Idiopathic intracranial hypertension secondary to fluoroquinolone therapy: French pharmacovigilance data review.

We investigate spontaneous reports of IIH related to fluoroquinolones recorded in the French national pharmacovigilance database in order to detect a possible pharmacovigilance signal. The association between IIH risk and fluoroquinolone exposure was assessed using a case/non-case study. Between 1985 and July 2023, 17 reports of IIH after fluoroquinolone exposure were recorded. No specific fluoroquinolone was predominant. IIH led to death in one case and blindness in one case. The Reporting Odds Ratio was 2.58 (95% confidence interval 1.59-4.19). We highlight statistically significant disproportionality, which constitutes a pharmacovigilance signal. IIH risk after fluoroquinolone exposure is a class effect.

Mindfulness in Parkinson's disease: A French national survey and a pilot intervention feasibility trial using the MBSR program (M-Park).

BACKGROUND: Non-pharmacological complementary interventions, particularly mind-body practices, are of growing importance in the management of Parkinson's disease (PD). Among these, mindfulness meditation seems particularly effective, especially on anxiety and depression symptoms. However, current knowledge on mindfulness standardized programs in PD is still limited, particularly in France. Aiming at improving this knowledge we designed the M-PARK study in two phases. Phase 1 consisted in a French national survey to explore expectations, needs and initiatives for mindfulness meditation for PD patients. Phase 2 was a clinical trial with objectives to assess feasibility, acceptability and effects of a mindfulness (MBSR) program proposed to PD patients. METHODS: In phase 1, online questionnaires were addressed to members of a French PD patient's association (France Parkinson) and French MBSR qualified instructors. In Phase 2, a clinical trial involving 30 PD patients consisted of a standard MBSR program with two additional evaluation visits one month before and after the program. Data collection included a global clinical evaluation, assessment of depression and anxiety symptoms, sleep, pain and quality of life and a face-to-face interview for qualitative assessment of the acceptability and lived experience during the program. Three MBSR programs were proposed to three groups of ten patients: two were online due to the pandemic situation, one proposed to patients with no or minor fluctuations (group 1) and one for patients with slight to moderate fluctuations (group 2), and the last one face-to-face for patients with no or minor fluctuations (group 3). RESULTS: French survey: 209 responses were collected for the questionnaire sent to the members of the association France Parkinson; and 68 for the questionnaire sent to the instructors. Two-thirds of patients surveyed had heard of mindfulness meditation (66%), but were unaware of what this approach really consisted and how it could really help them. Few instructors (29%) had had to deal with patients with PD in their current practice. Yet 90% of patients surveyed indicated they were in favor of introducing this type of approach into their care. CLINICAL TRIAL: The results indicated that the program is feasible and acceptable both online and face-to-face for patients with PD. Among the 30 patients enrolled, 25 completed the program. No unwanted effects related to mindfulness meditation practice were observed. The results showed a statistically significant reduction in anxiety symptoms, depressive symptoms, and improvement in quality of life. Furthermore, no statistically significant change was measured for pain or sleep quality. There was no striking difference in results observed between the patient groups. For the qualitative analysis, major themes highlighted were in relation with: (i) the lived experience during program; (ii) changes in the daily life; and (iii) disease-related changes. A large majority of patients who completed the program (24/25) described their participation as positive or very positive. They reported better management of stress and emotions, as well as greater autonomy in implementing new behavioral strategies, particularly in terms of self-care, acceptance, and de-identification from the disease. CONCLUSION: Despite high expectations, PD patients are poorly informed about available mindfulness programs. This study however shows that these programs, whether offered online or face-to-face, are particularly beneficial, especially for anxiety and depressive symptoms, at least in mild-to-moderate stages of the disease.

Towards the Improvement of Soil Salinity Mapping in a Data-Scarce Context Using Sentinel-2 Images in Machine-Learning Models.

