Low genitourinary tract risks in women living with the human immunodeficiency virus.

This review analyzes the clinical associations between specific low genitourinary tract clinical circumstances in perimenopausal and postmenopausal women living with human immunodeficiency virus (WLHIV). Modern antiretroviral therapy (ART) improves survival and reduces opportunistic infections and HIV transmission. Despite appropriate ART, WLHIV may display menstrual dysfunction, risk of early menopause, vaginal microbiome alterations, vaginal dryness, dyspareunia, vasomotor symptoms and low sexual function as compared to women without the infection. They have increased risks of intraepithelial and invasive cervical, vaginal and vulvar cancers. The reduced immunity capacity may also increase the risk of urinary tract infections, side-effects or toxicity of ARTs, and opportunistic infections. Menstrual dysfunction and early menopause may contribute to the early onset of vascular atherosclerosis and plaque formation, and increased osteoporosis risks requiring specific early interventions. On the other hand, the association between being postmenopausal and having a low sexual function is significant and related to low adherence to ART. WLHIV deserve a specific approach to manage different low genitourinary risks and complications related to hormone dysfunction and early menopause.

Protocol for assessing mortality reduction with the early use of noninvasive ventilation in prehospital emergency services: A multicentre, observational cohort study in Madrid, Spain.

BACKGROUND: Acute respiratory failure (ARF) has become one of the most prevalent serious pathologies encountered in the emergency medical service (EMS). In hospital settings, noninvasive ventilation (NIV) therapy prevents complications from more aggressive treatments for that condition. However, the scarce evidence on the benefits of NIV in prehospital EMS (i.e., during transport to the hospital) is inconclusive. OBJECTIVES: To determine whether the administration of NIV during prehospital EMS in cases of ARF reduces in-hospital mortality compared with starting NIV on arrival to in-patient EMS. METHODS: This is a multicentre, observational, prospective cohort study. We recruited a total of 317 patients from the Madrid region (Spain) who were prescribed NIV for their ARF using a nonprobabilistic consecutive sampling method. Analyses of the main outcome (in-hospital mortality) and secondary outcomes (length of hospital stay, readmissions, percentage of intensive care unit admissions, and cost-effectiveness) will include descriptive analyses of patients' characteristics, as well as bivariate and multivariate analyses and cost-effectiveness analysis. DISCUSSION: This study will provide data on NIV management in prehospital and in-patient EMS in patients with ARF. Results will contribute to the existing evidence on the benefits of NIV in the context of prehospital EMS while underlining the importance of a standardized formal training for physicians and nurses working in prehospital and in-patient EMSs. CONCLUSION: The VentilaMadrid study will provide valuable data on the clinical factors of patients receiving NIV in prehospital EMS. Further, were our hypothesis to be confirmed, our results would strongly suggest that the administration of NIV in prehospital EMS by medical and nursing profesionals formally trained in the technique reduces mortality and improves prognoses.

Three new HLA class I alleles with synonymous mutations: HLA-A*03:01:62, -C*07:02:82 and -C*12:03:42.

Three new HLA class I alleles with synonymous mutations were identified.

Pretransplant CD28 Biomarker (Levels of Expression and Quantification of Molecules per Cell) in Peripheral CD4+ T Cells Predicts Acute Rejection Episodes in Liver and Kidney Recipients.

BACKGROUND: Acute rejection (AR) remains a significant cause of graft loss. Better approaches to predict AR are being investigated. Surface CD28 protein is essential for T-cell proliferation and survival as well as cytokine production. PATIENTS AND METHODS: Pretransplant CD4+CD28+ peripheral T cells were examined in 30 liver recipients (LRs) and 31 kidney recipients (KRs) by flow cytometry. RESULTS: Pretransplant CD4+CD28+ T cells in LRs were significantly lower in rejectors than nonrejectors (P = .002). Furthermore, the total number of CD28 molecules per cell in LRs (P = .02) as well as KRs (P = .047) was significantly lower in rejectors than nonrejectors. The healthy group did not display differences when compared with patients with end-stage liver disease or renal failure; however, stratification analysis displayed higher levels of CD4+CD28+ when compared with rejected LRs (P = .04) but not KRs. CD28 levels <41.94% were able to discriminate LRs at high risk of AR (P = .003). Similarly, a total number of CD28 molecules ≤8359 (P = .031) in LRs and ≤7669 (P = .046) in KRs correlated with high risk of AR. CONCLUSION: The preliminary results presented herein exhibit a fast and noninvasive method that assists clinicians to prevent AR by monitoring CD4+CD28+ peripheral T cells.

