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1.
Proc Natl Acad Sci U S A ; 119(30): e2113912119, 2022 07 26.
Artigo em Inglês | MEDLINE | ID: mdl-35857871

RESUMO

Studies of active matter-systems consisting of individuals or ensembles of internally driven and damped locomotors-are of interest to physicists studying nonequilibrium dynamics, biologists interested in individuals and swarm locomotion, and engineers designing robot controllers. While principles governing active systems on hard ground or within fluids are well studied, another class of systems exists at deformable interfaces. Such environments can display mixes of fluid-like and elastic features, leading to locomotor dynamics that are strongly influenced by the geometry of the surface, which, in itself, can be a dynamical entity. To gain insight into principles by which locomotors are influenced via a deformation field alone (and can influence other locomotors), we study robot locomotion on an elastic membrane, which we propose as a model of active systems on highly deformable interfaces. As our active agent, we use a differential driven wheeled robotic vehicle which drives straight on flat homogeneous surfaces, but reorients in response to environmental curvature. We monitor the curvature field-mediated dynamics of a single vehicle interacting with a fixed deformation as well as multiple vehicles interacting with each other via local deformations. Single vehicles display precessing orbits in centrally deformed environments, while multiple vehicles influence each other by local deformation fields. The active nature of the system facilitates a differential geometry-inspired mathematical mapping from the vehicle dynamics to those of test particles in a fictitious "spacetime," allowing further understanding of the dynamics and how to control agent interactions to facilitate or avoid multivehicle membrane-induced cohesion.


Assuntos
Locomoção , Robótica , Humanos
2.
Anaesthesia ; 79(7): 725-734, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38385772

RESUMO

Non-steroidal anti-inflammatory drugs (NSAIDs) are one of the mainstays of multimodal pain management. While effective for acute pain control, recent pre-clinical evidence has raised concerns regarding an association between NSAIDs and chronic pain and potential opioid use. Our objective was to explore the association between peri-operative use of prescription NSAIDs and the need for continued opioid prescriptions lasting 90-180 days in previously opioid-naïve patients undergoing total knee arthroplasty. A database of health claims in the USA was used to identify all opioid-naïve adult patients who underwent primary knee arthroplasty between January 2010 and October 2021. We evaluated the magnitude of association between peri-operative prescription NSAID claims and claims for opioids at 90 days postoperatively using multivariable logistic regression models. Secondary outcomes included: the magnitude of association between peri-operative NSAID prescription and claims for opioids at 180 days postoperatively; and identifying other potential factors associated with opioid claims at 90 days postoperatively. After risk adjustment using multivariable logistic regression models in the 789,736-patient cohort, the adjusted odds ratio (95%CI) for a continuous claim of opioids at 90 and 180 days postoperatively among patients with a peri-operative NSAID prescription within 30 days was 1.32 (1.30-1.35), p < 0.001; and 1.12 (1.10-1.15), p < 0.001, respectively. This estimate of effect remained robust at 90 days after accounting for known potential confounders, including pre-existing knee pain and acute postoperative pain severity. Similar analysis of other pain medications (e.g. paracetamol) did not detect such an association. This population-based cohort study suggests that peri-operative prescription NSAID use may be associated with continued opioid prescription claims at 90 and 180 days after knee arthroplasty, even after adjusting for other observed covariates for continuous opioid claims. These novel findings can inform clinical decision-making for post-surgical pain management, risk-benefit discussions with patients and future research.


Assuntos
Analgésicos Opioides , Anti-Inflamatórios não Esteroides , Artroplastia do Joelho , Dor Pós-Operatória , Humanos , Analgésicos Opioides/uso terapêutico , Anti-Inflamatórios não Esteroides/uso terapêutico , Feminino , Masculino , Estudos Retrospectivos , Dor Pós-Operatória/tratamento farmacológico , Idoso , Pessoa de Meia-Idade , Estudos de Coortes , Prescrições de Medicamentos/estatística & dados numéricos , Adulto , Assistência Perioperatória/métodos
3.
Saudi Pharm J ; 32(3): 101964, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38328791

