A scoping review examining patient experience and what matters to people experiencing homelessness when seeking healthcare.

BACKGROUND: Homelessness is associated with significant health disparities. Conventional health services often fail to address the unique needs and lived experience of homeless individuals and fail to include participatory design when planning health services. This scoping review aimed to examine areas of patient experience that are most frequently reported by people experiencing homelessness when seeking and receiving healthcare, and to identify existing surveys used to measure patient experience for this cohort. METHODS: A scoping review was undertaken reported according to the PRISMA-ScR 2020 Statement. Databases were searched on 1 December 2022: MEDLINE, EMBASE, APA PsychINFO and CINAHL. Included studies focused on people experiencing homelessness, healthcare services and patient experience, primary research, published in English from 2010. Qualitative papers and findings were extracted and synthesized against a modified framework based on the National Institute for Health and Care Excellence guidelines for care for people experiencing homelessness, the Institute of Medicine Framework and Lachman's multidimensional quality model. People with lived experience of homelessness were employed as part of the research team. RESULTS: Thirty-two studies were included. Of these, 22 were qualitative, seven quantitative and three mixed methods, from the United States of America (n = 17), United Kingdom (n = 5), Australia (n = 5) and Canada (n = 4). Health services ranged from primary healthcare to outpatient management, acute care, emergency care and hospital based healthcare. In qualitative papers, the domains of 'accessible and timely', 'person-centred', and values of 'dignity and respect' and 'kindness with compassion' were most prevalent. Among the three patient experience surveys identified, 'accessible and timely' and 'person-centred' were the most frequent domains. The least frequently highlighted domains and values were 'equitable' and 'holistic'. No questions addressed the 'safety' domain. CONCLUSIONS: The Primary Care Quality-Homeless questionnaire best reflected the priorities for healthcare provision that were highlighted in the qualitative studies of people experiencing homelessness. The most frequently cited domains and values that people experiencing homelessness expressed as important when seeking healthcare were reflected in each of the three survey tools to varying degrees. Findings suggest that the principles of 'Kindness and compassion' require further emphasis when seeking feedback on healthcare experiences and the domains of 'safety', 'equitable', and 'efficiency' are not adequately represented in existing patient experience surveys.

Comprehensive Review of Epidemiology and Treatment of Snakebite Envenomation in West Africa: Case of Benin.

Snakebite envenomation (SBE) constitutes a public health, social, and economic problem affecting poor communities in intertropical and subtropical regions. This review sought to synthesize literature on snakebite envenomation in Benin to highlight research perspectives and strategies for better management of the menace. A literature search performed in multidisciplinary electronic databases showed that the prevalence of SBE is high in Benin, but the incidences, associated morbidities, and mortalities are greatly underestimated. Most snake envenomations are by Echis ocellatus in Northern Benin during the rainy season. Adults involved in agricultural activities are the most affected. The absence of antivenin serum in the most affected areas explains the preference for alternative and traditional medicine as the first-line treatment for SBE in Benin. In conclusion, it would be imperative to revitalize the snakebite reporting system in order to have better epidemiological data and to develop a sustainable national strategy for the control and management of snakebite envenomation.

Higher early pregnancy plasma myo-inositol associates with increased postprandial glycaemia later in pregnancy: Secondary analyses of the NiPPeR randomized controlled trial.

AIM: Myo-inositol supplementation from ~13 weeks' gestation reportedly improves glycaemia regulation in metabolically at-risk women, with speculation that earlier supplementation might bring further improvement. However, the NiPPeR trial of a myo-inositol-containing supplement starting preconception did not lower gestational glycaemia in generally healthy women. We postulated that the earlier timing of supplementation influences the maternal metabolic adaptation for gestational glycaemia regulation. METHODS: In total, 585 women were recruited from Singapore, UK and New Zealand for the NiPPeR study. We examined associations of plasma myo-inositol concentrations at 7 and 28 weeks' gestation with 28 weeks plasma glucose (PG; fasting, and 1 h and 2 h in 75 g oral glucose tolerance test) and insulin indices using linear regression adjusting for covariates. RESULTS: Higher 7-week myo-inositol, but not 28-week myo-inositol, associated with higher 1 h PG [ßadj (95% confidence intervals) 0.05 (0.01, 0.09) loge mmol/L per loge µmol/L, p = .022] and 2 h PG [0.08 (0.03, 0.12), p = .001]; equivalent to 0.39 mmol/L increase in 2 h PG for an average 7-week myo-inositol increase of 23.4 µmol/L with myo-inositol supplementation. Higher 7-week myo-inositol associated with a lower 28-week Stumvoll index (first phase), an approximation of insulin secretion [-0.08 (-0.15, -0.01), p = .020] but not with 28-week Matsuda insulin sensitivity index. However, the clinical significance of a 7-week myo-inositol-related increase in glycaemia was limited as there was no association with gestational diabetes risk, birthweight and cord C-peptide levels. In-silico modelling found higher 28-week myo-inositol was associated with lower gestational glycaemia in White, but not Asian, women after controlling for 7-week myo-inositol effects. CONCLUSION: To our knowledge, our study provides the first evidence that increasing first trimester plasma myo-inositol may slightly exacerbate later pregnancy post-challenge glycaemia, indicating that the optimal timing for starting prenatal myo-inositol supplementation needs further investigation.

