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1.
J Anim Sci ; 2024 Jul 20.
Article in English | MEDLINE | ID: mdl-39031085

ABSTRACT

The traditional approach to formulating pig diets is based only on minimizing cost while meeting nutritional requirements and thus does not consider the environmental impacts associated with producing feed ingredients. To reduce the overall environmental impact of pork production, that of feed ingredients can be considered to formulate environmentally friendly diets. However, their potential effects on pig performance could decrease environmental benefits at the farm gate. The objective of this study was to quantify the effects of such eco-friendly pig diets on nitrogen (N) and energy (E) balances, the components of heat production (HP) and the performance of growing pigs. Digestibility coefficients of dry matter (84.5% vs 88.2%, P < 0.01) and N (80.4% vs 86.3%, P < 0.01) were significantly lower for the eco-friendly diet than the Control-diet (a commercial diet used in France). N excretion in feces was significantly higher for the group of pigs fed the eco-friendly diet than for the group fed the Control-diet (9.8 vs 6.9 g/d, respectively, P = 0.01), while the N retention tended to be lower (27.8 vs 30.3 g/d, respectively; P = 0.06). The metabolizable E:digestible E ratio did not differ between diets, but total HP was significantly lower for the eco-friendly diet group than for the Control-diet group (1340 vs 1388 kJ/kg body weight (BW)0.60/d, respectively, P = 0.03). Using feed ingredients with lower environmental impacts, such as locally produced protein or co-products from wheat processing, is an effective way to decrease environmental impacts of pig production. However, the nutritional composition of these eco-friendly ingredients could be overestimated, in particular the true digestibility of amino acids. This indicates the need to better estimate and consider the true digestibility of eco-friendly diets to decrease environmental impacts of livestock production without decreasing animal performance.

2.
Child Dev ; 2024 Jul 18.
Article in English | MEDLINE | ID: mdl-39022837

ABSTRACT

During infancy, intersensory facilitation declines gradually as unisensory perception develops. However, this trade-off was mainly investigated using audiovisual stimulations. Here, fifty 4- to 12-month-old infants (26 females, predominately White) were tested in 2017-2020 to determine whether the facilitating effect of their mother's body odor on neural face categorization, as previously observed at 4 months, decreases with age. In a baseline odor context, the results revealed a face-selective electroencephalographic response that increases and changes qualitatively between 4 and 12 months, marking improved face categorization. At the same time, the benefit of adding maternal odor fades with age (R2 = .31), indicating an inverse relation with the amplitude of the visual response, and generalizing to olfactory-visual interactions previous evidence from the audiovisual domain.

3.
BMC Public Health ; 24(1): 1762, 2024 Jul 02.
Article in English | MEDLINE | ID: mdl-38956517

ABSTRACT

BACKGROUND: Pregnant women are a vulnerable population to COVID-19 given an increased susceptibility to severe SARS-CoV-2 infection and pregnancy complications. However, few SARS-CoV-2 serological surveys have been performed among this population to assess the extent of the infection in sub-Saharan countries. The objectives of this study were to determine SARS-CoV-2 seroprevalence among Beninese pregnant women, to identify spatial seropositivity clusters and to analyse factors associated with the infection. METHODS: A cross-sectional study including women in their third trimester of pregnancy attending the antenatal care (ANC) clinics at Allada (south Benin) and Natitingou (north Benin) was conducted. Rapid diagnostic tests (RDT) for detection of IgG/IgM against the SARS-CoV-2 spike protein were performed using capillary blood. Seroprevalence of SARS-CoV-2 antibodies and associations between SARS-CoV-2 serostatus and maternal characteristics were analyzed by multivariate logistic regression. Spatial analyses were performed using the spatial scan statistics to identify spatial clusters of SARS-CoV-2 infection. RESULTS: A total of 861 pregnant women were enrolled between May 4 and June 29, 2022. 58/861 (6.7%) participants reported having received COVID-19 vaccine. None of the participants had been diagnosed with COVID-19 during their pregnancy. SARS-CoV-2 antibodies were detected in 607/802 (75.7%; 95% CI 72.56%-78.62%) of unvaccinated participants. Several urban and rural spatial clusters of SARS-CoV-2 cases were identified in Allada and one urban spatial cluster was identified in Natitingou. Unvaccinated participants from Allada with at least one previous morbidity were at a three-times higher risk of presenting SARS-CoV-2 antibodies (OR = 2.89; 95%CI 1.19%-7.00%). CONCLUSION: Three out of four pregnant women had SARS-CoV-2 antibodies, suggesting a high virus circulation among pregnant women in Benin, while COVID-19 vaccination coverage was low. Pregnant women with comorbidities may be at increased risk of SARS-CoV-2 infection. This population should be prioritized for COVID-19 diagnosis and vaccination in order to prevent its deleterious effects. TRIAL REGISTRATION: NCT06170320 (retrospectively registered on December 21, 2023).


