Physiological Changes Research Articles

Diagnostic considerations and orthodontic treatment approaches of adolescents with the dentoalveolar form of class II malocclusion

Relevance. Class II malocclusion (distal occlusion) is a common pathology of the maxillofacial region in the sagittal plane and is one of the most prevalent malocclusions. Studies confirm that Class II malocclusion in adolescents exhibits significant variability, prompting the development of various treatment approaches using both removable and fixed orthodontic appliances. The challenges of adolescence include concurrent physiological and psychological changes, which can complicate the treatment process.Purpose. To enhance the effectiveness of orthodontic treatment for patients with the dentoalveolar form of Class II malocclusion by utilizing the Rotation-Torque Index (RTI).Material and methods. A study was conducted on 49 residents of St. Petersburg with physiological occlusion types, who were included in the control group. The main group comprised 95 adolescents (aged 12-18) with the dentoalveolar form of Class II malocclusion classified into three levels of severity, based on the proposed working prognostic classification.Results. A new method was developed to calculate a coefficient that describes the relationship between the position of the upper and lower jaws and the torque of the central incisors. This coefficient helps predict treatment outcomes and guides the selection of the optimal treatment strategy. The Rotation-Torque Index (RTI) was introduced to quantify the relationship between the position of the jaws in the skull (SNA, SNB) and the inclination of the central incisors of the upper jaw relative to the nasal line (NL) and those of the lower jaw relative to the mandibular line (ML).Conclusions. Based on the Rotation-Torque Index (RTI), a working prognostic classification and treatment strategies for patients with the dentoalveolar form of Class II malocclusion were proposed.

Prevalance of Lumbo-Sacral Dysfunction in Multiparous Women

Background: In pregnancy there is progressive anatomical, physiological, psychological and biochemical changes at various trimesters. These alterations might induce low back pain or lower pelvic discomfort during pregnancy or after delivery, restricting normal movement and causing misery. Objective: To identify the prevalence of lumbosacral dysfunction in women who have had two or more pregnancies. Methods: The study was an observational which includes 100 multiparrous women in and around Karad and the female residing in urban and rural areas were taken and the consent form were signed by the participants were explained regarding the test and then it was undertaken. The test performed was Specific lumbar spine torsion test. Result: On the basis of this study 58% women showed dysfunction of lumbosacral joint and 48 % have excellent joint conditions the women of both urban and rural areas were included. According to the number of gravida the women were having issues. Conclusion: The study concluded that there is prevalence of lumbo-sacral joint dysfunction is highly significant in multiparous pregnant women.

Examination of Exercise Physiological Traits According to Usage Grade of National Forest Trails

Forest trail difficulty levels must be investigated to promote their safe usage. However, exercise-based physiological changes are difficult to estimate in a forest environment. Hence, studies comparing indoor and outdoor environmental activities are required. We aimed to investigate the physiological traits associated with different usage grades of national forest trails in the Republic of Korea. We conducted both field and indoor experiments to measure different variables of 20 healthy participants aged 40–50 years to evaluate the exercise intensity and physiological effects of hiking on these trails. Significant variations in physiological responses were observed based on trail difficulty, with the highest heart rate and energy expenditure recorded during the most challenging uphill segments. Specifically, the heart rate increased from 115.4 ± 13.7 bpm in easy segments to 140.3 ± 15.6 bpm in difficult segments, whereas energy expenditure ranged from 404.1 ± 112.2 kcal/h to 518.1 ± 131.0 kcal/h. This study highlights the importance of considering both objective trail difficulty and users’ physiological reactions, including perceived exertion, to enhance user safety and optimize the health benefits of national forest trails. These findings provide essential data for developing comprehensive exercise programs and improving the national forest trail usage grade system.

