Neonatal SARS-CoV-2 immunoglobulin G antibodies at delivery and their impact on COVID-19.

OBJECTIVE: To assess neonatal SARS-CoV-2 anti-spike IgG antibody levels after maternal mRNA COVID-19 vaccination and/or infection during pregnancy and evaluate their protective effect. METHODS: Prospective observational study, conducted from January 2021 to December 2022. Infants were tested for anti-spike IgG antibodies at birth and then every 3 months until disappearance of titer. A follow-up was done for SARS-CoV-2 infection up to 12 months. RESULTS: In total, 147 newborns were enrolled with a median (IQR) gestational age of 39.60 weeks (38.3-40.4). Median (IQR) titers in UA/ml at 2 days were higher (P < .001) in newborns of vaccinated 7063.7 (2841.4-14,448.1), than of infected mothers 372.7 (158.00-884.90). Titers dropped significantly during the follow-up but 50% still had a detectable titer at 6 months. A high antibody titer at 2 days led to a longer persistence (HR 0.89, IC 95% 0.83-0.96, P = .004). In total, 36 infants were infected during the first months of life coinciding with the Omicron variant. Fifty percent had detectable antibodies during the infection period. Relationship between high IgG titers and month of infection was inverse (RHO - 0.52, P = .009). CONCLUSION: Though a high antibody titer at birth led to longer persistence, no protective effect against infection was found. As newborns are a high risk group for COVID-19, avoiding transmission during the first year of life is important.

Cognitive Impairment Related to Chronic Kidney Disease Is Associated with a Decreased Abundance of Membrane-Bound Klotho in the Cerebral Cortex.

Cognitive impairment (CI) is a complication of chronic kidney disease (CKD) that is frequently observed among patients. The aim of this study was to evaluate the potential crosstalk between changes in cognitive function and the levels of Klotho in the brain cortex in an experimental model of CKD. To induce renal damage, Wistar rats received a diet containing 0.25% adenine for six weeks, while the control group was fed a standard diet. The animals underwent different tests for the assessment of cognitive function. At sacrifice, changes in the parameters of mineral metabolism and the expression of Klotho in the kidney and frontal cortex were evaluated. The animals with CKD exhibited impaired behavior in the cognitive tests in comparison with the rats with normal renal function. At sacrifice, CKD-associated mineral disorder was confirmed by the presence of the expected disturbances in the plasma phosphorus, PTH, and both intact and c-terminal FGF23, along with a reduced abundance of renal Klotho. Interestingly, a marked and significant decrease in Klotho was observed in the cerebral cortex of the animals with renal dysfunction. In sum, the loss in cerebral Klotho observed in experimental CKD may contribute to the cognitive dysfunction frequently observed among patients. Although further studies are required, Klotho might have a relevant role in the development of CKD-associated CI and represent a potential target in the management of this complication.

Hyponatremia after craniotomy in children: a single-institution review.

PURPOSE: Hyponatremia after craniotomy can be associated with increased morbidity. However, the incidence of and factors associated with post-craniotomy hyponatremia in children are not known. METHODS: We performed a retrospective cohort study of patients aged 0-21 years who underwent craniotomy in 2017-2019 at a single center to determine the incidence of and to identify risk factors for hyponatremia after craniotomy. Indications for craniotomy included tumors (excluding craniopharyngioma), epilepsy, intracranial infection, trauma, craniofacial, suboccipital decompression for the treatment of Chiari malformation, and cerebrovascular disease. Hyponatremia was defined as a serum sodium level ≤ 135 mEq/L any time during the postoperative hospital stay. Statistical significance was defined a priori at p < 0.05. RESULTS: Postoperative hyponatremia occurred in 61 (25%) of 240 children. On univariate analysis, hyponatremia was associated with younger age (8.5 vs 6.3 years, p = 0.01), use of preoperative anti-epileptic drugs (p = 0.02), need for blood transfusion (p = 0.02), government/private insurance (p = 0.04), and pre-existing hydrocephalus, defined as the requirement for permanent cerebrospinal fluid (CSF) diversion (p = 0.04). On multivariate analysis, only hydrocephalus (OR 2.95, 95% CI 1.03-8.40) remained statistically significant. Hyponatremia most occurred on the first postoperative day, with normonatremia achieved in a median of 14 (IQR 9.8-24.3) h. Hyponatremia was significantly associated with longer length of stay (median 8 vs 3 days, p < 0.01). CONCLUSION: Hyponatremia was present in 25% of children after craniotomy. Preoperative hydrocephalus as an independent risk factor for hyponatremia after craniotomy.

