Trigger Factor Research Articles

Reactivity of stress-implementing system under conditions of light regime change in experiment

Influence of light exposure duration (model 18:6) on hormonal indices of stress-implementing system in laboratory animals blood is studied. Activity of stress systems central link was evaluated based on data on concentration of adrenocorticotrophic hormone, melatonin and β-endorphin in blood serum, observed during enzyme immunoassay. Reaction of peripheric link of the stress-implementing system was evaluated in blood smears based on results of qualitative count of catecholamine granules in erythrocytes. It was established, that variations of hormonal indices of the stress systems for laboratory animals depend on trigger factor activity periods. With increase of the experiment duration to 21-st days the most pronounced reduction of melatonin, β-endorphin and increase of adrenocorticotrophic hormone concentration, as well as sharp increase of catecholamines level are observed in the blood serum. These hormonal changes develop as a result of failure of compensation mechanisms of the stress-implementing systems in connection with melatonin rhythms disturbance, that indicates the gradual development of the general adaptation syndrome. Keywords: endocrine profile, stress-implementing system, general adaptation syndrome, biorhythms, light desynchronosis.

PKM2 Is Overexpressed in Glioma Tissues, and Its Inhibition Highly Increases Late Apoptosis in U87MG Cells With Low-density Specificity.

Pyruvate kinase M2 (PKM2) functions as an important rate-limiting enzyme in aerobic glycolysis and is involved in tumor initiation and progression. However, there are few studies on the correlation between PKM2 expression and its role in glioma. PKM2 expression was immunohistochemically examined in human brain tumor samples. Furthermore, we studied the effects of two PKM2 inhibitors (shikonin and compound 3K) on the U87MG glioma cell line. PKM2 was overexpressed in most glioma tissues when compared to controls. Interestingly, glioma-adjacent tissues from showed slight PKM2 overexpression. This suggests that PKM2 overexpression maybe an important trigger factor for glioma tumorigenesis. We found that the PKM2 inhibitor shikonin was effective against U87MG cells at a relatively low dose and was largely dependent on low cellular density compared to the effects of the anticancer drug vincristine. Shikonin highly increased late-apoptosis of U87MG cells. We also demonstrated that autophagy was involved in the increase in late-apoptosis levels caused by shikonin. Although vincristine treatment led to a high level of G2-phase arrest in U87MG cells, shikonin did not increase G2 arrest. Co-treatment with two PKM2 inhibitors, shikonin and compound 3K, increased the inhibitory effects. Combination therapy with PKM2 inhibitors together might be more effective than combination therapy with anticancer drugs. Our findings encourage the application of PKM2-targeting in gliomas, and lay the foundation for the development of PKM2 inhibitors as promising antitumor agents for glioma.

Migraine and light: A narrative review.

In this narrative review, we summarize clinical and experimental data on the effect of light in migraine and discuss future prospects. Effective nonpharmacological treatment of hypersensitivity to light in migraine is an unmet clinical need. Current management strategies primarily consist of seeking a dark room and avoiding light exposure. Advances in the past 2 decades have improved our understanding of the underlying pathophysiology of how migraine is influenced by light. This may provide promising avenues for novel approaches in clinical management. We searched MEDLINE for articles published from database inception up to September 1, 2021. We used the search term "migraine" with the search terms "light," "photophobia," "treatment," "trigger," "circadian rhythm," "environment," and/or "pathophysiology." Light is commonly reported as a trigger factor of migraine attacks, however, early manifestation of photophobia and false attribution is likely the actual cause based on data deriving from retrospective, prospective, and experimental studies. The most common photophobia symptoms in migraine are exacerbation of headache by light and abnormal sensitivity to light with the underlying neural pathways likely being dependent on ongoing activity in the trigeminovascular system. Clinical studies and experimental models have identified mediators of photophobia and uncovered narrow wavebands of the light spectrum that may reduce pain intensity during a migraine attack. Consequently, novel devices have undergone exploratory clinical trials with promising results. False attribution is likely the reason why light is commonly reported as a trigger factor of migraine attacks, and a prospective confirmation is required to prevent unnecessary avoidance. The observation that individuals with migraine are not equally photophobic to all wavebands of the light spectrum opens the potential for innovative pain management strategies. In this context, using human-centric lighting (also called integrative lighting) to mimic the natural daylight cycle and avoid harmful wavebands through modern technology may prove beneficial. Future research should identify direct and indirect consequences of light and other environmental factors in migraine to fill out knowledge gaps and enable evidence-based care strategies within institutions, work environments, and other settings.

