Clinical Research Insider [CLiR] number 0

ZERO

January 2 0 2 0

CLINICAL RESEARCH INSIDER

[ the

search for a clearer future ]

Federico Lerner • Guillermo Caletti • Thor Nissen Andrea Buschiazzo • Carmen de la Rocha • Dolores Garnica Alfredo Castro • Juan Francisco Pérez-Vargas • Édgar Mondragón Ángel Ortuño • Olga García • Diana Garza-Islas • Jorge Palos Francisco Payó González • Sergio Segovia • Tonatiuh Moreno

[

CLINICAL RESEARCH INSIDER

ZERO January 2 0 2 0

Table of Contents EDITORIAL

5

Yara Patiño-Estévez, EIC

COLUMN ACADEMICS

9

Aging & Age-Related Diseases

Guillermo Caletti, MD, PhD

COLUMN ECONOMICS

17

The Rebirth of Clinical Research in Latin America

Federico Lerner, MD, PhD

RESEARCH

21

New Paradigms in Clinical Research

Andrea Buschiazzo, MD, PhD

24

Age-Related Pain

Thor Nissen, MD, PhD

28

Vitamin and Mineral Supplementation

Carmen de la Rocha, PhD

PROFILE

GADGETS

James Lovelock’s One Hundred Years

Edgar Mondragón

30

Dolores Garnica

OPINION

34

China, R&D Haven?

38

Cybersecurity

Juan Francisco Pérez-Vargas Alfredo Castro

ART-LITERATURE

43

De Rerum Natura

44

Mismatched

48

Image May Contain

50

Visual Arts

Ángel Ortuño Olga Gutiérrez Diana Garza-Islas Jorge Palos

51

From AI Noses to Cyborgs

EDITION INQUIRY

53

What has been the most astonishing discovery in healthcare science in the last 20 years?

LUDIC

57

A Glimpse into Cyberpunk 2077

Sergio Segovia

61

To Live Again, To Live Forever, To Live on the Screen

Francisco Payó González

64

Humor

Tonatiuh Moreno

1

]

[

2

]

Staff Directory Direction

Translators

Collaborators

GENERA L DIR ECTO R

Kimrey Anna Batts Ramón Ramírez-Lomelí Gregory J. Dechant

Andrea Buschiazzo Guillermo Caletti Alfredo Castro Olga García Dolores Garnica Diana Garza-Islas Federico Lerner Édgar Mondragón Tonatiuh Moreno Thor Nissen Ángel Ortuño Jorge Palos Francisco Payó González Juan Francisco Pérez-Vargas Carmen de la Rocha Sergio Segovia

Marco Cid EX EC UTIVE DIR ECTO R

Ivette Venegas

Editorial

Comercial GE N E RA L M A N AGE R

Ana Paula Villarruel

EDITO R IN C HIEF

Yara Patiño-Estévez

SA L E S & SU SC R I PT I O N S

Dulce Besanilla STYLE C O R R ECTIO N

Kimrey Anna Batts Dolores Garnica

MARKETING

Laura Gonçalves

ORIGINA L LAYO UT DES IG N

Media

Luis Fernando Ortega

D I GI TA L L AYO U T

Plaza Network, LLC C OM M U N I T Y M A N AGE R

Patricio Muñoz

Clinical Research Insider www.clir ins ider.com

CLiR Insider is a trademark of CRPS, Clinical Research Professional Services, LLC. All rights reserved. CLiR Insider is published quarterly by CRPS, Clinical Research Professional Services, LLC.12550 Biscayne Blvd, STE 110, Miami, Fl. USA. Editor in Chief Yara Patiño Estévez. The content of the articles and publicity is responsibility of their authors and the sponsors. CLiR Insider is not responsible for information in advertising content. The prices shown in this publication are only for informational purposes only and are subject to change. Printed in Coloristas y Asociados, S.A. de C.V., México.

[

About CLiR Insider Clinical Research Insider [CLiR] is informative in nature and aims to be of interest for those in the fields of clinical research, healthcare, and life sciences, as well as for the public in general, along with forging a bridge between these two audiences.

We seek to address topics both current and timeless: such as the future of health, new paths being followed by researchers, the impact of technology and the economy, global perception, new paradigms, and even philosophical concerns, from existential to ethical and aesthetic issues – all of this using high-quality content, with clarity and seriousness, art and humor.

We aim to make this medium a reliable, accessible source that creates connections between all those who, in one way or another, are involved in clinical research. At CLiR we hold the conviction that as patients and users, all of us can enjoy the fruits of this important and relevant work.

3

]

[

4

]

“The essence of a scientific objective is its potential for surprise, its ability to surpass the expectations and the imagination allowed by the dominate manners of thinking and doing.�

Lorraine Daston

[

Editorial CLiR is a medium, a means for communication, a channel, a bridge. It is a giant ear and at the same time, a speaker. Its purpose is to ferry ideas from one sphere to the other, from one group of people to another.

Here we bring together researchers from different disciplines, a diversity of scientists, artists and creators, scientific objectives and users of science —which are all of us— subjectivities, discoveries, inventions, visual and written ideas, work and diversion, seriousness and a more recreational approach: whatever is necessary to clarify, in one way or another, knowledge, thought, and reality.

We use clinical research as a starting point, thanks to the collective experiences of those who have converged to create this object —this magazine, this meeting of ideas. We begin with a view through the microscope, one of observation and analysis. We move, by trial and error, towards evidence, discovery, towards what we can imagine. We move towards the collective production of new scientific objectives, of new ideas, of innovation - all of which will be shared, for such is the way forward.

Using this model —a network, a multiplicity— we seek to shine our own light and to receive light from others: to achieve greater clarity and to ensure that this feeling is collective. We wish to reach as far as possible: for in science, as in the imagination, there are no limits. Everything can be researched: we depart from this point, we arrive to this point, and we share it.

In both science and art, we begin the creative process by asking ourselves about life – about its start and its end. Here we ask the old and the new questions, which are at times one and the same. We recognize our most ancient desires and fears, and the dreams that accompany us. We thus choose to begin in this vein: this first edition’s central topic is the future of life, and we attempt to ponder this concept through the lens of clinical research, using the latest ideas and the newest technologies, bringing together different fields of knowledge and diverse ways of seeing, searching, and finding. We are in THE SEARCH FOR A CLEARER FUTURE. I invite you to read and write, to ask us and to help us respond. Welcome to this new experiment.

5

]

[

8

]

Aging & Age-Related Diseases

Aging can range from “successful” to “pathological”, depending on the reserve functions of the different physiological systems, their resilience, and the consequent appearance of disease.

Column Ac ademic s

Guillermo Caletti, MD, PhD

A ging Aging is a complex phenomenon which, on its various levels —molecular, cellular, physiological and psycho-social, etc.— proves difficult to define (1).

The definition of aging is difficult, and remains under discussion due to the undetermined factors causing this complex phenomenon. The most accepted functional definition is that a decrease in physiological reserves, while still supporting acceptable functioning in the steady state, cannot adapt to any additional stress, even if it is psychological in nature.

Aging itself is thus associated with progressive homeostatic/homeodynamic dysregulation that causes the organism to progressively lose resilience, until it becomes completely non-resilient (Yates 2002; Lipsitz 2004).

Aging can range from “successful” to “pathological”, depending on the reserve functions of the different physiological systems, their resilience, and the consequent appearance of disease. Frailty can be considered an intermediate, yet distinct state between these two extremes, where a certain possibility for reversal of pathological processes may still exist (Bortz, 2002).

[

9

]

[ 1 0 ]

The development of longevity drugs has evolved from a far-off goal into an industry priority. Several companies are working on developing drugs that target aging, and some of these drugs are currently in clinical trials.

Frailty may thus set off a chain of events that result in a pathological situation, or disease, in a formerly-healthy aging person. This occurs when there is no other reason available to explain the cause for a decline in health. The ability to predict frailty is key to its modulation and prevention.

