Ultrasound-guided suprainguinal fascia iliaca compartment block and early postoperative analgesia after total hip arthroplasty: a randomised controlled trial.

BACKGROUND: Hip replacement surgery can be painful; postoperative analgesia is crucial for comfort and to facilitate recovery. Regional anaesthesia can reduce pain and postoperative opioid requirements. The role of ultrasound-guided suprainguinal fascia iliaca block for analgesia after elective total hip arthroplasty is not well defined. This randomised trial evaluated its analgesic efficacy. METHODS: Consenting participants (134) scheduled for elective primary total hip arthroplasty under spinal anaesthesia were randomly allocated to receive ultrasound-guided fascia iliaca block with ropivacaine 0.5% or sham block with saline. The primary outcome was opioid consumption in the first 24 h after surgery. Additional outcomes included pain scores at 4, 8, 12, and 16 h, opioid-related side-effects (nausea, vomiting, pruritis), ability to perform physiotherapy on the first postoperative day, and physiotherapist-assessed quadriceps weakness. RESULTS: There were no significant differences in 24-h opioid consumption (block vs sham block, mean difference -3.2 mg oral morphine equivalent, 95% confidence interval -15.3 to 8.1 mg oral morphine equivalent, P=0.55) or any other prespecified outcomes. CONCLUSIONS: In patients undergoing primary total hip arthroplasty, ultrasound-guided suprainguinal fascia iliaca block with ropivacaine did not confer a significant opioid-sparing effect compared with sham block. There were no differences in other secondary outcomes including pain scores, opioid-related side-effects, or ability to perform physiotherapy on the first postoperative day. CLINICAL TRIAL REGISTRATION: www. CLINICALTRIALS: gov (NCT03069183).

2-Mercaptonicotinoyl glycine, a new potent melanogenesis inhibitor, exhibits a unique mode of action while preserving melanocyte integrity.

Research on new ingredients that can prevent excessive melanin production in the skin while considering efficacy, safety but also environmental impact is of great importance to significantly improve the profile of existing actives on the market and avoid undesirable side effects. Here, the discovery of an innovative technology for the management of hyperpigmentation is described. High-throughput screening tests on a wide chemical diversity of molecules and in silico predictive methodologies were essential to design an original thiopyridinone backbone and select 2-mercaptonicotinoyl glycine (2-MNG) as exhibiting the most favorable balance between the impact on water footprint, skin penetration potential and performance. The effectiveness of 2-MNG was confirmed by topical application on pigmented reconstructed epidermis and human skin explants. In addition, experiments have shown that unlike most melanogenesis inhibitors on the market, this molecule is not a tyrosinase inhibitor. 2-MNG binds to certain melanin precursors, preventing their integration into growing melanin and leading to inhibition of eumelanin and pheomelanin synthesis, without compromising the integrity of melanocytes.

Novel use of continuous pericapsular nerve group (PENG) block technique for traumatic superior and inferior pubic rami fractures: a case report.

BACKGROUND: Pubic rami fractures are painful injuries more commonly seen in the elderly with osteoporosis after high velocity trauma. In the most cases, management is conservative and non-operative with the goal to provide optimal pain relief to facilitate early mobilization and hospital discharge. Unfortunately, opioids remain the mainstay analgesic option and regional anesthesia techniques are limited but may include lumbar epidural anesthesia. CASE PRESENTATION: A female patient in her 80s presented to the emergency department of a level 1 trauma center following a high-speed motor vehicle collision. The patient suffered multiple non-life-threatening injuries. Notably, the patient was experiencing severe right groin and leg pain secondary to superior and inferior pubic rami fractures. Due to the severity of this pain, the patient was unable to mobilize or participate with physiotherapy. A lumbar epidural anesthesia technique was not deemed suitable and instead, we inserted a continuous pericapsular nerve group (PENG) block with a programmed intermittent bolus regimen. Immediate relief of pain was achieved and 48 hours later, the patient still reported satisfactory pain control and started to independently mobilize. CONCLUSION: Analgesia options are limited in pubic rami fractures. We present the first published case of a novel use of the PENG block with a continuous catheter technique for the analgesic management of a traumatic superior and inferior pubic rami fracture. The clinical utility of this technique in pubic ramus fractures warrants further clinical investigation.