Subject(s)
COVID-19 , Pregnancy Complications, Infectious , SARS-CoV-2 , Humans , Female , Pregnancy , COVID-19/epidemiology , COVID-19/diagnosis , Seroepidemiologic Studies , Adult , Cross-Sectional Studies , Pregnancy Complications, Infectious/epidemiology , Benin/epidemiology , SARS-CoV-2/immunology , Young Adult , Antibodies, Viral/blood , Pregnancy Trimester, Third
4.
Eur J Cancer ; 207: 114188, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38954898

ABSTRACT

INTRODUCTION: While available systemic treatments have modest long term efficacy in advanced angiosarcoma, immunotherapy represents an interesting new therapeutic opportunity. To establish its benefit, it is required to conduct a clinical trial assessing its efficacy and toxicity compared to standard treatments. MATERIAL AND METHODS: This is a literature review from PubMed search. RESULTS: Several systemic treatments (chemotherapy and TKI) are currently used in advanced angiosarcoma with ORR ranging from 12.5 to 68 % and PFS from 2 to 7 months. However, few randomized trials, mainly phase II, has been conducted to compare these treatments. While most centers propose doxorubicin containing regimens or paclitaxel in 1st or 2nd line, a high heterogeneity of regimens administered in this setting is observed even across sarcoma specialized centers with no consensual standard treatment. Encouraging signals of immunotherapy activity have been reported in angiosarcoma from several retrospective and phase II studies assessing anti-PD1 either alone or in combination with anti CTLA4 or TKI. Although cutaneous and head and neck location seems to benefit more from immunotherapy, response may be observed in any angiosarcoma subtype. In sarcoma in general and AS in particular, no biomarker has been clearly established to predict the efficacy of immunotherapy: high tumor mutational burden and presence of tertiary lymphoid structures are under assessment. DISCUSSION: Even essential, developing a randomized clinical trial in AS struggles with the heterogeneity of the disease, the lack of consensual standard regimen, the uncertainty on optimal immunotherapy administration and the absence of established predictive biomarkers. CONCLUSION: International collaboration is essential to run randomized trial in advanced AS and asses the efficacy of immune therapy in this rare and heterogeneous disease.


Subject(s)
Hemangiosarcoma , Humans , Hemangiosarcoma/therapy , Hemangiosarcoma/drug therapy , Hemangiosarcoma/pathology , Immunotherapy/methods , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Randomized Controlled Trials as Topic , Clinical Trials as Topic , Immune Checkpoint Inhibitors/therapeutic use
5.
Drug Saf ; 2024 Jun 29.
Article in English | MEDLINE | ID: mdl-38949714

ABSTRACT

BACKGROUND: Seasonal influenza is prevented through annual vaccination, especially in children and older adults. These vaccines are annually updated based on World Health Organization recommendations and require continuous safety monitoring. OBJECTIVE: We assessed the frequency and severity of adverse events within 7 days of administering GSK's inactivated quadrivalent seasonal influenza vaccine (IIV4) in Belgium, Germany, and Spain during the 2022/2023 influenza season. METHODS: In this enhanced safety surveillance study, adults who received GSK's IIV4 and parents/guardians/legally acceptable representatives of vaccinated children (aged 6 months-17 years) were invited to complete adverse drug reaction cards reporting adverse events within 7 days post-vaccination. RESULTS: In total, 1332 participants (53.6% female) received at least one dose of GSK's IIV4, including 43 children who received two doses. Overall, 97.8% of adverse drug reaction cards were completed and returned in the study. All participants in Belgium were adults, while 54.7% and 7.4% in Spain and Germany, respectively, were pediatric participants aged 6 months-17 years. After Dose 1, across all age groups, 49.8% of participants reported at least one adverse event. The most common adverse events (cumulative frequency >5%) following Dose 1 were injection-site pain (37.6%), fatigue (15.0%), headache (13.2%), injection-site swelling (9.3%), myalgia (7.6%), and injection-site erythema (7.4%). Across all countries, adverse events were most common in adults aged 18-65 years (59.7%), followed by those aged 3-17 years (47.0%), >65 years (35.7%), and 6-35 months (23.5%). After Dose 2, 18.6% of participants reported at least one adverse event, with general disorders and administration site conditions again being the most frequent. CONCLUSIONS: Across all age and risk groups for serious disease, no serious adverse events related to GSK's IIV4 were reported within 7 days post-vaccination. This study supports and confirms the acceptable safety profile of GSK's IIV4 across all recommended age groups. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov number: not applicable.

