Challenge For Contemporary Medicine Research Articles

Role of flavonoids in digestive tract cancer prevention - a review article

Introduction: Flavonoids are bioactive chemical compounds crucial for the functioning of plant organisms. Recently, they have been intensively studied in search of their potential application in medicine. One of the most popular fields in that regard is oncology. Digestive tract cancers are still a challenge for contemporary medicine. Our diet seems to have a direct impact on the etiology of colorectal, gastric, and esophageal cancers. The relationship between the consumption of flavonoids, their specific fractions, and digestive tract cancer morbidity is nowadays frequently investigated.Purpose: This review article aims to discuss the most recent scientific reports and summarize the current state of knowledge, considering the role of flavonoids in digestive tract cancer prevention.Materials and methods: Our work is based on articles accessed through medical information databases (Google Scholar, PubMed, CrossRef), various scientific books, and official NFZ and WHO-certified sites.Results: Total flavonoid intake lowers gastric and esophageal cancer morbidity. A high amount of dietary catechins prevents the growth of gastric and colorectal cancer. Increased consumption of anthocyanidins, flavones, and flavanones decreases esophageal cancer morbidity. Isoflavones, procyanidines, anthocyanidins, flaonols, and flavones severely decrease the chance of developing colorectal cancer.Conclusions: Flavonoids can play an important role in digestive tract cancer prevention. They suppress the growth of colorectal, gastric, and esophageal cancers. Nevertheless, new, high-quality studies are needed in order to compile adequate procedures and bring new, potential drugs to the market.

Control of arterial hypertension: a pending issueControle da hipertensão arterial: um assunto inacabado

RESUMENEl adecuado diagnóstico, tratamiento y control de la hipertensión arterial (HTA) continúa siendo una asignatura pendiente en nuestro intento de reducir la incidencia de mortalidad cardiovascular prematura y discapacidades, siendo esta una realidad a nivel mundial y particularmente cierta en la región de las Américas.A pesar de contar con adecuados algoritmos diagnósticos y eficientes esquemas de tratamiento, la brecha entre el conocimiento médico y la realidad nos muestra la gran dificultad para que nuestras recomendaciones sean adoptadas por nuestros pacientes. La adherencia representa un gran desafío y la adecuada comprensión de sus dimensiones resulta básico al momento de diseñar estrategias para mejorar el control de la HTA.Es claro que disponer y diseminar información adecuada es una parte de la solución, pero no menos importante son las acciones que garanticen su implementación. Es por lo que damos la bienvenida a guías de práctica clínica que intenten abordar esta problemática. La reciente publicación de guía de la Organización Mundial de la Salud en hipertensión arterial es un claro ejemplo de este tipo de iniciativas.Los programas de implementación posiblemente sean uno de los mayores desafíos de la medicina contemporánea. El desarrollo de intervenciones multimodales en el primer nivel de atención con el objetivo de mejorar su capacidad resolutiva y promover el desarrollo de redes integradas de servicios de salud, impresiona ser el camino mas adecuado para alcanzar niveles adecuados de control de la HTA.Estamos convencidos del importante rol que nuestras sociedades científicas tienen con estas iniciativas dando apoyo, soporte y articulando la interacción con los diferentes actores involucrados.

Serotonergic Neurotransmission System Modulator, Vortioxetine, and Dopaminergic D2/D3 Receptor Agonist, Ropinirole, Attenuate Fibromyalgia-Like Symptoms in Mice.

Fibromyalgia is a disease characterized by lowered pain threshold, mood disorders, and decreased muscular strength. It results from a complex dysfunction of the nervous system and due to unknown etiology, its diagnosis, treatment, and prevention are a serious challenge for contemporary medicine. Impaired serotonergic and dopaminergic neurotransmission are regarded as key factors contributing to fibromyalgia. The present research assessed the effect of serotonergic and dopaminergic system modulators (vortioxetine and ropinirole, respectively) on the pain threshold, depressive-like behavior, anxiety, and motor functions of mice with fibromyalgia-like symptoms induced by subcutaneous reserpine (0.25 mg/kg). By depleting serotonin and dopamine in the mouse brain, reserpine induced symptoms of human fibromyalgia. Intraperitoneal administration of vortioxetine and ropinirole at the dose of 10 mg/kg alleviated tactile allodynia. At 5 and 10 mg/kg ropinirole showed antidepressant-like properties, while vortioxetine had anxiolytic-like properties. None of these drugs influenced muscle strength but reserpine reduced locomotor activity of mice. Concluding, in the mouse model of fibromyalgia vortioxetine and ropinirole markedly reduced pain. These drugs affected emotional processes of mice in a distinct manner. Hence, these two repurposed drugs should be considered as potential drug candidates for fibromyalgia. The selection of a specific drug should depend on patient’s key symptoms.

