Nelly Altamirano-Bustamante

Promoting networks between evidence-based medicine and values-based medicine in continuing medical education

BackgroundIn recent years, medical practice has followed two different paradigms: evidence-based medicine (EBM) and values-based medicine (VBM). There is an urgent need to promote medical education that strengthens the relationship between these two paradigms. This work is designed to establish the foundations for a continuing medical education (CME) program aimed at encouraging the dialogue between EBM and VBM by determining the values relevant to everyday medical activities.MethodsA quasi-experimental, observational, comparative, prospective and qualitative study was conducted by analyzing through a concurrent triangulation strategy the correlation between healthcare personnel-patient relationship, healthcare personnels life history, and ethical judgments regarding dilemmas that arise in daily clinical practice.In 2009, healthcare personnel working in Mexico were invited to participate in a free, online clinical ethics course. Each participant responded to a set of online survey instruments before and after the CME program. Face-to-face semi-structured interviews were conducted with healthcare personnel, focusing on their views and representations of clinical practice.ResultsThe healthcare personnels core values were honesty and respect. There were significant differences in the clinical practice axiology before and after the course (P <0.001); notably, autonomy climbed from the 10th (order mean (OM) = 8.00) to the 3rd position (OM = 5.86). In ethical discernment, the CME program had an impact on autonomy (P ≤0.0001). Utilitarian autonomy was reinforced in the participants (P ≤0.0001). Regarding work values, significant differences due to the CME intervention were found in openness to change (OC) (P <0.000), self-transcendence (ST) (P <0.001), and self-enhancement (SE) (P <0.019). Predominant values in life history, ethical discernment and healthcare personnel-patient relation were beneficence, respect and compassion, respectively.ConclusionsThe healthcare personnel participating in a CME intervention in clinical ethics improved high-order values: Openness to change (OC) and Self Transcendence (ST), which are essential to fulfilling the healing ends of medicine. The CME intervention strengthened the role of educators and advisors with respect to healthcare personnel. The ethical values developed by healthcare professionals arise from their life history and their professional formation.

Drug Development in Conformational Diseases: A Novel Family of Chemical Chaperones that Bind and Stabilise Several Polymorphic Amyloid Structures

The increasing prevalence of conformational diseases, including Alzheimers disease, type 2 Diabetes Mellitus and Cancer, poses a global challenge at many different levels. It has devastating effects on the sufferers as well as a tremendous economic impact on families and the health system. In this work, we apply a cross-functional approach that combines ideas, concepts and technologies from several disciplines in order to study, in silico and in vitro, the role of a novel chemical chaperones family (NCHCHF) in processes of protein aggregation in conformational diseases. Given that Serum Albumin (SA) is the most abundant protein in the blood of mammals, and Bovine Serum Albumin (BSA) is an off-the-shelf protein available in most labs around the world, we compared the ligandability of BSA:NCHCHF with the interaction sites in the Human Islet Amyloid Polypeptide (hIAPP):NCHCHF, and in the amyloid pharmacophore fragments (Aβ17–42 and Aβ16–21):NCHCHF. We posit that the merging of this interaction sites is a meta-structure of pharmacophore which allows the development of chaperones that can prevent protein aggregation at various states from: stabilizing the native state to destabilizing oligomeric state and protofilament. Furthermore to stabilize fibrillar structures, thus decreasing the amount of toxic oligomers in solution, as is the case with the NCHCHF. The paper demonstrates how a set of NCHCHF can be used for studying and potentially treating the various physiopathological stages of a conformational disease. For instance, when dealing with an acute phase of cytotoxicity, what is needed is the recruitment of cytotoxic oligomers, thus chaperone F, which accelerates fiber formation, would be very useful; whereas in a chronic stage it is better to have chaperones A, B, C, and D, which stabilize the native and fibril structures halting self-catalysis and the creation of cytotoxic oligomers as a consequence of fiber formation. Furthermore, all the chaperones are able to protect and recondition the cerebellar granule cells (CGC) from the cytotoxicity produced by the hIAPP20–29 fragment or by a low potassium medium, regardless of their capacity for accelerating or inhibiting in vitro formation of fibers. In vivo animal experiments are required to study the impact of chemical chaperones in cognitive and metabolic syndromes.

