COVID-19 y la pandemia olvidada: el seguimiento de las enfermedades neurocognitivas durante la cuarentena en Argentina / COVID-19 and the forgotten pandemic: follow-up of neurocognitive disorders during lockdown in Argentina

INTRODUCCIÓN: Varios países del mundo padecen una grave carga en sus sistemas de salud como consecuencia de la pandemia por COVID-19. Esta realidad pone en riesgo el seguimiento de patologías crónicas como las demencias. Asimismo, la atención de las posibles complicaciones neuropsiquiátricas relacionadas con el aislamiento preventivo de la población (cuarentena), que en el caso de Argentina se considera la más prolongada de Latinoamérica. El objetivo del presente trabajo es determinar la frecuencia de las distintas modalidades de consulta médica en relación con la patología neurocognitiva del paciente y las variables predictoras de consulta desde el inicio de la cuarentena. MÉTODOS: Estudio descriptivo observacional y transversal basado en la recolección de datos a través de una encuesta. RESULTADOS: Hubo 324 participantes, 165 (50,9%) de los cuales realizaron al menos una consulta médica. Frecuencia de modalidades de consulta: teléfono, 109 (33,6%); correo electrónico, 62 (19,1%); videoconsulta, 30 (9,3%); servicio de emergencias, 23 (7,1%). Predictores de consulta: Clinical Dementia Rating ≥ 1 (p < 0,001); diagnóstico: Alzheimer (p = 0,017). Se encontraron puntajes más altos del Inventario Neuropsiquiátrico (NPI) en el grupo que ha realizado consultas médicas (p < 0,001). Dicha diferencia no fue observada en el puntaje de la escala de carga del cuidador (Zarit). CONCLUSIÓN: Evidenciamos alta prevalencia de trastornos conductuales en pacientes y de sobrecarga en cuidadores durante la cuarentena. Solamente el 50% accedió a una consulta médica (52,7% por modalidad telefónica y correo electrónico). Es necesario extremar los cuidados en personas con demencia, garantizando el seguimiento de su patología

INTRODUCTION: Health systems in numerous countries around the world are suffering a serious burden as a consequence of the COVID-19 pandemic. As a result of this situation, the follow-up of such chronic diseases as dementia may be at risk. Similarly, neuropsychiatric complications related to lockdown measures may also be neglected; Argentina's lockdown has been the longest implemented in Latin America. This study aims to determine the frequency of the different types of medical consultations for neurocognitive disorders and the predictors for requiring consultation since the beginning of the lockdown. METHODS: We performed a descriptive, observational, cross-sectional study based on data collected through an online survey. RESULTS: Data were collected on 324 participants, with 165 (50.9%) having had at least one medical consultation. Consultations were held by telephone in 109 cases (33.6%), by e-mail in 62 (19.1%), by video conference in 30 (9.3%), and at the emergency department in 23 (7.1%). Predictors of requiring consultation were Clinical Dementia Rating scores ≥1 (P < .001) and diagnosis of Alzheimer disease (P = .017). Higher Neuropsychiatric Inventory scores were found in the group of respondents who did require medical consultation (P < .001), but no significant differences were found between groups for Zarit Burden Interview scores. CONCLUSION: We identified a high prevalence of behavioural disorders and caregiver burden during lockdown. Nevertheless, only 50% of respondents had sought medical consultation (by telephone or email in 52.7% of cases). Care of people with dementia must be emphasised, guaranteeing follow-up of these patients

COVID-19 and the forgotten pandemic: follow-up of neurocognitive disorders during lockdown in Argentina. / COVID-19 y la pandemia olvidada: el seguimiento de las enfermedades neurocognitivas durante la cuarentena en Argentina.

INTRODUCTION: Health systems in numerous countries around the world are suffering a serious burden as a consequence of the COVID-19 pandemic. As a result of this situation, the follow-up of such chronic diseases as dementia may be at risk. Similarly, neuropsychiatric complications related to lockdown measures may also be neglected; Argentina's lockdown has been the longest implemented in Latin America. This study aims to determine the frequency of the different types of medical consultations for neurocognitive disorders and the predictors for requiring consultation since the beginning of the lockdown. METHODS: We performed a descriptive, observational, cross-sectional study based on data collected through an online survey. RESULTS: Data were collected on 324 participants, with 165 (50.9%) having had at least one medical consultation. Consultations were held by telephone in 109 cases (33.6%), by e-mail in 62 (19.1%), by video conference in 30 (9.3%), and at the emergency department in 23 (7.1%). Predictors of requiring consultation were Clinical Dementia Rating scores ≥1 (P<.001) and diagnosis of Alzheimer disease (P=.017). Higher Neuropsychiatric Inventory scores were found in the group of respondents who did require medical consultation (P<.001), but no significant differences were found between groups for Zarit Burden Interview scores. CONCLUSION: We identified a high prevalence of behavioural disorders and caregiver burden during lockdown. Nevertheless, only 50% of respondents had sought medical consultation (by telephone or email in 52.7% of cases). Care of people with dementia must be emphasised, guaranteeing follow-up of these patients.

