Chronic Stage Research Articles

Profiling hippocampal expression of long non-coding RNA GM12371 in a rat model of vascular dementia

BackgroundDementia, characterized by synaptic dysfunction and memory loss, presents a significant challenge in medical research. Long non-coding RNAs (lncRNAs), known for their crucial roles in regulating gene expression, represent a gap in knowledge regarding their specific involvement in synaptic structure, transmission, and plasticity. This study aims to investigate the dynamic changes in hippocampal lncRNA GM12371 expression in response to acute and chronic hypoperfusion in the rat brain using the 2VO model.MethodsThe 2VO model was induced by permanently occluding the common carotid arteries. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to evaluate hippocampal lncRNA GM12371 expression at both acute (day 4) and chronic (day 28) stages post-2VO surgery. Comparative analysis was conducted with a sham-operated group.ResultsA notable reduction in GM12371 expression was observed in the rat hippocampus on day 4 following 2VO surgery compared to the sham group (P < 0.05). However, there was no significant difference in GM12371 expression between the sham and 2VO-28 groups.ConclusionThese findings suggest that the downregulation of GM12371 is a response to acute hippocampal blood flow reduction but tends to normalize during the chronic phase of cerebral hypoperfusion. This dynamic regulation of GM12371 expression may be significant in the adaptive response to vascular dementia. Further clinical studies are warranted to investigate potential peripheral alterations in GM12371 expression in individuals with dementia.

8088 Connecting the Dots: Semaglutide, Constipation, and Diverticulitis - A case report

Abstract Disclosure: K. Tiwari: None. F. Sajid: None. J.G. Karam: None. Introduction: Semaglutide is a glucagon-like peptide-1 (GLP-1) receptor agonist used for the treatment of type 2 diabetes mellitus and weight management. Common side effects, primarily gastrointestinal (&amp;gt;10%), include nausea, vomiting, diarrhea, and constipation. Here, we present a case of acute sigmoid diverticulitis with an adjacent abscess in a patient who was recently initiated on GLP-1 receptor agonist therapy. Case presentation: A 76-year-old female with a medical history of type 2 diabetes mellitus on metformin and empagliflozin, hypertension, chronic kidney disease stage 3A, obesity (BMI: 43), and no known history of diverticulosis was started on semaglutide for additional glycemic, renal, and weight loss benefits, given suboptimal control of her obstructive sleep apnea, blood pressure, and knee arthritis. She received semaglutide subcutaneously at a dose of 0.25 mg weekly for 4 weeks, followed by an increased dosage of 0.5 mg for one week. However, she experienced a slight worsening of underlying constipation as a side effect. On the sixth week of therapy, she started having progressive lower abdominal pain with nausea, chills, and diarrhea, for which she presented to the Emergency Department. She was found to have leukocytosis, and a Computed Tomography (CT) of the abdomen/pelvis revealed peri-colonic fat stranding in the mid-ascending colon, wall thickening in the distal sigmoid colon, and a low-density fluid collection abutting the sigmoid/descending colonic wall, indicative of diverticulitis with a small abscess. She was admitted to the hospital for six days and was treated conservatively with Intravenous (IV) antibiotics, and her diet was slowly advanced as tolerated. Semaglutide was discontinued, and the patient was discharged home with outpatient endocrinology and gastrointestinal follow-up. A post-discharge colonoscopy showed diffuse diverticulosis. Conclusion: Constipation and old age are common risk factors for diverticulitis. While GLP1-1 receptor analogs have proven significant and multiple benefits, more knowledge about associated gastrointestinal complications resulting from slower food transit in the gastrointestinal tract is emerging. Older patients with underlying constipation and/or diverticulosis should particularly be monitored and treated for worsening constipation to avoid complications such as acute diverticulitis. Vigilance and awareness in recognizing and managing this potential complication are crucial with the wider indications and use of GLP-1 receptor analogs. Presentation: 6/3/2024