Application Of Murottal Therapy Of The Qur'an Surah Ar-Rahman As A Nursing Intervention In Tn.A With Decreasing Heart Output

Chronic kidney failure is a condition in which the kidneys experience a decrease in the glomerular filtration rate (GFR) which causes the kidneys to be unable to filter metabolic wastes to be removed and cause these metabolic wastes to accumulate in the body. The main trigger factor for kidney disease and kidney failure is an increase in blood pressure or vice versa when kidney function is impaired/kidney failure, blood pressure can also increase. Murottal Al-Qur'an Surah Ar-Rahman therapy is one of the interventions that can be done to reduce high blood pressure. Murottal Al-Qur'an therapy in this paper was carried out 3 times for 3 visits to post hemodialysis clients with a time of 10 minutes per session on clients with chronic kidney failure. The purpose of this paper is the application of the Surah Ar-Rahman Murottal Al-Qur'an Therapy intervention aimed at clients with nursing diagnoses of decreased cardiac output. Where the condition of the client before the nursing intervention experienced dizziness and headaches marked by an increase in blood pressure after hemodialysis, namely blood pressure: 191/83 mmHg, then after the intervention of Murottal Al-Qur'an Surah Ar-Rahman Therapy there was a decrease in blood pressure marked by the condition the client becomes relaxed and calm without any complaints with a final blood pressure measurement of 130/80 mmHg. So it can be concluded that murottal Al-Qur'an Surah Ar-Rahman therapy can reduce the increase in blood pressure in patients with chronic kidney failure post hemodialysis.

Pathway Analysis of Behavioral Determinants in Preventing Genital Infections of Santri Putri Pondok Pesantren : Application of The Integrated Behavior Model

Female students who live in Islamic boarding schools are a population at risk for genital infections. The practice of personal/vaginal hygiene or menstrual hygiene is a form of maintaining reproductive health by preventing genital infections. Some bad behavior related to vaginal hygiene is a trigger factor for female genital infections. This study aimed to examine the factors behind the behavior of preventing genital infection in female students in the Islamic boarding school environment. This study was a quantitative study with a cross-sectional design. The population in this study was all female students. Determination of the sample in this study was carried out randomly with the number of subjects determined based on the rule-of-thumb sample size for path analysis, namely a minimum of 100 subjects, a minimum of 5 subjects per parameter, and a minimum of 10 subjects per variable. So that a sample of 150 female students was determined. The independent variable in this study was the behavior of preventing genital infection, while the dependent variables was: (1) behavioral intentions, (2) correct knowledge about behavior, (3) perception of the meaning of behavior, (4) environmental barriers, (5) experiential attitudes, (6) instrumental attitudes, (7) injunctive norms, (8) descriptive norms, (9) perceived behavioral control, (10) self-efficacy. This study indicated that infection prevention behavior can be determined by the behavior of female students prevention of genital infection is not influenced by the behavior of environmental barriers. Good knowledge and skills did not affect female students in taking measures to prevent genital infections; therefore, it was necessary to develop a more heterogeneous number of respondents and a questionnaire that can be understood by respondents so that an integrated behavioral model can become a reference to change behavior, and use methods that can improve their behavior.

Regression analysis to estimate the response of the respiratory organs to exposure of air microtoxicants in chronic obstructive pulmonary disease

