Podocituria y preeclampsia

El podocito es una célula altamente diferenciada localizada en la membrana basal del glomérulo. Entre sus múltiples funciones está garantizar la integridad y funcionalidad de la principal unidad de filtración del riñón, pero carece de la capacidad de dividirse bajo condiciones normales y en situaciones de estrés presenta el riesgo de separarse de la membrana basal, lo que conlleva la posibilidad de desarrollar proteinuria como primer paso de un daño renal que puede llegar a ser permanente. Una de estas situaciones de estrés es el embarazo y, en particular, los trastornos hipertensivos gestacionales, lo que coloca al podocito en la peculiar posición de poderse utilizar como prueba diagnóstica o como marcador de pronóstico renal a largo plazo. En esta revisión veremos el papel del podocito en estos escenarios. (provisto por Infomedic International)

The podocyte is a highly differentiated cell located in the basement membrane of the glomerulus. Among its multiple functions is to guarantee the integrity and functionality of the main filtration unit of the kidney, but it lacks the capacity to divide under normal conditions and in stressful situations it presents the risk of separating from the basement membrane, leading to the possibility of developing proteinuria as the first step of renal damage that may become permanent. One of these stressful situations is pregnancy and, in particular, gestational hypertensive disorders, which places the podocyte in the peculiar position of being able to be used as a diagnostic test or as a marker of long-term renal prognosis. In this review we will look at the role of the podocyte in these scenarios. (provided by Infomedic International)

Editorial - ¿Por qué investigamos?

Si buscan los orígenes del "ayuno intermitente", una forma de restricción calórica donde solo se ingieren alimentos por periodos cortos de tiempo (generalmente 8 horas), descubrirán algo interesante. A pesar de la popularidad del concepto y de que en los tiempos modernos muchos gurús de la alimentación, incluyendo médicos, lo apoyan y promueven, sus raíces datan de 1915. Estos ensayos iniciales culminaron con un capítulo publicado en el libro Obesity: its pathogenesis and management. El capítulo mencionaba ayunos de uno a catorce días, sugiriendo resultados espectaculares. Esta información, que requería un riguroso proceso de replicabilidad para demostrar su eficacia, saltó a las revistas culturales sin ser confirmada por otros expertos. Una vez algo pasa del terreno científico al popular, se convierte en conocimiento público y su uso crece de manera exponencial. Esto llevó a que, ya en los setenta, médicos e investigadores advirtieran del riesgo de estas terapias que buscaban soluciones rápidas a un problema mucho más profundo. (provisto por Infomedic International)

If you look up the origins of intermittent fasting, a form of calorie restriction where food is only eaten for short periods of time (usually 8 hours), you will discover something interesting. Despite the popularity of the concept and the fact that in modern times many food gurus, including physicians, support and promote it, its roots date back to 1915. These early trials culminated in a chapter published in the book Obesity: its pathogenesis and management. The chapter mentioned fasts of one to fourteen days, suggesting spectacular results. This information, which required a rigorous replication process to prove its efficacy, jumped into the cultural magazines without being confirmed by other experts. Once something moves from the scientific to the popular arena, it becomes public knowledge and its use grows exponentially. This led, as early as the 1970s, physicians and researchers to warn of the risk of these therapies that sought quick fixes to a much deeper problem. (provided by Infomedic International)

Incidence of Respiratory Syncytial Virus-Associated Lower Respiratory Tract Illness in Infants in Low- and Middle-Income Regions During the Coronavirus Disease 2019 Pandemic.

