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1.
BMC Nephrol ; 16: 135, 2015 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-26268514

RESUMO

BACKGROUND: Anemia is a common disorder in CKD patients. It is largely attributed to decreased erythropoietin (EPO) production and iron deficiency. Therefore, besides EPO, therapy includes iron replenishment. However, the latter induces oxidative stress. Haptoglobin (Hp) protein is the main line of defense against the oxidative effects of Hemoglobin/Iron. There are 3 genotypes: 1-1, 2-1 and 2-2. Hp 2-2 protein is inferior to Hp 1-1 as antioxidant. So far, there is no evidence whether haptoglobin phenotype affects iron-induced oxidative stress in CKD patients. Therefore, the present study examines the influence of carnitine treatment on the intravenous iron administration (IVIR)-induced oxidative stress in CKD patients, and whether Hp phenotype affects this response. TRIAL REGISTRATION: Current Controlled Trials ISRCTN5700858. This study included 26 anemic (Hb = 10.23 ± 0.28) CKD patients (stages 3-4) that were given a weekly IVIR (Sodium ferric gluconate, [125 mg/100 ml] for 8 weeks, and during weeks 5-8 also received Carnitine (20 mg/kg, IV) prior to IVIR. Weekly blood samples were drawn before and after each IVIR for Hp phenotype, C-reactive protein (CRP), advanced oxidative protein products (AOPP), neutrophil gelatinase-associated lipocalin (NGAL), besides complete blood count and biochemical analyses. RESULTS: Eight percent of CKD patients were Hp1-1, 19 % Hp2-1, and 73 % Hp2-2. IVIR for 4 weeks did not increase hemoglobin levels, yet worsened the oxidative burden as was evident by elevated plasma levels of AOPP. The highest increase in AOPP was observed in Hp2-2 patients. Simultaneous administration of Carnitine with IVIR abolished the IVIR-induced oxidative stress as evident by preventing the elevations in AOPP and NGAL, preferentially in patients with Hp2-2 phenotype. CONCLUSIONS: This study demonstrates that Hp2-2 is a significant risk factor for IVIR-induced oxidative stress in CKD patients. Our finding, that co-administration of Carnitine with IVIR preferentially attenuates the adverse consequences of IVIR, suggests a role for Carnitine therapy in these patients.


Assuntos
Anemia Ferropriva/tratamento farmacológico , Carnitina/farmacologia , Compostos Férricos/administração & dosagem , Haptoglobinas/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Insuficiência Renal Crônica/genética , Proteínas de Fase Aguda , Produtos da Oxidação Avançada de Proteínas/sangue , Idoso , Anemia Ferropriva/etiologia , Proteína C-Reativa/metabolismo , Estudos Cross-Over , Feminino , Compostos Férricos/efeitos adversos , Genótipo , Haptoglobinas/genética , Humanos , Lipocalina-2 , Lipocalinas/sangue , Masculino , Pessoa de Meia-Idade , Estresse Oxidativo/genética , Fenótipo , Estudos Prospectivos , Proteínas Proto-Oncogênicas/sangue , Insuficiência Renal Crônica/complicações
2.
Brain Sci ; 14(7)2024 Jul 22.
Artigo em Inglês | MEDLINE | ID: mdl-39061473

RESUMO

Autism spectrum disorder (ASD) is primarily characterized by core deficits in social skills, communication, and cognition and by repetitive stereotyped behaviors. These manifestations are variable between individuals, and ASD pathogenesis is complex, with over a thousand implicated genes, many epigenetic factors, and multiple environmental influences. The mesolimbic dopamine (DA) mediated brain reward system is held to play a key role, but the rapidly expanding literature reveals intricate, nuanced signaling involving a wide array of mesolimbic loci, neurotransmitters and receptor subtypes, and neuronal variants. How altered DA signaling may constitute a downstream convergence of the manifold causal origins of ASD is not well understood. A clear working framework of ASD pathogenesis may help delineate common stages and potential diagnostic and interventional opportunities. Hence, we summarize the known natural history of ASD in the context of emerging data and perspectives to update ASD reward signaling. Then, against this backdrop, we proffer a provisional framework that organizes ASD pathogenesis into successive levels, including (1) genetic and epigenetic changes, (2) disrupted mesolimbic reward signaling pathways, (3) dysregulated neurotransmitter/DA signaling, and finally, (4) altered neurocognitive and social behavior and possible antagonist/agonist based ASD interventions. This subdivision of ASD into a logical progression of potentially addressable parts may help facilitate the rational formulation of diagnostics and targeted treatments.