Diagnosis and management of complications following pelvic organ prolapse surgery using a synthetic mesh: French national guidelines for clinical practice.

Complications associated with pelvic organ prolapse (POP) surgery using a synthetic non-absorbable mesh are uncommon (<5%) but may be severe and may hugely diminish the quality of life of some women. In drawing up these multidisciplinary clinical practice recommendations, the French National Authority for Health (Haute Autorité de santé, HAS) conducted an exhaustive review of the literature concerning the diagnosis, prevention, and management of complications associated with POP surgery using a synthetic mesh. Each recommendation for practice was allocated a grade (A,B or C; or expert opinion (EO)), which depends on the level of evidence (clinical practice guidelines). PREOPERATIVE PATIENTS' INFORMATION: Each patient must be informed concerning the risks associated with POP surgery (EO). HEMORRHAGE, HEMATOMA: Vaginal infiltration using a vasoconstrictive solution is not recommended during POP surgery by the vaginal route (grade C). The placement of vaginal packing is not recommended following POP surgery by the vaginal route (grade C). During laparoscopic sacral colpopexy, when the promontory seems highly dangerous or when severe adhesions prevent access to the anterior vertebral ligament, alternative surgical techniques should be discussed per operatively, including colpopexy by lateral mesh laparoscopic suspension, uterosacral ligament suspension, open abdominal mesh surgery, or surgery by the vaginal route (EO). BLADDER INJURY: When a bladder injury is diagnosed, bladder repair by suturing is recommended, using a slow resorption suture thread, plus monitoring of the permeability of the ureters (before and after bladder repair) when the injury is located at the level of the trigone (EO). When a bladder injury is diagnosed, after bladder repair, a prosthetic mesh (polypropylene or polyester material) can be placed between the repaired bladder and the vagina, if the quality of the suturing is good. The recommended duration of bladder catheterization following bladder repair in this context of POP mesh surgery is from 5 to 10 days (EO). URETER INJURY: After ureteral repair, it is possible to continue sacral colpopexy and place the mesh if it is located away from the ureteral repair (EO). RECTAL INJURY: Regardless of the approach, when a rectal injury occurs, a posterior mesh should not be placed between the rectum and the vagina wall (EO). Concerning the anterior mesh, it is recommended to use a macroporous monofilament polypropylene mesh (EO). A polyester mesh is not recommended in this situation (EO). VAGINAL WALL INJURY: After vaginal wall repair, an anterior or a posterior microporous polypropylene mesh can be placed, if the quality of the repair is found to be satisfactory (EO). A polyester mesh should not be used after vaginal wall repair (EO). MESH INFECTION (ABSCESS, CELLULITIS, SPONDYLODISCITIS): Regardless of the surgical approach, intravenous antibiotic prophylaxis is recommended (aminopenicillin + beta-lactamase inhibitor: 30 min before skin incision +/- repeated after 2 h if surgery lasts longer) (EO). When spondylodiscitis is diagnosed following sacral colpopexy, treatment should be discussed by a multidisciplinary group, including especially spine specialists (rheumatologists, orthopedists, neurosurgeons) and infectious disease specialists (EO). When a pelvic abscess occurs following synthetic mesh sacral colpopexy, it is recommended to carry out complete mesh removal as soon as possible, combined with collection of intraoperative bacteriological samples, drainage of the collection and targeted antibiotic therapy (EO). Non-surgical conservative management with antibiotic therapy may be an option (EO) in certain conditions (absence of signs of sepsis, macroporous monofilament polypropylene type 1 mesh, prior microbiological documentation and multidisciplinary consultation for the choice of type and duration of antibiotic therapy), associated with close monitoring of the patient. BOWEL OCCLUSION RELATED TO NON-CLOSURE OF THE PERITONEUM: Peritoneal closure is recommended after placement of a synthetic mesh by the abdominal approach (EO). URINARY RETENTION: Preoperative urodynamics is recommended in women presenting with urinary symptoms (bladder outlet obstruction symptoms, overactive bladder syndrome or incontinence) (EO). It is recommended to remove the bladder catheter at the end of the procedure or within 48 h after POP surgery (grade B). Bladder emptying and post-void residual should be checked following POP surgery, before discharge (EO). When postoperative urine retention occurs after POP surgery, it is recommended to carry out indwelling catheterization and to prefer intermittent self-catheterization (EO). POSTOPERATIVE PAIN: Before POP surgery, the patient should be asked about risk factors for prolonged and chronic postoperative pain (pain sensitization, allodynia, chronic pelvic or non-pelvic pain) (EO). Concerning the prevention of postoperative pain, it is recommended to carry out a pre-, per- and postoperative multimodal pain treatment (grade B). The use of ketamine intraoperatively is recommended for the prevention of chronic postoperative pelvic pain, especially for patients with risk factors (preoperative painful sensitization, allodynia, chronic pelvic or non-pelvic pain) (EO). Postoperative prescription of opioids should be limited in quantity and duration (grade C). When acute neuropathic pain (sciatalgia or pudendal neuralgia) resistant to level I and II analgesics occurs following sacrospinous fixation, a reintervention is recommended for suspension suture removal (EO). When chronic postoperative pain occurs after POP surgery, it is recommended to systematically seek arguments in favor of neuropathic pain with the DN4 questionnaire (EO). When chronic postoperative pelvic pain occurs after POP surgery, central sensitization should be identified since it requires a consultation in a chronic pain department (EO). Concerning myofascial pain syndrome (clinical pain condition associated with increased muscle tension caused by myofascial trigger points), when chronic postoperative pain occurs after POP surgery, it is recommended to examine the levator ani, piriformis and obturator internus muscles, so as to identify trigger points on the pathway of the synthetic mesh (EO). Pelvic floor muscle training with muscle relaxation is recommended when myofascial pain syndrome is associated with chronic postoperative pain following POP surgery (EO). After failure of pelvic floor muscle training (3 months), it is recommended to discuss surgical removal of the synthetic mesh, during a multidisciplinary discussion group meeting (EO). Partial removal of synthetic mesh is indicated when a trigger point is located on the pathway of the mesh (EO). Total removal of synthetic mesh should be discussed during a multidisciplinary discussion group meeting when diffuse (no trigger point) chronic postoperative pain occurs following POP surgery, with or without central sensitization or neuropathic pain syndromes (EO). POSTOPERATIVE DYSPAREUNIA: When de novo postoperative dyspareunia occurs after POP surgery, surgical removal of the mesh should be discussed (EO). VAGINAL MESH EXPOSURE: To reduce the risk of vaginal mesh exposure, when hysterectomy is required during sacral colpopexy, subtotal hysterectomy is recommended (grade C). When asymptomatic vaginal macroporous monofilament polypropylene mesh exposure occurs, systematic imaging is not recommended. When vaginal polyester mesh exposure occurs, pelvic +/- lumbar MRI (EO) should be used to look for an abscess or spondylodiscitis, given the greater risk of infection associated with this type of material. When asymptomatic vaginal mesh exposure of less than 1 cm2 occurs in a woman with no sexual intercourse, the patient should be offered observation (no treatment) or local estrogen therapy (EO). However, if the patient wishes, partial excision of the mesh can be offered. When asymptomatic vaginal mesh exposure of more than 1 cm2 occurs or if the woman has sexual intercourse, or if it is a polyester prosthesis, partial mesh excision, either immediately or after local estrogen therapy, should be offered (EO). When symptomatic vaginal mesh exposure occurs, but without infectious complications, surgical removal of the exposed part of the mesh by the vaginal route is recommended (EO), and not systematic complete excision of the mesh. Following sacral colpopexy, complete removal of the mesh (by laparoscopy or laparotomy) is only required in the presence of an abscess or spondylodiscitis (EO). When vaginal mesh exposure recurs after a first reoperation, the patient should be treated by an experienced team specialized in this type of complication (EO). SUTURE THREAD VAGINAL EXPOSURE: For women presenting with vaginal exposure to non-absorbable suture thread following POP surgery with mesh reinforcement, the suture thread should be removed by the vaginal route (EO). Removal of the surrounding mesh is only recommended when vaginal mesh exposure or associated abscess is diagnosed. BLADDER AND URETERAL MESH EXPOSURE: When bladder mesh exposure occurs, removal of the exposed part of the mesh is recommended (grade B). Both alternatives (total or partial mesh removal) should be discussed with the patient and should be debated during a multidisciplinary discussion group meeting (EO).