Inroduction. The assessment of the respiratory system is of particular importance in the context of increasing impact of anthropogenic factors on human health. Aim. Evaluation the response of the lung function indices to the effects of micro-suspensions and toxic metals in patients with chronic obstructive pulmonary disease (COPD), using regression models. Materials and methods. The study involved 60 patients with stable mild-to-moderate COPD and 30 healthy people (the control group). The analysis of lung function was carried out by spirometry and body plethysmography. Arterial oxygen saturation (SaO2 ) was measured by pulse oximetry. Exhaled CO2 concentration and blood carboxyhemoglobin (COHb%) concentration were assessed using a portable analyzer MicroCO Meter. The pollution of the city atmosphere was assessed by aerosol suspensions of solid particles in the areas of residence of the examined patients. Fractional composition of suspended particles (0-1, 1-10, 10-50, 50-100, 100-400, 400-700,> 700 μm; %) were analyzed in the areas of residence of the examined patients. Toxic metal (Pb, Cr, Mn, Fe, Co, Ni, Cu, Zn; μg/L) levels in the air samples were determined. The statistical module "Multiple regression" was used for assessing the response of functional parameters of the respiratory system. Results. The analysis of one-factor and multi-factor regression models made it possible to identify both trigger factors of dust and technogenic air pollution and the synergistic effect of the influence of dominant factors. It has been shown that multifactorial reactions to technogenic impact manifest as altered blood oxygen saturation and carboxyhemoglobin level and thereby contribute to the development of respiratory failure. Conclusion. Patients with COPD exhibited increased bronchial resistance to the effect of the trigger factor (Pb – 1 hazard class) associated with high motorization of the city. The response of pulmonary gas exchange (SaO2 ) to Pb in the control group indicates prolonged exposure to toxic metals can cause developing respiratory failure even in the healthy population of the city.

Biological Efficacy Evaluation of a Non-Cross-Linked Hyaluronic Acid Dermal Filler for Biomedical Application in Inflammatory Scalp Conditions.

(1) Background: The dysbiosis of some cutaneous commensal microorganisms is the trigger factor for the activation of the inflammatory cascade by keratinocytes in many skin disorders. Mesotherapy is an innovative technique for many scalp disorders, with the function of restoring the physiology of the skin. (2) Methods: the antimicrobial, antibiofilm and anti-inflammatory activity of the non-cross-linked HA formulation (Hydro Deluxe, Matex Lab S.p.a., Brindisi, Italy) was investigated against the most common microorganisms of the scalp (Staphyloccoccus epidermis, Staphyloccoccus aureus, Cutibacterium acnes and Malassezia furfur). Anti-inflammatory activity was evaluated on an internal 3D model of Reconstructed Human Epidermis (RHE) inserts infected with the strains as pro-inflammatory stimulus. (3) Results and Conclusions: the data collected showed a good antimicrobial and antibiofilm activity against all selected strains. The HA-based formulation did not show cytotoxicity on RHE, either alone or in presence of the infectious stimulus. The analysis of the expression of Interleukin (IL)-8 levels showed an excellent ability to reduce this pro-inflammatory marker. Overall, the efficacy assessment of the formulation supported its potential effectiveness in mesotherapy for the treatment of scalp disorders.

Common sequence motifs of nascent chains engage the ribosome surface and trigger factor

In the cell, the conformations of nascent polypeptide chains during translation are modulated by both the ribosome and its associated molecular chaperone, trigger factor. The specific interactions that underlie these modulations, however, are still not known in detail. Here, we combine protein engineering, in-cell and invitro NMR spectroscopy, and molecular dynamics simulations to explore how proteins interact with the ribosome during their biosynthesis before folding occurs. Our observations of α-synuclein nascent chains in living Escherichia coli cells reveal that ribosome surface interactions dictate the dynamics of emerging disordered polypeptides in the crowded cytosol. We show that specific basic and aromatic motifs drive such interactions and directly compete with trigger factor binding while biasing the direction of the nascent chain during its exit out of the tunnel. These results reveal a structural basis for the functional role of the ribosome as a scaffold with holdase characteristics and explain how handover of the nascent chain to specific auxiliary proteins occurs among a host of other factors in the cytosol.

OPTIMIZATION OF PREGRAVIDARY PREPARATION AND MONITORING OF PREGNANCY IN WOMEN WITH HISTORY OF EARLY GESTOSIS

In preparing women with a history of early gestosis for the next pregnancy, an important point is to determine the individual trigger factor and its maximum correction before pregnancy. Objective. To determine the effectiveness of the proposed set of treatment measures in pregnancy planning and in the first trimester of pregnancy in women with a history of early gestosis to reduce the incidence of gestational complications. Materials and methods. We examined 150 women – 100 re-pregnant women with a history of early gestosis (50 women received standard treatment, and 50 – we developed a set of treatment and prevention measures at the pre-pregnancy stage and in the first trimester of pregnancy) and 50 with physiological course in the first trimester. Research results and their discussion. In group II pregnant women the frequency of complications was significantly lower compared to group I patients: vomiting of pregnant women – 20 % against 62 %, the risk of abortion – 14 % against 36 %, the risk of premature birth – 18 % against 26 %, anemia – 18 % against 24 %, placental dysfunction – 24 % against 28 %. In women from group II, the symptoms of mild vomiting of pregnant women prevailed, and in women from group I – severe vomiting. Conclusions. The use of the proposed set of therapeutic measures in pregnancy planning and during gestation has a positive effect on the subsequent course of pregnancy, there is a lower frequency of complications of gestation and improved perinatal outcomes.

