Excessive Stimulation Research Articles

Recent Trends on Mitigative Effect of Probiotics on Oxidative-Stress-Induced Gut Dysfunction in Broilers under Necrotic Enteritis Challenge: A Review.

Gut health includes normal intestinal physiology, complete intestinal epithelial barrier, efficient immune response, sustained inflammatory balance, healthy microbiota, high nutrient absorption efficiency, nutrient metabolism, and energy balance. One of the diseases that causes severe economic losses to farmers is necrotic enteritis, which occurs primarily in the gut and is associated with high mortality rate. Necrotic enteritis (NE) primarily damages the intestinal mucosa, thereby inducing intestinal inflammation and high immune response which diverts nutrients and energy needed for growth to response mediated effects. In the era of antibiotic ban, dietary interventions like microbial therapy (probiotics) to reduce inflammation, paracellular permeability, and promote gut homeostasis may be the best way to reduce broiler production losses. The current review highlights the severity effects of NE; intestinal inflammation, gut lesions, alteration of gut microbiota balance, cell apoptosis, reduced growth performance, and death. These negative effects are consequences of; disrupted intestinal barrier function and villi development, altered expression of tight junction proteins and protein structure, increased translocation of endotoxins and excessive stimulation of proinflammatory cytokines. We further explored the mechanisms by which probiotics mitigate NE challenge and restore the gut integrity of birds under disease stress; synthesis of metabolites and bacteriocins, competitive exclusion of pathogens, upregulation of tight junction proteins and adhesion molecules, increased secretion of intestinal secretory immunoglobulins and enzymes, reduction in pro-inflammatory cytokines and immune response and the increased production of anti-inflammatory cytokines and immune boost via the modulation of the TLR/NF-ĸ pathway. Furthermore, increased beneficial microbes in the gut microbiome improve nutrient utilization, host immunity, and energy metabolism. Probiotics along with biosecurity measures could mitigate the adverse effects of NE in broiler production.

Практичні аспекти викладання неонатології студентам медико-психологічного факультету

Purpose - to devote the main peculiarities of teaching neonatology to students of the medical and psychological faculty (MPF). The main principles of distance learning are emphasized as problem-solving, interactivity and orientation on personal development. The advantages of problem-solving learning are declared; it helps students in the development of clinical thinking, of the ability to predict the occurrence of psychological problems, and develops optimal tactics in communication with parents and medical personnel. In teaching the neonatology cycle to MPF students, special emphasis is placed on certain pathological conditions in newborns, which require psychological support for families. The need to provide comprehensive medical and psychological assistance to mothers, the effectiveness of which is based on key professional competencies and in-depth clinical knowledge, is emphasized. A point is placed on the fact that in the process of training in neonatology, students of the MPF must understand their special role in preventing medical stress and medical trauma for both the child and the parents, since the environment of intensive neonatology contains numerous stress factors due to excessive sensory stimulation, such as light, sound and pain, which conflict with the requirements of the brain development of a newborn baby, especially in case of preterm birth. That is why it is important to providing complete information to the parents regarding the role of each member of the team of specialists in the organization of treatment and care of the child and the need to use developmental care that meets the needs of the early development of a premature child is also highlighted. The role of the future medical psychologist in providing support to parents with perinatal loss is also determined. This problem affects many families, most of whom are dealing with their loss often alone without adequate support and help. The problem of perinatal losses and recovery of mothers and families after them is the competence of medical psychologists. The underlined requirements for the teacher are the individual preparation of high-quality learning content, which may require additional time, but the involvement of the students themselves in the preparation of the necessary materials will even more increase the interactivity of the educational process. The possibilities of using the modern educational technologies are analyzed: these are «case technologies» in small groups, «business (role) games», an inverted classroom approach. No conflict of interests was declared by the authors.