The best-known aspect of frailty is its consequences, which include morbidity, institutionalization and ultimately, death.

Impaired nutritional status – primarily related to poor nutrient intake – is also one of the key characteristics in frailty.

Most frail patients experience fatigue, problems with balance, decreased endurance and difficulties adapting to changing circumstances (Pel-Little et al. 2009; De Lepeleire et al. 2009).

Not all frail elderly people will experience all the symptoms mentioned. This seems to be closely associated with remaining reserve capacity, and hence, with resilience. Only when this reserve capacity of interconnected physiological systems is reduced to a crucial level, will the signs and symptoms of frailty become clinically evident. This is the moment when the aging process may cause a clinically apparent disease entity, namely frailty. Reserve capacity is decreased and the adaptation mechanisms to stressors can no longer be mobilized, leading to a breakdown of homeostasis and crossing the threshold to clinically manifested frailty syndrome.

i nflAmm - Aging Inflammation is a physiological process that repairs tissues in response to endogenous or exogenous aggressions. A chronic state of inflammation may have detrimental consequences. Aging is associated with increased levels of circulating cytokines and proinflammatory markers. Age-related

changes in the immune system – known as immunosenescence – and increased secretion of cytokines by adipose tissue represent the major causes of chronic inflammation (M. Michaud et al. 2013). This phenomenon is known as “Inflamm-aging”. In older subjects, high levels of interleukin (IL)-6 , IL-1 tumor necrosis factor – α, and C-reactive protein are associated with an increased risk of morbidity and mortality. In particular, cohort studies have indicated that TNF-α and IL-6 levels are markers of frailty. The low-grade inflammation characterizing the aging process notably concurs at the pathophysiological mechanisms underlying sarcopenia. In addition, proinflammatory cytokines (through a variety of mechanisms, such as platelet activation and endothelial activation) may play a major role in the risk of cardiovascular events. Dysregulation of the inflammatory pathway may also affect the central nervous system and be involved in the pathophysiological mechanisms of neurodegenerative disorders (e.g., Alzheimer’s disease).

D rug D evelopment

for the

e lDerly

The development of longevity drugs has evolved from a faroff goal into an industry priority. Several companies are working on developing drugs that target aging, and some of these drugs are currently in clinical trials.

In the longevity industry, there are nine hallmarks of aging which are thought to be the root causes of aging.

g enomic i nstAbility Genomic instability refers to psychological stress, sun radiation, toxic chemicals, and biological agents which either di-

Column Ac ademic s

[ 1 1 ]

[ 1 2 ]

Not all frail elderly people will experience all the symptoms mentioned. This seems to be closely associated with remaining reserve capacity, and hence, with resilience.

rectly trigger replication errors in DNA, or induce DNA damage through reactive oxygen species activity. Our genomes are faced with possible damage on a daily basis. Genomes owe their integrity and stability to the inbuilt repair systems that fix this accumulated damage.

t elomere A ttrition The telomere theory of aging proposes that telomeres act as a protective cap for chromosomes and that as their length decreases with each division cycle, they lose their protective function. Telomere theory is one of the predominant hypotheses used to describe aging. Pharmacological attempts to restore telomeres are underway.

e pigenetic A lterAtion The aging process can cause alterations to our epigenome, which can in turn lead to alterations in gene expression that can potentially change and ultimately compromise cell function. As an example, epigenetic alterations of the immune system can harm activation and suppress immune cells, leaving humans vulnerable to immune system failure and inflammation. Few pharmacological solutions currently exist.

l oss

of

p roteostAsis

Loss of proteostasis is a common aging-related process and indicator of disease. This process is characterized by an accu-

mulation of harmful or misfolded proteins and unwelcome aggregates. With age, the degradation of these proteins is impaired. We know that aging cells have reduced autophagy capability, and that lysosomes become less efficient at eliminating cellular waste. Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, and prion diseases are examples of pathologies linked to loss of proteostasis.

D eregulAteD n utrient s ensing Metabolic activity is known to stress our cells. Caloric restriction is a preventive therapy for slowing metabolic dysfunction. Some byproducts of metabolism, such as mitochondrial dysfunction and oxidative stress, are harmful, and can dysregulate nutrient-sensing and lead to diabetes. There are several key metabolic signaling pathways that can regulate the speed of aging: IGF-1 and the IIS pathway, and the mTOR-Akt signaling axis. AMP-activated kinase and Sirtuins proteins also take part in nutrient sensing. All of these proteins are potential targets for anti-aging investigation. Intermittent caloric restriction remains the most widely recognized preventive therapy to slow down potential metabolic dysfunctions.

m itochonDriAl D ysfunction There are few drugs currently in development for mitochondrial dysfunction, but some are emerging in the area of regenerative medicine. Mitochondria are involved in the

Column Ac ademic s

metabolism of urea, cholesterol, and neurotransmitters, and are responsible for detoxification and free radical production, as well as for the digestion of fat, carbohydrates and proteins.

Their dysfunctions lead to a number of systemic disorders, and many common aging pathologies have been found to have their roots in mitochondrial dysfunction. Mitochondrial dysfunction has been implicated in type 2 diabetes, atherosclerotic heart disease, cancer, Alzheimer’s disease, Parkinson’s disease and stroke. Mitochondrial dysfunction is thought to be one of the key reasons why humans age.

c ellulAr s enescence With age, a buildup of cells that refuse to die in order to be replaced takes place. These cells have impaired cellular function, reduce tissue repair, accumulate potentially cancer-causing mutations, and increase chronic inflammation. This phenomenon of the irreversible arrest of cell division cycles is called cellular senescence. Senescence is a universal process that affects almost all cells. With age, immune reactivity declines and some senescent cells escape immune clearance. By the time humans reach old age, they have a massive accumulation of senescent cells. The long-term presence of senescence cells within tissues can potentially promote age-related diseases and may even cause aging itself.

[ 1 3 ]

[ 1 4 ]

Science is charting a path towards achieving our goal of eternal life �or at least of living a longer life, free from disease� and there are already a number of potential options that can offer longevity and happiness.

s tem c ell e xhAustion Stem cells can differentiate into many other cell types and serve as regenerative and renewing components within tissues. Stem cells replenish tissues with functional differentiated cells to maintain normal cellular and tissue functions.

Since the number of stem cells declines throughout life, younger people have higher replenishing potential. Stem cells accumulate genetic mutations and damage with age, and thus tend to lose their differentiation capacity. Stem cell exhaustion is a hallmark of aging, as it represents a failure to renew tissues.Â

A ltereD i ntercellulAr c ommunicAtion As humans age, the electrical and chemical signaling systems between cells become corrupted, resulting in distorted signals. Corrupted messages lead to an imbalance in cellular communication. As cells age, they produce more inflammation signals, due to dysfunction in the immune systems and accumulation of tissue damage. The result is chronic inflammation and disease, including atherosclerosis, type 2 diabetes, obesity, and chronic peptic ulcer.

Column Ac ademic s

c onclusions : Humans are always seeking options for a longer and fuller life.

Aging is a natural phenomenon that interferes with the normal desire to avoid old age.

Science is charting a path towards achieving our goal of eternal life —or at least of living a longer life, free from disease— and there are already a number of potential options that can offer longevity and happiness.

References: Fulop T, et al. (2010). Aging, frailty and age-related diseases. Biogerontology 11:547-563.

Yates FE. (2002). Complexity of human being: changes with age. Neurobiol Aging 23(1):17-19 Lipsitz LA. (2004). Physiological complexity, aging, and the path to frailty. Sci Aging Knowledge Envorin 2004 (16):pe16.

Bortz WM II (2002). A conceptual framework of frailty: a review. J Gerontol A Biol Sci Med Sci 57(5):M283-M288.

Pel-Little, et al (2009). Frailty: defining and measuring of a concept. J Nutr Health Aging 13(4):390-394.

