Microsatellite Genotyping of Plasmodium vivax Isolates from Pregnant Women in Four Malaria Endemic Countries

Plasmodium vivax is the most widely distributed human parasite and the main cause of human malaria outside the African continent. However, the knowledge about the genetic variability of P. vivax is limited when compared to the information available for P. falciparum. We present the results of a study aimed at characterizing the genetic structure of P. vivax populations obtained from pregnant women from different malaria endemic settings. Between June 2008 and October 2011 nearly 2000 pregnant women were recruited during routine antenatal care at each site and followed up until delivery. A capillary blood sample from the study participants was collected for genotyping at different time points. Seven P. vivax microsatellite markers were used for genotypic characterization on a total of 229 P. vivax isolates obtained from Brazil, Colombia, India and Papua New Guinea. In each population, the number of alleles per locus, the expected heterozygosity and the levels of multilocus linkage disequilibrium were assessed. The extent of genetic differentiation among populations was also estimated. Six microsatellite loci on 137 P. falciparum isolates from three countries were screened for comparison. The mean value of expected heterozygosity per country ranged from 0.839 to 0.874 for P. vivax and from 0.578 to 0.758 for P. falciparum. P. vivax populations were more diverse than those of P. falciparum. In some of the studied countries, the diversity of P. vivax population was very high compared to the respective level of endemicity. The level of inter-population differentiation was moderate to high in all P. vivax and P. falciparum populations studied

Implementation of a multidisciplinary psychoeducational intervention for Parkinson's disease patients and carers in the community: study protocol

Background: Parkinson’s disease progressively limits patients at different levels and as a result family members play a key role in their care. However, studies show lack of an integrative approach in Primary Care to respond to the difficulties and psychosocial changes experienced by them. The aim of this study is to evaluate the effects of a multidisciplinary psychoeducational intervention focusing on improving coping skills, the psychosocial adjustment to Parkinson’s disease and the quality of life in patients and family carers in a Primary Care setting. Methods: This quasi-experimental study with control group and mixed methods was designed to evaluate a multidisciplinary psychoeducational intervention. Based on the study power calculations, 100 people with Parkinson’s disease and 100 family carers will be recruited and assigned to two groups. The intervention group will receive the ReNACE psychoeducational intervention. The control group will be given a general educational programme. The study will be carried out in six community-based health centres. The results obtained from the two groups will be collected for evaluation at three time points: at baseline, immediately after the intervention and at 6 months post-intervention. The results will be measured with these instruments: the Quality of Life Scale PDQ39 for patients and the Scale of Quality of Life of Care-givers SQLC for family carers, and for all participants the Psychosocial Adjustment to Illness scale and the Brief COPE Inventory. Focus groups will be organised with some patients and family carers who will have received the ReNACE psychoeducational intervention and also with the healthcare professionals involved in its development. Discussion: An important gap exists in the knowledge and application of interventions with a psychosocial approach for people with PD and family carers as a whole. This study will promote this comprehensive approach in Primary Care, which will clearly contribute in the existing knowledge and could reduce the burden of PD for patients and family carers, and also in other long-term conditions

Naturally Acquired Binding-Inhibitory Antibodies to Plasmodium vivax Duffy Binding Protein in Pregnant Women Are Associated with Higher Birth Weight in a Multicenter Study

