Search

Mechanical problems like break or crack in Luer connectors or hubs, clamps, and tubings are common non-infectious complications of tunneled dialysis catheters (TDC), which may lead to other TDC complications and the need to insert a new catheter. These can be tackled using TDC repair kits or spare parts, which are often not available, resulting in the insertion of a new TDC that increases morbidity, TDC-related procedures, and healthcare costs. We discuss two cases of broken Luer connections of TDC, which were managed by exchanging the broken Luer connector of TDC with the similar Luer connector of a temporary dialysis catheter. Both the repaired TDCs are thereafter functioning well. This improvised technique provides an easy, effective, long-lasting option that salvages the existing TDC and reduces the cost factor. [ABSTRACT FROM AUTHOR]

Summary: There were more applications for higher specialty training posts in anaesthesia in the UK starting in August 2021 than in previous years, with approximately two‐thirds being unsuccessful. We surveyed applicants to investigate their experience of the recruitment process (response rate 536/1056; 51%). Approximately 61% of respondents were not offered ST3 posts (n = 326). We enquired about their career plans for the next 12–24 months. Most respondents (79%) intended to take up a post equivalent to a third year of core training or a clinical fellow post from August 2021. Other options considered included: pursuing work abroad (17%); embarking on career breaks (16%); taking up higher training posts in intensive care medicine (15%); and permanently leaving medicine (9%). Nine per cent of respondents also expressed plans to pursue training in another medical specialty. Some expressed an intention to pursue further education or research (10%). A large proportion (42%) expressed a lack of confidence in being able to achieve the training requirements to later apply for a higher training post. The majority reported not feeling confident in achieving specialist registration in anaesthesia in the future without a training number (75%), and noted disruption to their wider life plans from the impending time out of training (78%). Sentiment analysis of free‐text responses indicated generally negative sentiment about the recruitment process. Themes elicited included: feeling the recruitment process was unfair; burnout and negative impact on well‐being; difficulties in making life plans; and feeling undervalued and abandoned. These results suggest that junior anaesthetic doctors in the UK negatively perceived postgraduate training structures and changes to the postgraduate curriculum and experienced difficulties in securing higher training. [ABSTRACT FROM AUTHOR]

Methamphetamine (METH) is a popular but harmful psychostimulant. METH use disorder (MUD) is characterized by compulsive and continued use despite adverse life consequences. METH users experience impairments in learning and memory functions that are thought to be secondary to METH-induced abnormalities in the hippocampus. Recent studies have reported that about 50% of METH users develop MUD, suggesting that there may be differential molecular effects of METH between the brains of individuals who met criteria for addiction and those who did not after being exposed to the drug. The present study aimed at identifying potential transcriptional differences between compulsive and non-compulsive METH self-administering male rats by measuring global gene expression changes in the hippocampus using RNA sequencing. Herein, we used a model of METH self-administration (SA) accompanied by contingent foot-shock punishment. This approach led to the separation of animals into shock-resistant rats (compulsive) that continued to take METH and shock-sensitive rats (non-compulsive) that suppressed their METH intake in the presence of punished METH taking. Rats were euthanized 2 h after the last METH SA plus foot-shock session. Their hippocampi were immediately removed, frozen, and used later for RNA sequencing and qRT-PCR analyses. RNA sequencing analyses revealed differential expression of mRNAs encoding cell adhesion molecules (CAMs) between the two rat phenotypes. qRT-PCR analyses showed significant higher levels of Cdh1, Glycam1, and Mpzl2 mRNAs in the compulsive rats in comparison to non-compulsive rats. The present results implicate altered CAM expression in the hippocampus in the behavioral manifestations of continuous compulsive METH taking in the presence of adverse consequences. Our results raise the novel possibility that altered CAM expression might play a role in compulsive METH taking and the cognitive impairments observed in MUD patients.

