Association of peri-operative prescription of non-steroidal anti-inflammatory drugs with continued prescription of opioids after total knee arthroplasty: a retrospective claims-based cohort study.

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.

Monitoring bovine tick fever on a dairy farm: An economic proposal for rational use of medications.

In this study, we evaluated the monitoring of tick fever (TF) in a Brazilian dairy farm in the Minas Gerais state, Brazil, from July 10 to August 4, 2018. We aimed to identify diagnostic and treatment flaws in the protocol adopted by the farm, and to establish a novel and accurate TF monitoring protocol based on precision dairy farming and rational use of antimicrobials and antiparasitic drugs, while evaluating the economic benefits of the proposed strategy. We monitored TF in 395 heifer calves aged between 3 and 14 mo. According to the farm's standard protocol, all calves with an increase of 0.5°C in rectal temperature compared with the previous week's measurement were treated for Anaplasma spp. and Babesia spp. Blood smears were collected from the tail tip of the treated calves. During the last week of the study, we prepared blood smears of all calves regardless of treatment indication. Economic analysis was performed. The results indicated that at least 56.86% (261/459) of the calves did not require treatment for TF, whereas only 23.09% (106/459) had treatment indications. Negative blood smears (45.97%; 211/459) indicated the possibility of calves being affected by another disease or a condition that was not being adequately treated or those not necessarily sick. These results demonstrate the excessive use of medications, representing a direct economic loss, in addition to potentially favoring the occurrence of resistance to antimicrobials. In contrast, 9.42% (26/276) of calves had no treatment indication based on rectal temperature but had treatment indications based on blood smears. Only 5.73% (42/735) of blood smears had co-infection with hemopathogens, and none had triple co-infection. Therefore, we proposed the monitoring of TF using rectal temperature and microscopic analysis. If implemented, this strategy would result in a direct annual savings of approximately $22,638.96 (77.99%) related to medication for the treatment of TF. Therefore, implementing the proposed protocol would be cheaper than treatment based only on rectal temperatures. The currently implemented TF protocols overestimate the occurrence of TF, resulting in overtreatment. Thus, implementing a TF monitoring protocol based on a microscopy tool is justified, with benefits including rational use of medication, potential to generate savings, and reduced morbidity and mortality rates, in addition to enabling other diagnoses.

Culturable bacterial diversity from a feed water of a reverse osmosis system, evaluation of biofilm formation and biocontrol using phages.

Biofilm formation on reverse osmosis (RO) systems represents a drawback in the application of this technology by different industries, including oil refineries. In RO systems the feed water maybe a source of microbial contamination and thus contributes for the formation of biofilm and consequent biofouling. In this study the planktonic culturable bacterial community was characterized from a feed water of a RO system and their capacities were evaluated to form biofilm in vitro. Bacterial motility and biofilm control were also analysed using phages. As results, diverse Protobacteria, Actinobacteria and Bacteroidetes were identified. Alphaproteobacteria was the predominant group and Brevundimonas, Pseudomonas and Mycobacterium the most abundant genera. Among the 30 isolates, 11 showed at least one type of motility and 11 were classified as good biofilm formers. Additionally, the influence of non-specific bacteriophage in the bacterial biofilms formed in vitro was investigated by action of phages enzymes or phage infection. The vB_AspP-UFV1 (Podoviridae) interfered in biofilm formation of most tested bacteria and may represent a good alternative in biofilm control. These findings provide important information about the bacterial community from the feed water of a RO system that may be used for the development of strategies for biofilm prevention and control in such systems.

Chemical profile and biological potential of essential oil of Psidium bahianum Landrum & Funch (Myrtaceae).

