Prominent Symptoms Research Articles

Acute hyperglycemia exacerbates neuroinflammation and cognitive impairment in sepsis-associated encephalopathy by mediating the ChREBP/HIF-1α pathway.

Delirium is a prominent symptom of sepsis-associated encephalopathy (SAE) and is highly prevalent in septic patients hospitalized in the intensive care unit, being closely connected with raised mortality rates. Acute hyperglycemia (AH) has been recognized as a separate risk factor for delirium and a worse prognosis in critically sick patients. Nevertheless, the exact contribution of AH to the advancement of SAE is still unknown. This research retrospectively evaluated the connection between blood glucose levels (BGLs) and the incidence of delirium and death rates in septic patients in the ICU of a tertiary comprehensive hospital. In addition, a septic rat model was induced through cecal ligation and puncture (CLP), after which continuous glucose infusion was promptly initiated via a central venous catheter post-surgery to evaluate the potential implications of AH on SAE. Next, septic rats were assigned to four groups based on target BGLs: high glucose group (HG, ≥ 300mg/dL), moderate glucose group (MG, 200-300mg/dL), normal glucose group (NG, < 200mg/dL), and a high glucose insulin-treated group (HI, 200-300mg/dL) receiving recombinant human insulin treatment (0.1IU/kg/min). The sham group (SG) received an equivalent volume of saline infusion and denoted the NG group. The effects of AH on neuroinflammation and cognitive function in septic rats were evaluated using behavioral tests, histopathological examination, TUNEL staining, ELISA, and Western blot. The effects of glucose levels on microglial activation and glucose metabolism following lipopolysaccharide (LPS, 1μg/mL) exposure were assessed using CCK8 assay, qRT-PCR, Western blot, and ELISA. Our findings revealed that AH during sepsis was a separate risk factor for delirium and assisted in predicting delirium occurrence. AH raised the levels of systemic and central inflammatory cytokines in septic rats, promoting neuronal apoptosis, blood-brain barrier disruption, and cognitive impairment. In addition, both in vivo and in vitro, an elevated glucose challenge increased the ChREBP, HIF-1α, glycolytic enzymes, and inflammatory cytokines expressions in microglia after exposure to CLP or LPS. These results collectively suggest that hyperglycemia can exacerbate neuroinflammation and delirium by enhancing microglial glycolysis under septic conditions, potentially mediated by upregulation of the ChREBP/HIF-1α signaling pathway.

A Comparison of Clinical and Laboratory Features in Neonatal Proven Sepsis and COVID-19

Background: The clinical manifestations of COVID-19 in neonates are generally mild and commonly require only supportive treatment. However, it is important to note that they can sometimes present with symptoms like bacterial sepsis, which can lead to confusion in diagnosis. In this study, our objective was to compare laboratory data and clinical manifestations between 2 groups to identify opportunities for reducing the unnecessary use of antibiotics. Methods: The study was conducted as a cross-sectional study between January 2020 and 2023 on neonates who were admitted to the neonatal intensive care unit or the neonatal ward of Children’s Medical Center in Tehran, Iran. We specifically compared the laboratory data and clinical characteristics of neonates who tested positive for either a blood culture or a reverse transcription polymerase chain reaction for COVID-19. Results: Sixty-seven neonates in COVID-19 group and 68 neonates in the bacterial sepsis group entered. Prominent symptoms in the bacterial sepsis group include vomiting, seizure, apnea, mottling, increased need for ventilation and laboratory findings showing elevated levels of C-reactive protein and thrombocytopenia. In the COVID-19 group, patient exhibit symptoms such as cough, diarrhea, fever and laboratory findings that indicate neutropenia and leukopenia. Symptoms of nervous involvement were rare in this group. Conclusion: It is crucial to carefully assess the symptoms, laboratory results and overall condition of the patient before deciding on antibiotic initiation. By combining rapid COVID-19 testing and clinical variables, it is possible to identify low-risk infants who are unlikely to have bacterial infections.