RESUMO

Autism spectrum disorder (ASD) is a complex neurodevelopmental illness that often emerges in early childhood. The incidence of ASD has shown a notable rise in recent years. ASD is defined by deficits in social communication, and presence of rigid and repetitive behaviors and interests. The underlying mechanisms of ASD remain elusive. Multiple studies have documented the presence of neuroinflammation and increased levels of inflammatory cytokines, specifically, IL-6, TNF, and NF-κB, in various brain regions, including the prefrontal cortex (PFC) and hippocampus in individuals with ASD. Noradrenergic neurons play a crucial role in brain development and the regulation of motor, behavioral, and memory functions. This study sought to examine the impact of intracerebroventricular (icv.) injection of the neurotoxin, 6-hydroxydopamine (6-OHDA), in the caudal dorsal vagal complex A2 neurons on various neuroinflammatory pathways at the hippocampus and PFC in valproic acid (VPA) autistic animal model. This was done in conjunction with an intraperitoneal (i.p.) injection of Lipopolysaccharides (LPS) in animal models with VPA-induced autism. We specifically examined the impact of the caudal fourth ventricle 6-OHDA icv. injection and LPS (i.p.) injection on self-grooming behavior. We measured the mRNA expression of IL-6, TNF-a, and NF-κB using qRT-PCR, and the protein expression of COX-2, GPX-1, p-AMPK, and AMPK using western blot analysis. The self-grooming activity was considerably higher in the combined treatment group (6-OHDA icv. + LPS i.p.) compared to the control group. A substantial increase observed in the expression of IL-6, TNF-α, and NF-κB genes in the PFC of the treatment group that received icv. Administration of 6-OHDA, compared to the control group. The VPA-autism rats that received the combo treatment exhibited a slight increase in the expression level of NF-κB gene in the hippocampus, compared to the control group. At the PFC, we noticed a substantial drop in the expression of the antioxidant protein GPX-1 in the group that received the combo treatment compared to the control group. Our data investigates a novel aspect that the 6-OHDA-induced inhibition of hindbrain A2 neurons could be influencing the neuroinflammatory pathways in the PFC and hippocampus of autistic animal models.

4.
Anaesthesia ; 78(2): 207-224, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36326047

RESUMO

Anterior cruciate ligament reconstruction can cause moderate to severe acute postoperative pain. Despite advances in our understanding of knee innervation, consensus regarding the most effective regional anaesthesia techniques for this surgical population is lacking. This network meta-analysis compared effectiveness of regional anaesthesia techniques used to provide analgesia for anterior cruciate ligament reconstruction. Randomised trials examining regional anaesthesia techniques for analgesia following anterior cruciate ligament reconstruction were sought. The primary outcome was opioid consumption during the first 24 h postoperatively. Secondary outcomes were: rest pain at 0, 6, 12 and 24 h; area under the curve of pain over 24 h; and opioid-related adverse effects and functional recovery. Network meta-analysis was conducted using a frequentist approach. A total of 57 trials (4069 patients) investigating femoral nerve block, sciatic nerve block, adductor canal block, local anaesthetic infiltration, graft-donor site infiltration and systemic analgesia alone (control) were included. For opioid consumption, all regional anaesthesia techniques were superior to systemic analgesia alone, but differences between regional techniques were not significant. Single-injection femoral nerve block combined with sciatic nerve block had the highest p value probability for reducing postoperative opioid consumption and area under the curve for pain severity over 24 h (78% and 90%, respectively). Continuous femoral nerve block had the highest probability (87%) of reducing opioid-related adverse effects, while local infiltration analgesia had the highest probability (88%) of optimising functional recovery. In contrast, systemic analgesia, local infiltration analgesia and adductor canal block were each poor performers across all analgesic outcomes. Regional anaesthesia techniques that target both the femoral and sciatic nerve distributions, namely a combination of single-injection nerve blocks, provide the most consistent analgesic benefits for anterior cruciate ligament reconstruction compared with all other techniques but will most likely impair postoperative function. Importantly, adductor canal block, local infiltration analgesia and systemic analgesia alone each perform poorly for acute pain management following anterior cruciate ligament reconstruction.


Assuntos
Anestesia por Condução , Reconstrução do Ligamento Cruzado Anterior , Humanos , Analgésicos Opioides/uso terapêutico , Metanálise em Rede , Analgésicos , Anestesia por Condução/métodos , Dor Pós-Operatória/tratamento farmacológico , Dor Pós-Operatória/prevenção & controle , Dor Pós-Operatória/etiologia , Nervo Femoral , Reconstrução do Ligamento Cruzado Anterior/efeitos adversos , Reconstrução do Ligamento Cruzado Anterior/métodos
5.
Saudi Pharm J ; 31(2): 245-254, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36942275