6.
Sci Rep ; 14(1): 15244, 2024 07 02.
Article in English | MEDLINE | ID: mdl-38956407

ABSTRACT

TREK-1 is a mechanosensitive channel activated by polyunsaturated fatty acids (PUFAs). Its activation is supposed to be linked to changes in membrane tension following PUFAs insertion. Here, we compared the effect of 11 fatty acids and ML402 on TREK-1 channel activation using the whole cell and the inside-out configurations of the patch-clamp technique. Firstly, TREK-1 activation by PUFAs is variable and related to the variable constitutive activity of TREK-1. We observed no correlation between TREK-1 activation and acyl chain length or number of double bonds suggesting that the bilayer-couple hypothesis cannot explain by itself the activation of TREK-1 by PUFAs. The membrane fluidity measurement is not modified by PUFAs at 10 µM. The spectral shift analysis in TREK-1-enriched microsomes indicates a KD,TREK1 at 44 µM of C22:6 n-3. PUFAs display the same activation and reversible kinetics than the direct activator ML402 and activate TREK-1 in both whole-cell and inside-out configurations of patch-clamp suggesting that the binding site of PUFAs is accessible from both sides of the membrane, as for ML402. Finally, we proposed a two steps mechanism: first, insertion into the membrane, with no fluidity or curvature modifications at 10 µM, and then interaction with TREK-1 channel to open it.


Subject(s)
Fatty Acids, Unsaturated , Potassium Channels, Tandem Pore Domain , Potassium Channels, Tandem Pore Domain/metabolism , Fatty Acids, Unsaturated/metabolism , Fatty Acids, Unsaturated/pharmacology , Humans , HEK293 Cells , Patch-Clamp Techniques , Membrane Fluidity/drug effects
7.
JSES Int ; 8(4): 873-879, 2024 Jul.
Article in English | MEDLINE | ID: mdl-39035641

ABSTRACT

Background: Peripheral nerve injury is a recognized complication after reverse shoulder arthroplasty (RSA) that has mainly been studied at the level of the brachial plexus and its proximal branches. However, the impact of RSA on distal peripheral nerves and the influence of elbow and wrist position is not known. This cadaveric study aimed to analyze the effect of RSA implantation and upper limb position on tension in the distal median and radial nerves. The hypothesis was that RSA increased distal nerve tension, which could be further affected by elbow and wrist position. Methods: 12 upper limbs in 9 full fresh-frozen cadavers were dissected. Nerve tension was measured in the median nerve at the level of the proximal arm, elbow, and distal forearm, and in the radial nerve at the level of the elbow, using a customized three-point tensiometer. Measurements were carried out before and after RSA implantation, using a semi-inlay implant (Medacta, Castel San Pietro, Switzerland). Two different configurations were tested, using the smallest and largest available implant sizes. Three upper-limb key positions were considered (plexus at risk, plexus relief, and neutral), from which the effect of elbow and wrist position was further tested. Results: RSA implantation significantly increased median and radial nerve tension throughout the upper limb. The distal nerve segments were particularly dependent on elbow and wrist position. The plexus at risk position induced the most tension in all nerve segments, especially with the large implant configuration. On the other hand, the plexus relief position induced the least amount of tension. Flexing the elbow was the most efficient way to decrease nerve tension in all tested nerve segments and key positions. Wrist flexion significantly decreased nerve tension in the median nerve, whereas wrist extension decreased tension in the radial nerve. Conclusion: RSA significantly increases tension in the median and radial nerves and makes them more susceptible to wrist and elbow positioning. The mechanism behind distal peripheral neuropathy after RSA may thus result from increased compression of tensioned nerves against anatomical fulcrums rather than nerve elongation alone. Elbow flexion was the most effective way to decrease nerve tension, while elbow extension should be avoided when implanting the humeral component. Further studies are needed to assess the ulnar nerve.