6853 A Curious Case of MACS

Abstract Disclosure: M. Dillon: None. A. Syeda: None. V. Kantorovich: None. Introduction: Mild autonomous cortisol secretion (MACS) is characterized by biochemical evidence of mild hypercortisolemia inducing metabolic comorbidities without any obvious phenotypic stigmata of Cushing’s syndrome (CS). This case highlights the challenges faced in the diagnosis and management of MACS. Case: A 76-year-old female with past medical history of class II obesity (BMI 31.83 kg/m2), type 2 diabetes mellitus, hypertension, hyperlipidemia, osteoporosis and chronic kidney disease stage IIIb was diagnosed with MACS after an overnight 1 mg dexamethasone suppression test (DST) showed unsuppressed 8 AM cortisol of 2.4 mcg/dL (&amp;lt;1.8 mcg/dL). Dexamethasone level was appropriate at 355 ng/dL (180-550 ng/dL), ACTH was &amp;lt;5 pg/mL (6-50 pg/mL) and DHEA-S was normal. Late night salivary cortisol (LNSC) levels were elevated to 0.12 mcg/dL (&amp;lt; 0.09 mcg/dL). The 24-hour urine cortisol level was normal. Baseline 8 AM cortisol level was 17 mcg/dL and ACTH was 19 pg/mL. Abdominal CT scan showed a 1 cm left adrenal nodule of 25 HU density and a normal right adrenal with no atrophy. Phaeochromocytoma and primary hyperaldosteronism work up was negative. She started on Mifepristone 300 mg daily and titrated up to 600 mg daily. She presented to our institution one month later with 1 week of nausea, vomiting and muscle weakness. Laboratory studies revealed acute kidney injury with creatinine of 6.69 mg/dL (baseline Cr 1.5 mg/dL) and rhabdomyolysis with creatinine kinase level of 12,819 U/L (24-173 U/L) and urine myoglobin level of 888 ng/mL (0-13 ng/mL). It was evident that her catastrophic presentation was from development of adrenal insufficiency in the setting of Mifepristone glucocorticoid receptor blockade. The drug was discontinued immediately. She was treated with intravenous hydration and intermittent diuretics. Over 10 days, her clinical status gradually improved and creatinine decreased to baseline levels. Discussion: MACS is a challenging diagnosis as cortisol levels are affected by several variables including obesity, drugs, and poorly controlled diabetes. Hence, a meticulous evaluation is mandated before confirming the diagnosis. Our patient’s baseline cortisol and ACTH levels were normal, and her DST and LNSC levels were mildly elevated. Unilateral cortisol producing adenoma causes contralateral gland atrophy due to suppressed ACTH. This was not evident in our patient, thus making the diagnosis questionable. Adrenalectomy is the treatment of choice in MACS with adrenal adenoma. Off label medical management with Mifepristone, a glucocorticoid receptor antagonist, is being pursued in select cases and was trialed due to our patient's age and surgical risk. Mifepristone is approved for the treatment of hyperglycemia due to CS. The data supporting its use in MACS is sparse. Therefore, it is important to be aware of associated risks of Mifepristone when advising patients. Presentation: 6/3/2024

Stochastic Optimal Control Analysis for HBV Epidemic Model with Vaccination

In this study, we explore the concept of symmetry as it applies to the dynamics of the Hepatitis B Virus (HBV) epidemic model. By incorporating symmetric principles in the stochastic model, we ensure that the control strategies derived are not only effective but also consistent across varying conditions, and ensure the reliability of our predictions. This paper presents a stochastic optimal control analysis of an HBV epidemic model, incorporating vaccination as a pivotal control measure. We formulate a stochastic model to capture the complex dynamics of HBV transmission and its progression to acute and chronic stages. By leveraging stochastic differential equations, we examine the model’s stationary distribution and asymptotic behavior, elucidating the impact of random perturbations on disease dynamics. Optimal control theory is employed to derive control strategies aimed at minimizing the disease burden and vaccination costs. Through rigorous numerical simulations using the fourth-order Runge–Kutta method, we demonstrate the efficacy of the proposed control measures. Our findings highlight the critical role of vaccination in controlling HBV spread and provide insights into the optimization of vaccination strategies under stochastic conditions. The symmetry within the proposed model equations allows for a balanced approach to analyzing both acute and chronic stages of HBV.