New Functions of Intracellular LOXL2: Modulation of RNA-Binding Proteins.

Lysyl oxidase-like 2 (LOXL2) was initially described as an extracellular enzyme involved in extracellular matrix remodeling. Nevertheless, numerous recent reports have implicated intracellular LOXL2 in a wide variety of processes that impact on gene transcription, development, differentiation, proliferation, migration, cell adhesion, and angiogenesis, suggesting multiple different functions for this protein. In addition, increasing knowledge about LOXL2 points to a role in several types of human cancer. Moreover, LOXL2 is able to induce the epithelial-to-mesenchymal transition (EMT) process-the first step in the metastatic cascade. To uncover the underlying mechanisms of the great variety of functions of intracellular LOXL2, we carried out an analysis of LOXL2's nuclear interactome. This study reveals the interaction of LOXL2 with numerous RNA-binding proteins (RBPs) involved in several aspects of RNA metabolism. Gene expression profile analysis of cells silenced for LOXL2, combined with in silico identification of RBPs' targets, points to six RBPs as candidates to be substrates of LOXL2's action, and that deserve a more mechanistic analysis in the future. The results presented here allow us to hypothesize novel LOXL2 functions that might help to comprehend its multifaceted role in the tumorigenic process.

Virological and immunological characterization of novel NYVAC-based HIV/AIDS vaccine candidates expressing clade C trimeric soluble gp140(ZM96) and Gag(ZM96)-Pol-Nef(CN54) as virus-like particles.

UNLABELLED: The generation of vaccines against HIV/AIDS able to induce long-lasting protective immunity remains a major goal in the HIV field. The modest efficacy (31.2%) against HIV infection observed in the RV144 phase III clinical trial highlighted the need for further improvement of HIV vaccine candidates, formulation, and vaccine regimen. In this study, we have generated two novel NYVAC vectors, expressing HIV-1 clade C gp140(ZM96) (NYVAC-gp140) or Gag(ZM96)-Pol-Nef(CN54) (NYVAC-Gag-Pol-Nef), and defined their virological and immunological characteristics in cultured cells and in mice. The insertion of HIV genes does not affect the replication capacity of NYVAC recombinants in primary chicken embryo fibroblast cells, HIV sequences remain stable after multiple passages, and HIV antigens are correctly expressed and released from cells, with Env as a trimer (NYVAC-gp140), while in NYVAC-Gag-Pol-Nef-infected cells Gag-induced virus-like particles (VLPs) are abundant. Electron microscopy revealed that VLPs accumulated with time at the cell surface, with no interference with NYVAC morphogenesis. Both vectors trigger specific innate responses in human cells and show an attenuation profile in immunocompromised adult BALB/c and newborn CD1 mice after intracranial inoculation. Analysis of the immune responses elicited in mice after homologous NYVAC prime/NYVAC boost immunization shows that recombinant viruses induced polyfunctional Env-specific CD4 or Gag-specific CD8 T cell responses. Antibody responses against gp140 and p17/p24 were elicited. Our findings showed important insights into virus-host cell interactions of NYVAC vectors expressing HIV antigens, with the activation of specific immune parameters which will help to unravel potential correlates of protection against HIV in human clinical trials with these vectors. IMPORTANCE: We have generated two novel NYVAC-based HIV vaccine candidates expressing HIV-1 clade C trimeric soluble gp140 (ZM96) and Gag(ZM96)-Pol-Nef(CN54) as VLPs. These vectors are stable and express high levels of both HIV-1 antigens. Gag-induced VLPs do not interfere with NYVAC morphogenesis, are highly attenuated in immunocompromised and newborn mice after intracranial inoculation, trigger specific innate immune responses in human cells, and activate T (Env-specific CD4 and Gag-specific CD8) and B cell immune responses to the HIV antigens, leading to high antibody titers against gp140. For these reasons, these vectors can be considered vaccine candidates against HIV/AIDS and currently are being tested in macaques and humans.

