Germline mutations of breast cancer susceptibility genes through expanded genetic analysis in unselected Colombian patients.

BACKGROUND: In Colombia and worldwide, breast cancer (BC) is the most frequently diagnosed neoplasia and the leading cause of death from cancer among women. Studies predominantly involve hereditary and familial cases, demonstrating a gap in the literature regarding the identification of germline mutations in unselected patients from Latin-America. Identification of pathogenic/likely pathogenic (P/LP) variants is important for shaping national genetic analysis policies, genetic counseling, and early detection strategies. The present study included 400 women with unselected breast cancer (BC), in whom we analyzed ten genes, using Whole Exome Sequencing (WES), know to confer risk for BC, with the aim of determining the genomic profile of previously unreported P/LP variants in the affected population. Additionally, Multiplex Ligation-dependent Probe Amplification (MLPA) was performed to identify Large Genomic Rearrangements (LGRs) in the BRCA1/2 genes. To ascertain the functional impact of a recurrent intronic variant (ATM c.5496 + 2_5496 + 5delTAAG), a minigene assay was conducted. RESULTS: We ascertained the frequency of P/LP germline variants in BRCA2 (2.5%), ATM (1.25%), BRCA1 (0.75%), PALB2 (0.50%), CHEK2 (0.50%), BARD1 (0.25%), and RAD51D (0.25%) genes in the population of study. P/LP variants account for 6% of the total population analyzed. No LGRs were detected in our study. We identified 1.75% of recurrent variants in BRCA2 and ATM genes. One of them corresponds to the ATM c.5496 + 2_5496 + 5delTAAG. Functional validation of this variant demonstrated a splicing alteration probably modifying the Pincer domain and subsequent protein structure. CONCLUSION: This study described for the first time the genomic profile of ten risk genes in Colombian women with unselected BC. Our findings underscore the significance of population-based research, advocating the consideration of molecular testing in all women with cancer.

Scaling of stem diameter and height allometry in 14 neotropical palm species of different forest strata.

Tropical palms reach tree-like heights without a vascular cambium through sustained cell expansion and lignification of primary tissues, but only a fraction of palms have been explored in their allometric relationships. Here, our main question was to determine how palms depart from the traditional mechanical models developed for trees and how they approach the theoretical buckling limit. We analyzed the stem allometry of 1603 palms of 14 species from different strata at 10 sites in Costa Rica and Peru. We measured their fit to the stress, elastic, and geometric similarity models, and their position relative to the maximum theoretical buckling limit calculated for trees. We evaluated the slope of the linear and logarithmic regressions between stem diameter and height using logarithmic least squares, and standardized major axis regression (SMA), expecting segregation according to canopy position and geographic location. Seventeen out of 19 statistically significant models had SMA slopes > 1, and 11 had SMA slopes ≥ 2, departing from traditional mechanical models developed for trees. Many species varied their allometry relative to geographic location. Canopy palms showed the highest regression fit but had less steep slopes than understory and subcanopy species. Subcanopy and understory species were more underbuilt than canopy palms, increasing height faster than diameter. Some of the tallest canopy palms surpassed the maximum buckling limit whereas subcanopy and understory species were consistently below the buckling limit of record-size trees. Palm stem allometry changed in response to environmental conditions.

Precise control of intramolecular charge-transport: the interplay of distance and conformational effects.

A new series of donor-bridge-acceptor (D-B-A) compounds consisting of π-conjugated oligofluorene (oFL) bridges between a ferrocene (Fc) electron-donor and a fullerene (C60 ) electron-acceptor have been synthesized. In addition to varying the length of the bridge (i.e., mono- and bi-fluorene derivatives), four different ways of linking ferrocene to the bridge have been examined. The Fc moiety is linked to oFL: 1) directly without any spacer, 2) by an ethynyl linkage, 3) by a vinylene linkage, and 4) by a p-phenylene unit. The electronic interactions between the electroactive species have been characterized by cyclic voltammetry, absorption, fluorescence, and transient absorption spectroscopy in combination with quantum chemical calculations. The calculations reveal exceptionally close energy-matching between the Fc and the oFL units, which results in strong electronic-coupling. Hence, intramolecular charge-transfer may easily occur upon exciting either the oFLs or Fcs. Photoexcitation of Fc-oFL-C60 conjugates results in transient radical-ion-pair states. The mode of linkage of the Fc and FL bridge has a profound effect on the photophysical properties. Whereas intramolecular charge-separation is found to occur rather independently of the distance, the linker between Fc and oFL acts (at least in oFL) as a bottleneck and significantly impacts the intramolecular charge-separation rates, resulting in beta values between ßCS 0.08 and 0.19 Å(-1). In contrast, charge recombination depends strongly on the electron-donor-acceptor distance, but not at all on the linker. A value of ßCR (0.35±0.01 Å(-1)) was found for all the systems studied. Oligofluorenes prove, therefore, to be excellent bridges for probing how small structural variations affect charge transport in D-B-A systems.