Ultraviolet-selective organic phototransistors for low-power skin-inspired nociceptor

Skin-inspired nociceptors are particularly important for future neurorobotic technology. In this work, an artificial skin nociceptor based on ultraviolet (UV)-selective C8-BTBT phototransistors was reported. By using polymethyl methacrylate as an interfacial modification layer, a large number of standing crystals appeared in the C8-BTBT film, and the photo-dark current ratio of the devices exceeded the value of 1010. The main biological synaptic behaviors of the devices under UV light stimuli were also thoroughly investigated. Interestingly, the minimum power consumption per synaptic event (2.45 fJ) is comparable to the energy required by the biological synapses. The biological behavior of the skin-inspired nociceptor was further simulated, such as allodynia, hyperalgesia, and the self-protection behavior under UV light stimulation. Finally, as a proof of concept, the skin-inspired nociceptor was proposed to be integrated with the UV-transmittance modulator to protect against excess UV stimulation, which fully demonstrated its potential applications in bionic electronics technology.

Application of current steering with MICC directional lead in STN-DBS for Parkinson’s disease

BackgroundDeep brain stimulation (DBS) of the subthalamic nucleus (STN) has been widely performed for medically refractory Parkinson's disease (PD). Recent new technology of the multiple independent current control (MICC) with the directional lead provides both vertical and horizontal current steering on purposes. Consequently, MICC directional lead allows fine stimulation adjustment tailoring the condition of the individual patient. It is also expected to avoid stimulation induced adverse effects. MethodsWe retrospectively investigated the situation of current steering and the reason for doing so 3-month and 1-year after surgery in 80 patients who underwent bilateral STN-DBS for PD using MICC directional lead. ResultsIn 160 leads of 80 patients, current steering was used in 39 leads (24%) 3-month after surgery, but in 80 leads (50%) 1-year after surgery. As for the reason, vertical steering was used in 7 leads (4%) and horizontal steering was used in 28 leads (18%) to explore better stimulation effect for cardinal symptoms of PD. In addition, vertical steering was used for improving dyskinesia in 40 leads (25%) and alleviating tremor in 5 leads (3%). Horizontal steering was also used for avoiding adverse effects in 15 leads (9%), most of which were used to alleviate the symptoms of excessive stimulation of pyramidal tract. ConclusionsCurrent steering with the MICC directional lead was actually utilized in STN-DBS to explore more precise control of motor symptoms and also useful to avoid stimulation-induced adverse effect. Current steering is especially used in the later period after introduction of DBS.

Sex- and age-specific respiratory alterations induced by prenatal exposure to the cannabinoid receptor agonist WIN 55,212-2 in rats.

Cannabis legalization has risen in many countries, and its use during pregnancy has increased. The endocannabinoid system is present in the CNS at early stages of embryonic development, and regulates functional brain maturation including areas responsible for respiratory control, data on the influence of external cannabinoids on the development of the respiratory system and possible consequences during postnatal life are limited. We evaluated the effects of prenatal exposure to synthetic cannabinoid (WIN 55,212-2 [WIN], 0.5 mg·kg-1 ·day-1 ) on the respiratory control system in neonatal (P0, P6-7 and P12-13) and juvenile (P27-28) male and female rats. WIN administration to pregnant rats interfered sex-specifically with breathing regulation of offspring, promoting a greater sensitivity to CO2 at all ages in males (except P6-7) and in juvenile females. An altered hypoxic chemoreflex was observed in P0 (hyperventilation) and P6-7 (hypoventilation) males, which was absent in females. Along with breathing alterations, brainstem analysis showed an increase in the number of catecholaminergic neurons and cannabinoid receptor type 1 (CB1 ) and changes in tissue respiration in the early males. A reduction in pulmonary compliance was observed in juvenile male rats. Preexposure to WIN enhanced spontaneous apnoea and reduced the number of serotoninergic (5-HT) neurons in the raphe magnus nucleus of P0 females. These data demonstrate that excess stimulation of the endocannabinoid system during gestation has prolonged and sex-specific consequences for the respiratory control system.

