Search results for: autonomic dysfunction

Authors: A. Kherraf, M. Bouziane, L. Azzouzi, R. Habbal

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Introduction: Hypocalcaemia is a rare cause of heart failure. We report the clinical case of a young patient with reversible dilated cardiomyopathy secondary to hypocalcaemia in the context of hyperparathyroidism. Clinical case: We report the clinical case of a 23-year-old patient with a history of thyroidectomy for papillary thyroid carcinoma 3 years previously, who presented to the emergency room with a progressive onset dyspnea and edema of the lower limbs. Clinical examination showed hypotension at 90/70 mmHg, tachycardia at 102 bpm, and edema of the lower limbs. The ECG showed a regular sinus rhythm with a prolonged corrected QT interval to 520ms. The chest x-ray showed cardiomegaly. Echocardiography revealed dilated cardiomyopathy with biventricular dysfunction and a left ventricular ejection fraction of 45%, as well as moderate mitral insufficiency by restriction of the posterior mitral leaflet, moderate tricuspid insufficiency, and a dilated inferior vena cava with a pulmonary arterial pressure estimated at 46 mmHg. Blood tests revealed severe hypocalcemia at 38 mg / l with normal albumin and thyroxine levels, as well as hyperphosphatemia and increased TSH. The patient received calcium intake and vitamin D supplementation and was treated with beta blockers, ACE inhibitors, and diuretics with good progress and progressive normalization of cardiac function. Discussion: The cardiovascular manifestations of hypocalcaemia usually appear with deeply low serum calcium levels. This can lead to hypotension, arrhythmias, ventricular fibrillation, prolonged QT interval, or even heart failure. Heart failure is a rare and serious complication of hypocalcemia but most often characterized by complete normalization of myocardial function after treatment. The etiology of the hypocalcaemia, in this case, was probably related to accidental parathyroid removal during thyroidectomy. This is why careful monitoring of calcium levels is recommended after surgery. Conclusion: Hypocalcemic heart failure is rare but reversible heart disease. Systematic monitoring of serum calcium should be performed in all patients after thyroid surgery to avoid any complications related to hypoparathyroidism.

Keywords: hypocalcemia, heart failure, thyroid surgery, hypoparathyroidism

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Authors: Joyce K. Anastasi, Bernadette Capili

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Community Engagement Strategies to Assist with the Development of an RCT Among People Living with HIV Our research team focuses on developing and testing protocols to manage chronic symptoms. For many years, our team designed and implemented symptom management studies for people living with HIV (PLWH). We identify symptoms that are not curative and are not adequately controlled by conventional therapies. As an exemplar, we describe how we successfully engaged PLWH in developing and refining our research feasibility protocol for distal sensory peripheral neuropathy (DSP) associated with HIV. With input from PLWH with DSP, our research received National Institutes of Health (NIH) research funding support. Significance: DSP is one of the most common neurologic complications in HIV. It is estimated that DSP affects 21% to 50% of PLWH. The pathogenesis of DSP in HIV is complex and unclear. Proposed mechanisms include cytokine dysregulation, viral protein-produced neurotoxicity, and mitochondrial dysfunction associated with antiretroviral medications. There are no FDA-approved treatments for DSP in HIV. Purpose: Aims: 1) to explore the impact of DSP on the lives of PLWH, 2) to identify patients’ perspectives on successful treatments for DSP, 3) to identify interventions considered feasible and sensitive to the needs of PLWH with DSP, and 4) to obtain participant input for protocol/study design. Description of Process: We conducted a needs assessment with PLWH with DSP. From our needs assessment, we learned from the patients’ perspective detailed descriptions of their symptoms; physical functioning with DSP; self-care remedies tried, and desired interventions. We also asked about protocol scheduling, instrument clarity, study compensation, study-related burdens, and willingness to participate in a randomized controlled trial (RCT) with a placebo and a waitlist group. Implications: We incorporated many of the suggestions learned from the need assessment. We developed and completed a feasibility study that provided us with invaluable information that informed subsequent NIH-funded studies. In addition to our extensive clinical and research experience working with PLWH, learning from the patient perspective helped in developing our protocol and promoting a successful plan for recruitment and retention of study participants.

Keywords: clinical trial development, peripheral neuropathy, traditional medicine, HIV, AIDS

Procedia PDF Downloads 84

Authors: Anuschka Curran, Sandra Barnard

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Coral reefs are of the most diverse and productive ecosystems on the planet, but due to the impact of climate change, these infrastructures are dying off primarily through coral bleaching. Coral bleaching can be described as the process by which zooxanthellae (algal endosymbionts) are expelled from the gastrodermal cavity of the respective coral host, causing increased coral whitening. The general consensus is that mass coral bleaching is due to the dysfunction of photosynthetic processes in the zooxanthellae as a result of the combined action of elevated temperature and light-stress. The question then is, do zooxanthellae have the potential to play a key role in the future of coral reef restoration through genetic engineering? The aim of this study is firstly to review the different zooxanthellae taxa and their traits with respect to environmental stress, and secondly, to review the information available on the protective mechanisms present in zooxanthellae cells when experiencing temperature fluctuations, specifically concentrating on heat shock proteins and the antioxidant stress response of zooxanthellae. The eight clades (A-H) previously recognized were redefined into seven genera. Different zooxanthellae taxa exhibit different traits, such as their photosynthetic stress responses to light and temperature. Zooxanthellae have the ability to determine the amount and type of heat shock proteins (hsps) present during a heat response. The zooxanthellae can regulate both the host’s respective hsps as well as their own. Hsps, generally found in genotype C3 zooxanthellae, such as Hsp70 and Hsp90, contribute to the thermal stress response of the respective coral host. Antioxidant activity found both within exposed coral tissue, and the zooxanthellae cells can prevent coral hosts from expelling their endosymbionts. The up-regulation of gene expression, which may mitigate thermal stress induction of any of the physiological aspects discussed, can ensure stable coral-zooxanthellae symbiosis in the future. It presents a viable alternative strategy to preserve reefs amidst climate change. In conclusion, despite their unusual molecular design, genetic engineering poses as a useful tool in understanding and manipulating variables and systems within zooxanthellae and therefore presents a solution that can ensure stable coral-zooxanthellae symbiosis in the future.

Keywords: antioxidant enzymes, genetic engineering, heat-shock proteins, Symbiodinium

Procedia PDF Downloads 189

Authors: Jianming Cai

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Exposure to ionizing radiation causes severe damage to human body and an safe and effective radioprotector is urgently required for alleviating radiation damage. In 2008, flagellin, an agonist of TLR5, was found to exert radioprotective effects on radiation injury through activating NF-kB signaling pathway. From then, the radioprotective effects of TLR ligands has shed new lights on radiation protection. CpG-ODN is an unmethylated oligonucleotide which activates TLR9 signaling pathway. In this study, we demonstrated that CpG-ODN has therapeutic effects on radiation injuries induced by γ ray and 12C6+ heavy ion particles. Our data showed that CpG-ODN increased the survival rate of mice after whole body irradiation and increased the number of leukocytes as well as the bone marrow cells. CpG-ODN also alleviated radiation damage on intestinal crypt through regulating apoptosis signaling pathway including bcl2, bax, and caspase 3 etc. By using a radiation-induced pulmonary fibrosis model, we found that CpG-ODN could alleviate structural damage, within 20 week after whole–thorax 15Gy irradiation. In this model, Th1/Th2 imbalance induced by irradiation was also reversed by CpG-ODN. We also found that TGFβ-Smad signaling pathway was regulated by CpG-ODN, which accounts for the therapeutic effects of CpG-ODN in radiation-induced pulmonary injury. On another hand, for high LET radiation protection, we investigated protective effects of CpG-ODN against 12C6+ heavy ion irradiation and found that after CpG-ODN treatment, the apoptosis and cell cycle arrest induced by 12C6+ irradiation was reduced. CpG-ODN also reduced the expression of Bax and caspase 3, while increased the level of bcl2. Then we detected the effect of CpG-ODN on heavy ion induced immune dysfunction. Our data showed that CpG-ODN increased the survival rate of mice and also the leukocytes after 12C6+ irradiation. Besides, the structural damage of immune organ such as thymus and spleen was also alleviated by CpG-ODN treatment. In conclusion, we found that TLR9 ligand, CpG-ODN reduced radiation injuries in response to γ ray and 12C6+ heavy ion irradiation. On one hand, CpG-ODN inhibited the activation of apoptosis induced by radiation through regulating bcl2, bax and caspase 3. On another hand, through activating TLR9, CpG-ODN recruit MyD88-IRAK-TRAF6 complex, activating TAK1, IRF5 and NF-kB pathway, and thus alleviates radiation damage. This study provides novel insights into protection and therapy of radiation damages.