3.
Psychol Res Behav Manag ; 17: 2363-2376, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38895648

RESUMO

Alcohol use disorder (AUD) is a significant risk factor, accounting for approximately 13% of all deaths in the US. AUD not only destroys families but also causes economic losses due to reduced productivity, absenteeism, and healthcare expenses. Statistics revealing the sustained number of individuals affected by AUD over the years underscore the need for further understanding of the underlying pathophysiology to advance novel therapeutic strategies. Previous research has implicated the limbic brain regions N-methyl-D-aspartate glutamate receptors (NMDAR) in the emotional and behavioral effects of AUD. Given that aerobic exercise can modulate NMDAR activity and sensitivity to alcohol, this review presents a summary of clinical and basic science studies on NMDAR levels induced by alcohol consumption, as well as acute and protracted withdrawal, highlighting the potential role of aerobic exercise as an adjunctive therapy for AUD. Based on our findings, the utility of exercise in the modulation of reward-linked receptors and AUD may be mediated by its effects on NMDA signaling. These data support further consideration of the potential of aerobic exercise as a promising adjunctive therapy for AUD.

4.
J Pers Med ; 14(5)2024 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-38793071

RESUMO

Exercise promotes health and wellness, including its operation as a protective factor against a variety of psychological, neurological, and chronic diseases. Selenium and its biomarker, selenoprotein P (SEPP1), have been implicated in health, including cancer prevention, neurological function, and dopamine signaling. SEPP1 blood serum levels were compared with a one-way ANOVA between sedentary (SED), moderately exercised (MOD) [10 m/min starting at 10 min, increasing to 60 min], and high-intensity interval training (HIIT) exercised rats [30 min in intervals of 2-min followed by a 1-min break, speed progressively increased from 10 to 21 m/min]. HIIT rats showed significantly higher serum SEPP1 concentrations compared to MOD and SED. More specifically, HIIT exercise showed an 84% increase in SEPP1 levels compared to sedentary controls. MOD rats had greater serum SEPP1 concentrations compared to SED, a 33% increase. The results indicated that increased exercise intensity increases SEPP1 levels. Exercise-induced increases in SEPP1 may indicate an adaptive response to the heightened oxidative stress. Previous studies found a significant increase in dopamine D2 receptor (D2R) binding in these same rats, suggesting a potential association between SEPP1 and dopamine signaling during exercise. Modulating antioxidants like SEPP1 through personalized therapies, including exercise, has broad implications for health, disease, and addiction.

5.
INNOSC Theranostics Pharmacol Sci ; 7(2): 1472, 2024 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-38766548

RESUMO

The Carter Center has estimated that the addiction crisis in the United States (US), if continues to worsen at the same rate, may cost the country approximately 16 trillion dollars by 2030. In recent years, the well-being of youth has been compromised by not only the coronavirus disease 2019 pandemic but also the alarming global opioid crisis, particularly in the US. Each year, deadly opioid drugs claim hundreds of thousands of lives, contributing to an ever-rising death toll. In addition, maternal usage of opioids and other drugs during pregnancy could compromise the neurodevelopment of children. A high rate of DNA polymorphic antecedents compounds the occurrence of epigenetic insults involving methylation of specific essential genes related to normal brain function. These genetic antecedent insults affect healthy DNA and mRNA transcription, leading to a loss of proteins required for normal brain development and function in youth. Myelination in the frontal cortex, a process known to extend until the late 20s, delays the development of proficient executive function and decision-making abilities. Understanding this delay in brain development, along with the presence of potential high-risk antecedent polymorphic variants or alleles and generational epigenetics, provides a clear rationale for embracing the Brain Research Commission's suggestion to mimic fitness programs with an adaptable brain health check (BHC). Implementing the BHC within the educational systems in the US and other countries could serve as an effective initiative for proactive therapies aimed at reducing juvenile mental health problems and eventually criminal activities, addiction, and other behaviors associated with reward deficiency syndrome.