RESUMO

Store-operated calcium entry (SOCE) is an important pathway for calcium signaling that regulates calcium influx across the plasma membrane upon the depletion of calcium stores in the endoplasmic reticulum. SOCE participates in regulating a number of physiological processes including cell proliferation and migration while SOCE dysregulation has been linked with pathophysiological conditions such as inflammation and cancer. The crosslink between cancer and inflammation has been well-established where abundant evidence demonstrate that inflammation plays a role in cancer pathophysiology and the response of cancer cells to chemotherapeutic agents including cisplatin. Indeed, the efficacy of cisplatin against cancer cells is reduced by inflammation. Interestingly, it was shown that SOCE enhances inflammatory signaling in immune cells. Therefore, the main objectives of this study are to examine the impact of SOCE inhibition on the cisplatin sensitivity of breast cancer cells and to explore its related mechanism in modulating the inflammatory response in breast cancer cells. Our findings showed that SOCE inhibitor (BTP2) enhanced cisplatin cytotoxicity against resistant breast cancer cells via inhibition of cell proliferation and migration as well as induction of apoptosis. We also found an upregulation in the gene expression of two major components of SOCE, STIM1 and ORAI1, in cisplatin-resistant breast cancer cells compared to cisplatin-sensitive breast cancer cells. In addition, cisplatin treatment increased the gene expression of STIM1 and ORAI1 in cisplatin-resistant breast cancer cells. Finally, this study also demonstrated that cisplatin therapy caused an increase in the gene expression of inflammatory mediators COX2, IL-8, and TNF-α as well as COX2 protein and upon SOCE inhibition using BTP2, the effect of cisplatin on the inflammatory mediators was reversed. Altogether, this study has proven the pivotal role of SOCE in cisplatin resistance of breast cancer cells and showed the importance of targeting this pathway in improving breast cancer therapy.

6.
Saudi Pharm J ; 31(8): 101669, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37576853

RESUMO

Previous investigations have shown that D. viscosa herbal extract is often used to treat a variety of diseases. Therefore, the purpose of this study was to investigate any additional potential impacts on rat liver and kidney damage induced by diabetes. Streptozotocin (STZ) (60 mg/kg/day) was given as a single dosage to cause type 1 diabetes. After then, diabetic rats received oral doses of D. viscosa for four weeks at 150 and 300 mg/kg/day. Blood, liver, and kidney tissues were collected at the end of the treatment and examined. Analysis was made of the serum lipid profile, liver, and kidney functions, as well as blood biochemistry. Moreover, the levels of tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), interleukin-1 beta (IL-1ß), prostaglandin E-2 (PGE-2), and nitric oxide (NO) were estimated in serum. In liver and kidney samples, thiobarbituric acid reactive substances (TBARs) and reduced glutathione (GSH), as well as the pro-inflammatory cytokines and enzymatic activities of glutathione peroxidase (GPx), glutathione reeducates (GR), glutathione-S-transferase (GST), catalase (CAT), and superoxide dismutase (SOD) were analyzed. Histological changes in liver and kidney cross-sections were also observed. Our findings demonstrated that D. viscosa dramatically decreased pro-inflammatory indicators in blood, kidney, and liver tissues as well as blood glucose, and restored insulin levels, and lipid profiles. Additionally, it significantly raises the antioxidant enzyme activity SOD, CAT, GPx, and GST, while significantly lowering TBARs levels. The above-mentioned biochemical changes that took place in tissues were further supported by histological alterations. These findings imply that D. viscosa protects against STZ-induced hyperglycemia, aberrant lipid synthesis, and oxidative stress and that these benefits may be mediated by interacting with various targets to increase the levels of antioxidant enzymes in the liver and kidneys. Its mode of action and safety for use as medicine against various metabolic problems caused by diabetes require more research.

7.
Anaesthesia ; 77(10): 1152-1162, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-35947882

RESUMO

The quadratus lumborum block (QLB) is reported to reduce pain and improve function following total hip arthroplasty; however, randomised controlled trials evaluating the benefits of adding this block to general or spinal anaesthesia in this population are conflicting. We performed a systematic review seeking randomised controlled trials investigating QLB benefits for total hip arthroplasty, stratifying comparisons regarding the addition of QLB to either general or spinal anaesthesia. The primary outcome was 24-h area under the curve (AUC) pain score. Pain scores were interpreted in the context of a population-specific minimal clinically important difference of 1.86 cm on a 10-cm visual analogue scale, or an AUC pain score of 5.58 cm.h. Secondary outcomes included analgesic consumption, functional recovery and opioid-related side-effects. In all, 18 trials (1318 patients) were included. Adding QLB to general or spinal anaesthesia improved 24-h AUC rest pain scores by a mean difference (95%CI) of -3.56 cm.h (-6.70 to -0.42; p = 0.034) and - 4.19 cm.h (-7.20 to -1.18; p = 0.014), respectively. These improvements failed to reach the pre-determined minimal clinically important difference, as did the reduction in analgesic consumption. Quadratus lumborum block improved functional recovery for general, but not spinal, anaesthesia. Opioid-related side-effects were reduced with QLB regardless of anaesthetic modality. Low-to-moderate quality evidence suggests that the extent to which adding QLB to either general or spinal anaesthesia reduces postoperative pain and opioid consumption after total hip arthroplasty is statistically significant but may be clinically unimportant for most patients. However, adding QLB to general anaesthesia might enhance functional recovery. Taken together, our findings do not support the routine use of QLB as part of multimodal analgesic regimens for total hip arthroplasty.