Active CNS delivery of oxycodone in healthy and endotoxemic pigs

BackgroundThe primary objective of this study was to advance our understanding of active drug uptake at brain barriers in higher species than rodents, by examining oxycodone brain concentrations in pigs.MethodsThis was investigated by a microdialysis study in healthy and endotoxemic conditions to increase the understanding of inter-species translation of putative proton-coupled organic cation (H+/OC) antiporter-mediated central nervous system (CNS) drug delivery in health and pathology, and facilitate the extrapolation to humans for improved CNS drug treatment in patients. Additionally, we sought to evaluate the efficacy of lumbar cerebrospinal fluid (CSF) exposure readout as a proxy for brain unbound interstitial fluid (ISF) concentrations. By simultaneously monitoring unbound concentrations in blood, the frontal cortical area, the lateral ventricle (LV), and the lumbar intrathecal space in healthy and lipopolysaccharide (LPS)-induced inflammation states within the same animal, we achieved exceptional spatiotemporal resolution in mapping oxycodone transport across CNS barriers.ResultsOur findings provide novel evidence of higher unbound oxycodone concentrations in brain ISF compared to blood, yielding an unbound brain-to-plasma concentration ratio (Kp,uu,brain) of 2.5. This supports the hypothesis of the presence of the H+/OC antiporter system at the blood–brain barrier (BBB) in pigs. Despite significant physiological changes, reflected in pig Sequential Organ Failure Assessment, pSOFA scores, oxycodone blood concentrations and its active net uptake across the BBB remained nearly unchanged during three hours of i.v. infusion of 4 µg/kg/h LPS from Escherichia coli (O111:B4). Mean Kp,uu,LV values indicated active uptake also at the blood-CSF barrier in healthy and endotoxemic pigs. Lumbar CSF concentrations showed minimal inter-individual variability during the experiment, with a mean Kp,uu,lumbarCSF of 1.5. LPS challenge caused a slight decrease in Kp,uu,LV, while Kp,uu,lumbarCSF remained unaffected.ConclusionsThis study enhances our understanding of oxycodone pharmacokinetics and CNS drug delivery in both healthy and inflamed conditions, providing crucial insights for translating these findings to clinical settings.

The ameliorating effects of adipose-derived stromal vascular fraction cells on blue light-induced rat retinal injury via modulation of TLR4 signaling, apoptosis, and glial cell activity.

Blue light (BL)-induced retinal injury has become a very common problem due to over exposure to blue light-emitting sources. This study aimed to investigate the possible ameliorating impact of stromal vascular fraction cells (SVFCs) on BL-induced retinal injury. Forty male albino rats were randomly allocated into four groups. The control group rats were kept in 12-h light/12-h dark. Rats of SVFC-control as the control group, but rats were intravenously injected once by SVFCs. Rats of both the BL-group and BL-SVFC group were exposed to BL for 2 weeks; then rats of the BL-SVFC group were intravenously injected once by SVFCs. Following the BL exposure, rats were kept for 8 weeks. Physical and physiological studies were performed; then retinal tissues were collected for biochemical and histological studies. The BL-group showed physical and physiological changes indicating affection of the visual function. Biochemical marker assessment showed a significant increase in MDA, TLR4 and MYD88 tissue levels with a significant decrease in TAC levels. Histological and ultrastructural assessment showed disruption of the normal histological architecture with retinal pigment epithelium, photoreceptors, and ganglion cell deterioration. A significant increase in NF-κB, caspase-3, and GFAP immunoreactivity was also detected. BL-SVFC group showed a significant improvement in physical, physiological, and biochemical parameters. Retinal tissues revealed amelioration of retinal structural and ultrastructural deterioration and a significant decrease in NF-κB and caspase-3 immunoreactivity with a significant increase in GFAP immunoreaction. This study concluded that SVFCs could ameliorate the BL-induced retinal injury through TLR-4/MYD-88/NF-κB signaling inhibition, regenerative, anti-oxidative, and anti-apoptotic effects.

Thrombocytopenia as a Prognostic Marker in Patients with Acute Encephalitis at a Tertiary Care Center in Northern India.

