Protein-conformational diseases in childhood: Naturally-occurring hIAPP amyloid-oligomers and early ß-cell damage in obesity and diabetes.

BACKGROUND AND AIMS: This is the first time that obesity and diabetes mellitus (DM) as protein conformational diseases (PCD) are reported in children and they are typically diagnosed too late, when ß-cell damage is evident. Here we wanted to investigate the level of naturally-ocurring or real (not synthetic) oligomeric aggregates of the human islet amyloid polypeptide (hIAPP) that we called RIAO in sera of pediatric patients with obesity and diabetes. We aimed to reduce the gap between basic biomedical research, clinical practice-health decision making and to explore whether RIAO work as a potential biomarker of early ß-cell damage. MATERIALS AND METHODS: We performed a multicentric collaborative, cross-sectional, analytical, ambispective and blinded study; the RIAO from pretreated samples (PTS) of sera of 146 pediatric patients with obesity or DM and 16 healthy children, were isolated, measured by sound indirect ELISA with novel anti-hIAPP cytotoxic oligomers polyclonal antibody (MEX1). We carried out morphological and functional studied and cluster-clinical data driven analysis. RESULTS: We demonstrated by western blot, Transmission Electron Microscopy and cell viability experiments that RIAO circulate in the blood and can be measured by ELISA; are elevated in serum of childhood obesity and diabetes; are neurotoxics and works as biomarkers of early ß-cell failure. We explored the range of evidence-based medicine clusters that included the RIAO level, which allowed us to classify and stratify the obesity patients with high cardiometabolic risk. CONCLUSIONS: RIAO level increases as the number of complications rises; RIAOs > 3.35 µg/ml is a predictor of changes in the current indicators of ß-cell damage. We proposed a novel physio-pathological pathway and shows that PCD affect not only elderly patients but also children. Here we reduced the gap between basic biomedical research, clinical practice and health decision making.

Double-layer carbon nanocapsules with radioiodine content and its interaction with calcium, phosphorus, and strontium.

First principles calculations have been performed for C60@C180 carbon double-layer endofullerenes with up to: three diatomic radioiodine molecules (131I2), two potassium radio-iodide (K131I), and three sodium radio-iodide (Na131I) inside. The plane-wave pseudopotential (PP) method within the general gradient approximation (GGA) in the framework of the density functional theory (DFT) and time-dependent DFT (TD-DFT) was used to perform geometric optimizations (GOs) and molecular dynamics (MD) at 310 K and atmospheric pressure. We found that the double-layer carbon nanocapsules formed by two concentric fullerenes (C180 surrounding C60) are very stable and may contain a radiodosis, without altering their configuration; that is, the 3(131I2)@C60@C180, 2(K131I)@C60@C180, and 3(Na131I)@C60@C180 systems constitute stable nanocapsules. We analyzed the interaction of double-layer endofullerene with radioactive content with some calcium, phosphorus, and strontium atoms, [n(X131I)@C60@C180 + mY], for X = I, K, Na; Y = Ca, P, Sr; n = 1, 2, 3; m = 1, …, 20. Our calculations show that up to m = 20 calcium atoms can easily be physisorbed by the outer surface of the double-layer endofullerene, maintaining their integrity and shielding the radiodosis of any interaction that can proceed from the outside. It is thus concluded that these double-layer endofullerenes can be functionalized as vectors to deliver radiodosis with structural advantages over the single layer systems; as they are more robust, stable, and possess a larger surface to functionalize with some atoms serving as molecular recognizers. Graphical abstract Double-layer carbon nanocapsules with radioiodine content and its interaction with calcium, phosphorus and strontium.

Interactions of calcium with the external surfaces of fullerenes and endofullerenes doped with radioactive sodium iodide.

We report first-principles calculations carried out to analyze the adsorption of calcium on the outer surface of the fullerene C60, yielding [C60 + mCa]. Geometric optimization (GO) and molecular dynamics (MD) simulation were performed using the plane-wave pseudopotential method within the framework of density functional theory (DFT) and time-dependent DFT (TD-DFT) to investigate the configurations, the associated energies in the ground state, and the stabilities of fullerenes and endofullerenes doped with radioactive sodium iodide when they interact with calcium atoms on the outer fullerene surface (i.e., [nNa131I@C60 + mCa]). The reason for investigating these calcium-functionalized (endo)fullerene systems was to gauge their potential stability when used as vectors to deliver radioiodine to cancerous tissue in the human body. In the simulations, we found that the geometric limit on the number of calcium atoms that can be physisorbed on the outer surface of an empty fullerene while maintaining its structural stability is 28 calcium atoms, which also takes into account the proportional expansion of the fullerene as the number of absorbed calcium atoms increases. However, the stability of a fullerene system during calcium adsorption also strongly depends on whether any atoms or molecules are being encapsulated by the fullerene, as these encapsulated atoms/molecules can also interact with the fullerene and influence its stability. A Mulliken electronegativity analysis revealed that, when atoms inside and/or outside the fullerene donate charge (electrons) to the fullerene, the fullerene expands. The excess charge on the carbon atoms of the fullerene weakens some of the carbon-carbon bonds, potentially causing them to break, in which case the fullerene loses its ability to encapsulate molecules and releases them. Graphical Abstract DFT simulation of a endo fullerene doped with radioactive sodium iodide interacting with 28 calcium atoms in a geometric arrangement.

Self-stability of C60 nanocapsules with radio-iodide content and its interaction with calcium atoms.