Assuntos
Analgésicos Opioides , Artroplastia de Quadril , Analgésicos , Analgésicos Opioides/uso terapêutico , Anestésicos Locais/uso terapêutico , Humanos , Dor Pós-Operatória/prevenção & controle
8.
Saudi Pharm J ; 30(8): 1159-1169, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-36164571

RESUMO

Gefitinib is a tyrosine kinase inhibitor (TKI) of the epidermal growth factor receptor (EGFR), used for the treatment of advanced or metastatic non-small cell lung cancer. Recently, studies proved that Gefitinib-induced cardiotoxicity through induction of oxidative stress leads to cardiac hypertrophy. The current study was conducted to understand the mechanisms underlying gefitinib-induced cardiac hypertrophy through studying the roles of angiotensin II (AngII), oxidative stress, and mitogen-activated protein kinase (MAPK) pathway. Male Wistar albino rats were treated with valsartan, gefitinib, or both for four weeks. Blood samples were collected for AngII and cardiac markers measurement, and hearts were harvested for histological study and biochemical analysis. Gefitinib caused histological changes in the cardiac tissues and increased levels of cardiac hypertrophy markers, AngII and its receptors. Blocking of AngII type 1 receptor (AT1R) via valsartan protected hearts and normalized cardiac markers, AngII levels, and the expression of its receptors during gefitinib treatment. valsartan attenuated gefitinib-induced NADPH oxidase and oxidative stress leading to down-regulation of JNK/p38-MAPK pathway. Collectively, AT1R blockade adjusted AngII-induced NADPH oxidase and JNK/p38-MAPK leading to attenuation of gefitinib-induced cardiac hypertrophy. This study found a pivotal role of AngII/AT1R signaling in gefitinib-induced cardiac hypertrophy, which may provide novel approaches in the management of EGFRIs-induced cardiotoxicity.

9.
Ann Oncol ; 32(11): 1391-1399, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34400292

RESUMO

BACKGROUND: Prior antibiotic therapy (pATB) is known to impair efficacy of single-agent immune checkpoint inhibitors (ICIs), potentially through the induction of gut dysbiosis. Whether ATB also affects outcomes to chemo-immunotherapy combinations is still unknown. PATIENTS AND METHODS: In this international multicentre study, we evaluated the association between pATB, concurrent ATB (cATB) and overall survival (OS), progression-free survival (PFS) and objective response rate (ORR) in patients with non-small-cell lung cancer (NSCLC) treated with first-line chemo-immunotherapy at eight referral institutions. RESULTS: Among 302 patients with stage IV NSCLC, 216 (71.5%) and 61 (20.2%) patients were former and current smokers, respectively. Programmed death-ligand 1 tumour expression in assessable patients (274, 90.7%) was ≥50% in 76 (25.2%), 1%-49% in 84 (27.9%) and <1% in 113 (37.5%). Multivariable analysis showed pATB-exposed patients to have similar OS {hazard ratio (HR) = 1.42 [95% confidence interval (CI): 0.91-2.22]; P = 0.1207} and PFS [HR = 1.12 (95% CI: 0.76-1.63); P = 0.5552], compared to unexposed patients, regardless of performance status. Similarly, no difference with respect to ORR was found across pATB exposure groups (42.6% versus 57.4%, P = 0.1794). No differential effect was found depending on pATB exposure duration (≥7 versus <7 days) and route of administration (intravenous versus oral). Similarly, cATB was not associated with OS [HR = 1.29 (95% CI: 0.91-1.84); P = 0.149] and PFS [HR = 1.20 (95% CI: 0.89-1.63); P = 0.222] when evaluated as time-varying covariate in multivariable analysis. CONCLUSIONS: In contrast to what has been reported in patients receiving single-agent ICIs, pATB does not impair clinical outcomes to first-line chemo-immunotherapy of patients with NSCLC. pATB status should integrate currently available clinico-pathologic factors for guiding first-line treatment decisions, whilst there should be no concern in offering cATB during chemo-immunotherapy when needed.