Acute encephalitis (AE) is associated with a high burden of mortality and permanent disability and has a spectrum of underlying etiologies. The prognosis of encephalitis is difficult and almost all the patients seem to be at a high risk of poor outcomes. A number of physiological changes take place during encephalitis and have been evaluated for their prognostic value. Platelet count, which has been recognized as a surrogate prognostic marker in various viral illnesses, has recently been recognized to have a prognostic value in AE too. In the present study, we attempted to study the role of thrombocytopenia in the prognosis of AE. Total of 98 cases based on clinical, cerebrospinal fluid, and radiological profiles consistent with the diagnosis of AE were enrolled in the study. A clinical profile was noted, and platelet count was assessed. Thrombocytopenia was defined as platelet count <150,000/mm3. Platelet count 100,000-150,000, 50,000-99,999, and <50,000/mm3 were considered mild, moderate, and severe thrombocytopenia. The underlying etiology was explored, and patients were followed till discharge/outcome. The outcome was noted in terms of the Modified Rankin score (MRS). MRS 0-2 was considered good, 3-4 fair, and 5-6 as poor outcome. The mean age of patients was 34.06 ± 18.76 years. Majority of patients were women (54.1%). Prevalence of thrombocytopenia was 75.5%. A total of 34 (45.9%) had mild, 30 (40.5%) had moderate, and 10 (13.5%) had severe thrombocytopenia. Acute viral encephalitis (unclassified) was the most common etiology (33.7%), followed by scrub meningoencephalitis (24.5%) and Japanese encephalitis (12.2%), respectively. Good, fair, and poor outcomes were noted in 48 (49%), 21 (21.4%), and 29 (29.6%) cases. On univariate analysis, no significant association of poor outcome was seen with age, sex, duration of fever, and mechanical ventilation need (P > 0.05). Low Glasgow Coma Scale (GCS), splenomegaly, low platelet count, and Japanese encephalitis virus/scrub typhus etiologies were found to be significantly associated with poor outcomes (P < 0.05). Thrombocytopenia compared to normal platelet count and severe thrombocytopenia compared to mild and moderate thrombocytopenia were significantly associated with poor outcomes (P < 0.05). On multivariate analysis, GCS <8 (odds ratio [OR] =4.52; 95% confidence interval [CI] =1.56-13.20) and thrombocytopenia (OR = 11.92; 95% CI = 1.38-103.32) emerged as independent predictors of poor outcome. The findings of the study showed that low GCS and thrombocytopenia could be used as predictors of poor outcomes in AE cases.

The role of physical activity, diet, and stress management in maternal and infant health during pregnancy

Introduction and aim of the study: During pregnancy, significant physiological, hormonal and circulatory changes occur that affect both the health of the mother and the child. Therefore, it is important for the mother to maintain physical activity, a healthy diet, and reduce stress to prevent complications and health problems for the mother and the child. Material and Methods: The Pubmed database was searched. The criteria for qualifying the article for the review were the following keywords: pregnancy, exercise, rehabilitation, nutrition during pregnancy, postpartum depression, atopy, stress, asthma. 30 articles from 2002-2023 were analyzed. Description of the state of knowledge: Regular physical activity during pregnancy brings many benefits such as reducing the risk of complications during childbirth, postpartum depression and helps to maintain a healthy body weight. Diet also has an impact on the health of both mother and baby. It should be balanced, providing the necessary nutrients and taking into account the mother's caloric needs. It is very important to reduce stress due to its negative impact on the mother and child. Summary: Physical activity and a healthy diet directly affect the course of pregnancy and the health of the fetus and baby. Exercise prevents pregnancy complications and other diseases, and maternal nutritional status is critical for fetal growth. During pregnancy, women are exposed to stress, which can be the cause of chronic mental disorders. Depression is the most common mental illness that occurs during pregnancy, which is influenced by various factors. In addition, maternal stress has a negative impact on the child's health, potentially increasing the risk of a number of atopic and non-atopic diseases.