Several recent studies have evidenced the relevance of machine-learning for soil salinity mapping using Sentinel-2 reflectance as input data and field soil salinity measurement (i.e., Electrical Conductivity-EC) as the target. As soil EC monitoring is costly and time consuming, most learning databases used for training/validation rely on a limited number of soil samples, which can affect the model consistency. Based on the low soil salinity variation at the Sentinel-2 pixel resolution, this study proposes to increase the learning database's number of observations by assigning the EC value obtained on the sampled pixel to the eight neighboring pixels. The method allowed extending the original learning database made up of 97 field EC measurements (OD) to an enhanced learning database made up of 691 observations (ED). Two classification machine-learning models (i.e., Random Forest-RF and Support Vector Machine-SVM) were trained with both OD and ED to assess the efficiency of the proposed method by comparing the models' outcomes with EC observations not used in the models´ training. The use of ED led to a significant increase in both models' consistency with the overall accuracy of the RF (SVM) model increasing from 0.25 (0.26) when using the OD to 0.77 (0.55) when using ED. This corresponds to an improvement of approximately 208% and 111%, respectively. Besides the improved accuracy reached with the ED database, the results showed that the RF model provided better soil salinity estimations than the SVM model and that feature selection (i.e., Variance Inflation Factor-VIF and/or Genetic Algorithm-GA) increase both models´ reliability, with GA being the most efficient. This study highlights the potential of machine-learning and Sentinel-2 image combination for soil salinity monitoring in a data-scarce context, and shows the importance of both model and features selection for an optimum machine-learning set-up.

The ID NOW COVID-19, a high-speed high-performance assay.

The ID NOW COVID-19 assay is a promising tool for the rapid identification of COVID-19 patients. However, its performances were questioned. We evaluate the ID NOW COVID-19 in comparison to a reference RT-PCR using a collection of 48 fresh nasopharyngeal swabs sampled on universal transport media (UTM). Only 2 false negatives of the ID NOW COVID-19 were identified. They display PCR cycle threshold values of 37.5 and 39.2. The positive percent agreement and the negative percent agreement were 94.9% and 100%, respectively. The Kappa value was 0.88. The ID NOW COVID-19 combines high-speed and accurate processing. Using UTM, the ID NOW COVID-19 could be repeated in the case of invalid result. Further analyses, such as screening of genetic variants or genome sequencing, could also be performed with the same sample. As for all tests, the results should be interpreted according to clinical and epidemiological context.

Clinical profiles of placenta accreta spectrum: the PACCRETA population-based study.

OBJECTIVE: To describe and compare the characteristics of women with placenta accreta spectrum (PAS) and their pregnancy outcomes according to the presence of placenta praevia and a prior caesarean section. DESIGN: Prospective population-based study. SETTING: All 176 maternity hospitals of eight French regions. POPULATION: Two hundred and forty-nine women with PAS, from a source population of 520 114 deliveries. METHODS: Women with PAS were classified into two risk-profile groups, with or without the high-risk combination of placenta praevia (or an anterior low-lying placenta) and at least one prior caesarean. These two groups were described and compared. MAIN OUTCOME MEASURES: Population-based incidence of PAS, characteristics of women, pregnancies, deliveries and pregnancy outcomes. RESULTS: The PAS population-based incidence was 4.8/10 000 (95% CI 4.2-5.4/10 000). After exclusion of women lost to follow up from the analysis, the group with placenta praevia and a prior caesarean included 115 (48%) women and the group without this combination included 127 (52%). In the group with both factors, PAS was more often suspected antenatally (77% versus 17%; P < 0.001) and more often percreta (38% versus 5%; P < 0.001). This group also had more hysterectomies (53% versus 21%, P < 0.001) and higher rates of blood product transfusions, maternal complications, preterm births and neonatal intensive care unit admissions. Sensitivity analysis showed similar results after exclusion of women who delivered vaginally. CONCLUSION: More than half the cases of PAS occurred in women without the combination of placenta praevia and a prior caesarean delivery, and these women had better maternal and neonatal outcomes. We cannot completely rule out that some of the women who delivered vaginally had placental retention rather than PAS; however, we found similar results among women who delivered by caesarean. TWEETABLE ABSTRACT: Half the women with PAS do not have both placenta praevia and a prior caesarean delivery, and they have better maternal outcomes.

Gestational anaemia and severe acute maternal morbidity: a population-based study.