Report From the First and Second Spanish Killer Immunoglobulin-Like Receptor Genotyping Workshops: External Quality Control for Natural Killer Alloreactive Donor Selection in Haploidentical Stem Cell Transplantation.

An important factor affecting the success in the setting of related haploidentical hematopoietic stem cell transplantation (HSCT) is the graft-versus-leukemia effect mediated by natural killer (NK) cells when the donor displays NK alloreactivity versus the recipient. NK cell function is regulated by killer immunoglobulin-like receptors (KIR) and it has been described that donor KIR genotype influences transplantation outcome. This has led to a requirement of laboratories to have a quality assurance program for validation and control of their KIR genotyping methods. The goal of the 1st and 2nd Spanish KIR Genotyping Workshops was to provide an external proficiency testing program in KIR genotyping for Spanish immunology and transplant laboratories. These workshops were conducted during the years 2014-2016 and consisted of 17 participating laboratories typing a set of 20 samples. The presence/absence of 16 mandatory KIR loci (2DL1, 2DL2, 2DL3, 2DL4, 2DL5, 2DS1, 2DS2, 2DS3, 2DS4, 2DS5, 2DP1, 3DL1, 3DL2, 3DL3, 3DS1, and 3DP1) was evaluated per sample. Methods for KIR genotyping included polymerase chain reaction with the use of sequence-specific primers and sequence-specific oligoprobes. Consensus typing was reached in all samples, and the performance of laboratories in external proficiency testing was satisfactory in all cases. The polymorphism detected in the small sample studied in both workshops is indicative of an ample variety of KIR gene profiles in the Spanish population.

Electrostatically Guided Rydberg Positronium.

We report experiments in which positronium (Ps) atoms were guided using inhomogeneous electric fields. Ps atoms in Rydberg-Stark states with principal quantum number n=10 and electric dipole moments up to 610 D were prepared via two-color two-photon optical excitation in the presence of a 670 V cm^{-1} electric field. The Ps atoms were created at the entrance of a 0.4 m long electrostatic quadrupole guide, and were detected at the end of the guide via annihilation gamma radiation. When the lasers were tuned to excite low-field-seeking Stark states, a fivefold increase in the number of atoms reaching the end of the guide was observed, whereas no signal was detected when high-field-seeking states were produced. The data are consistent with the calculated geometrical guide acceptance.

Controlling Positronium Annihilation with Electric Fields.

We show that the annihilation dynamics of excited positronium (Ps) atoms can be controlled using parallel electric and magnetic fields. To achieve this, Ps atoms were optically excited to n=2 sublevels in fields that were adjusted to control the amount of short-lived and long-lived character of the resulting mixed states. Inclusion of the former offers a practical approach to detection via annihilation radiation, whereas the increased lifetimes due to the latter can be exploited to optimize resonance-enhanced two-photon excitation processes (e.g., 1^{3}S→2^{3}P→nS/nD), either by minimizing losses through intermediate state decay, or by making it possible to separate the excitation laser pulses in time. In addition, photoexcitation of mixed states with a 2^{3}S_{1} component represents an efficient route to producing long-lived pure 2^{3}S_{1} atoms via single-photon excitation.

A trap-based pulsed positron beam optimised for positronium laser spectroscopy.