Pathomechanism Underlying Intravenous Immunoglobulin Therapy for Chronic Inflammatory Demyelinating Polyneuropathy

Considering its proven clinical usefulness and supportive evidence, intravenous immunoglobulin (IVIg) is used as first-line therapy for chronic inflammatory demyelinating polyneuropathy (CIDP) during the acute and chronic stages. However, the pathomechanism underlying IVIg administration for CIDP remains unclear. Autoantibodies, complement, inflammatory cytokines, chemokines, T cells, B cells, macrophages, and the blood-nerve barrier contribute to the onset and progress of CIDP. The mechanisms underlying the actions of IVIg in CIDP include the following: (1)neutralization of pathological autoantibodies by anti-idiotype antibodies, (2)inhibition of the neonatal Fc receptor (FcRn) with a consequent decrease in pathological autoantibodies, (3)neutralization of cytokines, chemokines, and complement, (4)activity modulation of T cells, B cells, and macrophages, and (5) recovery of blood-nerve barrier function. Compared with the management of typical CIDP, IVIg therapy is less effective for management of autoimmune nodopathy associated with anti-neurofascin-155 or contactin-1 IgG4 antibodies because (1)anti-idiotype antibodies associated with IVIg cannot effectively neutralize IgG4 owing to the strong antigen specificity of IgG4 autoantibodies, and (2)complement, T cells, and macrophages play an insignificant role in the pathomechanism of autoimmune nodopathy. Further understanding of the mechanisms underlying IVIg action and effectiveness of molecular targeted therapy, such as use of FcRn or complement inhibitors and the CD20 monoclonal antibody, is warranted to develop novel therapeutic strategies against CIDP.

The effect of a low potential renal acid load diet on metabolic acidosis in patients with chronic kidney disease stage 4 and 5

The effect of a low potential renal acid load diet on metabolic acidosis in patients with chronic kidney disease stage 4 and 5

Prevalence and outcome of Gastroduodenal lesion and H pylori Infection in Chronic kidney disease, pretransplant and End stage renal disease patients

Prevalence and outcome of Gastroduodenal lesion and H pylori Infection in Chronic kidney disease, pretransplant and End stage renal disease patients

The effect of reduced L-glutathione supplementation on TNF-α, hs-CRP, and neutrophil-lymphocyte ratio in maintenance hemodialysis patients.

Cardiovascular disease is the main cause of mortality in patients with chronic kidney disease stage 5 on dialysis (CKD-5D). High sensitivity C-reactive protein (hs-CRP), tumor necrosis factor-α (TNF-α), and neutrophil-lymphocyte ratio (NLR) are several inflammatory parameters associated with high cardiovascular events in CKD-5D. The main aim of this study was to evaluate the effect of reduced L-glutathione supplementation on serum hs-CRP, TNF-α, and NLR in patients with CKD-5D. This study is a quasi-experimental research with one group pretest-posttest design. Subjects included were patients with CKD-5D who routinely underwent hemodialysis therapy two times a week in Hasan Sadikin General Hospital. Serum hs-CRP, TNF-α, and NLR levels were obtained before and after the intervention of reduced L-glutathione supplementation dosing of one thousand milligrams a day for four weeks. Statistical analysis was then conducted using the Wilcoxon test. There were 26 hemodialysis patients included in the study, with a median age of 43 years and a male predominance. There was a significant decrease in serum TNF-α level after reduced L-glutathione supplementation for 4 weeks, 5.40 (-10.80-0.00) pg/mL, p = 0.002. However, there was no statistically significant decrease in either serum hs-CRP level, 0.40 (-0.70-0.80) mg/L (p = 0.656), or NLR with a difference of 0.55 (0.30-1.00) p = 0.055. Exogenous oral reduced glutathione supplementation for four weeks significantly reduced TNF-α level, but no significant decrease in hs-CRP level and NLR in patients with CKD-5D.

Long-term transcranial ultrasound stimulation regulates neuroinflammation to ameliorate post–myocardial infarction cardiac arrhythmia and remodeling