Influence of Foliar Application of Nanoparticles on Low Temperature Resistance of Rice Seedlings

Chilling stress, a common abiotic factor, adversely affects the growth and biomass of rice seedlings during the early stages, ultimately reducing the yield. Effective strategies to mitigate these negative impacts are essential for improving rice productivity. The application of nanotechnology in agriculture, particularly nanoparticles (NPs), has shown a promising effect in alleviating chilling stress in plants. This study evaluates the effects of various nanoparticles, ZnO (0, 50, 100, and 200 mg/L), Fe2O3 (0, 50, 75, and 100 mg/L), TiO2 (0, 50, 75, and 100 mg/L), and CeO2 (0, 50, 75, and 100 mg/L) on the chilling resistance with one control (a water spray) under a normal temperature. Four rice cultivars: LLY-7108 and XZX-6 (Low-temperature-tolerant), and LLY-32 and ZJZ-17 (Low-temperature-susceptible) were tested in this experiment. Rice seedlings were subjected to low temperature conditions (12 h light 14 °C/12 h dark, at 10 °C) for five days, followed by seven days of recovery. The results of this study demonstrate that NPs significantly enhanced seedling height fresh/dry weight and root length compared to untreated controls under chilling stress. NP treatment also reduced the reactive oxygen species (ROS), malondialdehyde (MDA), and proline content, while enhancing superoxide dismutase (SOD), peroxidase (POD), and catalase (CAT) activities, thereby mitigating oxidative damage. The four rice varieties exhibited clear signs of rapid growth recovery and positive physiological changes due to NPs’ application. Among the tested cultivars, LLY-7108 showed the most substantial recovery and physiological responses, while ZJZ-17 exhibited the least. The findings of this study indicate that the foliar application of ZnO (100 mg/L), Fe2O3 (50 mg/L), TiO2 (50 mg/L), and CeO2 (75 mg/L) NPs effectively mitigates chilling stress in rice seedlings, likely by enhancing the antioxidant enzymatic activity while reducing the oxidative damage. This study highlights the potential of NPs as effective agents in reducing the adverse effects of chilling stress on rice.

Evaluation of Cross-Linked Actin Networks (CLANs) in Human Trabecular Meshwork Cells and Tissues.

Elevated intraocular pressure (IOP) is a major risk factor for the development and progression of glaucoma, the leading cause of irreversible vision loss and blindness. An overall increase in resistance to aqueous humor outflow causes sustained elevation in IOP. Glaucomatous insults in the aqueous humor outflow pathway, including the trabecular meshwork (TM), precede such chronic physiological changes in IOP. These insults include ultrastructural changes with excessive extracellular matrix deposition and actin cytoskeletal reorganization that leads to pathological stiffening of the ocular tissues. One of the most common cytoskeletal changes associated with TM tissue stiffness in glaucoma is the increased prevalence of cross-linked actin networks (CLANs) in cells of the trabecular meshwork (TM) and lamina cribrosa (LC). In glaucomatous cells, rearrangement of linear actin stress fibers leads to formation of polygonal arrays within the cytoplasm, resembling a geodesic dome-like structure, that we identified as CLANs. In addition to increased amounts of CLANs in POAG TM cells and tissues, we also discovered that glucocorticoid (GC) and TGFβ2 signaling pathways associated with the development of ocular hypertension (OHT) and glaucoma also induced CLANs in the TM. Despite a clear association, we are yet to completely understand the mechanisms involved in CLAN formation and their direct relevance to disease pathology. In this chapter, we will describe methods to identify and characterize CLANs using fluorescent microscopy in primary TM cell cultures, ex vivo perfusion cultured human anterior segments, and in situ in human donor eyes.

