Tag: pubmed

Transl Psychiatry. 2023 Dec 14;13(1):392. doi: 10.1038/s41398-023-02690-1.

ABSTRACT

Alcohol Use Disorder (AUD) adversely affects the lives of millions of people, but still lacks effective treatment options. Recent advancements in psychedelic research suggest psilocybin to be potentially efficacious for AUD. However, major knowledge gaps remain regarding (1) psilocybin’s general mode of action and (2) AUD-specific alterations of responsivity to psilocybin treatment in the brain that are crucial for treatment development. Here, we conducted a randomized, placebo-controlled crossover pharmaco-fMRI study on psilocybin effects using a translational approach with healthy rats and a rat model of alcohol relapse. Psilocybin effects were quantified with resting-state functional connectivity using data-driven whole-brain global brain connectivity, network-based statistics, graph theory, hypothesis-driven Default Mode Network (DMN)-specific connectivity, and entropy analyses. Results demonstrate that psilocybin induced an acute wide-spread decrease in different functional connectivity domains together with a distinct increase of connectivity between serotonergic core regions and cortical areas. We could further provide translational evidence for psilocybin-induced DMN hypoconnectivity reported in humans. Psilocybin showed an AUD-specific blunting of DMN hypoconnectivity, which strongly correlated to the alcohol relapse intensity and was mainly driven by medial prefrontal regions. In conclusion, our results provide translational validity for acute psilocybin-induced neural effects in the rodent brain. Furthermore, alcohol relapse severity was negatively correlated with neural responsivity to psilocybin treatment. Our data suggest that a clinical standard dose of psilocybin may not be sufficient to treat severe AUD cases; a finding that should be considered for future clinical trials.

PMID:38097569 | DOI:10.1038/s41398-023-02690-1

Nat Commun. 2023 Dec 14;14(1):8328. doi: 10.1038/s41467-023-43168-4.

ABSTRACT

The self-assembly of complex structures from a set of non-identical building blocks is a hallmark of soft matter and biological systems, including protein complexes, colloidal clusters, and DNA-based assemblies. Predicting the dependence of the equilibrium assembly yield on the concentrations and interaction energies of building blocks is highly challenging, owing to the difficulty of computing the entropic contributions to the free energy of the many structures that compete with the ground state configuration. While these calculations yield well known results for spherically symmetric building blocks, they do not hold when the building blocks have internal rotational degrees of freedom. Here we present an approach for solving this problem that works with arbitrary building blocks, including proteins with known structure and complex colloidal building blocks. Our algorithm combines classical statistical mechanics with recently developed computational tools for automatic differentiation. Automatic differentiation allows efficient evaluation of equilibrium averages over configurations that would otherwise be intractable. We demonstrate the validity of our framework by comparison to molecular dynamics simulations of simple examples, and apply it to calculate the yield curves for known protein complexes and for the assembly of colloidal shells.

PMID:38097568 | DOI:10.1038/s41467-023-43168-4

Nat Commun. 2023 Dec 14;14(1):7899. doi: 10.1038/s41467-023-43444-3.

ABSTRACT

Daily eating/fasting cycles synchronise circadian peripheral clocks, involved in the regulation of the cardiovascular system. However, the associations of daily meal and fasting timing with cardiovascular disease (CVD) incidence remain unclear. We used data from 103,389 adults in the NutriNet-Santé study. Meal timing and number of eating occasions were estimated from repeated 24 h dietary records. We built multivariable Cox proportional-hazards models to examine their association with the risk of CVD, coronary heart disease and cerebrovascular disease. In this study, having a later first meal (later than 9AM compared to earlier than 8AM) and last meal of the day (later than 9PM compared to earlier than 8PM) was associated with a higher risk of cardiovascular outcomes, especially among women. Our results suggest a potential benefit of adopting earlier eating timing patterns, and coupling a longer nighttime fasting period with an early last meal, rather than breakfast skipping, in CVD prevention.

PMID:38097547 | DOI:10.1038/s41467-023-43444-3

J Mech Behav Biomed Mater. 2023 Dec 7;150:106303. doi: 10.1016/j.jmbbm.2023.106303. Online ahead of print.