Keywords: TLR9, CpG-ODN, radiation injury, high LET radiation

Procedia PDF Downloads 480

Authors: Semyachkina-Glushkovskaya Oxana, Fedosov Ivan, Blokhina Inna, Terskov Andrey, Evsukova Arina, Elovenko Daria, Adushkina Viktoria, Dubrovsky Alexander, Jürgen Kurths

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In modern neurobiology, sleep is considered a novel biomarker and a promising therapeutic target for brain diseases. This is due to recent discoveries of the nighttime activation of the brain lymphatic system (BLS), playing an important role in the removal of wastes and toxins from the brain and contributes neuroprotection of the central nervous system (CNS). In our review, we discuss that night stimulation of BLS might be a breakthrough strategy in a new treatment of Alzheimer’s and Parkinson’s disease, stroke, brain trauma, and oncology. Although this research is in its infancy, however, there are pioneering and promising results suggesting that night transcranial photostimulation (tPBM) stimulates more effectively lymphatic removal of amyloid-beta from mouse brain than daily tPBM that is associated with a greater improvement of the neurological status and recognition memory of animals. In our previous study, we discovered that tPBM modulates the tone and permeability of the lymphatic endothelium by stimulating NO formation, promoting lymphatic clearance of wastes and toxins from the brain tissues. We also demonstrate that tPBM can also lead to angio- and lymphangiogenesis, which is another mechanism underlying tPBM-mediated stimulation of BLS. Thus, photo-augmentation of BLS might be a promising therapeutic target for preventing or delaying brain diseases associated with BLS dysfunction. Here we present pioneering technology for simultaneous tPBM in humans and sleep monitoring for stimulation of BLS to remove toxins from CNS and modulation of brain immunity. The wireless-controlled gadget includes a flexible organic light-emitting diode (LED) source that is controlled directly by a sleep-tracking device via a mobile application. The designed autonomous LED source is capable of providing the required therapeutic dose of light radiation at a certain region of the patient’s head without disturbing of sleeping patient. To minimize patients' discomfort, advanced materials like flexible organic LEDs were used. Acknowledgment: This study was supported by RSF project No. 23-75-30001.

Keywords: brain diseases, brain lymphatic system, phototherapy, sleep

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Authors: Shaimaa Eltanani, Thangal Yumnamcha, Ahmed S. Ibrahim

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Purpose: Mitochondria dysfunction is central to breaking the barrier integrity of retinal endothelial cells (RECs) in various blinding eye diseases such as diabetic retinopathy and retinopathy of prematurity. Therefore, we aimed to dissect the role of different mitochondrial components, specifically, those of oxidative phosphorylation (OxPhos), in maintaining the barrier function of RECs. Methods: Electric cell-substrate impedance sensing (ECIS) technology was used to assess in real-time the role of different mitochondrial components in the total impedance (Z) of human RECs (HRECs) and its components; the capacitance (C) and the total resistance (R). HRECs were treated with specific mitochondrial inhibitors that target different steps in OxPhos: Rotenone for complex I; Oligomycin for ATP synthase; and FCCP for uncoupling OxPhos. Furthermore, data were modeled to investigate the effects of these inhibitors on the three parameters that govern the total resistance of cells: cell-cell interactions (Rb), cell-matrix interactions (α), and cell membrane permeability (Cm). Results: Rotenone (1 µM) produced the greatest reduction in the Z, followed by FCCP (1 µM), whereas no reduction in the Z was observed after the treatment with Oligomycin (1 µM). Following this further, we deconvoluted the effect of these inhibitors on Rb, α, and Cm. Firstly, rotenone (1 µM) completely abolished the resistance contribution of Rb, as the Rb became zero immediately after the treatment. Secondly, FCCP (1 µM) eliminated the resistance contribution of Rb only after 2.5 hours and increased Cm without considerable effect on α. Lastly, Oligomycin had the lowest impact among these inhibitors on Rb, which became similar to the control group at the end of the experiment without noticeable effects on Cm or α. Conclusion: These results demonstrate differential roles for complex I, complex V, and coupling of OxPhos in maintaining the barrier functionality of HRECs, in which complex I being the most important component in regulating the barrier functionality and the spreading behavior of HRECs. Such differences can be used in investigating gene expression as well as for screening selective agents that improve the functionality of complex I to be used in the therapeutic approach for treating REC-related retinal diseases.

Keywords: human retinal endothelial cells (hrecs), rotenone, oligomycin, fccp, oxidative phosphorylation, oxphos, capacitance, impedance, ecis modeling, rb resistance, α resistance, and barrier integrity

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Authors: I. V. Palamarchuk, N. V. Zaichko

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Background and Aims: Galectin-3 is a marker of subclinical cardiac injury and is elevated in individuals with type 2 diabetes mellitus; while hydrogen sulfide (H₂S), metabolite of sulfur-containing amino acids, is considered having antifibrogenic effects. This study was designed to investigate whether metformin and its combination with NaHS can influence plasma galectin-3 and cystathionine-γ-lyase/hydrogen sulfide (CSE/H₂S) system in diabetic rat’s heart. Methods: 32 healthy male rats (180-250 g) were divided into 4 groups. To induct diabetes, rats (group 2-4) were injected with streptozotocin (STZ, 40 mg/kg/i.p., 0.1 M citrate buffer (pH 4.5). Rats from 3d (STZ+Metf) and 4th (STZ+Metf+NaHS) groups were given metformin (500 mg/kg/day) orally, and rats from 4th (STZ+Metf+NaHS) group were injected sodium hydrosulfide (NaHS, 3 mg/kg/i.p.) once per day starting from 3 to 28 day after streptozotocin injection. Rats of first group (control) were administered the equivalent volumes of 0.9% NaCl. Plasma galectin-3 was measured by ELISA. Rats’ hearts were sampled for determination of H2S by reaction with N,N-Dimethyl-p-phenylenediamine. Determination of CSE gene expression was performed in real time using PCR in the presence of SYBR Green I, using DT-Light detecting amplifier ('DNA-technology', Russia). Results: Induction of streptozotocin diabetes (STZ-diabetes, group 2) was followed by low myocardial H2S concentration and CSE expression (by 35%, p < 0.05 and 60.5%, p < 0.001 respectively, than that in controls), while plasma galectin-3 in this group was significantly higher than in controls (by 3.8 times, p < 0.05). Administration of metformin (group 3) resulted in significantly higher H₂S concentration (by 28.5%, p < 0.05), whereas CSE expression was only by 6% more than that in STZ-diabetes, as well as plasma galectin-3 was only by 14.8% lower in comparison with untreated diabetic rats. The inhibition of H₂S generation and CSE activity by diabetes was greatly attenuated in STZ+Metf+NaHS group. The combination of metformin with NaHS significantly stimulated H₂S production (by 48%, p < 0.05 and 15%, p < 0.05 more than STZ-diabetes and STZ+Metf respectively) and CSE gene expression (by 64.8%, p < 0.05 compared to STZ-diabetes and by 55.4%,p < 0.05 compared to STZ+Metf). Besides, plasma galectin-3 in rats receiving metformin and NaHS was significantly lower by 42%, p < 0.05 and 32.5%, p < 0.05 compared to STZ-diabetes and STZ+Metf groups respectively. Conclusions: To summarize, dysfunction of CSE/H2S system and galectin-3 stimulation was found in streptozotocin-induced diabetic rats. Metformin and its combination with exogenous H2S effectively prevented the development of metabolic changes induced by diabetes. These findings suggest that CSE/H₂S system can be integrated into pathogenesis of diabetic complications through modulation of pro-inflammatory and pro-fibrogenic mediator galectin-3.

Keywords: cystathionine-γ-lyase, diabetic heart, galectin-3, hydrogen sulfide, metformin, sodium hydrosulfide

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Authors: Sabri Sudirman, Yuan-Hua Hsu, Zwe-Ling Kong

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Male reproductive dysfunction is predominantly due to insulin resistance and hyperglycemia result in inflammation and oxidative stress. Furthermore, nanotechnology provides an alternative approach to improve the bioavailability of natural active food ingredients. Therefore, the aim of this study were to investigate nanoencapsulated triterpenoids from petri-dish cultured Antrodia cinnamomea (PAC) nanoparticles whether it could increase the bioavailability; in addition, the anti-inflammatory and anti-oxidative effects could more effectively ameliorate the reproductive function of diabetic male rats. First, PAC encapsulated in chitosan-silica nanoparticles (Nano-PAC) were prepared by biosilicification method. Scanning electron micrographs confirm the average particle size is about 30 nm, and the encapsulation efficiency is 83.7% by HPLC. Diabetic male Sprague-Dawley rats were induced by high fat diet (40% kcal from fat) and streptozotocin (35 mg/kg). Nano-PAC was administered by oral gavage in three doses (4, 8 and 20 mg/kg) for 6 weeks. Besides, metformin (300 mg/kg) and nanoparticles (Nano) were treated as the positive and negative control respectively. Results indicated that 4 mg/kg Nano-PAC administration for 6 weeks improved hyperglycemia, insulin resistance, and also reduced advanced glycation end products in plasma. In addition, 8 mg/kg Nano-PAC ameliorated morphological of testicular seminiferous tubules, sperm morphology and motility, reactive oxygen species production and mitochondrial membrane potential. Moreover, 20 mg/kg Nano-PAC restored reproductive endocrine system function and increased KiSS-1 level in plasma. In plasma or testis anti-oxidant superoxide dismutase, glutathione peroxidase and catalase were increased whereas malondialdehyde, as well as pro-inflammatory cytokines tumor necrosis factor-α, interleukin-6, and interferon-gamma, decreased. Most importantly, 8 mg/kg Nano-PAC down-regulated the oxidative stress induced c-Jun N-terminal kinase (JNK) signaling pathway. Our study successfully nanoencapsulated PAC to form nanoparticles and low-dose Nano-PAC improved diabetes-induced hyperglycemia, inflammation and oxidative stress to ameliorate the reproductive function of diabetic male rats.