Neural correlates of mindfulness meditation and hypnosis on magnetic resonance imaging: similarities and differences. A scoping review.

BACKGROUND: Mindfulness meditation (MM) and hypnosis practices are gaining interest in mental health, but their physiological mechanisms remain poorly understood. This study aimed to synthesize the functional, morphometric and metabolic changes associated with each practice using magnetic resonance imaging (MRI), and to identify their similarities and differences. METHODS: MRI studies investigating MM and hypnosis in mental health, specifically stress, anxiety, and depression, were systematically screened following PRISMA guidelines from four research databases (PubMed, Web of Science, Embase, PsycINFO) between 2010 and 2022. RESULTS: In total, 97 references met the inclusion criteria (84 for MM and 13 for hypnosis). This review showed common and divergent points regarding the regions involved and associated brain connectivity during MM practice and hypnosis. The primary commonality between mindfulness and hypnosis was decreased default mode network intrinsic activity and increased central executive network - salience network connectivity. Increased connectivity between the default mode network and the salience network was observed in meditative practice and mindfulness predisposition, but not in hypnosis. CONCLUSIONS: While MRI studies provide a better understanding of the neural basis of hypnosis and meditation, this review underscores the need for more rigorous studies.

Phytotoxic fungal secondary metabolites as herbicides.