INTEGRATIVE AND BIOCHEMICAL PARAMETERS IN RATS IN THE SIMULATION OF DOXORUBICIN CHRONIC HEART FAILURE AND DURING THE USE OF Β-ADRENERGIC BLOCKERS

β-adrenergic blockers have been actively used in the treatment of heart failure, which relieve excessive sympathetic stimulation of the myocardium, reduce calcium overload of cardiomyocytes, reduce the heart's oxygen demand, inhibit lipid peroxidation and stabilize cell membranes, have an antiarrhythmic effect. The aim: to compare efficiency of various drugs with new potential "Hypertril" in the conditions of modeling doxorubicin chronic heart failure (CHF) to improve parameters. Objective: CHF was modeled on 85 white outbred rats weighing 190–220g by administering doxorubicin at a cumulative dose of 15 mg/kg. Material and metods: Nebivalol, Carvedilol, Bisoprolol, Metoprolol and Hypertril were administered intragastrically once a day in the form of a suspension of 1% starch mucus for 30 days after a 14-day administration of doxorubicin. To determine damage, we used the solid-phase immunosorbent sandwich ELISA method, enzyme immunoassay and the immunoturbodimetric method. Result and discussion: Administration of Hypertril to rats with CHF led to a decrease in the blood of the main molecular markers of CHF to the values of intact animals, which indicated its significant cardioprotective effect in comparison with other drugs. Hypertril reduces manifestations of mitochondrial dysfunction, protects the myocardium and positively affects the morphological and functional parameters of cardiomyocytes, inhibits apoptosis

Bilayer Actuator with Overload Protection on the Basis of Semicrystalline Polyurethane.

Response to external stimuli plays a significant role in the environmental adaptation of living matters and intelligent devices. Most stimulus-response systems in nature can respond to appropriate stimuli, and inhibit the response under excessive stimuli, such as excessive heat or water, which could be called overload protection. However, even though various responsive materials have been developed for different stimuli, most of them are not protective against the overload stimuli. In this work, we have designed a bilayer actuator based on semicrystalline polyurethane, which can respond differently to proper stimuli and excessive stimuli, i.e., water. This actuator could bend gradually under the proper stimulation of water, but would straighten and even bend reversely with excessive stimulation. The mechanism behind the reversible and adjustable actuator with overload protection has been investigated both experimentally and theoretically, and the competition between dynamic factors and thermodynamic stability in the swelling process is considered the main cause. This article is protected by copyright. All rights reserved.

Downregulation of HbFPS1 affects rubber biosynthesis of Hevea brasiliensis suffering from tapping panel dryness.

Tapping panel dryness (TPD) is a century-old problem that has plagued the natural rubber production of Hevea brasiliensis. TPD may result from self-protective mechanisms of H. brasiliensis in response to stresses such as excessive hormone stimulation and mechanical wounding (bark tapping). It has been hypothesized that TPD impairs rubber biosynthesis; however, the underlying mechanisms remain poorly understood. In the present study, we firstly verified that TPD-affected rubber trees exhibited lower rubber biosynthesis activity and greater rubber molecular weight compared to healthy rubber trees. We then demonstrated that HbFPS1, a key gene of rubber biosynthesis, and its expression products were downregulated in the latex of TPD-affected rubber trees, as revealed by transcriptome sequencing and iTRAQ-based proteome analysis. We further discovered that the farnesyl diphosphate synthase HbFPS1 could be recruited to small rubber particles by HbSRPP1 through protein-protein interactions to catalyze farnesyl diphosphate (FPP) synthesis and facilitate rubber biosynthesis initiation. FPP content in the latex of TPD-affected rubber trees was significantly decreased with the downregulation of HbFPS1, ultimately resulting in abnormal development of rubber particles, decreased rubber biosynthesis activity, and increased rubber molecular weight. Upstream regulator assays indicated that a novel regulator, MYB2-like, may be an important regulator of downregulation of HbFPS1 in the latex of TPD-affected rubber trees. Our findings not only provide new directions for studying the molecular events involved in rubber biosynthesis and TPD syndrome and contribute to rubber management strategies, but also broaden our knowledge of plant isoprenoid metabolism and its regulatory networks.