Hypolipidemic Effects Of Aloe Vera (Aloe Vera L.)

Background: Chronic hyperlipidemia is a trigger factor for serious diseases, one of which is atherosclerosis. Lipid profile disorders in the form of increased total cholesterol, LDL and decreased HDL levels are believed to be one of the major triggering factors for cardiovascular disease. One of the treatments for hyperlipidemia in addition to using conventional therapy can also be with traditional treatments such as aloe vera (Aloe Vera L). The content of glucomannan in aloe vera is believed to act as a hypolipidemic agent. Method: This paper uses a literature study or literature review of research articles. Search articles through Google Scholar and Pubmed with keywords used hypolipidemia and Aloe vera. The criteria for the articles used were published in the last 5 years, namely from 2016 to 2021. Results: Based on the literature search, there were 8 studies related to the effect of aloe vera on lipid profile levels, of which there were 7 studies on experimental animals and 1 study on humans. Aloe vera used varies from extract form, gel and powder form in capsules. Conclusion: Based on the literature study, it was found that aloe vera is an herbal plant that has a fairly effective hypolipidemic effect.

C16. BRASH (Bradycardia, Renal Failure, AV Nodal Blocker, Shock, and Hyperkalemia) Syndrome: Lost in Plain Sight

Abstract Background Bradycardia, Renal failure, AV-Nodal blockers, Shock, Hyperkalemia (BRASH) Syndrome new clinical entities due to a vicious cycle in which hyperkalemia from renal failure synergizes with AV-nodal blockers, consequently between the clinical condition of patients with the degree of hyperkalemia and bradycardia are inappropriate, Furthermore, the symptoms may be refractory to typical positive chronotropic interventions or overdose antidotes. Case Illustration A hypertensive 70-years old female with history of heart failure with routinely consume spironolactone, diltiazem, and beta blocker admitted with bradycardia and shock after watery diarrhea and vomit 3 days before. The electrocardiogram showed junctional rhythm 40 beats per minutes. Laboratory findings Hyperkalemia (6.8 mEq/L) and acute kidney injury (urea 58.6 mg/dL, creatinine 3.13 mg/dL, eGFR 16.23) was presented. Refractory hyperkalemia occured, but by using pacemaker, providing adequate fluids, and the return of renal perfusion, hyperkalemia can be overcome. Discussion BRASH syndrome usually triggered by hypotension in the elderly due to hypovolemia or an overdose of antihypertensive drugs. The natural compensation response for hypotension is to increase heart rate, but AV-nodal blockers blunt this response, which causes a decrease in renal perfusion. This ultimately results in hyperkalemia and accumulation of AV-nodal blockers which produce a synergistic effect causes bradycardia and decreased renal perfusion. Treatment involves supportive care including hemodynamic support with fluids and management of bradycardia, and also avoid trigger factor.

C16. BRASH (Bradycardia, Renal Failure, AV Nodal Blocker, Shock, and Hyperkalemia) Syndrome: Lost in Plain Sight