Assuntos
Antibacterianos , Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Antibacterianos/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Humanos , Imunoterapia , Neoplasias Pulmonares/tratamento farmacológico , Resultado do Tratamento
10.
Helminthologia ; 58(2): 162-172, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34248376

RESUMO

Cystic echinococcosis (CE) is a zoonotic disease caused by the larval stage of Echinococcus granulosus tapeworms. These parasites have a worldwide geographic distribution and pose a serious threat to livestock industry as well as human health in the endemic areas. CE is widely distributed in Pakistan. However, very few reports are available related to the regional transmission of E. granulosus. A retrospective analysis was conducted of surgically confirmed CE patients who were treated at Shoukat Khanum Memorial Cancer Hospital and Research Centre in Lahore, Punjab Province, Pakistan from 2007 - 2018. In total, 536 CE patients were evaluated during the study period. Cases originated from the provinces of Khyber Pakhtunkhwa (n=336), Punjab (n=147), Baluchistan (n=18), Sindh (n=3), Islamabad (n=2), Gilgit Baltistan (n=1), and Azad Jammu and Kashmir (n=1). An additional 28 cases were from Afghanistan. The highest number of CE cases was reported in 2013 (n=90). Females made up a larger proportion of cases (n=310; 57.8 %) than males (n=226; 42.2 %). Most patients were members of the Pashtun (n=197; 36.7 %), Hindku (n=142; 26.5 %), and Punjabi (n=118; 22.0 %) ethnic groups. The largest number of cysts was obtained from the liver (137/536; 25.6 %). This study showed that CE is likely present throughout Pakistan. In order to control the disease, a comprehensive control program and regional surveillance are needed.

11.
Cryo Letters ; 40(3): 159-163, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31095664

RESUMO

BACKGROUND: Spermatozoa are prone to mechanical and biochemical stresses upon freezing. The influx of Ca++ causes early capacitation and production of reactive oxygen species. OBJECTIVE: To evaluate the effect of ethylenediaminetetraacetic acid (EDTA) as a calcium chelator in a semen extender. MATERIALS AND METHODS: The effect of EDTA concentrations (0%, 0.1%, 0.2% and 0.3%) on the post thaw quality of buffalo bull spermatozoa were studied. RESULTS: The extender with 0.2% EDTA improved significantly visual motility, progressive motility and plasma membrane integrity. Sperm kinematics, such as beat cross frequency (BCF), curved line velocity (VCL), straight line velocity (VSL) and average path velocity (VAP), were higher in the extender with 0.2% EDTA. EDTA at 0.2% improves semen parameters (visual motility, supra vital plasma membrane integrity, chromatin integrity and percentage viable spermatozoa with intact acrosome. CONCLUSION: The EDTA supplementation in a semen extender improves the post-thaw quality of Nili-Ravi buffalo bull semen.


Assuntos
Búfalos , Quelantes/química , Criopreservação/veterinária , Ácido Edético/química , Preservação do Sêmen/veterinária , Animais , Crioprotetores , Masculino , Motilidade dos Espermatozoides , Espermatozoides
12.
Exp Physiol ; 103(2): 236-249, 2018 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-29114945

RESUMO

NEW FINDINGS: What is the central question of the study? Chronic glucose feeding accompanied by glucose injection (i.p.) causes sustained hyperglycaemia and hypertension in rats. The exact reason for the hypertension is not known. We explore some molecular pathways of the renal proximal tubule that might promote Na+ retention. What is the main finding and its importance? Development of hypertension was mediated by upregulation of the renal renin-angiotensin system and oxidative stress, acting via the Na+ -K+ -ATPase α1 -subunit in the proximal tubule, which appears to pump intracellular Na+ into the extracellular space, increasing Na+ reabsorption and blood pressure. Targeting the Na+ -K+ -ATPase α1 -subunit might provide a therapeutic strategy for treatment of hypertension. Feeding animals glucose-, fructose-, sucrose- and fat-enriched diets can lead to diet-induced hyperglycaemia, the severity of which largely depends on the types and concentrations of the nutrients used and duration of the dietary intervention. As a dietary intervention strategy, we adopted glucose-enriched diet and drinking water, with i.p. glucose injection at a dose previously determined to be effective to establish a sustained hyperglycaemia over a period of 2 weeks. We used four groups of Sprague-Dawley rats: control; glucose treated; glucose plus tempol treated; and glucose plus captopril treated. Blood glucose concentrations started to increase gradually from day 3, peaked (321 mg dl-1 ) at day 12 and remained at similar levels until the end of the study on day 14 in the glucose treated-group compared with the control group. In contrast, the tempol- and captopril-treated groups showed significantly high glucose concentrations only in the second week. The plasma insulin concentration was significantly increased in glucose-treated animals but not in tempol- and captopril-treated groups when compared with the control rats. We also observed elevated blood pressure in the glucose-treated group compared with the control group, which can be attributed to the increase in angiotensin II concentrations from 46.67 to 99 pg ml-1 (control versus glucose), increased oxidative stress in the cortical proximal tubule (PT), decreased urine flow, and increased expression and activity of the PT-specific α1 -subunit of Na+ -K+ -ATPase in the renal cortex, which is responsible for increased sodium reabsorption from epithelial cells of PT into the peritubular capillaries, leading to increased blood volume and eventual blood pressure. All these events were reversed in captopril- and tempol-treated animals.