Anaemia is frequently diagnosed during pregnancy. However, there are few data regarding its incidence, and the association with severe maternal morbidity remains uncertain and potentially biased in high-resource countries. The purpose of this study was to explore the association between gestational anaemia and severe acute maternal morbidity during and after delivery. We performed a cohort-nested case-control analysis from the epidemiology of severe maternal mortality (EPIMOMS) prospective study conducted in six French regions (2012-2013, n = 182,309 deliveries). There were 1669 women with severe acute maternal morbidity during or after delivery, according to a standardised definition obtained by expert consensus. The control group were randomly selected among women without severe morbidity who delivered in the same health centres (n = 3234). We studied the association between gestational anaemia and severe acute maternal morbidity during or after delivery overall, by cause, and by mode of delivery, using multivariable logistic regression and multiple imputation. Gestational anaemia was significantly more frequent in women with severe acute maternal morbidity (25.3%) than in controls (16.3%), p < 0.001, and mostly mild in both groups. After adjustment for confounders, women with gestational anaemia were at increased risk of overall severe acute maternal morbidity during and after delivery (adjusted OR (95%CI) 1.8 (1.5-2.1)). This association was also found for severe postpartum haemorrhage (adjusted OR (95%CI) 1.7 (1.5-2.0)), even after omitting the transfusion criterion (adjusted OR (95%CI) 1.9 (1.6-2.3)), and for severe acute maternal morbidity secondary to causes other than haemorrhage or pregnancy-related hypertensive disorders (adjusted OR (95%CI) 2.7 (1.9-4.0)). These results highlight the importance of optimising the diagnosis and management of anaemia during pregnancy.

Anaphylaxis in pregnancy: a population-based multinational European study.

Anaphylaxis in pregnancy is a rare but severe complication for both mother and infant. Population-based data on anaphylaxis in pregnancy are lacking from mainland European countries. This multinational study presents the incidence, causative agents, management and maternal and infant outcomes of anaphylaxis in pregnancy. This descriptive multinational study used a combination of retrospective (Finnish medical registries) and prospective population-based studies (UK, France, Belgium and the Netherlands) to identify cases of anaphylaxis. Sixty-five cases were identified among 4,446,120 maternities (1.5 per 100,000 maternities; 95%CI 1.1-1.9). The incidence did not vary between countries. Approximately three-quarters of reactions occurred at the time of delivery. The most common causes were antibiotics in 27 women (43%), and anaesthetic agents in 11 women (17%; including neuromuscular blocking drugs, 7), which varied between countries. Anaphylaxis had very poor outcomes for one in seven mothers and one in seven babies; the maternal case fatality rate was 3.2% (95%CI 0.4-11.0) and the neonatal encephalopathy rate was 14.3% (95%CI 4.8-30.3). Across Europe, anaphylaxis related to pregnancy is rare despite having a multitude of causative agents and different antibiotic prophylaxis protocols.

Physiological effects of gamma irradiation in the honeybee, Apis mellifera.

Terrestrial ecosystems are exposed to various kinds of pollutants, including radionuclides. The honeybee, Apis mellifera, is commonly used in ecotoxicology as a model species for evaluating the effects of pollutants. In the present study, honeybees were irradiated right after birth for 14 days with gamma rays at dose rates ranging between 4.38 × 10-3 and 588 mGy/d. Biological tissues (head, intestine and abdomen) were sampled at D3, D10 and D14. Ten different physiological markers involved in nervous (acetylcholinesterase (AChE)), antioxidative (catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GPx) and glutathione-S-transferase (GST)), immune system (phenoloxidase (PO)) and metabolism (carboxylesterases (CaEs) and alkaline phosphatase (ALP)) were measured. Univariate analyses were conducted to determine whether each individual biomarker response was positively or negatively correlated with the dose rate. Then, multivariate analyses were applied to investigate the relationships between all the biomarker responses. Although no mortality occurred during the experiment, several biomarkers varied significantly in relation to the dose rate. Globally, the biomarkers of antioxidant and immune systems decreased as the dose rate increased. Reversible effects on the indicator of the neural system were found. Concerning indicators of metabolism (carboxylesterases), variations occurred but no clear pattern was found. Taken altogether, these results help better understand the effects of ionizing radiation on bees by identifying relevant physiological markers of effects. These results could improve the assessment of the environmental risk due to ionizing radiation in terrestrial ecosystems.

Study of gene expression alteration in male androgenetic alopecia: evidence of predominant molecular signalling pathways.