Finding the median of a set of data within a window of finite size is computationally challenging on account of the complexity in sorting. Compared with the established nine‐stage systolic arrays, an eight‐stage systolic array to find the median of a fixed 3 × 3 window of n bit integers is proposed. The proposed array requires a fewer number of signal paths, and is faster for fixed resource. The method employed uses selective comparators for finding the median by avoiding comparators required to obtain fully sorted list. This reduces the partial sorting to eight‐stage systolic array. However, this is applicable only to median sorting of 3 × 3 fixed window. The method employs combinatorial circuit implementation; consequently there is 12% gain in speed and 7% fewer signal paths. Circuit with memory cells at every stage and eight latency cycles results in 36% speed gain over the state‐of‐the‐art non‐sorting based methods. This method provides superior performance in comparison with the methods available for fixed 3 × 3 window‐based median filters. [ABSTRACT FROM AUTHOR]

Vector control is one of the most important components in combating vector-borne diseases throughout the world. Application of insecticides is a widely known and popular vector control strategy. The objective of the present study was to evaluate the larvicidal activity of the hexane, diethyl ether, ethyl acetate and acetone extracts of Abutilón indicum, Hyptis suaveolens and Leucas aspera against third-stage larvae of Anopheles culicifiacies. The results clearly suggest that all three selected plant extracts exhibited moderate larvicidal activity after 24, 48 and 72 h at 250, 500, 750 and 1000 ppm; the lethal concentrations (LC) at 50% and 90% of A. indicum, H. suaveolens against third instar larvae at 24, 48 and 72 h (hexane, diethyl ether, ethyl acetate and acetone) were as follows: A. indicum, LC50=1031.65, 949.18, 833.58 and 673.68 ppm; LCM=2215.87, 2234.39, 2152.97 and 2455.10 ppm; H. suaveolens, LC50=423.00, 347.50, 236.58 and 217.24 ppm; LC90=1431.91, 1292.15, 1138.49 and 1049.27 ppm and L. aspera, LC50=559.77, 401.56, 299.71 and 263.01 ppm; LCM=1400.80, 1549.31, 1157.96 and 1108.72 ppm at 24 h, respectively. Overall, the highest larvicidal activity was observed with H. suaveolens extract followed by L. aspera and A. indicum at various concentrations at 48 and 72 h, respectively. The objective of this investigation was an attempt to search for a user- and eco-friendly vector control agent. The study proved that the selected plant leaf extracts could serve as potent larvicidal agents against A. culicifacies in vector control programs. [ABSTRACT FROM AUTHOR]

Mosquitoes are one of the most medically significant groups of vectors, having an ability to transmit parasites and pathogens that can have devastating impacts on humans. The development of reliable and ecofriendly processes for the synthesis of metallic nanoparticles is an important step in the field of application of nanotechnology. In this study, we address the biosynthesis of silver nanoparticles (AgNPs) using Leucas aspera leaf extract, and evaluate its lethal concentration (LC50 and LC90) values against first to fourth instar larvae and pupae of the mosquito vectors, Aedes aegypti and Anopheles stephensi. The nanoparticles were characterized by UV-Vis spectrum, scanning electron microscopy, energy-dispersive X-ray spectroscopy, and Fourier-transformed infrared spectroscopy analysis. Larvae and pupae were exposed to varying concentrations of aqueous extracts of synthesized AgNPs for 24 h. The maximum mortality was observed from synthesized AgNPs, with LC50 values for I-IV instars and pupae ranging from 13.06 to 25.54, and LC90 values ranging from 24.11 to 47.34 for Ae. aegypti; for An. stephensi, the corresponding LC50 values ranged from 12.45 to 22.26, and the LC90 values ranged from 23.50 to 42.95. With methanol leaf extract of L. aspera against Ae. aegypti, the LC50 values ranged from 174.89 to 462.96 and the LC90 values ranged from 488.16 to 963.74; for An. stephensi, the corresponding LC50 values ranged from 148.93 to 417.07 and the LC90 values ranged from 449.72 to 912.94. The study suggests that nanoparticles could be a preferred alternative to the most hazardous existing chemical pesticides, contributing to a more healthy environment by providing an ideal ecological and user-friendly vector control strategy for managing malaria and dengue, and contributing to their eventual elimination in the near future. [ABSTRACT FROM AUTHOR]

This chapter presents research exploring firsthand experience concerning teaching poverty in social work, challenges, and opportunities at the National Institute of Social Development (NISD), Sri Lanka. It is noteworthy that relevant reading materials and conceptual frameworks in teaching poverty with social work flavor are almost non-existent in Sri Lanka. Based on an intensive analysis of curricula, lecture notes, PowerPoint slides, question papers, exam papers and assignments, and formal discussions using a guideline with third-year social work students, educators, field agencies, and field supervisors, this research focuses on the unique challenges and opportunities to be considered by different stakeholders, affiliated to the NISD in various capacities. In practice, though faculty members and students get ample opportunities to teach and learn poverty education in social work, they recommended that conventional approaches be replaced with innovative ways to make the poverty subject more worthwhile and practical.

