Evaluation of naturally acquired immune responses against novel pre-erythrocytic Plasmodium vivax proteins in a low endemic malaria population located in the Peruvian Amazon Basin.

BACKGROUND: Plasmodium vivax represents the most geographically widespread human malaria parasite affecting civilian and military populations in endemic areas. Targeting the pre-erythrocytic (PE) stage of the parasite life cycle is especially appealing for developing P. vivax vaccines as it would prevent disease and transmission. Here, naturally acquired immunity to a panel of P. vivax PE antigens was explored, which may facilitate vaccine development and lead to a better understanding of naturally acquired PE immunity. METHODS: Twelve P. vivax PE antigens orthologous to a panel of P. falciparum antigens previously identified as highly immunogenic in protected subjects after immunization with radiation attenuated sporozoites (RAS) were used for evaluation of humoral and cellular immunity by ELISA and IFN-γ ELISpot. Samples from P. vivax infected individuals (n = 76) from a low endemic malaria region in the Peruvian Amazon Basin were used. RESULTS: In those clinical samples, all PE antigens evaluated showed positive IgG antibody reactivity with a variable prevalence of 58-99% in recently P. vivax diagnosed patients. The magnitude of the IgG antibody response against PE antigens was lower compared with blood stage antigens MSP1 and DBP-II, although antibody levels persisted better for PE antigens (average decrease of 6% for PE antigens and 43% for MSP1, p < 0.05). Higher IgG antibodies was associated with one or more previous malaria episodes only for blood stage antigens (p < 0.001). High IgG responders across PE and blood stage antigens showed significantly lower parasitaemia compared to low IgG responders (median 1,921 vs 4,663 par/µl, p < 0.05). In a subgroup of volunteers (n = 17),positive IFN-γ T cell response by ELISPOT was observed in 35% vs 9-35% against blood stage MSP1 and PE antigens, respectively, but no correlation with IgG responses. CONCLUSIONS: These results demonstrate clear humoral and T cell responses against P. vivax PE antigens in individuals naturally infected with P. vivax. These data identify novel attractive PE antigens suitable for use in the potential development and selection of new malaria vaccine candidates which can be used as a part of malaria prevention strategies in civilian and military populations living in P. vivax endemic areas.

Socio-economic determinants of COVID-19 in Mexico.

OBJECTIVES: This study aimed to identify and quantify the role that social and economic determinants play in the probability of dying from COVID-19, in the case of Mexico. STUDY DESIGN: This was a cross-sectional study based on secondary data. METHODS: In this study, COVID-19 contagion and mortality data were used, as well as socio-economic variables, from public databases and open access, with which an econometric model was estimated. RESULTS: It shows that the number of deaths can rise when variables related to vulnerable groups increase, such as poverty, lack of services, gender, and age. In addition, having pre-existing medical conditions or lacking access to water can be a significant factor in the increase in deaths. CONCLUSIONS: Therefore, this study suggests more policies be developed for vulnerable groups to reduce gaps in inequality, particularly given the current situation in which greater inequality can exacerbate the impact of a disease or an unforeseen situation, as is the case of COVID-19.

Neural inertia and differences between loss of and recovery from consciousness during total intravenous anaesthesia: a narrative review.

Most anaesthetists using target-controlled infusion systems will have observed that the calculated effect-site concentration at loss of consciousness is usually higher than the concentration at emergence. Inertia is the ability of biological systems to keep a functional state at rest or in activity and is an active process of resistance to change in state. Hysteresis is a phenomenon whereby the value of a physical property lags behind changes in the effect that is causing it and this is also seen in anaesthesia pharmacology. Recently, a phenomenon called neuronal inertia has been proposed when trying to explain the resistance observed to changes in consciousness induced by general anaesthesia, independent of drug kinetics. This review discusses the existence of this phenomenon and the conceptual and practical impact it may have on induction and recovery from general anaesthesia.

Evidence of hysteresis in propofol pharmacodynamics.