Real-world evidence of nivolumab for non-small-cell lung cancer in a developing country.

Nivolumab is a human programmed death receptor-1 blocking antibody, used as treatment option in patients with advanced non-small-cell lung cancer (NSCLC). We assessed the nivolumab efficacy in terms of survival and response to treatment as second-line (2L) or third-line (3L) therapy in patients with advanced NSCLC. This is a multicentric observational study. Data of patients with advanced NSCLC who received nivolumab as 2L or 3L treatment were analyzed retrospectively. Information regarding patient demographics and clinical backgrounds, treatment patterns from diagnosis to post-nivolumab treatment, effectiveness, and safety of nivolumab treatment were collected. The outcomes evaluated were overall survival (OS), progression-free survival (PFS), and objective response rate (ORR) to treatment. OS and PFS were estimated with the Kaplan-Meier method and the differences were evaluated through the log-rank test. Data of 178 patients were included. The median follow-up was 26.8 months (interquartile range (IQR): 20.3-40.4). Nivolumab was commonly used as a 2L treatment (77.5%). The outcomes in this setting (2L) were as follows: ORR was 21.0%, and the median PFS and OS were 5.5 months (95% confidence interval (CI): 4.5-6.5) and 12.4 months (95% CI: 10.8-14.0), respectively. In 3L, the ORR with nivolumab was 15.0%, the median PFS and OS were 4.1 months (95% CI: 3.1-5.1) and 10.1 months (95% CI: 9.4-10.6), respectively. Three patients (1.7%) required discontinuation due to toxicity. Nivolumab effectiveness and safety in this scenario was consistent with that reported by previous trials and other real-world data.

Effects of Type of Concentrate and Timing of Supplementation on Feed Intake, Nitrogen Use, and Performance in Lactating Dairy Cows Grazing an Alfalfa-Ryegrass Sward.

The aim was to analyze the effects of two cereal grains differing in nutritional composition and starch degradation characteristics and the timing of their supplementation on feed intake, rumen microbial protein synthesis (MPS), performance, and nitrogen use of lactating dairy cows grazing an alfalfa-ryegrass sward. Four dietary treatments were tested in 24 lactating Brown Swiss cows in an incomplete 4 × 3 Latin square design. Cows were supplemented with 3.5 kg/d (as-fed basis) of a corn-based or an oat-based concentrate mixture (CM), of which either the majority (2.5 vs. 1.0 kg/d) was offered before or after grazing. Feed intake was similar across diets, but the interaction between type of CM and timing of supplementation affected eating time (p = 0.010), milk protein (p = 0.013) and energy-corrected milk yields (p = 0.025), efficiency of rumen MPS (p = 0.094), and nitrogen use efficiency (p = 0.081). Most of these variables were greater when the majority of the corn-based CM was offered after grazing and the oat-based CM before grazing. Supplementing slowly degradable starch sources after and rapidly degradable starch sources before grazing may improve the efficiency of rumen MPS, milk performance, and nitrogen use efficiency in dairy cows grazing alfalfa-ryegrass swards.

The kidnapping of mitochondrial function associated with the SARS-CoV-2 infection.

Infection by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) leads to multi-organ failure associated with a cytokine storm and septic shock. The virus evades the mitochondrial production of interferons through its N protein and, from that moment on, it hijacks the functions of these organelles. The aim of this study was to show how the virus kidnaps the mitochondrial machinery for its benefit and survival, leading to alterations of serum parameters and to nitrosative stress (NSS). In a prospective cohort of 15 postmortem patients who died from COVID-19, six markers of mitochondrial function (COX II, COX IV, MnSOD, nitrotyrosine, Bcl-2 and caspase-9) were analyzed by the immune colloidal gold technique in samples from the lung, heart, and liver. Biometric laboratory results from these patients showed alterations in hemoglobin, platelets, creatinine, urea nitrogen, glucose, C-reactive protein, albumin, D-dimer, ferritin, fibrinogen, Ca²âº, K⁺, lactate and troponin. These changes were associated with alterations in the mitochondrial structure and function. The multi-organ dysfunction present in COVID-19 patients may be caused, in part, by damage to the mitochondria that results in an inflammatory state that contributes to NSS, which activates the sepsis cascade and results in increased mortality in COVID-19 patients.

