Effectiveness of repeated injections of botulinum toxin A on gait and fatigue in adults with spastic paraparesis secondary to multiple sclerosis.

BACKGROUND: Multiple sclerosis (MS) is the most common neurologic disease in young adults. Spasticity is one of its most disabling symptoms, with botulinum toxin A type A (BoNT-A) being one of the treatments of choice for this symptom. OBJECTIVE: We assessed the response to abobotulinumtoxinA in improving walking ability and fatigue in patients with spastic paraparesis caused by MS. METHODS: We performed a real-world, multicenter, prospective, open-label low-intervention trial in 84 patients with MS and spastic paraparesis of the lower limbs infiltrated with abobotulinumtoxinA (LINITOX study). The response of spasticity, walking ability and fatigue is analyzed in 4 cycles of ultrasound-guided injection in the lower limbs. RESULTS: The patients improved their walking ability by an average of 11.34% meters measured with 6-Minute Walk Test (6MWT), and decreased the percentage of fatigue by 6.86% (4.66 percentage points less), in the 12-Item Multiple Sclerosis Walking Scale (MSWS-12) 4 weeks after abobotulinumtoxinA injection, both values are statistically significant. This improvement seems to persist over time, throughout the cycles. CONCLUSION: We found improved walking ability and less fatigue in patients with MS-related spastic paresis of the lower limbs after injection of abobotulinumtoxinA.

Immune response against the SARS-CoV-2 spike protein in cancer patients after COVID-19 vaccination during the Omicron wave: a prospective study.

BACKGROUND: Cancer patients often have weakened immune systems, resulting in a lower response to vaccines, especially those receiving immunosuppressive oncological treatment (OT). We aimed to assess the impact of OT on the humoral and T-cell response to the B.1 lineage and Omicron variant following COVID-19 vaccination in patients with solid and hematological neoplasms. METHODS: We conducted a prospective study on cancer patients, stratified into OT and non-OT groups, who received a two-dose series of the COVID-19 mRNA vaccine and a booster six months later. The outcomes measured were the humoral (anti-SARS-CoV-2 S IgG titers and ACE2-S interaction inhibition capacity) and cellular (SARS-CoV-2 S-specific T-cell spots per million PBMCs) responses against the B.1 lineage and Omicron variant. These responses were evaluated four weeks after the second dose (n = 98) and eight weeks after the booster dose (n = 71). RESULTS: The humoral response after the second vaccine dose against the B.1 lineage and Omicron variant was significantly weaker in the OT group compared to the non-OT group (q-value<0.05). A booster dose of the mRNA-1273 vaccine significantly improved the humoral response in the OT group, making it comparable to the non-OT group. The mRNA-1273 vaccine, designed for the original Wuhan strain, elicited a weaker humoral response against the Omicron variant compared to the B.1 lineage, regardless of oncological treatment or vaccine dose. In contrast, T-cell responses against SARS-CoV-2, including the Omicron variant, were already present after the second vaccine dose and were not significantly affected by oncological treatments. CONCLUSIONS: Cancer patients, particularly those receiving immunosuppressive oncological treatments, should require booster doses and adapted COVID-19 vaccines for new SARS-CoV-2 variants like Omicron. Future studies should evaluate the durability of the immune response and the efficacy of individualized regimens.

In vitro 3D co-culture model of human endothelial and smooth muscle cells to study pathological vascular remodeling. / Modelo de cocultivo 3D in vitro de células endoteliales y vasculares de músculo liso humanas para el estudio del remodelado vascular patológico.