De Lepeleire, et al (2009). Frailty: an emerging concept for general practice. Bt J Gen Pract 59(562):e177-e182.

Michaud M. et al. (2013). Proinflammatory Cytokines, Aging and Age-related diseases. JAMDA 14, 877 – 882.

Collangelo M. Current State of Longevity. 2019.

Linkedin. https://bit.ly/379QUs1

[ 1 5 ]

Column Ec onomic s

The Rebirth of Clinical Research in Latin America If I have seen further, it is by standing on the shoulders of giants: this is what has allowed me to see the rebirth of clinical research in Latin America.

by Federico Lerner, MD, PhD In order to tell the story correctly, we must travel back in time to the late 1980s and early 90s, when clinical research began in the region. At the time, a limited number of researchers sporadically carried out work for colleagues abroad. This activity was unregulated, and continued as such until it began to grow.

Some Latin American countries started to introduce regulations, and several companies (mostly CROs) also entered the region. Physicians began to invest in their sites, creating specific areas for clinical research. Sponsors began including Latin American countries in their development plans, allowing for the first big boom.

This first boom reached its peak in the early 2000´s and continued through the decade, with clinical research growing at a fast pace throughout the region and undergoing significant development.

Thousands of clinical trials were conducted, researchers chose to specialize in clinical research, and new, dedicated in-

[ 1 7 ]

[ 1 8 ]

Predicting the future is a difficult task, but we need to keep in mind our history, the changes we have undergone, and our own capacity for adaptation.

Column Ec onomic s

stitutions were created. The most important part of this story, however, is that thousands of patients benefited from having the ability to access alternate, innovative therapies and new techniques, devices and medications.

Medical innovations and breakthroughs in research spread throughout the medical community as part of the standard of care (such as RECIST criteria for tumor progression and rating scales for different CNS pathologies).

During these years, the early phases of clinical development were carried out in the region, both in patients and with healthy volunteers. Mega trials (those recruiting more than 15,000 patients) were conducted. Local companies grew and thrived during this period.

Fast-paced growth introduced new regulations, which tended to set the region back. Regulatory processes became more complex, with multiple steps and red tape. The need for more researchers prompted the introduction of people who lacked the proper training and background for the specific area in question. These factors, combined with the competition for studies and patients, caused the region to lose its competitive edge and its ability to deliver.

Quality issues, the financial problems of sponsors, and the longer and more complex regulatory process damaged the

region´s reputation, placing a “delay” sign above the first big boom. By the middle of this decade, a new era had begun.

Regulations were revised and rewritten, providing expedited evaluations and robust feedbacks for dossiers. The sites able to cope with these changes evolved, becoming more efficient and adaptable to a new research environment. Companies looked favorably upon this new era, and the region has reemerged on their radar.

Research, as it was carried out during that first big boom, has changed: clinical trials are no longer massive, medicine is more personalized, and research is more patient-centric and focused, more purposeful and targeted. Research into rare diseases is the most concrete example of this, but there are others. Once biomarkers expand, this new era will broaden research for disease subtypes.

Predicting the future is a difficult task, but we need to keep in mind our history, the changes we have undergone, and our own capacity for adaptation. Those of us able to understand these changes and adapt to them will most likely have bright futures ahead of us, since we are able to see beyond a particular circumstance or historical moment. As Bernoulli stated in the work of Isaac Newton, “If I have seen further it is by standing on the shoulders of giants.”

[ 1 9 ]

Researc h

New Paradigms in Clinical Research: Early Access Programs and Clinical Trials for Unmet Medical Needs

by Andrea Buschiazzo, MD

Despite a number of novel therapies having gained worldwide approval in recent years, there are still several diseases for which unmet medical needs persist. For this reason, there has been a dramatic increase in the approval of new medicines by the Food and Drug Administration (FDA) and the European Medicines Agency (EMA). The authorization for commercializing these new drugs is based on the data reported by pharmaceutical companies through their research, which resulted in the development of novel therapeutic approaches, such as new monoclonal antibodies for the treatment of autoimmune diseases and anticancer drugs that act on genetic biomarkers.

For patients with serious or life-threatening diseases who have failed to respond to the available treatment options and who are not eligible for participation in clinical trials, Early Access Programs (EAPs) provide access to investigational therapies (prelaunch and/or prior to country approval). Since they are governed by different regulatory authorities, EAPs vary by country.

It is a program that may be implemented at different levels of the

[ 2 1 ]

[ 2 2 ]

Lastly, in order to further implement clinical research, a strengthening in research infrastructure and training is needed to speed up the marketing process. product life cycle, during the regulatory submission process and prior to marketing authorization. Through this program, patients who demonstrate unmet medical needs can receive promising new treatments. Certain challenges should be considered, however, such as the high risk related to drug safety, high costs, and concerns regarding access.

The Challenges of New Paradigms in Clinical Research EAPs should be applied only in fully justified circumstances in order to ensure that the patient’s unmet medical needs are addressed. The majority of EAPs are based on surrogate endpoints, with less data related to efficacy, safety, and quality of life. However, the interpretation of data from clinical studies is critical. It is common knowledge that several drugs that were approved via fast-track procedures by the

FDA were withdrawn for safety reasons; this was the case with rofecoxib (VIOXXÂŽ), which was withdrawn due to an increased risk of cardiovascular events.

Conclusion Despite the progress made in the field of clinical research, unmet therapeutic needs are still identified in several clinical areas (Miller, 2009; Taiwo et al. 2010; Aceves, 2014; Markowitz, 2015; Morrow et al. 2017). Although EAPs improve the patient’s access to new medicines, data on their true effectiveness and safety could be a concern. The active participation of patients in clinical research studies will improve the reliability of trial results and lead to a better real-world approach.

Lastly, in order to further implement clinical research, a strengthening in research infrastructure and training is needed to speed up the marketing process.

[ 2 3 ]

Early Access Programs

Clinical Trials

Purpose

Allow patients who have failed Evaluate safety and efficacy of with all available approved a new medical treatment or a medicines to have access to medicines still in development. new indication

Criteria

Physicians’ discretion for patients with unmet medical needs

Protocol-specific requirements

Sponsor

Physicians

Pharmaceutical and Biotech companies in research centers

Drug Development Phase

Late Phase II and onwards

Starts from Phase I and onwards

There are four substantial differences between Clinical Trials and Early Access Programs.

References: Fountzilas E, Said R & Apostolia M, Tsimberidou AM. Expanded Access to Investigational Drugs: Balancing Patient Safety with Potential Therapeutic Benefits. Expert Opin Investig Drugs. 2018 Feb;27(2):155-162. doi: 10.1080/13543784.2018.1430137.

Miller, C. E. (2009). Unmet therapeutic needs for uterine myomas. J. Minim. Invasive Gynecol. 16, 11–21. doi: 10.1016/j.jmig.2008.08.015 Papaluca, M., Greco, M., Tognana, E., Ehmann, F., and Saint-Raymond, A. (2015). White spots in pharmaceutical pipelines-EMA identifies potential areas of unmet medical needs. Expert Rev. Clin. Pharmacol. 8, 353–360. doi: 10.1586/17512433.2015.1028918.

Andrea Paula Buschiazzo, MD Board Certified Rheumatologist, with over 25 years in clinical and academic Rheumatology. Over 25 years’ experience in Pharmaceutical Industry, and with CROs. Therapeutic Experience in Rheumatology/Autoimmune diseases (SLE, RA, Psoriatic Arthritis, Spondyloatrhritis, Gout, Paget, Sjogren, Vasculitis, Juvenile Arthritis, Scleroderma, Osteoporosis, Osteoarthritis, Fibromyalgia, and Biosimilar Studies) and others areas such as Infections diseases, Cardiovascular, CNS, Metabolic diseases, Vaccines, Urology, Psychiatry, Gastroenterology, Ophthalmology, Women& Health, Pediatric diseases, Nephrology, Dermatology, Hematology, Oncology)

[ 2 4 ]

Age-relAted PAin Are complaints about pain to be expected among the elderly?