A vaccine to eliminate malaria would need a multi-stage and multi-species composition to achieve robust protection, but the lack of knowledge about antigen targets and mechanisms of protection precludes the development of fully efficacious malaria vaccines, especially for Plasmodium vivax (Pv). Pregnant women constitute a risk population who would greatly benefit from a vaccine preventing the adverse events of Plasmodium infection during gestation. We hypothesized that functional immune responses against putative targets of naturally acquired immunity to malaria and vaccine candidates will be associated with protection against malaria infection and/or poor outcomes during pregnancy. We measured (i) IgG responses to a large panel of Pv and Plasmodium falciparum (Pf) antigens, (ii) the capacity of anti-Pv ligand Duffy binding protein (PvDBP) antibodies to inhibit binding to Duffy antigen, and (iii) cellular immune responses to two Pv antigens, in a subset of 1,056 pregnant women from Brazil, Colombia, Guatemala, India, and Papua New Guinea (PNG). There were significant intraspecies and interspecies correlations for most antibody responses (e.g., PfMSP119 versus PfAMA1, Spearman's rho = 0.81). Women from PNG and Colombia had the highest levels of IgG overall. Submicroscopic infections seemed sufficient to boost antibody responses in Guatemala but not antigen-specific cellular responses in PNG. Brazil had the highest percentage of Duffy binding inhibition (p-values versus Colombia: 0.040; Guatemala: 0.047; India: 0.003, and PNG: 0.153) despite having low anti-PvDBP IgG levels. Almost all antibodies had a positive association with present infection, and coinfection with the other species increased this association. Anti-PvDBP, anti-PfMSP1, and anti-PfAMA1 IgG levels at recruitment were positively associated with infection at delivery (p-values: 0.010, 0.003, and 0.023, respectively), suggesting that they are markers of malaria exposure. Peripheral blood mononuclear cells from Pv-infected women presented fewer CD8+IFN-gamma+ T cells and secreted more G-CSF and IL-4 independently of the stimulus used in vitro. Functional anti-PvDBP levels at recruitment had a positive association with birth weight (difference per doubling antibody levels: 45 g, p-value: 0.046). Thus, naturally acquired binding-inhibitory antibodies to PvDBP might confer protection against poor outcomes of Pv malaria in pregnancy

Estado general y recomendaciones para el manejo de cultivos y pasturas en el norte BA

El norte de la provincia de Buenos Aires atraviesa, como otras regiones del país, una situación extrema en relación con el déficit de precipitaciones, registrándose en algunos casos como el de Pergamino, uno de los menores registros histórico para el período junio a octubre desde el año 1910. Esta situación excepcional afecta tanto a los cultivos invernales como a las pasturas. En función de los informes que cada mesa local de emergencia ha requerido a las Agencias de Extensión Rural, compilamos la información generada a fin de brindar un panorama general del área de influencia de la Estación Experimental Agropecuaria INTA Pergamino. En el presente material se incorporan recomendaciones para manejo de cultivos y pasturas en un escenario complejo para la producción agropecuaria desde la perspectiva climática. Si bien el pronóstico indica una continuidad de efecto “Niña” hasta, al menos, fines de diciembre, en los últimos días de octubre han ocurrido precipitaciones de mayor significancia hacia el sur de la región analizada que seguramente tendrán incidencia en el desarrollo de las pasturas y las condiciones de siembras de los cultivos de soja y maíz, que será abordado en posteriores informes. El trabajo incluye el aporte de técnicos de los Grupos de Sistemas de Información Geográfica, Manejo de Cultivos y Bovinos, junto las Agencias de Extensión Rural de la Estación Experimental Agropecuaria de INTA Pergamino, así como el relevamiento del estado general de cultivos facilitado por el Centro Regional Buenos Aires Norte.EEA PergaminoFil: Casartelli, Miguel Ángel. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Pergamino. Agencia De Extensión Rural Lobos; ArgentinaFil: Contreras, Cecilia Inés. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Pergamino. Agencia de Extensión Rural Arrecifes; ArgentinaFil: Couretot, Lucrecia. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Pergamino. Fitopatología; ArgentinaFil: Fernández, Facundo. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Pergamino. Agencia de Extensión Rural Chacabuco; ArgentinaFil: Jecke, Fernando Ariel. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Pergamino. Agencia de Extensión Rural San Antonio de Areco; ArgentinaFil: Lisa, Juan Carlos. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Pergamino. Agencia de Extensión Rural Rojas; ArgentinaFil: Llovet, José Andrés. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Pergamino. Agronomía; ArgentinaFil: Magri, Laura Inés. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Pergamino. Agencia de Extensión Rural Arrecifes; ArgentinaFil: Marino, Magdalena Rosa. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Pergamino. Agencia de Extensión Rural Coronel Brandsen; ArgentinaFil: Martín, Antonio. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Pergamino. Agencia de Extensión Rural Chivilcoy; ArgentinaFil: Mattera, Juan. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Pergamino. Forrajeras; ArgentinaFil: Melilli, María Paula. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Pergamino. Agencia de Extensión Rural Junín; ArgentinaFil: Melión, David. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Pergamino. Agencia de Extensión Rural Bragado; ArgentinaFil: Mousegne, Fernando. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Pergamino. Agencia de Extensión Rural San Antonio de Areco; ArgentinaFil: Portillo, Javier. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Pergamino. Sección Sistema de Información Geográfica (SIG); ArgentinaFil: Sabio, Milton Nelson. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Pergamino. Agencia de Extensión Rural Lobos; ArgentinaFil: Serrano, Pedro Miguel. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Pergamino. Agencia de Extensión Rural Coronel Brandsen; ArgentinaFil: Signorelli, Alejandro. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Pergamino. Agencia de Extensión Rural Junín; ArgentinaFil: Sticconi, María Eugenia. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Pergamino. Desarrollo Rural; ArgentinaFil: Tellería, María Guadalupe. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Pergamino. Agencia de Extensión Rural Junín; ArgentinaFil: Terrile, Ignacio Ismael. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Pergamino. Departamento Trigo; ArgentinaFil: Zanettini, Jorge Luis. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Pergamino. Agencia de Extensión Rural 25 de Mayo; ArgentinaFil: Zuchini, Cristian Ariel. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Pergamino. Agencia de Extensión Rural Chivilcoy; ArgentinaFil: Zunino, Ignacio. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Pergamino. Agencia de Extensión Rural Mercedes; Argentin

