Functional Differences Research Articles

Dapagliflozin as an oral antihyperglycemic agent in the management of diabetes mellitus in patients with liver cirrhosis

BACKGROUND The use of dapagliflozin in patients with cirrhosis has been relatively restricted due to concerns regarding its overall safety and pharmacological profile in this population. AIM To determine the safety and effectiveness of dapagliflozin in the co-management of diabetes mellitus and cirrhosis with or without ascites. METHODS The patients studied were divided into two groups: 100 patients in the control group received insulin, while 200 patients received dapagliflozin. These patients were classified as Child A, B, or C based on the Child–Pugh classification. Child A or B and Child C were administered doses of 10 mg and 5 mg of dapagliflozin, respectively. RESULTS The rate of increased diuretics dose was markedly elevated in the group that received insulin compared to the group that received dapagliflozin. In addition, dapagliflozin treatment substantially reduced weight, body mass index, and fasting blood glucose compared to the insulin group during follow-up. However, there were no significant differences in hemoglobin A1c, liver function, or laboratory investigations between both groups during the follow-up period. The incidence of hypoglycemia, hepatic encephalopathy, variceal bleeding, and urinary tract infection was significantly higher in the insulin group compared to the dapagliflozin group. In contrast, the dapagliflozin group experienced significantly higher rates of frequent urination and dizziness. In addition, the insulin group exhibited a marked worsening of ascites compared to the dapagliflozin group. CONCLUSION Dapagliflozin demonstrated safety and efficacy in the treatment of diabetic patients who have cirrhosis with or without ascites. This resulted in an improvement of ascites, as well as a decrease in diuretic dose and Child–Pugh score.

Pain can’t be carved at the joints: defining function-based pain profiles and their relevance to chronic disease management in healthcare delivery design

BackgroundPain is a complex problem that is triaged, diagnosed, treated, and billed based on which body part is painful, almost without exception. While the “body part framework” guides the organization and treatment of individual patients’ pain conditions, it remains unclear how to best conceptualize, study, and treat pain conditions at the population level. Here, we investigate (1) how the body part framework agrees with population-level, biologically derived pain profiles; (2) how do data-derived pain profiles interface with other symptom domains from a whole-body perspective; and (3) whether biologically derived pain profiles capture clinically salient differences in medical history.MethodsTo understand how pain conditions might be best organized, we applied a carefully designed a multi-variate pattern-learning approach to a subset of the UK Biobank (n = 34,337), the largest publicly available set of real-world pain experience data to define common population-level profiles. We performed a series of post hoc analyses to validate that each pain profile reflects real-world, clinically relevant differences in patient function by probing associations of each profile across 137 medication categories, 1425 clinician-assigned ICD codes, and 757 expert-curated phenotypes.ResultsWe report four unique, biologically based pain profiles that cut across medical specialties: pain interference, depression, medical pain, and anxiety, each representing different facets of functional impairment. Importantly, these profiles do not specifically align with variables believed to be important to the standard pain evaluation, namely painful body part, pain intensity, sex, or BMI. Correlations with individual-level clinical histories reveal that our pain profiles are largely associated with clinical variables and treatments of modifiable, chronic diseases, rather than with specific body parts. Across profiles, notable differences include opioids being associated only with the pain interference profile, while antidepressants linked to the three complimentary profiles. We further provide evidence that our pain profiles offer valuable, additional insights into patients’ wellbeing that are not captured by the body-part framework and make recommendations for how our pain profiles might sculpt the future design of healthcare delivery systems.ConclusionOverall, we provide evidence for a shift in pain medicine delivery systems from the conventional, body-part-based approach to one anchored in the pain experience and holistic profiles of patient function. This transition facilitates a more comprehensive management of chronic diseases, wherein pain treatment is integrated into broader health strategies. By focusing on holistic patient profiles, our approach not only addresses pain symptoms but also supports the management of underlying chronic conditions, thereby enhancing patient outcomes and improving quality of life. This model advocates for a seamless integration of pain management within the continuum of care for chronic diseases, emphasizing the importance of understanding and treating the interdependencies between chronic conditions and pain.