Survival analysis of surgically evacuated supratentorial spontaneous intracerebral hemorrhage with intraventricular extension.

OBJECTIVE: To conduct a survival study and evaluation of surgical treatment in a cohort of patients with diagnosis of supratentorial spontaneous intracerebral hemorrhage (ICH). MATERIALS AND METHODS: The study included all consecutive patients with supratentorial ICH admitted to the Intensive Care Units of three Spanish hospitals with Neurosurgery Department between 2009 and 2012. DATA COLLECTED: age, APACHE-II, Glasgow Coma Score (GCS), and pupillary anomalies on admission, intracerebral hemorrhage (ICH) score, location/volume of hematoma, intraventricular hemorrhage (IVH), surgical evacuation alone or with additional external ventricular drain, and 30-days survival and at hospital discharge RESULTS: A total of 263 patients were included. Mean age: 59.74±14.14 years. GCS: 8±4 points, APACHE II: 20.7±7.68 points. ICH Score: 2.32+1.04 points. Pupillary anomalies were observed in 30%. The 30-day mortality: 51.3% (45.3% predicted by ICH-score), and 53.2% at hospital discharge. A significant difference (p=0.004) was observed in hospital mortality rates between surgically treated patients (39.7%, n=78) versus those conservatively managed (58.9%, n=185); specifically in those with IVH surgically treated (34.2%, n=38) versus non-operated IVH (67.2%, n=125), p<0.001. No significant difference was found between mortality rates in patients without IVH. Multiple logistic regression analysis showed an OR for surgery of 1.04 (95% CI; 0.33-3.22) in patients without IVH versus 0.19 (95% CI; 0.07-0.53) in patients with IVH (decreased mortality with surgical treatment). The propensity score analysis for IVH patients showed improved survival of operated group (OR 0.23, 95% CI; 0.07-0.75), p=0.01. CONCLUSIONS: Hospital mortality was lower in patients who underwent surgery compared to patients conservatively managed, specifically for the subgroup of patients with intraventricular hemorrhage.

Evaluation of prognostic scale Thrombolysis In Myocardial Infarction and Killip. An ST-elevation myocardial infarction new scale.