Keywords: Antrodia cinnamomea, diabetes mellitus, male reproduction, nanoparticles

Procedia PDF Downloads 222

Authors: Rebecca K. Blais, Lindsey Monteith, Hallie Tannahill

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Military sexual trauma (MST) includes sexual harassment or assault that occurred during military service. Studies conducted to date on the association of MST with mental health and suicide outcomes are generally circumscribed to either active duty or veteran samples, precluding a thorough analysis of developmental trajectories of distress following MST within the context of ongoing (vs. discharged from) military service. The Military Social Science Laboratory has collected data on mixed service samples of men and women service members, addressing this important literature gap. The purpose of this study was to examine the association of MST, suicide risk, PTSD, depression, alcohol use, and posttraumatic cognitions using two separate samples, which collectively allow for a comprehensive examination of the development of distress following MST. The first sample consisted of 1389 men and women service members and veterans with varying levels of MST severity, including no MST, harassment-only MST, and assault MST. The second sample consisted of 400 men and women service members, all reporting the highest severity of MST, assault MST. In both samples, roughly half reported being discharged from service. Participants completed self-report measures of MST exposure severity, suicide ideation, suicide risk, PTSD, depression, alcohol misuse, and posttraumatic cognitions, as well as perceptions of how the military responded to their MST. Relative to those still serving in the US military, veterans were more likely to endorse suicidal ideation, higher PTSD symptoms, and higher depression symptoms if they felt the military mishandled their experience of MST (referred to as perceived institutional betrayal). However, among those reporting the most severe MST, veterans reported lower alcohol misuse and more adaptive posttraumatic cognitions. These findings suggest that those separated from the military experience different posttraumatic aftermath following MST relative to those who are currently serving in the military. Such findings suggest critical differences in the developmental trajectory of distress, necessitating different interventions to successfully reduce distress and dysfunction. Additional analyses will explore the impact of gender on these associations and explore full mechanistic models of distress grouped by discharged status.

Keywords: military sexual trauma, PTSD, suicide, developmental trajectories, depression

Procedia PDF Downloads 124

Authors: Jan F. Talts, Amit Saxena, Kåre Engkilde

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Chemotherapy-induced peripheral neuropathy (CIPN) is one of the most frequent side effects caused by anti-neoplastic agents, with a prevalence from 19 % to 85 %. Clinically, CIPN is a mostly sensory neuropathy leading to pain and to motor and autonomic changes. Due to its high prevalence among cancer patients, CIPN constitutes a major problem for both cancer patients and survivors, especially because currently, there is no single effective method of preventing CIPN. Hearing loss is the most common form of sensory impairment in humans and can be caused by ototoxic chemical compounds such as chemotherapy (platinum-based antineoplastic agents).In rodents, single or repeated cisplatin injections induce peripheral neuropathy and hearing impairment mimicking human disorder, allowing studying the efficacy of new pharmacological candidates in chemotherapy-induced hearing loss and peripheral neuropathy. RNA sequencing data from full term amniotic fluid (TAF) mesenchymal stemcell (MSC) clones was used to identify neural-specific markers present on TAF-MSC. Several prospective neural markers were tested by flow cytometry on cultured TAF-MSC. One of these markers was used for cell-sorting using Tyto MACSQuant cell sorter, and the neural marker positive cell population was expanded for several passages to the final therapeutic product stage. Peripheral neuropathy and hearing loss was induced in mice by administration of cisplatin in three week-long cycles. The efficacy of neural-specific TAF-MSC in treating hearing loss and pain perception was evaluated by administration of three injections of 3 million cells/kg by intravenous route or three injections of 3 million cells/kg by intra-arterial route after each cisplatin cycle treatment. Auditory brainstem responses (ABR) are electric potentials recorded from scalp electrodes, and the first ABR wave represents the summed activity of the auditory nerve fibers contacting the inner hair cells. For ABR studies, mice were anesthetized, then earphones were placed in the left ear of each mouse, an active electrode was placed in the vertex of the skull, a reference electrode under the skin of the mastoid bone, and a ground electrode in the neck skin. The stimuli consisted of tone pips of five frequencies (2, 4, 6, 12, 16, and 24 kHz) at various sound levels (from 0 to 90 dB) ranging to cover the mouse auditory frequency range. The von Frey test was used to assess the onset and maintenance of mechanical allodynia over time. Mice were placed in clear plexiglass cages on an elevated mesh floor and tested after 30 min of habituation. Mechanical paw withdrawal threshold was examined using an electronic von Frey anesthesiometer. Cisplatin groups treated with three injections of 3 million cells/kg by intravenous route and three injections of 3 million cells/kg by intra-arterial route after each cisplatin cycle treatment presented, a significant increase of hearing acuity characterized by a decrease of ABR threshold and a decrease of neuropathic pain characterized by an increase of von Frey paw withdrawal threshold compared to controls only receiving cisplatin. This study shows that treatment with MSCselected for neural specificity presents significant positive efficacy on the chemotherapy-induced neuropathic pain and the chemotherapy-induced hearing loss.

Keywords: mesenchymal stem cell, peripheral neuropathy, amniotic fluid, regenerative medicine

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Authors: Dawid Jakimiuk, Krzysztof Mitura, Leszek Szpakowski, Sławomir Pilip, Daniel Celiński

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The Emergency Medical Teams (EMS) of the Ambulance Service in Siedlce serve the population living in the Mazowieckie Voivodeship (the area of eastern Poland with approximately 550,000 inhabitants). They provide health services at the pre-hospital stage to all life-threatening patients. The analysis covered the interventions of emergency medical teams in cases of suicide attempts that occurred in the years 2015-2018. The study was retrospective. The data was obtained on the basis of digital medical records of completed call-outs. When defining the disease entity, the International Statistical Classification of Diseases and Health Problems ICD-10 prepared by WHO was used. The relationship between selected disease entities and the area of EMT intervention, the patient's sex and age, and the time of occurrence of the event were investigated. Non-urban area was defined as the area inhabited by a population below 10,000 residents. Statistical analysis was performed using Pearson's Chi ^ 2 test and presenting the percentage of cases in the study group. Of all the suicide attempts, drug abuse cases were the most frequent, including: X60 (Intentional self-poisoning by and exposure to nonopioid analgesics, antipyretics and antirheumatics); X61 (Intentional self-poisoning by and exposure to antiepileptic, sedative-hypnotic, antiparkinsonian and psychotropic drugs, not elsewhere classified); X62 (Intentional self-poisoning by and exposure to narcotics and psycholeptics [hallucinogens], not elsewhere classified); X63 (Intentional self-poisoning by and exposure to other drugs acting on the autonomic nervous system); X64 (Intentional self-poisoning by and exposure to other and unspecified drugs, medicaments and biological substance) oraz X70 (Intentional self-harm by hanging, strangulation and suffocation). In total, they accounted for 69.4% of all interventions to suicide attempts in the studied period. Statistical analysis shows significant differences (χ2 = 39.30239, p <0.0001, n = 561) between the area of EMT intervention and the type of suicide attempt. In non-urban areas, a higher percentage of X70 diagnoses was recorded (55.67%), while in urban areas, X60-X64 (72.53%). In non-urban areas, a higher proportion of patients attempting suicide was observed compared to patients living in urban areas. For X70 and X60 - X64 in total, the incidence rates in non-urban areas were 80.8% and 56%, respectively. Significant differences were found (χ2 = 119.3304, p <0.0001, n = 561) depending on the method of attempting suicide in relation to the patient's sex. The percentage of women diagnosed with X60-X64 versus X70 was 87.50%, which was the largest number of patients (n = 154) as compared to men. In the case of X70 in relation to X60-X64, the percentage of men was 62.08%, which was the largest number of patients (n = 239) as compared to women (n = 22). In the case of X70, the percentage of men compared to women was as high as 92%. Significant differences were observed (χ2 = 14.94848, p <0.01058) between the hour of EMT intervention and the type of suicide attempt. The highest percentage of X70 occurred between 04:01 - 08:00 (64.44%), while X60-X64 between 00:01 - 04:00 (70.45%). The largest number of cases of all tested suicide attempts was recorded between 16:01 - 20:00 for X70 (n = 62), X60 - X64 (n = 82), respectively. The highest percentage of patients undertaking all suicide attempts studied at work was observed in the age range of 18-30 (31.5%), while the lowest was in the age group over 60 years of age. (11%). There was no significant correlation between the day of the week or individual months of the year and the type of suicide attempt - respectively (χ2 = 6.281729, p <0.39238, n = 561) and (χ2 = 3.348913, p <0.9857, n = 561). There were also no significant differences in the incidence of suicide attempts for each year in the study period (χ2 = 3.348913, p <0.9857 n = 561). The obtained results suggest the necessity to undertake preventive measures in order to minimize the number of suicide attempts. Such activities should be directed especially at young patients living in non-urban areas.