Background: Incidence data of respiratory syncytial virus-associated lower respiratory tract illness (RSV-LRTI) are sparse in low- and middle-income countries (LMICs). We estimated RSV-LRTI incidence rates (IRs) in infants in LMICs using World Health Organization case definitions. Methods: This prospective cohort study, conducted in 10 LMICs from May 2019 to October 2021 (largely overlapping with the coronavirus disease 2019 [COVID-19] pandemic), followed infants born to women with low-risk pregnancies for 1 year from birth using active and passive surveillance to detect potential LRTIs, and quantitative reverse-transcription polymerase chain reaction on nasal swabs to detect RSV. Results: Among 2094 infants, 32 (1.5%) experienced an RSV-LRTI (8 during their first 6 months of life, 24 thereafter). Seventeen (0.8%) infants had severe RSV-LRTI and 168 (8.0%) had all-cause LRTI. IRs (95% confidence intervals [CIs]) of first RSV-LRTI episode were 1.0 (.3-2.3), 0.8 (.3-1.5), and 1.6 (1.1-2.2) per 100 person-years for infants aged 0-2, 0-5, and 0-11 months, respectively. IRs (95% CIs) of the first all-cause LRTI episode were 10.7 (8.1-14.0), 11.7 (9.6-14.0), and 8.7 (7.5-10.2) per 100 person-years, respectively. IRs varied by country (RSV-LRTI: 0.0-8.3, all-cause LRTI: 0.0-49.6 per 100 person-years for 0- to 11-month-olds). Conclusions: RSV-LRTI IRs in infants in this study were relatively low, likely due to reduced viral circulation caused by COVID-19-related nonpharmaceutical interventions. Clinical Trials Registration: NCT03614676.

Del Impacto de las Investigaciones

Cuando un investigador se plantea esa primera pregunta que se convertirá en un protocolo, no sabe lo que se encontrará al final del camino. Puede tener una hipótesis de trabajo, pero la realidad es que el mundo real es muy peculiar y las respuestas obtenidas pueden no ser las esperadas. Sin embargo, ese es el propósito de cualquier investigación: llegar a un descubrimiento, sin olvidar que trabajamos con probabilidades y no con verdades absolutas. Lo que fallamos en contemplar es que esta cadena de procesos y decisiones van más allá de la sección "Resultados" del artículo que esperamos escribir. Una vez plasmamos en papel el fruto de nuestro trabajo, lo estamos convirtiendo en un material de uso global y el mismo puede ser utilizado de muchas formas. Puede ser aprovechado por miembros del personal de salud en el manejo de sus pacientes o servir de elemento educativo en programas de residencia de todo el mundo. En ambos escenarios vemos una arista de las repercusiones y del alcance que tiene el esfuerzo emprendido al iniciar un proyecto de investigación. Sage Policy Profiles es parte de la red Social Science Space y publicaron hace poco una herramienta de gran utilidad (https://policyprofiles.sagepub.com) que puede ser usada para responder esa interrogante. Permite buscar los artículos de un investigador y determinar en qué documentos de políticas públicas se han mencionado los mismos. Este simple ejercicio les abrirá los ojos al mostrarles el inmenso alcance que tienes sus estudios y, a la vez, funciona como un recordatorio de la importancia de ejecutar sus protocolos de la mejor manera posible. Lo que se publica no es un grupo de páginas llenas de letras. Es un conocimiento destilado, plasmado para ayudar en el progreso de la ciencia. Como tal, no se quedará en la institución en la que labora. Se esparcirá por el mundo, atravesando fronteras y modificando la atención de personas que nunca conocerán su nombre. Cambiemos el mundo un artículo a la vez.

Sobre el método científico

Se conoce como Método Científico a la secuencia de pasos que se deben seguir para obtener un conocimiento que sea válido desde la perspectiva de las ciencias. Este método, que rige la forma como hacemos investigaciones, se apoya sobre dos grandes pilares: la reproducibilidad y la refutabilidad. La reproducibilidad implica que un determinado experimento debe ser capaz de ser reproducido por cualquier persona en cualquier lugar, aunque no necesariamente obteniendo los mismos resultados. Es por esto por lo que insistimos en que las conclusiones alcanzadas por un determinado investigador no pueden ni deben ser tomadas como ley absoluta, ya que las estadísticas nos dicen que dicho resultado puede ser fruto del azar y que solo repitiendo el mismo podemos estar seguros de la veracidad de las conclusiones alcanzadas. Uno de los mayores errores cometidos por los investigadores modernos es perseguir la primicia de un hallazgo y querer ser los primeros en decir o encontrar algo, lo que no es más que un intento de satisfacer el ego. Es igual de importante repetir los estudios ejecutados por otras personas y ver si se obtienen los mismos resultados en idénticas circunstancias. Son estas evaluaciones subsecuentes las que dan valor a los resultados de una investigación y las que nos permiten establecer la utilidad de aplicarlos de manera global en la población general. (provisto por Infomedic International)