Among the alternatives to synthetic plant protection products, biocontrol appears as a promising method. This review reports on the diversity of fungal secondary metabolites phytotoxic to weeds and on the approach generally used to extract, characterize, identify and exploit them for weed management. The 183 phytotoxic fungal secondary metabolites discussed in this review fall into five main classes of molecules: 61 polyketides, 53 terpenoids, 36 nitrogenous metabolites, 18 phenols and phenolic acids, and 15 miscellaneous. They are mainly produced by the genera Drechslera, Fusarium and Alternaria. The phytotoxic effects, more often described by the symptoms they produce on plants than by their mode of action, range from inhibition of germination to inhibition of root and vegetative growth, including tissue and organ alterations. The biochemical characterization of fungal secondary metabolites requires expertise and tools to carry out fungal cultivation and metabolite extraction, phytotoxicity tests, purification and fractionation of the extracts, and chemical identification procedures. Phytotoxicity tests are mainly carried out under controlled laboratory conditions (not always on whole plants), while effectiveness against targeted weeds and environmental impacts must be assessed in greenhouses and open fields. These steps are necessary for the formulation of effective, environment-friendly fungal secondary metabolites-derived bioherbicides using new technologies such as nanomaterials. © 2023 Society of Chemical Industry.

Multiparametric MR Evaluation of the Photoperiodic Regulation of Hypothalamic Structures in Sheep.

Most organisms on earth, humans included, have developed strategies to cope with environmental day-night and seasonal cycles to survive. For most of them, their physiological and behavioral functions, including the reproductive function, are synchronized with the annual changes of day length, to ensure winter survival and subsequent reproductive success in the following spring. Sheep are sensitive to photoperiod, which also regulates natural adult neurogenesis in their hypothalamus. We postulate that the ovine model represents a good alternative to study the functional and metabolic changes occurring in response to photoperiodic changes in hypothalamic structures of the brain. Here, the impact of the photoperiod on the neurovascular coupling and the metabolism of the hypothalamic structures was investigated at 3T using BOLD fMRI, perfusion-MRI and proton magnetic resonance spectroscopy (1H-MRS). A longitudinal study involving 8 ewes was conducted during long days (LD) and short days (SD) revealing significant BOLD, rCBV and metabolic changes in hypothalamic structures of the ewe brain between LD and SD. More specifically, the transition between LD and SD revealed negative BOLD responses to hypercapnia at the beginning of SD period followed by significant increases in BOLD, rCBV, Glx and tNAA concentrations towards the end of the SD period. These observations suggest longitudinal mechanisms promoting the proliferation and differentiation of neural stem cells within the hypothalamic niche of breeding ewes. We conclude that multiparametric MRI studies including 1H-MRS could be promising non-invasive translational techniques to investigate the existence of natural adult neurogenesis in-vivo in gyrencephalic brains.

A Web-Based Mindfulness-Based Cognitive Therapy for Couples Dealing With Chronic Cancer-Related Fatigue: Protocol for a Single-Arm Pilot Trial.

BACKGROUND: Chronic fatigue is a common symptom among patients who have been treated for cancer. Current psychosocial interventions typically target the patient alone, despite growing evidence suggesting that a couples' approach can increase and broaden the efficacy of an intervention. Therefore, based on an existing web-based mindfulness-based cognitive therapy for patients, the couple intervention COMPANION was developed. OBJECTIVE: The primary objectives of this study are to determine the acceptability of COMPANION and its potential efficacy in reducing fatigue in patients with cancer. Our secondary objectives are to examine the feasibility of the trial procedures and the potential working mechanisms of the couple intervention. METHODS: We will conduct a single-arm pilot trial for couples (ie, patients with cancer with chronic fatigue and their partners). All couples are allocated to the web-based couple intervention that consists of psychoeducation, mindfulness, and cognitive-behavioral exercises. The 9 sessions of the intervention are supervised remotely by a trained therapist. Patients and partners will complete questionnaires before starting the intervention (T0), 2 weeks after completing the intervention (T1), and 1 month after T1 (T2). They will also fill out weekly diaries during the intervention period. A subsample of patients (n≈5) and partners (n≈5) as well as all the therapists providing COMPANION will participate in the final focus groups. Benchmark values have been defined to determine the acceptability (ie, ≥60% of couples complete the intervention and/or ≥70% of the participants are satisfied with the intervention) and potential efficacy (ie, a significant improvement in fatigue and/or a clinically relevant improvement in fatigue in 45% of the patients between T0 and T1) of the intervention. The trial procedures are deemed feasible if an average of at least three couples are included per recruiting month and/or adherence to the assessments is at least 65% for T1 and the diaries and 60% for T2. To establish potential working mechanisms, changes in affect, sleep, catastrophizing, partner communication and interactions, self-efficacy, mindfulness, and closeness will be examined. Quantitative outcomes will be interpreted along with the results from the focus groups. RESULTS: Data collection is expected to be completed by March 2024. CONCLUSIONS: This pilot trial will test the first web-based mindfulness-based cognitive therapy for couples targeting chronic cancer-related fatigue. Findings will indicate whether proceeding with a randomized controlled trial is warranted. TRIAL REGISTRATION: ClinicalTrials.gov NCT05636696; https://clinicaltrials.gov/study/NCT05636696. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/48329.

Central metabolism is a key player in E. coli biofilm stimulation by sub-MIC antibiotics.