JAK2 p.(V617F) mutation in Tunisian myeloproliferative neoplasms and its genotype-phenotype correlation.

Myeloproliferative neoplasms (MPNs) comprise polycythemia vera (PV), essential thrombocythemia (ET) and primary myelofibrosis (PMF). The relationship between JAK2 p.(V617F) mutation and MPNs was first described in 2005. The purpose of this study was to determine the prevalence of JAK2 p.(V617F) mutation in Tunisian patients assessed for MPNs and try to set a genotype-phenotype correlation. A retrospective study was conducted between January 2015 and April 2019. We collected the clinical data of all patients with MPNs suspicion or atypical splanchnic vein thrombosis (SVT). JAK2 p.(V617F) mutation was detected by allele specific real-time quantitative fluorescence PCR (AS-qPCR). We gathered 974 patients who underwent molecular analysis, 55.5% of them were male and 44.5% were female. The median age of all studied patients was 56 years. JAK2 p.(V617F) was found in 349 (35.8%) of total enrolled cases. It was reported in 44%, 37%, 29% and 25% of all patients diagnosed as having respectively ET, PV, PMF and atypical SVT. JAK2 p.(V617F) was negative in 62.2% of patients addressed for suspicion of PV. There was a significant positive correlation between the JAK2 p.(V617F) mutation status, age, gender, white blood cell counts and platelet counts. To our best knowledge, this is the first vast investigation of JAK2 p.(V617F) variant in Tunisia and North Africa with the lowest mutation rate in entire cohort and MPNs subgroups, underlying a specific presentation of this mutation. It is considered as an essential marker of MPNs' diagnosis and prognosis and is associated with differences in the phenotype of these disorders, helpful for the follow-up of these patients.

Comparison of the Analgesic Duration of 0.5% Bupivacaine With 1:200,000 Epinephrine Versus 0.5% Ropivacaine Versus 1% Ropivacaine for Low-Volume Ultrasound-Guided Interscalene Brachial Plexus Block: A Randomized Controlled Trial.

BACKGROUND: Bupivacaine and ropivacaine are the preferred long-acting local anesthetics for peripheral nerve blocks as they provide prolonged analgesia in the postoperative period. No studies have directly compared the analgesic duration of these commonly used local anesthetics in the setting of low-volume ultrasound-guided interscalene block (US-ISB). This study was designed to determine which local anesthetic and concentration provides superior analgesia (duration and quality) for low-volume US-ISB. METHODS: Sixty eligible patients scheduled for arthroscopic shoulder surgery were randomized (1:1:1) to receive US-ISB (5 mL) with 0.5% bupivacaine with 1:200,000 epinephrine, 0.5% ropivacaine, or 1% ropivacaine. All individuals were blinded including study participants, anesthesiologists, surgeons, research personnel, and statistician. All participants received a standardized general anesthetic and multimodal analgesia. The primary outcome was duration of analgesia defined as the time from the end of injection to the time that the patients reported a significant increase in pain (>3 numeric rating scale [NRS]) at the surgical site. RESULTS: The mean duration of analgesia for 0.5% bupivacaine with 1:200,000 epinephrine, 0.5% ropivacaine, or 1% ropivacaine was 14.1 ± 7.4, 13.8 ± 4.5, and 15.8 ± 6.3 hours, respectively (analysis of variance [ANOVA], P = .51). There were no observed differences in analgesic duration or other secondary outcomes between the 3 groups with the exception of a difference in cumulative opioid consumption up to 20h00 on the day of surgery in favor of ropivacaine 0.5% over bupivacaine of minimal clinical significance. CONCLUSIONS: In the context of single-injection low-volume US-ISB, we have demonstrated a similar efficacy between equal concentrations of ropivacaine and bupivacaine. In addition, increasing the concentration of ropivacaine from 0.5% to 1% did not prolong the duration of US-ISB.