The Scientific Method is the sequence of steps that must be followed to obtain knowledge that is valid from the perspective of science. This method, which governs the way we do research, rests on two main pillars: reproducibility and refutability. Reproducibility implies that a given experiment should be able to be reproduced by anyone anywhere, although not necessarily obtaining the same results. This is why we insist that the conclusions reached by a given researcher cannot and should not be taken as an absolute law, since statistics tell us that such a result may be the result of chance and that only by repeating it can we be sure of the veracity of the conclusions reached. One of the biggest mistakes made by modern researchers is to pursue the scoop of a finding and want to be the first to say or find something, which is nothing more than an attempt to satisfy the ego. It is just as important to repeat studies performed by others and see if the same results are obtained under identical circumstances. It is these subsequent evaluations that give value to the results of an investigation and that allow us to establish the usefulness of applying them globally in the general population. (provided by Infomedic International)

Safety and Immunogenicity of an Investigational Respiratory Syncytial Virus Vaccine (RSVPreF3) in Mothers and Their Infants: A Phase 2 Randomized Trial.

BACKGROUND: In a phase 1/2 study, a maternal respiratory syncytial virus vaccine candidate (RSVPreF3) demonstrated an acceptable safety profile and efficiently increased RSV-specific humoral immune responses in non-pregnant women. METHODS: In this phase 2 observer-blind, placebo-controlled, randomized clinical trial (NCT04126213), the safety of RSVPreF3 (60 or 120 µg), administered during late second or third trimester, was evaluated in 213 18- to 40-year-old healthy pregnant women through 6 months postdelivery and their offspring through infancy; immunogenicity was evaluated through day 43 postdelivery and day 181 postbirth, respectively. RESULTS: RSVPreF3 was well tolerated. No pregnancy-related or neonatal adverse events of special interest were considered vaccine/placebo related. In the 60 and 120 µg RSVPreF3 groups: (1) neutralizing antibody (nAb) titers in mothers increased 12.7- and 14.9-fold against RSV-A and 10.6- and 13.2-fold against RSV-B, respectively, 1 month postvaccination and remained 8.9-10.0-fold over prevaccination at day 43 postdelivery; (2) nAb titers were consistently higher compared to placebo recipients; (3) placental transfer ratios for anti-RSVPreF3 antibodies at birth were 1.62 and 1.90, respectively, and (4) nAb levels in infants were highest at birth and declined through day 181 postbirth. CONCLUSIONS: RSVPreF3 maternal vaccination had an acceptable safety risk profile and induced robust RSV-specific immune responses with successful antibody transfer to their newborns. CLINICAL TRIALS REGISTRATION: NCT04126213.

WHAT IS THE CONTEXT?: Infants, especially those less than 6 months of age, are at increased risk of lung infection caused by respiratory syncytial virus (RSV). However, this risk could be reduced with maternal vaccination against RSV during pregnancy. A previous clinical trial found that a vaccine candidate (named RSVPreF3) was well tolerated when given to non-pregnant women. WHAT IS NEW?: In pregnant women, RSVPreF3 was also well tolerated. Occurrence of unsolicited adverse events was similar between vaccine and placebo recipients. None of the serious adverse events or events of interest for pregnant women or newborns were considered related to the study intervention. One month after vaccination, mothers who received RSVPreF3 had 11­15 times higher levels of antibodies against RSV than before vaccination. These antibody levels remained similar until 43 days after delivery. In the infants born to mothers vaccinated during pregnancy with RSVPreF3, antibody levels were highest at birth, when levels were higher than in their mothers, and declined through day 181 postbirth. WHAT IS THE IMPACT?: RSVPreF3 had an acceptable safety risk profile in pregnant women and their babies. This vaccine induced potent immune responses against RSV, with maternal antibodies transferred to infants of the vaccinated mothers.