Pathological vascular remodeling of the vessel wall refers to the structural and functional changes of the vessel wall that occur in response to injury that eventually leads to cardiovascular disease. The vessel wall is composed of two main types of cells, endothelial cells and vascular smooth muscle cells, whose communication is crucial in both the development of the vasculature and the homeostasis of mature vessels. Changes in the dialogue between endothelial cells and vascular smooth muscle cells are associated with various pathological states that triggers remodeling of the vascular wall. For many years, considerable efforts have been made to develop effective diagnoses and treatments for these pathologies by studying their mechanisms in both in vitro and in vivo models. Compared to animal models, in vitro models can provide great opportunities to obtain data in a more homogeneous, economical and massive way, providing an overview of the signaling pathways responsible for these pathologies. The implementation of three-dimensional in vitro co-culture models for the study of other pathologies has been postulated as a potentially applicable methodology, which determines the importance of its application in studies of cardiovascular diseases. In this article we present a method for culturing human endothelial cells and vascular smooth muscle cells, grown under non-adherent conditions, that generate three-dimensional spheroidal structures with greater physiological equivalence to in vivo conditions. This in vitro modeling could be used as a study tool to identify cellular and molecular mechanisms involved in the pathological processes underlying vascular remodeling.

Severe Hypoplasia of Paranasal Sinuses and Turbinates.

This case report describes a patient in their 40s with a history of bronchiectasis, azoospermia, and epididymal cysts who presented with bilateral nasal obstruction.

Improving the Catalytic Performance of BaMn0.7Cu0.3O3 Perovskite for CO Oxidation in Simulated Cars Exhaust Conditions by Partial Substitution of Ba.

The sol-gel method, adapted to aqueous media, was used for the synthesis of BaMn0.7Cu0.3O3 (BMC) and Ba0.9A0.1Mn0.7Cu0.3O3 (BMC-A, A = Ce, La or Mg) perovskite-type mixed oxides. These samples were fully characterized by ICP-OES, XRD, XPS, H2-TPR, BET, and O2-TPD and, subsequently, they were evaluated as catalysts for CO oxidation under different conditions simulating that found in cars exhaust. The characterization results show that after the partial replacement of Ba by A metal in BMC perovskite: (i) a fraction of the polytype structure was converted to the hexagonal BaMnO3 perovskite structure, (ii) A metal used as dopant was incorporated into the lattice of the perovskite, (iii) oxygen vacancies existed on the surface of samples, and iv) Mn(IV) and Mn(III) coexisted on the surface and in the bulk, with Mn(IV) being the main oxidation state on the surface. In the three reactant atmospheres used, all samples catalysed the CO to CO2 oxidation reaction, showing better performances after the addition of A metal and for reactant mixtures with low CO/O2 ratios. BMC-Ce was the most active catalyst because it combined the highest reducibility and oxygen mobility, the presence of copper and of oxygen vacancies on the surface, the contribution of the Ce(IV)/Ce(III) redox pair, and a high proportion of surface and bulk Mn(IV). At 200 °C and in the 0.1% CO + 10% O2 reactant gas mixture, the CO conversion using BMC-Ce was very similar to the achieved with a 1% Pt/Al2O3 (Pt-Al) reference catalyst.

Physical Activity in Work and Leisure Time during Pregnancy, and Its Influence on Maternal Health and Perinatal Outcomes.

BACKGROUND: Physical inactivity during pregnancy has been shown to be linked to an increased risk of complications. However, during pregnancy, doubts arise about what type, intensity and frequency of physical activity are most recommended. OBJECTIVE: Our main objective was to know the level of physical activity (PA) and sedentary lifestyle in a representative sample of pregnant women in Málaga, one of the most populated cities in Spain. Also, we aimed to find out the effects of PA on obstetric and perinatal outcomes and on the mental health of pregnant women, differentiated according to PA intensity and domain. METHODS: Five hundred and forty full-term pregnant women who had their obstetric checks in the maternity ward of the Regional University Hospital of Málaga were recruited through consecutive sampling. Participants answered a questionnaire that included the WHO Global Physical Activity Questionnaire (GPAQ), the Edinburgh Depression Scale (EDS), the Generalized Anxiety Disorder Scale (GAD-7) and some other sociodemographic and health-related questions. Subsequently, information about perinatal outcomes was obtained after birth. RESULTS: Only 50.8% of women followed the WHO recommendations on activity. We found a high proportion of obese pregnant women and a direct effect of a sedentary lifestyle on the rate of cesarean sections and vulvovaginal tears in spontaneous births, as well as on the mental health of future mothers. Women's age, the number of children, BMI at the beginning of pregnancy and leisure time physical activity (LTPA) explained anxiety scores, and age, LTPA, BMI at the end of pregnancy and intense work-related physical activity (WTPA) predicted depression scores. CONCLUSIONS: LTPA improves obstetric outcomes, helping to reduce the rate of cesarean sections and vulvovaginal tears, as well as reducing prenatal anxiety and depression.