Survival prediction models since liver transplantation - comparisons between Cox models and machine learning techniques

BackgroundPredicting survival of recipients after liver transplantation is regarded as one of the most important challenges in contemporary medicine. Hence, improving on current prediction models is of great interest.Nowadays, there is a strong discussion in the medical field about machine learning (ML) and whether it has greater potential than traditional regression models when dealing with complex data. Criticism to ML is related to unsuitable performance measures and lack of interpretability which is important for clinicians.MethodsIn this paper, ML techniques such as random forests and neural networks are applied to large data of 62294 patients from the United States with 97 predictors selected on clinical/statistical grounds, over more than 600, to predict survival from transplantation. Of particular interest is also the identification of potential risk factors. A comparison is performed between 3 different Cox models (with all variables, backward selection and LASSO) and 3 machine learning techniques: a random survival forest and 2 partial logistic artificial neural networks (PLANNs). For PLANNs, novel extensions to their original specification are tested. Emphasis is given on the advantages and pitfalls of each method and on the interpretability of the ML techniques.ResultsWell-established predictive measures are employed from the survival field (C-index, Brier score and Integrated Brier Score) and the strongest prognostic factors are identified for each model. Clinical endpoint is overall graft-survival defined as the time between transplantation and the date of graft-failure or death. The random survival forest shows slightly better predictive performance than Cox models based on the C-index. Neural networks show better performance than both Cox models and random survival forest based on the Integrated Brier Score at 10 years.ConclusionIn this work, it is shown that machine learning techniques can be a useful tool for both prediction and interpretation in the survival context. From the ML techniques examined here, PLANN with 1 hidden layer predicts survival probabilities the most accurately, being as calibrated as the Cox model with all variables.Trial registrationRetrospective data were provided by the Scientific Registry of Transplant Recipients under Data Use Agreement number 9477 for analysis of risk factors after liver transplantation.

Agar-based ZIF-90 antibacterial hydrogels for biomedical applications

Bacterial infection is a major challenge for contemporary medicine, and antimicrobial hydrogels have been extensively studied for their excellent antimicrobial activity. However, the antibacterial agent also has high cytotoxicity and hemolytic activity while being significantly antibacterial. In this paper, we prepared a hydrogel by simple heating-cooling of ZIF-90 doped agar solution, which has obvious antibacterial activity against Gram-positive and Gram-negative bacteria. The test results show that the hydrogel has a uniform and stable structure and does not exhibit cytotoxicity and hemolytic activity while maintaining good bacteriostatic properties, so as to achieve the function of bacterial infection treatment and would healthcare.

Dealing with the unknown. Functional neurological disorder (FND) and the conversion of cultural meaning

Functional Neurological Disorder (FND), otherwise known as Conversion Disorder, is characterized by abnormal sensory or motor symptoms that are determined to be “incompatible” with neurological disease. FND patients are a challenge for contemporary medicine. They experience high levels of distress, disability, and social isolation, yet a large proportion of those treated do not get better. Patients with FNDs are often misdiagnosed and suffer from stigma, dysfunctional medical encounters and scarcity of adequate treatments. In this paper we argue that an anthropological understanding of these phenomena is needed for improving diagnosis and therapies. We argue that cultural meaning is pivotal in the development of FND on three levels. 1) The embodiment of cultural models, as shared representations and beliefs about illnesses shape the manifestation of symptoms and the meanings of sensations; 2) The socialization of personal trauma and chronic stress, as the way in which individuals are socially primed to cope or to reframe personal trauma and chronic stress affects bodily symptoms; 3) Moral judgment, as stigma and ethical evaluations of symptoms impact coping abilities and resilience. In particular, we focus on the disorder known as PNES (Psychogenic-Non-Epileptic Seizure) to show how cultural meaning co-determines the development of such seizures. We introduce the notion of interoceptive affordances to account for the cultural scaffolding of patients’ bodily experiences. Finally, we suggest that effective treatments of FND must act upon meaning in all of its aspects, and treatment adequacy must be assessed according to the cultural diversity of patients.