Preoperative vaginal cleansing with chlorhexidine vs placebo in patients with rupture of membranes: a prospective, randomized, double-blind, placebo-control study.

BACKGROUND: XXX OBJECTIVE: This study aimed to demonstrate that vaginal cleansing with a 4% chlorhexidine solution before cesarean delivery in patients with a history of rupture of membranes prevents postoperative infectious complications (endometritis, surgical site infections). STUDY DESIGN: A total of 204 patients with premature rupture of membranes or who were in labor for more than 6 hours after membranes ruptured were randomized before a cesarean delivery to preoperative vaginal cleansing with a chlorhexidine solution (n=97 patients) or to placebo cleansing with saline solution (n=107 patients). The management of the rupture of membranes and the cesarean delivery procedure were conducted according to standard local protocols for both groups, including the use of antibiotics. RESULTS: Vaginal cleansing with chlorhexidine reduced the risk for endometritis after cesarean delivery in patients with rupture of membranes when compared with placebo cleansing (chlorhexidine, 7.21% vs placebo, 18.8%; relative risk, 0.39; 95% confidence interval, 0.17-0.87; P=.015). Likewise, there was a statistically significant reduction in the number of cases of puerperal fever (chlorhexidine, 9.28% vs placebo, 19.8%; relative risk, 0.47; 95% confidence interval, 0.23-0.98; P=.037). There was a statistical difference between the groups in prolongation of hospitalization for >72 hours (chlorhexidine, 1.03% vs placebo, 7.55%; relative risk, 0.14; 95% confidence interval, 0.02-1.08; P=.02), although the confidence interval suggests that the effect was by chance. There were no statistical differences in surgical site infection at 7 days (chlorhexidine, 1.03% vs placebo, 0.94%; relative risk, 1.1; 95% confidence interval, 0.07-17.4; P=.94) and 15 days after the procedure (chlorhexidine, 1.03% vs placebo, 0%; relative risk, 3.31 [using a continuity correction]; 95% confidence interval, 0.14-80.21; P=.29). CONCLUSION: The use of chlorhexidine for vaginal cleansing before a cesarean delivery in patients with rupture of membranes reduced the risk for endometritis and puerperal fever. It also reduced the number of cases that required hospitalization for more than 3 days, but the confidence interval suggests that it could be by chance. It has no effect on the number of cases with surgical site infection.

Restless Legs Syndrome and Severe Preeclampsia: A Case-Control Study.

OBJECTIVE: This study sought to determine whether there is an association between restless legs syndrome (RLS) and severe preeclampsia using a case-control study design. METHODS: A total of 147 patients with severe preeclampsia and 147 patients with normal pregnancies were evaluated for symptoms of RLS. In the first phase, before or immediately after delivery, participants were given a questionnaire on common complaints experienced during pregnancy. Mixed with these complaints were the symptoms that comprised the diagnostic criteria for RLS. If a participant indicated she met the diagnositic criteria, she was informed about RLS. In the second phase, a severity evaluation was performed in this population using the International Restless Legs Syndrome Study Group Rating Scale. RESULTS: Among the participants, independent of the presence of preeclampsia, 13.61% met the criteria for a diagnosis of RLS. There was no statistical difference between groups (severe preeclampsia: 12.93% vs. controls: 14.29%; odds ratio [OR] 0.89; 95% CI 0.46-1.74, P = 0.37). After analysis, 65% of patients with RLS had a score on the International Restless Legs Syndrome Study Group Rating Scale compatible with "very severe" or "severe" RLS. There was again no statistical difference between groups for the combination of "severe" and "very severe" scoring criteria (severe preeclampsia: 68.42% vs. controls: 61.90%; OR 1.33; 95% CI 0.36-4.93, P = 0.66) and "very severe" alone (severe preeclampsia: 21.05% vs. controls: 4.76%; OR 5.33; 95% CI 0.54-52.73, P = 0.11). CONCLUSION: The prevalence of RLS among pregnant women in our study was in accordance with the medical literature and avoided the probable bias caused by the high number of other symptoms experienced during pregnancy. There were no significant differences between normotensive participants and those with severe preeclampsia. In general, symptom severity was high, with a tendency toward greater severity in patients with severe preeclampsia, but this difference did not reach statistical significance.