Keywords: emergency med, emergency medical team, attempted suicide, pre-hospital

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Authors: Divya Kanchibhotla, Shashank Kulkarni, Shweta Singh

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Chronic stress and sleep quality reduces mental health and increases the risk of developing depression and anxiety as well. There is increasing evidence for the utility of meditation as an adjunct clinical intervention for conditions like depression and anxiety. The present study is an attempt to explore the impact of Sahaj Samadhi Meditation (SSM), a category of Automatic Self Transcending Meditation (ASTM), on perceived stress and sleep quality in adults. The study design was a single group pre-post assessment. Perceived Stress Scale (PSS) and the Pittsburgh Sleep Quality Index (PSQI) were used in this study. Fifty-two participants filled PSS, and 60 participants filled PSQI at the beginning of the program (day 0), after two weeks (day 16) and at two months (day 60). Significant pre-post differences for the perceived stress level on Day 0 - Day 16 (p < 0.01; Cohen's d = 0.46) and Day 0 - Day 60 (p < 0.01; Cohen's d = 0.76) clearly demonstrated that by practicing SSM, participants experienced reduction in the perceived stress. The effect size of the intervention observed on the 16th day of assessment was small to medium, but on the 60th day, a medium to large effect size of the intervention was observed. In addition to this, significant pre-post differences for the sleep quality on Day 0 - Day 16 and Day 0 - Day 60 (p < 0.05) clearly demonstrated that by practicing SSM, participants experienced improvement in the sleep quality. Compared with Day 0 assessment, participants demonstrated significant improvement in the quality of sleep on Day 16 and Day 60. The effect size of the intervention observed on the 16th day of assessment was small, but on the 60th day, a small to medium effect size of the intervention was observed. In the current study we found out that after practicing SSM for two months, participants reported a reduction in the perceived stress, they felt that they are more confident about their ability to handle personal problems, were able to cope with all the things that they had to do, felt that they were on top of the things, and felt less angered. Participants also reported that their overall sleep quality improved; they took less time to fall asleep; they had less disturbances in sleep and less daytime dysfunction due to sleep deprivation. The present study provides clear evidence of the efficacy and safety of non-pharmacological interventions such as SSM in reducing stress and improving sleep quality. Thus, ASTM may be considered a useful intervention to reduce psychological distress in healthy, non-clinical populations, and it can be an alternative remedy for treating poor sleep among individuals and decreasing the use of harmful sedatives.

Keywords: automatic self transcending meditation, Sahaj Samadhi meditation, sleep, stress

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Authors: Laura M. Hovsepyan, Gayane S. Ghazaryan, Hasmik V. Zanginyan

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Hypertension (HD) is the most common cardiovascular pathology that causes disability and mortality in the working population. Most often, heart failure (HF), which is based on myocardial remodeling, leads to death in hypertension. Recently, endothelial dysfunction (EDF) or a violation of the functional state of the vascular endothelium has been assigned a significant role in the structural changes in the myocardium and the occurrence of heart failure in patients with hypertension. It has now been established that tissues affected by inflammation form increased amounts of superoxide radical and NO, which play a significant role in the development and pathogenesis of various pathologies. They mediate inflammation, modify proteins and damage nucleic acids. The aim of this work was to study the processes of oxidative modification of proteins (OMP) and the production of nitric oxide in hypertension. In the experimental work, the blood of 30 donors and 33 patients with hypertension was used. For the quantitative determination of OMP products, the based on the reaction of the interaction of oxidized amino acid residues of proteins and 2,4-dinitrophenylhydrazine (DNPH) with the formation of 2,4-dinitrophenylhydrazones, the amount of which was determined spectrophotometrically. The optical density of the formed carbonyl derivatives of dinitrophenylhydrazones was recorded at different wavelengths: 356 nm - aliphatic ketone dinitrophenylhydrazones (KDNPH) of neutral character; 370 nm - aliphatic aldehyde dinirophenylhydrazones (ADNPH) of neutral character; 430 nm - aliphatic KDNFG of the main character; 530 nm - basic aliphatic ADNPH. Nitric oxide was determined by photometry using Grace's solution. Adsorption was measured on a Thermo Scientific Evolution 201 SF at a wavelength of 546 nm. Thus, the results of the studies showed that in patients with arterial hypertension, an increased level of nitric oxide in the blood serum is observed, and there is also a tendency to an increase in the intensity of oxidative modification of proteins at a wavelength of 270 nm and 363 nm, which indicates a statistically significant increase in aliphatic aldehyde and ketone dinitrophenylhydrazones. The increase in the intensity of oxidative modification of blood plasma proteins in the studied patients, revealed by us, actually reflects the general direction of free radical processes and, in particular, the oxidation of proteins throughout the body. A decrease in the activity of the antioxidant system also leads to a violation of protein metabolism. The most important consequence of the oxidative modification of proteins is the inactivation of enzymes.

Keywords: hypertension (HD), oxidative modification of proteins (OMP), nitric oxide (NO), oxidative stress

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Authors: Fatimah Abd Elghani, Raymonde Szargel, Vered Shani, Hazem Safory, Haya Hamza, Mor Savyon, Ruth Rott, Rina Bandopadhyay, Simone Engelender

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Background: PINK1 is a mitochondrial kinase mutated in some familial cases of Parkinson’s disease. Down regulation of PINK1 results in abnormal mitochondrial morphology and altered membrane potential. Although PINK1 has a predicted mitochondrial import sequence, it’s cellular, and submitochondrial localization remains unclear, in part because it is rapidly degraded. In this work, we investigated the mechanisms involved in PINK1 degradation and how this may affect PINK1 stability and function, with implications for mitochondrial function in PD. In addition, pharmacological inhibition of proteasome activity was shown to lead to PINK1 accumulation, indicating that PINK1 degradation depends on the ubiquitin-proteasome system (UPS). Methods: Using co-immunoprecipitation assays, we identified E3 ubiquitin ligase SIAH1 as a PINK1-interacting protein in HEK293 cells as well as on rat brain tissues. In addition, we determined the effect of SIAH 1, SIAH2 and Parkin on PINK1 steady-state levels by Western blot analysis, and checked their possibility to ubiquitinate and mediate PINK1 degradation through the proteasome carried out in vivo ubiquitination experiments. Results: We have obtained results showing that SIAH-1 interacts with and ubiquitinates PINK1. The ubiquitination promoted by SIAH-1 leads to the proteasomal degradation of PINK1. We confirmed these findings by knocking down SIAH-1 and observing important accumulation of PINK1 in cells. Besides, we found that SIAH-1 decreases PINK1 steady-state levels but not the E3 ligase Parkin. We also investigated the interaction of SIAH-1 with PINK1 disease mutants and its ability to promote their ubiquitination and degradation. Although, no clear difference in the ability of SIAH-1 to promote the degradation of PINK1 disease mutants was observed. It is possible that dysfunction of proteasomal activity in the disease may lead to the accumulation and aggregation of ubiquitinated PINK1 in patients with PINK1 mutations, with possible implications to the pathogenesis of PD. Conclusions: Here, we demonstrated that SIAH-1 ubiquitinates and promotes the degradation of PINK1. In addition, SIAH-1 represents now a target that may help the improvement of mitophagy in PD. Further investigations needed to understand how mitophagy is regulated by PINK1-SIAH-1 axis to provide targets for future therapeutics.

Keywords: PD, Parkinson's disease, PINK1, PTEN-induced kinase1, SIAH, seven in absentia homolog, SN, substantia nigra

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Authors: Kamil Ganaev, Elina Vlasova, Andrei Shiryaev, Renat Akchurin

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De novo atrial fibrillation (AF) after coronary artery bypass grafting (CABG) is a common complication. To date, there are no data on the possible effect of diffuse lesions of coronary arteries on the incidence of postoperative AF complications. Methods. Patients operated on-pump under hypothermic conditions during the calendar year (2020) were studied. Inclusion criteria - isolated CABG and achievement of complete myocardial revascularization. Patients with a history of AF moderate and severe valve dysfunction, hormonal thyroid pathology, initial CHF(Congestive heart failure), as well as patients with developed perioperative complications (IM, acute heart failure, massive blood loss) and deceased were excluded. Thus 227 patients were included; mean age 65±9 years; 69% were men. 89% of patients had a 3-vessel lesion of the coronary artery; the remainder had a 2-vessel lesion. Mean LV size: 3.9±0.3 cm, indexed LV volume: 29.4±5.3 mL/m2. Two groups were considered: D (n=98), patients with diffuse coronary heart disease, and L (n=129), patients with local coronary heart disease. Clinical and demographic characteristics in the groups were comparable. Rhythm assessment: continuous bedside ECG monitoring up to 5 days; ECG CT at 5-7 days after CABG; daily routine ECG registration. Follow-up period - postoperative hospital period. Results. The Median follow-up period was 9 (7;11) days. POFP (Postoperative atrial fibrillation) was detected in 61/227 (27%) patients: 34/98 (35%) in group D versus 27/129 (21%) in group L; p<0.05. Moreover, the values of revascularization index in groups D and L (3.9±0.7 and 3.8±0.5, respectively) were equal, and the mean time Cardiopulmonary bypass (CPB) (107±27 and 80±13min), as well as the mean ischemic time (67±17 and 55±11min) were significantly longer in group D (p<0.05). However, a separate analysis of these parameters in patients with and without developed AF did not reveal any significant differences in group D (CPB time 99±21.2 min, ischemic time 63±12.2 min), or in group L (CPB time 88±13.1 min, ischemic time 58.7±13.2 min). Conclusion. With the diffuse nature of coronary lesions, the incidence of AF in the hospital period after isolated CABG definitely increases. To better understand the role of severe coronary atherosclerosis in the development of POAF, it is necessary to distinguish the influence of organic features of atrial and ventricular myocardium (as a consequence of chronic coronary disease) from the features of surgical correction in diffuse coronary lesions.