Polymerizations of vinyl and methacrylate monomers (2-hydroxyethyl methacrylate, styrene, and methyl methacrylate) were carried out in a choline formate ionic liquid at room temperature without the addition of peroxide-based initiators. Choline formate acted as both an initiator and a solvent and produced high-molecular-weight polymers. Gel permeation chromatography and electron paramagnetic resonance measurements indicated that the polymerizations predominantly occurred by a free-radical mechanism. This method of polymerization provides an alternate route to eliminate the use of toxic initiators and solvents. © 2011 Wiley Periodicals, Inc. J Appl Polym Sci, 2011 [ABSTRACT FROM AUTHOR]

Abstract Methamphetamine addiction is mimicked in rats that self-administer the drug. However, these self-administration (SA) models do not include adverse consequences that are necessary to reach a diagnosis of addiction in humans. Herein, we measured genome-wide transcriptional consequences of methamphetamine SA and footshocks in the rat brain. We trained rats to self-administer methamphetamine for 20 days. Thereafter, lever-presses for methamphetamine were punished by mild footshocks for 5 days. Response-contingent punishment significantly reduced methamphetamine taking in some rats (shock-sensitive, SS) but not in others (shock-resistant, SR). Rats also underwent extinction test at one day and 30 days after the last shock session. Rats were euthanized one day after the second extinction test and the nucleus accumbens (NAc) and dorsal striatum were collected to measure gene expression with microarray analysis. In the NAc, there were changes in the expression of 13 genes in the SRvsControl and 9 genes in the SRvsSS comparison. In the striatum, there were 9 (6 up, 3 down) affected genes in the SRvsSS comparison. Among the upregulated genes was oxytocin in the NAc and CARTpt in the striatum of SR rats. These observations support a regional role of neuropeptides in the brain after a long withdrawal interval when animals show incubation of methamphetamine craving.

Neuroplastic changes in the dorsal striatum participate in the transition from casual to habitual drug use and might play a critical role in the development of methamphetamine (METH) addiction. We examined the influence of METH self-administration on gene and protein expression that may form substrates for METH-induced neuronal plasticity in the dorsal striatum. Male Sprague–Dawley rats self-administered METH (0.1 mg/kg/injection, i.v.) or received yoked saline infusions during eight 15-h sessions and were euthanized 2 h, 24 h, or 1 month after cessation of METH exposure. Changes in gene and protein expression were assessed using microarray analysis, RT-PCR and Western blots. Chromatin immunoprecipitation (ChIP) followed by PCR was used to examine epigenetic regulation of METH-induced transcription. METH self-administration caused increases in mRNA expression of the transcription factors, c-fos and fosb, the neurotrophic factor, Bdnf, and the synaptic protein, synaptophysin (Syp) in the dorsal striatum. METH also caused changes in ΔFosB, BDNF and TrkB protein levels, with increases after 2 and 24 h, but decreases after 1 month of drug abstinence. Importantly, ChIP-PCR showed that METH self-administration caused enrichment of phosphorylated CREB (pCREB), but not of histone H3 trimethylated at lysine 4 (H3K4me3), on promoters of c-fos, fosb, Bdnf and Syp at 2 h after cessation of drug intake. These findings show that METH-induced changes in gene expression are mediated, in part, by pCREB-dependent epigenetic phenomena. Thus, METH self-administration might trigger epigenetic changes that mediate alterations in expression of genes and proteins serving as substrates for addiction-related synaptic plasticity.

Methamphetamine (METH) is a widely abused amphetamine analog. Few studies have investigated the molecular effects of METH exposure in adult animals. Herein, we determined the consequences of an injection of METH (10 mg/kg) on transcriptional effects of a second METH (2.5 mg/kg) injection given one month later. We thus measured gene expression by microarray analyses in the nucleus accumbens (NAc) of 4 groups of rats euthanized 2 hours after the second injection: saline-pretreated followed by saline-challenged (SS) or METH-challenged (SM); and METH-pretreated followed by saline-challenged (MS) or METH-challenged (MM). Microarray analyses revealed that METH (2.5 mg/kg) produced acute changes (1.8-fold; P