Novel insight into streptozotocin-induced diabetic rats from the protein misfolding perspective

Protein folding is a process of self-assembly defined by the sequence of the amino acids of the protein involved. Additionally, proteins tend to unfold, misfold and aggregate due to both intrinsic and extrinsic causes. Human islet amyloid polypeptide (hIAPP) aggregation is an early step in diabetes mellitus. However, the aggregation of rat IAPP (rIAPP) remains an open question. Adult female Sprague-Dawley rats weighing 150–250 g were divided into two groups. The experimental group (streptozotocin [STZ]) (n = 21) received an intraperitoneal injection of a single dose of 40 mg/kg STZ. We used the mouse anti-IAPP antibody and the anti-amyloid oligomer antibody to study the temporal course of rIAPP oligomerization during STZ-induced diabetes using a wide array of methods, strategies and ideas derived from biochemistry, cell biology, and proteomic medicine. Here, we demonstrated the tendency of rIAPP to aggregate and trigger cooperative processes of self-association or hetero-assembly that lead to the formation of amyloid oligomers (trimers and hexamers). Our results are the first to demonstrate the role of rIAPP amyloid oligomers in the development of STZ-induced diabetes in rats. The IAPP amyloid oligomers are biomarkers of the onset and progression of diabetes and could play a role as therapeutic targets.

Today´s medical self and the other: Challenges and evolving solutions for enhanced humanization and quality of care

Background Recent scientific developments, along with growing awareness of cultural and social diversity, have led to a continuously growing range of available treatment options; however, such developments occasionally lead to an undesirable imbalance between science, technology and humanism in clinical practice. This study explores the understanding and practice of values and value clusters in real-life clinical settings, as well as their role in the humanization of medicine and its institutions. The research focuses on the values of clinical practice as a means of finding ways to enhance the pairing of Evidence-Based Medicine (EBM) with Values-based Medicine (VBM) in daily practice. Methods and findings The views and representations of clinical practice in 15 pre-CME and 15 post-CME interviews were obtained from a random sampling of active healthcare professionals. These views were then identified and qualitatively analyzed using a three-step hermeneutical approach. A clinical values space was identified in which ethical and epistemic values emerge, grow and develop within the biomedical, ethical, and socio-economic dimensions of everyday health care. Three main values—as well as the dynamic clusters and networks that they tend to form—were recognized: healthcare personnel-patient relationships, empathy, and respect. An examination of the interviews suggested that an adequate conceptualization of values leads to the formation of a wider axiological system. The role of clinician-as-consociate emerged as an ideal for achieving medical excellence. Conclusions By showing the intricate clusters and networks into which values are interwoven, our analysis suggests methods for fine-tuning educational interventions so they can lead to demonstrable changes in attitudes and practices.

Amyloid Biomarkers in Conformational Diseases at Face Value: A Systematic Review

Conformational diseases represent a new aspect of proteomic medicine where diagnostic and therapeutic paradigms are evolving. In this context, the early biomarkers for target cell failure (neurons, β-cells, etc.) represent a challenge to translational medicine and play a multidimensional role as biomarkers and potential therapeutic targets. This systematic review, which follows the PICO and Prisma methods, analyses this new-fangled multidimensionality, its strengths and limitations, and presents the future possibilities it opens up. The nuclear diagnosis methods are immunoassays: ELISA, immunodot, western blot, etc., while the therapeutic approach is focused on pharmaco- and molecular chaperones.

