Cannabidivarin and cannabigerol induce unfolded protein response and angiogenesis dysregulation in placental trophoblast HTR-8/SVneo cells.

Cannabidivarin (CBDV) and cannabigerol (CBG) are minor phytocannabinoids from Cannabis sativa, whose health benefits have been reported. However, studies about the impact of these cannabinoids on fundamental cellular processes in placentation are scarce. Placental development involves physiological endoplasmic reticulum (ER) stress, however when exacerbated it can lead to altered angiogenesis and pregnancy disorders, such as intrauterine growth restriction and preeclampsia. In this work, the effects of CBDV and CBG (1-10 µM) on placental extravillous trophoblasts were studied, using the in vitro model HTR-8/SVneo cells. Both cannabinoids induced anti-proliferative effects and reactive oxygen/nitrogen species generation, which was dependent on transient receptor potential vanilloid 1 (TRPV1) activation. Moreover, CBDV and CBG significantly upregulated, in a TRPV-1 dependent manner, the gene expression of HSPA5/Glucose-regulated protein 78 (GRP78/BiP), a critical chaperone involved in ER stress and unfolded protein response (UPR) activation. Nevertheless, the UPR pathways were differentially activated. Both cannabinoids were able to recruit the IRE branch, while only CBDV enhanced the expression of downstream effectors of the PERK pathway, namely p-eIF2α, ATF4 and CHOP. It also augmented the activity of the apoptotic initiator caspases-8 and -9, though the effector caspases-3/-7 were not activated. TRB3 expression was increased by CBDV, which may hinder apoptosis termination. Moreover, both compounds upregulated the mRNA levels of the angiogenic factors VEGFA, PGF and sFLT1, and disrupted the endothelial-like behavior of HTR-8/SVneo cells, by reducing tube formation. Thus, CBDV and CBG treatment interferes with EVTs functions and may have a negative impact in placentation and in pregnancy outcome.

Treatment of atopic dermatitis with upadacitinib: adcare single center experience.

Introduction: The role of upadacitinib in the management of moderate to severe atopic dermatitis seems promising, but more data on its efficacy and safety are needed. This study endeavors to assess the practical impact and safety of upadacitinib in patients with moderate to severe atopic dermatitis. The study aims to evaluate the efficacy and safety of upadacitinib in the treatment of moderate to severe atopic dermatitis, focusing on analyzing patient responses to the treatment. Methods: In this study, adult patients diagnosed with moderate to severe atopic dermatitis received upadacitinib at daily doses of 15 mg or 30 mg, as prescribed by their attending physicians. The therapeutic efficacy of upadacitinib was meticulously assessed using established clinical metrics. Simultaneously, a comprehensive safety assessment was conducted through monthly monitoring, including the evaluation of potential effects of upadacitinib intake on hepatic function, lipid profile, and hematopoiesis using the pertinent laboratory tests. Results: Sixteen participants were enrolled in the study. At 1month follow-up, there was a significant reduction in the mean Eczema Area and Severity Index (EASI) score to 18.8 points, which further increased to 24 points at the 4-month mark. Additionally, 9 participants (56%) demonstrated an EASI-50 response after 1 month of treatment, with this response increasing to 9 participants (90%) after 4 months. Furthermore, enhanced therapeutic responses were observed at 4 months, with 6 patients (38%) achieving an EASI-75 response at 1month and 8 patients (80%) achieving this milestone at the 4-month follow-up. This study highlights the potential of upadacitinib as an effective treatment option for moderate to severe atopic dermatitis. While it demonstrates improved symptom management, close monitoring for potential adverse events, particularly infections and the known risks of Janus kinase inhibitors, is essential. Further research is essential to determine the long-term safety and efficacy of upadacitinib.

The effect of exposure to RF-EMF from the laboratory simulator of 5G NR base station on physiological parameters and cognitive abilities of male wistar rats of different ages.

In this article, the impact of radiofrequency electromagnetic field (RF-EMF) exposure from a simulated base station for the 5G New Radio (5G NR) telecommunication on rats was studied. The base station affects all age groups of the population, thus, for the first time, the experiment was conducted on male Wistar rats of three different ages (juvenile, adult, and presenile). The base station exposure parameters were chosen according to ICNIRP recommendations for limiting the exposure to radiofrequency electromagnetic field: frequency 2.4 GHz with an average specific absorption rate of 0.0076 W/kg and 0.0059 W/kg over the whole body of experimental animals. Throughout the experiment, body weight was examined weekly, and the dynamics of body weight gain was monitored. Rectal and skin surface temperature on the right hind limb was monitored weekly. Testing in the Morris water maze was performed during the last, Week 5, of RF-EMF exposure. After euthanasia, organ weights were determined in experimental and control animals. None of the investigated parameters did show any statistically significant differences between exposed and control animals of the same age. The data obtained can be used to assess the possible consequences of chronic exposure to RF-EMF from 5G NR base stations.