Use of Topical Lidocaine Gel Plus Paracervical Blockade vs. Paracervical Blockade Alone for Pain Management During Manual Vacuum Aspiration: ADouble-Blind, Randomized, Placebo-Controlled Trial.

OBJECTIVE: To evaluate if the use of lidocaine gel applied to the cervix prior to manual vacuum aspiration (MVA) in addition to paracervical blockade is useful in reducing the level of pain associated with the procedure. METHODS: A total of 88 patients were randomized to receive either 5 mL of lidocaine gel or a placebo applied topically to the cervix 5 minutes prior to paracervical blockade. Both groups received the same drugs for pain control (tramadol hydrochloride, diazepam, and sodium diclofenac). A visual analogue scale (VAS) was used for evaluation of pain intensity at two times: 2 minutes before the blockade (directly after tenaculum clamping of the anterior aspect of the cervix) and after MVA of the uterine cavity. RESULTS: There was a statistically significant difference in pain intensity between the arms of the study. At the first evaluation time (cervical clamping), VAS pain score for the placebo group (control) was 3.6 (2.1) and that for the lidocaine gel group (case) was 1.2 (1.4) (P < 0.01). At the second evaluation time (after manual vacuum aspiration), VAS pain score perceived by the control group was 5.3 (2.5) and that for the case group was 3.1 (1.9) (P < 0.01). The use of lidocaine gel was not associated with any adverse effects of interest. CONCLUSION: The use of a topical lidocaine gel plus paracervical blockade was effective in reducing the intensity of pain associated with MVA when compared to paracervical blockade alone.

Safety and Therapeutic Profile of a GnRH-Based Vaccine Candidate Directed to Prostate Cancer. A 10-Year Follow-Up of Patients Vaccinated With Heberprovac.

Heberprovac is a GnRH based vaccine candidate containing 2.4 mg of the GnRHm1-TT peptide as the main active principle; 245 µg of the very small size proteoliposomes adjuvant (VSSP); and 350 µL of Montanide ISA 51 VG oil adjuvant. The aim of this study was to assess the safety and tolerance of the Heberprovac in advanced prostate cancer patients as well as its capacity to induce anti-GnRH antibodies, the subsequent effects on serum levels of testosterone and PSA and the patient overall survival. The study included eight patients with histologically-proven advanced prostate cancer with indication for hormonal therapy, who received seven intramuscular immunizations with Heberprovac within 18 weeks. Anti-GnRH antibody titers, testosterone and PSA levels, as well as clinical parameters were recorded and evaluated. The vaccine was well tolerated. Significant reductions in serum levels of testosterone and PSA were seen after four immunizations. Castrate levels of testosterone were observed in all patients at the end of the immunization schedule, which remained at the lowest level for at least 20 months. In a 10-year follow-up three out of six patients who completed the entire trial survived. In contrast only one out eight patients survived in the same period in a matched randomly selected group receiving standard anti-hormonal treatment. Heberprovac vaccination showed a good security profile, as well as immunological, biochemical and, most importantly, clinical benefit. The vaccinated group displayed survival advantage compared with the reference group that received standard treatment. These results warrant further clinical trials with Heberprovac involving a larger cohort.

Type of Blunt Expansion of the Low Transverse Uterine Incision During Caesarean Section and the Risk of Postoperative Complications: A Prospective Randomized Controlled Trial.