Small size at birth predicts decreased cardiomyocyte number in the adult ovine heart.

Low birth weight is associated with increased risk of cardiovascular disease in adulthood. Intrauterine growth restriction (IUGR) hearts have fewer CMs in early postnatal life, which may impair postnatal cardiovascular function and hence, explain increased disease risk, but whether the cardiomyocyte deficit persists to adult life is unknown. We therefore studied the effects of experimentally induced placental restriction (PR) on cardiac outcomes in young adult sheep. Heart size, cardiomyocyte number, nuclearity and size were measured in control (n=5) and PR (n=5) male sheep at 1 year of age. PR lambs were 36% lighter at birth (P=0.007), had 38% faster neonatal relative growth rates (P=0.001) and had 21% lighter heart weights relative to body weight as adults (P=0.024) than control lambs. Cardiomyocyte number, nuclearity and size in the left ventricle did not differ between control and PR adults; hearts of both groups contained cardiomyocytes (CM) with between one and four nuclei. Overall, cardiomyocyte number in the adult left ventricle correlated positively with birth weight but not with adult weight. This study is the first to demonstrate that intrauterine growth directly influences the complement of CM in the adult heart. Cardiomyocyte size was not correlated with cardiomyocyte number or birth weight. Our results suggest that body weight at birth affects lifelong cardiac functional reserve. We hypothesise that decreased cardiomyocyte number of low birth weight individuals may impair their capacity to adapt to additional challenges such as obesity and ageing.

Circulating IGF1 and IGF2 and SNP genotypes in men and pregnant and non-pregnant women.

Circulating IGFs are important regulators of prenatal and postnatal growth, and of metabolism and pregnancy, and change with sex, age and pregnancy. Single-nucleotide polymorphisms (SNPs) in genes coding for these hormones associate with circulating abundance of IGF1 and IGF2 in non-pregnant adults and children, but whether this occurs in pregnancy is unknown. We therefore investigated associations of plasma IGF1 and IGF2 with age and genotype at candidate SNPs previously associated with circulating IGF1, IGF2 or methylation of the INS-IGF2-H19 locus in men (n=134), non-pregnant women (n=74) and women at 15 weeks of gestation (n=98). Plasma IGF1 concentrations decreased with age (P<0.001) and plasma IGF1 and IGF2 concentrations were lower in pregnant women than in non-pregnant women or men (each P<0.001). SNP genotypes in the INS-IGF2-H19 locus were associated with plasma IGF1 (IGF2 rs680, IGF2 rs1004446 and IGF2 rs3741204) and IGF2 (IGF2 rs1004446, IGF2 rs3741204 and H19 rs217727). In single SNP models, effects of IGF2 rs680 were similar between groups, with higher plasma IGF1 concentrations in individuals with the GG genotype when compared with GA (P=0.016), or combined GA and AA genotypes (P=0.003). SNPs in the IGF2 gene associated with IGF1 or IGF2 were in linkage disequilibrium, hence these associations could reflect other genotype variations within this region or be due to changes in INS-IGF2-H19 methylation previously associated with some of these variants. As IGF1 in early pregnancy promotes placental differentiation and function, lower IGF1 concentrations in pregnant women carrying IGF2 rs680 A alleles may affect placental development and/or risk of pregnancy complications.

Use of Matrigel in culture affects cell phenotype and gene expression in the first trimester trophoblast cell line HTR8/SVneo.

There is inconsistent use of Matrigel for experiments with the HTR8/SVneo first trimester trophoblast and other cell lines. We quantified the effects of Matrigel on the expression of genes considered to be markers of extravillous cytotrophoblast (EVT) differentiation and invasive potential. Culture on Matrigel promoted formation of "endothelial-like" tubes and reduced mRNA expression of matrix metalloproteinase 2 (MMP2), cytokeratin 7 (KRT7) and integrin alpha 1 (ITGA1), while increasing VE-cadherin (CDH5) expression consistent with a vascular phenotype. This process may constitute part of the endothelial cell mimicry exhibited by endovascular EVTs invading the maternal spiral arteries. HTR8/SVneo appears to be phenotypically polymorphic and adopt endovascular morphology on Matrigel.