A Study on the Efficacy and Safety of Pipeline Shield Stents and Nonmodified Surface Flow-Diverting Stents in Patients with Intracranial Aneurysms.

BACKGROUND: Few studies have compared the Pipeline Shield stents with previous generations of flow-diverting stents (FDSs) for the treatment of unruptured intracranial aneurysms. This study aimed to evaluate the efficacy and safety of Pipeline Shield stents and FDSs without modified surfaces. METHODS: The present evaluation is a retrospective cohort study of patients endovascularly treated with Pipeline Shield stents or FDSs without modified surfaces for unruptured intracranial aneurysms between January 2014 and June 2022. The data analyzed were obtained from the anonymized database of our institution's interventional radiology service. RESULTS: A total of 147 patients with 155 unruptured intracranial aneurysms were included. Of the 155 aneurysms, 96 were treated with Pipeline Shield stents and 59 with FDSs without modified surfaces. The aneurysms treated with Pipeline Shield stents had higher 6-month (O'Kelly-Marotta [OKM] D; 87.5% vs. 71.4%; P = 0.025) and 1-year (OKM D; 82.5% vs. 63.0%; P = 0.047) occlusion rates than the aneurysms treated using FDSs without modified surfaces. No differences between the devices were found at the 1-year follow-up in the incidence of ischemic stroke (P = 0.939) or hemorrhagic complications (P = 0.559). CONCLUSIONS: Pipeline Shield stents demonstrated superior complete occlusion rates (OKM D) at both the 6-month and the 1-year follow-up assessments compared with nonmodified surface FDSs. No significant differences were found in the safety profiles between the 2 types of stents with regard to thromboembolic complications and ischemic events. Further research with larger study populations is necessary to validate these findings.

Frank's sign associated with the severity of ischemic heart disease in patients under 65 years old / Signo de Frank asociado con la gravedad de la cardiopatía isquémica en adultos de edad inferior o igual a 65 años

Background and objective Frank's sign is the diagonal ear fold which has been associated with ischemic heart disease. The objective of this work was to evaluate the relationship of Frank's sign with severity of ischemic heart disease in adults ≤ 65 years old in the northeast of Mexico. Patients and methods A cross-sectional study was conducted in patients ≤ 65 years old who underwent coronary angiography consecutively over a period of 5 months in 2022. Severe coronary artery disease (CAD) was associated with Frank's sign and other common cardiovascular risks. To determine the association, bivariate and multivariate analysis was performed using logistic regression that included variables with a value of p<0.05. Statistical analysis was performed with SPSS version 22. Results We included 311 patients ≤ 65 years, of whom 80% were men. The median age was 57 years (range 28–65). Frank's sign was positive in 62% of the population. The main clinical characteristics in patients with Frank's sign were type 2 diabetes mellitus (55%), p=0.003, dyslipidemia (53%), p=0.026 and smoking (68%), p=0.002. In the multivariate analysis, the independent variables associated with severe CAD were Frank's Sign OR 3.26; 95% CI (1.98–5.38), p≤0.001, male gender OR 2.28; 95% CI (1.20–4.35), p=0.012, and dyslipidemia OR 1.81; 95% CI (1.11–2.97), p=0.017. Conclusions There is an independent association between Frank's sign with the presence of severe CAD in patients ≤ 65 years old, which may be useful for screening and prevention (AU)