We describe a pulsed positron beam that is optimised for positronium (Ps) laser-spectroscopy experiments. The system is based on a two-stage Surko-type buffer gas trap that produces 4 ns wide pulses containing up to 5 × 10(5) positrons at a rate of 0.5-10 Hz. By implanting positrons from the trap into a suitable target material, a dilute positronium gas with an initial density of the order of 10(7) cm(-3) is created in vacuum. This is then probed with pulsed (ns) laser systems, where various Ps-laser interactions have been observed via changes in Ps annihilation rates using a fast gamma ray detector. We demonstrate the capabilities of the apparatus and detection methodology via the observation of Rydberg positronium atoms with principal quantum numbers ranging from 11 to 22 and the Stark broadening of the n = 2 → 11 transition in electric fields.

Selective production of Rydberg-stark states of positronium.

Rydberg positronium (Ps) atoms have been prepared in selected Stark states via two-step (1s→2p→nd/ns) optical excitation. Two methods have been used to achieve Stark-state selection: a field ionization filter that transmits the outermost states with positive Stark shifts, and state-selected photoexcitation in a strong electric field. The former is demonstrated for n=17 and 18 while the latter is performed for n=11 in a homogeneous electric field of 1.9 kV/cm. The observed spectral intensities and their dependence on the polarization of the laser radiation are in agreement with calculations that include the perturbations of the intermediate n=2 manifold. Our results pave the way for the generation of Rydberg Ps atoms with large electric dipole moments that are required for the realization of schemes to control their motion using inhomogeneous electric fields, an essential feature of some proposed Ps free-fall measurements requiring focused beams of long-lived atoms.

The C-terminal tail of tetraspanin proteins regulates their intracellular distribution in the parasite Trichomonas vaginalis.

The parasite Trichomonas vaginalis is the causative agent of trichomoniasis, a prevalent sexually transmitted infection. Here, we report the cellular analysis of T.vaginalis tetraspanin family (TvTSPs). This family of membrane proteins has been implicated in cell adhesion, migration and proliferation in vertebrates. We found that the expression of several members of the family is up-regulated upon contact with vaginal ectocervical cells. We demonstrate that most TvTSPs are localized on the surface and intracellular vesicles and that the C-terminal intracellular tails of surface TvTSPs are necessary for proper localization. Analyses of full-length TvTSP8 and a mutant that lacks the C-terminal tail indicates that surface-localized TvTSP8 is involved in parasite aggregation, suggesting a role for this protein in parasite : parasite interaction.

Relación de la afectación motora con la patología foniátrica en niños con parálisis cerebral / Relation of motor abnormalities with swallowing disorders in children with cerebral palsy

Introducción. La parálisis cerebral (PC) incluye trastornos motores por alteraciones no progresivas en cerebro inmaduro que pueden producir patologías de la comunicación y deglución. Objetivos. Relacionar la afectación motora de niños con PC con el desarrollo de patologías foniátricas y conocer su evaluación en hospital de tercer nivel. Material y método. Estudio descriptivo retrospectivo (7 años) con niños con PC de 4-18 años de edad. Se excluyeron pacientes en etapa preverbal, con déficits sensoriales severos y/o trastornos motores por otras enfermedades. Se recogieron datos demográficos, obstétricos y perinatales, ítems del desarrollo psicomotor, niveles motores y de manipulación medidos con las escalas Gross Motor Functional Classification System (GMFCS) y Manual Ability Classification System (MACS) y patologías foniátricas. Se realizó análisis estadístico en el conjunto de datos y por estratos (puntuación de escalas y valoración/no por foniatra). Resultados. Revisamos 3.007 historias (n = 101 según criterios inclusión; 1,7:1 varones). El perfil obstétrico predominante era embarazo normal, bajo peso al nacer y período neonatal con múltiples complicaciones. El nivel cognitivo fue aceptable en el 74,42% (IC 95%, 65,20-83,64%).Un 25,74% (IC 95%, 17,21-34,27%) fue derivado a foniatría. La muestra tenía mayores alteraciones a nivel fonético-fonológico, pero los pacientes con puntuaciones GMFCS-MACS I - III presentaban además múltiples fallos a nivel morfosintáctico y los de GMFCS-MACS IV - V (más afectados en todos los campos medidos) gran prevalencia de disfagia y disartria. Conclusiones. Creemos necesario realizar en niños con PC un screening de comunicación y disfagia desde rehabilitación infantil, apoyándose en resultados de GMFCS y MACS(AU)