Microbiological and Haemato-biochemical Studies in Canine Pyometra

Background: Canine pyometra, is a pathological condition that results in the accumulation of purulent exudate in the uterus due to hormonal imbalance in female dogs. This is the most prevalent hormonally mediated reproductive disorder and life threatening disease of intact female dogs. The objective of the present study was to assess the physiological, haematological and biochemical changes and isolate the pathogenic microorganism present in the uterus of pyometra bitches. Methods: This study was carried out in ten bitches with a history of lethargy, depression, in appetence, polydipsia, occasional vomiting and vaginal discharge presented for treatment at the Veterinary Poly Clinic, Coimbatore, Tamil Nadu. The disease was diagnosed by history, clinical signs, physical examination, imaging techniques haematology and biochemical study. The involvement of the pathogenic organism was confirmed by microbial examination of the pus-filled uterus after the ovariohysterectomy. Result: The result showed that physiological parameters rectal temperature, heart rate and respiration rate were increased in pyometra affected dog than healthy one. The haematological parameters of red blood cell count, haemoglobin and packed cell volume were decreased in pyometra affected dogs than healthy dogs. Leukocytosis, neutrophilia, lymphocytosis, monocytosis and eosinophilia condition also observed in pyometra affected dogs. Biochemically, increased Blood urea nitrogen (BUN) creatinine and hyperprotenimia were observed in pyometra dogs. Increased activity of hepatic enzyme Alanine transaminase (ALT), Aspartate aminotransferase (AST) and Alkaline phosphatase (ALP) were also observed in pyometra dogs. The major pathogenic microorganisms involved in pyometra are Escherichia coli (40.25%), Staphylococcus (20.46%), Streptococcus (20.32%), Pseudomonas (6.41%), Proteus (6.32%) and Pasteurella (6.24%). Thus the dogs with pyometra show significant changes in physiological, haematological, biochemical parameters and growth of pathogenic microorganism in uterine fluid were the important indications of pyometra affected dogs.

Ionising radiation exposure-induced regulation of selected biomarkers and their impact in cancer and treatment.

Ionising radiation (IR) is a form of energy that travels as electromagnetic waves or particles. While it is vital in medical and occupational health settings, IR can also damage DNA, leading to mutations, chromosomal aberrations, and transcriptional changes that disrupt the functions of certain cell regulators, genes, and transcription factors. These disruptions can alter functions critical for cancer development, progression, and treatment response. Additionally, IR can affect various cellular proteins and their regulators within different cell signalling pathways, resulting in physiological changes that may promote cancer development, progression, and resistance to treatment. Understanding these impacts is crucial for developing strategies to mitigate the harmful effects of IR exposure and improve cancer treatment outcomes. This review focuses on specific genes and protein biomarkers regulated in response to chronic IR exposure, and how their regulation impacts disease onset, progression, and treatment response.

Mapping the physiological changes in sleep regulation across infancy and young childhood.

Sleep patterns in infancy and early childhood vary greatly and change rapidly during development. In adults, sleep patterns are regulated by interactions between neuronal populations in the brainstem and hypothalamus, driven by the circadian and sleep homeostatic processes. However, the neurophysiological mechanisms underlying the sleep patterns and their variations across infancy and early childhood are poorly understood. We investigated whether a well-established mathematical model for sleep regulation in adults can model infant sleep characteristics and explain the physiological basis for developmental changes. By fitting longitudinal sleep data spanning 2 to 540 days after birth, we inferred parameter trajectories across age. We found that the developmental changes in sleep patterns are consistent with a faster accumulation and faster clearance of sleep homeostatic pressure in infancy and a weaker circadian rhythm in early infancy. We also find greater sensitivity to phase-delaying effects of light in infancy and early childhood. These findings reveal fundamental mechanisms that regulate sleep in infancy and early childhood. Given the critical role of sleep in healthy neurodevelopment, this framework could be used to pinpoint pathophysiological mechanisms and identify ways to improve sleep quality in early life.