BackgroundSympathetic overactivation and neuroinflammation in the paraventricular nucleus (PVN) are crucial factors in post–myocardial infarction (MI) cardiac remodeling and ventricular arrhythmias (VAs). Prior study has indicated that low-intensity focused ultrasound stimulation could attenuate sympathetic neuroinflammation within the PVN to prevent the occurrence of VAs in an acute MI model. Meanwhile, the cGAS-STING pathway has shown potential to ameliorate the neuroinflammatory response. However, the effect and mechanisms of long-term transcranial ultrasound stimulation (LTUS) for modulating neuroinflammation in the chronic stage of MI remain unclear. ObjectiveThis study aimed to ascertain whether LTUS could mitigate post-MI neuroinflammation and improve cardiac arrhythmia and remodeling through the cGAS-STING pathway. MethodsThirty-six SD rats were equally randomized to the sham group (pseudo-MI modeling), chronic MI group (MI modeling), and LTUS group (MI modeling and long-term ultrasound stimulation). Transcranial ultrasound stimulation (15 min/d) was conducted on the PVN for 4 consecutive weeks. After 4-week intervention, echocardiography, electrophysiologic experiments, and histopathologic staining were performed to assess the role of LTUS on post-MI neuroinflammation and cardiac remodeling. ResultsThe results indicated that LTUS significantly facilitated microglial M1 to M2 polarization through the cGAS-STING signaling pathway within the PVN. Furthermore, LTUS inhibited MI-induced sympathetic neuroinflammation, thereby improving cardiac dysfunction, ameliorating cardiac remodeling, and reducing VA inducibility. ConclusionLong-term ultrasound stimulation of the PVN was found to alleviate post-MI neuroinflammation and to improve cardiac remodeling, which might inspire novel insights and clinical strategies for noninvasive neuromodulation and the treatment of post-MI VAs.

Hand eczema: a review of clinical, dermoscopic and histological features.

Hand eczema (HE) is a prevalent inflammatory skin condition, impacting 15-20% of individuals, with a notable incidence rate of approximately 7.3 cases per 1000 person/years. This condition exhibits significant gender-based variability, with a higher prevalence in females. The clinical presentation of HE is characterized by pruritic erythematous, edematous, weeping plaques, vesicles, and/or bullae, showcasing considerable heterogeneity. A literature search was conducted across multiple databases, including Medline, Pubmed, Scopus, and the Cochrane Library. The search was conducted using the following key words and medical subject heading (MeSH) terms: "hand," "eczema," "dermatitis," "dermoscopy," and "histology," employing the Boolean term "AND" to combine the research terms for optimal search precision. PRISMA algorithm has been used for article screening. The search scope included manuscripts published up to October 1, 2023. Up to 50% of HE cases are associated with atopic dermatitis, emphasizing the complex interplay between various dermatological conditions. Common subtypes of HE include irritant contact dermatitis (ICD), allergic contact dermatitis (ACD), atopic hand eczema (AHE), and protein contact dermatitis/contact urticaria (PCD). The chronic nature of HE presents a substantial management challenge, often underestimated, leading to delayed treatment and potential progression to chronic hand eczema (CHE). Beyond individual health implications, HE exerts a profound impact on occupational, domestic, social, and psychological aspects, establishing itself as the most prevalent occupation-related skin disease. This paper seeks to establish a comprehensive classification system for HE, integrating clinical, dermoscopic, and histological elements. Dermoscopy, specifically, proves instrumental in distinguishing HE from palmar psoriasis, revealing characteristic features such as yellow scales and irregular vessels. Histopathological findings underscore the dynamic changes observed from acute to chronic stages, while challenges in differentiating hyperkeratotic HE from psoriasis underscore the necessity for a holistic diagnostic approach. Accurate diagnosis and effective management of HE necessitate a holistic perspective that recognizes the inherent complexities of this inflammatory skin disease. By providing a multidimensional classification system, incorporating clinical, dermoscopic, and histological parameters, this paper aimed to contribute to a more nuanced understanding of HE and facilitate improved approaches to its diagnosis and treatment.

Toxoplasma-induced behavior changes - is microbial dysbiosis the missing link?

Toxoplasma gondii (T. gondii) is one of the most successful intracellular protozoa in that it can infect the majority of mammalian cell types during the acute phase of infection. Furthermore, it is able to establish a chronic infection for the host's entire lifespan by developing an encysted parasite form, primarily in the muscles and brain of the host, to avoid the host immune system. The infection affects one third of the world population and poses an increased risk for people with a suppressed immune system. Despite the dormant characteristics of chronic T. gondii infection, there is much evidence suggesting that this infection leads to specific behavior changes in both humans and rodents. Although numerous hypotheses have been put forth, the exact mechanisms underlying these behavior changes have yet to be understood. In recent years, several studies revealed a strong connection between the gut microbiome and the different organ systems that are affected in T. gondii infection. While it is widely studied and accepted that acute T. gondii infection can lead to a dramatic disruption of the host's normal, well-balanced microbial ecosystem (microbial dysbiosis), changes in the gut microbiome during the chronic stage of infection has not been well characterized. This review is intended to briefly inspect the different hypotheses that attempt to explain the behavior changes during T. gondii infection. Furthermore, this review proposes to consider the potential link between gut microbial dysbiosis, and behavior changes in T. gondii infection as a novel way to describe the underlying mechanism.