6.
Gene Protein Dis ; 3(1)2024 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-38766604

RESUMO

The D2 dopamine receptor (DRD2) gene has garnered substantial attention as one of the most extensively studied genes across various neuropsychiatric disorders. Since its initial association with severe alcoholism in 1990, particularly through the identification of the DRD2 Taq A1 allele, numerous international investigations have been conducted to elucidate its role in different conditions. As of February 22, 2024, there are 5485 articles focusing on the DRD2 gene listed in PUBMED. There have been 120 meta-analyses with mixed results. In our opinion, the primary cause of negative reports regarding the association of various DRD2 gene polymorphisms is the inadequate screening of controls, not adequately eliminating many hidden reward deficiency syndrome behaviors. Moreover, pleiotropic effects of DRD2 variants have been identified in neuropsychologic, neurophysiologic, stress response, social stress defeat, maternal deprivation, and gambling disorder, with epigenetic DNA methylation and histone post-translational negative methylation identified as discussed in this article. There are 70 articles listed in PUBMED for DNA methylation and 20 articles listed for histone methylation as of October 19, 2022. For this commentary, we did not denote DNA and/or histone methylation; instead, we provided a brief summary based on behavioral effects. Based on the fact that Blum and Noble characterized the DRD2 Taq A1 allele as a generalized reward gene and not necessarily specific alcoholism, it now behooves the field to find ways to either use effector moieties to edit the neuroepigenetic insults or possibly harness the idea of potentially removing negative mRNA-reduced expression by inducing "dopamine homeostasis."

7.
Ann Transl Med ; 11(12): 419, 2023 Dec 20.
Artigo em Inglês | MEDLINE | ID: mdl-38213800

RESUMO

Background: Natural and diet-derived angiogenesis inhibitors/promotors are widely found in diets. These compounds can in several ways impact the results of oncological research of angiogenesis inhibitors. Methods: We very briefly overview some of the most important examples to show how these compounds can create a bias in current research of cancer. Implications of this expert opinion cover similar angiogenesis-related diseases. Results: Significant intra-individual differences in terms of dietary intake and differential effect of food processing techniques result in differential bioactivity and bioavailability of these compounds. There are only a handful of validated dietary questionnaire to quantify natural angiogenesis inhibitors/promotors. A corollary consequence is that participants in non-randomized clinical trials will have different baseline levels of serum/plasma/tissue/organ diet-derived angiogenesis inhibitors/promotors. This will lead to creation of clinical uncertainty and a hidden bias and consequently creation of translational efficiency bias, sampling efficiency, and waste of resources. We call for developing and validating a semi-quantitative food frequency questionnaire (FFQ) to gather data on these agents, specifically designed for oncological research because there is a clear gap in the literature of oncology. Conclusions: This might facilitate the discovery of better prognostic, diagnostic, preventive measures, and therapeutic agents for the management of different cancers. Implications of this paper cover similar settings like ophthalmologic research.

8.
J Pers Med ; 13(2)2023 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-36836570

RESUMO

The North American opioid epidemic has resulted in over 800,000 related premature overdose fatalities since 2000, with the United States leading the world in highest opioid deaths per capita. Despite increased federal funding in recent years, intended to address this crisis, opioid overdose mortality has continued to increase. Legally prescribed opioids also chronically induce a problematic reduction in affect. While an ideal analgesic has yet to be developed, some effective multimodal non-opioid pharmacological regimens for acute pain management are being more widely utilized. Some investigators have suggested that a safer and more scientifically sound approach might be to induce "dopamine homeostasis" through non-pharmacological approaches, since opioid use even for acute pain of short duration is now being strongly questioned. There is also increasing evidence suggesting that some more robust forms of electrotherapy could be applied as an effective adjunct to avoid the problems associated with opioids. This 4-patient case-series presents such an approach to treatment of severe pain. All 4 of these chiropractic treatment cases involved a component of knee osteoarthritis, in addition to other reported areas of pain. Each patient engaged in a home recovery strategy using H-Wave® device stimulation (HWDS) to address residual extremity issues following treatment of spinal subluxation and other standard treatments. A simple statistical analysis was conducted to determine the change in pain scores (Visual Analogue Scale) of pre and post electrotherapy treatments, resulting in significant reductions in self-reported pain (p-value = 0.0002). Three of the four patients continued using the home therapy device long-term as determined by a post-analysis questionnaire. This small case-series demonstrated notably positive outcomes, suggesting consideration of home use of HWDS for safe, non-pharmacological and non-addictive treatment of severe pain.