Introduction. Cerebral palsy (CP) includes motor disorders due to non-progressive alterations in an immature brain that may cause communication and swallowing problems. Aims. The authors have aimed to relate motor conditions of CP children with the development of phoniatrics and to analyze their evaluation in a tertiary hospital. Material and methods. A retrospective descriptive study (7 years) was conducted with children having CP, with an age range of 4-18 years. Exclusion criteria were patients in the preverbal stage of language, with severe sensorial and/or motor deficits due to other diseases. Data were collected on demographics, obstetrics, psychomotor development, motor and manual ability levels. These were measured with the Gross Motor Functional Classification System (GMFCS) and Manual Ability Classification System (MACS) and phoniatric conditions. A statistical analysis was made of the combined data and by strata (Scale score and evaluation/not specific to speech. Results. We reviewed 3.007 histories (n=101 with inclusion criteria. Males 1.7:1). The most common obstetric profile was normal pregnancy, low birth weight and neonatal period with multiple complications. Cognitive level was described as normal in 74.42% (95% CI, 65.20-83.64%) of the records of the patients. A total of 25.74% (95% CI: 17.21-34.27%) were referred to a Language Unit. The sample showed greater alterations on the phonetic-phonology level. However, patients with GMFCS and MACS I - III scores also had multiple problems on the morphosyntactic level and those with GMFCS-MACS IV - V levels (more affected in all the fields measures) had great prevalence of dysphagia and dysarthria. Conclusions. We consider that children with CP should be screened for communication and dsyphagia from child rehabilitation, based on the results of GMFCS and MACS(AU)

Complement component C6 deficiency in a Spanish family: implications for clinical and molecular diagnosis.

Complement component C6 deficiency is a genetic disease presenting as increased susceptibility to invasive Neisseria meningitidis infections. This disorder has rarely been diagnosed in the Spanish population. In this work we report the immunochemical and molecular characterization of complement C6 deficiency in a Spanish patient showing no detectable functional activity of either the classical or alternative complement pathways and reporting a history of several episodes of meningococcal meningitis. The levels of individual complement components C3, C4, C5, C7, C8 and C9 were within the normal range. However, C6 level was low in the patient's serum as measured by radial immunodiffusion. Exon-specific polymerase chain reaction and sequencing of the C6 gene revealed a previously described homozygous single base deletion in exon 6 (c.821delA), leading to a shift in the reading frame that caused the generation of a downstream stop codon, which, in turn, provoked the truncation of the C6 protein (p.Gln274fs). To our knowledge, this is the first report on the c.821delA mutation in the Spanish population, which has previously only been identified in individuals of African ancestry. Characterization of this mutation was thought interesting in order to elucidate its source and help understand the molecular basis of this uncommon deficiency in our population. Moreover, this report highlights the importance of complement screening in cases of repeated meningococcal infections in order to establish its involvement and to consider adequate clinical recommendations such as prophylactic antibiotics or meningococcal vaccines and, subsequently, for genetic counselling.

Post-transplant increase in soluble human leukocyte antigen-G associated with non-severe cardiac allograft vasculopathy.

