Uterine receptivity and cytokines: new concepts and new applications

The implantation process, currently thought to be the most critical step in achieving a successful early pregnancy, remains one of the most important unsolved processes in reproductive medicine. It depends on uterine-dependent and embryo-specific events, which need to be critically coordinated. Early embryo signaling following a maternal hormonal or cytokine-mediated preparation phase seems to be involved in stages immediately before, during and just after the apposition step to permit adequate proliferation of the stroma. Our objective is to develop guidelines and diagnostic tools pertinent to appreciate uterine receptivity. We will focus our attention on the uterine luminal environment at the time of oocyte retrieval and on the monitoring of the endometrium using three-dimensional ultrasound associated with digital technology and cytokine quantification by real-time PCR during the implantation window in an IVF/ICSI population. There is an accumulating body of data which strongly suggests that both implantation and uterine receptivity are controlled, primarily, though not exclusively, by locally acting growth factors and cytokines, some under steroid control. Some specific cytokines (IL-12, IL-15 and IL-18) in the luminal environment and in the endometrium allow a distinct pattern of abnormal uterine receptivity. The identification of these distinct patterns of abnormal uterine receptivity and of the mechanisms leading to the abnormal angiogenesis before implantation strongly suggest that no single therapeutic scheme can correct all cases of implantation failure and should be adapted for each patient especially in the case of unexplained infertility.     

One Health surveillance of West Nile and Usutu viruses: a repeated cross-sectional study exploring seroprevalence and endemicity in Southern France, 2016 to 2020

BackgroundWest Nile virus (WNV) and Usutu virus (USUV), two closely related flaviviruses, mainly follow an enzootic cycle involving mosquitoes and birds, but also infect humans and other mammals. Since 2010, their epidemiological situation may have shifted from irregular epidemics to endemicity in several European regions; this requires confirmation, as it could have implications for risk assessment and surveillance strategies.AimTo explore the seroprevalence in animals and humans and potential endemicity of WNV and USUV in Southern France, given a long history of WNV outbreaks and the only severe human USUV case in France in this region.MethodsWe evaluated the prevalence of WNV and USUV in a repeated cross-sectional study by serological and molecular analyses of human, dog, horse, bird and mosquito samples in the Camargue area, including the city of Montpellier, between 2016 and 2020.ResultsWe observed the active transmission of both viruses and higher USUV prevalence in humans, dogs, birds and mosquitoes, while WNV prevalence was higher in horses. In 500 human samples, 15 were positive for USUV and 6 for WNV. Genetic data showed that the same lineages, WNV lineage 1a and USUV lineage Africa 3, were found in mosquitoes in 2015, 2018 and 2020.ConclusionThese findings support existing literature suggesting endemisation in the study region and contribute to a better understanding of USUV and WNV circulation in Southern France. Our study underlines the importance of a One Health approach for the surveillance of these viruses.     

Clinical Evidence of the Benefits of Phytonutrients in Human Healthcare

Phytonutrients comprise many different chemicals, including carotenoids, indoles, glucosinolates, organosulfur compounds, phytosterols, polyphenols, and saponins. This review focuses on the human healthcare benefits of seven phytochemical families and highlights the significant potential contribution of phytonutrients in the prevention and management of pathologies and symptoms in the field of family health. The structure and function of these phytochemical families and their dietary sources are presented, along with an overview of their potential activities across different health and therapeutic targets. This evaluation has enabled complementary effects of the different families of phytonutrients in the same area of health to be recognized.     

Post-PKS Tailoring Steps of the Spiramycin Macrolactone Ring in Streptomyces ambofaciens

Spiramycins are clinically important 16-member macrolide antibiotics produced by Streptomyces ambofaciens. Biosynthetic studies have established that the earliest lactonic intermediate in spiramycin biosynthesis, the macrolactone platenolide I, is synthesized by a type I modular polyketide synthase (PKS). Platenolide I then undergoes a series of post-PKS tailoring reactions yielding the final products, spiramycins I, II, and III. We recently characterized the post-PKS glycosylation steps of spiramycin biosynthesis in S. ambofaciens. We showed that three glycosyltransferases, Srm5, Srm29, and Srm38, catalyze the successive attachment of the three carbohydrates mycaminose, forosamine, and mycarose, respectively, with the help of two auxiliary proteins, Srm6 and Srm28. However, the enzymes responsible for the other tailoring steps, namely, the C-19 methyl group oxidation, the C-9 keto group reduction, and the C-3 hydroxyl group acylation, as well as the timing of the post-PKS tailoring reactions, remained to be established. In this study, we show that Srm13, a cytochrome P450, catalyzes the oxidation of the C-19 methyl group into a formyl group and that Srm26 catalyzes the reduction of the C-9 keto group, and we propose a timeline for spiramycin-biosynthetic post-PKS tailoring reactions.     

A difficult airway is not more prevalent in patients suffering from spasmodic torticollis: a case series

PURPOSE: We designed this retrospective study to assess the frequency of difficult airway and difficult intubation in patients with spasmodic torticollis and compare it to that of the general population. METHODS: After Institutional Review Board approval, data were collected from the charts of all the patients with spasmodic torticollis who underwent selective peripheral denervation at our institution between 1988 and 2001. The intubation grade was determined using the Cormack and Lehane laryngoscopic classification. The best laryngeal view was recorded. RESULTS: Data from 342 patients were available for analysis. Fourteen patients had a difficult airway. In two patients, intubation was difficult with three attempts at laryngoscopy in one patient and use of fibreoptic bronchoscopy in the other. Twelve (3.5%) patients presented with laryngoscopic grades of III or IV. The combined prevalence of laryngoscopic view grade III and IV and difficult intubation was 4.4%. CONCLUSIONS: This study assesses the frequency of difficult intubation in patients suffering from spasmodic torticollis. When compared to the general population, these patients do not appear to have a higher frequency of difficult airway or difficult intubation.     