P02-S Automatic analysis of sleep architecture and circadian rhythms for assessment of disorders of consciousness

Disorders of consciousness (DOC) are among the major challenges of contemporary medicine. Currently, clinical diagnosis of DOC is based upon behavioural scales like Coma Recovery Scale-Revised, which involves visual assessment of patient’s reactions. However, lack of communication with DOC patients, their potential sensory impairments, and fluctuating levels of attention cause high rates of misdiagnoses in clinical assessment. Since DOC are related with severe alterations of both sleep-wake patterns as well as sleep architecture, parameters supplementing assessment can be derived from methods like actigraphy and polysomnography. However, these recordings in the case of DOC patients differ significantly from standards derived for healthy subjects, so standard methods of their analysis usually fail. To overcome the limitations of standard sleep scoring, we proposed a continuous analysis of sleep architecture in terms of EEG profiles, based upon automatic matching pursuit detection and parameterization of sleep transients like sleep spindles and slow waves. In this presentation we briefly recall the framework, software availability, and results of application of this approach to the analysis of overnight polysomnographic recordings of pediatric patients from “The Alarm Clock” model hospital for children with severe brain damage, combined with an automatic analysis of actigraphic recordings of these patients.

The use of monoclonal antibodies in autoimmunity treatment

Recently, monoclonal antibodies (MA) have gained popularity as therapeutic agents for the treatment of autoimmune disorders. These antibodies target proinflammatory cytokines, as well as T and B cells potentially involved in the pathogenesis of such conditions. In the present work we attempt to give a systematic description of available therapeutic MA, highlight their key mechanisms of action and pinpoint their adverse effects. We believe that MA that are capable of recognizing and eliminating pathogenic T- and B-cell clones hold the most promise for medical application as biologics. Detection and identification of autoreactive lymphocyte clones is one of the most serious challenges of contemporary medicine.

Long-term results of physiotherapy in treatment of bronchial asthma – case study

AbstractBronchial asthma is a common disease in this day and age, but despite our vast knowledge on it, it still represents a great challenge for contemporary medicine. The paper describes a case of a bronchial asthma patient from the moment of diagnosis until the present day. Based on extensive documentation of multiple stays in sanatoriums, and of outpatient treatment, the paper shows the course of the disease, as well as the applied treatment, rehabilitation and diagnostic tests (spirometry, blood gas test, radiography) that gave grounds for objective assessment of patient’s health and demonstrated the improvement.

Abstract 5431: PPAR alpha independent effect of fenofibrate on glioblastoma cancer metabolism.

Abstract Glioblastoma multiforme is the most common and aggressive primary brain tumor in adults. It is characterized by a rapid cell growth, CNS infiltration and is resistant to all known anticancer regimens. Therefore, development of effective therapies against these malignant brain tumors represents challenge for contemporary medicine. Anti-neoplastic potential of a common lipid-lowering drug, fenofibrate, is gaining a lot of attention, however, the precise mechanism of fenofibrate anti-cancer action remain to be elucidated. Fenofibric acid, which is an active metabolite of fenofibrate, is a potent agonist of peroxisome proliferator activated receptor alpha (PPARα), which transcriptional activity is expected to shift energy metabolism from glycolysis to fatty acid β-oxidation, therefore, it may be toxic to glycolytic tumor cells (Warburg effect). In parallel, to PPARα- dependent action, we have observed a strong PPARα- independent effect of fenofibrate on cancer cell energy metabolism, which was specific only to fenofibrate but not to fenofibric acid or to other PPARα agonists. We detected fenofibrate in mitochondrial membrane fractions of LN-229 cells treated with fenofibrate by using HPLC and subcellular fractionation. The accumulation of fenofibrate in mitochondrial membrane was accompanied by significant change in mitochondrial function, including loss of mitochondrial membrane potential, dramatic loss of oxygen consumption and lack of respiratory capacity measured as oxygen consumption rate (OCR). At the same time, fenofibrate increased the level of glycolysis (extracellular acidification rate, ECAR), possibly as compensation for impaired oxidative phosphorylation. In addition, fenofibrate-induced reduction of ATP levels triggered phosphorylation of AMPK and activation of autophagy. In conclusion, our results demonstrate two seemingly independent mechanisms of fenofibrate anticancer action: PPARα-dependent, which shifts cell metabolism from glycolysis to fatty acid β-oxidation and PPARα-independent, which causes accumulation of fenofibrate in cell membranes and inhibition of oxidative phosphorylation. Both mechanisms counteract to make this drug very effective against Glioblastoma tumors causing inhibition of cell growth, survival and finally leading to massive apoptosis of these practically incurable tumors. Citation Format: Anna M. Wilk, Adriana M. Zapata, Jennifer R. Mullinax, Dorota D. Wyczechowska, Krzysztof Reiss. PPAR alpha independent effect of fenofibrate on glioblastoma cancer metabolism. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 5431. doi:10.1158/1538-7445.AM2013-5431 Note: This abstract was not presented at the AACR Annual Meeting 2013 because the presenter was unable to attend.