ABSTRACT

Underbody blasts (UBB) from mines and improvised explosive devices in military combat can cause debilitating spine injuries to vehicle mounted soldiers. Due to the exclusion of females in combat roles in prior US Department of Defense policy, UBB exposure and injury have predominantly affected male soldiers. Recent policy changes have opened many combat roles to women serving in the US Military (Carter, 2015) and have increased the need to understand the injury potential for female Warfighters. The goal of this study was to investigate the fracture response of adult female lumbar spines compared to adult male spines in UBB relevant loading to identify potential differences in either fracture mechanism or force. Results are presented for 15 simulated UBB spine compression tests using three small female (SF), five large female (LF), and seven mid-sized male (MM) post-mortem human subjects (PMHS). These PMHS groups align to 5th- and 75th-percentile female and 50th-percentile males, based on height and weight from the 2012 Anthropometric Survey of U.S. Army Personnel (Gordon et al., 2014). Both small females and large females (similar in size to the males) were included to assess the role of size and/or sex in the response. Tests were conducted at Virginia Tech on a cam-driven linear compression rig, which included a 6-axis load cell and ram accelerometer to evaluate the fracture. Fracture was visualized through high-speed x-ray video. All female and male spines exhibited similar fracture initiation at the end plates and progression through the vertebral body. The resulting severe compression and burst fractures were representative of reported theatre injuries (Freedman et al., 2014). Mean axial fracture forces were -4182 ± 940 N (SF), -6225 ± 1180 N (LF), -5459 ± 1472 N (All Females) and -7993 ± 2445 N (MM). The SF group was found to have statistically significant differences in mean fracture force compared to both LF and MM groups, while no significant difference was found between LF and MM groups, although the mean force at initial fracture was lower for the LF group. The All-Females group Fz mean was significantly different from the MM group. These data suggest that the significant difference in weight between the SF and LF groups, did have an influence on the Fz outcome, when controlling for sex. Conversely, controlling for size in the LF and MM comparison, sex did influence the mean Fz, but was not statistically significant. Groups with combined sex and size differences, however, did show significant differences in mean Fz. Further study is warranted to understand whether sex or size has a larger effect on fracture force. Mean ram displacement (spine compression) values at fracture initiation were -6.0 ± 5.3 mm (SF), -4.4 ± 0.8 mm (LF), -5.0 ± 3.0 mm (All Females), -6.2 ± 4.5 mm (MM). Spine compression did not seem to be largely influenced by either sex or size, and none of the groups was found to have significant differences in mean displacement values.

PMID:38096612 | DOI:10.1016/j.jmbbm.2023.106303

Bioinformatics. 2023 Dec 14:btad755. doi: 10.1093/bioinformatics/btad755. Online ahead of print.

ABSTRACT

In this article, we present IntelliGenes, a novel machine learning (ML) pipeline for the multi-genomics exploration to discover biomarkers significant in disease prediction with high accuracy. IntelliGenes is based on a novel approach, which consists of nexus of conventional statistical techniques and cutting-edge ML algorithms using multi-genomic, clinical, and demographic data. IntelliGenes introduces a new metric i.e., Intelligent Gene (I-Gene) score to measure the importance of individual biomarkers for prediction of complex traits. I-Gene scores can be utilized to generate I-Gene profiles of individuals to comprehend the intricacies of ML used in disease prediction. IntelliGenes is user-friendly, portable, and a cross-platform application, compatible with Microsoft Windows, macOS, and UNIX operating systems. IntelliGenes not only holds the potential for personalized early detection of common and rare diseases in individuals, but also opens avenues for broader research using novel ML methodologies, ultimately leading to personalized interventions and novel treatment targets.

AVAILABILITY: The source code of IntelliGenes is available on GitHub (https://github.com/drzeeshanahmed/intelligenes) and Code Ocean (https://codeocean.com/capsule/8638596/tree/v1).

SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

PMID:38096588 | DOI:10.1093/bioinformatics/btad755

J Breath Res. 2023 Dec 14. doi: 10.1088/1752-7163/ad15a3. Online ahead of print.