BACKGROUND: Male androgenetic alopecia (AGA) is the most common form of hair loss in men. It is characterized by a distinct pattern of progressive hair loss starting from the frontal area and the vertex of the scalp. Although several genetic risk loci have been identified, relevant genes for AGA remain to be defined. OBJECTIVES: To identify biomarkers associated with AGA. METHODS: Molecular biomarkers associated with premature AGA were identified through gene expression analysis using cDNA generated from scalp vertex biopsies of hairless or bald men with premature AGA, and healthy volunteers. RESULTS: This monocentric study reveals that genes encoding mast cell granule enzymes, inflammatory mediators and immunoglobulin-associated immune mediators were significantly overexpressed in AGA. In contrast, underexpressed genes appear to be associated with the Wnt/ß-catenin and bone morphogenic protein/transforming growth factor-ß signalling pathways. Although involvement of these pathways in hair follicle regeneration is well described, functional interpretation of the transcriptomic data highlights different events that account for their inhibition. In particular, one of these events depends on the dysregulated expression of proopiomelanocortin, as confirmed by polymerase chain reaction and immunohistochemistry. In addition, lower expression of CYP27B1 in patients with AGA supports the notion that changes in vitamin D metabolism contributes to hair loss. CONCLUSIONS: This study provides compelling evidence for distinct molecular events contributing to alopecia that may pave the way for new therapeutic approaches.

Evaluation of a chest radiograph reading and recording system for tuberculosis in a HIV-positive cohort.

AIM: To assess the impact of introducing a chest radiograph reading and recording system (CRRS) with a short training session, on the accuracy and inter-reader variability of tuberculosis (TB) interpretation of chest radiographs (CXRs) by a group of non-expert readers in a human immunodeficiency virus (HIV)-positive cohort. MATERIALS AND METHODS: A set of 139 CXRs was reviewed by a group of eight physicians pre- and post-intervention at two clinics in Shan State, Myanmar, providing HIV/TB diagnosis and treatment services. The results were compared against the consensus of expert radiologists for accuracy. RESULTS: Overall accuracy was similar pre- and post-intervention for most physicians with an average area under the receiver operating characteristic curve difference of 0.02 (95% confidence interval: -0.03, 0.07). The overall agreement among physicians was poor pre- and post-intervention (Fleiss κ=0.35 and κ=0.29 respectively). The assessment of agreement for specific disease patterns associated with active TB in HIV-infected patients showed that for intrinsically subtle findings, the agreement was generally poor but better for the more intrinsically obvious disease patterns: pleural effusion (Cohen's kappa range = 0.37-0.67) and milliary nodular pattern (Cohen's kappa range = 0.25-0.52). CONCLUSION: This study demonstrated limited impact of the introduction of a CRRS on CXR accuracy and agreement amongst non-expert readers. The role in which CXRs are used for TB diagnosis in a HIV-positive cohort in similar clinical contexts should be reviewed.

Pharmacokinetics of rifampin and isoniazid in tuberculosis-HIV-coinfected patients receiving nevirapine- or efavirenz-based antiretroviral treatment.

This is a substudy of the Agence Nationale de Recherches sur le Sida et les Hépatites Virales (ANRS) Comparison of Nevirapine and Efavirenz for the Treatment of HIV-TB Co-infected Patients (ANRS 12146-CARINEMO) trial, which assessed the pharmacokinetics of rifampin or isoniazid with or without the coadministration of nonnucleoside reverse transcriptase inhibitor-based HIV antiretroviral therapy in HIV-tuberculosis-coinfected patients in Mozambique. Thirty-eight patients on antituberculosis therapy based on rifampin and isoniazid participated in the substudy (57.9% males; median age, 33 years; median weight, 51.9 kg; median CD4(+) T cell count, 104 cells/µl; median HIV-1 RNA load, 5.5 log copies/ml). The daily doses of rifampin and isoniazid were 10 and 5 mg/kg of body weight, respectively. Twenty-one patients received 200 mg of nevirapine twice a day (b.i.d.), and 17 patients received 600 mg of efavirenz once a day (q.d.) in combination with lamivudine and stavudine from day 1 until the end of the study. Blood samples were collected at regular time-dosing intervals after morning administration of a fixed-dose combination of rifampin and isoniazid. When rifampin was administered alone, the median maximum concentration of drug in serum (Cmax) and the area under the concentration-time curve (AUC) at steady state were 6.59 mg/liter (range, 2.70 to 14.07 mg/liter) and 27.69 mg · h/liter (range, 11.41 to 109.75 mg · h/liter), respectively. Concentrations remained unchanged when rifampin was coadministered with nevirapine or efavirenz. When isoniazid was administered alone, the median isoniazid Cmax and AUC at steady state were 5.08 mg/liter (range, 1.26 to 11.51 mg/liter) and 20.92 mg · h/liter (range, 7.73 to 56.95 mg · h/liter), respectively. Concentrations remained unchanged when isoniazid was coadministered with nevirapine; however, a 29% decrease in the isoniazid AUC was observed when isoniazid was combined with efavirenz. The pharmacokinetic parameters of rifampin and isoniazid when coadministered with nevirapine or efavirenz were not altered to a clinically significant extent in these severely immunosuppressed HIV-infected patients. Patients experienced favorable clinical outcomes. (This study has been registered at ClinicalTrials.gov under registration no. NCT00495326.).

