on the riverbank. The targets were covered with a sticky film which caught tsetse as they contacted the target. The pirogue-mounted target caught twice as many G. tachinoides and G. p. gambiensis, and 8 times more G. morsitans submorsitans than the stationary one (P < 0.001). Pirogues are common vehicle for navigating the rivers, lakes and swamps of West Africa. The demonstration that tsetse can be attracted to targets mounted on such boats suggests that pirogues might provide a cost-effective and convenient platform for deploying targets to control tsetse in the mangrove systems of West Africa where HAT persists. Further studies to assess the impact of pirogue-mounted targets on tsetse populations in HAT foci and the protective value of targets for pirogue passengers are recommended.


Adaptation of macrophages to exercise training improves innate immunity.
The effects of 3-week exercise training on the functions of peritoneal macrophages from BALB/c mice were investigated. Lipopolysaccharide (LPS)-stimulated nitric oxide (NO) and proinflammatory cytokine production in macrophages from trained mice was markedly higher than those from control mice. Meanwhile, exercise training decreased the steady state level of beta(2)-adrenergic receptor (beta(2)AR) mRNA in macrophages. Overexpression of beta(2)AR in the macrophage cell line RAW264 by transfecting with beta(2)AR cDNA suppressed NO synthase (NOS) II expression but dose not influenced proinflammatory cytokine expression. When expression of transfected beta(2)AR in RAWar cells was downregulated by a tetracycline repressor-regulated mammalian expression system, NOS II mRNA expression was significantly increased; this suggested that the changes in the beta(2)AR expression level in macrophages associated with exercise training play a role in the regulation of NO production following LPS stimulation. These findings indicate that exercise training improves macrophage innate immune function in a beta(2)AR-dependent and -independent manner.


[Heat stability of potency of bacterial vaccines and the titer of tetanus antitoxin of Polish production].
Described the stability of potency vaccines (DTP, BCG) and immunoglobulins (human's and animal's) at storage and experimental temperatures. Thermal degradation rate and design of loss of potency in time have been determined by Arrhenius equation. Our results were similar to WHO data from preparations which have been made in another countries.


Hydrochar prepared from digestate improves anaerobic co-digestion of food waste and sewage sludge: Performance, mechanisms, and implication.
This work reported a new waste functionalization and utilization method, which use digestate to prepare hydrochar to improve methane production from food waste (FW) and sewage sludge (SS). Experimental results presented that 10 g/L hydrochar obtained the cumulative methane production of 133.11 ± 1.18 mL/g volatile solids added, 26.99 % higher than that without hydrochar addition. By monitoring the conversion of model metabolic intermediates, 10 g/L hydrochar was determined to favor hydrolysis, acidogenesis and methonogenesis bio-processes involved in methane production, thus improving the degradation of solubilized organics and consumption of short-chain fatty acids (SCFAs) during the co-digestion. Microbial investigation revealed that 10 g/L hydrochar enriched the microbes relevant to methane production (e.g., Methanosaeta and Syntrophomonas), but reduced the abundances of hydrolysis- and acidogenesis-related microbes (e.g., Acinetobacter). This hydrochar-based preparation and utilization strategy might offer a novel paradigm for waste-control-waste, bringing economic and environmental benefits.


Sorting of early and late flagellar subunits after docking at the membrane ATPase of the type III export pathway.
The bacterial flagellum assembles in a strict order, with structural subunits delivered to the growing flagellum by a type III export pathway. Early rod-and-hook subunits are exported before completion of the hook, at which point a subunit-specificity switch allows export of late filament subunits. This implies that in bacteria with multiple flagella at different stages of assembly, each export pathway can discriminate and sort unchaperoned early and chaperoned late subunits. To establish whether subunit sorting is distinct from subunit transition from the cytosol to the membrane, in particular docking at the membrane-associated FliI ATPase, the pathway was manipulated in vivo. When ATP hydrolysis by the FliI ATPase was disabled and when the pathway was locked into an early export state, both unchaperoned early and chaperoned late subunits stalled and accumulated at the inner membrane. Furthermore, a chaperone that attenuates late subunit export by stalling when docked at the wild-type ATPase also stalled at the ATPase in an early-locked pathway and inhibited export of early subunits in both native and early-locked pathways. These data indicate that the pathways for early and late subunits converge at the FliI ATPase, independent of ATP hydrolysis, before a distinct, separable sorting step. To ascertain the likely signals for sorting, the export of recombinant subunits was assayed. Late filament subunits unable to bind their chaperones were still sorted accurately, but chaperoned late subunits were directed through an early-locked pathway when fused to early subunit N-terminal export signal regions. Furthermore, while an early subunit signal directed export of a heterologous type III export substrate through both native and early-locked pathways, a late subunit signal only directed export via native pathways. These data suggest that subunits are distinguished not by late chaperones but by N-terminal export signals of the subunits themselves.