Antecedentes y objetivo El signo de pliegue diagonal de la oreja o signo de Frank se ha asociado con cardiopatía isquémica. El objetivo de este trabajo fue evaluar la relación del signo de Frank con la gravedad de la cardiopatía isquémica en adultos≤65años en el noreste de México. Pacientes y métodos Se realizó un estudio transversal en pacientes ≤65años sometidos a coronariografía de manera consecutiva en un periodo de 5 meses en 2022. Se relacionó la enfermedad arterial coronaria (EAC) grave con el signo de Frank y los factores de riesgo cardiovascular tradicionales. Para determinar la asociación se realizó análisis bivariado y multivariado mediante regresión logística que incluyó las variables con valor de p<0,05. El análisis estadístico se realizó con el programa SPSS versión 22. Resultados Se incluyeron 311 pacientes≤65años, de los cuales el 80% fueron hombres. La mediana de edad fue 57 años (rango de 28-65 años). El 62% de los pacientes presentó el signo de Frank. Las principales características clínicas en pacientes con signo de Frank fueron diabetes mellitus tipo 2 (55%), p=0,003, dislipidemia (53%), p=0,026 y tabaquismo (68%), p=0,002. En el análisis multivariado las variables independientes asociadas a EAC grave fueron el signo de Frank (OR: 3,26; IC 95%: 1,98-5,38; p≤0,001), sexo masculino (OR: 2,28; IC 95%: 1,20-4,35; p=0,012) y dislipidemia (OR: 1,81; IC 95%: 1,11-2,97; p=0,017). Conclusiones Existe asociación independiente del signo de Frank con la presencia de EAC grave en pacientes≤65años, que puede ser útil para el cribado y la prevención (AU)

Screening Ba0.9A0.1MnO3 and Ba0.9A0.1Mn0.7Cu0.3O3 (A = Mg, Ca, Sr, Ce, La) Sol-Gel Synthesised Perovskites as GPF Catalysts.

Ba0.9A0.1MnO3 (BM-A) and Ba0.9A0.1Mn0.7Cu0.3O3 (BMC-A) (A = Mg, Ca, Sr, Ce, La) perovskite-type mixed oxides were synthesised, characterised, and used for soot oxidation in simulated Gasoline Direct Injection (GDI) engine exhaust conditions. The samples have been obtained by the sol-gel method in an aqueous medium and deeply characterised. The characterization results indicate that the partial substitution of Ba by A metal in BaMnO3 (BM) and BaMn0.7Cu0.3O3 (BMC) perovskites: (i) favours the hexagonal structure of perovskite; (ii) improves the reducibility and the oxygen desorption during Temperature-Programmed Desorption (O2-TPD) tests and, consequently, the oxygen mobility; (iii) mantains the amount of oxygen vacancies and of Mn(IV) and Mn(III) oxidation states, being Mn(IV) the main one; and (iv) for Ba0.9A0.1Mn0.7Cu0.3O3 (BMC-A) series, copper is partially incorporated into the structure. The soot conversion data reveal that Ba0.9La0.1Mn0.7Cu0.3O3 (BMC-La) is the most active catalyst in an inert (100% He) reaction atmosphere, as it presents the highest amount of copper on the surface, and that Ba0.9Ce0.1MnO3 (BM-Ce) is the best one if a low amount of O2 (1% O2 in He) is present, as it combines the highest emission of oxygen with the good redox properties of Ce(IV)/Ce(III) and Mn(IV)/Mn(III) pairs.

Multicenter evaluation of BioFire JI panel related to improved microbiological diagnostics on acute osteoarticular infections.