Exposure of Escherichia coli to sub-inhibitory antibiotics stimulates biofilm formation through poorly characterized mechanisms. Using a high-throughput Congo Red binding assay to report on biofilm matrix production, we screened ~4000 E. coli K12 deletion mutants for deficiencies in this biofilm stimulation response. We screened using three different antibiotics to identify core components of the biofilm stimulation response. Mutants lacking acnA, nuoE, or lpdA failed to respond to sub-MIC cefixime and novobiocin, implicating central metabolism and aerobic respiration in biofilm stimulation. These genes are members of the ArcA/B regulon-controlled by a respiration-sensitive two-component system. Mutants of arcA and arcB had a 'pre-activated' phenotype, where biofilm formation was already high relative to wild type in vehicle control conditions, and failed to increase further with the addition of sub-MIC cefixime. Using a tetrazolium dye and an in vivo NADH sensor, we showed spatial co-localization of increased metabolic activity with sub-lethal concentrations of the bactericidal antibiotics cefixime and novobiocin. Supporting a role for respiratory stress, the biofilm stimulation response to cefixime and novobiocin was inhibited when nitrate was provided as an alternative electron acceptor. Deletion of a gene encoding part of the machinery for respiring nitrate abolished its ameliorating effects, and nitrate respiration increased during growth with sub-MIC cefixime. Finally, in probing the generalizability of biofilm stimulation, we found that the stimulation response to translation inhibitors, unlike other antibiotic classes, was minimally affected by nitrate supplementation, suggesting that targeting the ribosome stimulates biofilm formation in distinct ways. By characterizing the biofilm stimulation response to sub-MIC antibiotics at a systems level, we identified multiple avenues for design of therapeutics that impair bacterial stress management.

Thermodynamic and structural properties of lipid-photosensitizer conjugates mixed with phospholipids: Impact on the formation and stability of nano-assemblies.

The photosensitizer Phenalenone (PN) was grafted with one or two lipid (C18) chains to form pure nano-assemblies or mixed lipid vesicles suitable for photodynamic therapy. Mixtures of PN-C18 conjugates with stearoyl-oleoyl phosphatidylcholine (SOPC) form vesicles that disintegrate into bilayer sheets as the concentration of PN-C18 conjugates increases. We hypothesized that PN-C18 conjugates control the thermodynamic and structural properties of the mixtures and induce the disintegration of vesicles due to PN π-π-interactions. Monolayers were analyzed by surface pressure and grazing incidence X-ray diffraction (GIXD) measurements, and vesicles by differential scanning calorimetry and cryo-TEM. The results showed that PN-triazole-C18 (1A) and PN-NH-C18 (1B) segregate from the phospholipid domains. PN-(C18)2 (conjugate 2) develops favorable interactions with SOPC and distearoyl-phosphatidylcholine (DSPC). GIXD demonstrates the contribution of SOPC to the structuring of conjugate 2 and the role of the major component in controlling the structural properties of DSPC-conjugate 2 mixtures. Above 10 mol% conjugate 2 in SOPC vesicles, the coexistence of domains with different molecule packing leads to conjugate segregation, vesicle deformation, and the formation of small bilayer discs stabilized by the inter-bilayer π-π stacking of PN molecules.

Tension as a key factor in skin responses to pollution.

Being the more apparent organ exposed to the outdoor stressors, the effect of pollution on the skin has been widely studied in the last few decades. Although UV light is known as the most aggressive stressor to which our cutaneous tissue is daily exposed, other components of the tropospheric pollution have also shown to affect skin health and functionality. Among them, ozone has been proven to be one of the most toxic due to its high reactivity with the epidermal lipids. Studying the cutaneous effect of pollution in a laboratory setting presents challenges, therefore it becomes critical to employ appropriate and tailored models that aim to answer specific questions. Several skin models are available nowadays: in vitro models (2D cell lines and 3D cutaneous tissues), ex vivo skin explants and in vivo approaches (animals and humans). Although in the last 20 years researchers developed skin models that closely resemble human skin (3D cutaneous tissues), ex vivo skin explants still remain one of the best models to study cutaneous responses. Unfortunately, one important cutaneous property that is not present in the traditional ex vivo human skin explants is the physiological tension, which has been shown to be a cardinal player in skin structure, homeostasis, functional properties and responses to external stimuli. For this reason, in this study, to confirm and further comprehend the harmful mechanism of ozone exposure on the integumentary system, we have performed experiments using the state of art in cutaneous models: the innovative TenSkin™ model in which ex vivo human skin explants are cultured under physiologically relevant tension during the whole experimental procedure. Specifically, we were interested in corroborating previous findings showing that ozone exposure modulates the expression of cutaneous antimicrobial peptides (AMPs). The present work demonstrates that cutaneous exposure to ozone induces AMPs gene and protein levels (CAMP/LL-37, hBD2, hBD3) and that the presence of tension can further modulate their expression. In addition, different responses between tension and non-tension cultured skin were also observed during the evaluation of OxInflammatory markers [cyclooxygenase-2 (COX2), aryl hydrocarbon receptor (AhR), matrix-metallo-proteinase 9 (MMP9) and 4-hydroxy-nonenal (4HNE)]. This current study supports our previous findings confirming the ability of pollution to induce the cutaneous expression of AMPs via redox signaling and corroborates the principle that skin explants are a good and reliable model to study skin responses even though it underlines the need to holistically consider the role of skin tension before extrapolating the data to real life.

Methyl Donor Nutrient Intake and Incidence of Type 2 Diabetes: Results From Three Large U.S. Cohorts.