9.
Artigo em Inglês | MEDLINE | ID: mdl-37102488

RESUMO

INTRODUCTION: In this genomic era of addiction medicine, ideal treatment planning begins with genetic screening to determine neurogenetic antecedents of the Reward Deficiency Syndrome (RDS) phenotype. Patients suffering from endotype addictions, both substance and behavioral, and other mental health/comorbid disorders that share the neurobiological commonality of dopamine dysfunction, are ideal candidates for RDS solutions that facilitate dopamine homeostasis, addressing the cause, rather than symptoms. OBJECTIVE: Our goal is to promote the interplay of molecular biology and recovery as well as provide evidence linked to RDS and its scientific basis to primary care physicians and others. METHODS: This was an observational case study with a retrospective chart review in which an RDS treatment plan that utilized Genetic Addiction Risk Severity (GARS) analysis to evaluate neurogenetic challenges was used in order to develop appropriate short- and long-term pharmaceutical and nutraceutical interventions. RESULTS: A Substance Use Disorder (SUD) treatment-resistant patient was successfully treated utilizing the GARS test and RDS science. CONCLUSION: The RDS Solution Focused Brief Therapy (RDS-SFBT) and the RDS Severity of Symptoms Scale (SOS) may provide clinicians with a useful tool for establishing neurological balance and helping patients to achieve self-efficacy, self-actualization, and prosperity.

10.
Am J Biomed Sci Res ; 19(6): 709-715, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37885606

RESUMO

Spinal biomechanical alignment is now able to be altered through the use of unique sound wave technology. This methodological commentary will correlate recent studies demonstrating the ability of sound waves to carry mass, how the EPIC technique spinal procedure uses a sound wave impulse to create measurable changes in spinal alignment, and the clinical safety and efficacy of this approach. The EPIC technique is a direct genealogical descendant of the technique originally developed by the founding family of chiropractic. With sound wave therapies currently being used to break up kidney stones, called lithotripsy, in physical therapy for the treatment of soft tissue injuries, in the treatment of prostate cancer, and in the treatment of Alzheimer's disease, it is possible that the use of sound wave therapies may enter into the realm of altering joint biomechanics. Through a neurovascular examination, the EPIC technique spinal procedure can ascertain the presence of craniocervical subluxation, followed by acquiring multi-dimensional radiographic images for structural analysis. Currently using digital radiographic analysis, the EPIC technique acquires an epigenetic profile of structural asymmetries as well as a multi-directional biomechanical malposition profile of the spine, combining both profiles to ascertain the exact degrees for realignment. EPIC clinics have successfully utilized EPIC on over 20,000 cases. Comparison of pre-treatment biomechanical lateral displacement of the C1 vertebra around the Z-axis measured on digital radiographs, and post-treatment biomechanical lateral displacement of the C1 vertebra measured on digital radiographs immediately following the procedure, demonstrated an average 52% reduction in lateral biomechanical displacement around the Z-axis in a select group of over 2,000 cases. While more research is required, we are encouraged by these preliminary results. WC 265.

11.
Artigo em Inglês | MEDLINE | ID: mdl-36812107

RESUMO

Since 2000 there have been 915,515 people who have died from a drug overdose in the United States (US). This number continues to increase and in 2021 drug overdose deaths reached a record high of 107,622, and opioids specifically were responsible for 80,816 of those deaths. This unprecedented rate of drug overdose deaths is the direct result of increasing rates of illicit drug use in the US. It was estimated that in the US in 2020, approximately 59.3 million individuals had used illicit drugs, 40.3 million had a substance use disorder (SUD), and 2.7 million had opioid use disorder (OUD). Typical treatment for OUD involves an opioid agonist (i.e., buprenorphine or methadone) along with a variety of psychotherapeutic interventions (i.e., motivational interviewing, cognitive-behavioral therapy (CBT), behavioral family counseling, mutual help groups, etc.). In addition to the aforementioned treatment options, there is an urgent need for new therapies and screening methods that are reliable, safe, and effective. Similar to the concept of prediabetes is the novel concept of "preaddiction." Preaddiction is defined as individuals with mild to moderate SUD or those at risk for developing a severe SUD/addiction. Screening for preaddiction could be achieved through genetic testing (i.e., the genetic addiction risk severity (GARS) test) and/or through other neuropsychiatric testing (i.e., Memory (CNSVS), Attention (TOVA), Neuropsychiatric (MCMI-III), Neurological Imaging (qEEG/P300/EP)). The concept of preaddiction, when used in conjunction with standardized and objective diagnostic screening/testing, would halt the rise of SUD and overdoses with early detection and treatment.