ABSTRACT

Due to the overall low abundance of volatile compounds in exhaled breath, it is necessary to preconcentrate the sample prior to traditional thermal desorption gas chromatography mass spectrometry (TD-GC-MS) analysis. While certain aspects of thermal desorption tubes, such as volatile storage, have been evaluated, many aspects remain uncharacterized. Two common thermal desorption tubes, Tenax TA and Biomonitoring 5TD tubes, were evaluated for background content and flow rate variability. The data illustrate that the Biomonitoring 5TD tubes have the highest number (23) and abundance of background contamination greater than 3x the mean noise when compared to Tenax TA (13) and empty tubes (9). Tentative identifications of the compounds in the background contamination experiment show that greater than 59% (16/27) of the compounds identified have been reported in the breath literature. The data illustrate the TD tube background abundance could account for more than 70% of the chromatographic signal from exhaled breath for these select compounds. Flow rate measurements of 200 Tenax TA and 200 Biomonitoring 5TD tubes show a large range in measured flow rates among the TD tubes (Tenax: 252.9-284.0mL min-1, 5TD: 220.6-255.1mL min-1). Finally, TD tubes of each type, Tenax TA and Biomonitoring 5TD, previously established to have high, medium, and low flow rates, show insignificant differences (p>0.05) among the tubes of different flow rates, using both gas standards and an exhaled breath from a peppermint experiment. Collectively, these results establish overall background compounds attributed to each TD tube type tested. Additionally, while measured flow rate variability is present and plausibly impacts exhaled breath results, the data demonstrate no statistically significant difference was observed between tubes showing high, medium, and low flow rates from two separate sample types.

PMID:38096565 | DOI:10.1088/1752-7163/ad15a3

Georgian Med News. 2023 Oct;(343):172-178.