American trypanosomiasis

Objective: Due to the importance of Chagas disease as a public health problem in Brazil, this study aims to present a review of the epidemiological, treatment and control aspects of Chagas disease in Brazil. Literature review: American trypanosomiasis, popularly known as Chagas disease, is considered one of the most important neglected diseases in Latin America. The etiologic agent is Trypanosoma cruzi, which is primarily transmitted by hematofagous insects, known as kissing bugs, that belong to the subfamily Triatominae. Besides the primary form of transmission, other forms of transmission have been discovered over the years, such as oral, congenital, blood transfusion, transplant and accidental transmission. It is difficult to diagnose it in the acute phase because it presents generic and non-specific symptoms. It is usually diagnosed in the chronic stage, when the digestive and cardiac systems may be compromised. Since the end of 1960, treatment has been restricted to two drugs, but they are not so effective, and alternative medicines are necessary to improve the treatment and life quality of patients. Final considerations: In order to reduce Chagas disease transmission, Latin American countries, especially Brazil, must improve the surveillance system and provide primary care to the population.

Therapeutic effects of Kangxian Yanshen formula on patients with chronic kidney disease stages 3-4: a retrospective cohort study.

This study retrospectively evaluated the actual efficacy of Kangxian Yanshen Formula Chinese medicine on renal function-related indicators in chronic kidney disease (CKD) stage 3-4 patients. In this retrospective cohort study, we collected 212 adult CKD patients with baseline estimated glomerular filtration rate (eGFR) of 15-60 ml/min/1.73 m2. All participants received usual care (i.e., Western medications), and participants in the exposure group (n = 109) were additionally prescribed Kangxian Yanshen Formula Chinese medicine. The primary outcome was an adjusted hazard risk and 95% confidence interval (95% CI) of a 30% decrease in eGFR at month 36 from baseline. In terms of eGFR, among participants treated with additional Kangxian Yanshen Formula, after adjusting for covariates, there was a 57.1% reduction in the risk of a 30% decline from baseline in eGFR among participants in the Kangxian Yanshen Formula group compared with the Western medicine group (adjusted hazard risk: 0.429; 95% CI 0.269-0.682). In addition, participants in the Kangxian Yanshen Formula group had a significantly higher change in eGFR from baseline to month 12 than those in the western medicine group (3.40 ± 11.62 versus -3.87 ± 8.39; between-group difference Δ5.61 [± 2.26 standard deviation] mL/min/1.73 m2; P = 0.014). Participants in both groups showed a decreasing trend in eGFR at months 24 and 36. In patients with stage 3-4 CKD, Kangxian Yanshen Formula Chinese medicine therapy may help delay eGFR decline, but high-quality randomized controlled trials are needed to validate the results further.

Dry Eye Para-Inflammation Management: Preclinical and Clinical Evidence on a Novel 0.2% Hyaluronic Acid-Based Tear Substitute with 0.001% Hydrocortisone Sodium Phosphate.

Purpose: An innovative eyedrop formulation based on a combination of 0.2% hyaluronic acid and 0.001% hydrocortisone sodium phosphate (Idroflog®, Alfa Intes, Italy; HAC eyedrops) was granted a European Patent in 2016 and has been available on the market since 2019 in Europe and in other countries around the world. HAC eyedrops aim to synergize the moisturizing effects of hyaluronic acid with the mild anti-inflammatory properties of low-dose hydrocortisone, offering a more effective and safer alternative for treating dry eye disease (DED), targeting both tear film instability and dysfunctional para-inflammation. The activity of HAC eyedrops has been explored in different post-marketing clinical trials, in addition to preclinical studies. In this narrative review, we explored the available evidence on the use of HAC eyedrops for the management of para-inflammation in DED patients to provide a comprehensive overview of efficacy and safety data related to the use of this medical device in routine clinical practice. Methods: A literature search for preclinical and clinical data involving treatment with HAC eyedrops was conducted using PubMed/MEDLINE, considering only original research articles published in English, without time restrictions. Results: One preclinical and four clinical papers were retrieved. Preclinical evidence suggests that 0.001% hydrocortisone is able to control the expression of inflammatory markers, and this, together with the hydrating and lubricating properties of hyaluronic acid, leads to improvements in DED clinical signs, such as tear volume and the stability of the tear film. The results of clinical trials demonstrate that HAC eyedrops are able to improve the signs and symptoms of DED and that 0.001% low-dosage hydrocortisone can be helpful in preventing the progression to chronic stages of DED. Conclusions: HAC eyedrops represent a promising therapeutic strategy for the management of dysfunctional para-inflammation and offer a valuable addition to the armamentarium of treatments for DED.