The genus Psidium, belonging to the family Myrtaceae, encompasses several plant species rich in essential oils. Several studies involving different research areas have shown promising results for essential oils, which has attracted interest from diverse sectors, including pharmaceutical, food, and cosmetic industries. Thus, the objective of this study was to evaluate the biological activity of the essential oil extracted from Psidium bahianum leaves (EOPb) collected in an Atlantic Forest remnant in the northern coast of the state of Bahia, Brazil. EOPb was extracted by steam distillation and analyzed through proton nuclear magnetic resonance (1H-NMR). The free radical scavenging activity was assessed using the DPPH methodology (analyzing the scavenging of the stable free radical 1,1-diphenyl-2-picrylhydrazyl). Antimicrobial disk diffusion assays were conducted; toxicity was determined through assays on sheep erythrocytes and Artemia salina. 1H-NMR evaluation showed the presence mainly of monoterpenes and sesquisterpenes. The percentage of antioxidant activity was 18.03±2.53 53 for 125 125 µg mL-1. Antimicrobial assays showed that the essential oil at a concentration of 10 mg mL-1 inhibited the growth of the microorganisms Staphylococcus aureus, Bacillus subtilis, B. cereus, Micrococcus luteus, Escherichia coli, Aspergillus niger, Candida albicans, and C. glabrata. The toxicity results indicated that concentrations of EOPb at 10, 100, 250, and 500 µg mL-1 were not toxic to sheep erythrocytes. The toxicity assay on A. salina showed that the lethal concentration for 50% of individuals (LC50) within 24 and 48 hours were 371.48 and 302 µg mL-1 of EOPb, respectively, which were considered moderately toxic, whereas the LC50 within 72 horas was 33.11 µg mL-1, considered highly toxic. These findings are promising, as the essential oil from P. bahianum leaves showed antimicrobial activity against both Gram-positive and Gram-negative bacteria and fungi. The data obtained for the essential oil toxicity in A. salina could be tested on different tumor cell lines.

YouTube as a source of medical information about epidural analgesia for labor pain.

BACKGROUND: Large gaps remain in our understanding of the role of social media platforms in the dissemination of medical information. This cross-sectional study quantitatively assessed the accuracy and quality of information on YouTube regarding epidural labor analgesia. METHODS: YouTube was searched on May 23, 2020 using keywords 'epidural,' 'epidural for labor,' 'epidural for pregnancy,' 'epidural experience,' and 'epidural risks,' and the top 50 viewed videos from each search were screened. Primary outcomes included the proportion of videos containing non-factual information, and video quality analyzed using the modified DISCERN (mDISCERN) score. RESULTS: Thirteen of 60 (21.7%) videos included non-factual information about epidural analgesia; these videos were viewed more than 16.5 million times (60% of total viewership of the videos analyzed). Mean (standard deviation) mDISCERN score for all included videos was 1.9 (1.3), which is below the threshold for high video-quality. Videos from medical sources (hospitals, medical practices, physicians, other medical professionals) had a higher mDISCERN score compared with videos by non-medical sources (P <0.001). Educational videos from professional societies of obstetrics or obstetric anesthesiology were not captured. CONCLUSION: YouTube is an accessible platform for medical information on epidural labor analgesia, although a significant proportion of videos studied contained non-factual information and presented low video quality. Increased efforts by reputable sources including hospitals, physicians, other medical professionals, and professional societies, to disseminate accurate information, are warranted.

Development of Microbiome Biobanks - Challenges and Opportunities.

The microbiome research field is rapidly evolving, but the required biobanking infrastructure is currently fragmented and not prepared for the biobanking of microbiomes. The rapid advancement of technologies requires an urgent assessment of how biobanks can underpin research by preserving microbiome samples and their functional potential.

Microdissection testicular sperm extraction causes spermatogenic alterations in the contralateral testis.