Graded function of CD80 and CD86 in initiation of T-cell immune response and cardiac allograft survival.
CD28 and cytotoxic T-lymphocyte antigen-4 (CTLA-4), which have opposing functions in T-cell responses, share the two ligands, CD80 (B7-1) and CD86 (B7-2). To understand the functions of CD80 and CD86, respectively, CD80(low) dendritic cells (DCs) and CD86(low) DCs were prepared by using RNA interference. Then CD80 and CD86 functions were analysed by in vitro mixed lymphocyte reaction and cytokine production assay. Effect on cardiac allograft survival was assayed in vivo. In this study, graded stimulatory function of CD80 and CD86, stronger inhibition of proliferation, and stronger prolongation of transplant survival were observed when CD80 and CD86 were blocked simultaneously.


Uptake of 2-fluoro-2-deoxy-D-[U-14C]-glucose during chemotherapy in murine Lewis lung tumor.
Mice bearing intramuscular Lewis lung tumor were treated with BCNU and doxorubicin (ADM) to study chemotherapy-induced changes in the uptake of 2-fluoro-2-deoxy-[U-14C]glucose (FDG). A decreased FDG uptake, tumor regression and a diminished proportion of aneuploid versus diploid cells as evaluated by DNA flow cytometry were seen after treatment with BCNU but not with ADM; HPLC indicated that most of the 14C activity in tumors was from FDG6-phosphate. The results suggest that changes in FDG uptake reflect the effectiveness of antitumor therapy. FDG may be valuable in follow-up studies of cancer treatment.


A small molecule cell-impermeant Hsp90 antagonist inhibits tumor cell motility and invasion.
Heat shock protein 90 (Hsp90) is a molecular chaperone that maintains function of numerous intracellular signaling nodes utilized by cancer cells for proliferation and survival. Hsp90 is also detected on the plasma membrane of tumor cells and its expression has been suggested to correlate with metastatic potential. Given the abundance and diverse functions of the intracellular pool of this protein, the precise contribution of cell surface Hsp90 to cell motility and tumor metastasis remains to be determined. In this study we utilized the small molecule DMAG-N-oxide, a novel cell-impermeable Hsp90 inhibitor, to specifically examine the role of cell surface Hsp90 in cell motility. We observed that, while not affecting intracellular Hsp90 function, DMAG-N-oxide significantly retarded tumor cell migration and integrin/extracellular matrix-dependent cytoskeletal reorganization. Concomitant with these findings, targeting cell surface Hsp90 significantly inhibited tumor cell motility and invasion in vitro, and had a dramatic impact on melanoma cell lung colonization in vivo. These data indicate that cell surface Hsp90 plays an important role in modulating cancer cell migration that is independent of the function of the intracellular Hsp90 pool, and that small molecule inhibitors of surface Hsp90 may provide a new approach to targeting the metastatic phenotype.


Prospects of Rescuing Young Eggs for Oncofertility.
Childhood cancer patients undergoing cancer therapy can be rendered infertile during adulthood. With more girls surviving cancer, fertility preservation in young cancer patients is a major clinical challenge. Advances in egg culture may offer benefits for the fertility of these patients in the future.