Conjugated linoleic acid (CLA) modulates bovine peripheral blood mononuclear cells (PBMC) proteome in vitro.

Conjugated linoleic acid (CLA) is a group of natural isomers of the n-6 polyunsaturated fatty acid (PUFA) linoleic acid, exerting biological effects on cow physiology. This study assessed the impact of the mixture 50:50 (vol:vol) of CLA isomers (cis-9, trans-11 and trans-10, cis-12) on bovine peripheral blood mononuclear cells (PBMC) proteome, identifying 1608 quantifiable proteins. A supervised multivariate statistical analysis, sparse variant partial least squares - discriminant analysis (sPLS-DA) for paired data identified 407 discriminant proteins (DP), allowing the clustering between the CLA and controls. The ProteINSIDE workflow found that DP with higher abundance in the CLA group included proteins related to innate immune defenses (PLIN2, CD36, C3, C4, and AGP), with antiapoptotic (SERPINF2 and ITIH4) and antioxidant effects (HMOX1). These results demonstrated that CLA modulates the bovine PBMC proteome, supports the antiapoptotic and immunomodulatory effects observed in previous in vitro studies on bovine PBMC, and suggests a cytoprotective role against oxidative stress. SIGNIFICANCE: In this study, we report for the first time that the mixture 50:50 (vol:vol) of cis-9, trans-11, and trans-10, cis-12-CLA isomers modulates the bovine PBMC proteome. Our results support the immunomodulatory and antiapoptotic effects observed in bovine PBMC in vitro. In addition, the present study proposes a cytoprotective role of CLA mixture against oxidative stress. We suggest a molecular signature of CLA treatment based on combining a multivariate sparse discriminant analysis and a clustering method. This demonstrates the great value of sPLS-DA as an alternative option to identify discriminant proteins with relevant biological significance.

Comparative electroencephalography analysis: Marathon runners during tapering versus sedentary controls reveals no significant differences.

INTRODUCTION: Previous studies described various adaptive neuroplastic brain changes associated with physical activity (PA). EEG studies focused mostly on effects during or shortly after short bouts of exercise. This is the first study to investigate the capability of EEG to display PA-induced long-lasting plasticity in runners compared to a sedentary control group. METHODS: Thirty trained runners and 30 age- and sex-matched sedentary controls (SC) were included as a subpopulation of the ReCaP (Running effects on Cognition and Plasticity) study. PA was measured with the International Physical Activity Questionnaire (IPAQ). Resting-state EEG of the runners was recorded in the tapering phase of the training for the Munich marathon 2017. Power spectrum analyses were conducted using standardized low-resolution electromagnetic tomography (sLORETA) and included the following frequency bands: delta: 1.5-6 Hz, theta: 6.5-8.0 Hz, alpha1: 8.5-10 Hz, alpha2: 10.5-12.0 Hz, beta1: 12.5-18.0 Hz, beta2: 18.5-21.0 Hz, beta3: 21.5-30.0 Hz, and total power (1.5-30 Hz). RESULTS: PA (IPAQ) and BMI differed significantly between the groups. The other included demographic parameters were comparable. Statistical nonparametric mapping showed no significant power differences in EEG between the groups. DISCUSSION: Heterogeneity in study protocols, especially in time intervals between exercise cessation and EEG recordings and juxtaposition of acute exercise-induced effects on EEG in previous studies, could be possible reasons for the differences in results. Future studies should record EEG at different time points after exercise cessation and in a broader spectrum of exercise intensities and forms to further explore the capability of EEG in displaying long-term exercise-induced plasticity.