Abstract Background Bradycardia, Renal failure, AV-Nodal blockers, Shock, Hyperkalemia (BRASH) Syndrome new clinical entities due to a vicious cycle in which hyperkalemia from renal failure synergizes with AV-nodal blockers, consequently between the clinical condition of patients with the degree of hyperkalemia and bradycardia are inappropriate, Furthermore, the symptoms may be refractory to typical positive chronotropic interventions or overdose antidotes. Case Illustration A hypertensive 70-years old female with history of heart failure with routinely consume spironolactone, diltiazem, and beta blocker admitted with bradycardia and shock after watery diarrhea and vomit 3 days before. The electrocardiogram showed junctional rhythm 40 beats per minutes. Laboratory findings Hyperkalemia (6.8 mEq/L) and acute kidney injury (urea 58.6 mg/dL, creatinine 3.13 mg/dL, eGFR 16.23) was presented. Refractory hyperkalemia occured, but by using pacemaker, providing adequate fluids, and the return of renal perfusion, hyperkalemia can be overcome. Discussion BRASH syndrome usually triggered by hypotension in the elderly due to hypovolemia or an overdose of antihypertensive drugs. The natural compensation response for hypotension is to increase heart rate, but AV-nodal blockers blunt this response, which causes a decrease in renal perfusion. This ultimately results in hyperkalemia and accumulation of AV-nodal blockers which produce a synergistic effect causes bradycardia and decreased renal perfusion. Treatment involves supportive care including hemodynamic support with fluids and management of bradycardia, and also avoid trigger factor.

Identification and validation of objective triggers for initiation of resuscitation management of acutely ill non-trauma patients: the INITIATE IRON MAN study

BackgroundWhile there are clear national resuscitation room admission guidelines for major trauma patients, there are no comparable alarm criteria for critically ill nontrauma (CINT) patients in the emergency department (ED). The aim of this study was to define and validate specific trigger factor cut-offs for identification of CINT patients in need of a structured resuscitation management protocol.MethodsAll CINT patients at a German university hospital ED for whom structured resuscitation management would have been deemed desirable were prospectively enrolled over a 6-week period (derivation cohort, n = 108). The performance of different thresholds and/or combinations of trigger factors immediately available during triage were compared with the National Early Warning Score (NEWS) and Quick Sequential Organ Failure Assessment (qSOFA) score. Identified combinations were then tested in a retrospective sample of consecutive nontrauma patients presenting at the ED during a 4-week period (n = 996), and two large external datasets of CINT patients treated in two German university hospital EDs (validation cohorts 1 [n = 357] and 2 [n = 187]).ResultsThe any-of-the-following trigger factor iteration with the best performance in the derivation cohort included: systolic blood pressure < 90 mmHg, oxygen saturation < 90%, and Glasgow Coma Scale score < 15 points. This set of triggers identified > 80% of patients in the derivation cohort and performed better than NEWS and qSOFA scores in the internal validation cohort (sensitivity = 98.5%, specificity = 98.6%). When applied to the external validation cohorts, need for advanced resuscitation measures and hospital mortality (6.7 vs. 28.6%, p < 0.0001 and 2.7 vs. 20.0%, p < 0.012) were significantly lower in trigger factor-negative patients.ConclusionOur simple, any-of-the-following decision rule can serve as an objective trigger for initiating resuscitation room management of CINT patients in the ED.

Molecular Effects of Elongation Factor Ts and Trigger Factor on the Unfolding and Aggregation of Elongation Factor Tu Induced by the Prokaryotic Molecular Chaperone Hsp33.

Simple SummaryProteins are versatile biological macromolecules involved in most biological processes. However, because of the highly labile nature of protein structures, protein quality control (PQC) to ensure proteostasis (i.e., protein homeostasis)is difficult. Therefore, proteins of a specialized class (i.e., molecular chaperones) are required that assist in proper folding and prevent aberrant folding of other proteins. Hsp33 was originally discovered as a holding chaperone that is overexpressed upon heat shock and activated by oxidation to prevent the misfolding of client proteins. Recently, an unfoldase/aggregase activity of Hsp33 was identified in its reduced state against a specific substrate, EF-Tu, which plays a key role in protein biosynthesis in cells. The present study demonstrates that EF-Tu unfolding/aggregation by Hsp33 can be accelerated by another molecular chaperone trigger factor. Given that the unfolded/aggregated EF-Tu is finally degraded by another chaperone, Lon protease, it is likely that a chaperone network dysregulating EF-Tu operates in heat shock to attenuate protein biosynthesis, which is harmful to cell survival under stressed conditions. Therefore, the apparently contradictory chaperone function (i.e., promotion of client misfolding) of Hsp33 can also be associated with the PQC processes to ensure proteostasis in cells.Hsp33, a prokaryotic redox-regulated holding chaperone, has been recently identified to be able to exhibit an unfoldase and aggregase activity against elongation factor Tu (EF-Tu) in its reduced state. In this study, we investigated the effect of elongation factor Ts (EF-Ts) and trigger factor (TF) on Hsp33-mediated EF-Tu unfolding and aggregation using gel filtration, light scattering, circular dichroism, and isothermal titration calorimetry. We found that EF-Tu unfolding and subsequent aggregation induced by Hsp33 were evident even in its complex state with EF-Ts, which enhanced EF-Tu stability. In addition, although TF alone had no substantial effect on the stability of EF-Tu, it markedly amplified the Hsp33-mediated EF-Tu unfolding and aggregation. Collectively, the present results constitute the first example of synergistic unfoldase/aggregase activity of molecular chaperones and suggest that the stability of EF-Tu is modulated by a sophisticated network of molecular chaperones to regulate protein biosynthesis in cells under stress conditions.

