Anti-SARS-CoV-2 (COVID-19) vaccination efficacy in patients with severe neuromuscular diseases.

INTRODUCTION: Patients with severe neuromuscular disease (sNMD) are considered at high risk of severe COVID-19. Muscle tissue is often replaced by fibroadipose tissue in these diseases whereas the new mRNA-based vaccines are injected intramuscularly. We aimed at evaluating the efficacy of two injections associated with a booster injection of mRNA vaccine in these patients. METHODS: We performed an observational, prospective, single-centre study to investigate the level of anti-S antibodies (Abs) and their neutralization activity at weeks 6 (W6) and 24 (W24) after two injections of mRNA-1273 vaccine and at weeks 12 (BW12) and 29 (BW29) after a booster injection of BNT162b2 vaccine in patients with sNMD. RESULTS: Thirty-three patients with sNMD were included. At W6, 30 patients (90.1%) showed a protective serum level of specific anti-S Abs with a strong neutralization capacity. We observed a decline over time: only 12 patients (36.3%) retained anti-S Abs levels considered as protective at W24. The neutralization activity remained above the cut off in 23 (69.7%). The booster vaccination restored robust neutralization activity for all analysed 22 patients (100%) at BW12, which was maintained without any significant drop at BW29 (16). No severe adverse event was reported in this cohort and none of the 33 patients developed symptomatic COVID-19 over one year. CONCLUSIONS: This study provides evidence that most sNMD patients receiving two injections of COVID-19 mRNA-based vaccines develop a strong humoral response after vaccination. A decline over time was observed but a single booster injection restores a long-term immunity. Moreover, no safety issues were observed.

Influence of Unsaturations on the Organization and Air Reactivity of Triglyceride Monolayers.

The behavior of Langmuir monolayers of saturated and unsaturated C18 triglycerides (TAGs) was studied as two-dimensional (2D) models for paint systems at the air-water interface or transferred onto solid films. The organization of saturated tristearin (C18:0) monolayer was probed thanks to grazing incidence X-ray diffraction: one observes a hexagonal packing of the chains perpendicular to the air-water interface, in contrast to what is described in the literature. Conversely, the mono- and polyunsaturated TAGs (triolein C18:1, trilinolein C18:2, and trilinolenin C18:3) monolayers do not present any organization at the air-water interface but do exhibit peculiar reactivity regarding the air atmosphere. The obtained results derived from the evolution of surface pressure-molecular area isotherms and monolayer compressibility under different atmospheres over time, combined with ultrahigh-vacuum infrared (UHV-FTIR) spectroscopy, showed the adsorption of O2 molecules in the monolayer together with chemical reactions with hydrocarbon chains. The kinetic effect of lead ions, known to be efficient siccative agents in oil paints, was also assessed: the addition of Pb2+ in the subphase induces an increase of the O2 adsorption.

The small quinolone derived compound HT61 enhances the effect of tobramycin against Pseudomonas aeruginosa in vitro and in vivo.

HT61 is a small quinolone-derived compound previously demonstrated to exhibit bactericidal activity against gram-positive bacteria including methicillin-susceptible Staphylococcus aureus (MSSA) and methicillin-resistant Staphylococcus aureus (MRSA). When combined with the classical antibiotics and antiseptics neomycin, gentamicin, mupirocin and chlorhexidine, HT61 demonstrated synergistic bactericidal activity against both MSSA and MRSA infections in vitro. In this study, we investigated the individual antimicrobial activity of HT61 alongside its capability to potentiate the efficacy of tobramycin against both a tobramycin sensitive laboratory reference strain (PAO1) and tobramycin resistant clinical isolates (RP73, NN2) of the gram-negative bacteria Pseudomonas aeruginosa (P. aeruginosa). Using broth microdilution methods, the MICs of HT61 were assessed against all strains, as well as the effect of HT61 in combination with tobramycin using both the chequerboard method and bacterial time-kill assays. A murine model of pulmonary infection was also used to evaluate the combination therapy of tobramycin and HT61 in vivo. In these studies, we demonstrated significant synergism between HT61 and tobramycin against the tobramycin resistant P. aeruginosa strains RP73 and NN2, whilst an additive/intermediate effect was observed for P. aeruginosa strain PA01 which was further confirmed using bacterial time kill analysis. In addition, the enhancement of tobramycin by HT61 was also evident in in vitro assays of biofilm eradication. Finally, in vivo studies revealed analogous effects to those observed in vitro with HT61 significantly reducing bacterial load when administered in combination with tobramycin against each of the three P. aeruginosa strains at the highest tested dose (10 mg/kg).