Глобальні виклики для систем соціальної підтримки: сутність, компонентні ознаки та особливості

The article is devoted to issues of global challenges for social support systems. The relevance of the study is determined by the growing role of global challenges in the socio-economic life of states. The purpose of the article is to analyze the specifics of global challenges characterizing modern social support systems, including the social support system of Ukraine. The scientific novelty of the article lies in the identification of global challenges for social support systems. The basic methods of scientific research used in the article are analysis and synthesis (to identify the specifics of global challenges for social support systems), graphic method (to demonstrate the connection between the global basis of the emergence of global challenges and challenges for the social support system). It has been established that the main global challenges for social support systems are the following: the functional failure of the social support system; growing needs of recipients of social services, benefits, and payments; the transformation of a socially oriented state; the reduction in abilities of states to maintain social support systems. The functional failure of the social support system means its state in which the formal presence of agencies and institutions designed to guarantee the provision of social services, benefits and payments to the population is not accompanied by their effective work, that is, the system of social support does not solve the current social problems of society and becomes a burden for state budget. The most acute challenge for the social support system for Ukraine under war conditions is the growth in the needs of recipients of social services, benefits, and payments, which can occur in two ways: 1) an increase in the needs of existing recipients of social benefits, services, and payments on account of changes in the socio-economic, political, ecological, security situation in the region or objective physiological changes in certain groups of recipients (aging, deterioration of well-being); 2) an increase in the number (or share) of people applying for social support due to changes in the socio-economic, political, environmental, security situation in the region or subjective life circumstances. Closely related to this challenge is another challenge, namely the reduction in states’ ability to maintain social support systems. Particular attention is paid to the causes and potential consequences of the transformation of the concept of a socially oriented state. In addition, the author researched the global basis of challenges for social support systems, which combines the key factors of their occurrence.

Exploring Longitudinal Physiological Monitoring: Insights From Utilizing a Commercial Wearable Device Among Older Adults With Mild Cognitive Impairment

Commercial wearable technologies are becoming increasingly prevalent and offer the potential for monitoring physiological changes over time, particularly in older adults with Mild Cognitive Impairment (MCI). While literature suggests the utility of such devices, little evidence exists of their successful deployment among people with MCI. This feasibility study aimed to establish research guidelines, optimize participant training, and identify data collection challenges when collecting longitudinal physiological data using the Oura Ring. Our results indicated that adequate researcher support was crucial for study success and participant engagement. This involves including care partners of participants with MCI and providing appropriate technological training to participants. Care partner support reduced device troubleshooting instances and emotionally encouraged participants with MCI. Lastly, maintaining regular researcher-participant communication fostered rapport and ensured ongoing participant consent and data quality. This research lays the groundwork for future health monitoring studies by emphasizing the importance of tailored support, communication, and researcher involvement.

CONHECIMENTO DOS CUIDADORES DE IDOSOS DE INSTITUIÇÕES DE LONGA PERMANÊNCIA SOBRE AS ALTERAÇÕES DE MASTIGAÇÃO E DEGLUTIÇÃO

Physiological changes in old age significantly impact biopsychosocial life, especially in the areas of communication and eating, with eating being not only a source of pleasure but also a crucial facilitator of social interaction. The integrity of chewing and swallowing functions is essential to ensure safety. Elderly people who are unable to perform activities of daily living independently require the attention of caregivers, whether family members or professionals, to ensure their well-being and quality of life. Thus, this study aims to understand the perception of caregivers of elderly people regarding changes in chewing and swallowing of elderly people in Long-Term Care Facilities (LTCFs). This study is quantitative and analytical, carried out with caregivers of elderly people in LTCFs in Alagoas, using a form, with a random and non-probabilistic sample. Thirty-four questionnaires were collected. The average time working with elderly people was 3 years and 9 months, and they remained for an average of 1 year and 10 months. 94.1% of caregivers identified the presence of chewing disorders, correlating these with missing teeth and/or use of dentures (41.2%). Dietary adaptations to deal with these disorders are carried out individually by each caregiver, although they believe they know what is important for good chewing, they do not associate missing teeth with chewing impairment. It is clear that caregivers are unable to prevent choking, as 70.5% have had to perform the Heimlich maneuver while serving meals.