SeiVis: An Interactive Visual Subsurface Modeling Application.

The most important resources to fulfill today's energy demands are fossil fuels, such as oil and natural gas. When exploiting hydrocarbon reservoirs, a detailed and credible model of the subsurface structures is crucial in order to minimize economic and ecological risks. Creating such a model is an inverse problem: reconstructing structures from measured reflection seismics. The major challenge here is twofold: First, the structures in highly ambiguous seismic data are interpreted in the time domain. Second, a velocity model has to be built from this interpretation to match the model to depth measurements from wells. If it is not possible to obtain a match at all positions, the interpretation has to be updated, going back to the first step. This results in a lengthy back and forth between the different steps, or in an unphysical velocity model in many cases. This paper presents a novel, integrated approach to interactively creating subsurface models from reflection seismics. It integrates the interpretation of the seismic data using an interactive horizon extraction technique based on piecewise global optimization with velocity modeling. Computing and visualizing the effects of changes to the interpretation and velocity model on the depth-converted model on the fly enables an integrated feedback loop that enables a completely new connection of the seismic data in time domain and well data in depth domain. Using a novel joint time/depth visualization, depicting side-by-side views of the original and the resulting depth-converted data, domain experts can directly fit their interpretation in time domain to spatial ground truth data. We have conducted a domain expert evaluation, which illustrates that the presented workflow enables the creation of exact subsurface models much more rapidly than previous approaches.

[Managing the side effects of angiogenetic inhibitors in metastatic renal cell carcinoma]. / Antiangiogenetische Therapie beim Nierenzellkarzinom. Management der Nebenwirkungen.

Sunitinib and Sorafenib are both effective angiogenetic inhibitors for the treatment of renal cell carcinoma. With these drugs of a new class of chronic therapy is performed. During chronic treatment, the inherent side effects may necessitate stopping the application of these drugs thus preventing the required effective therapy. Most of the effects can be avoided or attenuated by prophylaxis. In this paper the published data are reviewed and added with our experience in 138 patients over up to two and a half years.

Informal roles and the stages of interdisciplinary team development.

After presenting a theory of team development, we propose that the informal role structure of a team is dependent upon the degree of anomie in the team culture, and we provide measures of anomie and informal roles that can be used in field settings. Then we test hypotheses on a national sample of 111 interdisciplinary health care teams in geriatrics in US Veterans Affairs medical centers. We find evidence that as teams develop from early to later stages, the interpersonal behavior of members becomes less differentiated on three dimensions: prominence, sociability, and task-orientation. In addition, we find that images of each member come into clearer focus, as evidenced by reduced variation in how each member is seen by other team members. Finally, we find that regardless of stage of team development, the more education the team members have, the more prominent and task-oriented they are. In general, physicians score highest in prominence and task-orientation, but relatively low in sociability.

Vanadium-contaminated perioperatively administered infusion solutions and drugs.

Vanadium was determined in 51 solutions and drugs for intravenous administration and in 6 salt components of a multitrace element solution using electrothermal atomic absorption spectrometry. The highest V contaminations were found in albumin solutions showing values of more than 600 microg/L V. Two heparines contained 14.3 and 122 microg/L V, respectively. In the ultratrace element solution, 14.8 microg/L vanadium were determined. The most contaminated salt of this solution was Mn(II)-DL-aspartate (12.8 microg V/g). The concentrations of unbound V (Vf) in the albumin solutions were between 0.31 and 299 microg/L. The manufacturing process is the reason for V contamination. The biological half-life of V administered intravenously by albumin solutions in man was about 125 h.

The effect of vanadium-contaminated commercially available albumin solutions on renal tubular function.

We report our findings in a patient with coronary heart disease who received an intravenous albumin solution that contained a significant level of vanadium on the first day after elective primary coronary revascularization. Six patients who underwent similar surgical procedures without albumin infusion were taken as a control group. After administration of the V-contaminated albumin solution, the urinary excretion rates of alpha-glutathione S-transferase, a marker of proximal tubular damage, showed a several-fold elevation above the reference value, and the mean excretion rate was significantly different from that of the control group (p < 0.05). pi-Glutathione S-transferase, a marker of distal tubular damage, only marginally exceeded the upper reference limit in two urine samples from this patient. In all urine samples from the control group the excretion rates of pi-GST were below the detection limit. No significant differences in the excretion rates of alpha1-microglobulin and N-acetyl-beta-D-glucosaminidase were found between the patient treated with the albumin infusion and the patients of the control group. The biological half-life of intravenously administered V was approximately 125 h. All commercially available albumin solutions contain traces of vanadium with the concentration varying between 1.1 and 677 microg/l. The free V fraction in the albumin solutions increased with total V concentration, the highest concentration of free V found being 299 microg/l. The data suggest that the use of albumin solutions containing high levels of vanadium can lead to renal injuries, especially in patients with existing impaired renal function, as is the case with extracorporal circulation. The contamination is believed to be a result of the commercial isolation process.