Testicular sperm extraction (TESE) associated with intracytoplasmic sperm injection has allowed many men presenting non-obstructive azoospermia to achieve fatherhood. Microdissection TESE (microTESE) was proposed as a method to improve sperm retrieval rates in these patients; however, there have been failures. Little is known about whether microTESE leads to spermatogenic alterations in the contralateral testis. We assessed histological outcomes of experimental microTESE in the contralateral testis of adult male rabbits. Nine adult male rabbits were divided into three groups: control (testicular biopsy to observe normal histological and morphometric values), sham (incision of the tunica vaginalis, and a contralateral testicular biopsy to observe histological and morphometric patterns, 45 days later), and study (left testicular microTESE, and a right testicular biopsy to observe histological and morphometric patterns, 45 days later). Sections were assessed by calculating Johnsen-like scores, and measuring total tubule diameter, lumen diameter and epithelial height. The results were compared using ANOVA and Bonferroni's statistical analysis. Morphometric evaluation of the seminiferous tubules did not demonstrate differences between the three groups. However, microTESE caused spermatogenic alterations, leading to maturation arrest in the contralateral testis.

Efficacy of 2-hydroxy-3-phenylsulfanylmethyl-[1,4]-naphthoquinone derivatives against different Trypanosoma cruzi discrete type units: Identification of a promising hit compound.

The limited efficacy of benznidazole (Bz) indicated by failures of current Phase II clinical trials emphasizes the urgent need to identify new drugs with improved safety and efficacy for treatment of Chagas disease (CD). Herein, we analyzed the efficacy of a series of 2-hydroxy-3-phenylsulfanylmethyl-[1,4]-naphthoquinones against different Trypanosoma cruzi discrete type units (DTUs) of relevant clinical forms of CD. Cytotoxic and trypanocidal effect of naphthoquinone derivatives were assessed in mammalian cells, trypomastigotes and intracellular amastigotes using, luminescent assays (CellTiter-Glo and T. cruzi Dm28c-luciferase) and/or counting with a light microscope. Reactive oxygen species (ROS) production and intracellular targets of promising compounds were assessed with 2',7'-dichlorodihydrofluorescein diacetate (H2DCFDA) probe and ultrastructural analysis, respectively. ADMET properties were analyzed by in silico modeling. Most of the compounds showed low cytotoxic effect. Only two compounds (Compounds 2 and 11) had IC50 values lower than Bz, showing higher susceptibility of bloodstream trypomastigotes. Compound 2 exhibited greater efficacy against trypomastigotes from different T. cruzi DTUs, even better than Bz against Brazil and CL strains. Ultrastructural analysis revealed changes in intracellular compartments, suggesting autophagy as one possible mechanism of action. Oxidative stress, induced by Compound 2, resulted in elevated level of ROS, leading to parasite death. Compound 2 was also effective against intracellular amastigotes, showing high selectivity index. ADMET analysis predicted good oral bioavailability, reduced drug metabolism and no carcinogenic potential for Compound 2. The data highlight Compound 2 as a hit compound and stimulate further structural and pharmacological optimization to potentiate its trypanocidal activity and selectivity.

Primary non-metastatic omental myofibrosarcoma in a horse / Miofibrossarcoma omental primário não metastático em um cavalo

Myofibrosarcoma in horses is a rare malignant tumor composed predominantly by myofibroblasts. A 15-year-old horse was referred to the Veterinary Hospital of the Federal University of Parana for evaluation of colic signs. Initial physical examination showed icteric mucous membrane and laboratory analysis found anemia, increased serum activity of ALT, GGT, ALP, and bilirubin. In the exploratory laparotomy a highly vascularized abdominal mass in the left hypochondrium region of approximately 50cm x 45cm x 30cm, adhered to the surrounding structures was observed. Due to the size and adhesions to the omentum, the mass was considered surgically unresectable, and euthanasia was performed followed by necropsy. The immunohistochemical and morphological results indicate the diagnosis of myofibrosarcoma since the neoplastic cells immunoexpressed Vimentin, HHF35 and S100. To the authors' knowledge, this is the first equine case of omental myofibrosarcoma described in the literature.