Developmental improvements in the ability to benefit from testing across middle childhood

Extensive behavioral research on adults has shown that retrieval practice is highly beneficial for long-term memory retention. However, limited evidence exists on the developmental course of this benefit. Here, we present data from a behavioral study involving 7–14-year-old children who had to encode a total of 60 weakly semantically related cue-target word pairs using either repeated retrieval or repeated study encoding strategies. Results revealed age-related increases in the ability to benefit from testing during encoding from early middle childhood to early adolescence. In contrast, repeated study during encoding did not lead to developmental improvements in long-term memory retention across this age range. Individual differences in vocabulary knowledge, short-term memory and working memory were positively associated with long-term memory retention only for those participants who encoded the information via repeated study. These results indicate that (1) the mechanisms determining the testing effect may not be fully in place by early middle childhood, (2) the ability to benefit from testing improves over the middle childhood years, and (3) these benefits are not associated with individual differences in memory and high-cognitive functioning. One potential interpretation of these findings is that changes in sleep-dependent consolidation processes during middle childhood may be critical for understanding the observed developmental differences in ability to enhance long-term memory via the testing effect.

Primary repair vs arthroscopic reconstruction for proximal anterior cruciate ligament tears: a comparative study

Background. Anterior cruciate ligament (ACL) reconstruction is the gold standard surgical option for ACL tears. Another treatment method is primary ACL repair. The latter has some limitations such as a small range of indications — proximal tears only. However, they still constitute a significant portion of ACL injuries. Although the primary repair has been known for a long time and is still developing, recent publications show conflicting opinions regarding its application. The aim of study is to compare functional outcomes of patients who underwent anterior cruciate ligament reconstruction and primary repair. Methods. In the period from 2020 to 2023, we conducted randomized prospective multicenter control comparative study, which enrolled 170 patients with the ACL tear types A, B, E according to the Gächter classification. The injuries were no older than 3 months. The patients were divided into two groups: Group 1 — primary repair of the ACL, Group 2 — standard technique of the ACL reconstruction with a tendon autograft. Knee function was assessed before surgery and 3, 6, 12, 24 months postoperatively using the IKDC 2000 and Lysholm Knee Score. Results. Type E of ACL injury prevailed in the sample. The most common associated injury in both cohorts was medial meniscus tear — 39.3±0.05% and 45.3±0.05% for Group1 and 2, relatively. Chondrolabral defects were observed in 15.5±0.04% of patients with primary repair, and in 10.5±0.03% of patients from the reconstruction group. Pain relief therapy in the form of opioid analgesics received 46.03±0.06% patients in Group 2 and 25.35±0.05% in Group 1 (p0.05). The proportion of patients requiring reoperation for ACL injury in Group 1 was 3.5% and 1.2% in Group 2 (p0,05). Both groups had a statistically significant increase in functional outcomes according to the scales at 3, 6, 12 months (p0.05). The difference in knee function between the groups was not statistically significant (p0.05). Conclusion. Primary ACL repair still retains a large number of limitations. It cannot and should not replace ACL reconstruction. However, with strict adherence to the indications and surgical technique, primary ACL repair demonstrates comparable functional outcomes.

Mitochondrial-related drug resistance lncRNAs as prognostic biomarkers in laryngeal squamous cell carcinoma

Laryngeal squamous cell carcinoma (LSCC) is a common malignant tumor of the head and neck that significantly impacts patients' quality of life, with chemotherapy resistance notably affecting prognosis. This study aims to identify prognostic biomarkers to optimize treatment strategies for LSCC. Using data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO), combined with mitochondrial gene database analysis, we identified mitochondrial lncRNAs associated with drug resistance genes. Key long non-coding RNAs (lncRNAs) were selected through univariate Cox regression and Lasso regression, and a multivariate Cox regression model was constructed to predict prognosis. We further analyzed the differences in immune function and biological pathway enrichment between high- and low-risk groups, developed a nomogram, and compared drug sensitivity. Results showed that the prognostic model based on seven mitochondrial lncRNAs could serve as an independent prognostic factor, with Area Under the Curve (AUC) values of 0.746, 0.827, and 0.771 at 1, 3, and 5 years, respectively, outperforming some existing models, demonstrating high predictive performance. Significant differences were observed in immune function and drug sensitivity between the high- and low-risk groups. The risk prediction model incorporating seven drug resistance-related mitochondrial lncRNAs can accurately and independently predict the prognosis of LSCC patients.