Researc h

Pain is recognized as a common and highly prevalent symptom in older adults.

It is likewise possible that pain goes underreported in the elderly, due to an incorrect belief that it is an inevitable part of aging.

by Thor Nissen, MD, PhD There are a variety of definitions of pain. This indicates that no one definition comprises the many components associated with this highly personal, subjective, and vivid phenomenon, which is experienced by every human being, starting soon after conception and persisting until the ceasing of all organic functions. According to the International Association for the Study of Pain (IASP), pain is: “An unpleasant sensory and emotional experience associated with actual or potential tissue damage, or described in terms of such damage (1).” Moreover, with general human life expectancy rising to 70 for men and 75 for women, there are more and more people each day who reach old age (2).

So, how are aging and pain connected? Both are generally considered unpleasant, even if it is understood that they are unavoidable and are ordinarily a natural warning sign of actual or potential damage. Furthermore, they both include an emotional component where state of mind, attitude, and attitude, and beliefs —among other adaptative processes— can serve to exacerbate or alleviate the experience.

Pain is recognized as a common and highly prevalent symptom in older adults. It is likewise possible that pain goes underreported in the elderly, due to an incorrect belief that it is an inevitable part of aging (3). The lack of systematic epidemiological investigation makes it difficult to accurately esti-

[ 2 5 ]

[ 2 6 ]

The real “must” is the comprehensive management of such conditions, always placing the emphasis on a sensible, customized, and successful analgesic approach.

mate the frequency of issues with pain for this demographic (4). Elderly people suffer from different kinds of conditions associated or coexisting with pain: progressive degenerative processes (e. g., arthrosis, osteoarthritis, degenerative spinal changes), cancer, polymorbidity (e.g., diabetes mellitus, vascular disease), declining immune competence, polyneuropathy, and other neuralgias. Insufficiently treated chronic or periodically reoccurring pain can lead to serious interferences with physical, cognitive, and everyday social abilities —and as such, to a limited quality of life. Due to existing comorbidity, polypharmacy, and impaired organ function, adequate pain treatment for the elderly goes beyond the boundaries set for younger individuals. Moreover, underqualified medical management and complicated pain capture in cognitive affected patients (5) results in significantly fewer analgesics being prescribed to the aging population. Published papers have found statistically significant differences in pain sensitivity response between old and younger adults, but the direction of change was inconsistent (6).

The relationship between pain and other neuropsychiatric or organic disorders remains controversial, with evidence supporting both increased and decreased unpleasantness and emotional responsiveness in, for example, people with dementia, in comparison with healthy controls (7).

Non-pharmacologic treatment of pain in the elderly plays an important role, as well, with psychological support and adequate exercise showing benefits up to the level of the endocannabinoid system (8,9,10).

Pain is not a must as people grow old. However, certain painful conditions are more prevalent in the elderly, such as chronic pain. Age-related cellular and organ changes are being studied as possible treatment targets in addressing both aging and pain (11,12,13,14).

The real “must” is the comprehensive management of such conditions, always placing the emphasis on a sensible, customized, and successful analgesic approach (15).

[ 2 7 ]

References: 1 Treede RD. The International Association for the Study of Pain definition of pain: as valid in 2018 as in 1979, but in need of regularly updated footnotes. Pain Rep. 2018; 3(2):e643. Published 2018 Mar 5. doi:10.1097/PR9.0000000000000643 2 Life expectancy by continent and gender 2019 Published by Erin Duffin, Sep 20, 2019 in Statista https://bit.ly/2v3CM5d 3 Prostran M, Vujović KS, Vučković S, et al. Pharmacotherapy of Pain in the Older Population: The Place of Opioids. Front Aging Neurosci. 2016;8:144. Published 2016 Jun 16. doi:10.3389/ fnagi.2016.00144 4 Mobily PR, Herr KA, Clark MK, Wallace RB. An Epidemiologic Analysis of Pain in the Elderly. Journal of Aging and Health. 2016; 6(2):139-154. doi:10.1177/089826439400600201 5 Eiche J, Schache F. Pain Management in geriatric patients. DMW -Deutsche Medizinische Wochenschrift. 2016;141(9):635-641. doi:10.1055/s-0041-106307 6 El Tumi H, Johnson MI, Dantas PBF, Maynard MJ, Tashani OA. Age‐related changes in pain sensitivity in healthy humans: A systematic review with meta‐analysis. European Journal of Pain.

2017; 21(6):955-964. doi:10.1002/ejp.1011 7 Gagliese, Gauthier, Narain, Freedman. Pain, aging and dementia: Towards a biopsychosocial model. Progress in Neuropsychopharmacology & Biological Psychiatry. 2018; 87:207-215. doi:10.1016/j.pnpbp.2017.09.022 8 Arewasikporn A, Roepke AM, Turner AP, et al. Goal Pursuit, Goal Adjustment, and Pain in Middle-Aged Adults Aging With Physical Disability. Journal of Aging and Health.

2019;31:214S-240S. doi:10.1177/0898264319827142 9 Zou L, Zhang Y, Liu Y, et al. The Effects of Tai Chi Chuan Versus Core Stability Training on Lower-Limb Neuromuscular Function in Aging Individuals with Non-Specific Chronic Lower Back Pain. Medicina. 2019;55(3). doi:10.3390/medicina55030060 10 Watkins. Endocannabinoids, exercise, pain, and a path to health with aging. Molecular Aspects of Medicine. 2018;64:68-78. doi:10.1016/j.mam.2018.10.001 11 Cruz-Almeida Y, Fillingim RB, Riley JL, et al. Chronic pain is associated with a brain aging biomarker in community-dwelling older adults. Pain. 2019;160(5):1119-1130. doi:10.1097/j. pain.0000000000001491 12 Johnson AJ, Terry E, Bartley EJ, et al. Resilience factors may buffer cellular aging in individuals with and without chronic knee pain. Molecular Pain. 2019;15:1744806919842962. doi:10.1177/1744806919842962 13 Hackett J, Naugle KE, Naugle KM. The Decline of Endogenous Pain Modulation With Aging: A Meta-Analysis of Temporal Summation and Conditioned Pain Modulation. Journal of Pain, The. 9999. doi:10.1016/j.jpain.2019.09.005 14 Cruz-Almeida Y, Sinha P, Rani A, Huo Z, Fillingim RB, Foster T. Epigenetic aging is associated with clinical and experimental pain in community-dwelling older adults. Molecular Pain.

2019;15:174480691987181. doi:10.1177/1744806919871819 15 Walco, Krane, Schmader, Weiner. Applying a Lifespan Developmental Perspective to Chronic Pain: Pediatrics to Geriatrics. Journal of Pain, The. 2016;17(9):T108-T117. doi:10.1016/j. jpain.2015.11.003

[ 2 8 ]

Vitamin and mineral supplementation and the effect on the genetic component in coming generations.

by Carmen de la Rocha, PhD Over the past few decades, a culture of supplementation has arisen in order to prevent deficiencies and undernutrition. This has been demonstrated to work in a number of cases: for example, thiamine (B1 vitamin) supplementation in Asiatic countries has reduced the incidence and prevalence of beriberi [1], and in Nordic countries, vitamin D supplementation in dairy products has prevented deficiencies resulting from a lack of exposure to sunlight [2]. During pregnancy, the practice of vitamin, mineral, and omega supplementation is used worldwide, and it has been shown to prevent complications such as preeclampsia and gestational diabetes along with benefiting birth weight, cognitive development, and other indicators favorable to the offspring’s health in their extrauterine life and into adulthood [3].

Pregnant women are of particular interest, since the influence of what they ingest during this period will have an effect on two subsequent generations: the baby developing in utero, and the generation after, whose germinal cells are also exposed during this period [4].