Keywords: atrial fibrillation, diffuse coronary artery disease, coronary artery bypass grafting, local coronary artery disease

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Authors: Deenadayalan Govender

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In South Africa, similar to nations globally, the prevailing tangible link between people and the state is public infrastructure. Services delivered through infrastructure to the people and to the state form a critical enabler for social development in communities and economic development in the country. In this regard, infrastructure, being the backbone to a nation’s prosperity, ideally should be effectively maintained for seamless delivery of services. South African infrastructure is in a state of deterioration, which is leading to infrastructure dysfunction and collapse and is negatively affecting development of the economy. This infrastructure deterioration stems from deficiencies in maintenance practices and strategies. From the birth of South African democracy, government has pursued socio-economic transformation and the delivery of critical basic services to decrease the broadening boundaries of disparity. In this regard, the National Infrastructure Plan borne from strategies encompassed in the National Development Plan is given priority by government in delivering strategic catalytic infrastructure projects. The National Infrastructure Plan is perceived to be the key in unlocking opportunities that generate economic growth, kerb joblessness, alleviate poverty, create new entrepreneurial prospects, and mitigate population expansion and rapid urbanisation. Socio-economic transformation benefits from new infrastructure spend is not being realised as initially anticipated. In this context, South Africa is currently in a state of weakening economic growth, with further amassed levels of joblessness, unremitting poverty and inequality. Due to investor reluctance, solicitation of strategic infrastructure funding is progressively becoming a debilitating challenge in all government institutions. Exacerbating these circumstances further, is substandard functionality of existing infrastructure subsequent to inadequate maintenance practices. This in-depth multi-sectoral study into the state of infrastructure is to understand the principal reasons for infrastructure functionality regression better; furthermore, prioritised investigations into progressive maintenance strategies is focused upon. Resultant recommendations reveal enhanced maintenance strategies, with a vision to capitalize on infrastructure design life, and also give special emphasis to socio-economic development imperatives in the long-term. The research method is principally based on descriptive methods (survey, historical, content analysis, qualitative).

Keywords: infrastructure, maintenance, socio-economic, strategies

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Authors: Ali Kamal M. Sami, Safa Almukhtar, Alaa Al-Krush, Ismael Hama-Amin Akha Weas, Ruqaya Ahmed Alqais

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Introduction and Objectives Lower urinary tract symptoms (LUTS) are common among men with benign prostatic hyperplasia (BPH). The combination of 5 alpha-reductase inhibitors and alpha-blockers has been used as a conservative treatment of male LUTS secondary to BPH. Nanotechnology structured water magnalife is a type of water that is produced by modulators and specific frequency and energy fields that transform ordinary water into this Nanowater. In this study, we evaluated the use of Nano-water with the conservative treatment and to see if it improves the outcome and gives better results in those patients with LUTS/BPH. Material and methods For a period of 3 months, 200 men with International Prostate Symptom Score (IPSS)≥13, maximum flow rate (Qmax)≤ 15ml/s, and prostate volume > 30 and <80 ccs were randomly divided into two groups. Group A 100 men were given Nano-water with the (tamsulosindutasteride) and group B 100 men were given ordinary bottled water with the (tamsulosindutasteride). The water bottles were unlabeled and were given in a daily dose of 20ml/kg body weight. Dutasteride 0.5mg and tamsulosin 0.4 mg daily doses. Both groups were evaluated for the IPSS, Qmax, Residual Urine (RU), International Index of Erectile Function–Erectile Function (IIEF-EF) domain at the beginning (baseline data), and at the end of the 3 months. Results Of the 200 men with LUTS who were included in this study, 193 men were followed, and 7 men dropped out of the study for different reasons. In group A which included 97 men with LUTS, IPSS decreased by 16.82 (from 20.47 to 6.65) (P<0.00001) and Qmax increased by 5.73 ml/s (from 11.71 to 17.44) (P<0.00001) and RU <50 ml in 88% of patients (P<0.00001) and IIEF-EF increased to 26.65 (from 16.85) (P<0.00001). While in group B, 96 men with LUTS, IPSS decreased by 8.74(from 19.59 to 10.85)(P<0.00001) and Qmax increased by 4.67 ml/s(from 10.74 to 15.41)(P<0.00001), RU<50 ml in 75% of patients (P<0.00001), and IIEF-EF increased to 21(from 15.87)(P<0.00001). Group A had better results than group B. IPSS in group A decreased to 6.65 vs 10.85 in group B(P<0.00001), also Qmax increased to 17.44 in group A vs 15.41 in group B(P<0.00001), group A had RU <50 ml in 88% of patients vs 75% of patients in group B(P<0.00001).Group A had better IIEF-EF which increased to 26.65 vs 21 in group B(P<0.00001). While the differences between the baseline data of both groups were statistically not significant. Conclusion The use of nanotechnology structured water magnalife gives a better result in terms of LUTS and scores in patients with BPH. This combination is showing improvements in IPSS and even in erectile function in those men after 3 months.

Keywords: nano water, lower urinary tract symptoms, benign prostatic hypertrophy, erectile dysfunction

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Authors: Jia-Ling Ho, Xiu-Ru Zhang, Zwe-Ling Kong

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Diabetes mellitus (DM) is a major health problem that affects patients’ life quality throughout the world due to its many complications. It characterized by chronic hyperglycemia with oxidative stress, which impaired male reproductive function. Fibroblast growth factor 21 (FGF21) is a metabolic regulator that is required for normal spermatogenesis and protects against diabetes-induced germ cell apoptosis. Echinacea purpurea ethanol extract (EE), which contain phenolic acid and isobutylamide, had been proven to have antidiabetic property. Silica-chitosan nanoparticles (Nano-CS) has drug delivery and controlled release properties. This study aims to investigate whether silica-chitosan nanoparticles encapsulated EE (Nano-EE) had more ameliorating male infertility by analyzing the effect of testicular FGF21. The Nano-EE was characterized before used to treatment the diabetic rat model. Male Sprague-Dawley (SD) rats were obtained and divided into seven groups. A group was no induced Streptozotocin (STZ), marked as normal group. Diabetic rats were induced into diabetes by STZ (33 mg/kg). A diabetic group was no treatment with sample (diabetic control group), and other groups were treatment by Nano-CS (465 mg/kg), Nano-EE (93, 279, 465 mg/kg), and metformin (Met) (200 mg/kg) used as reference drug for 7 weeks. Our results indicated that the average nanoparticle size and zeta potential of Nano-EE were 2630 nm and -21.3 mV, respectively. The encapsulation ratio of Nano-EE was about 70%. It also confirmed the antioxidative activity was unchanged by comparing the DPPH and ABTS scavenging of Nano-EE and EE. In vivo test, Nano-EE can improve the STZ induced hyperglycemia, insulin resistance, and plasma FGF21 levels. Nano-EE has increased sperm motility, mitochondria membrane potential (MMP), plasma testosterone level, and reduction of abnormal sperm, nitric oxide (NO), superoxide production as well as reactive oxygen species (ROS). In addition, in plasma antioxidant enzymes glutathione peroxidase (GPx) and superoxide dismutase (SOD) was increased whereas pro-inflammatory cytokines TNF-α, and IL-1β were decreased. Further, in testis, protein content of FGF21, PGC-1α, and SIRT1 were improved. Nano-EE might improve diabetes-induced down-regulation of testicular FGF21 and SIRT1/PGC-1α signaling hence maintain spermatogenesis.