Long-term adherence to ambulatory initiated continuous positive airway pressure in non-syndromic OSA children.

PURPOSE: In children, the usual indications for continuous positive airway pressure (CPAP) are residual OSA after adenotonsillectomy and/or persistent OSA due to obesity. Data concerning adherence (hours/night) following ambulatory CPAP initiation are scarce. METHODS: An observational cohort of 78 children was followed over 2 years. All exhibited sleep-disordered breathing (SDB) symptoms, were assessed by polysomnography, and prescribed CPAP. CPAP was initiated at hospital for 10 children. RESULTS: OSA children, mean age 10.4 ± 3.2 years, were mostly males (75.6%), with a mean body mass index of 21.2 ± 7.3 kg/m2, and mean apnea+hypopnea index of 12.2 ± 10.6 events/hour. Seventy-two children were still on CPAP at 3 months, 63 at 6 months, 55 at 1 year, and 34 at 2 years. CPAP was discontinued thanks to rehabilitation programs, dento-facial orthopedics, and/or weight loss. Mean CPAP adherence at 1, 3, 6, 12, and 24 months was respectively 6.1 ± 2.8, 6.2 ± 2.6, 6.2 ± 2.8, 6.3 ± 2.8, and 7.0 ± 2.7 h/night. There was a trend towards higher CPAP adherence and younger age, primary versus middle/high school attendance, higher baseline apnea+hypopnea index, and neurocognitive disorders. CONCLUSION: In our population, mean CPAP adherence defined in hours per night was high and did not decrease during the 24-month follow-up. These findings support the feasibility of ambulatory CPAP initiation in non-syndromic OSA. The high CPAP adherence is expected to be associated with improvements in neurocognition, and in metabolic and cardiovascular parameters.

[Malignant transformation of an eccrine spiradenoma]. / Transformation maligne d'un spiradénome eccrine.

INTRODUCTION: Malignant eccrine spiradenoma is a rare and aggressive tumor, developed on the epithelium of eccrine sweat glands. Typically, it occurs after malignant transformation of benign eccrine spiradenoma, but sometimes it happens de novo. OBSERVATION: We report a case of malignant eccrine spiradenoma in a 62-year-old woman. The patient presented a rapid increase in size of a long-standing tumoral lesion of her forearm. There was no secondary lesion on the chest, abdomen or pelvis at the CT-scanner. Cutaneous biopsy of the lesion was performed and showed a carcinoma with no contact with epidermis. On this biopsy, we could not affirm if the tumor was a metastatic process or a primary tumor of the skin. Histologic examination of the surgical removal of the tumor showed an undifferentiated carcinoma with adjacent nodules of eccrine spiradenoma. Immunohistochemical assessment of Ki67 expression showed a weak expression (5%) in the benign spiradenoma nodules and a high rate expression (80%) in the malignant neoplasm. The final diagnosis was an undifferentiated carcinoma arising from preexisting benign spiradenoma. DISCUSSION: Malignant eccrine spiradenoma is not frequent and is rarely described in the international literature that may lead to diagnostic difficulties.

The insulin sensitiser metformin regulates chicken Sertoli and germ cell populations.

Metformin, an insulin sensitiser from the biguanide family of molecules, is used for the treatment of insulin resistance in type 2 diabetes individuals. It increases peripheral glucose uptake and may reduce food intake. Based on the tight link between metabolism and fertility, we investigated the role of metformin on testicular function using in vitro culture of Sertoli cells and seminiferous tubules, complemented by in vivo data obtained following metformin administration to prepubertal chickens. In vitro, metformin treatment reduced Sertoli cell proliferation without inducing apoptosis and morphological changes. The metabolism of Sertoli cells was affected because lactate secretion by Sertoli cells increased approximately twofold and intracellular free ATP was negatively impacted. Two important pathways regulating proliferation and metabolism in Sertoli cells were assayed. Metformin exposure was not associated with an increased phosphorylation of AKT or ERK. There was a 90% reduction in the proportion of proliferating germ cells after a 96-h exposure of seminiferous tubule cultures to metformin. In vivo, 6-week-old chickens treated with metformin for 3 weeks exhibited reduced testicular weight and a 50% decrease in testosterone levels. The expression of a marker of undifferentiated germ cells was unchanged in contrast to the decrease in expression of 'protamine', a marker of differentiated germ cells. In conclusion, these results suggest that metformin affects the testicular energy content and the proliferative ability of Sertoli and germ cells.