Association between Postmortem Kidney Biopsy Findings and Acute Kidney Injury from Patients with SARS-CoV-2 (COVID-19).

BACKGROUND AND OBJECTIVES: AKI in coronavirus disease 2019 (COVID-19) is associated with higher morbidity and mortality. The objective of this study was to identify the kidney histopathologic characteristics of deceased patients with diagnosis of COVID-19 and evaluate the association between biopsy findings and clinical variables, including AKI severity. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Our multicenter, observational study of deceased patients with COVID-19 in three third-level centers in Mexico City evaluated postmortem kidney biopsy by light and electron microscopy analysis in all cases. Descriptive and association statistics were performed between the clinical and histologic variables. RESULTS: A total of 85 patients were included. Median age was 57 (49-66) years, 69% were men, body mass index was 29 (26-35) kg/m2, 51% had history of diabetes, 46% had history of hypertension, 98% received anticoagulation, 66% were on steroids, and 35% received at least one potential nephrotoxic medication. Severe AKI was present in 54% of patients. Biopsy findings included FSGS in 29%, diabetic nephropathy in 27%, and arteriosclerosis in 81%. Acute tubular injury grades 2-3 were observed in 49%. Histopathologic characteristics were not associated with severe AKI; however, pigment casts on the biopsy were associated with significantly lower probability of kidney function recovery (odds ratio, 0.07; 95% confidence interval, 0.01 to 0.77). The use of aminoglycosides/colistin, levels of C-reactive protein and serum albumin, previous use of angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers, antivirals, nonsteroid anti-inflammatory drugs, and anticoagulants were associated with specific histopathologic findings. CONCLUSIONS: A high prevalence of chronic comorbidities was found on kidney biopsies. Nonrecovery from severe AKI was associated with the presence of pigmented casts. Inflammatory markers and medications were associated with specific histopathologic findings in patients dying from COVID-19.

Activating multistep charge-transfer processes in fullerene-subphthalocyanine-ferrocene molecular hybrids as a function of π-π orbital overlap.

We have synthesized two different fullerene-subphthalocyanine-ferrocene conjugates. The molecules were designed so that the ferrocene unit is linked at the subphthalocyanine axial position through a phenoxy spacer while the C(60) is rigidly held close to the concave face of the macrocycle via a 3-fold C(3)-symmetrical anchoring. The Bingel trisaddition reaction leading to the final products proceeded with very high regioselectivities and full diastereoselectivity. The only difference between both systems is the length of the triple tether employed, which finely regulates the regioselectivity of the trisaddition reaction and the distance between the subphthalocyanine and the C(60) complementary π-π surfaces. Thus, when the tether is connected to the subphthalocyanine through a direct C-C bond, a short π-π distance of 3.25-3.30 Å was calculated. In contrast, when it is connected through a slightly longer C-O-C bond, the distance increases to 3.5-3.6 Å. This π-π distance has a strong influence on the ground-state electronic interactions between the subphthalocyanine and the C(60), as determined from electronic absorption and cyclic voltammetry measurements. In addition, fluorescence and time-resolved transient absorption experiments demonstrated that different mechanisms operate in the two systems after photoexcitation. Despite the similar HOMO-LUMO gaps, only when the two complementary π-π surfaces of the subphthalocyanine and the C(60) are held at a close distance, therefore showing a high degree of orbital overlap, is a multistep electron transfer process triggered, ultimately leading to the long-lived, spatially separated C(60) radical anion and ferrocenium radical cation pair. A full account of the synthesis, characterization, and studies of the ground- and excited-state electronic interactions occurring in these conjugates, as well as in their reference C(60)-subphthalocyanine and subphthalocyanine-ferrocene dyads, is presented in this article.

Electron donor-acceptor interactions in regioselectively synthesized exTTF(2)-C(70)(CF(3))(10) dyads.