Use of self-organizing maps and molecular descriptors to predict the cytotoxic activity of sesquiterpene lactones.
Some sesquiterpene lactones (SLs) are the active compounds of a great number of traditionally medicinal plants from the Asteraceae family and possess considerable cytotoxic activity. Several studies in vitro have shown the inhibitory activity against cells derived from human carcinoma of the nasopharynx (KB). Chemical studies showed that the cytotoxic activity is due to the reaction of alpha,beta-unsaturated carbonyl structures of the SLs with thiols, such as cysteine. These studies support the view that SLs inhibit tumour growth by selective alkylation of growth-regulatory biological macromolecules, such as key enzymes, which control cell division, thereby inhibiting a variety of cellular functions, which directs the cells into apoptosis. In this study we investigated a set of 55 different sesquiterpene lactones, represented by 5 skeletons (22 germacranolides, 6 elemanolides, 2 eudesmanolides, 16 guaianolides and nor-derivatives and 9 pseudoguaianolides), in respect to their cytotoxic properties. The experimental results and 3D molecular descriptors were submitted to Kohonen self-organizing map (SOM) to classify (training set) and predict (test set) the cytotoxic activity. From the obtained results, it was concluded that only the geometrical descriptors showed satisfactory values. The Kohonen map obtained after training set using 25 geometrical descriptors shows a very significant match, mainly among the inactive compounds (approximately 84%). Analyzing both groups, the percentage seen is high (83%). The test set shows the highest match, where 89% of the substances had their cytotoxic activity correctly predicted. From these results, important properties for the inhibition potency are discussed for the whole dataset and for subsets of the different structural skeletons.


Lower anterior crowding correction by a convenient lingual method.
In recent years, the increased esthetic demands of patients seeking orthodontic treatment have led to the development of various esthetic appliances and techniques. Lingual orthodontics is a major expression of this necessity. Several techniques and appliances have been introduced during the years, but they usually require special equipment and manipulation to be applied to patients. In this report, we present an easy, convenient, and effective lingual method for the management of specific simple cases with mild-to-moderate lower anterior crowding using conventional orthodontic means. In selected cases, the presented method may provide a viable simple solution for correcting a common orthodontic problem, the lower anterior crowding, while satisfying patients' increased esthetic requirements.


Cadmium coordination to the zinc binding domains of the non-classical zinc finger protein Tristetraprolin affects RNA binding selectivity.
Tristetraprolin [(TTP), also known as NUP475 and TIS11] is a non-classical zinc finger protein that regulates inflammatory response via a protein-RNA interaction. Specifically, TTP recognizes AU-rich RNA sequences located on the 3' untranslated region of messenger RNA associated with cytokines. Recently, TTP was shown to be upregulated when cells were exposed to cadmium. Other types of zinc finger proteins have been shown to bind Cd(II), thus the Cd(II) binding properties of TTP were pursued. Metal binding titrations using Co(II) as a spectroscopic probe for Cd(II) were performed. Cd(II) was found to coordinate to the two Cys(3)His structural zinc sites of TTP (TTP-2D) with an upper-limit dissociation constant, K(d), of 3.5±0.1 nM. Upon reconstitution of TTP-2D with Cd(II), the protein recognized target RNA, UUUAUUUAUUU, with a dissociation constant, K(d), of 2.4±0.2 nM. The Cd(II)TTP-2D/RNA binding event was more sensitive to base mutations than the Zn(II)TTP-2D/RNA binding event. A single base mutation within the UUUAUUUAUUU oligomer decreased the Cd(II)TTP-2D binding affinity 50-fold and a double mutation decreased the affinity 1000-2000 fold. In comparison, only 2-fold and 15-25 fold changes for Zn(II)TTP-2D binding to the identical RNA sequences are measured.