8.
Lab Chip ; 2024 Jul 12.
Article in English | MEDLINE | ID: mdl-38993177

ABSTRACT

The metastatic cascade includes a blood circulation step for cells detached from the primary tumor. This stage involves significant shear stress as well as large and fast deformation as the cells circulate through the microvasculature. These mechanical stimuli are well reproduced in microfluidic devices. However, the recovery dynamics after deformation is also pivotal to understand how a cell can pass through the multiple capillary constrictions encountered during a single hemodynamic cycle. The microfluidic system developed in this work allows single cell recovery to be studied under flow-free conditions following pressure-actuated cell deformation inside constricted microchannels. We used three breast cancer cell lines - namely MCF-7, SK-BR3 and MDA-MB231 - as cellular models representative of different cancer phenotypes. Changing the size of the constriction allows exploration of moderate to strong deformation regimes, the latter being associated with the formation of plasma membrane blebs. In the regime of moderate deformation, all cell types display a fast elastic recovery behavior followed by a slower viscoelastic regime, well described by a double exponential decay. Among the three cell types, cells of the mesenchymal phenotype, i.e. the MDA-MB231 cells, are softer and the most fluid-like, in agreement with previous studies. Our main finding here is that the fast elastic recovery regime revealed by our novel microfluidic system is under the control of cell contractility ensured by the integrity of the cell cortex. Our results suggest that the cell cortex plays a major role in the transit of circulating tumor cells by allowing their fast morphological recovery after deformation in blood capillaries.

9.
Am J Clin Oncol ; 2024 Jul 16.
Article in English | MEDLINE | ID: mdl-39011937

ABSTRACT

OBJECTIVES: Recent DESTINY-Breast trials have demonstrated trastuzumab deruxtecan's effectiveness in HER2-positive and HER2-low metastatic breast cancer. However, safety concerns remain regarding its combination with radiation therapy (RT). The purpose of this work is to assess the toxicity profile of combining trastuzumab deruxtecan and RT in patients with HER2-positive and HER2-low metastatic breast cancer to address these concerns. METHODS: We conducted a retrospective study which included patients treated at Institut Curie Paris between November 2020 and January 2024. Patients with HER2-positive and HER2-low metastatic breast cancer who received concurrent trastuzumab deruxtecan and RT were identified. Data on patient demographics, treatment regimens, radiation doses, toxicity profiles, and treatment discontinuations were collected. Follow-up was conducted from the last day of radiotherapy until death or the last examination and toxicities were graded using the CTCAE V5.0. RESULTS: The studied population includes all 33 patients with HER2-positive and HER2-low metastatic breast cancer who underwent concurrent treatment with trastuzumab deruxtecan and radiotherapy. The median follow-up was 11 months. The most common acute grade 1 toxicity was nausea. Grade 2 toxicities affected 21.2% of patients, including asthenia, mucositis, cardiac decompensation, and diarrhea. Trastuzumab deruxtecan discontinuation occurred in 5 patients due to systemic treatment-related toxicities, including nausea, thrombocytopenia, neutropenia, and cardiac decompensation. There were 21.2% reported with late toxicities, with nausea being the most prevalent. CONCLUSIONS: Our series of patients who received concurrent treatment of radiotherapy and trastuzumab deruxtecan are showing acceptable toxicity. Larger prospective studies are needed to evaluate the toxicity and efficacy of this combination.