Resistance of the Wheat Cultivar 'Renan' to Septoria Leaf Blotch Explained by a Combination of Strain Specific and Strain Non-Specific QTL Mapped on an Ultra-Dense Genetic Map.

Quantitative resistance is considered more durable than qualitative resistance as it does not involve major resistance genes that can be easily overcome by pathogen populations, but rather a combination of genes with a lower individual effect. This durability means that quantitative resistance could be an interesting tool for breeding crops that would not systematically require phytosanitary products. Quantitative resistance has yet to reveal all of its intricacies. Here, we delve into the case of the wheat/Septoria tritici blotch (STB) pathosystem. Using a population resulting from a cross between French cultivar Renan, generally resistant to STB, and Chinese Spring, a cultivar susceptible to the disease, we built an ultra-dense genetic map that carries 148,820 single nucleotide polymorphism (SNP) markers. Phenotyping the interaction was done with two different Zymoseptoria tritici strains with contrasted pathogenicities on Renan. A linkage analysis led to the detection of three quantitative trait loci (QTL) related to resistance in Renan. These QTL, on chromosomes 7B, 1D, and 5D, present with an interesting diversity as that on 7B was detected with both fungal strains, while those on 1D and 5D were strain-specific. The resistance on 7B was located in the region of Stb8 and the resistance on 1D colocalized with Stb19. However, the resistance on 5D was new, so further designated Stb20q. Several wall-associated kinases (WAK), nucleotide-binding and leucine-rich repeats (NB-LRR) type, and kinase domain carrying genes were present in the QTL regions, and some of them were expressed during the infection. These results advocate for a role of Stb genes in quantitative resistance and for resistance in the wheat/STB pathosystem being as a whole quantitative and polygenic.

Comparison of the effects of perineural or intravenous dexamethasone on low volume interscalene brachial plexus block: a randomised equivalence trial.

BACKGROUND: Efforts to prolong interscalene block (ISB) analgesia include the use of local anaesthetic adjuvants such as dexamethasone. Previous work showing prolonged block duration suggests that both perineural and intravenous (i.v.) routes can both prolong analgesia. The superiority of either route is controversial given the design of previous studies. As perineural dexamethasone is an off-label use, anaesthesiologists should be fully informed of the clinical differences, if any, on block duration. This study was designed to test whether perineural vs i.v. dexamethasone administration are equivalent. METHODS: We randomised 182 eligible patients scheduled for arthroscopic shoulder surgery to receive low-dose ISB (0.5% ropivacaine 5 ml) with perineural or i.v. dexamethasone 4 mg. Subjects, anaesthesiologists, and research personnel were blinded. All subjects also received a standardised general anaesthetic and multimodal analgesia. The primary outcome was duration of analgesia analysed as an equivalence outcome (2 h equivalency margin) using the two one-sided test (TOST) method. RESULTS: For the primary outcome, duration of analgesia, and perineural and i.v. administration of dexamethasone were not equivalent. The upper and lower bounds of the 90% confidence interval were 1 h (P=0.12) and -2.5 h (P=0.01), respectively. The observed difference in mean block duration was not clinically relevant (0.75 h longer for i.v. dexamethasone). There were no other clinically significant differences between groups. CONCLUSION: In the context of low-volume ISB with ropivacaine, perineural and i.v. dexamethasone were not equivalent in terms of their effects on block duration. However, there were no clinically significant differences in outcomes, and there is no advantage of perineural over intravenous dexamethasone. WWW.CLINICALTRIALS. GOV REGISTRATION: NCT02322242.