Longitudinal analysis of anxiety and sleep disorders in the Korean population with disabilities, from 2006 to 2017: Incidence, prevalence, and association with disability type and severity

BackgroundIndividuals with disabilities often face a higher risk of concurrent psychological problems, yet comprehensive assessments of the anxiety and sleep disorders in this population remain limited. This study examined longitudinal trends in the incidence and prevalence of anxiety and sleep disorders among people with disabilities and explored their associations with disability type and severity. MethodsUtilizing claim data from the National Health Insurance database and the National Disability Registry, which cover the entire Korean population, we estimated the age-standardized incidence and prevalence of anxiety and sleep disorders between 2006 and 2017. Logistic regression was used to analyze the associations between disability type and severity and these disorders. ResultsThe unadjusted incidence and prevalence of anxiety and sleep disorders were consistently higher among individuals with disabilities during the study period. A significant gap in the prevalence of these disorders persisted between individuals with and without disabilities in both sexes, even after accounting for socioeconomic status and comorbidities. However, the incidence showed mixed results, with some categories of disabilities showing lower likelihood of developing the conditions compared to individuals without disabilities. ConclusionsActions should also be taken to identify undiagnosed cases of anxiety and sleep disorders among individuals with disabilities. Moreover, individuals with disabilities who are diagnosed with these disorders should be more actively managed to avert the progression to the chronic stage.

SMART-goal domains and goal attainment in an individualized, goal-oriented intervention for children with acquired brain injury and their families

ABSTRACT Pediatric acquired brain injury (pABI) may lead to long-lasting challenges in need of rehabilitation-efforts years after the insult. The Child in Context Intervention (CICI) is an individualized, goal-oriented intervention targeting children with pABI, their families and schools in the chronic phase. This paper describes the goals that patients and families in the CICI intervention group identified to work on. The 29 participating families worked on 90 goals that were predominantly coded to the domains of Body functioning (46.6%) and Activities and participation (40.5%), according to the International Classification of functioning, Disability and Health (ICF). The most frequently used codes focused on fatigue and emotional symptoms, in addition to codes in the AP domain describing the need for increased independence in everyday life at school, at home, and socially. Goal attainment in the intervention group was high, with positive progress on 94.4% of the goals and positive goal achievement for all included families. The high level of goal attainment provides promising evidence of the CICI programme’s efficacy, and highlights the need to further develop evidence-based rehabilitation programs for children with pABI in the chronic stage of recovery. Trial registration ClinicalTrials.gov identifier: NCT04798859.

Characterizing the Longitudinal Impact of Backward Locomotor Treadmill Training on Walking and Balance Outcomes in Chronic Stroke Survivors: A Randomized Single Center Clinical Trial.

Walking and balance impairments after stroke are a global health concern, causing significant morbidity and mortality. However, effective strategies for achieving meaningful recovery in the chronic stages are limited. Backward locomotor treadmill training (BLTT) is a novel walking rehabilitation protocol that is safe, feasible, and likely beneficial in stroke survivors; however, its efficacy has not been tested. This single-center, randomized, assessor-blind clinical trial aims to test the preliminary efficacy of BLTT compared to forward locomotor treadmill training (FLTT) on walking speed, symmetry, and postural stability. Forty stroke survivors [BLTT (N=19), FLTT (N=21); mean age= 56.3 ± 8.6 years; 53% Female; 30% Non-Hispanic Black] with mild-moderate walking impairment were enrolled. Participants underwent nine 30-minute BLTT or FLTT sessions over three weeks. The primary outcome was the mean change in the 10-meter walk test (10 MWT) at 24 hours post-training (24 hr POST). Secondary outcome measures were changes in spatiotemporal walking symmetry and postural stability during quiet standing at 24 hr POST. Retention was explored at Days 30- and 90 POST. We report clinically meaningful (≥ 0.16 m/s) improvements in overground walking speed at 24 hr POST, with retention up to Day 90 POST with BLTT and FLTT. However, contrary to our working hypothesis, no between-group differences in walking speed were observed. Nonetheless, we found that BLTT resulted in offline improvements in spatial symmetry and retention of subcomponents of the modified clinical test of sensory interaction on balance (mCTSIB), including the testing of proprio-vestibular integration up to Day 30 POST. Among chronic stroke patients with mild-moderate walking impairment, BLTT and FLTT both resulted in long-lasting and clinically meaningful improvement in walking speed. However, preliminary findings suggest that BLTT may better comprehensively target walking asymmetry and sensory systems processing and integration.