A Way Forward for Health Care and Healers

The reaction1 to Egnew’s essay “Suffering, Meaning, and Healing: Challenges of Contemporary Medicine”2 reveals deep yearnings and strong convictions among clinicians, patients, and medical students. Clinicians describe a yearning for an integrative approach to medicine in which “relational wisdom and clinical wisdom [are] inextricably tied together”3 so that we can “reclaim our own souls, and…learn to heal again.”4 On an individual level, this requires self-awareness5 and a willingness to provide patients with space in which healing can take place.6 On a broader level, it requires medical training that emphasizes patient centeredness7 and the ability not only to communicate but to connect.6 In addition, according to a medical student, role models of physician healers “are essential to counteracting the sometimes unhealthy pressures we face as students.”8 Patients describe the transformative power in self-defined healing,9 and they challenge us to develop language that reflects a true partnership between clinicians and beneficiaries of care.10 Family medicine, which sprang from a desire to revolutionize care, may be a natural home for the physician-healer movement, according to Farber: “My hope is the old revolutionaries of Family Medicine will join forces with the new revolutionaries of Palliative Care to further move us along the path of training and supporting physician healers.”11 This powerful essay and compelling discussion light an undeniable path forward to re-form health care, starting with ourselves, to reduce suffering, restore meaning and promote true healing. Consider reading the essay and discussion on paper, away from your computer, but close to your heart. Then, consider how you can begin the inner transformation and external action that these words compel.

Suffering, meaning, and healing: challenges of contemporary medicine.

This essay explores the thesis that changes in contemporary society have transformed the work of doctoring and challenge doctors to be physician-healers. Medical advances in the prevention and management of acute disease have wrought a growing population of chronically ill patients whose care obliges physicians to become holistic healers. Holistic healing involves the transcendence of suffering. Suffering arises from perceptions of a threat to the integrity of person-hood, relates to the meaning patients ascribe to their illness experience, and is conveyed as an intensely personal narrative. Physician-healers use the power of the doctor-patient relationship to help patients discover or create new illness narratives with fresh meanings that reconnect them to the world and to others and thereby transcend suffering and experience healing. Physician-healers equipped with the attitudes, skills, and knowledge to assist patients to transcend suffering are indispensable if contemporary medicine is to maintain its tradition as a healing profession. In the process, physicians may discover meaningful connections with patients that bring new and refreshing perspectives to their work.

Lo último en diagnóstico y tratamiento de la obesidad: ¿Hay lugar aún para la terapia conservadora?

In Chile and other countries the actual prevalence of obesity is reaching 30% in selected populations (low income women). Nowadays bariatric surgery appears to be the treatment of choice. However, it is only indicated in selected patients and is not the first line treatment, since it does not prevent or reduce the appearance of this condition, a crucial challenge in its clinical management. The contemporary medical management of obesity should include changes in lifestyle habits and diet together with a behavioral therapy. However, this optimal management requires a multidisciplinary team. A challenge for contemporary medicine is to design efficient interventional strategies to change lifestyles among the obese. These interventions are the only way to reduce the adverse health consequences of obesity.

Chronic microbial infections: Manipulation of host immunity as interventional approach

Chronic viral infections represent major challenges in contemporary medicine, virology and pharmacology. The virus-bearing hosts are commonly found in every parts of the world and it is extremely difficult to manage these patients. In addition, considerable numbers of these patients develop progressive diseases and severe complications. Finally, most of these patients act as permanent reservoirs of virus. Understandings of viral life cycle during the last decade of 20th century and the first decade of 21st century have allowed development of hundreds of antiviral agents for different diseases. But, the clinical efficacy of these drugs is not yet satisfactory. In addition, virologists have provided conclusive evidences suggesting that eradication of most chronic virus from infected hosts may an unachievable goal. In this context, it is essential to develop alternative, novel, and evidence-based therapeutic maneuver for these patients. Manipulation of host immune system may be one of these approaches. We would discuss about scopes, limitations, and strategies for manipulation for controlling of chronic viral infections. The primary function of the host's immune system is to mount responses that protect the individual from various microbial infections including viruses. Host's immune responses also control the spread and virulence of the viruses [1]. This is applicable to viruses that cause acute infection. After entering the hosts, these viruses are localized in host's tissues, proliferate and induce antiviral immunity. These cellular events may cause damage and destruction of tissues and the host exhibit features of acute inflammatory diseases. However, the viruses are either almost completely eliminated from the hosts or adequately controlled in situ by host's immune systems. However, chronic infection is established by many viruses because the hosts induce improper and uncoordinated immune responses against these viruses. Most viruses cause persistent infection by evading the host immune surveillance mechanism. Both virus-related factors and host-dependent factors are primarily responsible for viral persistency in subjects with chronic viral infections. doi: 10.3329/blj.v1i1.2620 Bangladesh Liver Journal Vol.1(1) 2009 p.13-19