Observational study to assess pregnant women's knowledge and behaviour related to toxoplasmosis in Essaouira province, Morocco

Objective: To assess knowledge and behaviour related to toxoplasmosis which remains a neglected disease in Morocco. Methods: Observational investigations were conducted among 600 pregnant women from Essaouira Province. The interview items covered respondents' knowledge of the disease, its preventive practices and risk behaviours. Results: A total of 22/600 women had already carried out the anti-toxoplasmosis test, while, 96% have never done any screening of anti- Toxoplasma antibodies. Only 16/600 women have good information about the disease, its mode of transmission and its complications in both the fetus and his mother. Although most women adopt a healthy diet, the consumption of raw or undercooked meat is far to be considered as a risk factor, along with other potential factors that may foster the acquisition of the disease, such as possessing a domestic cat, educational status and knowledge of the disease. However, in this study, contact with soil was revealed the most important risk factor (P = 0.045), followed by the hygiene conditions after handling raw meat (P = 0.048). Conclusion: The underestimation of the Toxoplasma gondii sero-prevalence in Essaouira Province can be explained by the absence of toxoplasmosis serology in health institutions, as well as the gap of knowledge about the disease by local population.

Early-Life Exposure to Cadmium Triggers Distinct Zn-Dependent Protein Expression Patterns and Impairs Brain Development.

The objective of this study was to determine if the brain development impairment induced by early-life exposure to cadmium (Cd) could result from changes in the expression pattern of distinct zinc (Zn)-dependent proteins. For this purpose, adult female rats receiving either tap water, Cd, Zn, or Cd + Zn in their drinking water during gestation and lactation periods were used. After birth, the male offspring were screened for locomotors and sensorial defects. At postnatal day 21 (PND 21), the male pups were sacrificed and their brains, liver, and plasma were taken for chemical, biochemical, and molecular analyses. Our results show that exposure to Cd significantly increased the metal accumulation and decreased Zn concentrations in the brain of male pups from Cd-treated mothers. Besides, Cd exposure reduced significantly the locomotor activity of the offspring in open-field test, the body weight, and the cranio-caudal length at PND21. Insulin-like growth factor-I (IGF-1) levels in the plasma and liver were also decreased in male pups from Cd-treated mothers. Cd-induced brain development disruption was accompanied by a significant increase of the superoxide dismutase (SOD) activity, induction of the metallothionein (MT) synthesis, and, at the molecular level, by an upregulation of Zrt-,Irt-related protein 6 (ZIP6) gene and a significant downregulation of the expression of the Zn transporter 3 (ZnT3) and brain-derived neurotrophic factor (BDNF) genes in the brain. No significant changes on the expression of genes encoding other Zn-dependent proteins and factors such as ZnT1, ZIP12, NF-κB, and Zif268. Interestingly, Zn supplementation provided a total or partial correction of the changes induced by the Cd exposure. These data indicated that changes in expression of ZnT3 and ZIP6 as well as alteration of other transcription factors, such as BDNF, or Zn-dependent proteins, such as SOD and MTs, in response to Cd exposure might be an underlying mechanism of Cd-induced brain development impairment.

Involvement of Zn Depletion in Cd-Induced Toxicity on Prenatal Bone Formation in Rat.

This study explored the potential toxicity of Cd on the Zn bone depletion in prenatal bone formation. Female rats received either tap water, Cd, Zn, or Cd + Zn in their drinking water during gestation, and some markers of bone formation were studied in their fetuses removed at the 20th day of pregnancy (GD20). Cd exposure induced maternal hypozincemia and Zn depletion in the femur of the fetuses. A striking inhibition of bone formation in fetuses, expressed by decreases in femur length, width, and area, by the shortening of diaphysis, and by a decrease in length and area of distal and proximal proliferative zones, was observed in fetuses from Cd-exposed mothers. At the molecular level, Cd caused upregulation of MT-1 and ZIP2 genes and significantly depressed the expression of the ZnT5, colα1, osteocalcin, and ALP genes in the femur. Interestingly, Zn treatment ameliorated the Cd-induced maternal hypozincemia and femoral changes and partially restored the normal histomorphometry of the femur. These results suggest that the observed toxic effects of Cd are, at least in part, mediated by the disruption of maternal Zn metabolism during pregnancy leading to Zn depletion and thus to perturbation of prenatal bone formation.