Cardiac allograft vasculopathy (CAV) is the single most important long-term limitation to heart transplantation. This study aimed to assess the value of monitoring soluble human leukocyte antigen-G (sHLA-G) during the first year post-transplantation to predict the severity of CAV, in 21 out of 77 heart recipients assessed by intravascular ultrasound (IVUS). Serum sHLA-G concentration increased after transplant in recipients free of severe CAV, but decreased in recipients suffering from severe CAV, significant differences between these two groups were found 6 to 12 months post-transplantation. The optimal value of the change in post-transplant sHLA-G for identifying severe CAV was ≥0.062%, which maximized sensitivity (80%) and specificity (100%). Importantly, increases in post-transplant sHLA-G were inversely associated with severe CAV, but directly associated with human cytomegalovirus reactivation. In addition, recipients presenting non-severe CAV or an increased sHLA-G post-transplantation, showed higher numbers of CD8(+)CD28(-) T cells and a down-modulation of CD28 on CD4(+) lymphocytes, which typically identifies CD8(+) regulatory T cells and anergic/tolerogenic T helper cells, respectively. In conclusion, quantification of sHLA-G might offer a complementary non-invasive method for identifying recipients at risk of more severe CAV and who might benefit from earlier preventive therapies, although these results need to be confirmed in larger series.

C1q-fixing human leukocyte antigen assay in immunized renal patients: correlation between Luminex SAB-C1q and SAB-IgG.

BACKGROUND: There is no consensus about the impact of thresholds of complement-fixing antibody assays. Recently, a C1q-SAB assay has been developed to identify complement-fixing HLA antibodies with high sensitivity and specificity. Our aim was to determine the correlation between IgG single antigens beads (SAB) and C1q-SAB assay results among patients on the renal waiting list. PATIENTS AND METHODS: Serum samples from immunized renal waiting list patients as well as negative and positive controls were valided by Luminex (LMX). These sera, which were positive for 166 antibody specificities, were tested for HLA class I in parallel by LMX-IgG and LMX-C1q. RESULTS: Comparison of antibody detection revealed no correlation based on median fluorescent intensity (MFI), levels between the IgG SAB and the C1qSAB assay (P > .05). IgG-positive sera with MFIs as low as 700 were able to fix C1q, whereas other sera with MFIs as high 14,500 did not. Furthermore, there appeared to be disparities in the profiles of class I antigens able to fix C1q-SAB. In our series, only 34% class I IgG SAB antibodies were also C1qSAB+. In several patients, we detected C1qSAB+ against IgGSAB- that was surely due to IgM antibodies. So, the C1qSAB assay detected IgM antibodies that fix complement. CONCLUSION: These data suggested that the C1q-SAB assay could be an important method to evaluate pretransplant virtual crossmatch and to define nonpermitted specificities (C1q-fixing) in kidney transplantation.

Correlation between Alt a 1 levels and clinical symptoms in Alternaria alternata-monosensitized patients.

BACKGROUND: Alternaria alternata is a risk factor for developing asthma.Alt a 1, which has been described as the major allergen in A alternata, shows a good correlation with A alternata spores only when they have germinated. OBJECTIVES: The objective of this study was to determine the correlation between spore counts and clinical symptoms in patients with allergic asthma and/or rhinitis monosensitized to A alternata. METHODS: Two types of samplers were used to determine exposure: a Burkard spore trap to collect A alternata spores and a high-volume air sampler to collect airborne particles. A total of 366 air filters were collected. Alt a 1 levels were measured by monoclonal antibody-based enzyme-linked immunosorbent assay. Eighteen monosensitized patients were asked to record their daily symptoms throughout the year. RESULTS: A alternata spores were detected throughout the year, whereas Alt a 1 was detected only between March and December. Symptoms showed positive and significant correlations with spore counts (r=0.459, P<.001), and Alt a 1 levels (r=0.294, P<.001). The correlation between spores and Alt a 1 was low. The negative binomial model proved that an increase of 10 pg/m3 in Alt a 1 levels increased the number of symptoms at a 3-day lag by 5%. CONCLUSIONS: In patients who are allergic to A alternata, Alt a 1 levels can be considered an important marker for predicting the risk of respiratory symptoms.

Protein palmitoylation inhibition by 2-bromopalmitate alters gliding, host cell invasion and parasite morphology in Toxoplasma gondii.