Synthesis and Anti-Inflammatory and Analgesic Potentials of Ethyl 2-(2,5-Dioxo-1-Phenylpyrrolidin-3-yl)-2-Methylpropanoate

Background/Objectives: Inflammation and analgesia are two prominent symptoms and often lead to chronic medical conditions. To control inflammation and analgesia, many marketed drugs are in practice but the majority of them have severe side effects. Methods: This study involved the synthesis of a pivalate-based Michael product and evaluated it for in vitro COX-1, COX-2, and 5-LOX inhibitory potentials using specific assays. Molecular docking studies were also assessed. Based on the in vitro results, the compound was also subjected to in vivo anti-inflammatory and antinociceptive studies. Results: The pivalate-based Michael product (MAK01) was synthesized by an organocatalytic asymmetric Michael addition of ethyl isobutyrate to N-phenylmaleimide with an isolated yield of 96%. The structure of the compound was confirmed through 1H and 13C NMR analyses. The observed IC50 values for COX-1, COX-2, and 5-LOX were 314, 130, and 105 μg/mL, respectively. The molecular docking studies on the synthesized compound showed binding interactions with the minimized pockets of the respective enzymes. In a carrageenan model, a percent reduction in edema when administered at 10 mg/kg (a reduction of 33.3 ± 0.77% at the second hour), 20 mg/kg (a reduction of 34.7 ± 0.74% at the second hour), and 30 mg/kg (a reduction of 40.58% ± 0.84% after the fifth hour) was observed. The compound showed a significant response at concentrations of 50, 100, and 150 mg/kg with latency times of 10.32 ± 0.82, 12.16 ± 0.51, and 12.93 ± 0.45 s, respectively. Conclusion: In this study, we synthesized a pivalate-based Michael product for the first time. Moreover, based on its rationality and potency, it was found to be an effective future medicine for the management of analgesia and inflammation.

Clinical characteristics of patients with P4HTM variant-associated epilepsy and therapeutic exploration: a case report and literature review

The P4HTM gene encodes a transmembrane prolyl 4-hydroxylase, which is responsible for the degradation of hypoxia-inducible transcription factors (HIF) under normoxia. Clinically, biallelic P4HTM variants have been identified in patients with hypotonia, hypoventilation, intellectual disabilities, dysautonomia, epilepsy, and eye abnormalities (HIDEA syndrome). Seizure was one of the most prominent symptoms. However, the clinical features of patients with epilepsy associated with P4HTM variants remain unclear. In this report, we describe a one-month-old infant with HIDEA syndrome caused by compound heterozygous P4HTM variants (c.300dupG/p.Gly103Argfs*22 and c.488C &amp;gt; T/p.Ala163Val). The infant presented with clonic seizures of focal onset that responded well to valproate, but with profound intellectual disability and global developmental delay at the last follow-up at 3 years old. A review of the existing literature indicates that seizures in this population typically begin early in infancy, manifest in multiple types, and are relatively well controlled. Epilepsy seemed unrelated to developmental outcomes or disease progression. Valproate, which has HIF-1α inhibiting properties, may be a promising treatment avenue for this population.

Interaction among negative mood, sleep, and diet habits in adolescents with non-suicidal self-injury: A cross-sectional network analysis

BackgroundNon-suicidal self-injury (NSSI) is a serious public health problem that can lead to adverse effects such as cognitive impairment, poor interpersonal relationships and violent crime. The progress of preventing and treating NSSI in adolescents depends on other changeable risk factors, such as negative mood, sleep, and diet habits. However, the risk factors for adolescent NSSI remain unclear. Therefore, this study explores the key factors influencing adolescents' NSSI behavior through the use of network analysis. MethodsThe study recruited 4040 middle school students aged 12–18 years old. From November 1st, 2023 to January 1st, 2024, paper questionnaires were utilized to investigate the participants' basic conditions, negative mood, NSSI, sleep conditions, and diet habits. Network analysis was used to explore the interrelationship among risk factors and discover the core factor. ResultsIn the network structure of adolescents with NSSI behavior, the most correlated nodes were negative emotions (CDI2) and low self-esteem (CDI3). Compared with adolescents without NSSI behavior, adolescents with NSSI behavior showed prominent anxiety symptoms related to injury avoidance (MASC1) and social anxiety (MASC2). Anhedonia (CDI1) was both the central node and the bridge node of the network. LimitationThe cross-sectional design of this study couldn't clarify the causal inference between independent variables and results. ConclusionAnhedonia is the key factor affecting adolescents' emotion regulation. Furthermore, we hypothesize that adolescent NSSI is an emotional disorder, and anhedonia plays an important role in preventing and intervening in adolescents' NSSI behavior.