Canagliflozin and renal outcomes in type 2 diabetes and nephropathy

BACKGROUND Type 2 diabetes mellitus is the leading cause of kidney failure worldwide, but few effective long-term treatments are available. In cardiovascular trials of inhibitors of sodium–glucose cotransporter 2 (SGLT2), exploratory results have suggested that such drugs may improve renal outcomes in patients with type 2 diabetes. METHODS In this double-blind, randomized trial, we assigned patients with type 2 diabetes and albuminuric chronic kidney disease to receive canagliflozin, an oral SGLT2 inhibitor, at a dose of 100 mg daily or placebo. All the patients had an estimated glomerular filtration rate (GFR) of 30 to <90 ml per minute per 1.73 m2 of body-surface area and albuminuria (ratio of albumin [mg] to creatinine [g], >300 to 5000) and were treated with renin–angiotensin system blockade. The primary outcome was a composite of end-stage kidney disease (dialysis, transplantation, or a sustained estimated GFR of <15 ml per minute per 1.73 m2), a doubling of the serum creatinine level, or death from renal or cardiovascular causes. Prespecified secondary outcomes were tested hierarchically. RESULTS The trial was stopped early after a planned interim analysis on the recommendation of the data and safety monitoring committee. At that time, 4401 patients had undergone randomization, with a median follow-up of 2.62 years. The relative risk of the primary outcome was 30% lower in the canagliflozin group than in the placebo group, with event rates of 43.2 and 61.2 per 1000 patient-years, respectively (hazard ratio, 0.70; 95% confidence interval [CI], 0.59 to 0.82; P=0.00001). The relative risk of the renal-specific composite of end-stage kidney disease, a doubling of the creatinine level, or death from renal causes was lower by 34% (hazard ratio, 0.66; 95% CI, 0.53 to 0.81; P<0.001), and the relative risk of end-stage kidney disease was lower by 32% (hazard ratio, 0.68; 95% CI, 0.54 to 0.86; P=0.002). The canagliflozin group also had a lower risk of cardiovascular death, myocardial infarction, or stroke (hazard ratio, 0.80; 95% CI, 0.67 to 0.95; P=0.01) and hospitalization for heart failure (hazard ratio, 0.61; 95% CI, 0.47 to 0.80; P<0.001). There were no significant differences in rates of amputation or fracture. CONCLUSIONS In patients with type 2 diabetes and kidney disease, the risk of kidney failure and cardiovascular events was lower in the canagliflozin group than in the placebo group at a median follow-up of 2.62 years

