Nevin Manimala

Continence (Amst). 2022 Mar;1:100014. doi: 10.1016/j.cont.2022.100014. Epub 2022 Mar 18.

ABSTRACT

PURPOSE OR THE RESEARCH: Nearly 300,000 people are affected by spinal cord injury (SCI) with approximately 18,000 new cases annually, according to the National SCI Statistics Center. SCI affects physical mobility and impairs the function of multiple internal organs to cause lower urinary tract (LUT) dysfunctions manifesting as detrusor sphincter dyssynergia (DSD) and neurogenic detrusor overactivity (NDO) with detrimental consequences to the quality of life and increased morbidity. Multiple lines of evidence now support time dependent evolution of the complex SCI pathology which requires a multipronged treatment approach of immediate, specialized care after spinal cord trauma bookended by physical rehabilitation to improve the clinical outcomes. Instead of one size fits all treatment approach, we propose adaptive drug treatment to counter the time dependent evolution of SCI pathology, with three small molecule drugs with distinctive sites of action for the recovery of multiple functions.

PRINCIPAL RESULTS: Our findings demonstrate the improvement in the recovery of hindlimb mobility and bladder function of spinal cord contused mice following administration of small molecules targeting neurotrophin receptors, LM11A-31 and LM22B-10. While LM11A-31 reduced the cell death in the spinal cord, LM22B-10 promoted cell survival and axonal growth. Moreover, the soluble guanylate cyclase (sGC) activator, cinaciguat, enhanced the revascularization of the SCI injury site to promote vessel formation, dilation, and increased perfusion.

MAJOR CONCLUSIONS: Our adaptive three drug cocktail targets different stages of SCI and LUTD pathology: neuroprotective effect of LM11A-31 retards the cell death that occurs in the early stages of SCI; and LM22B-10 and cinaciguat promote neural remodeling and reperfusion at later stages to repair spinal cord scarring, DSD and NDO. LM11A-31 and cinaciguat have passed phase I and IIa clinical trials and possess significant potential for accelerated clinical testing in SCI/LUTD patients.

PMID:37207253 | PMC:PMC10194419 | DOI:10.1016/j.cont.2022.100014

J Ophthalmol. 2023 May 10;2023:5625990. doi: 10.1155/2023/5625990. eCollection 2023.

ABSTRACT

PURPOSE: To investigate the clinical effectiveness of canaloplasty performed with an ab interno technique using the iTrack microcatheter (Nova Eye Medical) in patients with mild-moderate glaucoma as compared to severe glaucoma.

METHODS: This is a retrospective single-center case series. Patients were preoperatively categorized as mild/moderate vs. severe glaucoma assessed using the mean deviation (MD) score and controlled group (baseline intraocular pressure (IOP) ≤18 mmHg) vs. uncontrolled group (>18 mmHg). All patients with glaucoma were eligible for recruitment except those who had undergone previous glaucoma surgery (with the exception of selective laser trabeculoplasty or SLT). Patients underwent canaloplasty via an ab interno surgical technique with or without phacoemulsification and were monitored for IOP, glaucoma medication usage, and surgical complications.

RESULTS: In total, 72 eyes were followed for 3.4 ± 0.5 years. Mean pre-op IOP (mmHg) was 19.3 ± 7.7 in the standalone group (n = 9) and 18.5 ± 5.6 in the combined group (n = 63) (p=0.38). At the last follow-up, mean IOP reduced by 36% to 12.4 ± 4.4 (p=0.02) in the standalone group and by 26% to 13.7 ± 4.8 in the combined group (p < 0.001). Mean pre-op IOP (mmHg) was 18.6 ± 5.2 in the severe group (n = 24) and 18.6 ± 6.2 in the mild-moderate group (n = 48) (p=0.48). Mean IOP was 14.1 ± 6.3 (-24%; p < 0.001) and 13.3 ± 3.7 (-29%; p < 0.001), respectively, at the last follow-up. Mean glaucoma medication usage decreased from 2.5 ± 0.9 to 2.1 ± 0.9 (-15%; p=0.083) in the severe group and 2.3 ± 1.0 to 1.4 ± 1.3 (-40%; p < 0.001) in the mild/moderate group. There was one localized Descemet’s membrane detachment in the moderate group.

CONCLUSION: iTrack canaloplasty achieved a statistically significant IOP reduction in mild-moderate and severe eyes and was found to be an effective option for reducing IOP and medications in patients with mild-moderate primary open-angle glaucoma (POAG). In severe eyes, it has reduced IOP while the medications remained stable.

PMID:37207241 | PMC:PMC10191748 | DOI:10.1155/2023/5625990

Eur Union Polit. 2023 Jun;24(2):327-347. doi: 10.1177/14651165221142504. Epub 2022 Dec 4.