Quantitative assessment of TLR4 gene polymorphisms and T2DM risk: A meta-analysis.
Numerous studies have evaluated the association between TLR4 gene polymorphisms and T2DM risk. However, the findings were inconsistent and controversial. In order to drive a more precise estimation, we carried out a meta-analysis based on 41 studies involving 23,250 cases and 24,760 controls. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated to assess the strength of association. Our meta-analysis provides evidence that rs4986790 polymorphism was associated with an increased risk of T2DM in Asian (AG vs. AA, OR = 1.23, 95% CI = 1.01-1.50, p = 0.042; G vs. A, OR = 1.21, 95% CI = 1.01-1.44, p = 0.041). Rs4986791 polymorphism was related to an increased risk of T2DM both in Asian (AG vs. AA, OR = 1.76, 95% CI = 1.11-2.80, p = 0.017; G vs. A, OR = 1.63, 95% CI = 1.04-2.55, p = 0.034) and Caucasian (GG vs. AA, OR = 2.42, 95% CI = 1.23-4.75, p = 0.010). Rs11536889 polymorphism may have a protective effect on T2DM in Chinese populations (CC vs. GG, OR = 0.62, 95% CI = 0.40-0.96, p = 0.031; GC vs. GG, OR = 0.77, 95% CI = 0.61-0.98, p = 0.034; CC vs. GC/GG, OR = 0.81, 95% CI = 0.69-0.96, p = 0.013; C vs. G, OR = 0.76, 95% CI = 0.59-0.97, p = 0.027), whereas rs1927911 may have no impact. These findings supported that rs4986790, rs4986791, and rs11536889 may contribute to the risk of T2DM.


The prevalence and clinical significance of chromogranin A and secretogranin II immunoreactivity in colorectal adenocarcinomas.
Colorectal adenocarcinomas may display features of endocrine differentiation, shown by argyrophil stains and by the expression of endocrine markers such as chromogranin A. We investigated chromogranin A and secretogranin II immunoreactivity in a series of 208 carcinomas of the large bowel to assess the prevalence and clinical significance of endocrine differentiation. Tumors expressing endocrine markers were classified as low expressors (< than 1 immunoreactive tumour cell/mm2) and high expressors (> than 1 immunoreactive tumour cell/mm2). There were 33 (16%) carcinomas showing both chromogranin A and secretogranin II immunoreactivity: 11 tumours (5%) were high expressors. Endocrine differentiation was not related to the disease stage, tumour location, grade, DNA ploidy and p53 protein accumulation. In the entire series chromogranin A immunoreactivity did not provide prognostic information using univariate and multivariate analysis. A worse overall survival (P = 0.048) was demonstrated for the stage III patients with high expressor tumours, but there were only five patients in this group. The results of our investigation suggest that chromogranin A immunoreactivity is not a useful variable in the prognostic assessment of colorectal adenocarcinomas.


Prevalence and clinical features of hepatitis delta virus infection in the Miyako Islands, Okinawa, Japan.
The aims of this study were twofold: (1) to determine the prevalence and clinical features of hepatitis delta virus (HDV) infection among subjects positive for hepatitis B surface antigen (HBsAg) living in the Miyako Islands, Okinawa Prefecture, Japan, and (2) to clarify the relationship between HDV-RNA level and severity of HDV-related liver disease. One hundred and ninety-nine HBsAg-positive subjects (123 asymptomatic carriers [ASCs], 3 patients with acute hepatitis [AH], 50 patients with chronic hepatitis [CH], 15 patients with liver cirrhosis [LC], and 8 patients with hepatocellular carcinoma [HCC], were tested for antibody to HDV (anti-HDV) by radioimmunoassay. Anti-HDV-positive individuals were examined to determine semi-quantified HDV-RNA level by polymerase chain reaction (PCR). The overall prevalence of anti-HDV among the 199 subjects was 21.1%. The positivity rate tended to increase with age or the severity of the underlying liver disease: anti-HDV-positive rates were 10.6% (13/123) in ASCs, 32.0% (16/50) in patients with CH, 40.0% (6/15) in patients with LC, and 87.5% (7/8) in patients with HCC. None of the patients with AH were positive for anti-HDV. There was no correlation between semi-quantified serum HDV-RNA levels and the severity of chronic liver disease in patients positive for anti-HDV. The present study showed the local spread of HDV infection in the Miyako Islands, Okinawa, Japan. Although the anti-HDV positivity rate tended to increase with the severity of the underlying liver disease, the severity of HDV-related liver disease did not correlate with the semi-quantified serum HDV-RNA level.