Epileptic seizure as the prominent symptom in Fahr syndrome, case report and literature review

Epileptic seizure as the prominent symptom in Fahr syndrome, case report and literature review

Surgical management of chronic pancreatitis: A narrative review.

Chronic pancreatitis is a severe disabling disease with persistent pain as the most prominent symptom often leading to significant quality of life (QoL) reduction. Current international guidelines propagate a step-up approach in which surgery should only be considered as a last resort in patients with failure of both medical and endoscopic interventions. Accumulating evidence, however, suggests that surgery is superior to endoscopic therapy and that early surgical intervention is beneficial in terms of pain relief, pancreatic function and QoL. Several surgical procedures are available with low morbidity and mortality rates, providing excellent long-term results. The purpose of this review was to present an overview of the surgical treatment options for chronic pancreatitis with a focus on the timing of surgery.

Serological Detection of Cucumber Mosaic Virus and Capsicum Chlorosis Virus in Pepper (Capsicum annuum L.) Germplasm

A survey was conducted on the basis of symptomatology for the screening of germplasm under insect proof glasshouse conditions in the Department of Vegetable Science, Dr. YSPUHF, Nauni, Solan to identify the sources of resistance in pepper crop. The most prominent symptoms were mosaic, mottling, leaf narrowing, stunted growth, mosaic with chlorotic lesions, formation of rings with necrotic lesions and mosaic with mottling. Forty-eight varieties or breeding lines were screened for the presence or absence of virus through DAS-ELISA. The study revealed that nineteen varieties or breeding lines tested positive and twenty-nine tested negative for virus infection. Sweet Banana variety recorded the least O.D. value followed by SB and UHF-Cap-30 whereas, UHF-Cap-22 was most susceptible variety with maximum O.D. value. Mixed infection of CMV and capsicum chlorosis orthotospovirus (CaCV) was recorded with six varieties or breeding lines during germplasm screening. This study signifies the presence of mixed infection with chlorotic lesions like symptoms and importance of DAS-ELISA in screening of pepper germplasm against CMV and CaCV.

Dopamine loss alters glutamate synapses and transporters in the medial prefrontal cortex and anxiety-related behaviour in a male MPTP rodent model of Parkinson's disease.

Anxiety is a prominent non-motor symptom of Parkinson's disease (PD). Changes in the B-spectrum recordings in PD patients of the prefrontal cortex correlate with increased anxiety. Using a rodent model of PD, we reported alterations in glutamate synapses in the striatum and substantia nigra following dopamine (DA) loss. We hypothesize that DA loss will result in increased anxiety-related behaviours and that this will be associated with alterations in glutamate synapses and transporters within the medial prefrontal cortex (mPFC). Following 4weeks of progressive 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) administration, there was an increase in anxiety-related behaviours and a 78% decrease in plasma corticosterone levels versus the vehicle (VEH)-treated mice. This was associated with a 30% decrease in the density of dendritic spines in Layers Il/Ill, and a 53% decrease in the density of glutamate immuno-gold labelling within vesicular glutamate transporter 1 (Vglut1)-labelled nerve terminals and spines, with no change within vesicular glutamate transporter 2 (Vglut2) positive terminals/spines in the MPTP versus VEH groups. Our prior work determined that a decrease in striatal glutamate terminal density was associated with an increase in extracellular glutamate levels. There was an increase in protein expression of Vglut1 (40%), Vglut2 (37%) and glutamate aspartate transporter (GLAST) (225%), and a decrease in glutamate transporter 1 (GLT-1) (50%) and excitatory amino acid carrier 1 (EAAC1) (51%), in the MPTP versus VEH groups within the mPFC. These data suggest that the decrease in dendritic spines within the mPFC following nigrostriatal DA loss may be due to increased extracellular glutamate levels (decrease in glutamate transporters), leading to an increase in anxiety-related behaviours.