Гиперпластические процессы эндометрия у пациенток с хронической болезнью почек: выбор тактики ведения

This article provides a literature review demonstrating modern paradigms concerning etiology, pathogenesis and management of endometrial hyperplasia processes in female patients with chronic kidney disease (CKD). Endometrial hyperplasia (EH) is a pathological process with various phenotypic cell changes and a characteristic predominance of glands over the stromal and epithelial components in the endometrium. Untimely diagnosis and treatment of EH can cause the pathology progression and the development of endometrium malignant transformation. Endometrial cancer (EC) refers to one of the most common malignant tumor forms of the female reproductive system, and EH, as a rule, is its precursor. In the gynecological morbidity structure, EH is 10 to 55%, and its incidence is steadily increasing. EH occurs as a result of excessive estrogen stimulation, when it is not compensated by the progesterone action. In addition, patients with CKD develop "immunosuppressive states" due to the use of various types of renal replacement therapy (hemodialysis, peritoneal dialysis, taking immunosuppressive drugs in patients with kidney transplant). Every year there are more and more such female patients. Over the past decade, there has been no reference in the Russian literature concerning a systematic approach to the diagnosis and treatment of EH in female patients with CKD. Considering that these were female patients of the reproductive period to a greater extent, who wanted to perform the childbearing function in the future, therefore, this problem is very relevant for the world medical community. KEYWORDS: endometrial hyperplasia, abnormal uterine bleeding, chronic kidney disease, hemodialysis, kidney transplant, peritoneal dialysis, immunosuppression. FOR CITATION: Dobrokhotova Yu.E., Lysenko M.A., Grabovsky V.M., Shevchenko N.A., Zapolskaya N.P. Endometrial hyperplasia process in female patients with chronic kidney disease: the choice of treatment tactics. Russian Journal of Woman and Child Health. 2023;6(4):380–384 (in Russ.). DOI: 10.32364/2618-8430-2023-6-4-9.

Integration of an intraoral scan and a conventional impression for fabricating complete dentures for a patient with flabby tissues

Inflammatory movable tissues in the maxillary anterior region are the result of excessive stimulation of the anterior alveolar ridge, as the maxillary denture habitually rotates anteriorly and upward during mastication. The pressure required for a functional impression makes it difficult to obtain the accurate anatomy of the inflamed mucosal tissues. An intraoral scanner can be used to record the movable tissues in an immobile state. However, for removable dentures, the oral scanner is limited by the difficulty in evaluating the denture borders or the posterior palatal seal area accurately. The fabrication of a complete denture by combining the use of an oral scanner to capture an anatomic impression without exerting pressure on the maxilla, including the movable tissues, and a traditional functional impression using the closed-mouth technique is described.

The Role of Immune Mechanisms, Inflammatory Pathways, and Macrophage Activation Syndrome in the Pathogenesis of Hemophagocytic Lymphohistiocytosis.

This review article describes the pathophysiology of hemophagocytic lymphohistiocytosis (HLH). The condition is characterized by excessive stimulation of inflammatory cytokines, lymphocytes, and macrophages, leading to hyperinflammatory disorder with immune dysfunction. The main clinical and diagnostic features include fever ≥38.5°C, splenomegaly, hyperferritinemia, cytopenia, hypofibrinogenemia, hemophagocytosis on the bone marrow, low or absent of natural killer (NK) cell activity, and elevated soluble CD25. Various immunological and inflammatory mechanisms are involved in the pathogenesis of HLH. Moreover, the condition can result in multisystem organ failure, contributing to the high mortality rate in hospital settings. A thorough literature search was conducted by collecting data from multiple articles published on PubMed, Medline, and Google Scholar. The article discusses the cellular and molecular pathways that lead to HLH. Due to the high rate of morbidity and mortality, early diagnosis needs to be established. More research pertaining to molecular biology, immunology, and the genetics of HLH is needed to explore the effective management and treatment of this rare disorder.

“I Don’t Think I Have an Attention Span for Real Life Anymore”: Excessive Stimulation, Sense of Meaninglessness, and Boredom in Sam Levinson’s Euphoria

The article analyzes selected episodes from the HBO teen drama Euphoria (2019–) and argues that it both reproduces and comments on the boredom of satiety. Directed by Sam Levinson, the show has been repeatedly praised for its dynamic aesthetic. The swirling kaleidoscope of scenes and images in Euphoria mimics the contemporary immersion in social media and digital representations. The frenetic visual pace of the show’s regular episodes, however, is broken with slow-paced and seemingly boring special episodes. Yet, I will show that their focus on in-person, engaged conversations is a refreshing break from the boredom of satiety and serves as an antidote to the loss of meaningfulness experienced by the teenage protagonists.