Local anaesthetic infiltration at the end of carotid endarterectomy improves post-operative analgesia.

BACKGROUND: Wound infiltration at the end of carotid endarterectomy under general anaesthesia is a simple technique that can be delegated to the surgeon. It was hypothesised that this technique could improve early post-operative analgesia by reducing the need for post-operative opioids. METHODS: Forty patients underwent carotid endarterectomy under general anaesthesia with desflurane and remifentanil supplemented with morphine for post-operative analgesia. In a prospective double-blinded randomised study, patients were allocated pre-operatively to receive either subcutaneous infiltration of both wound edges with 20 ml of 0.75% ropivacaine or infiltration with isotonic saline. The primary outcome was morphine consumption while in the post-anaesthesia care unit (PACU). Pain scores at rest and movement, sedation, and patient satisfaction were the other main outcomes used to assess post-operative analgesia. RESULTS: The median dose of morphine administered in the PACU was 2 mg [0-3] in the ropivacaine vs. 4 mg [3-6] in the placebo group (P = 0.0004, Mann-Whitney's test). Pain at rest and at movement was lower in the ropivacaine group throughout observation in the PACU. No difference was found for both pain and opioid consumption after discharge from the PACU or for patient satisfaction. Sedative events in the early post-operative period were less frequent in the ropivacaine group. CONCLUSIONS: Local anaesthetic wound infiltration performed before closure reduces the need for additional opioids, lowers the immediate post-operative pain and improves alertness. These results argue for the use of local infiltration anaesthesia for carotid endarterectomy.

[A single appointment with a speech therapist can release a patient, even from a long-term aphonic status! Three clinical cases]. / Consulter un(e) phoniatre peut "Libérer" d'une "aphonie rebelle"! Trois cas cliniques évoqués.

Those three clinical cases involved aphonic female patients without any laryngeal disorders for their ENTs. 1) The first one had been out of work since 11/2 year because of her aphonia. She was still suffering from it in spite of a weekly speech therapy session and a monthly psychotherapy appointment. 2) The second patient had been aphonic for 3 weeks. Three different ENTs had renewed her prescription of work stoppage, even with normal laryngeal exam. 3) The third had lost her singing voicing ability during a performance in a national festival of songs and had to cancel the followings events. Even if all of them were waiting for a "miracle pill" they recorded their training session and left this single phoniatrician appointment with their restored voicing ability.

Signal detection of drugs associated with obstructive and central sleep apnoea.

We aim to discover new safety signals of drug-induced sleep apnoea (SA), a global health problem affecting approximately 1 billion people worldwide. We first conducted a series of sequence symmetry analyses (SSA) in a cohort composed from all patients who received a first SA diagnosis or treatment between 2006 and 2018 in the Echantillon Généraliste des Bénéficaires (EGB), a random sample of the French healthcare database. We used two primary outcomes to estimate the sequence ratio (SR) for all drug classes available in France: a sensitive one (diagnosis or treatment of SA) and a specific one (Positive Airway Pressure (PAP) therapy). We then performed disproportionality analyses using the "Bayesian neural network method" on all cases of sleep apnoea (MedDRA high level term) reported up to November 2023 in the World Health Organisation (WHO) pharmacovigilance database. Among the 728,167 individuals, 46,193 had an incident diagnosis or treatment for SA and 17,080 had started an incident treatment by PAP therapy. Fifty-eight drug classes had a significant SR, with 7 considered highly plausible: opium alkaloids and derivatives, benzodiazepine derivatives, other centrally acting agents, other anxiolytics, carbamic acid esters, quinine and derivatives and antivertigo preparations; with consistent signals found for the first 3 drug classes in the disproportionality analysis. In this signal detection study, we found that opioids, benzodiazepines (but not Z-drugs) and myorelaxing agents are associated with the onset or aggravation of SA. Moreover, a new safety signal for antivertigo preparations such as betahistine emerged and needs to be further explored.