Keywords: diabetes mellitus, Echinacea purpurea, reproductive dysfunction, silica-chitosan nanoparticles

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Authors: Ei Ei Hlaing, Narissara Lailerd, Sittiruk Roytrakul, Pichapat Piamrojanaphat

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Type 2 diabetes is one of the most common metabolic diseases all over the world. The pathogenesis of type 2 diabetes is not the only dysfunction of pancreatic beta cells but also insulin resistance in muscle, liver and adipose tissue. High levels of circulating free fatty acids, an increased lipid content of muscle cells, impaired insulin-mediated glucose uptake and diminished mitochondrial functioning are pathophysiological hallmarks of diabetic skeletal muscles. Purple rice (Oryza sativa L. indica) has been shown to have antidiabetic effects. However, the underlying mechanism(s) of antidiabetic activity of purple rice is still unraveled. In this research, to explore in-depth cellular mechanism(s), proteomic profile of purple rice supplemented type 2 diabetic rats’ skeletal muscle were analyzed contract with non-supplemented rats. Diabetic rats were induced high-fat diet combined with streptozotocin injection. By using one- dimensional gel electrophoresis (1-DE) and LC-MS/MS quantitative proteomic method, we analyzed proteomic profiles in skeletal muscle of normal rats, normal rats with purple rice supplementation, type 2 diabetic rats, and type 2 diabetic rats with purple rice supplementation. Total 2676 polypeptide expressions were identified. Among them, 24 peptides were only expressed in type 2 diabetic rats, and 24 peptides were unique peptides in type 2 diabetic rats with purple rice supplementation. Acetyl CoA carboxylase 1 (ACACA) found as unique protein in type 2 diabetic rats which is the major enzyme in lipid synthesis and metabolism. Interestingly, DNA damage response protein, heterogeneous nuclear ribonucleoprotein K [Mus musculus] (Hnrnpk), was upregulated in type 2 diabetic rats’ skeletal muscle. Meanwhile, unique proteins of type 2 diabetic rats with purple rice supplementation (bone morphogenetic 7 protein preproprotein, BMP7; and forkhead box protein NX4, Foxn4) involved with muscle cells growth through the regulation of TGF-β/Smad signaling network. Moreover, BMP7 may effect on insulin signaling through the downstream signaling of protein kinase B (Akt) which acts in protein synthesis, glucose uptake, and glycogen synthesis. In conclusion, our study supports that type 2 diabetes impairs muscular lipid metabolism. In addition, purple rice might recover the muscle cells growth and insulin signaling.

Keywords: proteomics, purple rice bran, skeletal muscle, type 2 diabetic rats

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Authors: Rashid Azeem

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Introduction: Eosinophilia, which can be categorized as mild, moderate, and severe form on the basis of increasing eosinophil counts, might be responsible for a wide range of cardiac manifestations, varying from a simple myocarditis to a severe state like endomyocardial fibrosis. Eosinophils are involved in the pathogenesis of a variety of cardiovascular disorder like Loffler endocarditis, eosinophilic granulomatosis with polyangitis (EGPH), and hyper eosinophilic (HES). Among them HES carries and incidence rate b/w 48% and 75% and is the main causes of cardiac motility and mobility due to eosinophilia involvement. Aims and objectives: The aim of this study is to determine the frequency of eosinophilia in cardiac patients and to ascertain the evidence of endomyocardial diseases in eosinophilic patients in a cardiology institution Material and Methods: This cross sectional analytical study was conducted in hematology Department of Peshawar institute of Cardiology after approval from hospital ethical and research committee. All 70 patients were subjected to detailed history and clinical examination. Investigation like CBC, Chest X-ray, ECG, Echo, Angiography findings were used to monitor patient’s clinical status. Data is analyzed using SPSS version 25 and MS Excel. Results: Out of 70 patients in our study, a total of 66 patients(94 %) shows evidence of cardiac manifestations. In our study, we have observed a number of abnormal ECG patterns in cardiac patients presenting with eosinophilia, like T wave changes, loss of R wave, sinus bradycardia with LVH strain, and ST wave abnormality. abnormal echocardiographic findings were observed in our patients, like valvular abnormalities (in 45.7%), RWMA abnormalities (in 2.8%), isolated ventricular dysfunction (in 21.4%), and in 10% patients, normal echocardiography. We further noted abnormal coronary angiography findings in cardiac patients with eosinophilia ranging from single vessel to multi vessel occlusions. Conclusions: Eosinophils are involved in the pathogenesis of a variety of cardiovascular disorders which can be detected by various diagnostic means, and the severity of the disease increases with time and with increasing eosinophil count ranging from simple myocarditis to a fatal condition like endomyocardial fibrosis. Thus, increased eosinophilic count as a laboratory parameter in cardiac patients may be a sign of endomyocardial damage which will further help cardiologist to intervene more aggressively then routine approach to a cardiac patient.

Keywords: eosinophilia, endomyocardial fibrosis, cardiac, hypereosinophilic syndrome

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Authors: Nahla Al-Bayyari, Rae’d Hailat

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Vitamin D deficiency and overweight are common in women suffering from polycystic ovary syndrome (PCOS). Weight gain in PCOS is an important factor for the development of menstrual dysfunction and signs of hyperandrogenism and alopecia. Features of PCOS such as oligomenorrhea can be predicted by anthropometric measurements as body mass index (BMI). Therefore, the aim of this trial was to study the effect of 50,000 IU/week of vitamin D₃ supplementation on the body composition and on the anthropometric measurements of overweight women with PCOS and to examine the impact of this effect on ovaries ultrasonography and menstrual cycle regularity. The study design was a prospective randomized, double-blinded placebo-controlled clinical trial conducted on 60 overweight Jordanian women aged (18-49) years with PCOS and vitamin D deficiency. The study participants were divided into two groups; vitamin D group (n = 30) who were assigned to receive 50,000 IU/week of vitamin D₃ and placebo group (n = 30) who were assigned to receive placebo tablets orally for 90 days. The anthropometric measurements and body composition were measured at baseline and after treatment for the PCOS and vitamin D deficient women. Also, assessment of the participants’ picture of ovaries by ultrasound and menstrual cycle regulatory were performed before and after treatment. Results showed that there were no significant (p > 0.05) differences between the placebo and vitamin D group basal 25(OH)D levels, body composition and anthropometric parameters. After treatment, vitamin D group serum levels of 25(OH)D increased (12.5 ± 0.61 to 50.2 ± 2.04 ng/mL, (p < 0.001), and decreased (50.2 ± 2.04 to 48.2 ± 2.03 ng/mL, p < 0.001) after 14 days of vitamin D₃ treatment cessation. There were no significant changes in the placebo group. In the vitamin D group, there were significant (p < 0.001) decreases in body weight, BMI, waist, and hip circumferences and fat mass. In addition, there were significant increases (p < 0.05) in fat free mass and total body water. These improvements in both anthropometric and body composition as well as in 25(OH)D concentrations, resulted in significant improvements in the picture of PCOS women ovaries ultrasonography and in menstrual cycle regularity, where nearly most of them (93%) had regular cycles after vitamin D₃ supplementation. In the placebo group, there were only significant decreases (p < 0.05) in waist and hip circumferences. It can be concluded that vitamin D supplementation improving serum 25(OH)D levels and PCOS prognosis by reducing body weight of overweight PCOS women and regulating their menstrual cycle.

Keywords: anthropometric, overweight, polycystic ovary syndrome, vitamin D₃

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Authors: Noah Odion, Honest Jimu, Blessing Atinuke Afuape

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Introduction: Motor control and gait abnormalities are commonly observed in individuals with autism spectrum disorder (ASD), affecting their mobility and coordination. Understanding the underlying neurological and biomechanical factors is essential for designing effective interventions. This study focuses on developing microchip-integrated wearable devices to capture real-time movement data from individuals with autism. By applying computational models to the collected data, we aim to analyze motor control patterns and gait abnormalities, bridging a crucial knowledge gap in autism-related motor dysfunction. Methods: We designed microchip-enabled wearable devices capable of capturing precise kinematic data, including joint angles, acceleration, and velocity during movement. A cross-sectional study was conducted on individuals with ASD and a control group to collect comparative data. Computational modelling was applied using machine learning algorithms to analyse motor control patterns, focusing on gait variability, balance, and coordination. Finite element models were also used to simulate muscle and joint dynamics. The study employed descriptive and analytical methods to interpret the motor data. Results: The wearable devices effectively captured detailed movement data, revealing significant gait variability in the ASD group. For example, gait cycle time was 25% longer, and stride length was reduced by 15% compared to the control group. Motor control analysis showed a 30% reduction in balance stability in individuals with autism. Computational models successfully predicted movement irregularities and helped identify motor control deficits, particularly in the lower limbs. Conclusions: The integration of microchip-based wearable devices with computational models offers a powerful tool for diagnosing and treating motor control deficits in autism. These results have significant implications for patient care, providing objective data to guide personalized therapeutic interventions. The findings also contribute to the broader field of neuroscience by improving our understanding of the motor dysfunctions associated with ASD and other neurodevelopmental disorders.