OBJECTIVE: We examined whether intake of methyl donor nutrients, including vitamins B2, B6, and B12 and folate, from foods and/or supplements is associated with type 2 diabetes risk. RESEARCH DESIGN AND METHODS: We included 203,644 women and men from the Nurses' Health Study (1984-2016), Nurses' Health Study 2 (1991-2017), and Health Professionals Follow-Up Study (1986-2016). Dietary data were collected every 2-4 years with use of semiquantitative food-frequency questionnaires. Cox proportional hazards models with time-varying covariates were used to evaluate associations between each nutrient and type 2 diabetes risk. We combined cohort-specific hazard ratios (HRs) using inverse variance-weighted fixed-effects meta-analyses. RESULTS: During 4,900,181 person-years of follow-up, we documented 19,475 incident type 2 diabetes cases. In multivariable-adjusted meta-analyses, participants in the highest quintiles of total vitamin B2 and B6 intakes had lower risk of diabetes compared with those in the lowest quintiles (HR 0.93 [95% CI 0.89, 0.98] for B2 and 0.93 [0.89, 0.97] for B6). With stratification by source, significant associations remained for B2 from food but not from supplements. Neither association for B6 from food nor association for B6 from supplements attained significance. No association was observed between total B12 intake and diabetes. However, B12 from food was marginally associated with higher diabetes risk (1.05 [1.00-1.11]) but not after additional adjustment for red meat intake (1.04 [0.99-1.10]). No evidence of association was observed between intakes of folate and diabetes. CONCLUSIONS: The results of our study suggest that higher intake of vitamin B2 and B6, especially B2 from food sources, may be associated with a modestly lower type 2 diabetes risk.

The Aqueous Extract of Sclerocarya birrea, Nauclea latifolia, and Piper longum Mixture Protects Striatal Neurons and Movement-Associated Functionalities in a Rat Model of Diabetes-Induced Locomotion Dysfunction.

Among the many complications of type 2 diabetes (T2D), locomotor disorders have been poorly studied and understood. Therefore, no disease-modifying treatment is usually considered. The study aimed to investigate the effect of the aqueous extract of Sclerocarya birrea, Nauclea latifolia, and Piper longum (SNP) mixture on locomotor activity in fructose/streptozotocin-induced diabetic rats. T2D was induced by 10% fructose orally (6 weeks) and streptozotocin (STZ, 35 mg/kg, i.v.) in 25 male rats. Diabetic animals received distilled water, metformin (200 mg/kg), or the aqueous extract of the SNP mixture (75, 150, or 300 mg/kg). A 10-minute open field test was performed in diabetic rats (glycemia: 126 and 350 mg/dL) to assess locomotor activity before and after treatment. A group of 5 normal rats (NC) served as controls throughout the study. Rats were sacrificed, and the striatum was removed for biochemical and histological studies. In untreated diabetic rats, fructose/STZ administration resulted in hyperglycemia that altered locomotor function as characterized by increased freezing time, decreased mobility time, number of lines crossed, and total travel time compared to NC. MDA, TNF-α, INF-γ, and nitrite levels were elevated in the striatum of diabetic rats, while catalase activity and GSH levels were decreased, indicating oxidative stress and neuroinflammatory changes. In untreated diabetic rats, the microstructure of the HE-stained striatum revealed lipid vacuolation (hydropic degeneration) of the parenchyma, indicating a loss of neuronal integrity. The locomotor dysfunction was significantly improved by the aqueous extract of the SNP mixture, both biochemically and histologically. As a result, our findings support the mixture's ability to correct diabetes-related locomotion disorders as a glucose-lowering product and antioxidant, anti-inflammatory, and neuroprotective agent. These results justify the use of the aqueous extract of a combination of these three plants to manage diabetes and neuroinflammatory complications in Northern Cameroon.

Multi-scale structural alterations of the thalamus and basal ganglia in focal epilepsy using 7T MRI.

Focal epilepsy is characterized by repeated spontaneous seizures that originate from cortical epileptogenic zone networks (EZN). Analysis of intracerebral recordings showed that subcortical structures, and in particular the thalamus, play an important role in seizure dynamics as well, supporting their structural alterations reported in the neuroimaging literature. Nonetheless, between-patient differences in EZN localization (e.g., temporal vs. non-temporal lobe epilepsy) as well as extension (i.e., number of epileptogenic regions) might impact the magnitude as well as spatial distribution of subcortical structural changes. Here we used 7 Tesla MRI T1 data to provide an unprecedented description of subcortical morphological (volume, tissue deformation, and shape) and longitudinal relaxation (T1 ) changes in focal epilepsy patients and evaluate the impact of the EZN and other patient-specific clinical features. Our results showed variable levels of atrophy across thalamic nuclei that appeared most prominent in the temporal lobe epilepsy group and the side ipsilateral to the EZN, while shortening of T1 was especially observed for the lateral thalamus. Multivariate analyses across thalamic nuclei and basal ganglia showed that volume acted as the dominant discriminator between patients and controls, while (posterolateral) thalamic T1 measures looked promising to further differentiate patients based on EZN localization. In particular, the observed differences in T1 changes between thalamic nuclei indicated differential involvement based on EZN localization. Finally, EZN extension was found to best explain the observed variability between patients. To conclude, this work revealed multi-scale subcortical alterations in focal epilepsy as well as their dependence on several clinical characteristics.