Photocatalytic conversion of gaseous nitrogen trichloride into available chlorine--experimental and modeling study.

In water, chlorine reacts with nitrogen-containing compounds to produce disinfection byproducts such as nitrogen trichloride which induces ocular and respiratory irritations in swimming pool workers. A technical solution has been used to reduce NCl3 exposure to acceptable levels, by adding a stripping step to the water recycling loop. The pollutants extracted are currently rejected into the atmosphere without treatment. However, the physical properties of NCl3 could be harnessed to induce its controlled degradation by direct or indirect light. This paper describes the way to transform NCl3 into oxidizing chlorine by photocatalysis under laboratory conditions. Photocatalytic oxidation efficiently degrades gaseous nitrogen trichloride, producing compounds such as HClO. About 60% of NCl3 decomposed was converted into HClO which could be used as a disinfection compound. A kinetic model is proposed for the photocatalytic process based on a convection/diffusion model. The Langmuir-Hinshelwood model was applied to the chemical part of the mechanism. The apparent quantum yield was also estimated to assess the optimal irradiance for NCl3 transformation. The results show that photocatalysis performs much better than photolysis alone for NCl3 removal, i.e. at least 25 times more efficient.

The benefit of phoniatricians and ENT surgeons working together?

These 3 clinical cases relate dysphonia and dystonia with female speaking and singing performers whose medical care was messy and involving several physicians. A close collaboration between phoniatricians and phonosurgeons brought effective solutions to these cases.

Self-assembly of hydrophobin protein rodlets studied with atomic force spectroscopy in dynamic mode.

We have investigated the self-assembling properties of the class I hydrophobin Vmh2 isolated from the fungus Pleurotus ostreatus. Five different hydrophobin self assembled samples including monolayers, bilayers, and rodlets have been prepared by Langmuir technique and studied at the nanoscale. Local wettability and visco-elasticity of the different hydrophobins samples were obtained from atomic force spectroscopy experiments in dynamic mode performed at different, controlled relative humidity (RH) values. It was found that hydrophobins assembled either in rodlets or in bilayer films, display similar hydropathicity and viscoelasticity in contrast to the case of monolayers, whose hydropathicity and viscoelasticity depend on the adopted preparation method (Langmuir-Blodgett or Langmuir-Schaeffer). The comparison with monolayers properties evidences a rearrangement of the bilayers adsorbed onto solid substrates. It is shown that this rearrangement leads to the formation of a stable hydrophobic film, and that the rodlets structure consists in fragments of restructured proteins bilayers. Our results support the hypothesis that the observed variations in the viscoelastic properties could be ascribed to the localization of the large flexible loop, typical of Class I hydrophobins which appears free at the air interface for LB monolayers but not for the other samples. These findings should now serve future developments and applications of hydrophobin films beyond the archetypal monolayer.

Re-emergence of brucellosis in cattle in France and risk for human health.

A case of human brucellosis was diagnosed in France in January 2012. The investigation demonstrated that the case had been contaminated by raw milk cheese from a neighbouring dairy farm. As France has been officially free of bovine brucellosis since 2005, veterinary investigations are being conducted to determine the origin of the infection and avoid its spread among other herds. Hypotheses about the source of this infection are discussed.

Phoniatric management of 3 clinical cases of voice disorders involving the recurrent nerve.

These three cases involve aphonia or dysphonia as a consequence of entrapment of one of the recurrent nerves, in the absence of any prior surgical history. Depending on the particular case, one to two months was needed to normalize phonatory function; One case relapsed after a year. The phoniatric management of these cases involved: New functional and acoustic pattern, recorded by the patient as a form of daily maintenance; Laryngeal and perilaryngeal manual therapy, applied according to the "osteovox" method. Manual therapy and different phonatory habits, in association with alternative medicine can reduce the time to recovery in the case of cold-induced unilateral paresis.