Parameters of spontaneous and benzene-induced cell death of spermatozoa under in vitro conditions in male employees of an oil production enterprise with impaired fertility

Introduction. Every year there is a steady increase in the frequency of male infertility both in Russia and in other countries of the world with the concomitant low efficiency of recognizing the causes of its idiopathic forms. The explanation for the increase in infertility are: harmful production factors, including chemical ones, progressive deterioration of the quality of the urban environment, which has a significant impact on the reproductive health of the urbanized population, recurring economic crises that negatively affect the human psyche, mass consumption of substandard products and medicines. These factors, primarily chemical production, negatively affect the reproductive system, including the differentiation of male germ cells, as a cause of fertility disorders. The aim of the study to consider in vitro spontaneous and benzene-induced features of sperm apoptosis in male oil industry workers with impaired fertility. Materials and methods. We have conducted an experimental study of biological material (ejaculate) in 50 men with reproductive disorders (26-49 years old), employees of an oil production enterprise. To conduct the experiment in vitro, the researchers used seminal fluid samples. A benzene solution at a concentration of 0.001 micrograms/ml was used as an in vitro induction factor (selected experimentally). We divided the analyzed samples into 2 equal parts to study the spontaneous and benzene-induced expression of apoptosis markers (CD25+, CD95+, bax, p53, Annexin V-FITC and Propidium Iodide, Caspasa-3), which the researchers determined by flow cytometry. Results. There were no significant deviations of intracellular markers of sperm apoptosis (bax, p53, Annexin V-FITC+7AAD+, Annexin V-FITC+7AAD-, Caspasa-3), however, experts observed differences in the expression of CD95+ and CD25+ membrane proteins by 20% and 10% compared to the spontaneous level, which is associated with the acceleration of the events of programmed sperm death (p<0.05). Conclusion. The results obtained in an in vitro experiment on modeling the apoptosis program by induction with hapten (benzene) showed that violations of sperm cell death are associated with overexpression of the key receptor for triggering apoptosis CD95, as well as a marker of early activation of CD25 cells, which reflects benzene modification of the cell death scenario along the path of its excessive stimulation.

Cardiac β-Adrenoceptor Signaling: The New Insight on An Old Target in the Therapy of Cardiovascular Disease