Development of an Attitudes Toward Health Care Teams Scale.

The authors describe the development and psychometric testing across three study phases of an Attitudes Toward Health Care Teams Scale. The measure contains two subscales: Quality of Care/Process (14 items) and Physician Centrality (6 items). The Quality of Care/Process subscale measures team members' perceptions of the quality of care delivered by health care teams and the quality of teamwork to accomplish this. The Physician Centrality subscale measures team members' attitudes toward physicians' authority in teams and their control over information about patients. Tests of reliability and validity demonstrate that each subscale is a strong measure of its respective underlying concept. The measure has potential for use as a research tool and as a pre- and posttest tool for educational interventions with teams and for evaluating clinically based team training programs for medical and health professions students and residents.

Validation of a customized LIMS.

The advantages of customized Laboratory Information Management's Systems (LIMS) are their focus on the special aspects of their users' needs. Differences in the research and development or production chain in the individual organizations lead to an increase of interest in customized systems. Usually, also for customized systems, the core software is commercially available. The individual application modules as the Customized part of the LIMS are the most critical elements within the validation process. The topic of this paper is to give an example of the validation of a customized analytical LIMS. Validation of complex computerized systems guarantees the intended use and is therefore an unavoidable requirement of authorities. The audit of the supplier of the individual programmed modules, the user requirement specifications and the acceptance testing and results, respectively, on the software are of special interest within a customized LIMS. The hardware suitability and the principal processing routines are also a very important part of the whole validation process, but they will not be discussed in detail in this paper.

Comparative study of CD26 as a Th1-like and CD30 as a potential Th2-like operational marker in leprosy.

In the last years we have been able to establish CD26 as an operational marker for a human Th1-like reaction in various granulomatous diseases. Recently, CD30 was described as a marker for a Th2-type reaction, where CD30 is preferentially expressed and its soluble form released by human T cell clones producing Th2-type cytokines. To evaluate the possibility of CD30 as an eventual operational marker for a human Th2-like reaction in vivo, we performed immunohistological stainings on frozen sections of skin biopsies from patients with lepromatous and tuberculoid leprosy. A maximum of three to four CD30-positive cells was found per section, and there was no difference in the accumulation of CD30-positive cells between the tuberculoid and the lepromatous form of leprosy. With respect to CD26-positive cells, a high number was found in tuberculoid leprosy in contrast to a greatly reduced expression of CD26 in lepromatous leprosy. We conclude that, while CD26 was confirmed as an operational marker for a Th1-like reaction in leprosy, CD30 does not represent an operational Th2 marker in this disease.

Quantification of vanadium in serum by electrothermal atomic absorption spectrometry.

We describe an ultrasensitive and reliable method for determining vanadium in human serum by electrothermal atomic absorption spectrometry. After lyophilization, the serum is digested in acid at high pressure, and the digests are evaporated to a small volume. Vanadium in the digests is complexed with cupferron, extracted, and dried. The residue is redissolved in formic acid, where it is 15-fold more concentrated than in the original serum sample. To enhance the furnace sensitivity, we injected six 40-microL aliquots (total, 240 microL) of the concentrated extract. The median concentration of vanadium in 108 persons was 50 ng/L, in good agreement with previously reported results by neutron activation analysis. The characteristic mass obtained (the mass required to give a signal of 0.0044A. s) was 28 pg, the limit of detection 11 ng/L, the limit of quantification 17 ng/L, and the total imprecision (CV) 5.5% at 1.54 micrograms/L. In two assays of Standard Reference Material 1577a (certified vanadium content 99 +/- 8 ng/g), we obtained values of 94.1 and 97 ng/g.

Cloning and expression of carbonyl reductase from rat testis.