Field Testing the Family Behavior Support Mobile Application (FBSApp) During a Global Pandemic.

We developed and tested an evidence-based mobile application designed to support families in using functional assessment-based intervention strategies with their young children with disabilities and challenging behaviors in home settings. Five families participated in the study. We utilized a multiple-probe across participants design to examine the effects of the FBSApp on parents' use of intervention strategies and childrens' use of challenging behaviors and replacement behaviors. We adapted our procedures to include individualized coaching to provide meaningful and effective support after the onset of the COVID-19 pandemic. A functional relation was not identified between access to FBSApp and caregiver use of strategies; however, the addition of coaching did lead to increased strategy use for two of four caregivers. A functional relation was identified between the use of the FBSApp plus coaching and CB. Families reported the app and coaching procedures favorably. We found that responsive, family-centered research CAN be conducted in spite of significant history events, and that mobile apps and virtual meeting platforms can be an accessible and efficient method for supporting families. The use of single case design allowed for flexible, yet methodologically sound procedures. More work is needed examining effective and efficient virtual supports for families.

Measuring local genetic variation in permethrin-resistant head lice (Phthiraptera: Pediculidae) from Buenos Aires, Argentina.

The cosmopolitan ectoparasite human head louse, Pediculus humanus capitis (De Geer)(Phthiraptera:Pediculidae), affects mostly school-aged children, with infestations reported every year mainly due to louse resistance to pyrethroids. One of the main resistance mechanisms of pyrethroids is the target site insensitivity (kdr), which is caused by single-nucleotide point mutations (SNPs) located in the voltage-sensitive sodium channel gene. In this study, we analyzed individual head lice toxicologically via the description of their susceptibility profile to permethrin and genetically through the genotypification of their kdr alleles as well as nuclear microsatellite loci. Lice were collected from 4 schools in the city of Buenos Aires, Argentina. The resistance ratios varied from 33.3% to 71.4%, with a frequency of the T917I kdr mutation of 87.31% and with 83.6% of the head lice being homozygous resistant to pyrethroids. Microsatellite data indicated that all the louse school populations had genotype proportions that deviated from Hardy-Weinberg expectations, with FIS > 0 reflecting a deficit of heterozygotes. Bottleneck analysis suggested that all louse school populations underwent a recent reduction in population sizes, while 3 of the 4 schools had gene flow values around 1, indicating ongoing gene flow among those schools. Our study suggests that school louse populations in the city of Buenos Aires may form a metapopulation, where each school represents a small population that undergoes extinction and recolonization processes under strong permethrin selection. This is the first multilevel analysis integrating toxicological, kdr-genotyping, and microsatellite data in human louse populations.

Association between EEG metrics and continuous cerebrovascular autoregulation assessment: a scoping review.

OBJECTIVE: Cerebrovascular autoregulation is defined as the capacity of cerebral blood vessels to maintain stable cerebral blood flow despite changing blood pressure. It is assessed using the pressure reactivity index (the correlation coefficient between mean arterial blood pressure and intracranial pressure). The objective of this scoping review is to describe the existing evidence concerning the association of EEG and cerebrovascular autoregulation in order to identify key concepts and detect gaps in the current knowledge. METHODS: Embase, MEDLINE, SCOPUS, and Web of Science were searched considering articles between their inception up to September 2023. Inclusion criteria were human (paediatric and adult) and animal studies describing correlations between continuous EEG and cerebrovascular autoregulation assessments. RESULTS: Ten studies describing 481 human subjects (67% adult, 59% critically ill) were identified. Seven studies assessed qualitative (e.g. seizures, epileptiform potentials) and five evaluated quantitative (e.g. bispectral index, alpha-delta ratio) EEG metrics. Cerebrovascular autoregulation was evaluated based on intracranial pressure, transcranial Doppler, or near infrared spectroscopy. Specific combinations of cerebrovascular autoregulation and EEG metrics were evaluated by a maximum of two studies. Seizures, highly malignant patterns or burst suppression, alpha peak frequency, and bispectral index were associated with cerebrovascular autoregulation. The other metrics showed either no or inconsistent associations. CONCLUSION: There is a paucity of studies evaluating the link between EEG and cerebrovascular autoregulation. The studies identified included a variety of EEG and cerebrovascular autoregulation acquisition methods, age groups, and diseases allowing for few overarching conclusions. However, the preliminary evidence for the presence of an association between EEG metrics and cerebrovascular autoregulation prompts further in-depth investigations.