12.
Clin Exp Psychol ; 9(2): 1-3, 2023 Mar 02.
Artigo em Inglês | MEDLINE | ID: mdl-37363693

RESUMO

One important area for consideration especially in terms of combating the ongoing never ending opioid crisis, relates to novel newer assessments for all addictive behaviors both substance and non-substance behaviors (RDS). It is very important to identify early in one's life the possibility of, because of known DNA antecedents, the presence of pre-addiction. The development of the Genetic Addiction Risk Severity (GARS) test, Blum's group believes that this type of testing should be the "standard of care" following additional studies. Understandably that while polymorphisms in the Mu-Opioid receptor (MOR) is of real concern in terms of setting people up for predisposition to opioid dependence, the genetic and epigenetic status of dopaminergic function must be considered as well. While this sounds bold (which it is) the results should be protected by the G.I. N. A. law enacted in the USA in 2011. One avenue of further investigation, instead of providing powerful opioids for opioid dependence, is to seek out non-addictive alternatives. Accordingly, other non-addictive modalities including genetic guided KB220 (amino-acid-enkephalinase-N-acetylcysteine-NAD), non-invasive rTMS for psychiatry and pain, epigenetic remodeling, gene edits, non-invasive H-wave for pain management and enhanced functionality, brain spotting, cognitive behavioral therapy awarenesss integration therapy, NUCALM, trauma therapy, awareness tools, genograms, exercise, sports, fitness programs (one hour per day), light therapy and even laughing therapy as well as any other known modalities that can induce reward symmetry. While the short term use of opioids for opioid dependence to reduce harm is certainly acceptable, clinicians should consider a better long-term plan.

13.
J Neurol Sci ; 453: 120809, 2023 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-37774561

RESUMO

Reward Deficiency Syndrome (RDS), particularly linked to addictive disorders, costs billions of dollars globally and has resulted in over one million deaths in the United States (US). Illicit substance use has been steadily rising and in 2021 approximately 21.9% (61.2 million) of individuals living in the US aged 12 or older had used illicit drugs in the past year. However, only 1.5% (4.1 million) of these individuals had received any substance use treatment. This increase in use and failure to adequately treat or provide treatment to these individuals resulted in 106,699 overdose deaths in 2021 and increased in 2022. This article presents an alternative non-pharmaceutical treatment approach tied to gene-guided therapy, the subject of many decades of research. The cornerstone of this paradigm shift is the brain reward circuitry, brain stem physiology, and neurotransmitter deficits due to the effects of genetic and epigenetic insults on the interrelated cascade of neurotransmission and the net release of dopamine at the Ventral Tegmental Area -Nucleus Accumbens (VTA-NAc) reward site. The Genetic Addiction Risk Severity (GARS) test and pro-dopamine regulator nutraceutical KB220 were combined to induce "dopamine homeostasis" across the brain reward circuitry. This article aims to encourage four future actionable items: 1) the neurophysiologically accurate designation of, for example, "Hyperdopameism /Hyperdopameism" to replace the blaming nomenclature like alcoholism; 2) encouraging continued research into the nature of dysfunctional brainstem neurotransmitters across the brain reward circuitry; 3) early identification of people at risk for all RDS behaviors as a brain check (cognitive testing); 4) induction of dopamine homeostasis using "precision behavioral management" along with the coupling of GARS and precision Kb220 variants; 5) utilization of promising potential treatments include neuromodulating modalities such as Transmagnetic stimulation (TMS) and Deep Brain Stimulation(DBS), which target different areas of the neural circuitry involved in addiction and even neuroimmune agents like N-acetyl-cysteine.