BACKGROUND: Prognostic systems are complex. So it is necessary to find tools, which are easy to use and have good calibration and discrimination. OBJECTIVES: The objective of this study is to evaluate the usefulness of Killip, Thrombolysis In Myocardial Infarction (TIMI), and age to develop a new prognostic scale for patients with ST-elevation myocardial infarction (STEMI). METHODS: The study population included all patients with STEMI consecutively admitted to the Intensive Care Unit of Carlos Haya Hospital, Malaga, Spain. Top variables included are Killip and TIMI, hospital mortality, intensive care unit stay, treatment received, and care times intervals. RESULTS: The results are 806 patients; 75.6% men; age 63.11 ± 12.83 years old; TIMI, 3.57 ± 2.38; Killip I, 81.4%; and hospital mortality, 11.3%. Mortality increased in relation to age, TIMI, and Killip (P < .001). Receiver operating characteristic (ROC) area for TIMI is 0.832 (0.786-0.878) and Killip, 0.757 (0.698-0.822). Thrombolysis In Myocardial Infarction classification was associated with Killip and age by multiple linear regression. Patients were stratified into 5 groups according to Killip and age: Killip I and younger than 65 years (n = 369; mortality, 1.4%; odds ratio [OR], 1), Killip I and 65 to 75 years old (n = 173; mortality, 6.9%; OR, 5.43 [1.88-15.66]), Killip I and older than 75 years (n = 112; mortality, 18.9%; OR, 13.03 [4.69-36.21]), Killip II to III (n = 129; mortality, 31%; OR, 22.72 [12.55-85.29]), Killip IV (n = 20; mortality, 80%; OR, 291.2 [71.32-1189]). ROC area is 0.84 (0.798-0.883). We created a scale with scores based on the ß coefficient of logistical regression. CONCLUSIONS: The TIMI scale discriminated hospital mortality correctly for STEMI. It performed better than Killip alone and similar to a simple model that included age and Killip. The 2-variable model consists of a simple scale with 5 categories.

The integrated genomic surveillance system of Andalusia (SIEGA) provides a One Health regional resource connected with the clinic.

The One Health approach, recognizing the interconnectedness of human, animal, and environmental health, has gained significance amid emerging zoonotic diseases and antibiotic resistance concerns. This paper aims to demonstrate the utility of a collaborative tool, the SIEGA, for monitoring infectious diseases across domains, fostering a comprehensive understanding of disease dynamics and risk factors, highlighting the pivotal role of One Health surveillance systems. Raw whole-genome sequencing is processed through different species-specific open software that additionally reports the presence of genes associated to anti-microbial resistances and virulence. The SIEGA application is a Laboratory Information Management System, that allows customizing reports, detect transmission chains, and promptly alert on alarming genetic similarities. The SIEGA initiative has successfully accumulated a comprehensive collection of more than 1900 bacterial genomes, including Salmonella enterica, Listeria monocytogenes, Campylobacter jejuni, Escherichia coli, Yersinia enterocolitica and Legionella pneumophila, showcasing its potential in monitoring pathogen transmission, resistance patterns, and virulence factors. SIEGA enables customizable reports and prompt detection of transmission chains, highlighting its contribution to enhancing vigilance and response capabilities. Here we show the potential of genomics in One Health surveillance when supported by an appropriate bioinformatic tool. By facilitating precise disease control strategies and antimicrobial resistance management, SIEGA enhances global health security and reduces the burden of infectious diseases. The integration of health data from humans, animals, and the environment, coupled with advanced genomics, underscores the importance of a holistic One Health approach in mitigating health threats.

Removal of vaccinia virus genes that block interferon type I and II pathways improves adaptive and memory responses of the HIV/AIDS vaccine candidate NYVAC-C in mice.

Poxviruses encode multiple inhibitors of the interferon (IFN) system, acting at different levels and blocking the induction of host defense mechanisms. Two viral gene products, B19 and B8, have been shown to act as decoy receptors of type I and type II IFNs, blocking the binding of IFN to its receptor. Since IFN plays a major role in innate immune responses, in this investigation we asked to what extent the viral inhibitors of the IFN system impact the capacity of poxvirus vectors to activate immune responses. This was tested in a mouse model with single and double deletion mutants of the vaccine candidate NYVAC-C, which expresses the HIV-1 Env, Gag, Pol, and Nef antigens. When deleted individually or in double, the type I (B19) and type II (B8) IFN binding proteins were not required for virus replication in cultured cells. Studies of immune responses in mice after DNA prime/NYVAC boost revealed that deletion of B8R and/or B19R genes improved the magnitude and quality of HIV-1-specific CD8(+) T cell adaptive immune responses and impacted their memory phase, changing the contraction, the memory differentiation, the effect magnitude, and the functionality profile. For B cell responses, deletion of the viral gene B8R and/or B19R had no effect on antibody levels to HIV-1 Env. These findings revealed that single or double deletion of viral factors (B8 and B19) targeting the IFN pathway is a useful approach in the design of improved poxvirus-based vaccines.