Microbial metabolomics in acute myeloid leukemia: From pathogenesis to treatment.

Acute myeloid leukemia (AML), the most common leukemia in adults, is a biologically heterogeneous disease arising from clonally proliferating hematopoietic stem cells. Increased appreciation of novel genetic methods has improved the understanding of AML biology. Recently, the emerging field of metabolomics has indicated qualitative and quantitative alterations in metabolic profiles in AML pathogenesis, progression and treatment. Multiple metabolic and molecular pathways regulate human metabolism and host-microbiome interactions may significantly affect this biochemical machinery. Microbiota have been found to play a significant role in hematopoietic function, metabolism and immunity, contributing to AML occurrence. A large number of studies have highlighted the importance of the composition and diversity of the gut microbiota (GM) in response to treatment and prognosis in AML. Moreover, strong evidence emphasizes the detrimental link between dysbiosis and infectious complications, a leading cause of morbidity and mortality for patients with AML. Several microbiota-related mechanisms have been linked to particular changes in host physiology so far, and microbial-derived metabolites belong to one of the most important. Circulating in the body, they modulate human conditions both locally and systemically. The extensive and diverse repertoire of bacterial metabolic functions plays a critical role in numerous processes, including leukemogenesis. Integrative analysis of microbiome and metabolome data is a promising avenue for better understanding the complex relationship between the microbiota, biochemical alterations and AML pathogenesis to effectively prevent, treat and mitigate its outcomes. This review concentrates on the pathologic roles and therapeutic implications of microbe-derived metabolites in AML settings.

Placental small extracellular vesicles from normal pregnancy and gestational diabetes increase insulin genetranscription and content in β cells.

Insulin secretion increases progressively during pregnancy to maintain normal maternal blood glucose levels. The placenta plays a crucial role in this process by releasing hormones and extracellular vesicles into the maternal circulation, which drive significant changes in pregnancy physiology. Placental extracellular vesicles, which are detectable in the plasma of pregnant women, have been shown to signal peripheral tissues and contribute to pregnancy-related conditions. While studies using murine models have demonstrated that extracellular vesicles can modulate insulin secretion in pancreatic islets, it remains unclear whether these effects translate to human biology. Understanding how placental signals enhance insulin synthesis and secretion from β cells could be pivotal in developing new therapies for diabetes. In our study, we isolated placental small extracellular vesicles from human placentae and utilised the human β cell line, EndoC-βH3, to investigate their effects on β-cell function in vitro. Our results indicate that human β cells internalise placental small extracellular vesicles, leading to enhanced insulin gene expression and increased insulin content within the β cells. Moreover, these vesicles upregulated the expression of Annexin A1, a protein known to increase insulin content. This upregulation of Annexin A1 holds promise as a potential mechanism by which placental small extracellular vesicles enhance insulin biosynthesis.