Keywords: motor control, gait abnormalities, autism, wearable devices, microchips, computational modeling, kinematic analysis, neurodevelopmental disorders

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Authors: Balakumar Pitchai, Xiang Llan Ang, Sunil Prajapati, Varatharajan Rajavel, Sundram Karupiah, Mohd Baidi Bahari

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The study examined the pretreatment and post-treatment effects of low-doses of fenofibrate and rosuvastatin in gentamicin-induced acute nephrotoxicity in rats. Gentamicin (100 mg/kg/day, i.p.) was administered to rats for 8 days. In the pretreatment protocol, low-dose fenofibrate (30 mg/kg/day, p.o.) or low-dose rosuvastatin (2 mg/kg/day, p.o.) treatments were started a day before the administration of gentamicin and continued for 8 days. In the post-treatment protocol, rats administered gentamicin were treated with low-dose fenofibrate (30 mg/kg/day, p.o.) or low-dose rosuvastatin (2 mg/kg/day, p.o.) for 6 days after the completion of 8 days protocol of gentamicin administration. Gentamicin-associated acute nephrotoxicity in rats was assessed in terms of biochemical analysis and renal histopathological studies. Gentamicin-administered rats showed marked renal functional changes as assessed in terms of a significant increase in serum creatinine and urea levels as compared to normal rats. The renal dysfunction noted in gentamicin administered rats was accompanied with elevated serum uric acid level as compared to normal rats while there was no significant change in lipid profile. Low-dose fenofibrate pretreatment in gentamicin-administered rats afforded a significant renal functional improvements and renoprotection while its post-treatment showed no significant renoprotection. On the other hand, pretreatment with low-dose rosuvastatin partially reduced gentamicin-induced increase in serum creatinine level, but its post-treatment did not afford renal functional improvements in gentamicin-administered rats. However, all pre and post-treatments with low-doses of fenofibrate or rosuvastatin significantly reduced the elevated serum uric acid concentration in gentamicin-administered rats. Renal histopathological analysis showed a discernible incidence of acute tubular necrosis in gentamicin-administered rats which were markedly reduced by low-dose fenofibrate or low-dose rosuvastatin pretreatments; but, not by their post-treatments. In conclusion, low-dose fenofibrate pretreatment considerably prevented gentamicin-induced acute tubular necrosis and renal functional abnormalities in rats while its post-treatment resulted in no significant renoprotective action. In spite of effective prevention of gentamicin-induced acute tubular necrosis, the pretreatment with low-dose rosuvastatin had only a partial and fractional protection on renal functional abnormalities. The post-treatment with low-dose rosuvastatin was ineffective in affording a renoprotection in gentamicin-administered rats.

Keywords: gentamicin-nephrotoxicity, low-dose fenofibrate, low-dose rosuvastatin, renoprotection

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Authors: Marcio Freire Cruz, Naoaki Ono, Shigehiko Kanaya, Carlos Arthur Mattos Teixeira Cavalcante

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The systems that record patient care information, known as Electronic Medical Record (EMR) and those that monitor vital signs of patients, such as heart rate, body temperature, and blood pressure have been extremely valuable for the effectiveness of the patient’s treatment. Several kinds of research have been using data from EMRs and vital signs of patients to predict illnesses. Among them, we highlight those that intend to predict, classify, or, at least identify patterns, of sepsis illness in patients under vital signs monitoring. Sepsis is an organic dysfunction caused by a dysregulated patient's response to an infection that affects millions of people worldwide. Early detection of sepsis is expected to provide a significant improvement in its treatment. Preceding works usually combined medical, statistical, mathematical and computational models to develop detection methods for early prediction, getting higher accuracies, and using the smallest number of variables. Among other techniques, we could find researches using survival analysis, specialist systems, machine learning and deep learning that reached great results. In our research, patients are modeled as points moving each hour in an n-dimensional space where n is the number of vital signs (variables). These points can reach a sepsis target point after some time. For now, the sepsis target point was calculated using the median of all patients’ variables on the sepsis onset. From these points, we calculate for each hour the position vector, the first derivative (velocity vector) and the second derivative (acceleration vector) of the variables to evaluate their behavior. And we construct a prediction model based on a Long Short-Term Memory (LSTM) Network, including these derivatives as explanatory variables. The accuracy of the prediction 6 hours before the time of sepsis, considering only the vital signs reached 83.24% and by including the vectors position, speed, and acceleration, we obtained 94.96%. The data are being collected from Medical Information Mart for Intensive Care (MIMIC) Database, a public database that contains vital signs, laboratory test results, observations, notes, and so on, from more than 60.000 patients.

Keywords: dynamic analysis, long short-term memory, prediction, sepsis

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Authors: Tanima Chatterjee, Maitree Bhattacharyya

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The global challenge of type 2 diabetes mellitus is a major health concern in this millennium, and researchers are continuously exploring new targets to develop a novel therapeutic strategy. Type 2 diabetes mellitus (T2DM) is often coupled with dyslipidemia increasing the risks for cardiovascular (CVD) complications. Enhanced oxidative and nitrosative stresses appear to be the major risk factors underlying insulin resistance, dyslipidemia, β-cell dysfunction, and T2DM pathogenesis. Autophagy emerges to be a promising defense mechanism against stress-mediated cell damage regulating tissue homeostasis, cellular quality control, and energy production, promoting cell survival. In this study, we have attempted to explore the pivotal role of autophagy in T2DM subjects with or without dyslipidemia in peripheral blood mononuclear cells and insulin-resistant HepG2 cells utilizing flow cytometric platform, confocal microscopy, and molecular biology techniques like western blotting, immunofluorescence, and real-time polymerase chain reaction. In the case of T2DM with dyslipidemia higher population of autophagy, positive cells were detected compared to patients with the only T2DM, which might have resulted due to higher stress. Autophagy was observed to be triggered both by oxidative and nitrosative stress revealing a novel finding of our research. LC3 puncta was observed in peripheral blood mononuclear cells and periphery of HepG2 cells in the case of the diabetic and diabetic-dyslipidemic conditions. Increased expression of ATG5, LC3B, and Beclin supports the autophagic pathway in both PBMC and insulin-resistant Hep G2 cells. Upon blocking autophagy by 3-methyl adenine (3MA), the apoptotic cell population increased significantly, as observed by caspase‐3 cleavage and reduced expression of Bcl2. Autophagy has also been evidenced to control oxidative stress-mediated up-regulation of inflammatory markers like IL-6 and TNF-α. To conclude, this study elucidates autophagy to play a protective role in the case of diabetes mellitus with dyslipidemia. In the present scenario, this study demands to have a significant impact on developing a new therapeutic strategy for diabetic dyslipidemic subjects by enhancing autophagic activity.

Keywords: autophagy, apoptosis, dyslipidemia, reactive oxygen species, reactive nitrogen species, Type 2 diabetes

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Authors: Tahamina Begum, Wan Nor Azlen Wan Mohamad, Faruque Reza, Wan Rosilawati Wan Rosli

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To assess auditory perception and cognitive function during pregnancy is necessary as the pregnant women need extra effort for attention mainly for their executive function to maintain their quality of life. This study aimed to investigate neural correlates of cognitive and behavioral processing during mid trimester pregnancy. Event-Related Potentials (ERPs) were studied by using 128-sensor net and PAS or COWA (controlled Oral Word Association), WCST (Wisconsin Card Sorting Test), RAVLTIM (Rey Auditory Verbal and Learning Test: immediate or interference recall, delayed recall (RAVLT DR) and total score (RAVLT TS) were tested for neuropsychology assessment. In total 18 subjects were recruited (n= 9 in each group; control and pregnant group). All participants of the pregnant group were within 16-27 (mid trimester) weeks gestation. Age and education matched control healthy subjects were recruited in the control group. Participants were given a standardized test of auditory cognitive function as auditory oddball paradigm during ERP study. In this paradigm, two different auditory stimuli (standard and target stimuli) were used where subjects counted silently only target stimuli with giving attention by ignoring standard stimuli. Mean differences between target and standard stimuli were compared across groups. N100 (auditory sensory ERP component) and P300 (auditory cognitive ERP component) were recorded at T3, T4, T5, T6, Cz and Pz electrode sites. An equal number of electrodes showed non-significantly shorter amplitude of N100 component (except significantly shorter at T3, P= 0.05) and non-significant longer latencies (except significantly longer latency at T5, P= 0.008) of N100 component in pregnant group comparing control. In case of P300 component, maximum electrode sites showed non-significantly higher amplitudes and equal number of sites showed non-significant shorter latencies in pregnant group comparing control. Neuropsychology results revealed the non-significant higher score of PAS, lower score of WCST, lower score of RAVLTIM and RAVLTDR in pregnant group comparing control. The results of N100 component and RAVLT scores concluded that auditory perception is mildly impaired and P300 component proved very mild cognitive dysfunction with good executive functions in second trimester of pregnancy.