ABSTRACT

The rotating EU presidency’s relevance for EU politics has decreased since the introduction of a permanent council president. However, news salience and framing of the own government acting as the EU presidency can amplify publicity for EU affairs. We, therefore, evaluate the visibility and framing of the EU presidency in 12 Austrian newspapers for 2009-2019. We conduct an automated text analysis of 22 presidencies over 11 years, testing several hypotheses statistically, and qualify results via manually coded frames of the Austrian EU presidency in 2018. The results confirm the crucial importance of the domestication of EU politics, underscoring the potential of the presidency to serve as a window of opportunity for public debate. We discuss our findings with reference to the EU’s democratic deficit.

PMID:37207239 | PMC:PMC10189837 | DOI:10.1177/14651165221142504

Front Immunol. 2023 May 3;14:1160048. doi: 10.3389/fimmu.2023.1160048. eCollection 2023.

ABSTRACT

BACKGROUND: Immune thrombocytopenia (ITP) is an autoimmune disease characterized by isolated thrombocytopenia. Recently, the pathophysiology and novel drugs of ITP have been the focus of researchers with plenty of publications emerging. Bibliometrics is the process of extracting measurable data through statistical analysis of published research studies to provide an insight into the trends and hotspots.

OBJECTIVE: This study aimed to provide an insight into developing trends and hotspots in the field of ITP by bibliometric analysis.

METHODS: By using three bibliometric mapping tools (bibliometrix R package, VOSviewer, CiteSpace), we summarized the overview information of retrieved publications, as well as the analysis of keyword co-occurrence and reference co-citation.

RESULTS: A total of 3299 publications with 78066 citations on ITP research were included in the analysis. The keyword co-occurrence network identified 4 clusters relating to the diagnosis, pathophysiology, and treatment of ITP respectively. Then the reference co-citation analysis produced 12 clusters with a well-structured and highly credible clustering model, and they can be divided into 5 trends: second-line treatment, chronic ITP, novel therapy and pathogenesis, COVID-19 vaccine. Treg cells, spleen tyrosine kinase, and mesenchymal stem cells were the latest hotspots with strong burstness.

CONCLUSION: This bibliometric analysis provided a comprehensive insight into research hotspots and trends on ITP, which would enrich the review of the ITP research.

PMID:37207211 | PMC:PMC10189105 | DOI:10.3389/fimmu.2023.1160048

Front Immunol. 2023 May 3;14:1162669. doi: 10.3389/fimmu.2023.1162669. eCollection 2023.

ABSTRACT

BACKGROUND: Recent clinical trial data from Lynch Syndrome (LS) carriers demonstrated that naproxen administered for 6-months is a safe primary chemoprevention that promotes activation of different resident immune cell types without increasing lymphoid cellularity. While intriguing, the precise immune cell types enriched by naproxen remained unanswered. Here, we have utilized cutting-edge technology to elucidate the immune cell types activated by naproxen in mucosal tissue of LS patients.

METHODS: Normal colorectal mucosa samples (pre- and post-treatment) from a subset of patients enrolled in the randomized and placebo-controlled ‘Naproxen Study’ were obtained and subjected to a tissue microarray for image mass cytometry (IMC) analysis. IMC data was processed using tissue segmentation and functional markers to ascertain cell type abundance. Computational outputs were then used to quantitatively compare immune cell abundance in pre- and post-naproxen specimens.

RESULTS: Using data-driven exploration, unsupervised clustering identified four populations of immune cell types with statistically significant changes between treatment and control groups. These four populations collectively describe a unique cell population of proliferating lymphocytes within mucosal samples from LS patients exposed to naproxen.

CONCLUSIONS: Our findings show that daily exposure of naproxen promotes T-cell proliferation in the colonic mucosa, which paves way for developing combination of immunoprevention strategies including naproxen for LS patients.

PMID:37207208 | PMC:PMC10189148 | DOI:10.3389/fimmu.2023.1162669

Front Immunol. 2023 May 3;14:1164724. doi: 10.3389/fimmu.2023.1164724. eCollection 2023.

ABSTRACT

INTRODUCTION: Immune checkpoint inhibitors have had a major impact on cancer treatment. Gut microbiota plays a major role in the cancer microenvironment, affecting treatment response. The gut microbiota is highly individual, and varies with factors, such as age and race. Gut microbiota composition in Japanese cancer patients and the efficacy of immunotherapy remain unknown.

METHODS: We investigated the gut microbiota of 26 patients with solid tumors prior to immune checkpoint inhibitor monotherapy to identify bacteria involved in the efficacy of these drugs and immune-related adverse events (irAEs).