10.
Eur J Cancer ; 208: 114228, 2024 Jul 15.
Article in English | MEDLINE | ID: mdl-39018632

ABSTRACT

RATIONALE: We report a phase II trial (OSAD93) testing CDDP with ifosfamide (IFO), without doxorubicin in neoadjuvant phase, in adult osteosarcoma with a 25 years follow-up. PATIENTS AND METHODS: This is a multicentric phase II study of neoadjuvant chemotherapy with IFO and CDDP in localized high-grade osteosarcoma of patients. Patients received 4 pre-operative courses of IFO 9 g/m2 and CDDP 100 mg/m2 on day 4 (SHOC regimen), followed by local treatment. Doxorubicin was added post-operatively (HOCA regimen) in patients with > 10 % residual tumor cells. A Good Histological Response (GHR), ie ≤ 10 % residual tumor cells in > 30 % of patients, was the primary objective. Disease-free survival (DFS), overall survival (OS) and toxicity were secondary objectives. RESULTS: From Jan 1994 to Jun 1998, 60 patients were included. Median age was 27 (range: 16-63). Primary tumor sites were limbs (76 %), trunk, head or neck (24 %). After neoadjuvant SHOC, grade 3-4 and febrile neutropenia, thrombopenia, and re-hospitalization occurred in 58 %, 17 %, 17 % and 22 % of SHOC courses and in 76 %, 28 %, 47 %, 47 % of HOCA courses, respectively. GHR was obtained in 16/60 (27.5 %) patients. With a median follow-up of 322 months, the DFS and OS were 51.8 % and 64.4 % at 5 years. At 10 years, DFS and OS were 49.9 % and 64.4 %. At 25 years, DFS and OS were 47.8 % and 55.9 %. No long-term cardiac toxicity was observed. Three patients developed a second malignancy (one fatal) after 300 months. CONCLUSION: Though the primary endpoint of OSAD93 was not met, this pre-operative doxorubicin-free regimen led to excellent long-term survival with limited toxicity in localized osteosarcoma.

11.
EBioMedicine ; 106: 105220, 2024 Jul 16.
Article in English | MEDLINE | ID: mdl-39018755

ABSTRACT

BACKGROUND: Anthracycline-based neoadjuvant chemotherapy (NAC) may modify tumour immune infiltrate. This study characterized immune infiltrate spatial distribution after NAC in primary high-risk soft tissue sarcomas (STS) and investigate association with prognosis. METHODS: The ISG-STS 1001 trial randomized STS patients to anthracycline plus ifosfamide (AI) or a histology-tailored (HT) NAC. Four areas of tumour specimens were sampled: the area showing the highest lymphocyte infiltrate (HI) at H&E; the area with lack of post-treatment changes (highest grade, HG); the area with post-treatment changes (lowest grade, LG); and the tumour edge (TE). CD3, CD8, PD-1, CD20, FOXP3, and CD163 were analyzed at immunohistochemistry and digital pathology. A machine learning method was used to generate sarcoma immune index scores (SIS) that predict patient disease-free and overall survival (DFS and OS). FINDINGS: Tumour infiltrating lymphocytes and PD-1+ cells together with CD163+ cells were more represented in STS histologies with complex compared to simple karyotype, while CD20+ B-cells were detected in both these histology groups. PD-1+ cells exerted a negative prognostic value irrespectively of their spatial distribution. Enrichment in CD20+ B-cells at HI and TE areas was associated with better patient outcomes. We generated a prognostic SIS for each tumour area, having the HI-SIS the best performance. Such prognostic value was driven by treatment with AI. INTERPRETATION: The different spatial distribution of immune populations and their different association with prognosis support NAC as a modifier of tumour immune infiltrate in STS. FUNDING: Pharmamar; Italian Ministry of Health [RF-2019-12370923; GR-2016-02362609]; 5 × 1000 Funds-2016, Italian Ministry of Health; AIRC Grant [ID#28546].

12.
Int J Pediatr Otorhinolaryngol ; 183: 112032, 2024 Jul 14.
Article in English | MEDLINE | ID: mdl-39018964

ABSTRACT

OBJECTIVE: Peritonsillar abscess (PTA) is a common pediatric infection requiring drainage. Conscious Sedation (CS) can facilitate drainage in uncooperative children. However, it carries risks, especially if the airway is compromised. Moreover, evidence on its safety and efficacy is limited. This study examined the safety, pain reduction, and anxiety management of hospitalized pediatric patients treated for PTA under CS. MATERIALS AND METHODS: We performed a prospective observational case series of 118 children aged 2-15 years with 155 PTA episodes, managed from 2016 to 2023. Conscious sedation was used in 42 episodes. Outcomes were compared among CS and non-CS (local anesthesia only). Complications assessed safety. Efficacy was evaluated by the amount of pus, hospitalization parameters, pain scores, and recurrence. RESULTS: No significant differences were found regarding the demographic and presentation parameters except for younger age among the CS group (9 vs 11 years p = 0.001). One minor oxygen desaturation (2 %) event occurred with CS. Abscess drainage amount was greater with CS than non-CS, 4.9±4 mL vs. 3.2±2 mL, respectively (p = 0.03). Hospitalization stays were similar among groups. Maximum pain scores were lower with CS than non-CS, 1.4 ± 2 vs 4.2 ± 3 (p < 0.001); similarly, IV pain medication was used less frequently, 0.9 ± 1 vs. 1.6 ± 3 (p = 0.045), and the need for re-aspiration was less common 14 % vs. 28 % (p = 0.04), with CS than non-CS, respectively. The three-month recurrence rate was numerically lower with CS (5 % vs. 14 % non-CS). CONCLUSIONS: Conscious sedation facilitates PTA drainage with excellent safety and improved efficacy compared to local anesthesia in children. Pain scores are reduced both during drainage and hospitalization. Our prospective data add to the limited evidence supporting CS as a viable option for abscess drainage in uncooperative pediatric patients. Further study is warranted to confirm potential long-term reductions in recurrence.