Low income, being without employment, and living alone: how they are associated with cognitive functioning—Results from the German national cohort (NAKO)

ABSTRACT Aim was to investigate to what extent cognitive functioning differs by three socioeconomic conditions: low income, being without employment, and living alone. A total of N = 158,144 participants of the population-based German National Cohort (NAKO) provided data on socioeconomic conditions and completed cognitive tests. Multivariable confounder-adjusted regression analyses indicated that cognitive functioning was lower in those with low income (b = −0.21) compared to not having low income, living alone (b = −0.04) compared to not living alone, and being without employment (b = −0.09) compared to being employed. An interaction with age indicated that the difference in cognitive functioning was getting larger with age between the income groups and living alone status groups. Accordingly, the three conditions appear independently associated with poorer cognitive functioning. Pathways of how cognitive health in this population group can be improved need to be explored.

Sex differences in mitochondrial gene expression during viral myocarditis

BackgroundMyocarditis is an inflammation of the heart muscle most often caused by viral infections. Sex differences in the immune response during myocarditis have been well described but upstream mechanisms in the heart that might influence sex differences in disease are not completely understood.MethodsMale and female BALB/c wild type mice received an intraperitoneal injection of heart-passaged coxsackievirus B3 (CVB3) or vehicle control. Bulk-tissue RNA-sequencing was conducted to better understand sex differences in CVB3 myocarditis. We performed enrichment analysis and functional validation to understand sex differences in the transcriptional landscape of myocarditis and identify factors that might drive sex differences in myocarditis.ResultsAs expected, the hearts of male and female mice with myocarditis were significantly enriched for pathways related to an innate and adaptive immune response compared to uninfected controls. Unique to this study, we found that males were enriched for inflammatory pathways and gene changes that suggested worse mitochondrial electron transport function while females were enriched for pathways related to mitochondrial homeostasis. Mitochondria isolated from the heart of males were confirmed to have worse mitochondrial respiration than females during myocarditis. Unbiased TRANSFAC analysis identified estrogen-related receptor alpha (ERRα) as a transcription factor that may mediate sex differences in mitochondrial function during myocarditis. Transcript and protein levels of ERRα were confirmed as elevated in females with myocarditis compared to males. Differential binding analysis from chromatin immunoprecipitation (ChIP) sequencing confirmed that ERRα bound highly to select predicted respiratory chain genes in females more than males during myocarditis.ConclusionsFemales with viral myocarditis regulate mitochondrial homeostasis by upregulating master regulators of mitochondrial transcription including ERRα.

Subregions of the Rotator Cuff Muscles Present Distinct Anatomy, Biomechanics, and Function

Shoulder and elbow injuries are prevalent among baseball players, particularly pitchers, who experience repetitive eccentric loading of the shoulder, leading to muscle damage and increased injury risk. Nearly 40% of shoulder injuries in baseball occur in pitchers, with many facing low rates of return to sport. The rotator cuff (RC) muscles—supraspinatus (SSP), infraspinatus (ISP), subscapularis (SSC), and teres minor (TMin)—are crucial for shoulder stability, movement, and force generation, particularly in overhead sports. Each RC muscle comprises subregions with distinct biomechanical properties, such as strength, moment arm behavior, and activation patterns. These differences allow for a finely tuned balance between joint stability and mobility. For example, the superior subregion of the ISP significantly contributes to external rotation, a function critical in sports like baseball that require precision and power. During pitching, the SSP, ISP, and SSC stabilize the glenohumeral joint through high activation during explosive phases, such as stride, arm cocking, and arm acceleration. Understanding these functional subregional differences is vital for diagnosing and managing shoulder pathologies like RC tears. Despite advancements, clinicians face challenges in predicting re-injury risks and determining return-to-play readiness for athletes with shoulder injuries. Integrating insights into subregional biomechanics with patient care could enhance outcomes. Tailored interventions—whether surgical or rehabilitative—targeting specific subregions could improve recovery times, reduce re-injury risks, and enable more personalized treatment plans. Such approaches are especially beneficial for athletes, older individuals, and those prone to RC injuries, promoting better long-term shoulder health and performance. The present work aims to highlight some of the research on these subregions and their differences, providing insights to enhance treatment approaches for shoulder injuries.