OBJECTIVE: To evaluate two techniques of uterine incision expansion (cephalad-caudad vs. transverse) during Caesarean section (CS). METHODS: A total of 839 patients were randomized to either a cephalad-caudad blunt expansion of uterine incision during CS versus a transverse (lateral-lateral) expansion. The primary outcome was blood loss, measured with the descent of hemoglobin level. Secondary outcomes were the need for blood transfusion and the number of surgical or postoperative complications presented in both groups. RESULTS: There was no statistical difference with regard to decrease in hemoglobin level, but there was a higher number of surgical complications in the transverse expansion group (Cephalad-caudad: 11.53% vs. transverse: 16.42%; odds ratio [OR] 0.66; 95% confidence interval [CI] 0.45-0.98; P = 0.04). There were more cases of unintended extensions of uterine incision (10.35% vs. 16.18%; OR 0.6; 95% CI 0.4-0.9; P = 0.01) but no statistical difference in the number of hematomas, uterine vessel injury, or the need to transfuse. CONCLUSION: The cephalad-caudad blunt expansion technique of the low transverse uterine incision is safer than the transverse expansion. There was no difference in regard to decrease in hemoglobin level, but there is a lower risk of surgical complications not associated with an increased need for blood transfusions when compared with the transverse expansion.

Characterization of low-abundance species in the active pharmaceutical ingredient of CIGB-300: A clinical-grade anticancer synthetic peptide.

CIGB-300 is a first-in-class synthetic peptide-based drug of 25 amino acids currently undergoing clinical trials in cancer patients. It contains an amidated disulfide cyclic undecapeptide fused to the TAT cell-penetrating peptide through a beta-alanine spacer. CIGB-300 inhibits the CK2-mediated phosphorylation leading to apoptosis of tumor cells in vitro, and in vivo in cancer patients. Despite the clinical development of CIGB-300, the characterization of peptide-related impurities present in the active pharmaceutical ingredient has not been reported earlier. In the decision tree of ICHQ3A(R2) guidelines, the daily doses intake, the abundance, and the identity of the peptide-related species are pivotal nodes that define actions to be taken (reporting, identification, and qualification). For this, purity was first assessed by reverse-phase chromatography (>97%) and low-abundance impurities (≤0.27%) were collected and identified by mass spectrometry. Most of the impurities were generated during peptide synthesis, the spontaneous air oxidation of the reduced peptide, and the lyophilization step. The most abundant impurity, with no biological activity, was the full-length peptide containing Met17 transformed into a sulfoxide residue. Interestingly, parallel and antiparallel dimers of CIGB-300 linked by 2 intermolecular disulfide bonds exhibited a higher antiproliferative activity than the CIGB-300 monomer. Likewise, very low abundance trimers and tetramers of CIGB-300 linked by disulfide bonds (≤0.01%) were also detected. Here we describe for the first time the presence of active dimeric species whose feasibility as novel CIGB-300 derived entities merits further investigation.

Effects of postpartum uterine curettage in the recovery from Preeclampsia/Eclampsia. A randomized, controlled trial.

OBJECTIVE: To evaluate if postpartum uterine curettage improved the clinical and laboratory parameters in patients with preeclampsia or eclampsia. METHODS: A total of 442 patients with preeclampsia/eclampsia were randomized to postpartum curettage (223) or no procedure (219). Systolic and diastolic blood pressure were recorded and analyzed at hours 6, 12, 24 and 48. Also, several laboratory values and diuresis were evaluated. RESULTS: No statistical differences were found between groups (curettage vs. no procedure) in regards to systolic [155.74(15.43) vs. 156.81(15.58)] and/or diastolic blood pressure [101.51(11.44) vs. 101.70(11.20)] before and after the allocated procedure, starting at hour 6 [SBP: 134.19(13.11) vs. 136.65(15.36); DBP: 87.20(9.42) vs. 88.57(10.98)] and up to 48 h after delivery [SBP: 126.59(15.54) vs. 128.21(13.85); DBP: 81.86(9.92) vs. 81.67(11.33)]. No statistical differences between groups were found in the rate of recovery of laboratory values, as well as in the need for additional antihypertensive medications in the postpartum period. These results applied to patients with severe preeclampsia (210 patients in both arms) and eclampsia (13 vs. 9). There were no cases of postpartum eclampsia or acute renal failure after delivery in any of the groups. CONCLUSION: To perform a postpartum uterine curettage does not present an advantage in the patient with preeclampsia/eclampsia. The procedure dos not improve clinical or laboratory values.