Methamphetamine (METH) addiction is associated with several neuropsychiatric symptoms. Little is known about the effects of METH on gene expression and epigenetic modifications in the rat nucleus accumbens (NAC). Our study investigated the effects of a non-toxic METH injection (20 mg/kg) on gene expression, histone acetylation, and the expression of the histone acetyltransferase (HAT), ATF2, and of the histone deacetylases (HDACs), HDAC1 and HDAC2, in that structure. Microarray analyses done at 1, 8, 16 and 24 hrs after the METH injection identified METH-induced changes in the expression of genes previously implicated in the acute and longterm effects of psychostimulants, including immediate early genes and corticotropin-releasing factor (Crf). In contrast, the METH injection caused time-dependent decreases in the expression of other genes including Npas4 and cholecystokinin (Cck). Pathway analyses showed that genes with altered expression participated in behavioral performance, cell-to-cell signaling, and regulation of gene expression. PCR analyses confirmed the changes in the expression of c-fos, fosB, Crf, Cck, and Npas4 transcripts. To determine if the METH injection caused post-translational changes in histone markers, we used western blot analyses and identified METH-mediated decreases in histone H3 acetylated at lysine 9 (H3K9ac) and lysine 18 (H3K18ac) in nuclear sub-fractions. In contrast, the METH injection caused time-dependent increases in acetylated H4K5 and H4K8. The changes in histone acetylation were accompanied by decreased expression of HDAC1 but increased expression of HDAC2 protein levels. The histone acetyltransferase, ATF2, showed significant METH-induced increased in protein expression. These results suggest that METH-induced alterations in global gene expression seen in rat NAC might be related, in part, to METH-induced changes in histone acetylation secondary to changes in HAT and HDAC expression. The causal role that HATs and HDACs might play in METH-induced gene expression needs to be investigated further.

Single large doses of methamphetamine (METH) cause endoplasmic reticulum (ER) stress and mitochondrial dysfunctions in rodent striata. The dopamine D(1) receptor appears to be involved in these METH-mediated stresses. The purpose of this study was to investigate if dopamine D(1) and D(2) receptors are involved in ER and mitochondrial stresses caused by single-day METH binges in the rat striatum. Male Sprague-Dawley rats received 4 injections of 10 mg/kg of METH alone or in combination with a putative D(1) or D(2) receptor antagonist, SCH23390 or raclopride, respectively, given 30 min prior to each METH injection. Rats were euthanized at various timepoints afterwards. Striatal tissues were used in quantitative RT-PCR and western blot analyses. We found that binge METH injections caused increased expression of the pro-survival genes, BiP/GRP-78 and P58(IPK), in a SCH23390-sensitive manner. METH also caused up-regulation of ER-stress genes, Atf2, Atf3, Atf4, CHOP/Gadd153 and Gadd34. The expression of heat shock proteins (HSPs) was increased after METH injections. SCH23390 completely blocked induction in all analyzed ER stress-related proteins that included ATF3, ATF4, CHOP/Gadd153, HSPs and caspase-12. The dopamine D(2)-like antagonist, raclopride, exerted small to moderate inhibitory influence on some METH-induced changes in ER stress proteins. Importantly, METH caused decreases in the mitochondrial anti-apoptotic protein, Bcl-2, but increases in the pro-apoptotic proteins, Bax, Bad and cytochrome c, in a SCH23390-sensitive fashion. In contrast, raclopride provided only small inhibition of METH-induced changes in mitochondrial proteins. These findings indicate that METH-induced activation of striatal ER and mitochondrial stress pathways might be more related to activation of SCH23390-sensitive receptors.

Methamphetamine (meth) is an illicit psychostimulant that is abused throughout the world. Repeated passive injections of the drug given in a single day or over a few days cause significant and long-term depletion of dopamine and serotonin in the mammalian brain. Because meth self-administration may better mimic some aspects of human drug-taking behaviors, we examined to what extent this pattern of drug treatment might also result in damage to monoaminergic systems in the brain. Rats were allowed to intravenously self-administer meth (yoked control rats received vehicle) 15 hours per day for 8 days before being euthanized at either 24 hours or at 7 and 14 days after cessation of drug taking. Meth self-administration by the rats was associated with a progressive escalation of daily drug intake to 14 mg/kg per day. Animals that self-administered meth exhibited dose-dependent decreases in striatal dopamine levels during the period of observation. In addition, there were significant reductions in the levels of striatal dopamine transporter and tyrosine hydroxylase proteins. There were also significant decreases in the levels of dopamine, dopamine transporter, and tyrosine hydroxylase in the cortex. In contrast, meth self-administration caused only transient decreases in norepinephrine and serotonin levels in the two brain regions, with these values returning to normal at seven days after cessation of drug taking. Importantly, meth self-administration was associated with significant dose-dependent increases in glial fibrillary acidic protein in both striatum and cortex, with these changes being of greater magnitude in the striatum. These results suggest that meth self-administration by rats is associated with long-term biochemical changes that are reminiscent of those observed in post-mortem brain tissues of chronic meth abusers.