Gait analysis in the early stage of Parkinson's disease with a machine learning approach.

Gait disorder is a prominent motor symptom in Parkinson's disease (PD), objective and quantitative assessment of gait is essential for diagnosing and treating PD, particularly in its early stage. This study utilized a non-contact gait assessment system to investigate gait characteristics between individuals with PD and healthy controls, with a focus on early-stage PD. Additionally, we trained two machine learning models to differentiate early-stage PD patients from controls and to predict MDS-UPDRS III score. Early-stage PD patients demonstrated reduced stride length, decreased gait speed, slower stride and swing speeds, extended turning time, and reduced cadence compared to controls. Our model, after an integrated analysis of gait parameters, accurately identified early-stage PD patients. Moreover, the model indicated that gait parameters could predict the MDS-UPDRS III score using a machine learning regression approach. The non-contact gait assessment system facilitates the objective and quantitative evaluation of gait disorder in PD patients, effectively distinguishing those in the early stage from healthy individuals. The system holds significant potential for the early detection of PD. It also harnesses gait parameters for a reasoned prediction of the MDS-UPDRS III score, thereby quantifying disease severity. Overall, gait assessment is a valuable method for the early identification and ongoing monitoring of PD.

Interoceptive sensibility and alcohol craving in Polish prisoners: the role of alexithymia and emotional dysregulation.

Alcohol craving, characterized by a strong desire or compulsion to consume alcohol, is a prominent symptom of substance dependence syndrome. Research indicates that alcohol craving is a significant factor leading to the termination of abstinence. The mechanisms underlying the activation of alcohol craving remain not fully understood. The urge to reach for alcohol may be stimulated by emotions, memories, thoughts, or bodily sensations, as well as external factors. It has been postulated that individuals with high levels of interoceptive sensibility tend to exhibit a high degree of alexithymia and emotion dysregulation in the context of alcohol craving. Deficits in identifying and verbalizing emotions, along with an operational thinking style, facilitate alcohol consumption by impeding accurate insight into one's mental state, thereby hindering the comprehension of bodily states, emotions, and the regulation of self. This study involved 160 inmates incarcerated in a prison in Poland, awaiting participation in therapy for individuals with substance dependence following psychiatric diagnosis. Four questionnaires were used in the study: multidimensional Assessment of Interoceptive Sensibility (MAIA) for interoceptive sensibility, Toronto Alexithymia Scale (TAS-20) for alexithymia, Difficulties in Emotion Regulation Scale (DERS) for emotional dysregulation, and the Penn Alcohol Craving Scale (PACS) for alcohol craving assessment. The results of the study are as follows: the study findings indicated that alexithymia and emotional dysregulation significantly mediates the relationship between interoceptive sensibility and alcohol craving. The indirect effect for both factors was found to be significant, similar to the indirect effect observed for alexithymia as an mediator. However, in the case of emotional dysregulation, no significant indirect effect was observed. Our study provides insights into the potential contribution of interoceptive sensibility to the heightened risk of alcohol dependence. Specifically, impaired interoceptive sensibility may be associated with the development of alexithymia and emotional dysregulation, potentially rendering individuals more susceptible to alcohol craving. Interoceptive sensibility could serve as a prerequisite for the cultivation of positive emotional processing skills.