CERCETĂRI CU PRIVIRE LA DEZVOLTAREA UNEI METODOLOGII DE STUDIERE A INTERACȚIUNII RADON X FUMAT CA FACTOR TRIGGER ÎN DECLANȘAREA CANCERULUI BRONHOPULMONAR

Objectives. Residential exposure to radon is the second risk factor for lung cancer triggering for smokers and the first – for non-smokers. The obtaining reliable result in this area requires large-scale epidemiological scientific studies with the appropriate patient samples, but the results of some studies are controversial. The synthetic analysis of the specialized literature served as a basis for the methodology development to study the interaction of radon x smoking as a trigger factor in the occurrence of lung cancer at smokers in the Republic of Moldova. Material and methods. Global experience on the methodology for studying the interaction radon x smoking was examined about 30 publications on platforms of ResearchGate, Pubmed, BioMedCentral, RSCI, European Commission Webgate, WHO, AIEA, etc. A descriptive synthesis of current approaches to the development and implementation of research methods for studying the radon x smoking interaction on the triggering of bronchopulmonary cancer was performed. Results. A few researches have focused on the study of the effect of synergic exposure of radon/smoke on the occurrence of lung cancer. A review showed that the main methods for studying this phenomenon are and sociological. Combining the studied approaches and basing on the experience of international research, the methodology for estimating the interaction of radon x smoking on triggering the bronchopulmonary cancer was developed. Two directions are proposed in the research methods: (1) statistical with the use of smokers' data in the Republic of Moldova, radon concentration in dwellings and morbidity/mortality indices and (2) case-control with the use of the long-term study questionnaire in collaboration with the Institute of Oncology. Conclusions. The development of a methodological approach to the study of the radon x smoking interaction on the occurrence of bronchopulmonary cancer will allow the Public Health System to develop tools to control/prevent/reduce this disease.

Clearance of Bone Substitute in Gel Form Accidentally Dispersed into the Sinus Cavity during Transcrestal Maxillary Sinus Floor Elevation: Two-Case Report

Sinus membrane perforation is the most frequent intraoperative complication occurring during maxillary sinus floor elevation. Although numerous techniques for perforation management are present, grafting material dissemination may still occur, representing a potential trigger factor leading to acute or chronic sinusitis. This case report describes two cases of xenogeneic bone substitute in gel form accidentally dispersed into the sinus cavity during maxillary sinus floor elevation with a transcrestal approach. In both cases, immediately postoperative radiographic imaging showed an important amount of gel graft dislodged into the sinus cavity as a consequence of hidden perforations that remained undetected during surgery. Patients were monitored for 6 months after surgery and reported no signs or symptoms related to possible sinus disease. Control radiographs showed no sinus membrane hypertrophy and/or presence of residual disseminated gel, confirming complete clearance of the accidentally dispersed graft through the ostiomeatal complex. In order to minimize postoperative complications, bone substitutes in gel form could represent an interesting alternative to granular grafts for their easier clearance from the maxillary sinus cavity in case of accidental dissemination during sinus augmentation procedures.

Zinc-Dependent Oligomerization of Thermus thermophilus Trigger Factor Chaperone.