Lipid metabolism subtypes reflects the prognosis and immune profiles of bladder cancer patients by NMF clustering and building related signature

BackgroundLipid metabolism is crucial in tumor formation and progression. However, the role of lipid metabolism genes (LMGs) in bladder cancer (BLCA) are unknown. The purpose of this study was to construct a LMGs-related subtypes that predicted the treatment and prognosis of BLCA patients.MethodsThe Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases were used for this study. The gene set enrichment analysis (GSEA) was utilized to distinguish functional differences between high-risk (HR) and low-risk (LR) groups. Single-sample GSEA (ssGSEA) was employed to determine potential associations between prognostic outcomes and immune status.ResultsFirst, BLCA patients were divided into two subtypes by non-negative matrix factorization (NMF) clustering, and there were substantial variations in survival status, immune cell infiltration and immune classification between the two subtypes. Next, a prognostic signature involving 8 LMGs was identified (AKR1B1, SCD, CYP27B1, UGCG, SGPL1, FASN, TNFAIP8L3, PLA2G2A). HR patients exhibited worse outcome than LR patients. Multivariate Cox regression analysis confirmed that LMGs-related signature was an independent prognostic indicator of BLCA patients’ survival. Compared with clinicopathological variables, LMGs-related signature showed higher prognostic predictive ability, with an area under curve of 0.720 at 5 years of follow-up. Through immunotherapy analysis, drug sensitivity analysis, TIDE score and immune cell infiltration characteristics, LMGs-related signature was confirmed to accurately predict the prognosis and treatment response of BLCA patients.ConclusionOur newly established prognostic signature, which involved eight LMGs, can give prognostic distinction for BLCA and may eventually lead to novel targets for treatment.

Microbiome-proteome analysis of gastrointestinal microbiota and longissimus thoracis muscle proteins in cattle with high and low grades of marbling

Marbling is a key indicator of the meat quality of ruminants. Gastrointestinal microbiota may regulate the formation of marbling by influencing the nutritional metabolism of animals. This study analyzed the composition and functional differences of microbiota in the rumen and cecum, the differences in volatile fatty acids (VFAs) content in the longissimus thoracis muscle, and the differences in protein abundance in the longissimus thoracis muscle of ruminants with different marbling grades through microbiome-proteome analysis. The results showed that the diversity of gastrointestinal microbiota in high-marbling ruminants was significantly higher than that in low-marbling ruminants. The relative abundance of Firmicutes and Akkermansia in the gastrointestinal of high-marbling ruminants was higher than that in low-marbling ruminants, while the relative abundance of Bacteroidetes and Prevotella was lower. In addition, PICRUST2 functional prediction results of the microbiota revealed that the gastrointestinal microbiota of high-marbling ruminants was mainly involved in the biosynthesis pathways of fat and lipids. The metabolomics results showed that the content of VFAs (acetic acid, propionic acid, butyric acid, isovaleric acid, valeric acid, and hexanoic acid) in the rumen of high-marbling ruminants was significantly higher than that in low-marbling ruminants. The proteome analysis results indicated that the differential proteins in the longissimus thoracis muscle of high-marbling ruminants were mainly involved in lipid transport and metabolism compared to low-marbling ruminants. In summary, the differences in the composition and function of the gastrointestinal microbiota led to higher levels of VFAs in the gastrointestinal tract of high-marbling ruminants, which provides the basis for lipid/fat synthesis. The proteome results of the longissimus thoracis muscle support the view that high-marbling ruminants have richer lipid transport and metabolic functions in their muscle.

Functional, instrumental test of flexion-extension movements of the wrist joint. Normative parameters.

Background: Stroke is a significant medical and social issue due to its high incidence and mortality rates, with a trend toward increasing overall cases. In 80% of patients, upper limb dysfunction persists. Existing methods, such as clinical scales and questionnaires, are criticized for their subjectivity and lack of precision. There is a need to develop an instrumental method for assessing upper limb function that can be applied in clinical settings. Aims: To develop a functional test for the objective diagnosis of wrist joint function applicable in clinical settings. Methods: A functional test was proposed to assess the biomechanics of the wrist joint using inertial sensors. The study involved 15 healthy volunteers (5 men and 10 women, aged 23 to 33), with no joint diseases or neurological disorders. The study was conducted over one year (2022–2023). The primary endpoint was to determine the amplitude, time, and trajectory of wrist joint movements during two tests—"Wrist-0" and "Wrist-Flex." Evaluation was based on the duration of the movement cycle, maximum amplitude, and movement phase. Results: Assessment of upper limb function using clinical scales (ARAT, FMA-UE, MRC) showed that parameters were consistent with those of healthy individuals. In the "Wrist-0" test, movement amplitude was significantly lower compared to the "Wrist-Flex" test (p0.05). There were no statistically significant differences in movement amplitude between the right and left limbs in either test (p0.05). The phase of maximum flexion in the "Wrist-0" test occurred significantly earlier than in the "Wrist-Flex" test for the right hand (p0.05). The movement cycle duration did not differ significantly between tests for the right hand (p0.05) but was significantly longer in the "Wrist-Flex" test for the left hand (p0.05). Conclusions: Normative parameters for the functional test have been established. Minor differences in function between the right and left wrist joints were observed. The proposed test requires minimal time to administer and can be used for the objective diagnosis of wrist joint function in patients.