Microbiological diagnosis of osteoarticular infections (OI) is crucial for a successful treatment. A prospective multicenter study including 262 synovial fluids with suspicion of acute OI was performed between July 2021 and October of 2022. BioFire Joint Infection Panel multiplex-PCR test was performed and results were compared with conventional cultures of synovial fluid specimens. In total, 136 microorganisms were detected, and fourteen samples were positive for more than one microorganism. In monomicrobial infections (n = 87) agreement with culture was 69%. In 26 samples, the multiplex PCR yield an additional positive result when culture result was negative. It helped in the detection of fastidious microorganisms as K. kingae and N. gonorrhoeae. This multiplex PCR has proven to be a useful technique that can be used for patients with high suspicion of acute OI in a rapid and automated manner.

IgG antibody levels against the SARS-CoV-2 spike protein in mother-child dyads after COVID-19 vaccination.

PURPOSE: We aimed to assess IgG antibodies against the SARS-CoV-2 spike protein (anti-SARS-CoV-2 S IgG) in vaccinated mothers and their infants at delivery and 2-3 months of age. METHODS: We conducted a prospective study on mothers who received at least one dose of the COVID-19 vaccine (Pfizer-BNT162b2, Moderna mRNA-1273, or Oxford-AstraZeneca ChAdOx1-S) during pregnancy and on their infants. The baseline was at the time of delivery (n = 93), and the end of follow-up was 2 to 3 months post-partum (n = 53). Serum anti-SARS-CoV-2 S IgG titers and ACE2 binding inhibition levels were quantified by immunoassays. RESULTS: Mothers and infants had high anti-SARS-CoV-2 S IgG titers against the B.1 lineage at birth. However, while antibody titers were maintained at 2-3 months post-partum in mothers, they decreased significantly in infants (p < 0.001). Positive and significant correlations were found between anti-SARS-CoV-2 S IgG titers and ACE2-binding inhibition levels in mothers and infants at birth and 2-3 months post-partum (r > 0.8, p < 0.001). Anti-S antibodies were also quantified for the Omicron variant at 2-3 months post-partum. The antibody titers against Omicron were significantly lower in mothers and infants than those against B.1 (p < 0.001). Again, a positive correlation was observed for Omicron between IgG titers and ACE2-binding inhibition both in mothers (r = 0.818, p < 0.001) and infants (r = 0.386, p < 0.005). Previous SARS-CoV-2 infection and COVID-19 vaccination near delivery positively impacted anti-SARS-CoV-2 S IgG levels. CONCLUSIONS: COVID-19 mRNA vaccines induce high anti-SARS-CoV-2 S titers in pregnant women, which can inhibit the binding of ACE2 to protein S and are efficiently transferred to the fetus. However, there was a rapid decrease in antibody levels at 2 to 3 months post-partum, particularly in infants.

Frank's sign associated with the severity of ischemic heart disease in patients under 65 years old.

BACKGROUND AND OBJECTIVE: Frank's sign is the diagonal ear fold which has been associated with ischemic heart disease. The objective of this work was to evaluate the relationship of Frank's sign with severity of ischemic heart disease in adults ≤ 65 years old in the northeast of Mexico. PATIENTS AND METHODS: A cross-sectional study was conducted in patients ≤ 65 years old who underwent coronary angiography consecutively over a period of 5 months in 2022. Severe coronary artery disease (CAD) was associated with Frank's sign and other common cardiovascular risks. To determine the association, bivariate and multivariate analysis was performed using logistic regression that included variables with a value of p<0.05. Statistical analysis was performed with SPSS version 22. RESULTS: We included 311 patients ≤ 65 years, of whom 80% were men. The median age was 57 years (range 28-65). Frank's sign was positive in 62% of the population. The main clinical characteristics in patients with Frank's sign were type 2 diabetes mellitus (55%), p=0.003, dyslipidemia (53%), p=0.026 and smoking (68%), p=0.002. In the multivariate analysis, the independent variables associated with severe CAD were Frank's Sign OR 3.26; 95% CI (1.98-5.38), p≤0.001, male gender OR 2.28; 95% CI (1.20-4.35), p=0.012, and dyslipidemia OR 1.81; 95% CI (1.11-2.97), p=0.017. CONCLUSIONS: There is an independent association between Frank's sign with the presence of severe CAD in patients ≤ 65 years old, which may be useful for screening and prevention.