Simple SummaryMetal ions often play important roles in biological processes. Thermus thermophilus trigger factor (TtTF) is a zinc-dependent molecular chaperone where Zn2+ has been shown to enhance its folding-arrest activity. However, the mechanisms of how Zn2+ binds to TtTF and how Zn2+ affects the activity of TtTF are yet to be elucidated. As a first step in understanding the mechanism, we performed in vitro biophysical experiments on TtTF to investigate the zinc-binding site on TtTF and unveil how Zn2+ alters the physical properties of TtTF, including secondary structure, thermal stability, and oligomeric state. Our results showed that TtTF binds Zn2+ in a 1:1 ratio, and all three domains of TtTF are involved in zinc-binding. We found that Zn2+ does not affect the thermal stability of TtTF, whereas it does induce partial structural change and promote the oligomerization of TtTF. Given that the folding-arrest activity of Escherichia coli TF (EcTF) is regulated by its oligomerization, our results imply that TtTF exploits Zn2+ to modulate its oligomeric state to regulate the activity.Thermus thermophilus trigger factor (TtTF) is a zinc-dependent molecular chaperone whose folding-arrest activity is regulated by Zn2+. However, little is known about the mechanism of zinc-dependent regulation of the TtTF activity. Here we exploit in vitro biophysical experiments to investigate zinc-binding, the oligomeric state, the secondary structure, and the thermal stability of TtTF in the absence and presence of Zn2+. The data show that full-length TtTF binds Zn2+, but the isolated domains and tandem domains of TtTF do not bind to Zn2+. Furthermore, circular dichroism (CD) and nuclear magnetic resonance (NMR) spectra suggested that Zn2+-binding induces the partial structural changes of TtTF, and size exclusion chromatography-multi-angle light scattering (SEC-MALS) showed that Zn2+ promotes TtTF oligomerization. Given the previous work showing that the activity regulation of E. coli trigger factor is accompanied by oligomerization, the data suggest that TtTF exploits zinc ions to induce the structural change coupled with the oligomerization to assemble the client-binding site, thereby effectively preventing proteins from misfolding in the thermal environment.

A 5-Year Prospective Study on Effect of Antimicrobial Surgical Prophylaxis in the Department of General Surgery

Background: Antibiotic-resistant infections have elevated rates of morbidity and mortality, and antibiotic exposure is a significant trigger factor for drug resistance growth. If surgical antibiotic prophylaxis (SAP) increases risk for antibiotic-resistant infections, it may cause significant harm even if it decreases overall infection rates. The present study is planned to study the effect of antimicrobial surgical prophylaxis in the department of general surgery. Materials and Methods: This prospective study included young age people to old age people who underwent elective surgical procedures. The study was carried for 5 successive years from 2016 to 2020. Surgeries from multiple disciplines were included if SAP was considered discretionary by current guidelines. Results: According to the observations, the antibiotics were administered in all the surgical interventions and most of the pre-operatively antibiotics were administered by IV route. Graph showcases a gradual increase in antibiotic misuse both before and during the surgery. In the year 2016, the antibiotic usage in surgical prophylaxis was observed to be an average of 65.89%. This value was found to be progressively increasing in the successive years. By the year of 2020, the average hiked to the value of 97.11%. This is conclusive of the decreasing misuse of antibiotics with years. Especially the recent times reaching the maximum peak, as appreciated in the graph. This could be attributed as one of the major factors in development of resistance towards various microorganisms that has been managed. Conclusion: Surgical antibiotic prophylaxis is an important treatment technique for preventing postoperative infections, if the right antibiotics are administered at the right moment, for the right length of time, and for the right surgical procedures. It is crucial to use a narrow-spectrum antibiotic that is safe for the surgical venue. The expense of specific antibiotics and the endemicity of multi-resistant bacteria in specific units or clinics are also subject to periodic modification, so hospital surgical antibiotic prophylaxis procedures should be checked on a regular basis.

Clinical characteristics and outcomes in young patients with myocardial infarction