Tramadol added to 1.5% mepivacaine for axillary brachial plexus block improves postoperative analgesia dose-dependently

Adjuncts to local anesthetics for peripheral plexus blockade may enhance the quality and duration of anesthesia and postoperative analgesia. The analgesic, tramadol, has a unique mechanism of action that suggests efficacy as such an adjunct. It displays a central analgesic and peripheral local anesthetic effect. We designed a prospective, randomized, controlled and double-blind clinical trial to assess the effect of tramadol added to brachial plexus anesthesia. One-hundred patients scheduled for carpal tunnel release surgery under brachial plexus anesthesia were randomized into four groups. All patients received 1.5% mepivacaine 40 mL plus a study solution containing either isotonic sodium chloride (Group P, n = 17), tramadol 40 mg (Group T(40), n = 22), tramadol 100 mg (Group T(100), n = 20) or tramadol 200 mg (Group T(200), n = 20). We evaluated the time of onset of anesthesia, duration of sensory and motor blockade, duration and quality of postoperative analgesia, and occurrence of adverse effects. Onset and duration of sensory and motor blocks were not different among groups. The number of patients requesting analgesia in the postoperative period was significantly less in the 3 tramadol groups compared with the placebo group (P = 0.02); this was also noted with the placebo and T(40) groups compared with the T(200) group. No statistical significance was demonstrated between the placebo and the T(40) group or the T(100) group and the T(200) group. Furthermore, there was a significant trend effect among groups applying the Cochran-Armitage tendency test (P = 0.003), suggesting a dose-dependent decrease for additional postoperative analgesia requirements when tramadol was added. Side effects did not differ among groups, although they were more frequently recorded in the T groups. Our study suggests that tramadol added to 1.5% mepivacaine for brachial plexus block enhances in a dose-dependent manner the duration of analgesia with acceptable side effects. However, the safety of tramadol has to be investigated before allowing its use in clinical practice. IMPLICATIONS: Tramadol's unique mechanism of action suggests efficacy as a local anesthetic adjunct for peripheral plexus blockade. Our study demonstrates that tramadol, added to mepivacaine for brachial plexus anesthesia, extends the duration and improves the quality of postoperative analgesia in a dose dependent fashion with acceptable side effects.     

Influence of Oral Vitamin E Therapy on Micro-Inflammation and Cardiovascular Disease Markers in Chronic Hemodialysis Patients

Background. The aim of this study was to evaluate the influence of oral vitamin E therapy on serum concentrations of several markers of micro-inflammation and cardiovascular disease in chronic hemodialysis (HD) patients. Methods. 29 HD patients were randomized into two groups: 15 patients were treated orally with 400mg of vitamin E daily for a period of five weeks, and 14 patients received no antioxidant supplementation. Before and after vitamin E therapy, serum concentrations of vitamin E (high-performance liquid chromatography), pregnancy-associated plasma protein-A (immunochemical – TRACE assay), C-reactive protein (nephelometry), intercellular adhesion molecule-1 (ELISA), and E-selectin (ELISA) were measured. HD patients were compared with 16 healthy controls. Results. Baseline serum concentrations of PAPP-A and CRP were significantly higher in HD patients than in healthy controls (PAPP-A: 26.23±11.94 vs. 11.41±1.94 mIU/L, p<0.001; CRP: 5.20±3.50 vs. 3.40±3.80 mg/L, p<0.05). After five weeks of oral vitamin E intake, serum PAPP-A, CRP, ICAM-1, and E-selectin concentrations remained unchanged in both groups of HD patients. Conclusion. Chronic micro-inflammation in HD patients is documented by the elevation of CRP and PAPP-A. A daily oral dose of 400 mg of vitamin E does not seem to be able to reduce enhanced oxidative stress and micro-inflammation in chronic HD patients.     

Major healing of refractory mandible osteoradionecrosis after treatment combining pentoxifylline and tocopherol: a phase II trial

BACKGROUND: Osteoradionecrosis (ORN) is a nonhealing wound of the bone that is difficult to manage. Is a treatment combining pentoxifylline (PTX) and tocopherol (vitamin E) boosted by clodronate effective in reversing this fibronecrotic process? METHODS: Eighteen consecutive patients previously irradiated for head and neck cancer had exteriorized mandible ORN. Length of exposed bone (L) was 13.4 +/- 8 mm, and the mean subjective objective medical management and analytic evaluation of injury (SOMA) score was 12.6 +/- 4.9. Between June 1995 and January 2002, all 18 were given a daily oral combination of 800 mg of PTX and 1000 IU of vitamin E for 6 to 24 months. In addition, the last eight patients who were the worst cases were given 1600 mg/day clodronate 5 days a week. RESULTS: The treatment was well tolerated. All patients improved at 6 months, with 84% mean L and 67% mean SOMA score reductions. Sixteen (89%) of 18 patients achieved complete recovery, 14 in 5 +/- 2.6 months. The remaining two patients exhibited a 75% response at 6 months. CONCLUSION: PTX-vitamin E boosted by clodronate is an effective treatment of mandibular ORN that induces mucosal and bone healing in a median period of 6 months.