Biocatalytic Production of Odor-Active Fatty Aldehydes from Fungal Lipids.

Odor-active fatty aldehydes are important compounds for the flavor and fragrance industry. By a coupled enzymatic reaction using an α-dioxygenase (α-DOX) and an aldehyde dehydrogenase (FALDH), scarcely available aldehydes from the biotransformation of margaroleic acid [17:1(9Z)] were characterized and have shown highly interesting odor profiles, including citrus-like, soapy, herbaceous, and savory notes. In particular, (Z)-8-hexadecenal and (Z)-7-pentadecenal exhibited notable meaty odor characteristics. Submerged cultivation of Mortierella hyalina revealed the accumulation of the above-mentioned, naturally uncommon fatty acid 17:1(9Z). Its production was significantly increased by the modulation of culture conditions, whereas the highest accumulation was observed after 4 days at 24 °C and l-isoleucine supplementation. The lipase-, α-DOX-, and FALDH-mediated biotransformation of M. hyalina lipid extract resulted in a complex aldehyde mixture with a high aldehyde yield of ∼50%. The odor qualities of the formed aldehydes were assessed by means of gas chromatography-olfactometry, and several of the obtained fatty aldehydes have been sensorially described for the first time. To assess the aldehyde mixture's potential as a flavor ingredient, a sensory evaluation was conducted. The obtained product exhibited intense citrus-like, green, and soapy odor impressions.

Seasonal remodeling of the progenitor pool and its distribution in the ewe mediobasal hypothalamus.

Recent studies have reported the presence of adult neurogenesis in the arcuate nucleus periventricular space (pvARH) and in the median eminence (ME), two structures involved in reproductive function. In sheep, a seasonal mammal, decreasing daylight in autumn induces a higher neurogenic activity in these two structures. However, the different types of neural stem and progenitor cells (NSCs/NPCs) that populate the arcuate nucleus and median eminence, as well as their location, have not been evaluated. Here, using semi-automatic image analyzing processes, we identified and quantified the different populations of NSCs/NPCs, showing that, during short days, higher densities of [SOX2 +] cells are found in pvARH and ME. In the pvARH, higher densities of astrocytic and oligodendrocitic progenitors mainly contribute to these variations. The different populations of NSCs/NPCs were mapped according to their position relative to the third ventricle and their proximity to the vasculature. We showed that [SOX2 +] cells extended deeper into the hypothalamic parenchyma during short days. Similarly, [SOX2 +] cells were found further from the vasculature in the pvARH and the ME, at this time of year, indicating the existence of migratory signals. The expression levels of neuregulin transcripts (NRGs), whose proteins are known to stimulate proliferation and adult neurogenesis and to regulate progenitor migration, as well as the expression levels of ERBB mRNAs, cognate receptors for NRGs, were assessed. We showed that mRNA expression changed seasonally in pvARH and ME, suggesting that the ErbB-NRG system is potentially involved in the photoperiodic regulation of neurogenesis in seasonal adult mammals.

Microalgae adaptation as a strategy to recycle the aqueous phase from hydrothermal liquefaction.

Hydrothermal liquefaction (HTL) produces bio-crude oil from wet algae along with an aqueous phase (AP). This effluent contains minerals that can be reused for cultivating new microalgae but whose utility remains limited due to the presence of inhibitors. Reduced photosynthetic performance, growth, and null lipid accumulation were observed in wild-type Chlorella vulgaris NIES 227 cultivated in AP (1/200). Adaptive laboratory evolution was studied by batch transfers and turbidostat mode. Both methods effectively counterbalanced AP toxicity and restored the fitness of the microalgae. After adaptation, a higher AP addition was achieved, from 1/600 to 1/200, without inhibition. As compared with the wild typein control medium (0.261 g/L/d), both adapted-strains maintained competitive productivity (0.310 and 0.258 g/L/d) of lipid-rich biomass (37 %-56 %). The improved tolerance of the adapted strains persisted after the removal of AP and under axenic conditions. Adaptive laboratory evolution is suggested for AP reutilization in the algae production process.

Antithrombotic therapy and cardiovascular outcomes after transcatheter aortic valve implantation in patients without indications for chronic oral anticoagulation: a systematic review and network meta-analysis of randomized controlled trials.

AIMS: As the antithrombotic regimen that may best prevent ischaemic complications along with the lowest bleeding risk offset following transcatheter aortic valve implantation (TAVI) remains unclear, we aimed to compare the safety and efficacy of antithrombotic regimens in patients without having an indication for chronic oral anticoagulation. METHODS AND RESULTS: We conducted a PROSPERO-registered (CRD42021247924) systematic review and network meta-analysis of randomized controlled trials evaluating post-TAVI antithrombotic regimens up to April 2022. We estimated the relative risk (RR) and 95% confidence intervals (95% CIs) using a random-effects model in a frequentist pairwise and network metanalytic approach. We included seven studies comprising 4006 patients with a mean weighted follow-up of 12.9 months. Risk of all-cause death was significantly reduced with dual antiplatelet therapy (DAPT) compared with low-dose rivaroxaban + 3-month single antiplatelet therapy (SAPT) (RR 0.60, 95% CI 0.41-0.88), while no significant reduction was observed with SAPT vs. DAPT (RR 1.02, 95% CI 0.67-1.58) and SAPT and DAPT compared with apixaban or edoxaban (RR 0.60, 95% CI 0.32-1.14 and RR 0.59, 95% CI 0.34-1.02, respectively). SAPT was associated with a significant reduction of life-threatening, disabling, or major bleeding compared with DAPT (RR 0.45, 95% CI 0.29-0.70), apixaban or edoxaban alone (RR 0.45, 95% CI 0.25-0.79), and low-dose rivaroxaban + 3-month SAPT (RR 0.30, 95% CI 0.16-0.57). There were no differences between the various regimens with respect to myocardial infarction, stroke, or systemic embolism. CONCLUSION: Following TAVI in patients without an indication for chronic oral anticoagulant, SAPT more than halved the risk of bleeding compared with DAPT and direct oral anticoagulant-based regimens without significant ischaemic offset.