The first report of cases of pet dogs with naturally occurring cancer treated with the antitumor peptide CIGB-552.

The absence of an effective therapy against human solid tumors has fostered the development of promising antineoplastic therapeutic candidates, as the CIGB-552 peptide. This synthetic peptide has shown to be effective in reducing tumor size and increasing the lifespan in tumor-bearing mice. Therefore, this work was aimed to explore the safety profile and preliminary assessment of antitumor activity of the CIGB-552 peptide therapeutic candidate in a small population of dogs (n=9) having malignant spontaneously-arising solid tumors. The peptide was administered by subcutaneous (s.c.) route, at three dosage levels (0.075, 0.15 and 0.3mg/kg). The results showed no dose-limiting toxicities in any dogs. The antitumor activity observed in dogs receiving CIGB-552 was associated with the reduction in the tumor volume. Given the antitumor effects of CIGB-552 as mediated by COMMD1 protein, which function is highly conserved among eukaryotic organisms, and the similarities of canine and human types of cancer with respect to tumor biology, it is likely that CIGB-552 could demonstrate comparable anti-cancer activity in human patients. Synthetic peptide, COMMD1, Tumor, Dog, CIGB-552.

A deeper mining on the protein composition of VA-MENGOC-BC®: An OMV-based vaccine against N. meningitidis serogroup B and C.

The protein composition of an Outer Membrane Vesicle (OMV) preparation that constitutes the active pharmaceutical ingredient of VA-MENGOC-BC®, an effective vaccine against Neisseria meningitidis serogroups B, and C is presented. This preparation has a high lipid content and five abundant membrane proteins (FetA, PorA, PorB, RmpM, and Opc), constituting approximately 70% of the total protein mass. The protein composition was determined by combining the use of the Hexapeptide Ligand Library and an orthogonal tandem fractionation of tryptic peptides by reverse-phase chromatography at alkaline and acid pH. This approach equalizes the concentration of tryptic peptides derived from low- and high-abundance proteins as well as considerably simplifying the number of peptides analyzed by LC-MS/MS, enhancing the possibility of identifying low-abundance species. Fifty-one percent of the proteins originally annotated as membrane proteins in the genome of the MC58 strain were identified. One hundred and sixty-eight low-abundance cytosolic proteins presumably occluded within OMV were also identified. Four (NadA, NUbp, GNA2091, and fHbp), out of the five antigens constituting the Bexsero® vaccine, were detected in this OMV preparation. In particular, fHbp is also the active principle of the Trumenba® vaccine developed by Pfizer. The HpuA and HpuB gene products (not annotated in the MC58 genome) were identified in the CU385 strain, a clinical isolate that is used to produce this OMV. Considering the proteins identified here and previous work done by our group, the protein catalogue of this OMV preparation was extended to 266 different protein species.

Gradual reduction of testosterone using a gonadotropin-releasing hormone vaccination delays castration resistance in a prostate cancer model.