Key Anabolic Markers in Human M. Soleus after 21-Day Head-Down Tilt Bedrest

Prolonged bed rest can have a significant negative effect on skeletal muscle, leading to muscle wasting and reduced strength. This process can occur in as little as 10 days in healthy individuals, with the loss of muscle mass and strength being particularly pronounced during the first week of immobilization. Head-down tilt bed rest (HDT) is a method used to simulate the physiological changes that occur in weightlessness during spaceflight. This technique involves lying in bed with the head tilted downward. This paper is dedicated to the analysis of key anabolic markers of the soleus muscle during 21 days of HDT BR. The HDT BR experiment was conducted at the Institute of Biomedical Problems, Russian Academy of Sciences. Six healthy male volunteers, aged 25–35 years, were subjected to 21 days of strict bed rest with a tilt angle of –6°. A needle biopsy of the m.soleus was performed using the Bergström method before the start of HDT BR and on day 21 of HDT BR. The biopsy material was immediately frozen in liquid nitrogen for further Western blot and PCR analysis. Examination of mTORC1 substrates showed a significant decrease in p70 and 4EBP1 phosphorylation after HDT BR. We also observed a significant decrease in the phosphorylation of another ribosomal kinase, p90RSK, a significant increase in eEF2 phosphorylation and an increase in eEF2k mRNA expression. In addition, the phosphorylation of AMPK and its substrate ACC decreased after HDT BR. The data obtained in this work support the hypothesis that a decrease in protein synthesis, together with an increase in proteolysis, contributes to the development of human m. soleus atrophy after 21 days of HDT BR.

Startle sign events induced by mechanical manipulation during surgery for neuroma localization: a retrospective cohort study

BackgroundChronic pain from peripheral neuromas is difficult to manage and often requires surgical excision, though intraoperative identification of neuromas can be challenging due to anatomical ambiguity. Mechanical manipulation of the neuroma during surgery can elicit a characteristic “startle sign”, which can help guide surgical management. However, it is unknown how anesthetic management affects detection of the startle sign.MethodsWe performed a retrospective cohort study of 73 neuroma excision surgeries performed recently at Massachusetts General Hospital. Physiological changes in the anesthetic record were analyzed to identify associations with a startle sign event. Anesthesia type and doses of pharmacological agents were analyzed between startle sign and no-startle sign groups.ResultsOf the 64 neuroma resection surgeries included, 13 had a startle sign. Combined intravenous and inhalation anesthesia (CIVIA) was more frequently used in the startle sign group vs. no-startle sign group (54% vs. 8%), while regional blockade with monitored anesthetic care was not associated with the startle sign group (12% vs. 0%), p = 0.001 for anesthesia type. Other factors, such as neuromuscular blocking agents, ketamine infusion, remifentanil infusion, and intravenous morphine equivalents showed no differences between groups.ConclusionsHere, we identified hypothesis-generating descriptive differences in anesthetic management associated with the detection of the neuroma startle sign during neuroma excision surgery, suggesting ways to deliver anesthesia facilitating detection of this phenomenon. Prospective trials are needed to further validate the hypotheses generated.

Long-term, Dynamic Remodelling of the Corticotroph Transcriptome and Excitability After a Period of Chronic Stress.

Chronic stress results in long-term dynamic changes at multiple levels of the hypothalamic-pituitary-adrenal (HPA) axis resulting in stress axis dysregulation with long-term impacts on human and animal health. However, the underlying mechanisms and dynamics of altered of HPA axis function, in particular at the level of pituitary corticotrophs, during a period of chronic stress and in the weeks after its cessation (defined as "recovery") are very poorly understood. Here, we address the fundamental question of how a period of chronic stress results in altered anterior pituitary corticotroph function and whether this persists in recovery, as well as the transcriptomic changes underlying this. We demonstrate that, in mice, spontaneous and corticotrophin-releasing hormone-stimulated electrical excitability of corticotrophs, essential for ACTH secretion, is suppressed for weeks to months of recovery following a period of chronic stress. Surprisingly, there are only modest changes in the corticotroph transcriptome during the period of stress, but major alterations occur in recovery. Importantly, although transcriptional changes for a large proportion of mRNAs follow the time course suppression of corticotroph excitability, many other genes display highly dynamic transcriptional changes with distinct time courses throughout recovery. Taken together, this suggests that chronic stress results in complex dynamic transcriptional and functional changes in corticotroph physiology, which are highly dynamic for weeks following cessation of chronic stress. These insights provide a fundamental new framework to further understand underlying molecular mechanisms as well approaches to both diagnosis and treatment of stress-related dysfunction of the HPA axis.