ABSTRACT

Drug-induced Nitrosogenesis/Carcinogenesis turns out to be a ubiquitous, pervasive, large-scale, poorly controllable concept for the academic community, which underlies the long-term, permanent modification of the human genome by contact with nitrosamines/NDSRIs, which ultimately leads to the generation of diverse cancers, but also melanoma in particular. The discovery of a (currently) unclassifiable number of nitroso derivatives/genome modifiers in the most commonly distributed drugs worldwide (in about 300 preparations according to the FDA/includes beta blockers/bisoprolol/nebivolol and ACE inhibitors/perindopril), their forced tolerability, attributed as a necessity or lack of alternative also to the present (but also to future periods), and their proven carcinogenicity (already 70 years ago), suggest a kind of creepy form of experiment to which public health is subjected worldwide. The creation of a universal nitroso-comfort of pharmaceutical companies and the regulation of a permanent intake of carcinogens in drugs for years to come, but also decades back, suggest possible cartel agreements between the regulation/distribution unit and that of production cycles. These “agreements” are becoming increasingly evident and in all likelihood position nitrosogenesis from a until recently unknown element, to a pathogenetic factor of paramount importance. Melanoma could be viewed precisely as the controlled end gene-modified product of drug-mediated nitrosogenesis/carcinogenesis, proven to be a locoregional (but not only) phenomenon hundreds if not thousands of times. The dilemma stays: Are the nitrosamines in drugs genetic weapons, ethnic bioweapons for silent war ? The nitrosogenesis concerning melanoma leads to the logical conclusion that cancer is in fact a largely controlled set event or, according to others, a forced necessity of evolutionary globalization processes to purge the population in certain regions. In favor of this statement indicative are namely: 1) lack of regulatory control/results of such conducted, 2) complete information veil for the end user regarding contamination with carcinogens/nitrosamines in certain batches or all batches of drugs, 3) misinformation and lack of transparency regarding the concept of nitrosogenesis also for the academic community, as well as 4) the impunity to pharmaceutical conglomerates after criminal negligence/controlled criminogenicity proven thousands of times by the FDA/EMA leading to regulatory controlled drug mediated genocide of the human population in certain areas on a daily basis. And most important of all: 5) the lack of refusal to eliminate these drugs, i.e. – the imposition of forced tolerance at any cost. It is extremely unfortunate that the mentioned and identified grotesque/situation, its tolerance on a global scale, lead to a misjudgement of the significance of real tumor inducers within the global health map//statistics as well as melanoma. The focus of prevention is being displaced, while the incidence of cancer in general and that of melanoma is skyrocketing. Nitrosamines could be defined as the newest, modern, until recently invisible and unknown, but -controllable form of genetic weapon to modify the human genome. Because of these very facts, the likelihood that clinicians and the academic community are in the frozen and permanent state of the Dunning-Kruger effect is very real. Certain globalization regulatory elements create problems and assignments that must be solved ˝competently˝ by incompetent, fully regulatable compartments. As their state of competence depends again and entirely on ˝their incompetence˝. Until now. After the formalization of the concept of Nitrosogenesis (as a form of genetic weapon) and melanoma for example, but not only, it remains to be seen whether universal incompetence will become a guarantee of competence and the survival. Or- will it remain again at the level of globalized, criminally conditioned, appointed and regulated from above “competent incompetence”. The dilemmas to regulators and manufacturers remain open : Is it competent to take drugs that contain carcinogens/nitrosamines? Is it competent for this issue to continue for decades with impunity? Is it competent for regulators not to inform consumers about the presence of carcinogens/genome modifiers in medicines for decades? Is it competent for certain regions to be affected by nitrosamine contamination and not others? Is it competent not to reflect this in regional and global health bulletins on side effects? Is it competent to make thousands of times the profits from the modified genetic map business, regulated and legally initiated through the intake of carcinogens? Is it competent to have the concentration of carcinogens within polymedication exceeding many times the daily allowable doses of carcinogens and have no solution for this? Is it competent, when the intake of nitrosamines in medicines is associated with the generation of melanomas and heterogeneous cancers- to have no alternative to this or when one is available- to conceal it skillfully? Is it competent to determine carcinogenic activity based on mutagenic tests? Is it competent to be polyincompetent within a framework of mass (in)competence? We report systemically administered drugs for the treatment of high blood pressure from the group of beta blockers (bisoprolol/nebivolol) and ACE inhibitors (perindopril) that have been identified by regulators in the face of FDA as hypothetically contaminated with nitrosamines/NDSRIs with a carcinogenic potency between 4 and 5, respectively. Within this cumulative intake, (which according to the regulators was not at risk of developing cancerous forms), similar to other cases in the world literature, the patient developed a relatively short-term, metastatic nevus spilus-based nodular melanoma. The paper analyses not only the role of nitrosogenesis, but also that of two pregnancies and painful sunburns as potential cofactors for melanoma genesis. Academic attention is drawn to the potential impact of drug-mediated nitrosogenesis/carcinogenesis. Nitrosamines in the framework of polycontamination and polymedication could also be identified as one of the most effective, until recently unknown, modern generation genetic weapons for modifying the human genome and controlling cancer. Moreover, they could be controllably applied and skillfully targeted. At least until now. The officialization of carcinogens in more than 250 of the most common drugs and the clinico-pathological correlations concerning the development of cancer/melanoma in poorly controlled geographical regions represent a kind of in vivo prospective study to determine precisely the real carcinogenic role of nitrosamines to date.

PMID:38096536

Georgian Med News. 2023 Oct;(343):165-171.

ABSTRACT

Parkinson’s Disease in Mild Cognitive Impairment (PD-MCI) is a complex condition characterized by a variety of cognitive problems that coexist with the physical symptoms of Parkinson’s disease (PD). This study aims to examine the different medical indicators and associated tendencies among different PD-MCI groups. We investigated 132 people who had been given PD-MCI diagnoses. Utilizing SPSS, statistical evaluations are carried out. In overall PD-MCI variants, this investigation found that visuospatial ability and attentional/executive performance are the most impaired cognitive areas. It was also noticed that distinct PD-MCI groups had variances in their neurological characteristics, in multi domain amnesia (Non-Memory) PD-MCI patients exhibiting especially severe issues with unstable posture and walking. The intricacy of PD- Mild Cognitive Impairment (MCI) is highlighted by those results, which also imply that the interplay between mental and physical signs may be controlled by a number of interrelated factors, such as particular cognitive areas, brain surfaces, and the general level of cognitive impairment.

PMID:38096535

Georgian Med News. 2023 Oct;(343):139-143.