8800 A Case of Hypopituitarism Due to Sheehan Syndrome

Abstract Disclosure: N. Akabogu: None. S. Dejhansathit: None. F. Marium: None. B. Stanley: None. E.M. Bazuaye: None. L.S. Krusniak: None. L.G. Kurukulasuriya: None. U.Z. Khan: None. Background: Sheehan syndrome, which is also known as postpartum pituitary infarction, refers to the necrosis of the anterior pituitary gland due to postpartum hypovolemia, hemorrhage, shock, resulting in various degrees of hypopituitarism. The pituitary gland enlarges during pregnancy due to estrogen stimulation and becomes hyper-vascular, making it prone to infarction with postpartum hemorrhage. The initial symptoms include hyponatremia, weakness, weight loss, but the most prominent specific symptoms are inability to nurse and postpartum amenorrhea. Depending on the severity of hypopituitarism, symptoms may develop within the first few days to weeks after delivery or may take months to years to develop. Case presentation: 35year-old Caucasian female with a medical history of gestational diabetes, hyperlipidemia, and hypertension, who presented to the hospital with flu-like symptoms, leg pain, abdominal pain, and proximal muscle weakness. The evaluating hospitalist observed that patient appeared sluggish and spoke with a deep coarse voice, which concerned him for hypothyroidism. Thyroid function test revealed undetectable free T4 with inappropriately normal TSH of 1.38 – consistent with secondary hypothyroidism. Additional history from patient uncovered 9 months history of constant fatigue, weight gain, dry skin, hair loss, cold intolerance, and intermittent ankle swelling. There is no history of brain irradiation or head trauma. She has 4 biological children, and her last childbirth 3years ago was complicated by severe bleeding from her incision site, requiring transfusion of 6 units of blood. She has been amenorrheic since and is neither on birth control nor had hysterectomy. Physical exam showed mildly enlarged tongue, diffuse pallor, dry scaly skin on upper arms, scanty eyebrows, and slowed speech. Further work-up for pituitary insufficiency showed secondary adrenal insufficiency, secondary hypogonadism, low prolactin, and growth hormone deficiency. There was no evidence of AVP deficiency. Other lab and clinical findings were hypoglycemia, hyperlipidemia, elevated CK, elevated Cr, pericardial effusion, and diastolic hypertension. Pituitary MRI showed markedly attenuated and flattened pituitary gland with no focal mass. Patient was given stress dose hydrocortisone and thyroid hormone replacement, initially IV then oral. Following hydrocortisone and thyroid hormone replacement, her diastolic BP, hypoglycemia, CK, and Cr improved. Further management plans include initiating estrogen (plus progesterone) for bone health. Conclusion: Although Sheehan syndrome is rare in developed countries, it does occur. This case emphasizes the importance of detailed history taking, to discover the root of patients’ presentation. Even though TSH is the screening test for thyroid disease, when pituitary etiology is suspected, it is important to also check a free T4. Presentation: 6/1/2024

MrgprA3+ Primary Sensory Neurons Mediate Acute Allergic Itch Responses in Atopic Dermatitis Model Mice.

Itch is a prominent symptom of atopic dermatitis (AD). However, the underlying mechanism remains complex and has not yet been fully elucidated. Mas-related G protein-coupled receptor A3 (MrgprA3) has emerged attention as a marker of primary sensory neurons that specifically transmit itch signals; however, its involvement in AD-related itch has not been extensively explored. In this study, we developed an AD itch mouse model by repeatedly applying house dust mite (HDM) extract to barrier-impaired skin via a special diet. To clarify the role of MrgprA3+ neurons in itch behavior in our AD model, we adopted a toxin receptor-mediated cell knockout strategy using transgenic mice in which the diphtheria toxin receptor (DTR) gene was placed under the control of the Mrgpra3 promoter. When the HDM extract was repeatedly applied to the face and back skin of special diet-fed mice, the mice exhibited AD-like dry and eczematous skin lesions accompanied by three types of itch-related behaviors:1) spontaneous scratching, 2) acute scratching after antigen challenge, and 3) light touch-evoked scratching. Upon diphtheria toxin administration, substantial depletion of DTR+/MrgprA3+ neurons was observed in the dorsal root ganglion. Ablation of MrgprA3+ neurons suppressed acute itch responses after HDM application, whereas spontaneous and touch-evoked itch behaviors remained unaffected. Our findings unequivocally demonstrate that in our AD model, MrgprA3+ primary sensory neurons mediate acute allergic itch responses, whereas these neurons are not involved in spontaneous itch or alloknesis.

Diagnostic evaluation for abnormal uterine bleeding at emergency departments in the United States.