Review Cardiac β-Adrenoceptor Signaling: The New Insight on An Old Target in the Therapy of Cardiovascular Disease Ying Song 1, Anthony Yiu-Ho Woo 2,*, Yan Zhang 3,4,*, and Ruiping Xiao 5,6,7,8 1 Center of Basic Medical Research, Institute of Medical Innovation and Research, Peking University Third Hospital, Beijing, 100191, China. 2 School of Life Sciences and Biopharmaceutics, Shenyang Pharmaceutical University, Shenyang, 110016, China. 3 Institute of Cardiovascular Sciences and Key Laboratory of Molecular Cardiovascular Sciences, School of Basic Medical Sciences, Ministry of Education, Peking University Health Science Center, Beijing, 100191, China. 4 Beijing Key Laboratory of Cardiovascular Receptors Research, Peking University, Beijing, 100191, China. 5 State Key Laboratory of Membrane Biology, Institute of Molecular Medicine, College of Future Technology, Peking University, Beijing, 100871, China. 6 Peking-Tsinghua Center for Life Sciences, Peking University, Beijing, China. 7 Beijing City Key Laboratory of Cardiometabolic Molecular Medicine, Peking University, Beijing, 100871, China. 8 PKU-Nanjing Joint Institute of Translational Medicine, Nanjing, 210000, China. * Correspondence: yiuhowoo@syphu.edu.cn (Anthony Yiu-Ho Woo), Tel.: +86-24-23986375; zhangyan9876@pku.edu.cn (Yan Zhang), Tel.: +86-10-82805945. Received: 19 October 2022 Accepted: 28 October 2022 Published: 21 December 2022 Abstract: A variety of G protein-coupled receptors (GPCRs) are involved in the regulation of cardiovascular function. The β-adrenoceptors (β-ARs), with three subtypes, are the dominant receptor species in the heart, in which the β1-AR and the β2-AR are considered functional. Stimulation of the β-ARs produces myocardial inotropy via activation of the Gs-cAMP-PKA signaling cascade. Prolonged stimulation of the β1-AR is cardiac harmful because the stimulated β1-AR couples only to Gs proteins and it mediates a cardiotoxic signal. On the other hand, the β2-AR couples dually to both Gs and Gi proteins and the β2-AR-Gi pathway is antiapoptotic. The activated Gi signal also counteracts the β-AR-Gs-promoted positive inotropic effect. Other key players in cardiac β-AR signaling include Ca2+/calmodulin-dependent protein kinases (CaMKs), GPCR kinases (GRKs), β-arrestins and phosphodiesterases. During heart failure, excessive sympathetic stimulation results in the activation of the cardiotoxic β1-AR-CaMKIIδ pathway and the upregulation of GRK2 and Gi in the heart. GRK2 promotes the desensitization of β-ARs and enhances a β2-AR-mediated Gi signaling. These signal transduction processes accompanying the downregulation of the β1-AR are involved in cardiac dysfunction, maladaptive cardiac remodeling, and the progression of chronic heart failure. β-Blockers are widely used in the treatment of cardiovascular disease. They have established their position as one of the “four pillars of heart failure” thirty years ago. In the present review, we provide an overview of the recent progress in the basic research of GPCRs focusing on cardiac β-AR signal transduction.

Excessive audio-visual stimulation leads to impaired social behaviour with an effect on amygdala: Early life excessive exposure to digital devices in male rats.

Today, the effect of extreme early-life exposure to digital devices is suggested as a risk factor for neurodevelopmental disorders. However, the multitude of factors that influence brain development with subsequent behavioural abnormalities have not been fully elucidated. Herein, we simulated extreme early-life exposure to digital devices in rats by audio and visual stimulation and investigated its effects on autism-related behaviours and brain structural alteration. Male rat pups were exposed to excessive audio-visual stimulation (EAVS) from PND (post-natal day) 12 to PND 35, with and without maternal separation (MS). Autism-related behaviours including abnormal sociability, stereotype behaviours, anxiety and locomotor dysfunction were tested at PND 42. Brain structural alternation was examined by considering the amygdala, mPFC (medial prefrontal cortex) and hippocampal regions while performing 3D quantitative stereological analysis. We found that EAVS led to social behaviour deficit and higher locomotion in rats, which were associated with increases in the number of neurons and volume of the amygdala. We also showed that MS did not exaggerate the effect of extreme sensory stimulation on behaviour and the structure of the brain. This study proposed EAVS in rats as an animal model of early exposure to digital devices for investigating possible neurobiological alternations underlying autistic-like behaviours with an emphasis on the amygdala area.

PSUN369 Glucagonoma-Associated Dilated Cardiomyopathy in a Young Female: A Case Report