O miofibrossarcoma em cavalos é um raro tumor maligno, composto predominantemente por miofibroblastos. Um equino, de 15 anos de idade, foi encaminhado ao Hospital Veterinário da Universidade Federal do Paraná, para avaliação de sinais de cólica. O exame clínico inicial apresentou mucosas ictéricas e, nos exames laboratoriais, revelou anemia e aumento sérico de ALT, GGT, ALP e bilirrubina. Na laparotomia exploratória, observou-se massa abdominal vascularizada de aproximadamente 50cm x 45cm x 30cm na região do hipocôndrio esquerdo e aderida às estruturas circunvizinhas. Devido ao tamanho e às aderências ao omento, a massa foi considerada irressecável cirurgicamente, portanto foi realizada a eutanásia e a necropsia. Os resultados imuno-histoquímicos e morfológicos indicam o diagnóstico de miofibrossarcoma, visto que as células neoplásicas imunoexpressaram Vimentin, HHF35 e S100. Portanto, esse é o primeiro caso em equinos de miofibrossarcoma omental descrito na literatura.

A new method for recognizing hand configurations of Brazilian gesture language.

This paper describes a new method for recognizing hand configurations of the Brazilian Gesture Language - LIBRAS - using depth maps obtained with a Kinect® camera. The proposed method comprised three phases: hand segmentation, feature extraction, and classification. The segmentation phase is independent from the background and depends only on pixel depth information. Using geometric operations and numerical normalization, the feature extraction process was done independent from rotation and translation. The features are extracted employing two techniques: (2D)2LDA and (2D)2PCA. The classification is made with a novelty classifier. A robust database was constructed for classifier evaluation, with 12,200 images of LIBRAS and 200 gestures of each hand configuration. The best accuracy obtained was 95.41%, which was greater than previous values obtained in the literature.

Dual action of clonidine on ethanol-induced gastric lesions: is the imidazoline-preferring receptor involved?

The imidazole alpha 2-adrenoceptor agonist, clonidine, exerts a dual action on ethanol-induced gastric lesions. At lower doses, it has a gastroprotective effect which is also seen with two other alpha 2-adrenoceptor agonists - the catecholamine, alpha-methyldopa and the guanidine, guanabenz. The gastroprotective action of the three drugs is prevented by the selective alpha 2-adrenoceptor antagonist, yohimbine, suggesting that the action is mediated by alpha 2-adrenoceptors. However, at higher doses clonidine aggravates ethanol-induced gastric lesions, an effect also seen with another imidazole, oxymetazoline. The aggravating action is not prevented by yohimbine and is not seen with alpha-methyldopa and guanabenz. This suggests that it involves a receptor/mechanism other than alpha 2- possibly an imidazoline-preferring receptor but further work, including radioligand binding studies, is needed to confirm this.

Effect of captopril on oxyphenbutazone and ethanol-induced gastric lesions in rats.

We studied the effect of the angiotensin converting enzyme inhibitor, captopril, on two models of gastric ulcers; oxyphenbutazone and ethanol-induced lesions. There was a significant protective effect against oxyphenbutazone-induced ulcers, which was prevented by prior administration of indomethacin. Captopril, however, failed to protect against ethanol-induced lesions. These findings are discussed in the light of captopril being a sulfhydryl compound with prostaglandin-releasing activity.

Gastric cytoprotection.

The term 'cytoprotection' means protection against gastric mucosal injury by a mechanism other than inhibition or neutralisation of gastric acid. Several mechanisms of gastric cytoprotection have been proposed like increased mucus and bicarbonate secretion, strengthening of gastric mucosal barrier, increased gastric mucosal blood flow, decreased gastric motility, increased formation of prostaglandins and sulfhydryls, scavenging of free radicals, stimulation of cellular growth and repair, decreased release of leukotrienes etc. Some of the drugs widely used in therapy of peptic ulcer are cytoprotective e.g. sucralfate, colloidal bismuth and aluminium containing antacids. As the concept of gastric cytoprotection is becoming widely accepted, the list of drugs which have shown a cytoprotective action in animal experiments is growing rapidly. This list includes zinc sulphate, meciadanol, propranolol, dipyridamole etc.