Refining Flash Visual Evoked Potential Analysis in Rats: A Novel Approach Using Bilateral Epidural Electrodes.

Visual evoked potentials (VEPs) are electrical signals generated at the visual cortex following visual stimulation. Flash VEPs (fVEPs) are produced by global retinal stimulation and are considered an objective measure of the integrity of the entire visual pathway. However, fVEP measurements are highly sensitive to external variables, making relative comparisons of the fVEP waveforms between the two eyes in the same individual challenging. We used the rodent non-arteritic anterior ischemic optic neuropathy (rNAION) model to induce unilateral ischemic optic neuropathy. The severity of optic disc edema was measured with spectral-domain optical coherence tomography, and visual acuity was measured using a virtual optokinetic system. We developed a procedure utilizing implanted bilateral epidural electrodes and derived a mathematical formula to accurately estimate functional differences between the optic nerves. Immunohistology was performed to quantify retinal ganglion cell (RGC) survival using stereology. Compared to subcutaneous methods, the new approach significantly improves the signal-to-noise ratio and is more repeatable when comparing the two eyes. The derived formula accounts for asymmetry in the afferent inputs to the visual cortex. Visual function calculated using the formula correlates strongly with other recognized metrics of visual function, including RGC survival and visual acuity. We have developed a repeatable and accurate method to calculate the relative visual function of diseased optic nerves compared with a contralateral control eye. Our novel method improves fVEP measurement sensitivity and accuracy in rodent preclinical trials, reducing the number of animals needed to achieve statistical significance.

Abnormal characteristics in disorders of consciousness: A resting-state functional magnetic resonance imaging study.

To explore the functional brain imaging characteristics of patients with disorders of consciousness (DoC). This prospective cohort study consecutively enrolled 27 patients in minimally conscious state (MCS), 23 in vegetative state (VS), and 25 age-matched healthy controls (HC). Resting-state functional magnetic resonance imaging (rs-fMRI) was employed to evaluate the amplitude of low-frequency fluctuation (ALFF), regional homogeneity (ReHo), degree centrality (DC), and functional connectivity (FC). Sliding windows approach was conducted to construct dynamic FC (dFC) matrices. Moreover, receiver operating characteristic analysis and Pearson correlation were used to distinguish these altered characteristics in DoC. Both MCS and VS exhibited lower ALFF, ReHo, and DC values, along with reduced FC in multiple brain regions compared with HC. Furthermore, the values in certain regions of VS were lower than those in MCS. The primary differences in brain function between patients with varying levels of consciousness were evident in the cortico-striatopallidal-thalamo-cortical mesocircuit. Significant differences in the temporal properties of dFC (including frequency, mean dwell time, number of transitions, and transition probability) were also noted among the three groups. Moreover, these multimodal alterations demonstrated high classificatory accuracy (AUC>0.8) and were correlated with the Coma Recovery Scale-Revised (CRS-R). Patients with DoC displayed abnormal patterns in local and global dynamic and static brain functions. These alterations in rs-fMRI were closely related to the level of consciousness.