Assuntos
Pressão Sanguínea/efeitos dos fármacos , Captopril/farmacologia , Glucose/metabolismo , Hiperglicemia/fisiopatologia , Hipertensão/fisiopatologia , Animais , Túbulos Renais Proximais/efeitos dos fármacos , Masculino , Estresse Oxidativo/efeitos dos fármacos , Ratos Sprague-Dawley , Sistema Renina-Angiotensina/efeitos dos fármacos , Sódio/metabolismo
13.
J Inherit Metab Dis ; 41(6): 1275-1283, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-30167885

RESUMO

OBJECTIVES: To describe the spectrum of movement disorders and cerebrospinal fluid (CSF) neurotransmitter profiles in paediatric patients with POLG disease. METHODS: We identified children with genetically confirmed POLG disease, in whom CSF neurotransmitter analysis had been undertaken. Clinical data were collected retrospectively. CSF neurotransmitter levels were compared to both standardised age-related reference ranges and to non-POLG patients presenting with status epilepticus. RESULTS: Forty-one patients with POLG disease were identified. Almost 50% of the patients had documented evidence of a movement disorder, including non-epileptic myoclonus, choreoathetosis and ataxia. CSF neurotransmitter analysis was undertaken in 15 cases and abnormalities were seen in the majority (87%) of cases tested. In many patients, distinctive patterns were evident, including raised neopterin, homovanillic acid and 5-hydroxyindoleacetic acid levels. CONCLUSIONS: Children with POLG mutations can manifest with a wide spectrum of abnormal movements, which are often prominent features of the clinical syndrome. Underlying pathophysiology is probably multifactorial, and aberrant monoamine metabolism is likely to play a role.


Assuntos
Doenças Mitocondriais/líquido cefalorraquidiano , Transtornos dos Movimentos/etiologia , Neurotransmissores/líquido cefalorraquidiano , Adolescente , Criança , Pré-Escolar , DNA Polimerase gama/genética , Feminino , Ácido Homovanílico/líquido cefalorraquidiano , Humanos , Ácido Hidroxi-Indolacético/líquido cefalorraquidiano , Lactente , Masculino , Doenças Mitocondriais/genética , Mutação , Neopterina/líquido cefalorraquidiano , Estudos Retrospectivos
15.
Br J Anaesth ; 121(4): 822-841, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30236244

RESUMO

Recent reports of local-anaesthetic (LA)-induced myotoxicity after peripheral nerve blocks have increased the interest in this less commonly known complication. Basic science evidence investigating LA-induced myotoxicity seems to demonstrate a pattern, but findings from human studies vary. This systematic review summarises the existing myotoxicity evidence and empirically examines its implications. Databases were searched for all in vitro animal and human studies evaluating LA-induced myotoxicity. Studies were stratified by design. Data sought included the model examined, LA used, injury mechanisms, nature of damage, and extent of recovery. For human studies, we also aimed to estimate prevalence and recovery rates. One hundred and fifteen studies, mainly animal and ophthalmic, were included. Myotoxicity risk factors included higher concentrations and prolonged exposure to LA, and use of bupivacaine. Injury mechanisms involved early and late aberrations to cytoplasmic calcium (Ca2+) homeostasis by the sarcoplasmic reticulum Ca2+ ATPase. Incidence in ophthalmic studies was 0.77% (392 of 50 618). Inflammatory changes within a few days after exposure marked the onset of myotoxicity, and myo-degeneration followed within the first week post-exposure. Time to recovery in human muscles ranged between 4 days to 1 yr. None/partial and complete recovery were observed in 61% and 38% of patients, respectively. Across all experimental models, skeletal muscles exposed to LA consistently display myotoxic effects. Evidence is robust in animal and ophthalmic studies, and displays a concerning signal with continuous adductor canal block use in human case reports. Exploring the clinical prevalence, severity, and risk-reducing strategies of myotoxicity should be prioritised.