14.
EC Psychol Psychiatr ; 12(3): 26-32, 2023 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-37361347

RESUMO

It is with a saddened heart that we are dedicating this article to the loving memory of our dear departed friend and associate B. William Downs. Bill was well known in the nutritional space worldwide for his major contributions to the health and welfare of millions around the globe. The founder of Victory Nutrition International (VNI) in conjunction with Kim Downs, as well as so many contributions to scientific literature, to those that knew him personally will forever be touched. Bill was a highly spirited human with a never ending love for caring and helping so many individuals. To know Bill is to walk in the face of a music lover playing drums, trained as a martial artist, and riding through the winds of a Beamer driven by an iconic man driven to victory. Our hearts may be saddened but Bills spirit to those that know him will be forever. In this article we discuss and review some potential futuristic concepts and technological advancements in terms of geneospirituality engineering to help prevent relapse and or even protect against an unwanted predisposition to RDS behaviors. Futuristic development may contribute to an attenuation of both DNA antecedents as well as epigenetic reward system insults leading to unwanted substance and non-substance addictive behaviors.

15.
J Addict Psychiatry ; 7(1): 5-516, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38164471

RESUMO

In the USA alone, opioid use disorder (OUD) affects approximately 27 million people. While the number of prescriptions may be declining due to increased CDC guidance and prescriber education, fatalities due to fentanyl-laced street heroin are still rising. Our laboratory has extended the overall concept of both substance and non-substance addictive behaviors, calling it "Reward Deficiency Syndrome (RDS)." Who are its victims, and how do we get this unwanted disorder? Is RDS caused by genes (Nature), environment (Neuro-epigenetics, Nurture), or both? Recent research identifies resting-state functional connectivity in the brain reward circuitry as a crucial factor. Analogously, it is of importance to acknowledge that the cumulative discharge of dopamine, governed by the nucleus accumbens (NAc) and modulated by an array of additional neurotransmitters, constitutes a cornerstone of an individual's overall well-being. Neuroimaging reveals that high-risk individuals exhibit a blunted response to stimuli, potentially due to DNA polymorphisms or epigenetic alterations. This discovery has given rise to the idea of a diminished 'thrill,' though we must consider whether this 'thrill' may have been absent from birth due to high-risk genetic predispositions for addiction. This article reviews this issue and suggests the general concept of the importance of "induction of dopamine homeostasis." We suggest coupling a validated genetic assessment (e.g., GARS) with pro-dopamine regulation (KB220) as one possible frontline modality in place of prescribing potent addictive opioids for OUD except for short time harm reduction. Could gene editing offer a 'cure' for this undesirable genetic modification at birth, influenced by the environment and carried over generations, leading to impaired dopamine and other neurotransmitter imbalances, as seen in RDS? Through dedicated global scientific exploration, we hope for a future where individuals are liberated from pain and disease, achieving an optimal state of well-being akin to the proverbial 'Garden of Eden'.

16.
Psychol Res Behav Manag ; 16: 4839-4857, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38050640

RESUMO

Loneliness, an established risk factor for both, mental and physical morbidity, is a mounting public health concern. However, the neurobiological mechanisms underlying loneliness-related morbidity are not yet well defined. Here we examined the role of genes and associated DNA risk polymorphic variants that are implicated in loneliness via genetic and epigenetic mechanisms and may thus point to specific therapeutic targets. Searches were conducted on PubMed, Medline, and EMBASE databases using specific Medical Subject Headings terms such as loneliness and genes, neuro- and epigenetics, addiction, affective disorders, alcohol, anti-reward, anxiety, depression, dopamine, cancer, cardiovascular, cognitive, hypodopaminergia, medical, motivation, (neuro)psychopathology, social isolation, and reward deficiency. The narrative literature review yielded recursive collections of scientific and clinical evidence, which were subsequently condensed and summarized in the following key areas: (1) Genetic Antecedents: Exploration of multiple genes mediating reward, stress, immunity and other important vital functions; (2) Genes and Mental Health: Examination of genes linked to personality traits and mental illnesses providing insights into the intricate network of interaction converging on the experience of loneliness; (3) Epigenetic Effects: Inquiry into instances of loneliness and social isolation that are driven by epigenetic methylations associated with negative childhood experiences; and (4) Neural Correlates: Analysis of loneliness-related affective states and cognitions with a focus on hypodopaminergic reward deficiency arising in the context of early life stress, eg, maternal separation, underscoring the importance of parental support early in life. Identification of the individual contributions by various (epi)genetic factors presents opportunities for the creation of innovative preventive, diagnostic, and therapeutic approaches for individuals who cope with persistent feelings of loneliness. The clinical facets and therapeutic prospects associated with the current understanding of loneliness, are discussed emphasizing the relevance of genes and DNA risk polymorphic variants in the context of loneliness-related morbidity.