Effect of antihypertensive drugs on ethanol induced gastric lesions: is there a correlation with mucosal blood flow?

We studied the effect of five antihypertensive drugs on ethanol-induced gastric haemorrhagic lesions in rats. While hydralazine aggravates these lesions, nifedipine and propranolol have a protective action. On the other hand, enalapril and prazosin have no effect. Thus the effects of antihypertensive drugs on ethanol-induced lesions do not always correlate with their reported actions on gastric mucosal blood flow.

Comparison of the effects of captopril and enalapril on oxyphenbutazone and ethanol-induced gastric lesions in rats.

We have compared the effect of the converting enzyme inhibitors, captopril and enalapril, on two models of gastric ulcers, viz; ethanol and oxyphenbutazone-induced lesions in rats. Both captopril and enalapril did not affect ethanol-induced lesions. While captopril significantly protected against oxyphenbutazone-induced lesions, enalapril aggravated the lesions. This difference is probably due to the lack of the protective sulfhydryl group in the chemical structure of enalapril.

Aggravating action of clonidine on ethanol-induced gastric lesions: probable mechanism of action.

Large doses of the imidazoline alpha 2 adrenoreceptor agonist clonidine aggravate ethanol-induced gastric lesions. The alpha 2 adrenoceptor antagonist phentolamine, the opioid antagonist naloxone and the H2 antagonist cimetidine do not prevent this action of clonidine suggesting that it is not mediated by alpha 2, opioid or H2 receptors. Further, like clonidine, high doses of phentolamine and cimetidine aggravate gastric lesions per se, suggesting that all three may be acting at a common 'receptor' site, possibly the imidazoline-preferring receptor (IPR).

Vascular desensitisation--possible role of prostaglandins.

Prolonged exposure to noradrenaline (NA) brings about an increase in the release of prostaglandin (PG)-like material from rat aortic strip. The release is greater with oxymetazoline while methoxamine decreases it. These effects are blocked by yohimbine and prazosin respectively. Pretreatment with 6-OHDA or reserpine diminishes the release of PG-like material. Barium chloride, a non-specific spasmogen, does not affect the release significantly. It appears therefore that the source of PG-like material is presynaptic and that its release mechanism is linked to an alpha 2 (alpha 2) adrenoceptor. It is proposed that this release of PG-like material contributes to the development of desensitisation in vascular tissue.

Aggravating action of hydralazine on ethanol-induced gastric lesions.

Endogenous nitric oxide has been proposed as one of the mediators of gastric cytoprotection. We studied the effect of the vasodilator hydralazine which acts via nitric oxide and thus is expected to have a gastroprotective action. However, hydralazine aggravates ethanol-induced gastric lesions. This effect is not influenced by pretreatment with the selective alpha 1 adrenergic antagonist prazosin but is abolished by the angiotensin converting enzyme inhibitor, captopril suggesting the involvement of the renin-angiotensin system.

Protective effect of propranolol on ethanol-induced gastric lesions in rats: probable mechanism of action.

The non-selective beta-adrenoceptor antagonist, propranolol, has been reported to protect against gastric injury in mice, an effect only partly due to prostaglandin release. This study was designed to confirm the gastric cytoprotective effect of propranolol in another species of animal, the rat, and investigate further its mechanism of action. Our results show that propranolol prevents both ethanol-induced gastric lesions as well as ethanol-induced contraction of the circular muscle of rat fundic strip. The local anaesthetic, lignocaine also inhibited the effect of ethanol on circular muscle. However, timolol, another non-selective beta-adrenoceptor antagonist, failed to produce such an action. The effect of propranolol was abolished by the cyclooxygenase inhibitor, indomethacin and a high dose of the guanylate cyclase inhibitor, methylene blue. The results suggest that in addition to prostaglandins, endogenous nitric oxide and the membrane stabilising action of propranolol may also be involved in its gastroprotective action.