Keywords: auditory perception, pregnancy, stimuli, trimester

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Authors: Ibrahim M Hassan, Lorna Que, Michael Rutland

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Type I SOD is usually diagnosed by anatomical imaging such as ultrasound, CT and MRCP. However, the types II and III SOD yield negative results despite the presence of significant symptoms. In particular, the type III is difficult to diagnose due to the absence of significant biochemical or anatomical abnormalities. Nuclear Medicine can aid in this diagnostic dilemma by demonstrating functional changes in the bile flow. Low dose Morphine (0.04mg/Kg) stimulates the tone of the sphincter of Oddi (SO) and its usefulness has been shown in diagnosing SOD by causing a delay in bile flow when compared to a non morphine provoked - baseline scan. This work expands on that process by using sublingual GTN at 60 minutes post tracer and morphine injection to relax the SO and induce an improvement in bile outflow, and in some cases show immediate relief of morphine induced abdominal pain. The criteria for positive SOD are as follows: if during the first hour of the morphine provocation showed (1) delayed intrahepatic biliary ducts tracer accumulation; plus (2) delayed appearance but persistent retention of activity in the common bile duct, and (3) delayed bile flow into the duodenum. In addition, patients who required GTN within the first hour to relieve abdominal pain were regarded as highly supportive of the diagnosis. Retrospective analysis of 85 patients (pts) (78F and 6M) referred for suspected SOD (type III) who had been intensively investigated because of recurrent right upper quadrant or abdominal pain post cholecystectomy. 99mTc-HIDA scan with morphine-provocation is performed followed by GTN at 60 minutes post tracer injection and a further thirty minutes of dynamic imaging are acquired. 30 pts were negative. 55 pts were regarded as positive for SOD and 38/55 (60%) of these patients with an abnormal result were further evaluated with a baseline 99mTc-HIDA. As expected, all 38 pts showed better bile flow characteristics than during the morphine provocation. 20/55 (36%) patients were treated by ERCP sphincterotomy and the rest were managed conservatively by medical therapy. In all cases regarded as positive for SOD, the sublingual GTN at 60 minutes showed immediate improvement in bile flow. 11/55(20%) who developed severe post-morphine abdominal pain were relieved by GTN almost instantaneously. We propose that GTN is a useful agent in the diagnosis of SOD when performing 99mTc-HIDA scan and that the satisfactory response to the sublingual GTN could offer additional information in patients who have severe pain at the time the procedure or when presenting to the emergency unit because of biliary pain. And also in determining whether a trial of medical therapy may be used before considering surgery.

Keywords: GTN, HIDA, MORPHINE, SOD

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Authors: Yuji Fujino, Kazu Amimoto, Kazuhiro Fukata, Masahide Inoue, Hidetoshi Takahashi, Shigeru Makita

Abstract:

Aim: Pusher behavior (PB) is a disorder in which stroke patients shift their body weight toward the affected side of the body (the hemiparetic side) and push away from the non-hemiparetic side. These patients often use further pushing to resist any attempts to correct their position to upright. It is known that the subcortical white matter lesion (SWML) usually correlates of gait or balance function in stroke patients. However, it is unclear whether the SWML influences PB. The purpose of this study was to investigate if the damage of SWML affects the severity of PB on acute stroke patients. Methods: Fourteen PB patients without thalamic or cortical lesions (mean age 73.4 years, 17.5 days from onset) participated in this study. Evaluation of PB was performed according to the Scale for Contraversive Pushing (SCP) for sitting and/or standing. We used modified criteria wherein the SCP subscale scores in each section of the scale were >0. As a clinical measurement, patients were evaluated by the Stroke Impairment Assessment Set (SIAS). For the depiction of SWML, we used T2-weighted fluid-attenuated inversion-recovery imaging. The degree of damage on SWML was assessed using the Fazekas scale. Patients were divided into two groups in the presence of SWML (SWML+ group; Fazekas scale grade 1-3, SWML- group; Fazekas scale grade 0). The independent t-test was used to compare the SCP and SIAS. This retrospective study was approved by the Ethics Committee. Results: In SWML+ group, the SCP was 3.7±1.0 points (mean±SD), the SIAS was 28.0 points (median). In SWML- group, the SCP was 2.0±0.2 points, and the SIAS was 31.5 points. The SCP was significantly higher in SWML+ group than in SWML- group (p<0.05). The SIAS was not significant in both groups (p>0.05). Discussion: It has been considered that the posterior thalamus is the neural structures that process the afferent sensory signals mediating graviceptive information about upright body orientation in humans. Therefore, many studies reported that PB was typically associated with unilateral lesions of the posterior thalamus. However, the result indicates that these extra-thalamic brain areas also contribute to the network controlling upright body posture. Therefore, SMWL might induce dysfunction through malperfusion in distant thalamic or other structurally intact neural structures. This study had a small sample size. Therefore, future studies should be performed with a large number of PB patients. Conclusion: The present study suggests that SWML can be definitely associated with PB. The patients with SWML may be severely incapacitating.

Keywords: pushing behavior, subcortical white matter lesion, acute phase, stroke

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Authors: Yasmeen Jamal Alabdallat, Almutazballlah Bassam Qablan, Obada Ahmad Al Jayyousi, Ihdaa Mahmoud Bani Khalaf, Eman E. Alshial

Abstract:

Background: Bipolar disorder, formerly known as manic depression, is a mental health status that leads to extreme mood swings that include emotional lows (depression) and highs (mania or hypomania). This systematic review and meta-analysis aimed to assess the safety and efficacy of lithium versus valproate among bipolar patients. Methods: A computer literature search of PubMed, Scopus, Web of Science, and Cochrane Central Register of Controlled Trials was conducted from inception until June 2022. Studies comparing lithium versus valproate among bipolar patients were selected for the analysis, and all relevant outcomes were pooled in the meta-analysis using Review Manager Software. Results: 11 Randomized Clinical Trials were included in this meta-analysis with a total of 4159 patients. Our meta showed that lithium was superior to valproate in terms of Young Mania Rating Scale (YMRS) (MD = 0.00 with 95% CI, (-0.55 – 0.55; I2 = 0%), P = 1.00). The results of the Hamilton Depression Rating Scale (HDRS) showed that the overall effect favored the valproate treated group (MD = 1.41 with 95% CI, (-0.15 – 2.67; I2 = 0%), P = 0.03). Concerning the results of the Montgomery-Asberg Depression Rating Scale (MADRS), the results showed that the lithium was superior to valproate (MD = 0.03 with 95% CI, (-0.80 to 0.87; I2 = 40%), P = 0.94). In terms of the sexual side effect, we found that the valproate was superior to lithium (RR 1.19 with 95% CI, (0.74 to 1.91; I2 = 0%), P = 0.47). The lithium-treated group was superior in comparison to valproate treated group in terms of Abnormal Involuntary Movement Scale (AIMS) (MD = -0.03 with 95% CI (-0.38 to 0.32; I2 = 0%), P = 0.87). The lithium was more favorable in terms of Simpson-Agnes scale (MD = -0.40 with 95% CI, (-0.86 to 0.06; I2 = 0%), P = 0.09). The results of the Barnes akathisia scale showed that the overall effect of the valproate was more favorable in comparison to lithium (MD = 0.05 with 95% CI, (-0.12 to 0.22; I2 = 0%), P = 0.57). Conclusion: Our study revealed that on the scales of efficacy Lithium treated group surpassed Valproate treated group in terms of Young Mania Rating Scale (YMRS), Abnormal Involuntary Movement Scale (AIMS) and Simpson-Agnes scale, but valproate surpassed it in Barnes Akathisia scale. Furthermore, on the scales of depression Hamilton Depression Rating Scale (HDRS) showed that the overall effect favored Valproate treated group, but Lithium surpassed valproate in terms of Montgomery-Asberg Depression Rating Scale (MADRS). Valproate surpassed Lithium in terms of sexual side effects.

Keywords: bipolar, mania, bipolar-depression, sexual dysfunction, sexual side effects, treatment

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Authors: Gizaw Mamo Gebeyehu, Marianna Pap, Geza Makkai, Tibor Z. Janosi, Shima Rashidian, Tibor A. Rauch

Abstract:

Sepsis poses a significant global health threat, necessitating extensive exploration of indicators tied to its pathological mechanisms and multi-organ dysfunction. While murine studies have shed light on sepsis, the intricate cellular and molecular landscape in human sepsis remains enigmatic. Exploring the influence of activated monocyte-derived exosomes in sepsis sheds light on a promising pathway for understanding the intricate cellular and molecular mechanisms involved in this condition in humans. In sepsis, exosome-borne mRNA and miRNA orchestrate immune response gene expression in recipient cells. Yet, the specifics of exosome-mediated cell-to-cell communication, especially how mRNA cargoes modulate gene expression in recipient cells, remain poorly understood. This study aims to elucidate the precise molecular pathways through which exosomal mRNA cargo, particularly MAFB, contributes to the developing sepsis-induced molecular aberrations in liver tissues, employing rigorously defined cell culture conditions. THP-1 cells were treated with LPS to induce changes in exosomal RNA profiles. Exosomes were isolated and characterized using microscopy and mass spectrometry. RNA was extracted from exosomes and sequenced. The most abundant exosomal mRNAs were subjected to GO analysis for functional annotation analysis and KEGG database analysis to identify the involved enriched pathways. PCR (Polymerase Chain Reaction), RNA sequencing, and Western blotting were involved to analyze changes in gene expression, protein levels, and signaling pathways within the liver cells( HepG2) after exposure to exosomal MAFB. This study pinpoints exosomal MAFB as a potential key regulator linked to liver cell damage during sepsis, along with associated genes (miR155HG, H3F3A, and possibly JARD2) forming a crucial molecular pathway contributing to liver cell injury, Together, these elements indicate a vital molecular pathway that plays a significant role in the emergence of liver cell injury during sepsis.. These findings suggest the importance of further research on these components for potential therapeutic interventions in managing acute liver damage in sepsis.

Keywords: sepsis, exososome, exosomal MAFB, LPS-induced THP-1 cells, RNA profiles, sepsis-triggered liver injury

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