Hallux Partial Necrosis Associated with Antiphospholipid Syndrome: The Importance of Early Accurate Diagnosis.

This study highlights the importance of having a high clinical suspicion of hypercoagulopathy such as antiphospholipid syndrome (APS) in podiatric patients with normal foot pulses and normal standard coagulation tests. APS is an autoimmune disease that is characterized by inflammatory thrombosis in the arteries and veins and obstetric complications such as pregnancy loss. APS usually affects vessels of the lower extremities. We report herein the case of a 46-year-old woman with previous episodes of pre-eclampsia who suffered from partial ischemic necrosis of the hallux of the left foot. After several ischemic episodes of the hallux, with increased risk of toe amputation, the patient was finally diagnosed with APS and treated with specific anticoagulant medication. The patient's symptoms subsided, and toe amputation was prevented. Early accurate diagnosis and appropriate clinical management are critical to providing optimal outcomes and reducing the risk of amputation.

First Trimester Evaluation of Maternal Visceral Fat and Its Relationship with Adverse Pregnancy Outcomes.

Obese women are more likely to experience pregnancy complications. The distribution of fat, and more particularly the rise in visceral fat, is well established to be more closely linked to the onset of cardiovascular disease and metabolic syndrome than obesity itself. We aim to examine the relationship between maternal visceral fat assessment in the first trimester and the appearance of adverse pregnancy outcomes. A prospective cohort study including 416 pregnant women was conducted. During the first trimester scan (11-13 + 6 weeks), all individuals had their visceral fat and subcutaneous thicknesses measured by ultrasonography. Blood samples were obtained, and maternal demographics and clinical information were documented. After delivery, the obstetric outcomes were evaluated. We contrasted two groups: one with healthy pregnancies and the other with adverse pregnancy outcomes (APO), defined as the development of at least one of the following complications: gestational diabetes mellitus, hypertensive disorders of pregnancy, abnormal fetal growth, preterm delivery or preterm premature rupture of membranes. Median maternal age was 33 and 34 years old for the uncomplicated and adverse pregnancy outcomes groups, respectively. We found that women with adverse pregnancy outcomes had higher VFT (median 30 vs. 26.5 mm, p = 0.001) and SFT (median 18.9 vs. 17.1 mm, p = 0.03). However, the visceral/subcutaneous fat ratio was not statistically different between groups. Finally, we performed a subanalysis for metabolic and placental vascular dysfunction complications. After performing a multivariate logistic regression analysis adjusted for maternal age, smoking, and mean arterial pressure, both the VFT (aOR 1.03, p < 0.001) and the ratio of visceral/subcutaneous fat (aOR 1.37, p = 0.04) were significantly associated with the development of adverse pregnancy outcomes; however, the associations of VFT and the VFT-to-SFT ratio were higher for the occurrence of gestational diabetes (aOR 1.07, p < 0.001; aOR 2.09, p = 0.001; respectively) and showed no relationships with placental complications. When conducting a first-trimester ultrasound assessment, sonographers may measure VFT without additional time or cost involved. Identification of pregnant women with increased VFT (>37 mm) may benefit from a close follow-up, especially for the development of gestational diabetes, independent of BMI.

The HIV/AIDS vaccine candidate MVA-B administered as a single immunogen in humans triggers robust, polyfunctional, and selective effector memory T cell responses to HIV-1 antigens.