It is commonly assumed that loss of responsiveness and recovery of responsiveness occur at similar concentrations of propofol. However, the 'conscious' and 'anaesthetised' conditions produced by general anaesthetics may behave as two bistable states. We hypothesised that loss of responsiveness and recovery of responsiveness occur at different propofol concentrations. Propofol was administered to 19 healthy volunteers by effect-site target-controlled infusion using increasing and decreasing stable concentration steps of 7 min. Propofol serum concentrations were measured from venous blood samples at the end of each 7-min step. A long step of 14 min was performed at loss of responsiveness. At this step, propofol concentrations were measured at 7 and 14 min. Propofol concentrations measured at loss of responsiveness and recovery of responsiveness were 2.6 (1.2-4.7) µg.ml-1 and 1.6 (0.6-3.3) µg.ml-1 , respectively (p < 0.001). Propofol plasma concentration and the corresponding bispectral index values measured at minute 7 and minute 14 of the long step performed at loss of responsiveness were 2.6 (1.2-4.7) vs. 2.6 (1.3-4.3) at recovery of responsiveness, (p = 0.96) and 61.2 (49.0-77.0) vs. 58.4 (45.0-74.0), (p = 0.058), respectively. Loss of responsiveness and recovery of responsiveness appear to occur at different propofol concentrations. However, it is possible that, if equilibration was not achieved between plasma and effect-sites at the end of each 7-min step, the higher concentrations found at loss of responsiveness compared with those observed during recovery of responsiveness could be explained by a possible bias in estimations of the effect-site concentrations of propofol by the Schnider model, rather than neural inertia.

Retromer-dependent neurotransmitter receptor trafficking to synapses is altered by the Parkinson's disease VPS35 mutation p.D620N.

Vacuolar protein sorting 35 (VPS35) is a core component of the retromer complex, crucial to endosomal protein sorting and intracellular trafficking. We recently linked a mutation in VPS35 (p.D620N) to familial parkinsonism. Here, we characterize human VPS35 and retromer function in mature murine neuronal cultures and investigate neuron-specific consequences of the p.D620N mutation. We find VPS35 localizes to dendritic spines and is involved in the trafficking of excitatory AMPA-type glutamate receptors (AMPARs). Fundamental neuronal processes, including excitatory synaptic transmission, AMPAR surface expression and synaptic recycling are altered by VPS35 overexpression. VPS35 p.D620N acts as a loss-of-function mutation with respect to VPS35 activity regulating synaptic transmission and AMPAR recycling in mouse cortical neurons and dopamine neuron-like cells produced from induced pluripotent stem cells of human p.D620N carriers. Such perturbations to synaptic function likely produce chronic pathophysiological stress upon neuronal circuits that may contribute to neurodegeneration in this, and other, forms of parkinsonism.

Lymphedema: A General Outline of Its Anatomical Base.

The anatomic research of the lymphatic system has been a very controversial subject throughout due to the complexity of the methods for its visualization. More than 30 years ago, together with Prof. Caplan, we began the vascular anatomy research, focusing on the lymphatic anatomy, developing and adapting different techniques of injection. On the third Normal Anatomy Chair of Buenos Aires University, we summarized the lymphatic drainage of the breast and the limbs to interpret the anatomic bases of lymphedema.

Molecular Epidemiology of Plasmodium falciparum Malaria Outbreak, Tumbes, Peru, 2010-2012.

During 2010-2012, an outbreak of 210 cases of malaria occurred in Tumbes, in the northern coast of Peru, where no Plasmodium falciparum malaria case had been reported since 2006. To identify the source of the parasite causing this outbreak, we conducted a molecular epidemiology investigation. Microsatellite typing showed an identical genotype in all 54 available isolates. This genotype was also identical to that of parasites isolated in 2010 in the Loreto region of the Peruvian Amazon and closely related to clonet B, a parasite lineage previously reported in the Amazon during 1998-2000. These findings are consistent with travel history of index case-patients. DNA sequencing revealed mutations in the Pfdhfr, Pfdhps, Pfcrt, and Pfmdr1 loci, which are strongly associated with resistance to chloroquine and sulfadoxine/pyrimethamine, and deletion of the Pfhrp2 gene. These results highlight the need for timely molecular epidemiology investigations to trace the parasite source during malaria reintroduction events.

DigiDOP: A framework for applying digital technology to the Differential Outcomes Procedure (DOP) for cognitive interventions in persons with neurocognitive disorders.

We present a framework -Digi-DOP- that includes a series of evidence-based recommendations to design and apply cognitive interventions for people with Neurocognitive Disorders (NCDs) using a relatively new approach, the Differential Outcomes Procedure (DOP). To do so, we critically review the substantial experimental research conducted with relevant clinical and non-clinical populations, and the theoretical underpinnings of this procedure. We further discuss how existing digital technologies that have been used for cognitive interventions could be applied to overcome some of the limitations of DOP-based interventions and further enhance DOP benefits. Specifically, we present three digital DOP developments that are currently being designed, investigated and/or tested. Finally, we discuss constraints, ethical and legal considerations that need to be taken into account to ensure that the use of technology in DOP-based interventions proposed here does not widen disparities and inequalities. We hope that this framework will inform and guide digital health leaders and developers, researchers and healthcare professionals to design and apply DOP-based interventions for people with NCDs.