This paper inquires the C60 capabilities to contain radio-iodide ((131)I2) molecules. The encapsulation conditions are investigated applying first principles method to simulate with geometric optimizations and molecular dynamics at 310 K and atmospheric pressure. We find that the n(131)I2@C60 system, where n = 1, 2, 3…, is stable if the content does not exceed three molecules of radio-iodide. The application of density functional theory allows us to determine that, the nanocapsules content limit is related with the amount of charge that is transferred from the iodine (131)I2 molecules to the carbon atoms in the fullerene surface. The Mulliken population analysis reveals that the excess of charge increases the repulsive forces between atoms and the bond length average in the C60 structure. The weakened bonds easily break and will critically damage the encapsulation properties. Additionally, we test the interaction nanocapsules with different amounts of radioactive iodine diatomic molecules content with calcium atoms, and find that only the fullerene containing one radioactive iodine diatomic molecule was able to interact with up to nine atoms of calcium without disrupting or cracking. Other fullerenes with two and three radio iodine diatomic molecules cannot resist the interaction with a single calcium atom without cracking or being broken.

Novel ethical dilemmas arising in geriatric clinical practice.

The purpose of this study is to determine empirically the state of the art of the medical care, when healthcare personal is confronted with ethical dilemmas related with the care they give to the geriatric population. An observational, longitudinal, prospective and qualitative study was conducted by analyzing the correlation between healthcare personnel-patient relationship, and ethical judgments regarding dilemmas that arise in daily clinical practice with geriatric patients. Mexican healthcare personnel with current active practices were asked to write up an ethical dilemma that arose frequently or that had impacted their medical practice. From the narrative input, we were able to draw up a database with 421 dilemmas, and those corresponding to patients 60 years and older were selected (n = 54, 12.8 %). The axiological analysis of the narrative dilemmas of geriatric patients was made using dialectical empiricism. The axiological analysis values found most frequently were classified into three groups: the impact of healthcare, the roles of the physician, and refusal of therapy; the healthcare role of educator, caring for the patients' life and the risk of imminent death where the values found more often. The persistence and universality of certain dilemmas in geriatrics calls for awareness and requires a good training in the ethical discernment of these dilemmas. This would help to improve substantially the care and the life quality of this population.

Encapsulation of sodium radio-iodide in fullerene C60.

In this work we have studied the well-known "Buckminsterfullerene" C60 containing different amounts, from one to four molecules, of sodium radio-iodide (Na(131)I), with density functional theory geometrical optimizations and molecular dynamics at 310 K and atmospheric pressure. We found that nanocapsules with the radioactive content Na¹³¹I@C60, 2Na¹³¹I@C60 and 3Na¹³¹I@C60 are stable. Furthermore, the C60 fullerene undergoes expansion when the number of sodium radio-iodide molecules inside increases. Utilizing the Mulliken charge distribution analysis it was shown that a small charge transfer occurs from iodine to fullerene's carbon atoms. This produces repulsion which increases bond lengths thus the structure is weakened while the binding energy per atom decreases. For the case in which the fullerene initially contains four sodium radio-iodide molecules the expansion is greater than that which the structure can withstand. So the fullerene breaks and releases its contents. This result leads us to conclude that the fullerene can encapsulate up to three molecules of sodium radio-iodide.

Economic family burden of metabolic control in children and adolescents with type 1 diabetes mellitus.

AIM: To appraise the economic burden for families of patients with type 1 diabetes mellitus (DM1) at the Instituto Nacional de Pediatria in Mexico City. PATIENTS AND METHODS: DM1 family direct costs were obtained from a standardized economic survey in 59 children with no chronic severe complications such as kidney failure in 2002-3. RESULTS: Mean family annual direct cost of treatment and monitoring was US $1689.87 which includes government funding given to both outpatients and inpatients. Despite this, DM1 out-of-pocket cost for families is very high compared to the minimum official wage of approximately $4.00 dollar/day versus $4.06 cost DM1/day. No correlation between parents' age, education or socio-economic level and direct cost was statistically significant. CONCLUSIONS: The highest economic burden was due to self-monitoring of blood glucose (SMBG) 53.0% and insulin 14.8%. The costs were higher in children with poor metabolic control who performed SMBG less often.

[Bone marrow aplasia associated to the use of ticlopidine]. / Aplasia medular asociada al uso de ticlopidina.

We report a 58 years old male that developed a bone marrow aplasia associated to the use of ticlopidine, prescribed after coronary artery stenting. The patient developed a pneumonia as a complication. He was admitted to the Intermediate Treatment Unit, receiving wide spectrum antimicrobial therapy and a granulocyte colony stimulating factor (Neupogen(r)) with favourable response. Ticlodipine is an effective antiplatelet agent, but has serious hematological and other side effects. Its prescription requires a close follow up and search for complications.

Hemodiálisis y embarazo: experiencia clínica de 6 embarazos con recién nacido vivo / Hemodyalisis and pregnancy: clinical experience of 6 alive newborns

Se analiza el total de nueve embarazos en pacientes hemodializadas ocurridos desde 1990 hasta septiembre del año 2001. Se hace referencia especialmente a las seis gestaciones con feto vivo. De un total de 9 embarazos hubo 3 abortos, lo que equivale a un 33 por ciento, y 6 casos con feto vivo, 66 por ciento. El tiempo de diálisis fluctuó entre los 12 y 78 meses, con un promedio de 46. La edad gestacional al término osciló entre las 30 y las 37 semanas, y todas las gestaciones fueron de pretérmino. En el 66 por ciento (4) de las pacientes el parto se resolvió por cesárea. Hubo 5 RN con RCIU, 83,3 por ciento. El peso de los RN fluctuó entre los 1100 y los 2800 gramos con un promedio de 1948 gramos. En 5 pacientes hubo presencia de polihidroamnios. No hubo malformaciones congénicas de los RN ni mortalidad materna

Hemodiálisis y embarazo: experiencia clínica / Hemodialysis and pregnancy: clinical experience

Se presenta un caso clínico exitoso de manejo de hemodiálisis y embarazo