Attenuated poxvirus vectors expressing human immunodeficiency virus type 1 (HIV-1) antigens are considered promising HIV/AIDS vaccine candidates. Here, we describe the nature of T cell immune responses induced in healthy volunteers participating in a phase I clinical trial in Spain after intramuscular administration of three doses of the recombinant MVA-B-expressing monomeric gp120 and the fused Gag-Pol-Nef (GPN) polyprotein of clade B. The majority (92.3%) of the volunteers immunized had a positive specific T cell response at any time postvaccination as detected by gamma interferon (IFN-γ) intracellular cytokine staining (ICS) assay. The CD4(+) T cell responses were predominantly Env directed, whereas the CD8(+) T cell responses were similarly distributed against Env, Gag, and GPN. The proportion of responders after two doses of MVA-B was similar to that obtained after the third dose of MVA-B vaccination, and the responses were sustained (84.6% at week 48). Vaccine-induced CD8(+) T cells to HIV-1 antigens after 1 year were polyfunctional and distributed mainly within the effector memory (TEM) and terminally differentiated effector memory (TEMRA) T cell populations. Antivector T cell responses were mostly induced by CD8(+) T cells, highly polyfunctional, and of TEMRA phenotype. These findings demonstrate that the poxvirus MVA-B vaccine candidate given alone is highly immunogenic, inducing broad, polyfunctional, and long-lasting CD4 and CD8 T cell responses to HIV-1 antigens, with preference for TEM. Thus, on the basis of the immune profile of MVA-B in humans, this immunogen can be considered a promising HIV/AIDS vaccine candidate.

Large Lobular Capillary Hemangioma Associated with Ingrown Toenail: Histopathological Features and Case Report.

Lobular capillary hemangioma (LCH-PG) is a type of pyogenic granuloma characterized by proliferating blood vessels that resemble conventional granulation tissue. Granulation tissue is very often seen in association with ingrown toenails. Despite the close relationship between both entities, LCH-PG shows clinically different behaviors, such as rapid growth and frequent recurrence. Currently, it is unknown exactly how the different etiological factors contribute to the formation of differences between entities. We present a case of a large LCH-PG associated with chronic onychocryptosis in a 26-year-old man. Histopathological features included extensive signs of ulceration, hyperkeratosis, and patchy epidermal acanthosis with the presence of fibrous septa with lobular areas beneath the ulcerative area. The presence of stroma with a marked proliferation of blood vessels with wall thickening and mixed-type inflammatory changes was also characteristic. In advanced stages of onychocryptosis, as presented here, conventional granulation tissue or pyogenic granuloma can be clinically difficult to distinguish from other benign or malignant neoplasms. Histological examination is mandatory, and excisional biopsy can provide a definitive diagnosis.

Emulsion Polymerization Using an Amphiphilic Oligoether Ionic Liquid as a Surfactant.

We investigate the use of an ionic liquid (IL) as a surfactant in emulsion polymerization (EP) reactions. ILs have been proposed as surfactants for micellar dispersions, emulsions, micro-emulsions and suspensions. Thus, it is important to acquire knowledge of the application of ILs in heterogeneous polymerizations. We selected the amphiphile cationic oligoether IoLiLyte C1EG™ as an IL for this purpose and compared its performance to that of the conventional surfactant dodecyl trimethyl ammonium bromide (DTAB) in the EP of methyl methacrylate and styrene. After we found the proper concentration range of the IL, this amphiphile showed similar polymerization rates to those observed with DTAB for both monomers. The evolution of monomer conversion and the final average diameter of formed polymeric particles were similar for both evaluated surfactants, demonstrating their capability to stabilize the EPs of the investigated monomers. We simulated the evolution of monomer conversion and particle size using a conventional model for emulsion polymerization, which showed good agreement with the experimental data, suggesting that the EP with this IL follows Smith-Ewart kinetics.

The PANDORA Study: Prevalence and Outcome of Acute Hypoxemic Respiratory Failure in the Pre-COVID-19 Era.