Carbonyl reductase is a cytosolic, monomeric, NADPH-dependent oxidoreductase with broad specificity for carbonyl compounds and a general distribution in human and many animal tissues. A carbonyl-reductase-like enzyme is exclusively expressed in rat reproductive tissues and adrenal glands. To understand the structural and functional relationships between the two enzymes, we cloned and sequenced the cDNA for the enzyme from rat testis and overexpressed the encoded protein in Escherichia coli. Three types of cDNA coding for the same protein but differing in their 5'-untranslated regions were isolated. The encoded protein had the same length as, and showed 86% positional identity with, carbonyl reductase from human placenta and liver. The recombinant enzyme exhibited the same substrate specificity and susceptibility to inhibitors as the enzyme isolated from rat testis, and also closely resembled human carbonyl reductase. Similar to the human enzyme, the recombinant rat enzyme catalyzed its own modification by pyruvate and 2-oxoglutarate, respectively. We conclude that carbonyl reductase from rat testis and human tissues represent species-specific forms of the same enzyme.

A new substitution, gamma 358 Ser-->Cys, in fibrinogen Milano VII causes defective fibrin polymerization.

Fibrinogen Milano VII is a hereditary fibrinogen variant detected in a woman with no clinical symptoms of bleeding or thrombosis. Thrombin and reptilase clotting times were prolonged in six family members from three generations. Release of fibrinopeptides A and B was normal. Fibrin polymerization was strongly delayed both in the presence and in the absence of calcium. The structural defect was determined by sequence analysis of a 290-bp fragment of genomic DNA amplified by polymerase chain reaction and cloned in M13mp19. The triplet TCT coding for the amino acid residue gamma 358 was found to be replaced by TGT, resulting in the substitution gamma 358 Ser-->Cys. Immunoblot analysis demonstrated the presence of covalently linked fibrinogen albumin and fibrinogen (albumin)2 complexes. Albumin was released from fibrinogen Milano VII by limited reduction with 2-mercaptoethanol. Fibrin polymerization was not normalized after removal of albumin from fibrinogen Milano VII, suggesting that the delayed clot formation is not due to steric hindrance caused by bound albumin but by substitution of gamma 358 Ser by Cys itself. Our results indicate that the residue gamma 358 Ser is essential for normal expression of the carboxy terminal polymerization site on the fibrinogen gamma-chain.

Fibrinogen Milano V: a congenital dysfibrinogenaemia with a gamma 275 Arg-->Cys substitution.

An abnormal fibrinogen was discovered in a clinically asymptomatic woman from Italy. Routine coagulation studies revealed prolonged thrombin and reptilase clotting times and a discrepancy between the plasma fibrinogen levels determined by the clotting assay and electroimmunoassay. Release of fibrinopeptides A and B from fibrinogen Milano V by thrombin was normal. Fibrin polymerization was strongly delayed in the presence of EDTA and was partially corrected at physiological calcium concentration. Normal migration of mercaptolysed polypeptide chains was observed in polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulphate. Moreover, there was no apparent abnormality in the charge of the reduced chains of the variant fibrinogen, as judged by two-dimensional gel electrophoresis. A fragment of the gamma-chain gene coding for the amino acids 259-350 was amplified and cloned. The amino acid gamma 275 arginine was found to be substituted by cysteine. Immunoblotting analysis with a rabbit antiserum against human serum albumin indicated that albumin was not linked to the odd sulphydryl group of fibrinogen Milano V. Treatment of fibrinogen Milano V with cysteamine, that is surmised to convert the mutant cysteine to a positively charged lysine analogue, did not improve the clotting properties of fibrinogen Milano V.

Fibrinogen Bern I: substitution gamma 337 Asn-->Lys is responsible for defective fibrin monomer polymerization.

An inherited fibrinogen variant, fibrinogen Bern I, was isolated from plasma of an asymptomatic woman. Routine coagulation studies showed prolonged thrombin and reptilase clotting times. Fibrinogen concentration was diminished when determined by a functional assay, but was normal by the heat precipitation method. The release of fibrinopeptides A and B was not delayed. Two-dimensional gel electrophoresis of mercaptolyzed fragments D of fibrinogen, obtained by digestion with plasmin, showed an abnormal electrophoretic mobility in the gamma-chain remnants of fragments D1 and D2 from fibrinogen Bern I, whereas conversion of D2 to D3 by plasmin resulted in the loss of the abnormal charge, suggesting that the structural abnormality in this variant is located in the region gamma 303 through 356. The molecular defect in fibrinogen Bern I was identified by sequence analysis of genomic DNA amplified by polymerase chain reaction and cloned in M13mp19. The triplet AAC coding for asparagine at position gamma 337 was found to be substituted by AAA coding for lysine. We conclude that the substitution gamma 337 Asn-->Lys in fibrinogen Bern I is responsible for defective polymerization of fibrin monomers and for impaired protection by calcium against plasmic degradation.