Protein palmitoylation is the reversible covalent attachment of palmitic acid onto proteins. This post-translational modification has been shown to play a part in diverse processes such as signal transduction, cellular localization and regulation of protein activity. Although many aspects of protein palmitoylation have been identified in mammalian and yeast cells, little is known of this modification in Toxoplasma gondii. In order to determine the functional role of protein palmitoylation in T. gondii, tachyzoites were treated with the palmitoylation inhibitor 2-bromopalmitate (2-BP). Parasites treated with 2-BP displayed a significant increase in non-circular trails which were longer than those trails left by non-treated parasites. Furthermore, 2-BP treatment reduced the invasion process to the host cells. Long-term treatment of intracellular tachyzoites resulted in major changes in parasite morphology and shape in a dose-dependent manner. These results suggest that palmitoylation could be modifying proteins that are key players in gliding, invasion and cytoskeletal proteins in T. gondii.

Afección musculoesquelética asociada a amputados de miembro inferior / Musculoskeletal diseases associated with leg amputees

Introducción. La amputación de miembros inferiores supone nuevos patrones biomecánicos de carga y marcha, pudiendo aparecer lesiones por sobrecarga o desuso. Objetivo. Describir la prevalencia y el tratamiento de estas lesiones en la Unidad de Amputados de un hospital de tercer nivel y compararlos con la bibliografía. Material y método. Se realizó un estudio descriptivo transversal (n=46) de 6 meses de duración usando un cuestionario propio en el que se incluían los datos demográficos, la fecha y etiología de amputación, uso o no de prótesis, existencia de «síndrome del dolor del miembro fantasma (MF)», crisis de lumbalgias recientes, osteoporosis, fracturas y/o caídas en los últimos 6 meses, artrosis en miembros inferiores, osificaciones anómalas y tendinitis. Se recogió la localización, frecuencia, intensidad del dolor (medida con Escala Visual Analógica, EVA) y el tratamiento de cada uno de ellos. Los datos se analizaron con SPSS Stadistics 18.0, en conjunto y por estratos de nivel de amputación y protetización y se compararon con la bibliografía. Resultados. La edad media de los encuestados era de 60,15±14,07 años, con predominio de varones (86,95%) y etiología vascular (61%).El tiempo de amputación medio era de 5 años y el 56% de ellos estaba protetizado. La afección dolorosa predominante fue el «síndrome del dolor del MF». En cuanto a la afección traumática, hallamos el 15,2% de tendinitis, el 61,3% de caídas y el 6,5% de fracturas en los últimos 6 meses. El 21,6% presentaban alteraciones óseas no traumáticas tales como osteoporosis y osificaciones anómalas. Conclusiones. En la planificación del tratamiento integral de amputados es importante atender a las afecciones musculoesqueléticas por su frecuente asociación (AU)

Introduction. Lower limbs amputations and the use of prostheses require new biomechanical walk patterns that can produce injuries. Aim. To describe the prevalence and treatment of these diseases in lower limb amputees in the 'Amputees unit' of a tertiary hospital and to compare these with the literature. Material and methods. A cross-sectional, descriptive study of 6 months duration was conducted on 46 subjects. A self-administered questionnaire was used, which included, demography data, the date and aetiology of amputation, the use or not of a prosthesis, 'Phantom Pain Syndrome', low back pain, osteoporosis, fractures or falls in the last 6 months, osteoarthritis, poor ossifications, and tendon inflammation. We also collected the location, frequency, intensity (EVA) and treatment of all of them. The data were analysed using the program SPSS Statistics 18.0 and then compared with that in the literature. Results. The mean age was 60±14.07 years. The predominant sex was male (86.95%), and the most frequent aetiology was vascular limb damage (61%). The mean time since amputation was 5 years, and 56% of the patients used a prosthesis. The most frequent source of pain was 'phantom'. Traumatic pathology: 15.2% of tendon injuries, 61.3% of falls in the last 6months, and 6.5% of bone fractures. Non-traumatic pathologies: 21.6%. Conclusion. In order to offer an integral treatment to amputees it is important to know these pathologies because of the frequent association (AU)