Characteristics of airway microbiome co-occurrence network in patients with type 2 and non-type 2 asthma

Objective: To study the characteristics of the airway microbiome co-occurrence network in patients with type 2 and non-type 2 asthma. Methods: In a prospective study based on a cohort of asthma patients, respiratory induced sputum samples were collected from 55 asthma patients [25 males and 30 females, with a median age of 47.7 years (age range 34.3-63.0 years)] admitted to the Department of Respiratory and Critical Care, Beijing Chaoyang Hospital, Capital Medical University and 12 healthy controls from the Physical Examination Centre of Beijing Chaoyang Hospital, Capital Medical University, from May 2021 to May 2022. According to the level of exhaled breath nitric oxide (FeNO), the asthma patients were divided into 22 cases in the high FeNO group (FeNO≥40 ppb, i.e., type 2 asthma group) and 33 cases in the low FeNO group (FeNO<40 ppb, i.e., non-type 2 asthma group). All induced sputum samples were subjected to second-generation macrogenomic sequencing and bioinformatic analyses of microbial community diversity, compositional characteristics, symbiotic network characteristics and metabolic function prediction. The Kruskal-Wallis rank sum test was used for between-group comparisons, and the linear discriminant analysis (LEfSe) method was used to compare the differences in flora composition between groups. The R language was used for microbial network analysis. In addition, PICRUSt was used to predict the metabolic-functional characteristics of the microbial communities. Results: The microbial communities in the healthy control group had a lower proportion of p_Firmicutes and p_Proteobacteria than asthma patients, 29% and 21%, respectively; 37% and 33% in the low FeNO group and 42% and 26% in the high FeNO group. The microbial network in the low FeNO group had 64 pairs of edges forming 16 communities, and about 75% of the nodes had eigenvector centrality values between 0 and 0.05, and 25% of the nodes had eigenvector centrality values between 0.10 and 0.45. There were four layers of κ-nucleosynthesis, and about 42% of the vertices were in the centre of the two layers. The microbial network of the high-FeNO group had 80 pairs of edges forming 18 clusters, and 81% of the nodes had eigenvector centrality values between 0 and 0.05, and 19% of the nodes had eigenvector centrality values between 0.10 and 0.35. The κ-nucleus decomposition had eight layers, and 21% of the vertices were located in the centre's two layers. The main functional differences between the low and high FeNO groups were shown in metabolic pathways (including sugar, lipid, amino acid, and energy metabolism), drug resistance, biofilm transport, signalling, intercellular communication, and cellular repair. Conclusions: Compared with non-type 2 asthmatics, type 2 asthmatics had a higher alpha diversity of respiratory microbiota, lower levels of microorganisms in the p_Proteobacteria, and a more aggregated microbial network. There was a significant difference in the predicted metabolic function of the two endotypes of asthmatics.

Evolutionary Adaptations in Biliverdin Reductase B: Insights into Coenzyme Dynamics and Catalytic Efficiency

Biliverdin reductase B (BLVRB) is a redox regulator that catalyzes nicotinamide adenine dinucleotide phosphate (NADPH)-dependent reductions of multiple substrates, including flavins and biliverdin-β. BLVRB has emerging roles in redox regulation and post-translational modifications, highlighting its importance in various physiological contexts. In this study, we explore the structural and functional differences between human BLVRB and its hyrax homologue, focusing on evolutionary adaptations at the active site and allosteric regions. Using NMR spectroscopy, we compared coenzyme binding, catalytic turnover, and dynamic behavior between the two homologues. Despite lacking the arginine “clamp” present in human BLVRB, hyrax BLVRB still undergoes conformational changes in response to the oxidative state of the coenzyme. Mutations at the allosteric site (position 164) show that threonine at this position enhances coenzyme discrimination and allosteric coupling in human BLVRB, while hyrax BLVRB does not display the same allosteric effects. Relaxation experiments revealed distinct dynamic behaviors in hyrax BLVRB, with increased flexibility in its holo form due to the absence of the clamp. Our findings suggest that the evolutionary loss of the active site clamp and modifications at position 164 in hyrax BLVRB alter the enzyme’s conformational dynamics and coenzyme interactions. Identified similarities and differences underscore how key regions modulate catalytic efficiency and suggest that coenzyme isomerization may represent the rate-limiting step in both homologues.