Prophylactic tranexamic acid in Cesarean delivery: an updated meta-analysis with a trial sequential analysis.

PURPOSE: Postpartum hemorrhage (PPH) is a leading cause of maternal mortality worldwide. Although several studies on the prophylactic use of tranexamic acid (TXA) in parturients undergoing Cesarean delivery have been published, conflicting results raise questions regarding its use. Thus, we aimed to investigate the safety and efficacy of PPH prophylaxis with TXA. SOURCE: We searched PubMed®, Embase, Cochrane Central, and ClinicalTrials.gov for randomized controlled trials (RCTs) comparing prophylactic TXA with placebo or no treatment in parturients undergoing Cesarean delivery. Our main outcomes were PPH, any blood transfusion, need for additional uterotonics, and adverse events. We performed a trial sequential analysis (TSA) of all outcomes to investigate the reliability and conclusiveness of findings. PRINCIPAL FINDINGS: We included 38 RCTs including 22,940 parturients, 11,535 (50%) of whom were randomized to receive prophylactic TXA. Patients treated with TXA had significantly fewer cases of PPH (risk ratio [RR], 0.51; 95% confidence interval [CI], 0.38 to 0.69; P < 0.001); less blood transfusion (RR, 0.43; 95% CI, 0.30 to 0.61; P < 0.001), and less use of additional uterotonics (RR, 0.52; 95% CI, 0.40 to 0.68; P < 0.001). No significant differences were found between the groups in terms of adverse effects and thromboembolic events. CONCLUSION: Prophylactic TXA administration for parturients undergoing Cesarean delivery significantly reduced blood loss, without increasing adverse events, supporting its use as a safe and effective strategy for reducing PPH in this population. STUDY REGISTRATION: PROSPERO (CRD42023422188); first submitted 27 April 2023.

RéSUMé: OBJECTIF: L'hémorragie du post-partum (HPP) est l'une des principales causes de mortalité maternelle dans le monde. Bien que plusieurs études sur l'utilisation prophylactique d'acide tranexamique (TXA) chez les personnes parturientes ayant accouché par césarienne aient été publiées, des résultats contradictoires soulèvent des questions quant à son utilisation. Ainsi, nous avons cherché à étudier l'innocuité et l'efficacité de la prophylaxie à base de TXA pour l'HPP. SOURCES: Nous avons fait une recherche sur PubMed®, Embase, Cochrane Central et ClinicalTrials.gov pour en tirer les études randomisées contrôlées (ERC) comparant le TXA prophylactique à un placebo ou à l'absence de traitement chez les personnes parturientes accouchant par césarienne. Nos principaux critères d'évaluation étaient l'HPP, toute transfusion sanguine, la nécessité d'un utérotonique supplémentaire et les événements indésirables. Nous avons effectué une analyse séquentielle des études pour tous les résultats afin d'examiner la fiabilité et le caractère concluant des conclusions. CONSTATATIONS PRINCIPALES: Nous avons inclus 38 ERC comprenant 22 940 personnes parturientes, dont 11 535 (50 %) ont été randomisées pour recevoir du TXA prophylactique. La patientèle traitée par TXA présentait significativement moins de cas d'HPP (risque relatif [RR], 0,51; intervalle de confiance [IC] à 95 %, 0,38 à 0,69; P < 0,001); moins de transfusion sanguine (RR, 0,43; IC 95 %, 0,30 à 0,61; P < 0,001) et moins d'utilisation d'utérotoniques supplémentaires (RR, 0,52; IC 95 %, 0,40 à 0,68; P < 0,001). Aucune différence significative n'a été constatée entre les groupes en termes d'effets indésirables et d'événements thromboemboliques. CONCLUSION: L'administration prophylactique de TXA pour les personnes parturientes accouchant par césarienne a considérablement réduit les pertes de sang sans augmenter les événements indésirables, ce qui soutient son utilisation comme stratégie sécuritaire et efficace pour réduire l'HPP dans cette population. ENREGISTREMENT DE L'éTUDE: PROSPERO (CRD42023422188); première soumission le 27 avril 2023.