The decakis(trifluoromethyl)fullerene C(1)-C(70)(CF(3))(10), in which the CF(3) groups are arranged on a para(7)-meta-para ribbon of C(6)(CF(3))(2) edge-sharing hexagons, and which has now been prepared in quantities of hundreds of milligrams, was reacted under standard Bingel-Hirsch conditions with a bis-pi-extended tetrathiafulvalene (exTTF) malonate derivative to afford a single exTTF(2)-C(70)(CF(3))(10) regioisomer in 80 % yield based on consumed starting material. The highly soluble hybrid was thoroughly characterized by using 1D (1)H, (13)C, and (19)F NMR, 2D NMR, and UV/Vis spectroscopy; matrix-assisted laser desorption ionization (MALDI) mass spectrometry; and electrochemistry. The cyclic voltammogram of the exTTF(2)-C(70)(CF(3))(10) dyad revealed an irreversible second reduction process, which is indicative of a typical retro-Bingel reaction; whereas the usual phenomenon of exTTF inverted potentials (E1ox>E2ox), resulting in a single, two-electron oxidation process, was also observed. Steady-state and time-resolved photolytic techniques demonstrated that the C(1)-C(70)(CF(3))(10) singlet excited state is subject to a rapid electron-transfer quenching. The resulting charge-separated states were identified by transient absorption spectroscopy, and radical pair lifetimes of the order of 300 ps in toluene were determined. The exTTF(2)-C(70)(CF(3))(10) dyad represents the first example of exploitation of the highly soluble trifluoromethylated fullerenes for the construction of systems able to mimic the photosynthetic process, and is therefore of interest in the search for new materials for photovoltaic applications.

Dendritic porphyrin-fullerene conjugates: efficient light-harvesting and charge-transfer events.

A novel dendritic C(60)-H(2)P-(ZnP)(3) (P=porphyrin) conjugate gives rise to the successful mimicry of the primary events in photosynthesis, that is, light harvesting, unidirectional energy transfer, charge transfer, and charge-shift reactions. Owing, however, to the flexibility of the linkers that connect the C(60), H(2)P, and ZnP units, the outcome depends strongly on the rigidity/viscosity of the environment. In an agar matrix or Triton X-100, time-resolved transient absorption spectroscopic analysis and fluorescence-lifetime measurements confirm the following sequence. Initially, light harvesting is seen by the peripheral C(60)-H(2)P- *(ZnP)(3) conjugate. Once photoexcited, a unidirectional energy transfer funnels the singlet excited-state energy to H(2)P to form C(60)-*(H(2)P)-(ZnP)(3), which powers an intramolecular charge transfer that oxidizes the photoexcited H(2)P and reduces the adjacent C(60) species. In the correspondingly formed (C(60))(*-)-(H(2)P)(*+)-(ZnP)(3) conjugate, an intramolecular charge-shift reaction generates (C(60))(*-)-H(2)P-(ZnP)(3) (.+), in which the radical cation resides on one of the three ZnP moieties, and for which lifetimes of up to 460 ns are found. On the other hand, investigations in organic media (i.e., toluene, THF, and benzonitrile) reveal a short cut, that is, the peripheral ZnP unit reacts directly with C(60) to form (C(60))(*-)-H(2)P-(ZnP)(3) (*+). Substantial configurational rearrangements- placing ZnP and C(60) in proximity to each other-are, however, necessary to ensure the required through space interactions (i.e., close approach). Consequently, the lifetime of (C(60))(*-)-H(2)P-(ZnP)(3) (*+) is as short as 100 ps in benzonitrile.

Palatal fistulae resulting from cocaine abuse.

Cocaine fistulae require repair with well-vascularized material. In the technique used this is accomplished by closure of the nasal layer by delayed palatal flaps and the oral layer with a tongue flap. Three cases are presented.

Efficacy and safety of two whole IgG polyvalent antivenoms, refined by caprylic acid fractionation with or without beta-propiolactone, in the treatment of Bothrops asper bites in Colombia.

The efficacy and safety of two whole IgG polyvalent antivenoms (A and B) were compared in a randomised, blinded clinical trial in 67 patients systemically envenomed by Bothrops asper in Colombia. Both antivenoms were fractionated by caprylic acid precipitation and had similar neutralising potencies, protein concentrations and aggregate contents. Antivenom B was additionally treated with beta-propiolactone to lower its anticomplementary activity. Analysing all treatment regimens together, there were no significant differences between the two antivenoms (A=34 patients; B=33 patients) in the time taken to reverse venom-induced bleeding and coagulopathy, to restore physiological fibrinogen concentrations and to clear serum venom antigenaemia. Blood coagulability was restored within 6-24 h in 97% of patients, all of whom had normal coagulation and plasma fibrinogen levels 48 h after the start of antivenom treatment. Two patients (3.0%) had recurrent coagulopathy and eight patients suffered recurrence of antigenaemia within 72 h of treatment. None of the dosage regimens of either antivenom used guaranteed resolution of venom-induced coagulopathy within 6 h, nor did they prevent recurrences. A further dose of antivenom at 6 h also did not guarantee resolution of coagulopathy within 12-24 h in all patients. The incidence of early adverse reactions (all mild) was similar for both antivenoms (15% and 24%; P>0.05).