Hepatitis C virus (HCV) protease variability and anti-HCV protease inhibitor resistance in HIV/HCV-coinfected patients.

OBJECTIVES: Data on the natural selection of isolates harbouring mutations within the NS3 protease, conferring resistance to hepatitis C virus (HCV) protease inhibitors (PIs), are limited for HIV/HCV-coinfected patients. The aim of this study was to describe the natural prevalence of mutations conferring resistance to HCV PIs in HIV/HCV-coinfected patients compared with HCV-monoinfected patients. METHODS: The natural prevalences of HCV PI resistance mutations in 120 sequences from HIV/HCV-coinfected patients (58 genotype 1a, 18 genotype 1b and 44 genotype 4) and 501 sequences from HCV-monoinfected patients (476 genotype 1 and 25 genotype 4), retrieved from GenBank as a control group, were compared. RESULTS: Of 76 sequences from HIV/HCV genotype 1-coinfected patients, six (7.9%) showed amino acid substitutions associated with HCV PI resistance (V36L, n=1; V36M, n=2; T54S, n=2; R155K, n=1). In 31 of 476 (6.5%) HCV genotype 1 sequences retrieved from the GenBank database, HCV PI resistance mutations were found. The difference was not statistically significant (P=0.6). All of the sequences from HIV/HCV genotype 4-coinfected patients and those retrieved from the GenBank database had amino acid changes at position 36 (V36L). CONCLUSION: Our study suggests that the natural prevalence of strains resistant to HCV PIs does not differ between HCV-monoinfected and HIV/HCV-coinfected patients. Further studies on larger cohorts are needed to confirm these findings and to evaluate the impact of these mutations in clinical practice.

Circumscribed palmo-plantar hypokeratosis: a disease of desquamation? Immunohistological study of five cases and literature review.

BACKGROUND: Circumscribed palmoplantar hypokeratosis (CPH) is a recently recognized, rarely reported dermatosis that shows characteristic clinicopathological features; however, its pathogenesis remains unknown. OBJECTIVE: The aim of this study was to get further insight into the pathogenesis of CPH. METHODS: An immunohistological study was performed on five cases of CPH to investigate the expression of several epidermal proliferation and differentiation proteins, with emphasis on those involved in corneocyte desquamation [including corneodesmosin, kallikrein 5 and lympho-epithelial Kazal type inhibitor (LEKTI)]. RESULTS: In three of five cases, a decreased expression of LEKTI, corneodesmosin and filaggrin was found, along with an increased expression of kallikrein 5 and keratin 6. The expression of several other antigens (including involucrin, Ki67, p63, CD138/syndecan I, EGF-R) did not present a consistently different pattern as compared with the unaffected epidermis. CONCLUSION: The immunohistopathologic features of CPH suggest that an altered (accelerated) corneocyte desquamation process could be the main pathological mechanism underlying the development of lesions.

Development and evaluation of a Global Acne Severity Scale (GEA Scale) suitable for France and Europe.

BACKGROUND AND OBJECTIVE: Many acne grading methods exist; however, there is no agreed-upon standard. Our objective was to create and validate a reproducible acne assessment scale for rating the severity of juvenile facial acne suitable for use in France and Europe. METHODS: The scale we created described the different types of acne lesions in a manner similar to global assessment scales used in clinical trials. The scale was then validated by seven expert dermatologists in the field of acne [the Global Evaluation Acne (GEA) group] first on 34 photographic cases of Caucasian acne patients and second by clinical examination of 22 acne patients. RESULTS: There was good agreement in Investigators' assessments of acne both on photographs and patients (R = 0.8057; P < 0.0001, and R = 0.8437; P = 0.0015). CONCLUSION: The GEA Scale is a global scale validated both on photographs and acne patients which can be used either in clinical research or by the dermatologist in his office.

When some clinical cases can challenge the phoniatric taxonomy.

It is proposed that taxonomy--the science and practice of classification--can offer significant help in the assessment of vocal dysfunction and in expanding the range of treatment options available to physicians. The first two clinical cases involve instances of "spasmodic dysphonia" which are susceptible to the usual botulinum toxin injections; those two cases were improved by an equally-effective phoniatric orientation that does not subject the patient to repeated injections. Treatment in the second two cases was also redesigned using a phoniatric approach to the patients' problem, after earlier ENT consultations had failed to diagnose malignancy.