Assuntos
Anestesia por Condução/efeitos adversos , Anestésicos Locais/efeitos adversos , Doenças Musculares/induzido quimicamente , Anestésicos Locais/toxicidade , Animais , Humanos , Bloqueio Nervoso/efeitos adversos
16.
Eur J Prosthodont Restor Dent ; 26(2): 86-93, 2018 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-29517876

RESUMO

OBJECTIVES: The 3 objectives are to assess current preferences for impressions for complete dentures, audit practice and compare practice to current UK teaching. METHODS: Three surveys where undertaken; a survey of GDPs preferences, an audit of practice and a survey of teaching in UK dental schools. RESULTS: UK Universities advocate border moulded custom trays. In stated preferences, 99% of practitioners used custom trays for private practice; 67% for NHS work. In actual use, the audit found 91% practitioners in private practice used custom trays; in NHS practice 78% did so. The most widely taught materials were silicone (43%), alginate (29%), & zinc oxide eugenol paste (19%). In practitioners stated preferences, 97% of NHS and 53% of private dentists listed alginate as an option; however the audit showed only 74% (NHS) and 52% (private) actually used alginate, with 20% (NHS) and 48% (private) using silicone. CONCLUSIONS: Definitive impressions in custom trays are used by GDPs for both private and NHS work; they are universally taught at UK dental schools. Alginate is popular in NHS practice; however, silicone is more widely taught in UK Universities. The use of silicone materials for definitive impressions has increased since 1999. In UK private practice silicone usage is aligned in popularity with alginate.


Assuntos
Técnica de Moldagem Odontológica , Planejamento de Dentadura , Prótese Total , Educação em Odontologia , Padrões de Prática Odontológica/estatística & dados numéricos , Materiais para Moldagem Odontológica , Humanos , Inquéritos e Questionários , Reino Unido
17.
J Appl Microbiol ; 123(1): 204-216, 2017 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-28423218

RESUMO

AIM: Analysis of a blend of volatile organic compounds (VOCs) released by Pseudomonas spp. with growth-promoting effect in Vigna radiata seedlings. METHODS AND RESULTS: Plant growth-promoting activity of VOCs produced by five different Pseudomonas spp. was investigated by I-plate technique. VOCs produced by different organisms were extracted by various solvents (methanol, ethyl acetate, hexane and butanol) and were identified by gas chromatography-mass spectrometric analysis. The major VOCs identified were undecane, nonadecane, hexacosane, tetradecane, heptacosane, pentadecane, dodecane and tetratetracontane. The cultural conditions for the production of VOCs with plant growth enhancement effect were optimized and further confirmed using pure pentadecane as a candidate VOC. CONCLUSIONS: The study provides insight into plant beneficial effect of VOCs produced by Pseudomonas spp. Remarkable modulation in the production of VOCs with plant growth-promoting effect by rhizobacteria was found to be dependent on the bacterial strain and its concentration. SIGNIFICANCE AND IMPACT OF THE STUDY: The study describes the requirement to consider bacterial VOC production also for preparing plant probiotic formulations. As VOCs are least considered for preparation of commercial plant growth-promoting rhizobacterial strain formulation, the results of the study is highly significant.

18.
Adv Exp Med Biol ; 1043: 359-383, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29224103

RESUMO

Vital nerve cell functions, including maintenance of transmembrane voltage and information transfer, occur at high energy expense. Inadequate provision of the obligate metabolic fuel glucose exposes neurons to risk of dysfunction or injury. Clinical hypoglycemia rarely occurs in nondiabetic individuals but is an unfortunate regular occurrence in patients with type 1 or advanced insulin-treated type 2 diabetes mellitus. Requisite strict glycemic control, involving treatment with insulin, sulfonylureas, or glinides, can cause frequent episodes of iatrogenic hypoglycemia due to defective counter-regulation, including reduced glycemic thresholds and diminished magnitude of motor responses. Multiple components of the body's far-reaching energy balance regulatory network, including the hindbrain dorsal vagal complex, provide dynamic readout of cellular energetic disequilibrium, signals that are utilized by the hypothalamus to shape counterregulatory autonomic, neuroendocrine, and behavioral outflow toward restoration of glucostasis. The ovarian steroid hormone 17ß-estradiol acts on central substrates to preserve nerve cell energy stability brain-wide, thereby providing neuroprotection against bio-energetic insults such as neurodegenerative diseases and acute brain ischemia. The current review highlights recent evidence implicating estrogen in gluco-regulation in females by control of hindbrain metabolic sensor screening and signaling of hypoglycemia-associated neuro-energetic instability. It is anticipated that new understanding of the mechanistic basis of how estradiol influences metabolic sensory input from this critical brain locus to discrete downstream regulatory network substrates will likely reveal viable new molecular targets for therapeutic simulation of hormone actions that promote positive neuronal metabolic state during acute and recurring hypoglycemia.