Evaluation of a short training course of chest X-ray interpretation for the diagnosis of paediatric TB.

BACKGROUND: Chest X-ray (CXR) interpretation is challenging for the diagnosis of paediatric TB. We assessed the performance of a three half-day CXR training module for healthcare workers (HCWs) at low healthcare levels in six high TB incidence countries. METHODS: Within the TB-Speed Decentralization Study, we developed a three half-day training course to identify normal CXR, CXR of good quality and identify six TB-suggestive features. We performed a pre-post training assessment on a pre-defined set of 20 CXR readings. We compared the proportion of correctly interpreted CXRs and the median reading score before and after the training using the McNemar test and a linear mixed model. RESULTS: Of 191 HCWs, 43 (23%) were physicians, 103 (54%) nurses, 18 (9.4%) radiology technicians and 12 (6.3%) other professionals. Of 2,840 CXRs with both assessment, respectively 1,843 (64.9%) and 2,277 (80.2%) were correctly interpreted during pre-training and post-training (P < 0.001). The median reading score improved significantly from 13/20 to 16/20 after the training, after adjusting by country, facility and profession (adjusted ß = 3.31, 95% CI 2.44-4.47). CONCLUSION: Despite some limitations of the course assessment that did not include abnormal non-TB suggestive CXR, study findings suggest that a short CXR training course could improve HCWs' interpretation skills in diagnosing paediatric TB.

CONTEXTE: L'interprétation de la radiographie thoracique (CXR) est un défi pour le diagnostic de la TB pédiatrique. Nous avons évalué la performance d'un module de formation de trois demi-journées sur la CXR destiné aux agents de santé (HCWs) dans six pays où l'incidence de la TB est élevée et où les ressources en services de santé sont limitées. MÉTHODES: Dans le cadre de l'étude de décentralisation TB-Speed, nous avons mis au point un cours de formation de trois demi-journées pour identifier une CXR normale, une CXR de bonne qualité et six caractéristiques suggestives de la TB. Nous avons effectué une évaluation avant et après la formation sur un ensemble prédéfini de 20 clichés radiologiques. Nous avons comparé la proportion de CXR correctement interprétées et le score médian de lecture avant et après la formation à l'aide du test de McNemar et d'un modèle linéaire mixte. RÉSULTATS: Sur les 191 HCWs, 43 (23%) étaient des médecins, 103 (54%) des infirmières, 18 (9,4%) des techniciens en radiologie et 12 (6,3%) d'autres professionnels. Sur 2 840 CXR avec les deux évaluations, respectivement 1 843 (64,9%) et 2 277 (80,2%) ont été correctement interprétées avant et après la formation (P < 0,001). Le score médian de lecture s'est amélioré de manière significative, passant de 13/20 à 16/20 après la formation, après ajustement par pays, établissement et profession (ß ajusté = 3,31; IC 95% 2,44­4,47). CONCLUSION: Malgré certaines limites de l'évaluation du cours qui n'incluait pas de CXR anormale non évocatrice de TB, les résultats de l'étude suggèrent qu'une formation courte sur la CXR pourrait améliorer les compétences d'interprétation des HCWs dans le diagnostic de la TB pédiatrique.

Seasonal effect on trace metal elements behaviour in a reservoir of northern Thailand.

Trace metal elements (TME) can be real threats for living organisms. However, few studies dealt with TME in reservoirs in rural areas where farming practises could induce negative effects. Mae Thang reservoir (northern Thailand) has been studied for 3 years to understand the seasonal behaviour of dissolved TME: Fe, Mn, Cd, Al, Pb, V, Cr, Co, Ni, Cu, Zn, Mo, U and As and associated physicochemical parameters. In situ measurements of these parameters were done during the dry and the wet seasons as well as water samples along the water column for further analyses and TME determination by inductively coupled plasma-mass spectrometry (ICP-MS). In the dry season, the water column was characterized by a strong stratification and anoxic conditions in the hypolimnion. High rain and water input from the watershed during the wet season induced mixing of the water. All TME, except Ni, Co and Cr were less concentrated in the wet season indicating a dilution effect by water input. There was thus no important dissolved pollution coming from the watershed. The anoxic conditions in the dry season enhanced the reduction of Fe and Mn and the desorption processes. Depth, and thus oxic-anoxic conditions were the main drivers of TME in the dry season, while in the wet season, dissolution processes from parent rocks of watershed were favoured. The average concentrations of TME in the reservoir were in the limit of the international and Thai standards. Only localized values in the bottom of the reservoir for Fe and Mn were higher than the limits.