Abstract Background Dilated cardiomyopathy has been reported in patients with glucagonoma. Since glucagon increases myocardial cAMP levels independent of beta adrenoreceptor blockade, thereby increasing heart rate and cardiac output, chronic excessive glucagon stimulation of the heart may lead to cardiomyopathy (Chang-Chretien, 2004). Clinical Case A 26 year old female presented with a 2-year history of palpable epigastric mass, vomiting and weight loss. Abdominal CT showed a heterogeneously enhancing, lobulated pancreatic head-body mass measuring 6.7×6.1×9.9 cm and a hypo-enhancing nodule in hepatic segment IVb, worrisome for metastasis. Endoscopy-guided FNAB of the pancreatic mass revealed a well-differentiated pNET, Grade 3. Chromogranin and synaptophysin stains were positive, Ki-67 index was 33.6%. She was lost to follow-up. After 4 months, she was admitted due to 1 week history of increased vomiting episodes up to 10x daily and abdominal discomfort with 2 day history of incomprehensible speech and right-sided weakness. On examination, she was weak-looking, tachycardic (114 bpm), underweight (BMI 17.45 kg/m2) and with palpable, hard, non-tender epigastric mass measuring 10×7 cm. She also had hyperpigmented patches on both legs initially manifesting as intermittent oozing excoriations over the past 2 years. Cranial MRI revealed subacute CVD infarct. Anticoagulation was given. On the second day, she started having diarrheal episodes. Supportive management was given. Serum glucagon was markedly elevated (>25,000 pg/mL, normal <80). Serum PP (6562 pg/mL, normal <228) and gastrin (621 pg/mL, normal 13-115) were elevated. Serum VIP (<50 pg/mL, normal <75) was normal. Further investigations showed prediabetes (FBS 112 mg/dL, HbA1c 5.7%) and normocytic, normochromic anemia. Screening for MEN1 was unremarkable. On the third day, she had progression of slurred speech and right-sided weakness. Cranial MRI revealed acute lacunar infarcts. As part of hypercoagulability workup, 2D-Echocardiogram showed depressed ejection fraction (20.9%), dilated LV with normal relative wall thickness, and global hypokinesia of the LV wall, confirming dilated cardiomyopathy. Carotid and Venous Duplex scans were normal. Anti-heart failure regimen was initiated. Due to her current neurologic, cardiac and metabolic conditions, she cannot proceed with surgery and chemotherapy. She was given octreotide injection 30 mg every 4 weeks for 3 doses. Post-treatment, repeat abdominal CT and 2D-Echocardiogram showed no significant change. In the meantime, she had improved appetite and no recurrence of vomiting nor diarrhea. She denies palpitations and can better tolerate walking and climbing stairs. Conclusion We reported a rare case of glucagonoma in a young female with documented constellation of symptoms and complications associated with the syndrome, prominently including dilated cardiomyopathy. It is therefore recommended that cardiovascular evaluation should be initiated at the time of glucagonoma diagnosis for timely and appropriate management. Presentation: Sunday, June 12, 2022 12:30 p.m. - 2:30 p.m.

Successful Use of Continuous Erector Spinae Plane Blocks in a Patient With Variant Angina After Large Ventral Hernia Repair

Coronary artery spasm constitutes the primary underlying pathology of variant angina. Because provocation of coronary artery spasm may occur with both excess sympathetic and excess parasympathetic stimulation, patients with this disorder have extremely limited options for perioperative pain control. This is especially true for procedures involving extensive abdominal incision/manipulation. Whereas neuraxial analgesia might otherwise be appropriate in these cases, several studies have demonstrated that coronary artery spasm can occur as a result of epidural placement, and therefore, that this may not be an optimal choice for patients with variant angina. This report discusses the case of a patient with a preexisting diagnosis of variant angina who underwent an exploratory laparotomy with large ventral hernia repair and for whom continuous erector spinae plane blocks were successfully used as analgesic adjuncts without triggering coronary artery spasm.

The Proteomic and Transcriptomic Landscapes Altered by Rgg2/3 Activity in Streptococcus pyogenes.