Biomechanical CT-computed bone strength predicts the risk of subsequent vertebral fracture.
Following primary fractures and percutaneous kyphoplasty (PKP), patients have a high risk of incurring a subsequent vertebral fracture (SVF). Given that SVF is a consequence of mechanical deterioration of the vertebra, we sought to examine whether vertebral strength derived from QCT-based finite element analysis (i.e., BCT) can predict the risk of SVF. Sixty-six patients who underwent PKP were categorized into two groups: control or non-SVF group (age: 70 ± 7 years; n = 40) and SVF group (age: 69 ± 8 years; n = 26). BCT was performed on L4 or L3 vertebrae to noninvasively measure vertebral strength. Vertebral strength was also estimated based upon the geometry and material properties of the vertebra. Additionally, trabecular volumetric bone mineral density (vBMD) and L1 Hounsfield unit (HU) were measured. t-Test, χ2 test or Mann Whitney U test were used to compare differences in these parameters between the two groups. The predictive abilities of BCT strength and other measured parameters were evaluated using the receiver operating characteristic (ROC) analysis. Results showed no significant difference in either vBMD or L1 HU between the control and SVF groups (p > 0.05), whereas BCT-computed and estimated vertebral strength values were significantly reduced by 33 % and 24 % for the SVF group relative to the non-SVF group, respectively. ROC curve indicated that BCT strength had the largest area under the curve, compared to other parameters. These results suggest that BCT-computed vertebral strength may serve as a surrogate for assessing risk of SVF.


The internal representation of temporal orienting: A temporal pulse-accumulation and attentional-gating-based account.
Timing can be processed explicitly or implicitly. Temporal orienting is a typical implicit timing through which we can anticipate and prepare an optimized response to forthcoming events. It is, however, not yet clear whether mechanisms such as temporal-pulse accumulation and attentional gating (more attention, more accumulated temporal pulses) underly the internal representations of temporal orienting, as in explicit timing. To clarify this, a dual-task paradigm, consisting of a temporal orienting and an interference task, was adopted. Consistent with the temporal-pulse-accumulation and attentional-gating model, reaction times to the target detection of temporal orienting increased as the interference stimuli were temporally closer to the target, i.e., a location effect for temporal orienting. This effect is likely due to attention being diverted away from temporal orienting to monitor the occurrence of the interference stimuli for a longer time, resulting in greater temporal pulse loss and less accurate temporal orienting for conditions with later interference stimuli. The temporal-pulse-accumulation aspect in temporal orienting received further support by taking an explicit duration reproduction (containing a second temporal-pulse accumulation) as the interference task. On the one hand, temporal orienting became less accurate with increased temporal-pulse-accumulation overlaps between the dual tasks; on the other hand, two-way (one for temporal orienting and the other for duration reproduction), rather than one-way, location effects were observed, implying processing conflicts between the two temporal-pulse accumulations. Taken together, these results suggest that implicit and explicit timing may share common mechanisms upon internal temporal representations.


t(2;8) variant translocation in Burkitt's lymphoma: mapping of chromosomal breakpoints by in situ hybridization.
In 6 different Burkitt lymphoma cell lines with t(2;8) variant translocations (J1, LY66, LY91, BL21, BL64, JBL2) the breakpoints on chromosome 8q+ were mapped in relation to each other and to c-myc by in situ hybridization. The probes used were derived from chromosome 8q24 and comprised a c-myc probe, a probe located 48 kb downstream of c-myc, 3 probes adjacent to the chromosomal breakpoints of BL64, LY91 and JBL2, respectively, and 2 probes located in the 5' and 3' part of the thyroglobulin gene. The breakpoints of LY91 and JBL2 lie less than 200 kb and greater than 200 kb downstream of c-myc, whereas the distance to c-myc of the BL64 breakpoint and of the thyroglobulin probes is unknown. By recording the hybridization signals specific for these probes on chromosomes 2p- and 8q+ of each cell line it was possible to establish the order of breakpoints on band 8q24 relative to the c-myc and thyroglobulin genes as follows: centromere--c-myc--J1--BL64--BL21--LY91--JBL2--+ ++LY66--thyroglobulin--telomere. This information is essential for further mapping of this important chromosomal region.