OBJECTIVES: To establish the epidemiological characteristics, ventilator management, and outcomes in patients with acute hypoxemic respiratory failure (AHRF), with or without acute respiratory distress syndrome (ARDS), in the era of lung-protective mechanical ventilation (MV). DESIGN: A 6-month prospective, epidemiological, observational study. SETTING: A network of 22 multidisciplinary ICUs in Spain. PATIENTS: Consecutive mechanically ventilated patients with AHRF (defined as Pao2/Fio2 ≤ 300 mm Hg on positive end-expiratory pressure [PEEP] ≥ 5 cm H2O and Fio2 ≥ 0.3) and followed-up until hospital discharge. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Primary outcomes were prevalence of AHRF and ICU mortality. Secondary outcomes included prevalence of ARDS, ventilatory management, and use of adjunctive therapies. During the study period, 9,803 patients were admitted: 4,456 (45.5%) received MV, 1,271 (13%) met AHRF criteria (1,241 were included into the study: 333 [26.8%] met Berlin ARDS criteria and 908 [73.2%] did not). At baseline, tidal volume was 6.9 ± 1.1 mL/kg predicted body weight, PEEP 8.4 ± 3.1 cm H2O, Fio2 0.63 ± 0.22, and plateau pressure 21.5 ± 5.4 cm H2O. ARDS patients received higher Fio2 and PEEP than non-ARDS (0.75 ± 0.22 vs 0.59 ± 0.20 cm H2O and 10.3 ± 3.4 vs 7.7 ± 2.6 cm H2O, respectively [p < 0.0001]). Adjunctive therapies were rarely used in non-ARDS patients. Patients without ARDS had higher ventilator-free days than ARDS (12.2 ± 11.6 vs 9.3 ± 9.7 d; p < 0.001). All-cause ICU mortality was similar in AHRF with or without ARDS (34.8% [95% CI, 29.7-40.2] vs 35.5% [95% CI, 32.3-38.7]; p = 0.837). CONCLUSIONS: AHRF without ARDS is a very common syndrome in the ICU with a high mortality that requires specific studies into its epidemiology and ventilatory management. We found that the prevalence of ARDS was much lower than reported in recent observational studies.

Heterotopic triplets: tubal ectopic and twin intrauterine pregnancy. A review of obstetric outcomes with a case report.

INTRODUCTION: Heterotopic triplets hardly take place, but nowadays the extended use of assisted reproductive technologies is increasing the ectopic pregnancies rate and subsequently the heterotopic pregnancies, leading to a potentially dangerous condition for the woman and the intrauterine pregnancy. MATERIAL AND METHODS: Fourteen cases previously reported in the literature of patients presenting an intrauterine twin pregnancy which became complicated by a tubal ectopic pregnancy have been reviewed. The case of a patient following a homologous intrauterine insemination treatment, resulting in live birth of both twins, is also described. CONCLUSION: Although the diagnosis of heterotopic triplets with tubal ectopic is challenging, a timely surgical treatment will preserve intrauterine gestation with a great chance of a successful obstetric outcome for both twins.

Review of mobile applications for the detection and management of atrial fibrillation.

BACKGROUND: Free mobile applications (apps) that use photoplethysmography (PPG) waveforms may extend atrial fibrillation (AF) detection to underserved populations, but they have not been rigorously evaluated. OBJECTIVE: The purpose of this study was to systematically review and evaluate the quality, functionality, and adherence to self-management behaviors of existing mobile apps for AF. METHODS: We systematically searched 3 app stores for apps that were free, available in English, and intended for use by patients to detect and manage AF. A minimum of 2 reviewers evaluated (1) app quality, using the Mobile Application Rating Scale (MARS); (2) functionality using published criteria; and (3) features that support 4 self-management behaviors (including PPG waveform monitoring) identified using evidence-based guidelines. Interrater reliability between the reviewers was calculated. RESULTS: Of 12 included apps, 5 (42%) scored above average for quality (MARS score ≥3.0). App quality was highest for their ease of use, navigation, layout, and visual appeal (eg, functionality and aesthetics) and lowest for their behavioral change support and subjective impressions of quality. The most common app functionalities were capturing and graphically displaying user-entered data (n = 9 [75%]). Nearly all apps (n = 11 [92%]) supported PPG waveform monitoring, but only 2 (17%) supported all 4 self-management behaviors. Interrater reliability was high (0.75-0.83). CONCLUSION: The reviewed apps had wide variability in quality, functionality, and adherence to self-management behaviors. Given the accessibility of these apps to underserved populations and the tremendous potential they hold for improving AF detection and management, high priority should be given to improving app quality and functionality.