Work-related traumatic spinal cord lesions in Chile, a 20-year epidemiological analysis.

STUDY DESIGN: Retrospective cohort study. OBJECTIVE: To describe the characteristics of patients with work-related traumatic spinal cord injuries (TSCI) in Chile. SETTING: Hospital del Trabajador in Santiago, Santiago, Chile. METHODS: Patients suffering from TSCI incurred at the workplace from 1986 to 2005 were identified through records of the Asociación Chilena de Seguridad (ACHS, Chilean Safety Association). RESULTS: The medical records of 173 patients, 172 men and 1 woman, were analyzed. The yearly average incidence was 7.8 per million workers. Age at TSCI onset was 38.2 ± 12.1 years. The principal external causes for TSCI incurred at the workplace were falls from a height in 86 cases (49.7%) and trauma blows to the vertebral spine in 61 cases (35.3 %). More falls occurred in the field construction, and other traumas occurred as a result of traumatic blows caused by tree trunks and stones in forestry and mining sectors. Mortality in this series was 8.7%, and the worst prognosis was for older patients with complete tetraplegia. The paraplegia:tetraplegia ratio was 3.2:1. CONCLUSIONS: The characteristics of workplace TSCI are specific to this population. It is important therefore to develop prevention programs for specific work-related TSCI.

Whole-Genome Sequences of SARS-CoV-2 Isolates from the Dominican Republic.

Here, we report the genome sequences of five severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) strains that were obtained from symptomatic individuals with travel histories during community surveillance in the Dominican Republic in 2020. These sequences provide a starting point for further genomic studies of gene flow and molecular diversity in the Caribbean nation. Phylogenetic analysis suggests that all genomes correspond to the B.1 variant.

Genetic Variability of Plasmodium vivax in the North Coast of Peru and the Ecuadorian Amazon Basin.

In the Peruvian North Coast (PNC), the number of Plasmodium vivax malaria cases increased steadily from 2007 to 2010 despite a significant decline in the overall number of cases in Peru during the same period. To better understand the transmission dynamics of P. vivax populations in the PNC and the neighboring Ecuadorian Amazon Basin (EAB), we studied the genetic variability and population structure of P. vivax in these areas. One hundred and twenty P. vivax isolates (58 from Piura and 37 from Tumbes in the PNC collected from 2008 to 2010 and 25 from the EAB collected in Pastaza from 2001 to 2004) were assessed by five polymorphic microsatellite markers. Genetic variability was determined by expected heterozygosity (He) and population structure by Bayesian inference cluster analysis. We found very low genetic diversity in the PNC (He = 0-0.32) but high genetic diversity in the EAB (He = 0.43-0.70). Population structure analysis revealed three distinct populations in the three locations. Six of 37 (16%) isolates from Tumbes had an identical haplotype to that found in Piura, suggesting unidirectional flow from Piura to Tumbes. In addition, one haplotype from Tumbes showed similarity to a haplotype found in Pastaza, suggesting that this could be an imported case from EAB. These findings strongly suggest a minimal population flow and different levels of genetic variability between these two areas divided by the Andes Mountains. This work presents molecular markers that could be used to increase our understanding of regional malaria transmission dynamics, which has implications for the development of strategies for P. vivax control.

[Cognitive Reserve Scale: testing the theoretical model and norms]. / Escala de reserva cognitiva: ajuste del modelo teorico y baremacion.

INTRODUCTION: The cognitive reserve theory may contribute to explain cognitive performance differences among individuals with similar cognitive decline and among healthy ones. However, more psychometric analysis are needed to guarantee the usage of tests for assessing cognitive reserve. AIMS: To study validity evidences in relation to the structure of the Cognitive Reserve Scale (CRS) and to create reference norms to interpret the scores. SUBJECTS AND METHODS: A total of 172 participants completed the scale and they were classified into two age groups: aged 36-64 years (n = 110) and 65-88 years (n = 62). RESULTS: The exploratory factor analysis using ESEM revealed that the data fitted the proposed model. Overall, the discriminative indices were acceptable (between 0.21 and 0.50) and congruence was observed in the periods of young adulthood, adulthood and late adulthood, in both age group. Besides, the index of reliability (Cronbach's alpha: 0.80) and the typical mean error test (mean: 51.40 ± 11.11) showed adequate values for this type of instrument. CONCLUSION: The CRS seemed to be set under the hypothetical theoretical model, and the scores might be interpreted by the norms showed. This study provided guarantees for the usage of the CRS in research.