Crystal structure and characterization of a new one-dimensional copper(II) coordination polymer containing a 4-amino-benzoic acid ligand.

A CuII coordination polymer, catena-poly[[[aqua-copper(II)]-bis-(µ-4-amino-benz-o-ato)-κ2 N:O;κ2 O:N] monohydrate], {[Cu(pABA)2(H2O)]·H2O}n (pABA = p-amino-benzoate, C7H4NO2 -), was synthesized and characterized. It exhibits a one-dimensional chain structure extended into a three-dimensional supra-molecular assembly through hydrogen bonds and π-π inter-actions. While the twinned crystal shows a metrically ortho-rhom-bic lattice and an apparent space group Pbcm, the true symmetry is monoclinic (space group P2/c), with disordered Cu atoms and mixed roles of water mol-ecules (aqua ligand/crystallization water). The luminescence spectrum of the complex shows an emission at 345 nm, cf. 349 nm for pABAH.

Systematic computer-aided disulfide design as a general strategy to stabilize prefusion class I fusion proteins.

Numerous enveloped viruses, such as coronaviruses, influenza, and respiratory syncytial virus (RSV), utilize class I fusion proteins for cell entry. During this process, the proteins transition from a prefusion to a postfusion state, undergoing substantial and irreversible conformational changes. The prefusion conformation has repeatedly shown significant potential in vaccine development. However, the instability of this state poses challenges for its practical application in vaccines. While non-native disulfides have been effective in maintaining the prefusion structure, identifying stabilizing disulfide bonds remains an intricated task. Here, we present a general computational approach to systematically identify prefusion-stabilizing disulfides. Our method assesses the geometric constraints of disulfide bonds and introduces a ranking system to estimate their potential in stabilizing the prefusion conformation. We found, for the RSV F protein, that disulfides restricting the initial stages of the conformational switch can offer higher stability to the prefusion state than those preventing unfolding at a later stage. The implementation of our algorithm on the RSV F protein led to the discovery of prefusion-stabilizing disulfides, providing evidence that supports our hypothesis. Furthermore, the evaluation of our top design as a vaccine candidate in a cotton rat model demonstrated robust protection against RSV infection, highlighting the potential of our approach for vaccine development.

Current recommendations for procedure selection in class I and II obesity developed by an expert modified Delphi consensus.

Metabolic and bariatric surgery (MBS) is widely considered the most effective option for treating obesity, a chronic, relapsing, and progressive disease. Recently, the American Society of Metabolic and Bariatric Surgery (ASMBS) and the International Federation for the Surgery of Obesity and Metabolic Disorders (IFSO) issued new guidelines on the indications for MBS, which have superseded the previous 1991 National Institutes of Health guidelines. The aim of this study is to establish the first set of consensus guidelines for selecting procedures in Class I and II obesity, using an Expert Modified Delphi Method. In this study, 78 experienced bariatric surgeons from 32 countries participated in a two-round Modified Delphi consensus voting process. The threshold for consensus was set at an agreement or disagreement of ≥ 70.0% among the experts. The experts reached a consensus on 54 statements. The committee of experts reached a consensus that MBS is a cost-effective treatment option for Class II obesity and for patients with Class I obesity who have not achieved significant weight loss through non-surgical methods. MBS was also considered suitable for patients with Type 2 diabetes mellitus (T2DM) and a body mass index (BMI) of 30 kg/m2 or higher. The committee identified intra-gastric balloon (IGB) as a treatment option for patients with class I obesity and endoscopic sleeve gastroplasty (ESG) as an option for patients with class I and II obesity, as well as for patients with T2DM and a BMI of ≥ 30 kg/m2. Sleeve gastrectomy (1) and Roux-en-Y gastric bypass (RYGB) were also recognized as viable treatment options for these patient groups. The committee also agreed that one anastomosis gastric bypass (OAGB) is a suitable option for patients with Class II obesity and T2DM, regardless of the presence or severity of obesity-related medical problems. The recommendations for selecting procedures in Class I and II obesity, developed through an Expert Modified Delphi Consensus, suggest that the use of standard primary bariatric endoscopic (IGB, ESG) and surgical procedures (SG, RYGB, OAGB) are acceptable in these patient groups, as consensus was reached regarding these procedures. However, randomized controlled trials are still needed in Class I and II Obesity to identify the best treatment approach for these patients in the future.