A deficient immune response to SARS-CoV-2 in the nasopharynx is associated with severe COVID-19 pneumonia.

OBJECTIVES: We analyzed the expression of inflammatory and antiviral genes in the nasopharynx of SARS-CoV-2 infected patients and their association with the severity of COVID-19 pneumonia. METHODS: We conducted a cross-sectional study on 223 SARS-CoV-2 infected patients. Clinical data were collected from medical records, and nasopharyngeal samples were collected in the first 24 hours after admission to the emergency room. The gene expression of eight proinflammatory/antiviral genes (plasminogen activator urokinase receptor [PLAUR], interleukin [IL]-6, IL-8, interferon [IFN]-ß, IFN-stimulated gene 15 [ISG15], retinoic acid-inducible gene I [RIG-I], C-C motif ligand 5 [CCL5], and chemokine C-X-C motif ligand 10 [CXCL10]) were quantified by real-time polymerase chain reaction. Outcome variables were: (i) pneumonia; (ii) severe pneumonia or acute respiratory distress syndrome. Statistical analysis was performed using multivariate logistic regression analyses. RESULTS: We enrolled 84 mild, 88 moderate, and 51 severe/critical cases. High expression of PLAUR (adjusted odds ratio [aOR] = 1.25; P = 0.032, risk factor) and low expression of CXCL10 (aOR = 0.89; P = 0.048, protective factor) were associated with pneumonia. Furthermore, lower values of ISG15 (aOR = 0.88, P = 0.021), RIG-I (aOR = 0.87, P = 0.034), CCL5 (aOR = 0.73, P <0.001), and CXCL10 (aOR = 0.84, P = 0.002) were risk factors for severe pneumonia/acute respiratory distress syndrome. CONCLUSION: An unbalanced early innate immune response to SARS-CoV-2 in the nasopharynx, characterized by high expression of PLAUR and low expression of antiviral genes (ISG15 and RIG-I), and chemokines (CCL5 and CXCL10), was associated with COVID-19 severity.

Analyzing the Effect of Zr, W, and V Isomorph Framework Substitution on ZSM-5 and Beta Zeolites for Their Use as Hydrocarbon Trap.

This work evaluates the effect on the adsorption and desorption kinetics of propene and toluene (used as probe molecules for vehicle cold-start emissions) of the isomorph framework substitution of Zr, W, and V on commercial ZSM-5 and beta zeolites. TG-DTA and XRD characterization data indicated that: (i) Zr does not modify the crystalline structure of the parent zeolites, (ii) W develops a new crystalline phase, and (iii) V causes the breakdown of the zeolite structure during the aging step. The CO2 and N2 adsorption data revealed that the substituted zeolites present a narrower microporosity than pristine zeolites. As a consequence of all these modifications, the modified zeolites feature different adsorption capacity and kinetics of HCs, so, different hydrocarbon trapping ability than pristine zeolites. However, a clear correlation is not observed between the changes in the porosity/acidity of zeolites and the adsorption capacity and kinetics, which depends on: (i) the zeolite (ZSM-5 or BEA), (ii) the hydrocarbon (toluene or propene), and (iii) the cation to be inserted (Zr, W, or V).

Tailoring the Composition of BaxBO3 (B = Fe, Mn) Mixed Oxides as CO or Soot Oxidation Catalysts in Simulated GDI Engine Exhaust Conditions.