ABSTRACT

There are many unresolved questions regarding the features of surgical aggression in the open method of treatment of severe forms of peritonitis. There are isolated publications in the literature on the risk features of these interventions, despite the high prevalence of the problem. The purpose of this study was to study the features of surgical aggression in the open method of treatment of severe forms of peritonitis. The study included 205 patients with severe forms of purulent peritonitis treated at the Emergency Hospital in Aktobe (n=205). To assess the factors of surgical aggression, the reliability of the results was evaluated by variational statistics according to the Student’s t-criterion, taking into account the degree of freedom, at p<0.05 and p<0.01, with the calculation of arithmetic averages and their average errors (M+m). The data are presented as an average value±standard deviation or median and percentiles, p-values less than 0.05 were considered significant. Based on the results obtained, it was found that the frequency of repeated laparosanation surgical interventions in one patient was 2.8±0.3 times against the background of purulent-inflammatory process in the abdominal cavity, a high degree of stress index of the regulatory systems of the body during sanitation was revealed – up to 1460.9±101.5 units, postural reactions of blood circulation and respiration in 7.55% and metabolic disorders homeostasis. Aggressive factors affecting patients and causing the risk of multiple laparosanation interventions at the stages of open surgical treatment of severe forms of peritonitis have been identified. The data obtained can be used to develop therapeutic and preventive measures to improve the results of treatment of severe peritonitis.

PMID:38096531

Georgian Med News. 2023 Oct;(343):127-133.

ABSTRACT

The design of studies on the immune system does not have gender peculiarities, but the information about the higher frequency of pathology of the female reproductive system in the presence of immunodeficiency condition determines the purpose of this study, namely, to identify the features of immune status in the presence of secondary immunodeficiency of infectious (i.e., HIV infection, AIDS stage) and non-infectious origin (alcohol dependence syndrome) and their combination in women of reproductive age. The material for the study of cellular and humoral immunity was a lymphocyte suspension obtained by centrifugation of peripheral blood (taken within 12 hours after death) in women of reproductive age with HIV infection (AIDS stage), alcohol dependence syndrome and their combination. Immunological examination included the determination of quantitative indicators of cellular immunity using monoclonal antibodies: T-lymphocytes (CD3) and their main subpopulations of T-helper cells (CD4), cytotoxic lymphocytes (CD8), CD4/CD8 immunoregulatory index; as well as indicators of humoral immunity: B-lymphocytes (CD19) and immunoglobulins of the main classes (IgA, IgG, IgM). Additionally, interleukins IL-6 and IL-10 were studied to determine the parameters of the cytokine profile. The study indicates that the number of leukocytes and lymphocytes in the group of deceased women with alcohol dependence syndrome was 3.6±0.38×109/l and 0.82±0.35×109/l; in deceased women with HIV/AIDS, these indicators were reduced – 2.9±0.03×109/l and 0.39±0.04×109/l, respectively; and in deceased women with combined pathology (AIDS and alcohol dependence syndrome), they were reduced even more intensively – 2.7±0.04×109/l and 0.35±0.06×109/l (p<0.01). Compared to the control group – 5.22±0.4×109/l and 1.73±0.21×109/l – the number of leukocytes and lymphocytes was reduced in all study groups. In the group of deceased women with alcohol dependence syndrome, significant impairments in the proliferative activity of T-lymphocytes (CD3) and their subpopulation (CD4), as well as B lymphocytes (CD19) and natural killer cells (CD16) were found compared to the group of healthy individuals. Thus, in the control group, the percentage, and absolute values of CD3 were 60.37±4.2% and 1.04±0.05×106/l, and in women suffering from chronic alcoholism, they were statistically significantly lower – 49.1±3.1% and 0.42±0.08×106/l, respectively, p<0.01. The same tendency was found when comparing the values of T-helper cells (CD4) in the control group (44.2±2.9% and 0.76±0.13×106/l) and in deceased patients suffering from chronic alcoholism (33.7±4.6% and 0.28±0.23×106/l), p<0.01. Secondary immunodeficiencies of infectious and non-infectious origin in women (in particular, those formed in HIV/AIDS, alcohol dependence syndrome and their combination) are characterized by negative changes in the cellular and humoral components of the immune system, as evidenced by the presence of transient immunodeficiency, activation of cytolytic and auto aggressive reactions. As a result of these processes, systemic and organ pathology develops, in particular, weakening of the body’s resistance to various infections and pathological changes in organs and tissues, which may be one of the links in the development of pathological processes in internal organs and tissues.

PMID:38096529