The minimal effective volume (MEAV 95) for interscalene brachial plexus block for surgical anesthesia under sedation: A prospective observational dose finding study.

Background: Interscalene brachial plexus (ISB) block is routinely used to provide anesthesia and analgesia for shoulder surgery. Traditional local anesthetic volumes for ISB result in near universal ipsilateral phrenic nerve paresis potentially including oxygenation and ventilation. Aims: The purpose of this study was to determine the lowest minimal effective anesthetic volume in 95% of patients (MEAV 95) of ropivacaine 0.75% for ISB that provides surgical anesthesia for arthroscopic shoulder surgery. Methods: Prospective observational cohort study in patients undergoing arthroscopic shoulder surgery under ISB (C6 level) with sedation. The dose finding protocol used the Narayana rule for up/down sequential allocation to estimate the MEAV 95 of ropivacaine 0.75%. Successful ISB was defined as complete absence of pinprick sensation in the C5 and C6 dermatomes 30 min postblock. Secondary outcomes assessed included ability to complete surgery with propofol sedation, change in slow vital capacity, room air oxygen saturation postblock, block duration, ISB complications, and numeric rating scale for pain immediately after surgery. Results: The study was stopped early due to futility. Among 225 participants approached, 54 consented to participate. The MEAV 95 for ultrasound-guided ISB of ropivacaine 0.75% for shoulder surgery was unable to be accurately estimated. Local anesthetic volumes between 5 and 20 ml did not influence any of the predefined secondary outcomes. Conclusions: The MEAV 95 (at 30 min) of ropivacaine 0.75% for ultrasound-guided ISB exceeds the local anesthetic volumes that consistently produces hemidiaphragmatic impairment. ISB cannot be guaranteed to provide surgical anesthesia at 30 min without the potential for concomitant phrenic nerve block.

Contexte: Le bloc du plexus brachial par approche interscalénique (BIS) est régulièrement utilisé pour l'anesthésie et l'analgésie lors de chirurgies de l'épaule. Les volumes d'anesthésique local traditionnellement utilisés pour le BIS entraînent couramment une parésie ipsilatérale du nerf phrénique compromettant l'oxygénation et la ventilation.Objectifs: Le but de cette étude était de déterminer le plus petit volume minimal effectif chez 95% des patients (VME 95) de la ropivacaïne 0,75 % lorsqu'utilisé pour un BIS lors d'une chirurgie arthroscopique de l'épaule.Méthodes: Étude de cohorte prospective observationnelle auprès de patients subissant une chirurgie arthroscopique de l'épaule sous BIS (niveau C6) avec sédation. Le protocole d'identification du VME 95 de la ropivacaïne 0,75% a été effectué selon la règle de Narayana pour augmenter ou diminuer l'allocation séquentielle des doses. Un BIS réussi était défini comme l'absence totale de sensation de picotement dans les dermatomes aux niveaux C5 et C6 30 minutes après le bloc. Les critères d'évaluation secondaires comprenaient la capacité de compléter la chirurgie avec une sédation à base de propofol, les changements dans la capacité vitale lente, la saturation de l'oxygène de l'air ambiant après le bloc, la durée du bloc, les complications rencontrées avec le BIS et l'intensité de la douleur immédiatement après la chirurgie mesurée à l'aide d'une échelle numérique.Résultats: L'étude a été arrêtée avant terme en raison de son insuccès. Parmi les 225 patients approchés, 54 ont accepté d'y participer. Le VME 95 de la ropivacaïne 0,75 % pour un BIS écho-guidé lors d'une chirurgie de l'épaule n'a pu être estimé avec précision. Les volumes d'anesthésique local entre 5 et 20 ml n'ont influencé aucun des critères d'évaluation secondaires prédéfinis.Conclusions: Le VME 95 de la ropivacaïne 0,75 % (à 30 minutes) pour un BIS écho-guidé excède les volumes d'anesthésique local qui entraînent systématiquement une déficience au niveau du l'hémidiaphragme. Le BIS ne peut fournir une anesthésie de 30 minutes pour une chirurgie arthroscopique de l'épaule sans risque concomitant de bloquer le nerf phrénique.