269 Background: Uterine cancer is the most common gynecologic malignancy in the U.S. with well-documented racial disparity in stage at diagnosis (more advanced stage among Black women). As there is no routine screening for uterine cancer, timely and proper evaluation of relevant symptoms is important for early diagnosis. Abnormal uterine bleeding (AUB) is a prominent symptom of uterine cancer, yet data on the quality of care around AUB evaluation are sparse, especially among patients presenting to the emergency departments (ED) who are particularly at risk for delayed diagnosis due to lack of access to primary care. This study aimed to examine the pattern of diagnostic evaluation for AUB in a national sample of women seeking care at EDs and potential racial and ethnic differences. Methods: Using the 2014-2021 National Hospital Ambulatory Medical Care Survey (NHAMCS) data, we identified 7,900,653 (weighted) women without previous cancer diagnosis who visited ED for non-pregnancy related AUB. The primary outcomes were whether an ultrasound was performed/ordered at the ED visit and whether a referral/return to a physician or clinic for follow-up consultation was recommended. Multivariable logistic regressions were fit to assess the association of race and ethnicity with these diagnostic evaluations, while accounting for other characteristics of the ED visit (e.g. patient age, comorbidities, involvement of a consulting physician, type of insurance, geographic region, and metropolitan area location). All analyses accounted for the NHAMCS complex sample design and sampling weight to generate nationally representative estimates. Results: Non-Hispanic Black women were less likely than non-Hispanic White women to receive or have an ultrasound ordered (34.9% vs 42.5%, P = 0.004), which remained statistically significant after adjusting for other characteristics of the visit in multivariable analysis (adjusted OR = 0.58, 95% CI 0.36-0.92). Multivariable analysis also showed a lower likelihood of non-Hispanic Black women receiving referral or recommendation for follow-up consultation, compared to non-Hispanic White women (adjusted OR = 0.54, 95% CI 0.31-0.94). Hispanic women did not differ significantly from non-Hispanic White women in these measures. Perimenopausal age (45-54 years) and location in a non-metropolitan area were associated with a lower likelihood of having an ultrasound performed/ordered or a referral/follow-up consultation recommended. Involvement of a consulting physician at the ED visit increased the likelihood of having an ultrasound performed/ordered while reducing the likelihood of referral/recommendation for follow-up consultation. Conclusions: There is racial disparity in the diagnostic evaluation of AUB among women seeking care at EDs. Future efforts to improve care quality and equity in this area may help reduce disparities in early diagnosis of uterine cancer.

Acute Augmented Effect of Virtual Reality (VR)-Integrated Relaxation and Mindfulness Exercising on Anxiety and Insomnia Symptoms: A Retrospective Analysis of 103 Anxiety Disorder Patients With Prominent Insomnia.

Anxiety disorder is one of the most common mental disorders and often accompanied with sleep disturbance which can in turn exacerbate anxiety symptoms, creating a vicious cycle. In addition to psychopharmacological therapy, the effectiveness of psychotherapy as cognitive behavioral therapy (CBT) for treating anxiety disorders and insomnia has been well documented and widely accepted, but it is labor-intensive and costly. However, virtual reality (VR)-integrated CBT may improve this condition but needs more evidences to support its extensive application in routine clinical practice. This explorative study was aimed to conduct a retrospective analysis to evaluate the acute (2 weeks) augmented effect of VR-integrated relaxation and mindfulness exercising in improving anxiety and insomnia symptoms for patients who were diagnosed with anxiety disorders and concurrently with prominent insomnia symptoms and admitted to the Department of Psychiatry, The Affiliated Guangdong Second Provincial General Hospital of Jinan University during January 2021 to June 2021. All patients who were admitted to the department of psychiatry during January 1, 2021 to June 30, 2021 were screened with inclusion criteria and exclusion criteria, and the sociodemographic and clinical data of those included patients were collected from the electronic medical record system of the hospital using a self-designed case report form (CRF). Subjects who were administrated with medication alone were designated as conventional group, and those receiving treatment of medication combined with VR-integrated CBT (VR relaxation and mindfulness exercising) as VR group. The baseline and 2-week posttreatment data were compared between the two groups. In total, there were 103 patients (70 female, 68%) included in the study. Among all, 68 (66.02%) were designated as the "VR group," and 35 (33.98%) as the "conventional group." The majority of patients (67%) were diagnosed with generalized anxiety disorder (GAD). Twenty-three (22.3%) patients had a comorbid diagnosis with primary insomnia, and insomnia was just one of the accompanying symptoms with anxiety for the rest 80 subjects. No statistically significant differences were found between VR and conventional groups in all baseline sociodemographic and clinical characteristics except for occupation. There were statistically significant differences for the remission rates of anxiety symptoms or insomnia symptoms and reduction of Hamilton Anxiety Rating Scale or Insomnia Severity Index total scores between conventional and VR groups. Greater remission rates or score reductions were found in VR group than in conventional group either for anxiety or for insomnia. Robust differences still existed when controlled for the variable "occupation." Two-week augmented VR-integrated relaxation and mindfulness exercising is acutely beneficial for relieving both anxiety and insomnia symptoms and worth being recommended for routine clinical practice. Further prospective and randomized study compared to traditional CBT to explore its acute and long-term effect on anxiety and insomnia is needed.