13.
Osteoporos Int ; 2024 Jul 23.
Article in English | MEDLINE | ID: mdl-39042292

ABSTRACT

This 78-week (18-month) study conducted in 479 postmenopausal women with osteoporosis evaluated the efficacy, pharmacodynamics, pharmacokinetics, safety, and immunogenicity of candidate biosimilar CT-P41 relative to US reference denosumab. CT-P41 had equivalent efficacy and pharmacodynamics to US-denosumab, with similar pharmacokinetics and comparable safety and immunogenicity profiles. PURPOSE: To demonstrate equivalence of candidate biosimilar CT-P41 and US reference denosumab (US-denosumab) in postmenopausal women with osteoporosis. METHODS: This 78-week (18-month), double-blind, randomized, active-controlled Phase 3 study (NCT04757376) comprised two treatment periods (TPs). In TPI, patients (N = 479) were randomized 1:1 to 60 mg subcutaneous CT-P41 or US-denosumab. At Week 52, those who had received CT-P41 in TPI continued to do so. Those who had received US-denosumab were randomized (1:1) to continue treatment or switch to CT-P41 in TPII. The primary efficacy endpoint was percent change from baseline in lumbar spine bone mineral density at Week 52. Efficacy equivalence was concluded if associated 95% confidence intervals (CI) for least squares (LS) mean group differences fell within ± 1.503%. The primary pharmacodynamic (PD) endpoint was area under the effect curve for serum carboxy-terminal cross-linking telopeptide of type I collagen through the first 26 weeks, with an equivalence margin of 80-125% (for 95% CIs associated with geometric LS mean ratios). RESULTS: Equivalence was demonstrated for CT-P41 and US-denosumab with respect to primary efficacy (LS mean difference [95% CI]: - 0.139 [- 0.826, 0.548] in the full analysis set and - 0.280 [- 0.973, 0.414] in the per-protocol set) and PD (geometric LS mean ratio [95% CI]: 94.94 [90.75, 99.32]) endpoints. Secondary efficacy, PD, pharmacokinetics, and safety results were comparable among all groups up to Week 78, including after transitioning to CT-P41 from US-denosumab. CONCLUSIONS: CT-P41 was equivalent to US-denosumab in women with postmenopausal osteoporosis, with respect to primary efficacy and PD endpoints.

14.
PLoS Biol ; 22(7): e3002724, 2024 Jul 25.
Article in English | MEDLINE | ID: mdl-39052688

ABSTRACT

Alternative transcription start site (TSS) usage regulation has been identified as a major means of gene expression regulation in metazoans. However, in fungi, its impact remains elusive as its study has thus far been restricted to model yeasts. Here, we first re-analyzed TSS-seq data to define genuine TSS clusters in 2 species of pathogenic Cryptococcus. We identified 2 types of TSS clusters associated with specific DNA sequence motifs. Our analysis also revealed that alternative TSS usage regulation in response to environmental cues is widespread in Cryptococcus, altering gene expression and protein targeting. Importantly, we performed a forward genetic screen to identify a unique transcription factor (TF) named Tur1, which regulates alternative TSS (altTSS) usage genome-wide when cells switch from exponential phase to stationary phase. ChiP-Seq and DamID-Seq analyses suggest that at some loci, the role of Tur1 might be direct. Tur1 has been previously shown to be essential for virulence in C. neoformans. We demonstrated here that a tur1Δ mutant strain is more sensitive to superoxide stress and phagocytosed more efficiently by macrophages than the wild-type (WT) strain.