Effect of iron chelation on anti-pseudomonal activity of doxycycline.

BACKGROUND: Increasing resistance of microorganisms to antimicrobial agents is a growing concern and there is a lack of novel agents. This has stimulated the exploration of novel strategies for treatment of infection. OBJECTIVE: To investigate synergistic interactions between five tetracyclines and tobramycin with an iron chelator (CP762) against two reference strains and nine clinical isolates of Pseudomonas aeruginosa from cystic fibrosis patients. METHOD: Microdilution assays for minimal inhibitory concentration determination and checkerboard assays were used to assess synergy between antibiotics and CP762. Given the iron-binding capacity of tetracyclines, the binding of iron with doxycycline was investigated using Job's plot methodology. Synergy between the iron-bound form of doxycycline and CP762 was compared with that of unbound doxycycline and CP762. Enhancement of doxycycline anti-biofilm activity was also assessed. RESULTS: There was synergy between CP762 and all tetracyclines, except minocycline, against the reference strains but that against clinical isolates was variable. Synergy was not demonstrated for tobramycin against any of the strains tested. This led to the hypothesis that iron chelation preserves the binding of tetracyclines to the bacterial ribosome. Susceptibility to iron-bound doxycycline was decreased by two- to four-fold and synergistic interactions with the iron chelator were consistently more intense with iron-bound doxycycline than with doxycycline alone. The doxycycline-iron chelator combination also significantly reduced cell viability in established biofilms. CONCLUSION: The data in this study provide evidence that iron chelation enhances the anti-pseudomonal activity of tetracyclines, specifically doxycycline.

A multiparametric approach to assessing residual pain experienced by dairy cows undergoing digestive tract surgery under multimodal analgesia.

This study assessed residual pain responses of dairy cows undergoing fistulation surgery under multimodal analgesia using a multiparametric method combining behavioural and physiological indicators. A longitudinal study was conducted on five dairy cows, each acting as her own control. The surgery consisted of implanting a ruminal and a duodenal cannula in each cow. The multimodal drug protocol consisted of a combination of N-Methyl-D aspartic Acid antagonists, α2-agonists, and local anaesthetic during surgery, and non-steroidal anti-inflammatory drugs (NSAIDs) and opioid treatment postsurgery. Cow responses to surgery were monitored by direct behavioural observation, physiological assay indicators, and milk production from day (D) -6 days before surgery (D-6) to D13 postsurgery. From the data recorded, the variables that contributed most to the discrimination of days pre- and postsurgery were identified using factorial discriminant analysis. Components 1 and 2 of the factorial discriminant analysis explained 68.2% and 17.9%, respectively, of the total variance. Component 1 was mainly explained by haptoglobin (contribution to axis: 0.885), oxidative stress (ratio of oxidized gluthatione to reduced glutathione (GSH/GSSG), -0.746; vitamin E, -0.683; vitamin A, -0.597; malondialdehyde (MDA), 0.416), and behavioural indicators (general attitude, 0.594). On this axis, the higher the score, the higher were the apathy and haptoglobin and MDA concentrations, and the lower were the GSH/GSSG ratio and concentrations of vitamins A and E. This axis opposed cows on D-6 to cows on D3 and D5; cows on D1 and D13 were intermediate. Component 2 was mainly explained by the Hypothalamic-pituitary-adrenal axis (non-esterified fatty acid (NEFA), 0.686; cortisol, 0.669), milk yield (-0.725), oxidative stress (MDA, -0.584; nitric oxide (NO), 0.454), and behavioural indicators of pain (ear position, 0.467; leg postures, 0.431). On this axis, the higher the score, the higher the NEFA, cortisol, and nitric oxide concentrations; the more the ear and leg pain postures; and the lower the milk production and MDA concentrations. This axis opposed cows on D13 to cows on D1. These results suggest that cows may experience some pain only on D1, whereas on subsequent days, the inflammatory response and oxidative stress did not seem to be associated with pain. Our results should be considered for different surgeries to improve analgesia immediately after surgery, and to provide antioxidants along with NSAIDs to promote recovery.