Diabetes Drug Discovery: hIAPP1–37 Polymorphic Amyloid Structures as Novel Therapeutic Targets

Human islet amyloid peptide (hIAPP1–37) aggregation is an early step in Diabetes Mellitus. We aimed to evaluate a family of pharmaco-chaperones to act as modulators that provide dynamic interventions and the multi-target capacity (native state, cytotoxic oligomers, protofilaments and fibrils of hIAPP1–37) required to meet the treatment challenges of diabetes. We used a cross-functional approach that combines in silico and in vitro biochemical and biophysical methods to study the hIAPP1–37 aggregation-oligomerization process as to reveal novel potential anti-diabetic drugs. The family of pharmaco-chaperones are modulators of the oligomerization and fibre formation of hIAPP1–37. When they interact with the amino acid in the amyloid-like steric zipper zone, they inhibit and/or delay the aggregation-oligomerization pathway by binding and stabilizing several amyloid structures of hIAPP1–37. Moreover, they can protect cerebellar granule cells (CGC) from the cytotoxicity produced by the hIAPP1–37 oligomers. The modulation of proteostasis by the family of pharmaco-chaperones A–F is a promising potential approach to limit the onset and progression of diabetes and its comorbidities.

Smoothed Body Composition Percentiles Curves for Mexican Children Aged 6 to 12 Years

Overweight children and childhood obesity are a public health problem in Mexico. Obesity is traditionally assessed using body mass index (BMI), but an excess of adiposity does not necessarily reflect a high BMI. Thus, body composition indexes are a better alternative. Our objective was to generate body composition percentile curves in children from Mexico City. A total of 2026 boys and 1488 girls aged 6 to 12 years old were studied in Mexico City. Body weight, height, and BMI calculation were measured. Total body fat percentage (TBFP) was derived from the skinfold thicknesses, and fat mass (FMI) and free fat mass indexes (FFMI) were calculated. Finally, age- and gender-specifıc smoothed percentile curves were generated with Cole’s Lambda, Mu, and Sigma (LMS) method. In general, height, weight, waist circumference (WC), and TBFP were higher in boys, but FFM was higher in girls. TBFP appeared to increase significantly between ages 8 and 9 in boys (+2.9%) and between ages 10 and 11 in girls (+1.2%). In contrast, FFM% decreased noticeably between ages 8 and 9 until 12 years old in boys and girls. FMI values peaked in boys at age 12 (P97 = 14.1 kg/m2) and in girls at age 11 (P97 = 8.8 kg/m2). FFMI percentiles increase at a steady state reaching a peak at age 12 in boys and girls. Smoothed body composition percentiles showed a different pattern in boys and girls. The use of TBFP, FMI, and FFMI along with BMI provides valuable information in epidemiological, nutritional, and clinical research.

Evaluación de la calcinosis distrófica en dermatomiositis juvenil y esclerosis sistémica

Background: Dystrophic calcinosis is associated with juvenile dermatomyositis and systemic sclerosis. Clini- cal diagnosis is performed through the detection of sub- cutaneous, hard nodules. Conventional radiographic studies may demonstrate calcium deposits, however, with very early lesions X-rays may prove insufficient. There are a few studies where scintilliography has been used to identify dystrophic calcinosis. Objectives: To estimate the frequency of dystrophic calcinosis in patients with juvenile dermatomyositis and systemic sclerosis/CREST syndrome. To estimate the concordance between the diagnoses of dystrophic calcinosis obtained by physical examination and scin- tigraphy. Patients and Methods: Observational, transversal and comparative study in which patients of both genders, between 5 and 7 years of age with the diagnoses of juvenile dermatomyositis and systemic sclerosis/CREST syndrome were included in order to detect dystrophic calcinosis by physical examination and scintigraphy. Fisher’s exact test was used to evaluate the association between both diagnostic methods, Kappa test was used to evaluate the level of concordance between both methods and a distribution by group analysis was used to analyze the extent of dystrophic calcinosis with both methods. Sensitivity and specificity for scintigraphic findings in soft tissues, bony protrusions , ribs and vertebrae was also estimated. Results: The frequency of dystrophic calcinosis was 80%. Dystrophic calcinosis was detected through physical examination in 16 patients and through scin- tigraphy in 9 patients. No association or concordance was found between the clinical and the scintigraphic findings. Scintigraphy has a 37.5% sensitivity for the detection of dystrophic calcinosis in soft tissues and 43.8% in bony protrusions, but is ideal for its detec- tion in the ribs. Conclusions: Both, physicial examination and scin- tigraphy are complementary tools for the detection of dystrophic calcinosis.