15.
J Orthop Traumatol ; 25(1): 37, 2024 Jul 24.
Article in English | MEDLINE | ID: mdl-39048851

ABSTRACT

PURPOSE: The aim of this study was to quantify the prophylactic effect of high-dose gentamicin and clindamycin antibiotic-loaded bone cement (ALBC) during revision total hip (rTHA) or knee (rTKA) arthroplasty for aseptic reasons. The hypothesis was that the raw surgical site infection (SSI) rate is lower when this particular cement is used in comparison with cement loaded with standard-dose gentamicin during rTHA or rTKA for aseptic reasons. METHODS: This retrospective study included 290 consecutive patients undergoing aseptic rTHA or rTKA. Two consecutive cohorts were defined: the first (control group) involved 145 patients where ALBC with gentamicin only was used; the second (study group) involved 145 patients where ALBC with high-dose gentamicin and clindamycin was used. The primary endpoint was the raw SSI rate after 24 months. RESULTS: The raw SSI rate was 8/145 (6%) in the control group and 13/145 (9%) in the study group (odds ratio 0.62, p = 0.26). There was a significant impact of the presence of any risk factor on the SSI rate (15/100 versus 6/169, odds ratio = 4.25, p = 0.002), but no significant impact of any individual risk factor. No complication or side effect related to ALBC was observed in either group. CONCLUSION: These results do not support the routine use of gentamicin and clindamycin ALBC for fixation of revision implants after rTHA and rTKA for aseptic reasons.


Subject(s)
Anti-Bacterial Agents , Arthroplasty, Replacement, Hip , Arthroplasty, Replacement, Knee , Bone Cements , Clindamycin , Gentamicins , Prosthesis-Related Infections , Reoperation , Surgical Wound Infection , Humans , Gentamicins/administration & dosage , Clindamycin/administration & dosage , Arthroplasty, Replacement, Hip/adverse effects , Arthroplasty, Replacement, Hip/methods , Retrospective Studies , Male , Female , Arthroplasty, Replacement, Knee/adverse effects , Aged , Anti-Bacterial Agents/administration & dosage , Middle Aged , Surgical Wound Infection/prevention & control , Prosthesis-Related Infections/prevention & control , Prosthesis-Related Infections/etiology , Risk Factors
19.
Microbiol Mol Biol Rev ; : e0020522, 2024 Jul 03.
Article in English | MEDLINE | ID: mdl-38958456

ABSTRACT

SUMMARYUnderstanding how commonly used chemical microbicides affect pathogenic microorganisms is important for formulation of microbicides. This review focuses on the mechanism(s) of action of chemical microbicides commonly used in infection prevention and control. Contrary to the typical site-specific mode of action of antibiotics, microbicides often act via multiple targets, causing rapid and irreversible damage to microbes. In the case of viruses, the envelope or protein capsid is usually the primary structural target, resulting in loss of envelope integrity or denaturation of proteins in the capsid, causing loss of the receptor-binding domain for host cell receptors, and/or breakdown of other viral proteins or nucleic acids. However, for certain virucidal microbicides, the nucleic acid may be a significant site of action. The region of primary damage to the protein or nucleic acid is site-specific and may vary with the virus type. Due to their greater complexity and metabolism, bacteria and fungi offer more targets. The rapid and irreversible damage to microbes may result from solubilization of lipid components and denaturation of enzymes involved in the transport of nutrients. Formulation of microbicidal actives that attack multiple sites on microbes, or control of the pH, addition of preservatives or potentiators, and so on, can increase the spectrum of action against pathogens and reduce both the concentrations and times needed to achieve microbicidal activity against the target pathogens.

20.
Osteoporos Int ; 2024 Jul 03.
Article in English | MEDLINE | ID: mdl-38960982

ABSTRACT

Task Force on 'Clinical Algorithms for Fracture Risk' commissioned by the American Society for Bone and Mineral Research (ASBMR) Professional Practice Committee has recommended that FRAX® models in the US do not include adjustment for race and ethnicity. This position paper finds that an agnostic model would unfairly discriminate against the Black, Asian and Hispanic communities and recommends the retention of ethnic and race-specific FRAX models for the US, preferably with updated data on fracture and death hazards. In contrast, the use of intervention thresholds based on a fixed bone mineral density unfairly discriminates against the Black, Asian and Hispanic communities in the US. This position of the Working Group on Epidemiology and Quality of Life of the International Osteoporosis Foundation (IOF) is endorsed both by the IOF and the European Society for Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases (ESCEO).

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