Assuntos
Glicemia/metabolismo , Encéfalo/metabolismo , Metabolismo Energético , Estradiol/metabolismo , Hipoglicemia/sangue , Hipoglicemiantes/efeitos adversos , Insulina/efeitos adversos , Animais , Biomarcadores/sangue , Encéfalo/efeitos dos fármacos , Encéfalo/patologia , Encéfalo/fisiopatologia , Metabolismo Energético/efeitos dos fármacos , Feminino , Disparidades nos Níveis de Saúde , Humanos , Hipoglicemia/induzido quimicamente , Hipoglicemia/patologia , Hipoglicemia/fisiopatologia , Masculino , Caracteres Sexuais , Fatores Sexuais , Transdução de Sinais
19.
Int Nurs Rev ; 64(4): 502-510, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28093735

RESUMO

BACKGROUND: In Singapore, employees aged 62-65 can continue to be employed if they meet the re-employment eligibility criteria. This policy, coupled with an ageing workforce, calls for age-friendly initiatives, specific to work-related challenges faced by older nurses. AIM: To determine work-related challenges faced by older nurses. METHODS: A mixed method sequential explanatory study was conducted with nurses, aged 50 and above, working in a healthcare cluster in Singapore. In the quantitative phase, a questionnaire was administered to 534 nurses to elicit work-related challenges, then in-depth interviews with 30 nurses were carried out to help explain why certain tasks and work circumstances became harder. RESULTS: Results of the survey indicated that the top three challenges were coping with changes, working with computers and reading labels. Place of work, salary range, gender and race were significantly associated with different work-related challenges. Five themes emerged from the qualitative data: physical demands of work and workload, new technology, need for further education, working with younger nurses and in intercultural teams, and changing public expectations and professional image. DISCUSSION AND CONCLUSION: The study supports the current literature on the challenges older nurses face with technological advancement. However, older nurses in our study reported less aches and pain as compared to that reported elsewhere. There is a need for specific strategies that will address changes in work processes and environment in order to retain older nurses. IMPLICATIONS FOR NURSING AND NURSING POLICY: When devising age-friendly work improvement initiatives, it is important for nurse leaders to factor in the needs of nurses working in different care environments, who are of different ranks, or are from different ethnic backgrounds.


Assuntos
Envelhecimento/psicologia , Emprego/psicologia , Emprego/normas , Recursos Humanos de Enfermagem Hospitalar/psicologia , Recursos Humanos de Enfermagem Hospitalar/normas , Local de Trabalho/organização & administração , Local de Trabalho/psicologia , Adaptação Psicológica , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Cultura Organizacional , Retenção Psicológica , Singapura , Inquéritos e Questionários
20.
Crit Care Med ; 44(10): e940-8, 2016 10.
Artigo em Inglês | MEDLINE | ID: mdl-27347762

RESUMO

OBJECTIVES: Despite being the epicenter of recent pandemics, little is known about critical care in Asia. Our objective was to describe the structure, organization, and delivery in Asian ICUs. DESIGN: A web-based survey with the following domains: hospital organizational characteristics, ICU organizational characteristics, staffing, procedures and therapies available in the ICU and written protocols and policies. SETTING: ICUs from 20 Asian countries from April 2013 to January 2014. Countries were divided into low-, middle-, and high-income based on the 2011 World Bank Classification. SUBJECTS: ICU directors or representatives. MEASUREMENTS AND MAIN RESULTS: Of 672 representatives, 335 (50%) responded. The average number of hospital beds was 973 (SE of the mean [SEM], 271) with 9% (SEM, 3%) being ICU beds. In the index ICUs, the average number of beds was 21 (SEM, 3), of single rooms 8 (SEM, 2), of negative-pressure rooms 3 (SEM, 1), and of board-certified intensivists 7 (SEM, 3). Most ICUs (65%) functioned as closed units. The nurse-to-patient ratio was 1:1 or 1:2 in most ICUs (84%). On multivariable analysis, single rooms were less likely in low-income countries (p = 0.01) and nonreferral hospitals (p = 0.01); negative-pressure rooms were less likely in private hospitals (p = 0.03) and low-income countries (p = 0.005); 1:1 nurse-to-patient ratio was lower in private hospitals (p = 0.005); board-certified intensivists were less common in low-income countries (p < 0.0001) and closed ICUs were less likely in private (p = 0.02) and smaller hospitals (p < 0.001). CONCLUSIONS: This survey highlights considerable variation in critical care structure, organization, and delivery in Asia, which was related to hospital funding source and size, and country income. The lack of single and negative-pressure rooms in many Asian ICUs should be addressed before any future pandemic of severe respiratory illness.


Assuntos
Cuidados Críticos/organização & administração , Atenção à Saúde/organização & administração , Unidades de Terapia Intensiva/organização & administração , Ásia , Protocolos Clínicos , Países Desenvolvidos/estatística & dados numéricos , Países em Desenvolvimento/estatística & dados numéricos , Pesquisa sobre Serviços de Saúde , Número de Leitos em Hospital , Admissão e Escalonamento de Pessoal , Políticas
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