17.
J Transl Med ; 10: 34, 2012 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-22380642

RESUMO

BACKGROUND: Medication non adherence is a global epidemic perplexing phenomenon that is eminent, but not insurmountable. Our first objective was to explore whether providing pharmacist's counseling to cardiac patients prior to discharge can increase patient's medication adherence, and our second objective was to assess whether better medication adherence leads to reduction of hospital readmissions. METHODS: Observational study was conducted among diagnosed cardiac patients using an intervention strategy at discharge from two hospitals in Israel; The Nazareth and the Haemek hospital. 74 patients were recruited between January 2010 and January 2011. Two separate groups were selected; intervention group: 33 patients who prior to discharge received nurse, pharmacist interventions, and control group: 41 patients who had received the nurse and hospital discharge counseling only. RESULTS: Regression analysis for examining the first objective reflected significant effect when having a pharmacist interventions, which explains the increasing 11.6% of the variance in medication adherence, [F change (1,73) = 9.43, p < 0.003]. Stepwise regression analysis for examining the second objective demonstrated that the relation between medication adherence and readmissions was insignificant [F (1,73) = 9.43, n.s]. CONCLUSIONS: While physicians and nurses can have an impact on improving adherence, pharmacists have demonstrated the ability to inform, problem-solve and provide performance support directly to patients.


Assuntos
Doenças Cardiovasculares/tratamento farmacológico , Doenças Cardiovasculares/psicologia , Aconselhamento , Hospitais , Adesão à Medicação/psicologia , Alta do Paciente , Farmacêuticos , Idoso , Estudos de Casos e Controles , Feminino , Humanos , Israel , Masculino , Análise de Regressão , Resultado do Tratamento
18.
J Transl Med ; 10: 126, 2012 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-22709610

RESUMO

OBJECTIVE: To determine whether the consumption of tobacco used in Water-Pipe by drivers increases the risk of a motor vehicle collision as a consequence of hypoxia. DESIGN: Analytical case-control study. DATA SOURCES: Seventy exclusive Water-Pipe smokers (Experimental Group--EG)--mean age ± SD: 29.47 ± 10.45 years; mean number of weekly WPS, (6.9 ± 3.7); mean duration of WPS (WPS) is (7.5 ± 2.1 years)--and thirty non-smoker (Control Group--CG; mean age ± SD: 36.33 ± 13.92 years) were recruited during 2011 from two Arab villages located in the Galilee, northern Israel. METHODS: We performed a case-control study exclusively among Water-Pipe smokers with an appropriate non smokers control group. Demographic questionnaire, Pulse Oxymeter for blood oxygenation measure and a driver simulator for measuring various participants driving behaviors were utilized. Statistical analysis for analyzing the different variables, Pearson's x2 analysis for the comparison of categorical variables, continuous variable is compared using Student's t-test and for testing the correlation between the different variables and bivariate correlation analysis were applied. RESULTS: In the (EG) following WPS, we observed increase in the pulse rate--from 80 to 95 (t = 11.84, p < 0.05) and decrease in saturation level from 97.9 to 97.32, the decrease is statistically significant (t = 3.01, p < 0.05) versus no change in (CG). An increased number of accidents among EG (OR is 1.333 with CI of 1.008-1.776), while in CG, an insignificantly decrease (t = 3.08, p < 0.05). In EG an increase in centerline crossings (OR is 1.306 with CI of 1.016-1.679), also the total time not being within the lane was increased and the estimated (OR: 1.329; CI: 1.025-1.722). WPS increases the number of accidents by 33% and Hypoxia can cause driving behavioral turbulences. CONCLUSION: The results show that WPS has a significant impact on driving behavior and on the risk of being involved in road accidents and causing driving to become riskier and less careful and stable. To the best of our knowledge, this is the first time such relationships have been tested. After WPS the total number of traffic accidents and driving violations increase. The results show a significant increase in the pulse rate immediately after WPS with a decrease in the saturation rate (the level of blood oxygenation); these changes continue half an hour after WPS.