Methamphetamine (METH) is an illicit toxic psychostimulant which is widely abused. Its toxic effects depend on the release of excessive levels of dopamine (DA) that activates striatal DA receptors. Inhibition of DA-mediated neurotransmission by the DA D1 receptor antagonist, SCH23390, protects against METH-induced neuronal apoptosis. The initial purpose of the present study was to investigate, using microarray analyses, the influence of SCH23390 on transcriptional responses in the rat striatum caused by a single METH injection at 2 and 4 hours after drug administration. We identified 545 out of a total of 22,227 genes as METH-responsive. These include genes which are involved in apoptotic pathways, endoplasmic reticulum (ER) stress, and in transcription regulation, among others. Of these, a total of 172 genes showed SCH23390-induced inhibition of METH-mediated changes. Among these SCH23390-responsive genes were several genes that are regulated during ER stress, namely ATF3, HSP27, Hmox1, HSP40, and CHOP/Gadd153. The secondary goal of the study was to investigate the role of DA D1 receptor stimulation on the expression of genes that participate in ER stress-mediated molecular events. We thus used quantitative PCR to confirm changes in the METH-responsive ER genes identified by the microarray analyses. We also measured the expression of these genes and of ATF4, ATF6, BiP/GRP78, and of GADD34 over a more extended time course. SCH23390 attenuated or blocked METH-induced increases in the expression of the majority of these genes. Western blot analysis revealed METH-induced increases in the expression of the antioxidant protein, Hmox1, which lasted for about 24 hours after the METH injection. Additionally, METH caused DA D1 receptor-dependent transit of the Hmox1 regulator protein, Nrf2, from cytosolic into nuclear fractions where the protein exerts its regulatory functions. When taken together, these findings indicate that SCH23390 can provide protection against neuronal apoptosis by inhibiting METH-mediated DA D1 receptor-mediated ER stress in the rat striatum. Our data also suggest that METH-induced toxicity might be a useful model to dissect molecular mechanisms involved in ER stress-dependent events in the rodent brain.

Abstract Background Oxaliplatin and related chemotherapeutic drugs cause painful chronic peripheral neuropathies in cancer patients. We investigated changes in neuronal size profiles and neurofilament immunoreactivity in L5 dorsal root ganglion (DRG) tissue of adult female Wistar rats after multiple-dose treatment with oxaliplatin, cisplatin, carboplatin or paclitaxel. Results After treatment with oxaliplatin, phosphorylated neurofilament heavy subunit (pNF-H) immunoreactivity was reduced in neuronal cell bodies, but unchanged in nerve fibres, of the L5 DRG. Morphometric analysis confirmed significant changes in the number (-75%; P < 0.0002) and size (-45%; P < 0.0001) of pNF-H-immunoreactive neurons after oxaliplatin treatment. pNF-H-immunoreactive neurons had overlapping size profiles and co-localisation with neurons displaying cell body immunoreactivity for parvalbumin, non-phospho-specific neurofilament medium subunit (NF-M) and non-phospho-specific neurofilament heavy subunit (NF-H), in control DRG. However, there were no significant changes in the numbers of neurons with immunoreactivity for parvalbumin (4.6%, P = 0.82), NF-M (-1%, P = 0.96) or NF-H (0%; P = 0.93) after oxaliplatin treatment, although the sizes of parvalbumin (-29%, P = 0.047), NF-M (-11%, P = 0.038) and NF-H (-28%; P = 0.0033) immunoreactive neurons were reduced. In an independent comparison of different chemotherapeutic agents, the number of pNF-H-immunoreactive neurons was significantly altered by oxaliplatin (-77.2%; P < 0.0001) and cisplatin (-35.2%; P = 0.03) but not by carboplatin or paclitaxel, and their mean cell body area was significantly changed by oxaliplatin (-31.1%; P = 0.008) but not by cisplatin, carboplatin or paclitaxel. Conclusion This study has demonstrated a specific pattern of loss of pNF-H immunoreactivity in rat DRG tissue that corresponds with the relative neurotoxicity of oxaliplatin, cisplatin and carboplatin. Loss of pNF-H may be mechanistically linked to oxaliplatin-induced neuronal atrophy, and serves as a readily measureable endpoint of its neurotoxicity in the rat model.