Rifampin-moxifloxacin-metronidazole combination therapy for severe Hurley stage 1 hidradenitis suppurativa: prospective short-term trial and 1-year follow-up in 28 consecutive patients.

BACKGROUND: Severe Hurley stage 1 hidradenitis suppurativa (HS1) is a difficult-to-treat form of the disease. OBJECTIVE: To assess the efficacy and tolerance of the oral combination of rifampin (10 mg/kg once daily)/moxifloxacin (400 mg once daily)/metronidazole (250-500 mg 3 times daily) (RMoM) treatment strategy in patients with severe HS1. METHODS: Prospective, open-label, noncomparative cohort study in 28 consecutive patients. Nineteen patients were treated for 6 weeks by RMoM, followed by 4 weeks of rifampin/moxifloxacin alone, then by cotrimoxazole after remission. Moxifloxacin was replaced by pristinamycin (1 g 3 times daily) in 9 patients because of contraindications or intolerance. The primary endpoint was a Sartorius score of 0 (clinical remission) at week 12. RESULTS: The median Sartorius score dropped from 14 to 0 (P = 6 × 10-6) at week 12, with 75% of patients reaching clinical remission. A low initial Sartorius score was a prognosis factor for clinical remission (P = .049). The main adverse effects were mild gastrointestinal discomfort, mucosal candidiasis, and asthenia. At 1 year of follow-up, the median number of flares dropped from 21/year to 1 (P = 1 × 10-5). LIMITATIONS: Small, monocentric, noncontrolled study. CONCLUSIONS: Complete and prolonged remission can be obtained in severe HS1 by using targeted antimicrobial treatments.

Last resort beta-lactam antibiotics for treatment of New-Delhi Metallo-Beta-Lactamase producing Enterobacterales and other Difficult-to-Treat Resistance in Gram-negative bacteria: A real-life study.

Introduction: Novel last resort beta-lactam antibiotics are now available for management of infections due to New-Delhi Metallo-Beta-Lactamase (NDM) producing Enterobacterales and non-fermenters with Difficult-to-Treat Resistance. However, data regarding the use of imipenem-cilastatin-relebactam (IMI-REL), cefiderocol (CFD) and ceftazidime-avibactam plus aztreonam (CAZ-AVI-ATM) are scarce in real-life settings. This study aimed to describe the use of last resort beta-lactam antibiotics, the microbiology and the outcome, in patients hospitalized in a tertiary hospital. Methods: We conducted a monocentric observational cohort study from 2020/01/01, to 2022/08/31. We screened all patients admitted to Nimes University Hospital who have received ≥ 1 dose of last resort beta-lactam antibiotics during the study period, using the Pharmacy database. We included patients treated with IMI-REL, CFD and CAZ-AVI-ATM. The primary endpoint was the infection-free survival rate. We also calculated rates of microbiological and clinical cure, recurrent infection, death and adverse events. Results: Twenty-seven patients were included in the study and 30 treatment courses were analyzed: CFD (N=24; 80%), CAZ-AVI-ATM (N=3; 10%) and IMI-REL (N=3; 10%). Antibiotics were used in 21 males (70%) and 9 females (30%) with a median age at 65-year-old [50-73.5] and a median Charlson index at 1 [0-2]. Almost all the patients had ≥ 1 risk factor for carbapenem resistant bacteria, a half of them was hospitalized for severe COVID-19, and most of antibiotic courses (N=26; 87%) were associated with ICU admission. In the study population, the probability of infection-free survival at day-90 after last resort beta-lactam therapy initiation was 48.4% CI95% [33.2-70.5]. Clinical failure rate was at 30%, microbiological failure rate at 33% and mortality rate at 23%. Adverse events were documented in 5 antibiotic courses (17%). In details, P. aeruginosa were mainly treated with CFD and IMI-REL, S. maltophilia with CFD and CAZ-AVI-ATM, A. baumannii with CFD, and NDM producing-K. pneumoniae with CAZ-AVI-ATM and CFD. After a treatment course with CFD, CAZ-AVI-ATM and IMI-REL, the probability of infection-free survival was 48% CI95% [10.4-73.5], 33.3% CI95% [6.7-100], 66.7% CI95% [30-100], respectively. Discussion/conclusion: Use of last resort beta-lactam antimicrobials in real-life settings was a safe and efficient therapeutic option for severe infections related to Gram-negative bacteria with Difficult-to-Treat Resistance.