Neutralization of four Peruvian Bothrops sp. snake venoms by polyvalent antivenoms produced in Perú and Costa Rica: preclinical assessment.

Envenomations after bites inflicted by snakes of the genus Bothrops constitute a public health hazard in Perú, and the intravenous administration of equine-derived antivenoms represents the only scientifically validated treatment. This study presents a preclinical assessment of the efficacy of two whole IgG antivenoms, prepared in Perú and Costa Rica, to neutralize the most relevant toxic effects induced by the venoms of Bothrops atrox, B. brazili, B. barnetti and B. pictus from Perú. Peruvian antivenom is produced by immunizing horses with Bothrops sp. venoms from this country, whereas the production of Costa Rican antivenom involves immunization with venoms from Central American snakes. The neutralization of lethal, hemorrhagic, edema-forming, myotoxic, coagulant and defibrinating activities was evaluated in assays involving incubation of venom and antivenom prior to testing. Both antivenoms were effective in the neutralization of these effects, with quantitative variations in the values of effective dose 50% depending on the effects being studied. Peruvian antivenom was more effective in the neutralization of lethality induced by B. atrox and B. barnetti venoms. However, Peruvian antivenom failed to neutralize coagulant activity of B. barnetti venom and edema-forming activity of B. brazili venom, whereas neutralization was achieved by Costa Rican antivenom. It is concluded that an extensive immunological cross-reactivity exists between Bothrops sp. venoms from Perú and Costa Rica, and that both antivenoms are effective in the neutralization of these four venoms in a rodent model of envenoming.

Factores psicosociales y familiares que influyen en la deserción en estudiantes universitarios en el contexto de los países en desarrollo / Psycho-social and familial factors influencing drop-out rates among university students in the context of developing countries / Fatores psicossociais e familiares que influenciam na deserção em estudantes universitários no contexto dos países em desenvolvimento

Resumen Introducción. La deserción universitaria es un problema de gran interés para diferentes agentes del sistema educativo, pues su ocurrencia en las sociedades es un indicador de ineficiencia, que genera considerables costos para los Estados, las universidades, los estudiantes y sus familias. Objetivo. Examinar los factores que influyen en la decisión de desertar de los estudiantes universitarios de la ciudad de Medellín (Colombia) para el año 2018. Materiales y métodos. Se llevó a cabo un estudio con enfoque cuantitativo, a partir de un diseño exploratorio-descriptivo de campo, de carácter transversal, en el que participaron 3026 estudiantes mediante la aplicación de un cuestionario autoadministrado. Resultados. Además de los factores económicos, que tradicionalmente son evaluados en este tipo de literatura, las condiciones sociales, familiares y afectivas se convierten en incidentes clave al momento de abordar la deserción escolar como un fenómeno estructural. Conclusiones. La articulación entre directivos, administrativos docentes y estudiantes se consolida como un elemento clave en los procesos de retención académica, como una estrategia para combatir el fenómeno de deserción universitaria.

Abstract Introduction: University dropout is a problem of great interest to different agents of the education system, since its presence in societies is an indicator of inefficiency, which generates considerable costs for states, universities, students and their families. Objective: Examine the factors that influence students' decision to drop out of university in the city of Medellin (Colombia) for the year 2018. Methods and instruments: A quantitative study was carried out, based on a cross-cutting exploratory-descriptive field design, in which 3026 students participated through the application of a self-administered questionnaire. Results: In addition to economic factors, which are traditionally evaluated in this type of literature, social, family and affective conditions become key incidents when dealing with school dropout as a structural phenomenon. Conclusions: The articulation between directors, administrators, teachers and students is consolidated as a key element in academic retention processes, as a strategy to combat the phenomenon of university dropout.

Resumo Introdução. A deserção universitária é um problema de grande interesse para os diferentes agentes do sistema educativo, pois sua ocorrência nas sociedades é um indicador de ineficiência, que gera consideráveis custos para os Estados, as universidades, os estudantes e suas famílias. Objetivo. Examinar os fatores que influenciam na decisão de desertar dos estudantes universitários da cidade de Medellín (Colômbia) para o ano 2018. Materiais e métodos. Foi realizado um estudo com foco no quantitativo, a partir de um desenho exploratório-descritivo do campo, de caráter transversal, onde participaram 3026 estudantes mediante a aplicação de um questionário autoadministrado. Resultados. Além dos fatores económicos, que tradicionalmente são avaliados neste tipo de literatura, as condições sociais, familiares e afetivas se convertem em incidentes chave no momento de abordar a deserção escolar como um fenômeno estrutural. Conclusões. A articulação entre diretivos, administrativos docentes e estudantes se consolida como um elemento chave nos processos de retenção académica, como uma estratégia para combater o fenômeno de deserção universitária.