One of the most widely-used supplements during pregnancy is folic acid (FA), due to its relation with the reduction of the rate of neural tube defects. However, this vitamin is associated with an epigenetic mark called DNA methylation, which influences gene regulation [5].

Researc h

Pregnant women are of particular interest, since the influence of what they ingest during this period will have an effect on two subsequent generations.

Furthermore, recent reports show that women tend to exceed the recommended tolerable upper limit when taking folic acid supplements during pregnancy. This is of concern, since evidence from studies in rodents showed that FA exposure during gestation caused changes in gene expression and anxiety and hyperactivity in offspring.

It is known that supplementation during pregnancy is associated with increased DNA methylation in mice progeny in mice, which leads to a differential gene expression in comparison with their unsupplemented controls. Exposure to a higher-dose FA diet during gestation caused dysregulation of the expression of many genes, including neurodevelopmental genes, and epigenomic changes [6].

It is imperative that clinical research be carried out in order to understand the implication of over-supplementation. While for certain supplements no toxic effects are observed in the short term, it is possible that there are associated genetic marks that could have long-term repercussions and impact future generations.

References: [1] J. J. Dinicolantonio, A. K. Niazi, C. J. Lavie, J. H. O’Keefe, and H. O. Ventura, “Thiamine supplementation for the treatment of heart failure: A review of the literature,” Congest. Hear. Fail., vol. 19, no. 4, pp. 214-222, 2013.

[2] I. M. Grønborg, I. Tetens, M. Ege, T. Christensen, E. W. Andersen, and R. Andersen, “Modelling of adequate and safe vitamin D intake in Danish women using different fortification and supplementation scenarios to inform fortification policies,” Eur. J. Nutr., vol. 58, no. 1, pp. 227–232, 2019.

[3] T. A. Zerfu and H. T. Ayele, “Micronutrients and pregnancy; Effect of supplementation on pregnancy and pregnancy outcomes: A systematic review,” Nutr. J., vol.

12, no. 1, pp. 1–5, 2013.

[4] C. E. Aiken and S. E. Ozanne, “Transgenerational developmental programming,” Hum. Reprod. Update, vol. 20, no. 1, pp. 63-75, 2014.

[5] M. Valentin, P. Coste Mazeau, M. Zerah, P. F. Ceccaldi, A. Benachi, and D. Luton, “Acid folic and pregnancy: A mandatory supplementation,” Ann. Endocrinol. (Paris)., vol. 79, no. 2, pp. 91–94, 2018.

[6] D. Wiens and M. C. Desoto, “Is high folic acid intake a risk factor for autism?–a review,” Brain Sci., vol. 7, no. 11, 2017.

[ 2 9 ]

[ 3 0 ]

Encyclopaedia Britannica. Tim Cuff/Alamy.

Prof ile

James Lovelock’s One Hundred Years

by Dolores Garnica

James Lovelock’s temperature varies —according to the American Medical Association— between 36.5 and 37.2 degrees Celsius. The cells of the English scientist, meteorologist, writer, inventor, atmospheric chemist, and environmentalist, who recently turned one hundred, continue to regulate his temperature in spite of his surroundings and the time of day, his age and his ailments, his level of stress and other factors that may raise or lower the degrees of body heat that keep him alive.

The fact that cells maintain his temperature, as they do for all of us, seems miraculous to many, even as it constitutes a given to his doctors, a challenge for manufacturers of pharmaceuticals, and an inspiration for the recipient of the Wollaston Medal in 2006 for having, according to the citation, “opened up a whole new field of Earth science study.” Lovelock is the ideologue of the Gaia hypothesis, which proposes, in broad terms, that our planet regulates its own temperature by means of its cells, just as our bodies do, a fact that entails significant changes in how we define, observe, and study the earth. As he wrote in The Ages of Gaia (1988): “If we see the world as a superorganism of which we are a part —not the owner, nor the tenant; not even a passenger— we could have a long time

[ 3 1 ]

[ 3 2 ]

ahead of us and our species might survive…”

For Lovelock, this selfregulation would explain the vast climatic changes we are undergoing and, although it augurs still worse ones for the future, it suggests, far from certain pessimistic, apocalyptic theories, that it is precisely through the study of this planetary cellular self-defense mechanism that the care of the earth might be ensured. According to Lovelock (The Ages of Gaia), “the self-regulation of climate and chemical composition is a process that emerges from the tightly coupled evolution of rocks, air, and ocean —in addition to that of organisms. Such interlocking self-regulation, while rarely optimal —consider the cold and hot places of the earth, the wet and the dry— nevertheless keeps the Earth a fit place for life.” Precisely. For Lovelock, the planet regulates itself in order to preserve the

life existing on it, and that is perhaps the most controversial feature of a theory used, for example, to buttress the idea of a god that created human life and seeks to preserve it, or the existence of an energy that cares for the planet. Theories such as these, formulated outside of the scientific limits within which Lovelock works, show how influential his hypothesis has been since the 1970s, when it brought the issue of a planetary environmental crisis to the forefront.

The story of the Gaia hypothesis began with one of the inventions considered a key to the twentieth-century ecologist narrative, also created by James Lovelock (a Commander of the Order of the British Empire since 1990): the electron capture detector, the use of which led to the discovery of the distribution of pesticide residues in the environment, one of

Prof ile

An electron-capture detector (ECD) for a gas chromatograph, invented by James Lovelock.

Science Museum London.

the inspirations for the book Silent Spring, by Rachel Carson, known as the founder of the environmentalist movement, whose temperature was also regulated by her cells until her death in 1964.

The detector was so important to science that Lovelock, who was working at the time for NASA in the United States, had to surrender the patent, along with many of the results of the climate studies that led him to formulate his hypothesis.

“I suspect the Earth behaves like a gigantic living being,” he told his friend and neighbor William Golding, whose cells were also maintaining his body temperature, and who suggested the name Gaia to Lovelock in the late 1960s. In 1979 Lovelock published Gaia: A New Look at Life on Earth, followed by The Ages of Gaia in 1988 and The Revenge of Gaia in 2006, in addition to many other books and more than two hundred articles.

Ninety years ago, James Lovelock’s father gave him a kit for performing household electrical experiments, stimulating an interest in scientific work that has earned him eight honorary degrees, though no Nobel Prize. Currently Honorary Visiting Fellow at Green Templeton College, Oxford, but still an independent researcher, at one hundred, James Lovelock still has a great deal of work to do, as reflected in his optimism about nuclear energy, not as an armament, but as a contribution to the reduction of fossil fuels. As he explained in an interview: “There have been seven disasters since humans came on the earth, very similar to the one that’s just about to happen. I think these events keep sepa- rating the wheat from the chaff. And eventually we’ll have a human on the planet that really does understand it and can live with it properly. That’s the source of my optimism.” Lovelock’s wise cells continue to regulate his temperature.

[ 3 3 ]

[ 3 4 ]

China, R&D Haven?

by Juan Francisco Pérez-Vargas

It all started with an egg. Inside that egg was P’an-Ku, who hacked his way out of the shell and cleaved the earth from the sky, and yin from yang, with his bare hands, creating the Universe. His children, Nüwa and Fuxi, created the human race and invented hunting and writing. Huangdi, the Yellow Emperor, virtually invented civilization, with innovations ranging from agriculture to the calendar, and, of all things, soccer (this is completely factual: the first mention of this sport is contained in the Zhan Guo Ze, a military and political maneuvering text from the 5th Century BCE). Following him came Shennong, the Divine Peasant. Back in those days, people’s diets consisted of what amounted to raw shellfish, herbs, fruits of dubious origin, and river water. Needless to say, people spent most of the time collectively sick to their stomachs, and Shennong thus took on the task of teaching people which fruits to gather, which fruits to avoid and —most importantly— which ones possessed medicinal qualities.