NGFR regulates stromal cell activation in germinal centers.

Nerve growth factor receptor (NGFR) is expressed by follicular dendritic cells (FDCs). However, the role of NGFR in the humoral response is not well defined. Here, we study the effect of Ngfr loss on lymph node organization and function, demonstrating that Ngfr depletion leads to spontaneous germinal center (GC) formation and an expansion of the GC B cell compartment. In accordance with this effect, stromal cells are altered in Ngfr-/- mice with a higher frequency of FDCs, characterized by CD21/35, MAdCAM-1, and VCAM-1 overexpression. GCs are located ectopically in Ngfr-/- mice, with lost polarization together with impaired high-affinity antibody production and an increase in circulating autoantibodies. We observe higher levels of autoantibodies in Bcl2 Tg/Ngfr-/- mice, concomitant with a higher incidence of autoimmunity and lower overall survival. Our work shows that NGFR is involved in maintaining GC structure and function, participating in GC activation, antibody production, and immune tolerance.

Structure of the O-polysaccharide from the moderately halophilic bacterium Halomonas fontilapidosi KR26.

Lipopolysaccharide was obtained from the aerobic moderately halophilic bacterium Halomonas fontilapidosi KR26. The O-polysaccharide was isolated by mild acid degradation of the lipopolysaccharide and was examined by chemical methods and by 1H and 13C NMR spectroscopy, including 1H,1H COSY, TOCSY, ROESY, and 1H,13C HSQC, and HMBC experiments. The following structure of the linear tetrasaccharide repeating unit was deduced. →2)-α-l-Rhap-(1→2)-α-l-Rhap-(1→3)-α-l-Rhap-(1→3)-ß-d-Galp-(1→.

Identification of novel F2-isoprostane metabolites by specific UDP-glucuronosyltransferases.

UDP-glucuronosyltransferases (UGTs) catalyze the conjugation of glucuronic acid with endogenous and exogenous lipophilic small molecules to facilitate their inactivation and excretion from the body. This represents approximately 35 % of all phase II metabolic transformations. Fatty acids and their oxidized eicosanoid derivatives can be metabolized by UGTs. F2-isoprostanes (F2-IsoPs) are eicosanoids formed from the free radical oxidation of arachidonic acid. These molecules are potent vasoconstrictors and are widely used as biomarkers of endogenous oxidative damage. An increasing body of evidence demonstrates the efficacy of measuring the ß-oxidation metabolites of F2-IsoPs rather than the unmetabolized F2-IsoPs to quantify oxidative damage in certain settings. Yet, the metabolism of F2-IsoPs is incompletely understood. This study sought to identify and characterize novel phase II metabolites of 15-F2t-IsoP and 5-epi-5-F2t-IsoP, two abundantly produced F2-IsoPs, in human liver microsomes (HLM). Utilizing liquid chromatography-mass spectrometry, we demonstrated that glucuronide conjugates are the major metabolites of these F2-IsoPs in HLM. Further, we showed that these molecules are metabolized by specific UGT isoforms. 15-F2t-IsoP is metabolized by UGT1A3, 1A9, and 2B7, while 5-epi-5-F2t-IsoP is metabolized by UGT1A7, 1A9, and 2B7. We identified, for the first time, the formation of intact glucuronide F2-IsoPs in human urine and showed that F2-IsoP glucuronidation is reduced in people supplemented with eicosapentaenoic and docosahexaenoic acids for 12 weeks. These studies demonstrate that endogenous F2-IsoP levels can be modified by factors other than redox mechanisms.

Inactivated whole virion vaccine protects K18-hACE2 Tg mice against the Omicron SARS-CoV-2 variant via cross-reactive T cells and nonneutralizing antibody responses.