Preclinical assessment of the ability of polyvalent (Crotalinae) and anticoral (Elapidae) antivenoms produced in Costa Rica to neutralize the venoms of North American snakes.

Polyvalent (Crotalinae) and anticoral (Elapidae) antivenoms produced by Instituto Clodomiro Picado, Costa Rica, were assessed for their ability to neutralize various toxic activities of the venoms of North American snakes of the genera Crotalus, Agkistrodon and Micrurus, in assays involving preincubation of venom and antivenom. When the intraperitoneal route of injection was utilized, polyvalent (Crotalinae) antivenom was effective in the neutralization of the venoms of Crotalus atrox, Crotalus adamanteus, Crotalus viridis viridis, Crotalus horridus atricaudatus, Agkistrodon contortrix contortrix and Agkistrodon piscivorus piscivorus, whereas the venom of Crotalus scutulatus was not neutralized. When the intravenous route was used, results differed depending on the "challenge dose" of venom employed. Polyvalent antivenom neutralized all venoms when mice were challenged with 2 LD(50)s of venom. When 5 LD(50)s were used, antivenom neutralized the venoms of C. atrox, C. adamanteus, C. v. viridis and C. h. atricaudatus, being ineffective in the neutralization of C. scutulatus, A. c. contortrix and A. p. piscivorus. Polyvalent antivenom was effective in the neutralization of hemorrhagic and myotoxic activities of all venoms studied. It also neutralized coagulant activity of C. adamanteus venom, whereas most of the venoms were devoid of clotting activity on plasma in vitro. Moreover, it neutralized defibrinating activity of the only three venoms that induced this effect (i.e. C. adamanteus, A. c. contortrix and A. p. piscivorus). Anticoral (Elapidae) antivenom neutralized lethality induced by the venom of Micrurus fulvius, using either the intravenous or the intraperitoneal routes of injection. Moreover, it neutralized myotoxic effect of this venom as well. It is concluded that polyvalent antivenom neutralizes lethality and other activities of most of the crotaline venoms tested. However, since it is ineffective in neutralizing the lethal effect of C. scutulatus venom, it is suggested that a venom containing presynaptically-active neurotoxic phospholipases A(2) related to "mojave toxin" needs to be introduced in the immunizing mixture in order to increase the neutralizing scope of this product in North America. Anticoral antivenom is highly effective in the neutralization of the venom of M. fulvius.

Geographic and ontogenic variability in the venom of the neotropical rattlesnake Crotalus durissus: pathophysiological and therapeutic implications.

A comparative study was performed on the venoms of adult specimens of the neotropical rattlesnake, Crotalus durissus, from Guatemala, Costa Rica, Venezuela and Brazil, together with the venom of newborn specimens of C. d. durissus from Costa Rica. Venoms from Brazil (C. d. terrificus) and from newborn specimens of C. d. durissus presented an electrophoretic pattern characterized by the predominance of bands with molecular mass of 36 and 15 kDa, whereas those of adult specimens of C. d. durissus from Guatemala and Costa Rica, and C. d. cumanensis from Venezuela, showed a conspicuous band of 62 kDa, and additional bands of 36, 29 and 15 kDa. Moreover, venoms from C. d. terrificus and C. d. cumanensis showed a prominent band of < 10 kDa that probably corresponds to crotamine, since a 'crotamine-like' activity was detected in these venoms upon intraperitoneal injection in mice. Venoms of C. d. terrificus, C. d cumanensis and newborn C. d. durissus induced higher lethal and myotoxic effects than those of adult C. d. durissus. In contrast, adult C. d. durissus and C. d. cumanensis venoms induced hemorrhage, whereas venoms of C. d. terrificus and newborn C. d. durissus lacked this effect. All venoms showed coagulant effect in plasma, the highest activity being observed in the venom of newborn C. d. durissus. An anti-crotalic antivenom produced by Instituto Butantan (Brazil), using C. d. terrificus venom as antigen, was effective in the neutralization of lethal, myotoxic and coagulant effects of all venoms studied, being ineffective in the neutralization of hemorrhagic activity of the venoms of C. d. cumanensis and C. d. durissus. On the other hand, a polyvalent antivenom produced by Instituto Clodomiro Picado (Costa Rica), using the venoms of C. d. durissus. Bothrops asper and Lachesis stenophrys as antigens, was able to neutralize lethal, myotoxic, coagulant and hemorrhagic effects of C. d. durissus venom, but was ineffective in the neutralization of lethality and myotoxicity of C. d. terrificus, C. d. cumanensis and newborn C. d. durissus venom. The high toxicity of South American and newborn C. d. durissus venoms is related to the presence of high concentrations of the neurotoxic phospholipase A2 complex 'crotoxin'. Accordingly, antivenom from Instituto Butantan has a much higher titer of anti-crotoxin antibodies than antivenom from Instituto Clodomiro Picado. Crotalus durissus represents an example of intraspecies variation in venom composition and pharmacology that has relevant pathophysiologic and therapeutic implications.