Investigation of functional connectivity differences based on anxiety tendencies

IntroductionAnxiety is an emotion necessary for human survival. However, persistent and excessive anxiety can be clinically challenging. Increased anxiety affects daily life and requires early detection and intervention. Therefore, a better understanding of the neural basis of mild anxiety is needed. However, previous studies have focused primarily on resting-state functional magnetic resonance imaging (rs-fMRI) in patients with psychiatric disorders presenting with anxiety. Notably, only a few studies have been conducted on healthy participants, and the relationship between anxiety and functional brain connectivity in the healthy range remains unclear. Therefore, in this study, we aimed to clarify the differences in functional brain connectivity at different degrees of anxiety among healthy participants.MethodsThis study included 48 healthy participants with no history of psychiatric disorders. Participants were administered The General Health Questionnaire (GHQ) 60, a psychological test for assessing anxiety, and the Manifest Anxiety Scale (MAS). The participants then underwent rs-fMRI. Based on the results of each psychological test, the participants were classified into normal and anxiety groups, and the functional connectivity between the two groups was compared using a seed-to-voxel analysis.ResultsComparison of functional brain connectivity between the normal and anxiety groups classified based on the GHQ60 and MAS revealed differences between brain regions comprising the salience network (SN) in both psychological tests. For the GHQ60, the anxiety group showed reduced connectivity between the right supramarginal gyrus and insular cortex compared with the normal group. However, for the MAS, the anxiety group showed reduced connectivity between the right supramarginal and anterior cingulate cortical gyri compared with the normal group.ConclusionFunctional connectivity within the SN was reduced in the group with higher anxiety when functional brain connectivity at different anxiety levels was examined in healthy participants. This suggests that anxiety is involved in changes in the functional brain connectivity associated with emotional processing and cognitive control.

The impact of surgery with general anesthesia on cognitive function and putamen volume: a cross-sectional study among older adults

BackgroundPrevious studies have shown that surgery under general anesthesia may diminish cognitive function; however, the proposed mechanisms need further elucidation. The purpose of the current study was twofold: (1) to compare overall and domain-specific differences in cognitive function between the surgery under general anesthesia group and the control group, and (2) to investigate the possible mechanisms of surgery under general anesthesia affecting cognitive function, using T1-structural magnetic resonance imaging.MethodsA total of 194 older adults were included in this study. Patients were divided into a surgery under general anesthesia group (n = 92) and a control group (n = 104). The two groups were matched for age, sex, and educational level. All participants underwent clinical evaluation, neuropsychological testing, blood biochemistry analysis, and T1 phase structural magnetic resonance imaging.ResultsWe found that older adults with a history of surgery under general anesthesia had lower Montreal Cognitive Assessment (MoCA) scores and smaller right putamen volumes (p &amp;lt; 0.05). Linear regression analysis (mediation model) indicated that surgery under general anesthesia affected MoCA scores by diminishing the volume of the right putamen (B = 1.360, p = 0.030).ConclusionWe found evidence that older adults who underwent surgery under general anesthesia had poorer cognitive function, which may have been caused by an apoptotic or otherwise toxic effect of anesthetic drugs on the volume of the right putamen.

Effect of ICG fluorescence-assisted new nerve-sparing of robot-assisted radical prostatectomy on lower urinary tract symptoms.

The aim of the present study was to determine the efficacy and safety of our newly developed ICG-assisted nerve-sparing (NS) robot-assisted radical prostatectomy (RARP) through subjective and objective data. This study included 43 NS RARP patients, divided into ICG (23 patients) and non-ICG (20 patients) groups. Immunohistochemical staining with nNOS antibodies was conducted on specimens of resected prostate from the base, middle, and apex to count nNOS-positive cells. Fewer nNOS-positive cells suggested higher quality for the NS procedure. Postoperative erectile function, urinary incontinence, lower urinary tract symptoms (LUTS) as evaluated by the International Prostate Symptom Score (IPSS), and lower urinary tract function were compared between groups, operative time, and adverse events. Only the number of n-NOS-positive cells at the base differed significantly between the ICG group (15.0 ± 6.9) and the non-ICG group (26.9 ± 21.4, p = 0.02). Regarding LUTS, in the ICG group, significant improvement was only seen in postoperative IPSS scores (13.6 ± 4.9 to 8.7 ± 5.0, p = 0.02). No significant differences in the postoperative erectile function, urinary incontinence, and lower urinary tract function were seen between groups. In addition, significant differences in operative time and rate of adverse events were not observed between groups. Our innovative approach enhances the visualization of prostatic boundaries, suggesting potential for reliable and straightforward NS procedures, with a significant improvement in LUTS, without evidence of prolonged operative time or an increased frequency of adverse events.