China’s pharmaceutical industry is, to say the least, unusual. The country represents 20% of the world’s total population, but its pharma market represents barely1.5% of the global market. The 1980s marked the collapse of the Rural Cooperative Medical System (RCMS), an innovative,

Opinion

three-tiered system of medical attention consisting of barefoot doctors (trained in very basic first aid techniques and traditional Chinese medicine; think a nurse with acupuncture needles). The second tier consisted of township medical centers, staffed with western medicine-trained professionals. The first two tiers handled the most common ailments and general medicine, and a third, far more specialized tier consisted of county hospitals. The system was partially subsidized by the central government, and fees charged to patients were calculated based on the general population and income by province. The RCMS significantly improved life expectancy, reduced the infant mortality rate, and increased women’s health in general (villages were required to have a female doctor, as women felt uncomfortable being diagnosed by a man). The system was unsustainable, however.

By the 1980s, the Chinese economy had shifted from collectivism to individual production units, effectively defunding the program and collapsing the healthcare system. After the state stopped subsidizing healthcare, doctors started charging patients, and things deteriorated rapidly.

By 2003, due to the disastrous effects of the SARS epidemic, the Chinese government had made an effort to

[ 3 5 ]

[ 3 6 ]

The general consumption of western-produced medicines has also increased dramatically in the years since the sweeping healthcare reforms began, and a growing middle class and higher incomes indicate that China will become the world’s second-largest pharmaceutical market.

re-reform the healthcare system, attempting to bring steady services to the rural population using a largely state-operated and heavily subsidized health insurance institution that managed to increase general coverage but was still lacking in quality and availability.

For decades, internal pharmaceutical production in China has been plagued by a range of problems and setbacks, including a general lack of quality, the population’s erratic geographical distribution (which in turn leads to countless logistical issues), clinical data manipulation, and very low levels of R&D investment. However, things have begun to change, and projections indicate that the Chinese market will grow to 170 billion dollars in 2023.

In 2015, Primer Li Keqiang, alongside the members of his cabinet, unveiled “Made in China 2025,” an ambitious industrial development plan that aims to transition the People’s Republic of China from a gigantic factory for cheap products to a manufacturing powerhouse for higher-end, higher-value goods. A combination of internal and external factors —such as environmental degradation, marked social inequality, an aging population, the aforementioned,

Opinion

problem-ridden healthcare system and steep competition from other Asian countries with lower-cost labor— has forced the Chinese government to re-think its approach to economic growth.

In 2015, President Xi Jinping announced the beginning of a new global strategy called the Belt and Road Initiative (BRI), which involved multi-billion dollar investments in infrastructure throughout Europe, Asia, Oceania, and Africa, aimed at broader global market integration through land and sea corridors that seek to recreate the ancient Silk Road.

Together with Made in China 2025, the BRI has stimulated investments and substantial development in major industries within the country with the lofty goal of entirely transforming the world’s economy by 2049, the centennial of the founding of the People’s Republic of China. The pharma industry is an instrumental area, whose growth and earnings will propel a necessary modernization of the health sector.

As of 2019, there are approximately 1,407 billion people in the People’s Republic of China, making it an unsurpassed source of Big Data: there are a variety of opportunities for

studying rare diseases and certain types of cancer that afflict the Asian diaspora, as well as detailed genetic databases that can significantly improve the qualitative results of clinical testing. The general consumption of western-produced medicines has also increased dramatically in the years since the sweeping healthcare reforms began, and a growing middle class and higher incomes indicate that China will become the world’s second-largest pharmaceutical market.

In the year 2001, the People’s Republic of China became a member of the World Trade Organization, which accelerated the entrance of foreign pharmaceutical firms. Assisted by the above-mentioned reforms, these firms have begun to see the enormous investment potential in China: clinical trials have very competitive costs, a large pool of talent is stimulating the creation of R&D hubs, and Pfizer, GSK, Roche, Novo Nordisk have opened research facilities in Continental China. Despite increasing labor costs, the People’s Republic of China has all the ingredients necessary to become not only the paradise of smartphones, but the pharmaceutical industry’s Mecca.

[ 3 7 ]

[ 3 8 ]

Confidentiality: Keep information and systems secure against the non-authorized access (including hacking). Keep data secure and prevent email accounts from being compromised.

Integrity: Prevent data manipulation. Ensure that criminals cannot send emails from compromised accounts by pretending to be the owner. Block criminals from manipulating account balances and commercial data.

Availability: Guarantee that data and systems remain accessible. Ransomware, hurricanes and other disasters could affect the ability to continue with commercial operations.

Opinion

Cybersecurity, Information Security and CIA

by Alfredo Castro

No longer just a fashionable word, modern-day cybersecurity forms part of work regulations and frameworks. Cybersecurity focuses on threats that, from the Internet, attack digital data.

It forms part of a broader discipline known as information security, which also includes physical security, environmental controls, business continuity, recovery in the event of a disaster and data governance.

There is no need to spend hours teasing apart the differences between cybersecurity and information security — simply approach them both thoroughly. Information security includes disasters such as floods, earthquakes, fires, and even terrorist attacks. Not only is response planning for such events required by regulations, it is what ensures that an organization is able to survive them.

There are three basic principles for Information Security, known by the initials CIA. There is a series of well-known information security frameworks to guide large organizations, including the NIST Cybersecurity Framework and Critical Security Controls of the Center for Internet Security. For those beginning at home, consider the following simplified framework from the book

“Cybersecurity for the Home and Office, The Lawyer’s Guide to Taking Charge of Your Information Security,” which lays out four pillars for Cybersecurity:

Knowledge and Awareness Devices Data Networks (and Internet)

Each of these will be dealt with separately.

Knowledge and Awareness Knowledge and experience are developed through “common sense.” Be aware of malicious emails, since they may jeopardize an organization’s equipment and information. Have respect for cybercriminals’ creativity and resourcefulness, as well as for their ability to trick you using social engineering.

As controls are implemented to cut down on a certain type of fraud, criminals will adapt, improvise and experiment.

Make sure that all wire transfer instructions, and changes to these instructions, are verified through a return call to the client or to the supplier. It is likely that clients lack proper training on the subject of fraud and money laundering, so this

[ 3 9 ]

[ 4 0 ]

Did you speak with the person who sent you the wire transfer instructions

this telephone conversation should be used to educate them, regarding the wire fraud schemes known as “Business Email Compromise” or “CEO fraud.” These types of scams account for the theft of billions of dollars, devastate victims, and damage customer relations. After confirming the identity of the client and the authenticity of the client’s instruction, ask the following question: “Did you speak with the person who sent you the wire transfer instructions?”

If the client has not had a verbal conversation with the person who sent the wire transfer instructions, ask them to do so and explain why. Also remember that this call serves as an opportunity to improve on personal relations with the client.

Devices Which computer devices are being used? Use a device password, have patches in place and keep the device free of malware, disable or uninstall unnecessary software and functions, and verify security and privacy configurations. Think of physical security: avoid losses of smartphones and laptops and control who has access to offices and server rooms. When devices are no longer needed, dismantle them securely, eliminating stored data and access to cloud accounts.

?

Data Know which data accumulates, where it is stored, and when it should be purged. Make sure that data is periodically saved in a safe location and that it is recoverable in the event of an attack, fire or flood. Evaluate if data should be encrypted, such as confidential data that leaves the office.

Keep control over email accounts and other important cloud accounts with solid passwords and two-factor authentication, also known as two-step sign in.

Networks and Internet Network routers should be kept up-to-date and should require a unique username and password to access the administrator portal, rather than the predetermined passwords that cybercriminals know and will use. Avoid connecting to public or unsecured Wi-Fi networks, and remember that, unless encrypted, data transmitted over the Internet is visible to computers in the current network and along the path of transmission.

From Home to the Company At home, you’re the head of security, striving to protect information systems, home and family. Matters are more complicated in the workplace, but with learning and practice, all

Opinion

of the concepts presented here will be beneficial to both readers and their organizations.