Novel semiautomated method for assessing in vitro cellular antioxidant activity using the light-scattering properties of human erythrocytes.

The novel method developed for screening cellular antioxidant activity relies on differences in light-scattering properties (turbidity) between intact and lysed human erythrocytes. AAPH, a peroxyl radical generator, was used to enhance lipid peroxidation. The consequent hemolysis triggered a loss of the light-scattering ability in the lysed erythrocytes. When an antioxidant was added, the area under the absorbance decay curve (AUC) was linearly proportional to the concentration of antioxidant compound. This erythrocyte cellular antioxidant activity (ERYCA) method was found to be relatively fast, sensitive, accurate, and repeatable, even when using erythrocytes from different donors and for different storage times. The method was used to assess the antioxidant capacity of pure phenolic compounds, fruit juices, stimulant beverages, and blood plasma and compared with ORAC values. The values resulting from the two methods did not correlate as the mechanisms involved were different.

Control over charge transfer through molecular wires by temperature and chemical structure modifications.

A series of electron donor-acceptor arrays containing π-conjugated oligofluorenes (oFL) of variable length between a zinc porphyrin (ZnP) as electron donor and fullerene (C(60)) as electron acceptor have been prepared by following a convergent synthesis. The electronic interactions between the electroactive species were determined by cyclic voltammetry, UV-visible, fluorescence, and femto/nanosecond transient absorption spectroscopy. Our studies clearly confirm that, although the C(60) units are connected to the ZnP donor through π-conjugated oFL frameworks, no significant electronic interactions prevail in the ground state. Theoretical calculations predict that a long-range electron transfer occurs primarily due to a maximized π-conjugated pathway from the donor to the acceptor. Photoexcitation of ZnP-oFL(n)-C(60) results in transient absorption maxima at 715 and 1010 nm, which are unambiguously attributed to the photolytically generated radical ion pair state, [ZnP(•+)-oFL(n)-C(60)(•-)], with lifetimes in the microsecond time regime. Temperature-dependent photophysical experiments have shown that the charge-transfer mechanism is controllable by temperature. Both charge separation and charge recombination processes give rise to a molecular wire behavior of the oFL moiety with an attenuation factor (ß) of 0.097 Å(-1). The correlation ß to the connection pattern between the ZnP donor and the oFL linker revealed that even small alterations of the linker π-electron system break the homogeneous π-conjugation pattern, leading to higher values of ß.

Proteinuria asociada al dengue

Objetivos: describir el grado de proteinuria y albuminemia en pacientes con dengue, correlacionar la proteinuria con la fuga capilar medida por el nivel de hemoconcentración de la hemoglobina y hematocrito. Metodología: diseño observacional, descriptivo, prospectivo, de corte transversal. Población de estudio: varones y mujeres, mayores de edad, portadores de dengue, internados en el Dpto. de Medicina Interna entre diciembre 2012 y mayo 2013. Criterios de inclusión: dengue grave con signos de alarma, confirmado por antígeno NS1 y/o IgM positivo, en periodo crítico o postfebril. Criterios de exclusión: portadores de afecciones renales conocidas. Muestreo no probabilístico de casos consecutivos. Variables: datos demográficos, hemograma, proteinuria de 24 hs, albuminemia. Resultados: ingresaron al estudio 26 varones con edad media 42±21 años y 28 mujeres con edad media 41±21 años. Se detectó proteinuria en 43 sujetos (79,6%). La misma se hallaba en rango nefrótico (media 3184±916 mg/24 hs) en 8 casos (14,8%) y dentro de valores elevados (media 669±494 mg/24 hs) en 35 casos (64,8%). La albuminemia en los sujetos con rango nefrótico fue 3±0,7 mg/dL, en los que tenían valores elevados de proteinuria fue 2,9±0,4 mg/dL y en los sujetos sin proteinuria fue 2,6±0,4 mg/dL (p 0,09 prueba ANOVA). La correlación entre proteinuria y grado de hemoconcentración de hemoglobina fue -0,01 y con el grado de hemoconcentración del hematocrito fue -0,04. Conclusiones: el dengue produjo proteinuria en 79,6% de los pacientes, llegando a rango nefrótico en 14,8%. La proteinuria no se asoció con el grado de hemoconcentración de la hemoglobina ni del hematocrito, parámetros utilizados como indicadores de gravedad de la fuga capilar. Se recomienda agregar el dosaje de proteínas en orina de 24 hs al protocolo de tratamiento del dengue y el seguimiento prospectivo de los afectados con rango nefrótico.