Advances in the Microbiological Diagnosis of Prosthetic Joint Infections

A significant number of prosthetic joint infections (PJI) are culture-negative and/or misinterpreted as aseptic failures in spite of the correct implementation of diagnostic culture techniques, such as tissue sample processing in a bead mill, prolonged incubation time, or sonication of removed implants. Misinterpretation may lead to unnecessary surgery and needless antimicrobial treatment. The diagnostic value of non-culture techniques has been investigated in synovial fluid, periprosthetic tissues, and sonication fluid. Different feasible improvements, such as real-time technology, automated systems and commercial kits are now available to support microbiologists. In this review, we describe non-culture techniques based on nucleic acid amplification and sequencing methods. Polymerase chain reaction (PCR) is a frequently used technique in most microbiology laboratories which allows the detection of a nucleic acid fragment by sequence amplification. Different PCR types can be used to diagnose PJI, each one requiring the selection of appropriate primers. Henceforward, thanks to the reduced cost of sequencing and the availability of next-generation sequencing (NGS), it will be possible to identify the whole pathogen genome sequence and, additionally, to detect all the pathogen sequences present in the joint. Although these new techniques have proved helpful, strict conditions need to be observed in order to detect fastidious microorganisms and rule out contaminants. Specialized microbiologists should assist clinicians in interpreting the result of the analyses at interdisciplinary meetings. New technologies will gradually be made available to improve the etiologic diagnoses of PJI, which will remain an important cornerstone of treatment. Strong collaboration among all specialists involved is essential for the correct diagnosis of PJI

Molecular Epidemiology of Multidrug-Resistant <i>Pseudomonas aeruginosa</i> Acquired in a Spanish Intensive Care Unit: Using Diverse Typing Methods to Identify Clonal Types

The increasing number of infections from multidrug-resistant P. aeruginosa (MDRPA) has compromised the selection of appropriate treatment in critically ill patients. Recent investigations have shown the existence of MDRPA global clones that have been disseminated in hospitals worldwide. We aimed to describe the molecular epidemiology and genetic diversity of the MDRPA acquired by Intensive Care Units (ICU) patients in our hospital. We used phenotypic methods to define the MDRPA and molecular methods were used to illustrate the presence of carbapenemase encoding genes. To characterize the MDRPA isolates, we used MALDI-TOF biomarker peaks, O-antigen serotyping, and multi-locus sequence typing analyses. Our data show that the most widely distributed MDRPA clone in our ICU unit was the ST175 strain. These isolates were further investigated by the whole-genome sequencing technique to determine the resistome profile and phylogenetic relationships, which showed, as previously described, that the MDR profile was due to the intrinsic resistance mechanisms and not the carbapenemase encoding genes. In addition, this study suggests that the combination of environmental focus and cross-transmission are responsible for the spread of MDRPA clones within our ICU unit. Serotyping and MALDI-TOF analyses are useful tools for the early detection of the most prevalent MDRPA clones in our hospital. Using these methods, semi-directed treatments can be introduced at earlier stages and healthcare professionals can actively search for environmental foci as possible sources of outbreaks

Redo DAIR: The Game Is Seldom Worth the Candle

Debridement, antibiotics and implant retention (DAIR) remains a commonly utilized technique in the treatment of acute prosthetic joint infections despite its inconsistent outcomes. The performance of a second DAIR after a failed first debridement is controversial as outcomes are uncertain and the final prognosis in the event of failure may be unfavorable. This study analyzes 84 cases of acute prosthetic (hip & knee) joint infection treated with DAIR between 2011 and 2020 at the same institution. In 12 failed cases, a second DAIR was performed, whose success rate was significantly lower than that of the first procedure (8% [95% CI, 0–38] vs. 57% [46–68]). Moreover, the ultimate outcome of the second failed DAIRs was unfavorable with eradication of the infection being achieved in none of the patients. Due to the high likelihood of failure and the potentially grim final prognosis following a second debridement, removal of the components should be considered