Protein signatures of spontaneous lipolysis and lipoprotein lipase activity in cow's milk.

Spontaneous milk lipolysis refers to the breakdown of triacylglycerols in milk. Lipolysis impacts the organoleptic value of milk by causing off-flavours and reduces the technological properties of milk. Lipolysis is caused by lipoprotein lipase (LPL), a tightly regulated enzyme in milk. Our objective was to identify robust biomarkers of lipolysis and putative regulators of LPL enzyme in bovine milk. To achieve this goal, we used feed restriction as a lever to generate highly contrasted samples with regard to milk lipolysis. We combined statistical methods on proteomics data, milk lipolysis and LPL activity values. Following this strategy, we identified CD5L and GP2 as robust biomarkers of high lipolysis in cow milk. We also identified HID1, SURF4 and CUL9 as putative inhibitors of the lipolytic process in the milk. We thus proposed 5 putative biomarkers to be considered in future tools to manage milk lipolysis. SIGNIFICANCE: This manuscript is notable in three aspects. First, this is the first evaluation of the milk proteome relative to milk lipolysis or LPL activity. Second, the relationship between the abundance of proteins and milk traits was evaluated by a combination of univariate and multivariate analyses. Third, we provide a short list of five proteins to be tested in a larger population to feed the pipeline of biomarker discovery.

Evaluating newly approved drugs in combination regimens for multidrug-resistant tuberculosis with fluoroquinolone resistance (endTB-Q): study protocol for a multi-country randomized controlled trial.

BACKGROUND: Treatment for fluoroquinolone-resistant multidrug-resistant/rifampicin-resistant tuberculosis (pre-XDR TB) often lasts longer than treatment for less resistant strains, yields worse efficacy results, and causes substantial toxicity. The newer anti-tuberculosis drugs, bedaquiline and delamanid, and repurposed drugs clofazimine and linezolid, show great promise for combination in shorter, less-toxic, and effective regimens. To date, there has been no randomized, internally and concurrently controlled trial of a shorter, all-oral regimen comprising these newer and repurposed drugs sufficiently powered to produce results for pre-XDR TB patients. METHODS: endTB-Q is a phase III, multi-country, randomized, controlled, parallel, open-label clinical trial evaluating the efficacy and safety of a treatment strategy for patients with pre-XDR TB. Study participants are randomized 2:1 to experimental or control arms, respectively. The experimental arm contains bedaquiline, linezolid, clofazimine, and delamanid. The control comprises the contemporaneous WHO standard of care for pre-XDR TB. Experimental arm duration is determined by a composite of smear microscopy and chest radiographic imaging at baseline and re-evaluated at 6 months using sputum culture results: participants with less extensive disease receive 6 months and participants with more extensive disease receive 9 months of treatment. Randomization is stratified by country and by participant extent-of-TB-disease phenotype defined according to screening/baseline characteristics. Study participation lasts up to 104 weeks post randomization. The primary objective is to assess whether the efficacy of experimental regimens at 73 weeks is non-inferior to that of the control. A sample size of 324 participants across 2 arms affords at least 80% power to show the non-inferiority, with a one-sided alpha of 0.025 and a non-inferiority margin of 12%, against the control in both modified intention-to-treat and per-protocol populations. DISCUSSION: This internally controlled study of shortened treatment for pre-XDR TB will provide urgently needed data and evidence for clinical and policy decision-making around the treatment of pre-XDR TB with a four-drug, all-oral, shortened regimen. TRIAL REGISTRATION: ClinicalTrials.Gov NCT03896685. Registered on 1 April 2018; the record was last updated for study protocol version 4.3 on 17 March 2023.

Effect of the level and type of starchy concentrate on tissue lipid metabolism, gene expression and milk fatty acid secretion in Alpine goats receiving a diet rich in sunflower-seed oil.