Protective role of zinc against the toxicity induced by exposure to cadmium during gestation and lactation on testis development.

To assess the effects of exposure to Cd and Zn on rat testicular development, offspring, from mothers receiving either tap water, Cd, Zn or Cd+Zn during gestation and lactation periods, were observed on gestational day (GD) 20 and on postnatal days (PND) 12, 21 and 35. During gestation, Cd induced maternal hypozincemia and less transfer of Zn to the fetus. During lactation, progressive Cd accumulation and Zn depletion in testis at PND12 and PND21 were noted. An increase of abnormal seminiferous tubules and a decrease in testis weight and plasmatic testosterone concentration were also observed at PND21 and PND35 respectively. Interestingly, Zn supply induced a significant protection against Cd toxicity. These results suggest that the toxic effects of Cd observed during development are mediated by the disruption of Zn metabolism, which is established in mothers during pregnancy causing Zn deficiency in fetuses and continues to become more pronounced during lactation.

Changes of the mRNA expression pattern of Zn transporters: a probable mechanism for cadmium retention and zinc redistribution in the suckling rat tissues.

The present study was conducted to provide potential mechanism that may be responsible for Cd retention and Cd-induced Zn redistribution in tissues of suckling rat. For this purpose, suckling rats from mother receiving either tap water, Cd, or Cd + Zn during lactation period were sacrificed on postnatal day (PND) 14 and PND 21 for performing chemical and molecular analysis. Our results show that Cd exposure, although it does not affect the milk consumption, it clearly alters the lactational transfer, absorption, and distribution of Zn in the suckling rat organism. At the molecular level, Cd caused upregulation of ZIP 3, ZIP 4, and ZIP 8 gene expressions in the mammary gland of mothers rats and in the intestine of their pups but decreased the expression of ZnT 2 and ZnT 4 only in the mammary tissue at PND 14 and PND 21. Zn supply reversed the Cd-induced decrease in the neonatal Zn apparent absorption and restores the gastrointestinal, brain, and plasma levels of this essential element in the suckling rat organism at PND 14 and PND 21. Also, with this treatment, the gene expressions of ZnT 1 in the mammary gland and ZnT 4 in the neonatal intestine were found to be upregulated at PND 21. Furthermore, our results show that Cd or Cd + Zn treatment increase the neonatal hepatic MTs accumulation at PND 14 only. These results imply that the downregulation of ZnT as well as the overexpression of ZIP transporters, in responses to the Zn depletion induced by Cd in the tissues of lactating rat and their offspring, play a major role in Cd accumulation and Zn redistribution in tissues of suckling rat.

Comparing the effects of single shot sciatic nerve block versus posterior capsule local anesthetic infiltration on analgesia and functional outcome after total knee arthroplasty: a prospective, randomized, double-blinded, controlled trial.

Peripheral nerve blocks appear to provide effective analgesia for patients undergoing total knee arthroplasty. Although the literature supports the use of femoral nerve block, addition of sciatic nerve block is controversial. In this study we investigated the value of sciatic nerve block and an alternative technique of posterior capsule local anesthetic infiltration analgesia. 100 patients were prospectively randomized into three groups. Group 1: sciatic nerve block; Group 2: posterior local anesthetic infiltration; Group 3: control. All patients received a femoral nerve block and spinal anesthesia. There were no differences in pain scores between groups. Sciatic nerve block provided a brief clinically insignificant opioid sparing effect. We conclude that sciatic nerve block and posterior local anesthetic infiltration do not provide significant analgesic benefits.