Mixed oxides with perovskite-type structure (ABO3) are promising catalysts for atmospheric pollution control due to their interesting and tunable physicochemical properties. In this work, two series of BaxMnO3 and BaxFeO3 (x = 1 and 0.7) catalysts were synthesized using the sol-gel method adapted to aqueous medium. The samples were characterized by µ-XRF, XRD, FT-IR, XPS, H2-TPR, and O2-TPD. The catalytic activity for CO and GDI soot oxidation was determined by temperature-programmed reaction experiments (CO-TPR and soot-TPR, respectively). The results reveal that a decrease in the Ba content improved the catalytic performance of both catalysts, as B0.7M-E is more active than BM-E for CO oxidation, and B0.7F-E presents higher activity than BF for soot conversion in simulated GDI engine exhaust conditions. Manganese-based perovskites (BM-E and B0.7M-E) achieve better catalytic performance than iron-based perovskite (BF) for CO oxidation reaction due to the higher generation of actives sites.

Hepatitis E Virus Seroprevalence is Associated with Neurodegenerative Disorders in Older People with Dementia: A Case-Control Study.

In this case-control study, we evaluated the association between serum antibodies against hepatitis E virus (HEV) and central nervous system (CNS) neurodegenerative disorders (NDs) in older people with dementia. The presence of anti-HEV antibodies was related to a higher adjusted odds ratio (aOR) of having CNS NDs by neuropathological diagnosis (aOR, 2.13; P = .007) and clinical/neuropathological diagnosis (1.84; P = .02). Besides, serum anti-HEV antibodies were directly related to neuropathological injury (higher vascular pathology [aOR, 1.97; P = .006]) and higher probability of Alzheimer-type pathology (1.84; P = .02). In conclusion, the presence of anti-HEV antibodies was related to higher odds of CNS NDs and neuropathological injury in older people.

Antibody levels to SARS-CoV-2 spike protein in mothers and children from delivery to six months later.

INTRODUCTION: Pregnant women are vulnerable to severe acute respiratory syndrome coronavirus (SARS-CoV-2) infection. Neutralizing antibodies against the SARS-CoV-2 spike (S) protein protect from severe disease. This study analyzes the antibody titers to SARS-CoV-2 S protein in pregnant women and their newborns at delivery, and six months later. METHODS: We conducted a prospective study on pregnant women with confirmed SARS-CoV-2 infection and newborns. Antibody (IgG, IgM, and IgA) titers were determined using immunoassays in serum and milk samples. An angiotensin-converting enzyme 2 (ACE2) receptor-binding inhibition assay to the S protein was performed on the same serum and milk samples. RESULTS: At birth, antibodies to SARS-CoV-2 spike protein were detected in 81.9% of mothers' sera, 78.9% of cord blood samples, and 63.2% of milk samples. Symptomatic women had higher antibody titers (IgG, IgM, and IgA) than the asymptomatic ones (P < 0.05). At six months postpartum, IgG levels decreased drastically in children's serum (P < 0.001) but remained high in mothers' serum. Antibody titers correlated positively with its capacity to inhibit the ACE2-spike protein interaction at baseline in maternal sera (R2  = 0.203; P < 0.001), cord sera (R2  = 0.378; P < 0.001), and milk (R2  = 0.564; P < 0.001), and at six months in maternal sera (R2  = 0.600; P < 0.001). CONCLUSIONS: High antibody levels against SARS-CoV-2 spike protein were found in most pregnant women. Due to the efficient transfer of IgG to cord blood and high IgA titers in breast milk, neonates may be passively immunized to SARS-CoV-2 infection. Our findings could guide newborn management and maternal vaccination policies.

Role of the multi-drug efflux systems on the baseline susceptibility to ceftazidime/avibactam and ceftolozane/tazobactam in clinical isolates of non-carbapenemase-producing carbapenem-resistant Pseudomonas aeruginosa.