Objectives: To describe the degree of proteinuria and serum albumin in patients with dengue and correlate the proteinuria with the capillary leakage measured by the level of hemoglobin and hematocrit hemoconcentration. Methods: This was a cross-sectional, prospective, descriptive and observational study. Study population: adult men and women, dengue carriers and admitted in the Department of Internal Medicine between December 2012 and May 2013. Inclusion criteria: severe dengue with warning signs, confirmed by positive NS1 antigen and/or IgM in post-febrile or critical period. Exclusion criteria: known kidney disease carriers. Non-probabilistic sampling of consecutive cases. Variables: demographic data, hemogram, 24-hour proteinuria, serum albumin. Results: Twenty six men with a mean age of 42 ± 21 years and 28 women with a mean age of 41±21 years were included in the study. Proteinuria was detected in 43 subjects (79.6%). The proteinuria was in nephrotic range (mean 3,184±916 mg/24 h) in 8 cases (14.8%) and in high values (mean 669±494 mg/24 h) in 35 cases (64.8%). The serum albumin was 3±0.7 mg/dL in patients with nephrotic range, 2.9±0.4 mg/dL in those with high levels of proteinuria and 2.6±0.4 mg/dL (p=0.09 ANOVA test) in subjects without proteinuria. The correlation between the proteinuria and degree of hemoglobin hemoconcentration was -0.01 while the correlation between the proteinuria and degree of hematocrit hemoconcentration was -0.04. Conclusions: Proteinuria associated with dengue was observed in 79.6% of the patients reaching the nephrotic range in 14.8%. The proteinuria was not associated with the degree of hemoglobin or hematocrit hemoconcentration, the parameters commonly used as indicators of the severity of the capillary leakage. It is recommended to add protein dosage in 24-hour urine in the treatment protocol of dengue as well as the prospective follow-up of those patients with nephrotic range.

Percepción de docentes de la escuela de medicina sede Aragua de la Universidad de Carabobo sobre la atención en salud a población sexo-genero-diversa / Perception of teachers from the medicine school Dr. Witremundo torrealba, Carabobo university on health care to population sex-gender diverse

En Venezuela el tema sexo-género-diversidad ha sido tabú, aún más en nuestros centros de estudios profesionales, teniendo como consecuencia desconocimiento, estigmatización y rechazo para dicha población, e innegables impactos negativos en su situación de salud y calidad de vida. El objetivo de esta investigación es determinar la Percepción de los docentes de la Escuela de Medicina Dr. Witremundo Torrealba, Universidad de Carabobo, sobre la atención en salud a la población sexo-género-diversa. Se realizó un estudio de corte transversal, donde participaron 136 docentes de todos los años de la carrera de Medicina, a través de una encuesta anónima con preguntas cerradas. Se logró evidenciar que en los y las docentes de nuestra Escuela de Medicina se mantiene un rechazo hacia la población sexo-género-diversa; los docentes están de acuerdo en que la escasa formación del personal de salud está íntimamente ligada a discriminación y maltrato a la población sexogénero-diversa. Paradójicamente, aunque los/las docentes mantienen una posición de rechazo hacia la población sexo género diversa, homolesbotransfobia; se evidencian posibilidades para la aceptación de cambios en la formación de nuevos profesionales de salud, y así disminuir la estigmatización y el maltrato de la población sexo-génerodiversa en nuestros centros de salud.

In Venezuela the sex gender diversity issue has been taboo, even more in our professional training centers, with the consequence of ignorance, stigmatization and rejection for this population, and our medical school Dr. Witremundo Torrealba does not escape that. The objective of this research is to determine the perception of teachers of medical school UCSA, on health care to sex gender diverse population. This is a cross-sectional study of field, participants were 136 teachers from all years of the medical career, and data were collected with a anonymous survey with closed questions. It was possible to show that the teachers in our school of medicine remains a rejection diverse population gender sex, teachers estànde agree that the lack of training of health is closely linked to discrimination and abuse in our health centers. Paradoxically, the teachers maintain a position of rejection of sex gender diverse population, but, in other way, open possibilities for acceptance of changes in training new health professionals, and to reduce stigma and mistreatment of the population sex-gender diverse in our health centers.