Assuntos
Condução de Veículo , Equipamentos e Provisões , Nicotiana , Fumar , Adulto , Estudos de Casos e Controles , Feminino , Humanos , Israel , Masculino , Pessoa de Meia-Idade
19.
J Psychoactive Drugs ; 44(1): 38-55, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22641964

RESUMO

The nucleus accumbens, a site within the ventral striatum, plays a prominent role in mediating the reinforcing effects of drugs of abuse, food, sex, and other addictions. Indeed, it is generally believed that this structure mandates motivated behaviors such as eating, drinking, and sexual activity, which are elicited by natural rewards and other strong incentive stimuli. This article focuses on sex addiction, but we hypothesize that there is a common underlying mechanism of action for the powerful effects that all addictions have on human motivation. That is, biological drives may have common molecular genetic antecedents, which if impaired, lead to aberrant behaviors. Based on abundant scientific support, we further hypothesize that dopaminergic genes, and possibly other candidate neurotransmitter-related gene polymorphisms, affect both hedonic and anhedonic behavioral outcomes. Genotyping studies already have linked gene polymorphic associations with alcohol and drug addictions and obesity, and we anticipate that future genotyping studies of sex addicts will provide evidence for polymorphic associations with specific clustering of sexual typologies based on clinical instrument assessments. We recommend that scientists and clinicians embark on research coupling the use of neuroimaging tools with dopaminergic agonistic agents to target specific gene polymorphisms systematically for normalizing hyper- or hypo-sexual behaviors.


Assuntos
Sistema Límbico/fisiologia , Núcleo Accumbens/fisiologia , Polimorfismo Genético , Recompensa , Comportamento Sexual , Transtornos Relacionados ao Uso de Substâncias/genética , Feminino , Genótipo , Humanos , Masculino
20.
J Psychoactive Drugs ; 44(5): 398-409, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-23457891

RESUMO

Substance use disorders (SUD) are inheritable and the culprit is hypodopaminergic function regulated by reward genes. We evaluated a natural dopaminergic agonist; KB220 intravenous (IV) and oral variants, to improve dopaminergic function in SUD. Our pilot experiment found a significant reduction of chronic symptoms, measured by the Chronic Abstinence Symptom Severity (CASS) Scale. The combined group (IV and oral) did significantly better than the oral-only group over the first week and 30-day follow-up period. Next, the combination was given to 129 subjects and three factors; Emotion, Somatic, and Impaired Cognition, with eigenvalues greater than one were extracted for baseline CASS-Revised (CASS-R) variables. Paired sample t-tests for pre and post-treatment scales showed significant declines (p = .00001) from pre- to post-treatment: t = 19.1 for Emotion, t = 16.1 for Somatic, and t = 14.9 for Impaired Cognition. In a two-year follow-up of 23 subjects who underwent KB220IV therapy (at least five IV treatments over seven days) plus orals for 30+ days: 21 (91%) were sober at six months, 19 (82%) having no relapse; 19 (82%) were sober at one year, 18 (78%) having no relapse; and 21 (91%) were sober two-years post-treatment, 16(70%) having no relapse. We await additional research and advise caution in interpreting these encouraging results.


Assuntos
Aminoácidos/uso terapêutico , Comportamento/efeitos dos fármacos , Agonistas de Dopamina/uso terapêutico , Transtornos Relacionados ao Uso de Substâncias/reabilitação , Administração Oral , Adulto , Aminoácidos/administração & dosagem , Doença Crônica , Cognição/efeitos dos fármacos , Agonistas de Dopamina/administração & dosagem , Emoções/efeitos dos fármacos , Emoções/fisiologia , Feminino , Humanos , Injeções Intravenosas , Masculino , Pessoa de Meia-Idade , Testes Neuropsicológicos , Projetos Piloto , Recidiva , Recompensa , Centros de Tratamento de Abuso de Substâncias , Síndrome de Abstinência a Substâncias/psicologia
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