Abstract Background Young people hold a stable or increasing percentage of patients with acute myocardial infarction in many countries. However, data on clinical characteristics and outcomes in young patients are lacking. Purpose To compare clinical characteristics and outcomes between patients aged ≤45 years and those aged &amp;gt;45 years with acute myocardial infarction. Methods A total of 24125 patients with acute myocardial infarction between January 2013 and September 2014 from China Acute Myocardial Infarction (CAMI) registry were included in this study. Clinical characteristics, in-hospital and 2-year outcomes were compared between patients aged ≤45 years (young) and those aged &amp;gt;45 years (older). Gender disparity in prognosis of myocardial infarction was analyzed among young patients. Results Of 24125 patients, 2042 (8.5%, 116 female) were aged ≤45 years. Compared with patients aged &amp;gt;45 years, young patients were more often male, current smokers, having medical history of hyperlipidemia and family history of premature coronary artery disease. Young patients were significantly more likely to have clear trigger factor, present with persistent chest pain and suffer ST-segment elevation myocardial infarction. Symptom onset to admission time was shorter in patients aged ≤45 years. For patients undergoing emergency coronary angiography, those aged ≤45 years were more likely to suffer left anterior descending coronary artery related myocardial infarction. Young patients were significantly more likely to receive percutaneous coronary intervention and other medications at discharge, including dual antiplatelet therapy, statins, angiotensin converting enzyme inhibitors or angiotensin II receptor blockers and β blockers. Compared with patients aged &amp;gt;45 years, young patients experienced significantly lower in-hospital and 2-year mortality and major adverse cardiac and cerebrovascular events (MACCE, a composite of death, reinfarction and stroke) rates (Table 1). Among young patients, women experienced higher in-hospital mortality and MACCE rates than men (Table 2). Women who survived at discharge experienced significantly higher 2-year mortality (1.4% vs 3.8%, Log-rank P=0.0412, Table 2). Conclusions Compared with the older patients, young patients were more likely to present with typical symptoms and receive guideline-recommended medications. Clinical outcomes of patients aged ≤45 years were significantly better than older patients. However, our results showed significant gender disparity in both short- and long-term outcomes of young patients. More efforts are needed to improve prognosis in young patients with acute myocardial infarction. Funding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): The Twelfth Five-Year Planning Project of the Scientific and Technological Department of China

Better Response to Influenza Virus Vaccination in Physically Trained Older Adults Is Associated With Reductions of Cytomegalovirus-Specific Immunoglobulins as Well as Improvements in the Inflammatory and CD8+ T-Cell Profiles.

Chronic cytomegalovirus (CMV) infection is a trigger factor for the development of immunosenescence and negatively impacts the immune response to influenza virus vaccination (IVV) in older adults. However, the role of physical exercise training in this context is unknown. Thus, the aim of this study was to investigate whether the regular practice of combined exercise training can improve the specific antibody response to IVV in CMV-seropositive older adults. Eighty older adults were distributed into two groups—non-practitioners (NP, n = 31, age = 74.06 ± 6.4 years) and practitioners of combined exercise training (CET, n = 49, age = 71.7 ± 5.8 years)—for at least 12 months. Both volunteer groups were submitted to IVV and blood samples were collected before (pre) and 30 days after (post) the vaccination. Concerning the specific antibody response to IVV, higher serum levels of specific immunoglobulin A (IgA) were found in the CET group post- than pre-vaccination (p < 0.01), whereas higher levels of specific immunoglobulin M (IgM) were observed both in the NP (p < 0.05) and CET (p < 0.001) groups post-vaccination as compared to the pre-vaccination values. Serum levels of specific immunoglobulin G (IgG) for IVV and CMV, as well as interleukin 6 (IL-6) and IL-10, were similar between the time points evaluated. However, the IL-10/IL-6 ratio post-vaccination was higher (p < 0.05) in the CET group than that before vaccination. Negative correlations were observed between the specific IgG levels for IVV and CMV only in the CET group, both pre- and post-vaccination. In addition, negative correlations were found between IL-10 and specific IgG for CMV in all volunteer groups pre- and post-vaccination, whereas a positive correlation between IL-10 and specific-IgG for IVV pre- and post-vaccination was observed in the CET group. In addition, with the hemagglutination inhibition (HAI) assay, it was found that 32.2% of the NP group and 32.6% of the CET group were responders to IVV and displayed reductions in the CMV serostatus (p < 0.05 and p < 0.001, respectively) and increases in naive and effector CD8+ T cells post-vaccination (p < 0.01). However, only the responders from the CET group showed significant reductions in the ratio of effector to naive CD8+ T cells (p < 0.05) and increased IL-10 levels post-vaccination (p < 0.001). In summary, this study demonstrates that the improvement in the response to IVV in CMV-seropositive older adults was related to an anti-inflammatory status and enhancement of naive CD8+ T cells, particularly associated with regular practice of CET.