Pemafibrate Induces a Low Level of PPARα Agonist-Stimulated mRNA Expression of ANGPTL4 in ARPE19 Cell

To elucidate the unidentified roles of a selective peroxisome proliferator-activated receptor α (PPARα) agonist, pemafibrate (Pema), on the pathogenesis of retinal ischemic diseases (RID)s, the pharmacological effects of Pema on the retinal pigment epithelium (RPE), which is involved in the pathogenesis of RID, were compared with the pharmacological effects of the non-fibrate PPARα agonist GW7647 (GW). For this purpose, the human RPE cell line ARPE19 that was untreated (NT) or treated with Pema or GW was subjected to Seahorse cellular metabolic analysis and RNA sequencing analysis. Real-time cellular metabolic function analysis revealed that pharmacological effects of the PPARα agonist actions on essential metabolic functions in RPE cells were substantially different between Pema-treated cells and GW-treated cells. RNA sequencing analysis revealed the following differentially expressed genes (DEGs): (1) NT vs. Pema-treated cells, 37 substantially upregulated and 72 substantially downregulated DEGs; (2) NT vs. GW-treated cells, 32 substantially upregulated and 54 substantially downregulated DEGs; and (3) Pema vs. GW, 67 substantially upregulated and 51 markedly downregulated DEGs. Gene ontology (GO) analysis and ingenuity pathway analysis (IPA) showed several overlaps or differences in biological functions and pathways estimated by the DEGs between NT and Pema-treated cells and between NT and GW-treated cells, presumably due to common PPARα agonist actions or unspecific off-target effects to each. For further estimation, overlaps of DEGs among different pairs of comparisons (NT vs. Pema, NT vs. GW, and Pema vs. GW) were listed up. Angiopoietin-like 4 (ANGPTL4), which has been shown to cause deterioration of RID, was the only DEG identified as a common significantly upregulated DEG in all three pairs of comparisons, suggesting that ANGPTL4 was upregulated by the PPARα agonist action but that its levels were substantially lower in Pema-treated cells than in GW-treated cells. In qPCR analysis, such lower efficacy for upregulation of the mRNA expression of ANGPTL4 by Pema than by GW was confirmed, in addition to substantial upregulation of the mRNA expression of HIF1α by both agonists. However, different Pema and GW-induced effects on mRNA expression of HIF1α (Pema, no change; GW, significantly downregulated) and mRNA expression of ANGPTL4 (Pema, significantly upregulated; GW, significantly downregulated) were observed in HepG2 cells, a human hepatocyte cell line. The results of this study suggest that actions of the PPARα agonists Pema and GW are significantly organ-specific and that lower upregulation of mRNA expression of the DR-worsening factor ANGPTL4 by Pema than by GW in ARPE19 cells may minimize the risk for development of RID.

Ethnicity as a Risk Factor for Early Neurological Deterioration: A Post Hoc Analysis of the Secondary Prevention of Small Subcortical Strokes Trial.

Nearly 25% of those with a small vessel stroke will develop early neurological deterioration (END). The objectives of this study were to identify clinical risk factors for small vessel stroke-related END and its associated impact on functional outcomes in an ethnically diverse data set. We performed a post hoc analysis of the "Secondary Prevention of Small Subcortical Strokes" trial. The primary outcome was END defined as progressive or stuttering stroke-related neurological symptoms. Standard descriptive and inferential statistical methods were used for analysis. Functional outcomes are reported by modified Rankin Scale score and analyzed by the Wilcoxon signed-rank test. In all, 69 participants met the inclusion criteria; 21 (30%) had END. Of the cohort, Spanish, Hispanic, or Latino ethnicity (grouping per trial definition) most frequently developed END [11 (52.4%) vs 4 (8.3%), P < 0.001] with a higher adjusted likelihood of END (odds ratio: 14.1, 95% CI: 2.57-76.7, P = 0.002). Black or African-American race less commonly had END [3 (14.3%) vs 21 (43.8%), P = 0.03] but lost significance after adjustment (odds ratio: 1.46, 95% CI: 0.26-8.17, P = 0.67) due to powering. END was associated with a higher mean modified Rankin Scale (2.06 ± 0.94 vs 1.17 ± 0.79, P = 0.006) but did not differ in the shift analysis. We found that Spanish, Hispanic, or Latino ethnicity was the most consistent risk factor for END though it was without meaningful functional outcome differences.