A financial institution’s written policies must comply with all laws and regulations related to information security, privacy and reporting of incidents and suspicious operations.

And of course, behaviors should be adjusted to these policies accordingly. Cybercrimes must be reported to the Financial Crime Compliance Network through suspicious transaction reports, and institutions must comply with the information privacy and security requirements of the Gramm-Leach-Bliley Act. If an institution is regulated by the New York State Department of Financial Services, it must comply with Rule 500, which includes having a complete written information security program and reporting cybercrimes to the state. In addition, each state has its own laws regarding notification of data breaches, information security, and privacy. Remember that the spirit of these rules, and the damages they seek to avoid, reduce high-priority risks while taking into account commercial efficiency and the needs of businesses.

Whatever your current level of knowledge and your stance regarding security at home and at work, make a commitment towards continual improvement. This is good for compliance, for business and �most importantly of all� for the family.

[ 4 1 ]

Ar t-Literature

De Rerum Natura

by Ángel Ortuño

Prime numbers are the atoms of math. This, according to the philosopher Roy Sorensen, who proceeds to explain the metaphor: all other numbers can be analyzed as a product of prime numbers. They are, in this sense, the material from which the intangible nature of numbers is constructed.

True metaphors work in exactly this way: they are not verbal decorations, but rather powerful lenses that provide us with clarity of vision; what is there exists because, thanks to them, we can see.

Such is the logic of the contemporary Mexican poets Olga Gutiérrez and Diana Garza-Islas, whose writing engages in a close, intimate conversation with different scientific fields, and possesses an ambition that demonstrates why the first great treatise on the nature of the world was, in fact, a poem: De Rerum Natura, by Lucrecio.

Jorge Palos’ painting has been defined as a “specialized toy for paranoid imaginations” (Eduardo Padilla). One part of the title of the work presented here would seem to be a sarcastic response to this, and to any other option for interpretation: “I restrict myself to allowing things to happen.” Notwithstanding, its apparently casual composition is an insinuation, a triggering of the ever-present impulse to connect the dots, to look for meaning because, out of the blue, our brain hungers for significance. And everything is a question of, as the other part of the work’s title states, waiting just a little longer.

[ 4 3 ]

[ 4 4 ]

In ten sity

Time

Ar t-Literature

M I S M ATC H E D

by Olga Gutiérrez to enriKetta luissi

In spite that I’m always Ritalinized and you Valiumized In spite that our erythrocytes, lipoproteins, lymphocytes and the rest are a mess, and you are a neutron star of glucose and I’m a supernova of salt In spite that you are the daughter of Wonder Woman and I, the daughter of number Pi In spite that you chew gum while in the toilet, and I eat rice with toothpicks In spite of the weird look of the people at the bar when we walk in disguised as Elvis and Chavela In spite that our orgasms are mismatched functions, that never intersect (mine never touches the x axis), different wavelengths, and different amplitudes In spite of it all, when having sex we love to sing It’s now or never, and Pónme la mano aquí Macorina

Olga Gutiérrez is a poet, translator, physicist and mathematician, who writes in English and Spanish under the pseudonym enriKetta luissi. She has written a novel El Peso de los Ovarios, and ten books of poetry: Re-Versed, Ostrich Sky, Disclosed, In Vitro, Poetica Mathematica, ÍÍÉ, Binaria, Dark Matter, Emily and Visitaciones.

[ 4 5 ]

[ 4 6 ]

by Diana Garza-Islas Image may contain: button, spiders, pumice.

Image may contain: ginger, rabbit tea, hog fat, to sin.

Image may contain: the nest’s eye, there.

Image may contain: polkas, herds in fruit.

Image may contain: make-up kits and theories about how you doing.

Image may contain: tears, rheums, invaders.

Image may contain: empty spaces in the lawn.

The End. Beware. Objects may be or may be not — closer than I appear.

Ar t-Literature

[ 4 7 ]

La imagen puede contener: botón, arañas, piedra pómez.

La imagen puede contener: jengibre, té de conejos, grasa de cerdo, pecar.

La imagen puede contener: los ojos del nido ahí.

La imagen puede contener: polkas, manadas en la fruta.

La imagen puede contener: cosmetiqueras y teorías de cómo estás.

La imagen puede contener: lágrimas, legañas, invasiones.

La imagen puede contener: espacios vacíos en la yerba.

FIN. Mucho cuidado. Los objetos podrían estar —o no— más cerca de lo que aparento.

Diana Garza-Islas (Santiago, NL, México, 1985) She has published various collections of poetry, the majority of which can be downloaded at: dianagarzaislas.net Maintains a visual diary on @ hastrolabia

[ 4 8 ]

Visual Art

Jorge Palos

–I restrict myself to allowing things to happen –Wait just a little longer and you’ll see how you’ll get hungry Acrylic on wood 122 x 83 cm 2006

[ 4 9 ]

[ 5 0 ]

Joy Milne can smell Parkinson’s disease before it is medically diagnosed

Gadgets

From AI Noses to Cyborgs by Édgar Mondragón

One time, a diagnosis came attached to a nose. While Hippocrates intuited that the aromas of patients’ urine could provide clues for evaluation, modern science’s interest in olfactory diagnoses is a novelty of this century. The omnipresence of Artificial Intelligence and advances in nanotechnology-based sensors have made this option feasible. Earlier this year scientists —inspired by Joy Milne, the Scottish nurse who can “smell” Parkinson’s— published the results of a study that found volatile biomarkers in the sebum of patients with this disease. In October, Google likewise announced the development of the world’s most sophisticated Artificial Intelligence electronic nose, which can directly predict the smell descriptor for individual molecules. Everything would seem indicate that, next to the stethoscope, we will soon see a portable artificial nose hanging around each doctor’s neck.

Cyborgs, speedy thumbs, and whale song. In a recent talk with his colleague, Alibaba founder Jack Ma, Tesla CEO Elon Musk spoke about his project Neuralink, a company aimed at creating a high bandwidth human-machine interface. “We are already a cyborg [...] If you forget your phone, it is like a missing limb” Musk said. “Input bandwidth to computers has actually gone down, because typing with two thumbs, as opposed to 10 fingers, is a big reduction in bandwidth. [...] human speech, to a computer, will sound like very slow tonal wheezing. It is kind of like whale sounds.” If Musk is right, you can soon expect that the white papers of our robot overlords to be attempting to decipher “Human Song.”

References: https://bbc.in/2G7iERW

https://bit.ly/2R85Il3

http://bit.ly/2uWVrzM

[ 5 1 ]

Edition Inquir y

[?]

ANSWERS:

What has been the most astonishing discovery in healthcare science in the last 20 years?

Over the past century, healthcare has undergone continuous improvements. However, one of the most significant issues has been the antivaccine movement, which has caused social damage and has set populations back in the face of once-eradicated diseases. Its consequences are catastrophic, and many scientists and physicians still have a heavy burden to carry in their efforts to prevent the spread of false information.

We all need to work together to restore the power of science and trust in data, so that our communities understand the crucial benefits of vaccines – which, after clean water, represent the most significant health improvement in the modern world.

Federico Lerner, MD, PhD

[ 5 3 ]

[ 5 4 ]

While the idea of personalized medicine has been around for more than 50 years, it was not until the beginning of the 21st century that significant progress was made in the field. The discovery of single nucleotide polymorphism genotyping and microarray/ biochips now allows segregation of patients for studies and clinical trials, even when they are diagnosed with the same disease. Hopefully, in the coming years, more and more personalized treatments will emerge and achieve success.

Thor Nissen, MD, PhD

ANSWERS:

Edition Inquir y

What has been the most astonishing discovery in healthcare science in the last 20 years?

A significant reduction of cardiovascular deaths in Diabetics Patients at high risk of cardiovascular events was demonstrated with Empagliflozin in 2015 in the EMPA-REG Outcome trial. (N Engl J Med 2015;373:2117-28.)