COVID-19 is a systemic inflammatory disease initiated by SARS-CoV-2 virus infection. Multiple vaccines against the Wuhan variant of SARS-CoV-2 have been developed including a whole virion beta-propiolactone-inactivated vaccine based on the B.1.1 strain (CoviVac). Since most of the population has been vaccinated by targeting the original or early variants of SARS-CoV-2, the emergence of novel mutant variants raises concern over possible evasion of vaccine-induced immune responses. Here, we report on the mechanism of protection by CoviVac, a whole virion-based vaccine, against the Omicron variant. CoviVac-immunized K18-hACE2 Tg mice were protected against both prototype B.1.1 and BA.1-like (Omicron) variants. Subsequently, vaccinated K18-hACE2 Tg mice rapidly cleared the infection via cross-reactive T-cell responses and cross-reactive, non-neutralizing antibodies recognizing the Omicron variant Spike protein. Thus, our data indicate that efficient protection from SARS-CoV-2 variants can be achieved by the orchestrated action of cross-reactive T cells and non-neutralizing antibodies.

Association between F2-Isoprostane Metabolites and Weight Change in Older Women: A Longitudinal Analysis.

INTRODUCTION: Theoretically, some metabolic traits may predispose older individuals to weight loss during aging, leading to increased all-cause mortality and many serious health issues. Biomarkers to robustly predict progressive weight loss during aging are, however, lacking. We prospectively assessed if urinary levels of F2-isoprostanes and their peroxisomal ß-oxidation metabolite, 2,3-dinor-5,6-dihydro-15-F2t-isoprostane (F2-IsoP-M), were associated with subsequent weight loss in middle-aged and older women. METHODS: Included in the analysis were 2,066 women aged 40-70 years, a subset of a prospective cohort study. F2-isoprostanes (F2-IsoPs) and its ß-oxidation metabolite, F2-IsoP-M, were measured in urine using gas chromatography-mass spectrometry. Measurements of anthropometry and exposures to major determinants of body weight were performed at baseline and repeated thrice over 15-year follow-up. The longitudinal associations of F2-IsoP-M and the F2-IsoP-M to its parent compound, F2-IsoP, ratio (MPR) with repeatedly measured weight changes were examined using linear mixed-effect models. RESULTS: After adjusting for time-varying covariates: energy intake, physical activity, and comorbidity index, among others, levels of F2-IsoP-M and the MPR were both inversely associated with percentage of weight change. Weight in the highest quartile of these two biomarkers was 1.33% (95% CI = -2.41, -0.24) and 1.09% (95% CI = -2.16, -0.02) lower than those in the lowest quartile group, with p for trend of 0.01 and 0.03, respectively. The inverse association was consistently seen across follow-up periods, although appearing stronger with prolonged follow-up. There was no association between the parent compound, F2-IsoPs, and weight change. CONCLUSION: This study demonstrates the first piece of evidence to associate F2-IsoP metabolism, peroxisomal ß-oxidation, with weight loss in older women. Further investigations into the role of lipid peroxidation and peroxisomal ß-oxidation in weight change among older individuals are warranted.

Communicating Patient Discharge Readiness: An Implementation Evaluation in an Inpatient Hospital Medicine Setting.

BACKGROUND: The progression of patients through a hospital from admission to discharge can be slowed by delays in patient discharge, increasing pressure on health care staff. We designed and piloted the Discharge Today tool, with the goal of improving the efficiency of patient discharge; however, adoption remained low. PURPOSE: To close this implementation gap, we deployed and evaluated a 4-part implementation strategy bundle. METHODS: We measured the success of implementation by evaluating validated implementation outcomes using both quantitative and qualitative methods, grounded in Normalization Process Theory. RESULTS: The implementation strategies used were effective for increasing use of the Discharge Today tool by hospital medicine physicians and advanced practice providers during both the active and passive implementation periods. CONCLUSIONS: While the implementation strategies used were effective, qualitative findings indicate that limitations in the functionality of the tool, alongside inconsistent use of the tool across clinical staff, continued to inhibit adoption.

Efficacy and safety of tixagevimab-cilgavimab versus SARS-CoV-2 breakthrough infection in the hematological conditions.