RESULTS: The genera Prevotella and Parabacteroides were relatively common in the group showing efficacy towards the anti-PD-1 antibody treatment (effective group). The proportions of Catenibacterium (P = 0.022) and Turicibacter (P = 0.049) were significantly higher in the effective group than in the ineffective group. In addition, the proportion of Desulfovibrion (P = 0.033) was significantly higher in the ineffective group. Next, they were divided into irAE and non-irAE groups. The proportions of Turicibacter (P = 0.001) and Acidaminococcus (P = 0.001) were significantly higher in the group with irAEs than in those without, while the proportions of Blautia (P = 0.013) and the unclassified Clostridiales (P = 0.027) were significantly higher in the group without irAEs than those with. Furthermore, within the Effective group, Acidaminococcus and Turicibacter (both P = 0.001) were more abundant in the subgroup with irAEs than in those without them. In contrast, Blautia (P = 0.021) and Bilophila (P= 0.033) were statistically significantly more common in those without irAEs.

DISCUSSION: Our Study suggests that the analysis of the gut microbiota may provide future predictive markers for the efficacy of cancer immunotherapy or the selection of candidates for fecal transplantation for cancer immunotherapy.

PMID:37207204 | PMC:PMC10189048 | DOI:10.3389/fimmu.2023.1164724

Int J Nurs Health Care Res (Lisle). 2022;5(7):1324. doi: 10.29011/2688-9501.101324. Epub 2022 Aug 17.

ABSTRACT

This pilot-cross sectional study compared Urinary Incontinence symptom type and severity, and impact of UI on Quality of Life among older White and Black women. Outcome measures included a three-day bladder diary (3dbd), Incontinence Impact Questionnaire Short Form (IIQ-7), Urinary Distress Inventory Short Form (UDI-6), Medical Epidemiological Social Aspects of Ageing (MESA) questionnaire, and Patient Global Impact of Severity Scale (PGI-S). Participants’ characteristics and UI outcomes were analysed with descriptive statistics, Fisher’s Exact and Mann-Whitney U tests. Twenty women (10 White, and 10 Black) with mean age of 76.5 (± 4.9 years) participated in the study. There were no significant differences in most UI symptoms based on 3dbd, MESA, PGI-S, UDI-6, and IIQ-7. However, older Black women reported moderate and/or severe impact of UI on their emotional health more frequently (n=7, 70%) compared to White women (n=1, 10%, p=0.02) based on the IIQ-7.

PMID:37207183 | PMC:PMC10195058 | DOI:10.29011/2688-9501.101324

Front Oncol. 2023 May 3;13:1150539. doi: 10.3389/fonc.2023.1150539. eCollection 2023.

ABSTRACT

OBJECTIVE: Preoperative noninvasive diagnosis of the benign or malignant solitary pulmonary nodule (SPN) is still important and difficult for clinical decisions and treatment. This study aimed to assist in the preoperative diagnosis of benign or malignant SPN using blood biomarkers.

METHODS: A total of 286 patients were recruited for this study. The serum FR⁺CTC, TK1, TP, TPS, ALB, Pre-ALB, ProGRP, CYFRA21-1, NSE, CA50, CA199, and CA242 were detected and analyzed.

RESULTS: In the univariate analysis, age, FR⁺CTC, TK1, CA50, CA19.9, CA242, ProGRP, NSE, CYFRA21-1, and TPS showed the statistical significance of a correlation with malignant SPNs (P <0.05). The highest performing biomarker is FR⁺CTC (odd ratio [OR], 4.47; 95% CI: 2.57-7.89; P <0.001). The multivariate analysis identified that age (OR, 2.69; 95% CI: 1.34-5.59, P = 0.006), FR⁺CTC (OR, 6.26; 95% CI: 3.09-13.37, P <0.001), TK1 (OR, 4.82; 95% CI: 2.4-10.27, P <0.001), and NSE (OR, 2.06; 95% CI: 1.07-4.06, P = 0.033) are independent predictors. A prediction model based on age, FR⁺CTC, TK1, CA50, CA242, ProGRP, NSE, and TPS was developed and presented as a nomogram, with a sensitivity of 71.1% and a specificity of 81.3%, and the AUC was 0.826 (95% CI: 0.768-0.884).

CONCLUSIONS: The novel prediction model based on FR⁺CTC showed much stronger performance than any single biomarker, and it can assist in predicting benign or malignant SPNs.

PMID:37207165 | PMC:PMC10189144 | DOI:10.3389/fonc.2023.1150539

Front Oncol. 2023 May 3;13:1143059. doi: 10.3389/fonc.2023.1143059. eCollection 2023.

ABSTRACT

OBJECTIVE: The purpose of this study was to verify whether there are direct or mediated causal associations between socioeconomic status and lung cancer.