The volumes of amygdala subregions and peripheral programmed cell death protein-1 levels are associated with cognitive decline in individuals with knee osteoarthritis.

Persistent pain is a prominent symptom of knee osteoarthritis (KOA) and has been associated with cognitive decline in individuals with KOA. The amygdala, a complex structure consisting of nine subnuclei, and programmed cell death protein-1 (PD-1) levels play crucial roles in pain regulation and cognitive processing. This study aims to investigate the relationships among amygdala subregion volumes, cognitive function, and PD-1 levels to elucidate the underlying mechanism of cognitive decline in KOA. In this cross-sectional study, we recruited 36 patients with KOA and 25 age/gender-matched healthy controls for neuropsychological tests, structural magnetic resonance imaging scanning, and measurement of serum PD-1 levels. We used the atlas provided by FreeSurfer software to automatically segment the amygdala subnuclei. Subsequently, we compared the volumes of amygdala subregions between groups and explored their correlation with clinical scores and PD-1 levels. Compared to healthy controls, individuals with KOA exhibited significantly lower scores on global cognition tasks, such as long-delay free recall, short-delay free recall, and immediate recall tasks. Moreover, they displayed decreased volumes in lateral nucleus basal nucleus paralaminar nucleus while showing increased volumes in accessory basal nucleus, central nucleus, medial nucleus, and cortical nucleus. Within the KOA group specifically, paralaminar volume was negatively correlated with immediate recall scores; pain scores were negatively correlated with global cognition; basal volume was negatively correlated with PD-1 levels. Our findings highlight those alterations in amygdala subregion volumes along with changes in serum PD-1 levels may contribute to observe cognitive decline among individuals suffering from KOA.

Styphnolobium japonicum Fruit and Germinated Soybean Embryo Complex Extract for Postmenopausal-Symptom Relief.

Hormonal alterations during menopause result in substantial physiological changes. Although hormone replacement therapy (HRT) is widely used as a treatment strategy for these changes, its use remains controversial due to its associated risks. Plant isoflavones are phytoestrogens that are considered a potential alternative therapy for postmenopausal syndrome. We aimed to investigate the efficacy of ethanolic extracts from Styphnolobium japonicum fruit (SJF) and germinated soybean embryo (GSE) in alleviating prominent menopausal symptoms. A cell model (MCF7 human breast cancer cells) was used to investigate estrogen-like activity. A rat ovariectomy model was used to simulate estrogen depletion after menopause and to evaluate the efficacy of the SJF-GSE complex extract at ratios of 1:1, 1:2, and 2:1. Treatment with the SJF-GSE extract elicited estrogen-like effects, raising pS2 and estrogen receptor α expression in MCF7 cells. The extract was found to contain 48-72 mg/g sophoricoside and 8-12 mg/g soyasaponin 1, identified as active compounds. In ovariectomized rats, the extract effectively reduced body weight and fat content, alleviated vasomotor symptoms, improved vaginal mucosal health, and exerted osteoprotective effects by enhancing bone density and structure, reducing bone-resorption markers and positively altering estradiol levels and lipid profiles. The SJF-GSE extract, working synergistically, provides a safe and effective alternative to HRT for managing postmenopausal symptoms and enhancing bone health, without adverse effects. These findings support the inclusion of SJF and GSE in health-functional foods and underscore the importance of further research into plant-based therapies for menopause.

Neurological Restorative Effects of (-)-Epicatechin in a Model of Gulf War Illness.