TITLE: Escala de reserva cognitiva: ajuste del modelo teorico y baremacion.Introduccion. La teoria de la reserva cognitiva contribuiria a explicar las diferencias en el rendimiento intelectual en sujetos con deterioro cognitivo similar y en sujetos sanos. Sin embargo, son necesarios mas datos psicometricos que garanticen el uso de los instrumentos de medicion de reserva cognitiva. Objetivo. Aportar evidencias de validez respecto a la estructura interna de la escala de reserva cognitiva (ERC) y establecer un baremo de referencia para la interpretacion de sus puntuaciones. Sujetos y metodos. Un total de 172 sujetos completaron la ERC y fueron distribuidos en dos grupos en funcion de la edad: 36-64 años (n = 110) y 65-88 años (n = 62). Resultados. El analisis factorial mediante modelos de ecuaciones estructurales exploratorios indico un moderado ajuste de los datos al modelo propuesto. En general, los indices de discriminacion fueron correctos (entre 0,21 y 0,50), y se registro congruencia entre los items a lo largo de los periodos de juventud, adultez y madurez para ambos grupos de edad. Se observaron valores adecuados del indice de fiabilidad (alfa de Cronbach: 0,80) y de los errores tipicos de medida (media: 51,40 ± 11,11). Conclusiones. La ERC se enmarcaria dentro del modelo teorico hipotetizado y las puntuaciones podrian interpretarse mediante el baremo ofrecido, lo que avalaria su empleo en la investigacion en este campo.

[Anticholinesterases in the treatment of Alzheimer's disease]. / Anticolinesterásicos en el tratamiento de la enfermedad de Alzheimer.

INTRODUCTION: Among the numerous pathophysiological theories that attempt to explain the development of Alzheimer's disease (AD) there are two facts that stand out above the rest: on the one hand, the formation of neurofibrillary tangles inside cells and, on the other, the extra-cellular deposition of beta-amyloid protein. These two mechanisms lead to neurodegeneration and the death of cells by means of a process called 'apoptosis' or 'programmed cell death'. In the early stages of this neurodegenerative process it is more pronounced in cholinergic-type brain centres. This led to the formulation of the so-called cholinergic theory of Alzheimer, which provides the rationale behind the use of the drugs that are currently available to treat this disease, namely, acetylcholine esterase (AChE) inhibitors (rivastigmine, donepezil and galanthamine). DEVELOPMENT AND CONCLUSIONS: We review the possible pharmacological approaches that could help to prevent or delay cell death, and which act on the mechanisms involved in the production of neurofibrillary tangles or the deposition of beta-amyloid protein. We also review the main characteristics of cholinergic neurotransmission, which will help us to understand the therapeutic approaches that have been applied in an attempt to enhance deficient cholinergic neurotransmission. One of the most notable of these is the amount of attention recently being paid to the enzyme AChE, which increases the bioavailability of the neurotransmitter in the cholinergic synapses by preventing the hydrolysis of acetylcholine; these are the only drugs currently available for the symptomatic treatment of this disease.

Invasive trichophyton rubrum infection in an immunocompromised host. Case report and review of the literature.

Typically confined within the keratinized, epithelial layer of the skin and hence categorized among the dermatophytoses, Trichophyton rubrum infections usually present as superficial, scaling eruptions. In certain clinical settings, however, such as in immunosuppressed hosts, deep local invasion, multivisceral dissemination, and even death due to T. rubrum granulomas have been described. A case of multiple, subcutaneous, neutrophilic abscesses due to T. rubrum in an immunosuppressed renal allograft recipient is described. The pathogenesis, diagnosis, and immunology of invasive T. rubrum infections in immunocompromised hosts are reviewed.

Clinical effects of bilateral nephrectomy.

The effects of removal of all renal tissue on hematopoiesis, osteodystrophy, blood pressure regulation and metabolic functions are reviewed; and, the indications for, and results of, bilateral nephrectomy are discussed. Nephrectomy results in a more severe anemia in dialysis patients which is poorly responsive to androgen therapy. No differences were detected in the severity of osteodystrophy between nephric and anephric patients. However, bilateral nephrectomy can occasionally result in the acute onset of hypocalcemia. Blood pressure regulation must be accomplished in the absence of a functioning renin-angiotensin system. This is largely on the basis of volume, but changes in vascular tone may also be significant. Little is known about the metabolic consequences of nephrectomies. The effect on substances metabolized by the kidney is an area for further investigation. Kidney tissue should be preserved, if at all possible, and nephrectomy performed only for specific indications.