In a previous study aimed to design a novel prostate cancer vaccine, the authors of the present study demonstrated the advantage of combining the adjuvants Montanide ISA 51 with very small size proteoliposomes (VSSP) to promote a significant humoral immune response to gonadotropin-releasing hormone (GnRH) in healthy animals. The present study compared the efficacy of this vaccine formulation versus the standard treatment currently available in terms of preventing the development of tumors in DD/S mice injected with Shionogi carcinoma (SC) 115 cells. The results demonstrated that 5 non-vaccinated control mice exhibited a fast tumor growth, and succumbed to the disease within 19-31 days. Mice immunized with the GnRH/Montanide ISA 51/VSSP vaccine exhibited a moderate decline in testosterone levels that was associated with a decrease in anti-GnRH antibody titers, which lead to a sustained tumor growth inhibition. In total, 2 mice in the immunized group exhibited complete remission of the tumor for the duration of the present study. In addition, castrated mice, which were used as a control for standard hormonal therapy, exhibited an accelerated decrease in tumor size. However, tumor relapse was observed between days 50 and 54, and between days 65 and 85, following the injection of SC 155 cells. Therefore, these mice were sacrificed at day 90. The present study concludes that the slow and moderate reduction of testosterone levels observed using the GnRH-based vaccine may delay the appearance of castration resistance in a Shionogi prostate cancer model. These findings suggest that this vaccine may be used to delay castration resistance in patients with prostate cancer.

Identification of Vimentin as a Potential Therapeutic Target against HIV Infection.

A combination of antiviral drugs known as antiretroviral therapy (ART) has shown effectiveness against the human immunodeficiency virus (HIV). ART has markedly decreased mortality and morbidity among HIV-infected patients, having even reduced HIV transmission. However, an important current disadvantage, resistance development, remains to be solved. Hope is focused on developing drugs against cellular targets. This strategy is expected to prevent the emergence of viral resistance. In this study, using a comparative proteomic approach in MT4 cells treated with an anti-HIV leukocyte extract, we identified vimentin, a molecule forming intermediate filaments in the cell, as a possible target against HIV infection. We demonstrated a strong reduction of an HIV-1 based lentivirus expressing the enhanced green fluorescent protein (eGFP) in vimentin knockdown cells, and a noteworthy decrease of HIV-1 capsid protein antigen (CAp24) in those cells using a multiround infectivity assay. Electron micrographs showed changes in the structure of intermediate filaments when MT4 cells were treated with an anti-HIV leukocyte extract. Changes in the structure of intermediate filaments were also observed in vimentin knockdown MT4 cells. A synthetic peptide derived from a cytoskeleton protein showed potent inhibitory activity on HIV-1 infection, and low cytotoxicity. Our data suggest that vimentin can be a suitable target to inhibit HIV-1.

Zika y defecto del tubo neural

Presentamos el primer caso confirmado de neonato con microcefalia relacionado a Zika en Panamá, quien además presentaba lesión a nivel del occipucio compatible con encefalocele.

We report the first confirmed case of newborn with microcephaly related with Zika in Panama, who also had lesions to the occiput compatible with encephalocele.

Incidence of eclampsia with HELLP syndrome and associated mortality in Latin America.

OBJECTIVE: To describe the maternal outcome among women with eclampsia with and without HELLP syndrome (hemolysis, elevated liver enzymes, and low platelet count). METHODS: A cross-sectional study of women with eclampsia was undertaken in 14 maternity units in Latin America between January 1 and December 31, 2012. Outcomes were compared between women with and without concomitant HELLP syndrome. Logistic regression analysis was performed to identify independent risk factors of maternal mortality. RESULTS: There were 196 eclampsia cases among 115 038 deliveries; 142 (72.4%) women had eclampsia alone and 54 (27.6%) women had concomitant HELLP syndrome. Severe systolic hypertension (≥160 mm Hg), severe diastolic hypertension (≥110 mm Hg), and hypertensive encephalopathy were significantly more common among women with HELLP than among those with eclampsia alone (P=0.01 for all). There were 8 (4.1%) maternal deaths, all in the group with HELLP syndrome, and 18 (9.1%) perinatal deaths. In a multivariate regression model, maternal mortality was significantly associated with low platelet count and severe systolic hypertension (P<0.05). CONCLUSION: Eclampsia with HELLP syndrome is a dangerous complication associated with pregnancy. Low platelet count secondary to HELLP syndrome and severe systolic hypertension were independently associated with maternal mortality from eclampsia.