Gulf War Illness (GWI) afflicts US military personnel who served in the Persian Gulf War. Suspect causal agents include exposure to pyridostigmine (PB), permethrin (PM) and N,N-diethyl-m-toluamide (DEET). Prominent symptoms include cognitive deficits, such as memory impairment. In aging animal models, we have documented the beneficial effect of the flavanol (-)-epicatechin (Epi) on hippocampus structure and related function. Using a rat model of GWI, we examined the effects of Epi on hippocampus inflammation, oxidative stress, mitochondrial dysfunction, cell death/survival pathways, and memory endpoints. Male Wistar rats underwent 3 weeks of exposure to either vehicles or DEET, PM, PB, and stress. Subgroups of GWI rats were then allocated to receive orally 15 days of either water (vehicle) or 1 mg/kg/day of Epi treatment. Object recognition tasks were performed to assess memory. Hippocampus samples were analyzed. Epi treatment yields significant improvements in short- and long-term memory versus GWI rats. Hippocampus oxidative stress and pro-inflammatory cytokine levels showed significant increases with GWI that were largely normalized with Epi becoming comparable to controls. Significant increases in markers of hippocampus neuroinflammation and cell death were noted with GWI and were also largely reduced with Epi. Neuronal survival signaling pathways were adversely impacted by GWI and were partially or fully restored by Epi. Markers of mitochondrial function were adversely impacted by GWI and were fully restored by Epi. In conclusion, in an animal model of GWI, Epi beneficially impacts recognized markers of hippocampus neuroinflammation, oxidative stress, cell survival, neurotoxicity and mitochondrial function leading to improved memory.

Early diagnosis of Alzheimer's Disease based on multi-attention mechanism.

Alzheimer's Disease is a neurodegenerative disorder, and one of its common and prominent early symptoms is language impairment. Therefore, early diagnosis of Alzheimer's Disease through speech and text information is of significant importance. However, the multimodal data is often complex and inconsistent, which leads to inadequate feature extraction. To address the problem, We propose a model for early diagnosis of Alzheimer's Disease based on multimodal attention(EDAMM). Specifically, we first evaluate and select three optimal feature extraction methods, Wav2Vec2.0, TF-IDF and Word2Vec, to extract acoustic and linguistic features. Next, by leveraging self-attention mechanism and cross-modal attention mechanisms, we generate fused features to enhance and capture the inter-modal correlation information. Finally, we concatenate the multimodal features into a composite feature vector and employ a Neural Network(NN) classifier to diagnose Alzheimer's Disease. To evaluate EDAMM, we perform experiments on two public datasets, i.e., NCMMSC2021 and ADReSSo. The results show that EDAMM improves the performance of Alzheimer's Disease diagnosis over state-of-the-art baseline approaches on both datasets.

Gender differences in the co-occurrence of anxiety and depressive symptoms among early adolescents: A network approach

Gender differences have been identified in the co-occurrence of anxiety and depressive symptoms. However, the underlying mechanisms that give rise to this gender difference remain unclear, and few studies have examined the issue at the symptom level. The current study employed the 7-item Generalized Anxiety Disorder scale (GAD-7) and the 9-item Patient Health Questionnaire (PHQ-9) to assess anxiety and depressive symptoms in a national sample of early adolescents (N = 15 391). A network approach was applied to investigate the gender differences in symptom interconnectivity. Gender differences were found in the co-occurrence of anxiety and depressive symptoms. The results indicated that girls with higher global strength (p < 0.01) exhibited stronger interconnectivity between symptoms. Central symptom PHQ2 (Sad mood) was significantly stronger in girls (p < 0.01), whereas PHQ6 (Guilt) was stronger in boys (p < 0.05). GAD7 (Feeling afraid) was identified as a prominent bridge symptom in girls, while PHQ6 (Guilt) was observed to play a similar role in boys. The directed acyclic graphs (DAGs) demonstrated that one symptom of anxiety triggered a series of emotional symptoms of anxiety and depression, ultimately resulting in a depressive somatic symptom in girls, whereas leading to both depressive somatic and anxiety symptoms in boys. These findings enhance our understanding and provide insights into potential intervention targets to prevent the co-occurrence of anxiety and depressive symptoms at an early stage.