Empagliflozin (marketed as Jardiance®) is an oral, once daily, highly selective sodium glucose cotransporter 2 (SGLT2) inhibitor that lowers the blood glucose level (Antidiabetic).

Empagliflozin is unique and has the most robust evidence for cardiovascular benefits. It was the first type 2 diabetes medicine to include cardiovascular death-risk reduction data on the label in several countries.

[ 5 5 ]

[?]

Inhibition of SGLT2 with empagliflozin in people with type 2 diabetes and high blood sugar levels leads to excretion of excess sugar in the urine.

In addition, initiation of empagliflozin increases excretion of salt from the body and reduces the fluid load of the body’s blood vessel system (i.e. intravascular volume).

Jardiance® has won the prestigious Prix Galien International 2018 as best pharmaceutical product. Worldwide, the award is regarded as the equivalent of the Nobel Prize in the field of pharmaceutical research and innovation.

Guillermo Caletti, MD, PhD

[ 5 6 ]

Ludic

A Glimpse into Cyberpunk 2077 High-tech, Low-life

by Sergio Segovia

There are amazing medical advancements that serve both the strictly medical purpose of replacing organs and limbs, along with enhancing human functions and responding to aesthetic desires.

Announced in 2012 by the Polish developer CD Projekt, a dedicated team of around 500 people have worked to complete the game. The company’s history is fascinating in and of itself: at a time when Poland was still under the influence of the Soviet Union, one of company’s founders, Marcin Iwiński, sold cracked copies of videogames in high school.

He met Michał Kiciński, who likewise sold video games, and eventually they became business partners — a true embodiment of the cyberpunk attitude. During the early nineties they founded the “CD Projekt” company, with the mission of localizing western games into their local language. In the early 2000’s they decided to develop their first original game and secured the rights to “The Witcher” book series. The games they developed under The Witcher banner became a massive success with a cult following around the globe. In 2008, the company created the online videogame distribution service Good Old Games (GOG), whose mission is to preserve classic games and recover old code for

conversion and optimization on modern platforms — and to the delight of customers, the service is entirely free of digital rights management fees.

And what better project to follow up on the success of The Witcher (now also a highly successful Netflix series, thanks in no small part to the video game adaptation) than Cyberpunk 2077?

This game is a follow-up/adaptation of the 1988 tabletop role-playing game Cyberpunk and its sequels (Cyberpunk 2020, Cybergeneration, Cyberpunk 203X, and Cyberpunk Red), which originally attempted to replicate the gritty realism of the Cyberpunk genre, primarily taking cues from the novels of William Gibson and Walter Jon Williams.

The Cyberpunk genre usually tackles dystopian futuristic settings with a combination of “low-life and high-tech” There are amazing medical advancements that serve both the strictly medical purpose of replacing organs and limbs, along with enhancing human functions and responding to

[ 5 7 ]

[ 5 8 ]

aesthetical desires: artificial intelligences that blur the line between human and machine, and give rise to a host of associated ethical implications.

In this game, the player will play as the character “V” and will have the option of customizing the character as they see fit. They cannot choose the character’s gender (there is no binary gender choice), only its looks and a feminine- or masculine-sounding voice. There will be a wide variety of skin tones, tattoos, and hairstyles. Romantic encounters (long-lasting or short-term) will be a possibility; it was also revealed that many of the characters are bisexual and, as such, open to a complete spectrum of relationships with other characters.

Another interesting detail is the inclusion of the highly charismatic Keanu Reeves as Johnny Silverhand, a non-playable character who interacts with the player. This would

seem to hit all the right notes, since Reeves has a lot of cyberpunk-genre films under his belt.

According to Philipp Webber, one of the developers, “In 2077, body modification is fashion and it’s a part of everyday life.” Modifications are so completely normal in this future that Weber states that “not having enhanced cyberware, [is like] not having a smartphone nowadays.”

One of the most important themes in the cyberpunk genre is transhumanism, or the belief that humanity can transcend its current mental and physical form with the help of technology. The game’s developers have made it quite clear that this is exactly what they have in mind for this game, and somehow all the possibilities shown in this world seem neither very farfetched or too sci-fi: at this point, it may be just a matter of time until they become our new normal.

Ludic

[ 5 9 ]

[ 6 0 ]

Ludic

To Live Again,

To Live Forever, To Live on The Screen

by Francisco Payó González Defeating death and achieving immortality thanks to science, improving our quality of life thanks to the latest advancements and to experiments where the human and the robotic, the real and the virtual, the ethical and the monstrous meet – such material has formed a broad and fertile field for the audiovisual imagination.

And, while we are still linked to our human mortality and fragility, many of these stories have or will live beyond their creators’ lifetimes, by turns inspiring us, amusing us and terrifying us. A few such examples are given below:

1

Frankenstein (1931): The classic par excellence, in which the unsurpassable Boris Karloff succeeds in drawing us into the soul of a “monster” created by a scientist using parts from various corpses.

The scientist is the actual Frankenstein giving the work its title and, deep down, the story’s true monster – a man whose obsession with defying death and creating life ends in tragedy.

2

The Boys from Brazil (1978):

Based on Ira Levin’s novel (Rosemary’s Baby), this movie ventures into the topic of human cloning as a tool that could be employed to bring back one of history’s most notorious monsters, Adolf Hitler, through the diabolic genius of another monster: Doctor Josef Mengele.

3

Star Wars (1977 - ?): And speaking

of characters who stay alive thanks to science, few examples of fiction are as emblematic as Darth Vader, the saga’s villain-hero, who, after losing an arm and both legs and suffering burns over his entire body, is reconstructed to continue with his dark work, his raspy breathing a symbol of eternal agony.

[ 6 1 ]

[ 6 2 ]

Ludic

4

8

5

9

Blade Runner (1982): Humans figure out how manufacture disposable beings – called Replicants – who are mainly used for dangerous space exploration and who, for safety reasons, are programed to live no more than four years. The Replicants are outfitted with false memories to provide them with a questionable emotional stability when faced with death’s inevitable threshold.

Robocop (1987):

Both the original version by Netherlander Paul Verhoeven and Brazilian José Padilha’s 2014 remake explore the dilemma of a honest policeman who, after being murdered, awakes – or rather, turns on – to find himself converted into a cyborg at the service of a corrupt corporation that controls the police and the criminals guilty of his homicide.

6

Ironman

(2008):

Scientist-Playboy Tony Stark turns into the titular superhero thanks to the construction of an electromagnet, which is the only thing preventing bomb fragments from piercing his heart. In the saga’s later installments, Stark resorts to nanotechnology to ward off the electromagnet.

7

Avatar (2009):

From the mind of a filmmaker obsessed with scientific research, submarine and space exploration, and technology in general, comes this story, in which a marine who has lost the use of his legs gets the opportunity for a second shot at life by transferring his mind to an alien body.

Altered Carbon (2018 - ?): This series shows a world where the human mind can be digitalized and stored like a database that can be downloaded, even 250 years in the future, into whichever body is desired and in order to fulfill specific missions.

Few things are less pleasant than waking up in a future you had hoped to avoid.

Never let me go (2010): Based on Kazuo Ishiguro’s novel (The Remains of the Day) and written for the screen by Alex Garland (Ex Machina), this film shows a group of young people who discover that their purpose in life is to serve as organ donors to others. A cruder version of this premise can be seen in the movie The Island (2005).

10

Prometheus (2012): In this prequel to the Alien saga, we see how the creation of humans was the result of an alien experiment.

In the search for these Creators, an elderly millionaire finances the most expensive space mission in the history of humanity, with a sole and egotistical purpose: to ask the Creators for the secret to eternal life.

11

Gattaca (1997): In a not-to-distant

future, genetic advancements establish that the worst way to bring a human being into the world is though natural means. Those who dare to procreate “inferior humans” are thus condemned to live as a servile caste without aspirations – that is, until one of them cheats the system to become astronaut.

[ 6 3 ]

[ 6 4 ]