METHODS: Pooled statistics were obtained from corresponding genome-wide association studies. The inverse-variance weighted, weighted median, MR-Egger, MR-PRESSO and contamination-mixture methods were used as supplements to Mendelian randomization (MR) statistical analysis. Cochrane’s Q value and the MR-Egger intercept were used for sensitivity analysis.

RESULTS: In the univariate MR analysis, household income and education had protective effects on overall lung cancer (income: P = 5.46×10^-4; education: P = 4.79×10^-7) and squamous cell lung cancer (income: P = 2.67×10^-3; education: P = 1.42×10^-10). Smoking and BMI had adverse effects on overall lung cancer (smoking: P = 2.10×10^-7; BMI: P = 5.67×10^-4) and squamous cell lung cancer (smoking: P = 5.02×10^-6; BMI: P = 2.03×10^-7). Multivariate MR analysis found that smoking and education were independent risk factors for overall lung cancer (smoking: P = 1.96×10^-7; education: P = 3.11×10^-3), while smoking was an independent risk factor for squamous cell lung cancer (P = 2.35×10^-6). Smoking, education, and household income mediate the effect of BMI on overall lung cancer (smoking 50.0%, education 49.2%, income 25.3%) and squamous cell lung cancer (smoking 34.8%, education 30.8%, income 21.2%). Smoking, education, and BMI mediate the effect of income on overall lung cancer (smoking 13.9%, education 54.8%, BMI 9.4%) and squamous cell lung cancer (smoking 12.6%, education 63.3%, BMI 11.6%). Smoking, BMI, and income mediate the effect of education on squamous cell lung cancer (smoking 24.0%, BMI 6.2%, income 19.4%).

CONCLUSION: Income, education, BMI, and smoking are causally associated with both overall lung cancer and squamous cell lung cancer. Smoking and education are independent association factors for overall lung cancer, while smoking is an independent association factor for squamous cell lung cancer. Smoking and education also play important mediating roles in overall lung cancer and squamous cell lung cancer. No causal relationship was found between multiple risk factors associated with socioeconomic status and lung adenocarcinoma.

PMID:37207156 | PMC:PMC10189779 | DOI:10.3389/fonc.2023.1143059

J Med Internet Res. 2023 May 19;25:e42365. doi: 10.2196/42365.

ABSTRACT

BACKGROUND: Interest in sensory rooms or so-called “calm rooms” in psychiatric inpatient care has increased significantly. In a hospital setting, their purpose is to introduce a relaxing environment to increase well-being as well as to decrease anxiety and aggressive behaviors. Calm rooms can also be used as a tool to provide self-help through a convenient environment for the patients and, at the same time, strengthen the therapeutic relationship between the patient and the professional. Recent developments in virtual reality (VR) have made virtual calm rooms possible, but these have not yet been evaluated in psychiatric inpatient care.

OBJECTIVE: This study aimed to compare the effects of VR and physical calm rooms on self-reported well-being and physiological markers of arousal.

METHODS: The study was conducted in 2 inpatient psychiatric wards specializing in bipolar disorder from March 2019 to February 2021. Patients who were already admitted were asked if they were interested in using a calm room and willing to provide ratings. This study relied on the quasi-randomized allocation of patients to the wards, which either had a physical or VR calm room. Self-assessment scales (Montgomery-Åsberg Depression Rating Scale-Self Assessment [MADRS-S], Beck Anxiety Scale, and Clinical Global Impression) were used to determine the participants’ baseline level of depressive and anxiety symptoms before their use of the physical or VR calm room. The study determined the state of well-being measured using an 11-point visual analog scale (VAS) as well as arousal measured by blood pressure (systolic and diastolic) and heart rate before and after the use of the calm rooms. The primary end point was self-reported well-being using the VAS.

RESULTS: A total of 60 participants were included-40 used the VR calm room and 20 used the physical calm room. The mean age of participants was 39 years and the majority were women (35/60, 58%). Analysis of VAS measurement showed improved well-being at the group level from before to after the intervention (P<.05), with no statistically significant difference in effects between the 2 different interventions. Effects were not moderated by baseline depression levels (dichotomized as MADRS-S >20 or ≤20) despite an overall difference in reported well-being between subgroups.

CONCLUSIONS: Although the power in this study was low, the findings of this first study indicate comparable effects with respect to well-being and arousal of a VR calm room and a physical calm room. This suggests that a VR calm room can be a viable alternative when the use of a physical calm room is not an option for logistic or other reasons.

TRIAL REGISTRATION: ClinicalTrials.gov NCT03918954; https://clinicaltrials.gov/ct2/show/NCT03918954.

PMID:37204858 | DOI:10.2196/42365