Streptococcus pyogenes, otherwise known as Group A Streptococcus (GAS), is an important and highly adaptable human pathogen with the ability to cause both superficial and severe diseases. Understanding how S. pyogenes senses and responds to its environment will likely aid in determining how it causes a breadth of diseases. One regulatory network involved in GAS's ability to sense and respond to the changing environment is the Rgg2/3 quorum sensing (QS) system, which responds to metal and carbohydrate availability and regulates changes to the bacterial surface. To better understand the impact of Rgg2/3 QS on S. pyogenes physiology, we performed RNA-seq and tandem mass tag (TMT)-LC-MS/MS analysis on cells in which this system was induced with short hydrophobic peptide (SHP) pheromone or disrupted. Primary findings confirmed that pheromone stimulation in wild-type cultures is limited to the induction of operons whose promoters contain previously determined Rgg2/3 binding sequences. However, a deletion mutant of rgg3, a strain that endogenously produces elevated amounts of pheromone, led to extended alterations of the transcriptome and proteome, ostensibly by stress-induced pathways. Under such exaggerated pheromone conditions, a connection was identified between Rgg2/3 and the stringent response. Mutation of relA, the bifunctional guanosine tetra- and penta-phosphate nucleoside synthetase/hydrolase, and alarmone synthase genes sasA and sasB, impacted culture doubling times and disabled induction of Rgg2/3 in response to mannose, while manipulation of Rgg2/3 signaling modestly altered nucleotide levels. Our findings indicate that excessive pheromone production or exposure places stress on GAS resulting in an indirect altered proteome and transcriptome beyond primary pheromone signaling. IMPORTANCE Streptococcus pyogenes causes several important human diseases. This study evaluates how the induction or disruption of a cell-cell communication system alters S. pyogenes's gene expression and, in extreme conditions, its physiology. Using transcriptomic and proteomic approaches, the results define the pheromone-dependent regulon of the Rgg2/3 quorum sensing system. In addition, we find that excessive pheromone stimulation, generated by genetic disruption of the Rgg2/3 system, leads to stress responses that are associated with the stringent response. Disruption of stringent response affects the ability of the cell-cell communication system to respond under normally inducing conditions. These findings assist in the determination of how S. pyogenes is impacted by and responds to nontraditional sources of stress.

A Case Report of Hemophagocytic Lymph Histiocytosis in a Young Male

Hemophagocytic Lymph Histiocytosis (HLH) is a clinical syndrome affected by excessive immune stimulation and tissue hyperinflammation, which is relatively underdiagnosed because of its various clinical manifestations. This case described a young male whose body temperature measured at 39°C and only dropped briefly due to a fever reducer. He had a painless inflammation in the neck during the fever. Cold and stuffy nose emerged before the fever appeared. Moreover, stuffy nose caused snoring sleep. The patient also faced bleeding gums and nosebleeds. However, he did not experience body ache or weight loss. Various clinical tests, such as clinical chemistry laboratory tests, blood and bone marrow tests, and radiological tests were conducted. Clinical chemistry test revealed a decrease in albumin levels. Additionally, peripheral blood test showed a smear of microcytic hypochromic anemia, leukopenia and thrombocytopenia, while bone marrow examination showed a process of hem phagocytosis/metabolic disease. Furthermore, radiological tests showed no abnormalities.

Determinants of ventilatory inefficiency in transthyretin cardiac amyloidosis: The role of excessive ventilatory drive.

Background and objective: Along with impaired aerobic capacity, increased slope of the relationship between ventilation (VE) and pulmonary CO2 output (VCO2), i.e., VE-VCO2 slope is a common finding in patients with cardiac amyloidosis (CA), which suggests ventilatory inefficiency. Little is known about mechanisms leading to ventilatory inefficiency in CA patients. The purpose of this investigation was to examine the factors that underlie the abnormal ventilatory efficiency in transthyretin hereditary CA patients, such as excessive ventilatory drive, inability of pulmonary blood flow to increase adequately during exercise and excessive sympathetic stimulation, which are known mechanisms of VE-VCO2 slope increase. Methods: In this single-center retrospective observational study, consecutive patients (n = 41) with known familial transthyretin amyloidosis p.Val142Ile mutation carriers with confirmed cardiac phenotype were included. Results: Compared with CA patients without ventilatory inefficiency (VE-VCO2 slope < 36), patients with ventilatory inefficiency (VE-VCO2 slope ≥ 36) had increased inter-ventricular septum thickness, lower VO2 peak along with hyperventilation, and prolonged post-exercise heart rate recovery. By multivariate analysis, only excess of minute-ventilation at anaerobic threshold (β = 0.127; p = 0.011) remained an independent predictor of ventilatory inefficiency. Conclusion: Our data suggest that high ventilatory stimulation during exercise leading to hyperventilation is the main determinant of ventilatory inefficiency in hereditary transthyretin cardiac amyloidosis patients. This novel finding helps to better understand the mechanism of exercise intolerance in these patients where physiological limitation may be related to both heart dysfunction and abnormal pulmonary response.