Percutaneous transluminal dilation in renal transplant arterial stenosis.

Twelve hypertensive patients underwent percutaneous transluminal dilation (PTD) for relief of arterial stenosis complicating renal allotransplantation. Two patients underwent repeat PTD for recurrent stenosis and hypertension. Six patients had end to end anastomosis of the donor renal artery to the recipient hypogastric artery; four of six PTDs were successful. Six patients had end to side anastomosis of the donor renal artery to the recipient external iliac artery; seven of eight PTDs, including one of two repeat PTDs, were successful. Prior to PTD, all patients were using several antihypertensive medications. Following successful PTD, the mean blood pressure dropped from 184 +/- 15/118 +/- 9 to 133 +/- 13/89 +/- 11 mm Hg (P < 0.001) and remained at that level for up to 15 months (average followup 9 months) with decreased or no antihypertensive medications. Since surgical correction of arterial stenosis occurring after renal transplantation is difficult and may endanger the graft, PTD should be the first interventional therapy.

Hypertension in kidney transplant recipients. Effect on long-term renal allograft survival.

To examine the effects of hypertension on renal graft function, we studied the clinical course of 144 kidney transplant recipients who had functioning grafts for three to 13 years. The patients were divided into three groups: normotensive (n = 32), controlled hypertensive (n = 49) and uncontrolled hypertensive group (n = 63). In addition to the difference in their blood pressure status, the three groups had significantly different levels of serum creatinine at entry to the study (mean +/- SE in mg/dL: 1.41 +/- 0.02, 8.89 +/- 0.02 and 2.30 +/- 0.03, respectively, P = .0002). Cumulative graft survival (CGS) at ten years for normotensive patients was 81%, whereas it was 58% for controlled hypertensive patients and 50% for uncontrolled hypertensive patients. The difference of CGS between normotensive and hypertensive patients was significant (P = .01), whereas the difference between the two hypertensive groups, controlled v. uncontrolled, was not. If serum creatinine levels at entry to the study were adjusted and the CGS of hypertensive patients was compared to normotensive patients with comparable levels of serum creatinine, the differences in CGS between the two groups were no longer significant. Regression analyses for potential prognostic factors revealed that serum creatinine levels were of more primary importance as a prognostic variable than blood pressure status. We conclude that hypertension is an important risk factor for renal graft survival, but control of hypertension alone does not appear to improve it. Graft survival appears to be influenced more by the severity of graft dysfunction at entry to the study irrespective of blood pressure control.

Urinary infection in kidney transplantation.

Urinary tract infection is the most frequent complication following renal transplantation and is important in the etiology of post-transplantation sepsis. The 87 renal homografts done in 1974 at The New York Hospital-Cornell Medical Center were reviewed retrospectively, with at least one year follow-up, in all cases, with particular attention to factors relating urinary tract infection to ultimate success or failure of the renal graft. The over-all incidence of urinary tract infection was 61%. Early infection was associated with a particularly poor prognosis for graft survival. Most patients with urinary infections after successful transplantation experience a combination of both early and late infections. Anatomic factors constitute a remediable cause of urinary infections after transplantation and should be searched for in cases of multiple, recurrent infections, de novo hypertension, or deterioration of previously stable graft function. There were significant differences in the bacteriologic spectrum of urinary tract infections associated with successful transplants as opposed to unsuccessful transplants.

Anaerobic bacteriuria in renal transplantation.

Renal allograft recipients were studied prospectively utilizing improved culture techniques to investigate anaerobic bacteriuria. The study population was compared with a population of patients with chronic renal insufficiency and end stage renal disease. The over-all incidence of anaerobic urinary tract infection was 7.5 per cent while the over-all incidence of aerobic urinary tract infection was 23.5 per cent. Patients with cadaver renal transplants during the early postoperative period had the highest incidnece of both anaerobic (42.9 per cent) and aerobic (71.4 per cent) urinary tract infection of all groups. The potential association between significant anaerobic bacteriuria during the first postoperative month and poor prognosis for cadaver renal allografts merits further investigation.

Renal transplantation between HL-A identical siblings with partial nephrectomy and machine preservation for ossified renal cell carcinoma.

A case of renal transplantation between HL-A identical siblings is reported in which the donor kidney was found to have a calcified mass in the upper pole. Because an immediate pathologic diagnosis could not be made at the time of nephrectomy, the kidney was preserved with pulsatile perfusion for fifty-four hours after excision of the upper pole. At that time the diagnosis was still not available, and transplantation was performed only to have the report of ossified renal cell carcinoma established the following day.