Differential CD4+ versus CD8+ T-cell responses elicited by different poxvirus-based human immunodeficiency virus type 1 vaccine candidates provide comparable efficacies in primates.

Poxvirus vectors have proven to be highly effective for boosting immune responses in diverse vaccine settings. Recent reports reveal marked differences in the gene expression of human dendritic cells infected with two leading poxvirus-based human immunodeficiency virus (HIV) vaccine candidates, New York vaccinia virus (NYVAC) and modified vaccinia virus Ankara (MVA). To understand how complex genomic changes in these two vaccine vectors translate into antigen-specific systemic immune responses, we undertook a head-to-head vaccine immunogenicity and efficacy study in the pathogenic HIV type 1 (HIV-1) model of AIDS in Indian rhesus macaques. Differences in the immune responses in outbred animals were not distinguished by enzyme-linked immunospot assays, but differences were distinguished by multiparameter fluorescence-activated cell sorter analysis, revealing a difference between the number of animals with both CD4(+) and CD8(+) T-cell responses to vaccine inserts (MVA) and those that elicit a dominant CD4(+) T-cell response (NYVAC). Remarkably, vector-induced differences in CD4(+)/CD8(+) T-cell immune responses persisted for more than a year after challenge and even accompanied antigenic modulation throughout the control of chronic infection. Importantly, strong preexposure HIV-1/simian immunodeficiency virus-specific CD4(+) T-cell responses did not prove deleterious with respect to accelerated disease progression. In contrast, in this setting, animals with strong vaccine-induced polyfunctional CD4(+) T-cell responses showed efficacies similar to those with stronger CD8(+) T-cell responses.

Influence of human T cell lymphotropic virus type 2 coinfection on virological and immunological parameters in HIV type 1-infected patients.

BACKGROUND: Human T cell lymphotropic virus type 2 (HTLV-2) infection is not rare among injection drug users with human immunodeficiency virus (HIV) infection and may exert a protective role in the progression of HIV disease. METHODS: Immunological and virological parameters were compared in HIV-HTLV-2-coinfected patients and a control group of HIV-monoinfected subjects. All individuals were antiretroviral therapy naive. HIV-specific CD8+ T cell levels were measured using an interferon-gamma assay in response to 125 optimally defined HIV peptides divided into 5 pools. Immune activation was evaluated by measuring levels of CD38 in different CD4+ and CD8+ T cell subsets. In a subgroup of patients, the production of CCL4 in parallel with interferon-gamma was assessed in response to Gag peptides. RESULTS: Lower plasma HIV-RNA levels were found in HIV-HTLV-2-coinfected patients than in HIV-monoinfected patients, despite the 2 groups having similar CD4+ T cell counts. Coinfected patients also had significantly lower levels of CD38 expression in total CD8+ T cells and in its naive subset. CD8+ T cell levels specific for each pool of peptides were similar in both groups, but cells mainly contributing to HIV Gag-specific responses in coinfected patients were CCL4 positive and interferon-gamma negative, whereas for HIV-monoinfected subjects, the response was dominated by CCL4-positive and interferon-gamma-positive cells. CONCLUSIONS: HTLV-2 coinfection may exert a protective role on HIV disease progression by lowering HIV replication and immune activation. A predominance of CCL4 single positive HIV-specific CD8+ T cells in HIV-HTLV-2-coinfected patients could explain this effect.