Carbapenem-resistant Pseudomonas aeruginosa (CRPA) is one of the pathogens that urgently needs new drugs and new alternatives for its control. The primary strategy to combat this bacterium is combining treatments of beta-lactam with a beta-lactamase inhibitor. The most used combinations against P. aeruginosa are ceftazidime/avibactam (CZA) and ceftolozane/tazobactam (C/T). Although mechanisms leading to CZA and C/T resistance have already been described, among which are the resistance-nodulation-division (RND) efflux pumps, the role that these extrusion systems may play in CZA, and C/T baseline susceptibility of clinical isolates remains unknown. For this purpose, 161 isolates of non-carbapenemase-producing (Non-CP) CRPA were selected, and susceptibility tests to CZA and C/T were performed in the presence and absence of the RND efflux pumps inhibitor, Phenylalanine-arginine ß-naphthylamide (PAßN). In the absence of PAßN, C/T showed markedly higher activity against Non-CP-CRPA isolates than observed for CZA. These results were even more evident in isolates classified as extremely-drug resistant (XDR) or with difficult-to-treat resistance (DTR), where CZA decreased its activity up to 55.2% and 20.0%, respectively, whereas C/T did it up to 82.8% (XDR), and 73.3% (DTR). The presence of PAßN showed an increase in both CZA (37.6%) and C/T (44.6%) activity, and 25.5% of Non-CP-CRPA isolates increased their susceptibility to these two combined antibiotics. However, statistical analysis showed that only the C/T susceptibility of Non-CP-CRPA isolates was significantly increased. Although the contribution of RND activity to CZA and C/T baseline susceptibility was generally low (two-fold decrease of minimal inhibitory concentrations [MIC]), a more evident contribution was observed in a non-minor proportion of the Non-CP-CRPA isolates affected by PAßN [CZA: 25.4% (15/59); C/T: 30% (21/70)]. These isolates presented significantly higher MIC values for C/T. Therefore, we conclude that RND efflux pumps are participating in the phenomenon of baseline susceptibility to CZA and, even more, to C/T. However, the genomic diversity of clinical isolates is so great that deeper analyzes are necessary to determine which elements are directly involved in this phenomenon.

Frontoparietal and temporal white matter diffusion MRI in children and youth with prenatal alcohol exposure.

BACKGROUND: Prenatal alcohol exposure (PAE) is associated with brain alterations and neurocognitive deficits, but relationships between brain alterations and neurocognitive deficits remain unclear. METHODS: Diffusion tensor imaging (DTI) data were obtained from 31 participants with PAE and 31 unexposed controls aged 7-15 years. Mean diffusivity (MD) and fractional anisotropy (FA) were derived from the genu, body, and splenium of the corpus callosum (CC), bilateral cingulum, and inferior and superior longitudinal fasciculus (ILF, SLF). Participants completed language subtests from the NEPSY-II. Executive functioning was measured using the Behavior Rating Inventory of Executive Functioning (BRIEF-PR) and verbal learning was assessed using the California Verbal Learning Test-Children's Version (CVLT-C) only in children with PAE. Group differences in diffusion metrics and cognitive scores were tested. Principal component analysis was used to reduce redundancy in cognitive and behavior variables; associations between components and brain measures were then assessed. RESULTS: Children with PAE had lower MD in the right SLF compared with unexposed controls. FA was positively related to age in 6 of 9 tracts and MD negatively related to age in all tracts; there were no significant age-by-group interactions. Participants with PAE scored lower than unexposed peers on the NEPSY-II Comprehension of Instructions and Phonological Processing and above population norms (indicating worse performance) on the BRIEF-PR. Children with PAE had a negative association between a principal component closely associated with Speeded Naming and FA in the left SLF (PAE: p = 0.002) and left ILF (PAE: p = 0.002); unexposed controls showed no significant associations. CONCLUSION: We found widespread cognitive difficulties in children with PAE, but relatively limited differences in brain metrics and associations with age. Different brain-cognitive relationships were found in children with PAE compared with controls. Overall, the results provide additional evidence that PAE may lead to cognitive difficulties and disrupt typical brain-function relationships.