The potential benefits on human health have prompted an interest in developing nutritional strategies for reducing saturated and increasing specific unsaturated fatty acids (FA) in ruminant milk. The impact of the level and type of starchy concentrate added to diets supplemented with sunflower-seed oil on caprine milk FA composition and on mammary, omental and perirenal adipose, and liver lipid metabolism was examined in fourteen Alpine goats in a replicated 3 × 3 Latin square with 21 d experimental periods. Treatments were a grass hay-based diet with a high level of forage (F) or a high level of concentrate with either maize grain (CM) or flattened wheat (CW) as source of starch and supplemented with 130 g/d sunflower-seed oil. Milk yield was enhanced (P<0·01) and milk fat content was decreased on the CM and CW diets compared with the F diet, resulting in similar milk fat secretion. Both high-concentrate diets increased (P<0·05) milk yield of 10 : 0-16 : 0 and decreased trans-9,11-18 : 1 and cis-9, trans-11-18 : 2. The CW diet decreased (P<0·05) the output of ΣC18 and Σcis-18 : 1 and increased (P<0·05) the output of trans-10-18 : 1 in milk. The expression and/or activity of fourteen proteins involved in the major lipogenic pathways in mammary tissues and of lipogenic genes in adipose and liver tissues were similar among treatments. In conclusion, high starch concentrates alter milk FA yield via mechanisms independent of changes in mammary, liver or adipose tissue lipogenic gene expression. Furthermore, data provided indications that mammary lipogenic responses to starch-rich diets differ between caprine and bovine ruminants.

Refractory hypercapnia: a simplified technique for extracorporeal CO2 removal (ECCO2R) in the presence of therapeutic limitations.

Refractory hypercapnia with severe acidosis appeared in a 67-year-old man who presented with lung fibrosis and a left pneumothorax as delayed complications of bleomycin chemotherapy for advanced grade lymphoma. Due to failure of noninvasive ventilation using a high-flow nasal cannula oxygen system, the patient was mechanically ventilated with two ventilators at different settings, after intubation with a double-lumen tube. As he had a poor haematological prognosis, extracorporeal membranous oxygenation was not considered. To remove some amount of carbon dioxide, we used a simplified method based on a veno-venous hemofiltration circuit coupled to a paediatric oxygenator and an air/oxygen blender. The efficacy on carbon dioxide removal was modest, with a percentage of CO2 total extraction ranging from 10.5 to 20.4%, but the system was immediately available, well tolerated and not very expensive.

Risk factors for conversion to general anesthesia for urgent cesarean among women with labor epidural analgesia: A retrospective case-control study.

OBJECTIVES: General anesthesia for cesarean is associated with an increased risk of maternal morbidity compared with neuraxial anesthesia. Reducing the rate of general anesthesia for urgent cesarean in women with epidural analgesia may improve maternal outcomes. Our objective was to identify the rate and factors associated with the conversion to general anesthesia for urgent cesarean among women with labor epidural analgesia. STUDY DESIGN: We performed a retrospective case-control study including singleton-laboring women with epidural analgesia who delivered after 37 gestational weeks by urgent cesarean (Port Royal Maternity unit, 2012-2017). Cases were all women who required conversion from neuraxial analgesia to general anesthesia. Controls were women just before and after each case included. Factors associated with the conversion to general anesthesia were identified using logistic regression analysis. RESULTS: Among 3,300 laboring women with an epidural analgesia who delivered by urgent cesarean during the study period, 113 (3.4%,) had a conversion to general anesthesia. Factors associated with conversion to general anesthesia were a cervical dilation ≥ 5 cm at the time of epidural placement (aOR 2.55, 95%CI 1.05-6.21), asymmetric sensory blockade (aOR 3.39, 95%CI 1.11-10.36), need for ≥2 rescue top-ups (aOR 2.88, 95%CI 1.29-6.44), and category 1 cesarean (aOR 3.61, 95%CI 1.77-7.33). CONCLUSION: Among women with labor epidural analgesia, suboptimal analgesia significantly increased the risk for conversion to general anesthesia for urgent cesarean. Epidural placement without delay during labor, regular checks of epidural analgesia efficiency, and epidural replacement in case of inadequate epidural analgesia may decrease the rate of avoidable general anesthesia for urgent cesarean.