BACKGROUND: Managing SARS-CoV-2 infection in frail and immunosuppressed patients still represents an open challenge, but, starting from the phase 3 PROVENT study, prophylaxis with tixagevimab-cilgavimab has improved the approach in this category of patients, guaranteeing a better outcome and inferior mortality. Real-life data in a heterogeneous cohort are few. METHODS: The aim of this study is to evaluate the benefit of prophylaxis with tixagevimab-cilgavimab in a cohort of 202 patients affected by different hematological diseases (lymphoproliferative, myeloproliferative, autoimmune, patients recently receiving a bone marrow transplant), active (with ongoing treatment), or in watch-and-wait strategy, followed in our center, during a median follow-up of 249 (45-325) days. RESULTS: An incidence of 44 breakthrough infections (21.8%) is reported, with no treatment-related adverse effects. Age ≥70 years, ongoing treatment (above all with monoclonal antibodies), baseline lymphoproliferative disorders, and prior virus exposure are identified as risk factors related to subsequent infection (p < 0.05). Moreover, the incidence is higher in low/nonresponse to prior vaccination (p = .002). Patients treated with tixagevimab-cilgavimab had a mild course of the infection and a reduction of the duration compared with preprophylaxis infection (11 vs. 15 days, p < .001). The concurrent treatment with anti-CD20 monoclonal antibodies and B-non-Hodgkin lymphoma still confers a higher duration of infection despite prophylaxis. No deaths attributable to the infection occurred. CONCLUSION: Prophylaxis treatment seems to be a valid and safe strategy, although not preventing breakthrough infection, but the severe complications associated with the infection and the possible delays in administering lifesaving therapies from long positivity.

Detection of plasma anti-lipopolysaccharide (LPS) antibodies against enterohemorrhagic Escherichia coli (EHEC) in asymptomatic kindergarten teachers from Buenos Aires province.

In Argentina, hemolytic uremic syndrome (HUS) caused by EHEC has the highest incidence in the world. EHEC infection has an endemo-epidemic behavior, causing 20-30% of acute bloody diarrhea syndrome in children under 5 years old. In the period 2016-2020, 272 new cases per year were notified to the National Health Surveillance System. Multiple factors are responsible for HUS incidence in Argentina including person-to-person transmission. In order to detect possible EHEC carriers, we carried out a preliminary study of the frequency of kindergarten teachers with anti-LPS antibodies against the most prevalent EHEC serotypes in Argentina. We analyzed 61 kindergarten teachers from 26 institutions from José C. Paz district, located in the suburban area of Buenos Aires province, Argentina. Fifty-one percent of the plasma samples had antibodies against O157, O145, O121 and O103 LPS: 6.4% of the positive samples had IgM isotype (n=2), 61.3% IgG isotype (n=19) and 32.3% IgM and IgG (n=10). Given that antibodies against LPS antigens are usually short-lived specific IgM detection may indicate a recent infection. In addition, the high percentage of positive samples may indicate a frequent exposure to EHEC strains in the cohort studied, as well as the existence of a large non-symptomatic population of adults carrying pathogenic strains that could contribute to the endemic behavior through person-to-person transmission. The improvement of continuous educational programs in kindergarten institutions could be a mandatory measure to reduce HUS cases not only in Argentina but also globally.

Corneal Irregularity Induced by Transepithelial Photorefractive Keratectomy in a Patient With Partial Limbal Stem Cell Deficiency.

PURPOSE: The aim of this study was to present a case of transepithelial photorefractive keratectomy (trans-PRK) laser ablation in a patient with partial limbal stem cell deficiency (LSCD) that resulted in corneal irregularity. METHODS: A 23-year-old man with bilateral partial LSCD underwent trans-PRK for myopia correction 2 months before presentation to our department. Trans-PRK ablation was performed with a phototherapeutic keratectomy ablation profile set at 60 µm in the OD and 57 µm in the OS and 8 mm zone. At the time of presentation, the patient complained of decreased visual acuity. Corrected distant visual acuity was 20/20 (-3.25, -0.75 × 180 degrees) and 20/50 (-3.00, -3.00 × 180 degrees) in the OD and the OS, respectively. No further ocular history was reported other than prolonged soft contact lens use for myopia. Pre-trans-PRK tomography (WaveLight Oculyzer II diagnostic system, WaveLight GmbH, Germany) revealed bilateral superior steepening with corresponding epithelial thinning as obtained by the epithelial map using Optovue optical coherence tomography (Visionix Luneau technology). Slit-lamp examination showed bilateral superficial neovascularization, suggestive of early-stage LSCD. RESULTS: A nonuniform laser stromal ablation resulting in corneal irregularity and decreased visual acuity was observed 2 months postoperatively. During the 6-month follow-up, corneal tomography was stable with only minimal improvement. At that time, corrected distant visual acuity remained 20/20 (-2.75, -0.75 × 160 degrees) in the OD and 20/50 (-3.00, -3.00 × 180 degrees) in the OS. CONCLUSIONS: Trans-PRK seems to be a contraindication in cases with corneal epithelial irregularities and could lead to abnormal and nonuniform stromal ablation .