Evaluating the Safety and effectivenesS in adult KorEaN patients treated with Tolvaptan for management of autosomal domInAnt poLycystic kidney disease (ESSENTIAL): final report.

Tolvaptan, a selective vasopressin V2 receptor antagonist, was first approved by the Korean Ministry of Food and Drug Safety in 2015 as a treatment option for autosomal dominant polycystic kidney disease (ADPKD). To prescribe tolvaptan safely and effectively, we designed the phase 4 clinical trial among Korean ADPKD patients with chronic kidney disease stages 1 to 3. A total of 117 Korean patients aged 19 to 50 years with rapidly progressing ADPKD were enrolled in the study. Tolvaptan was prescribed for 24 months with the maximum tolerable dose up to 120 mg/day. The primary outcome was the incidence of treatment-emergent adverse events (TEAEs) including hepatic adverse events. The secondary outcomes were the annual mean percent change of total kidney volume (TKV) and the annual mean change of estimated glomerular filtration rate (eGFR). A total of 489 TEAEs occurred in 106 patients (90.6%). A total of 17 cases of hepatic adverse events (14.5%) occurred during the study period and mostly within the first 18-month period. However, liver enzymes were normalized after drug discontinuation. Although it was not statistically significant, patients with a previous history of liver disease as well as those with mild elevation of liver enzyme showed a higher frequency of hepatic adverse events. Compared with the predicted value from the calculation, tolvaptan attenuated both TKV growth and eGFR decline rate. Although the incidence of hepatic adverse events was higher in Korean ADPKD patients compared to the previous studies, tolvaptan can be prescribed safely and effectively using meticulous titration and 1-month interval monitoring.

“Partner” cellulose gel with “dialysis” function: Achieve the integration of filtration-enrichment-SERS detection

Hydrogel and aerogel materials have garnered significant attention in constructing effective surface-enhanced Raman spectroscopy (SERS) substrates due to their excellent adsorption capabilities, high specific surface area, and abundant chemical groups. However, in liquids with complex compositions, non-specific adsorption of macromolecules can lead to surface scaling and pore clogging of the substrate material, limiting the selective enrichment and SERS detection of target molecules. To address this, an innovative aerogel-chimeric hydrogel material (CH@S-CNF/SA/Ag NPs) was developed. The aerogel component, with its high specific surface area and electronegative properties, functions as a SERS “chip” for adsorption and detection of target molecules. Simultaneously, the mesoporous structure of the hydrogel “shell” effectively filters macromolecules from the solution. These CH@S-CNF/SA/Ag NPs were utilized as SERS substrate materials for detecting urine from healthy individuals and patients with chronic kidney disease stage 5 (CKD5). When combined with machine learning algorithms, the detection accuracy reached 99.50%. This work represents a significant advancement in the specific adsorption and SERS detection of small molecules in complex biological samples such as urine and blood.

Mast cells promote pathology and susceptibility in tuberculosis.

Tuberculosis (TB), caused by the bacterium Mycobacterium tuberculosis (Mtb), infects approximately one-fourth of the world's population. While most infected individuals are asymptomatic, latent TB infection (LTBI) can progress to cause pulmonary TB (PTB). We recently reported an increased accumulation of mast cells (MCs) in lungs of macaques with PTB, compared with LTBI in macaques. MCs respond in vitro to Mtb exposure via degranulation and by inducing proinflammatory cytokines. In the current study, we show the dominant production of chymase by MCs in granulomas of humans and macaques with PTB. Using scRNA seq analysis, we show that MCs found in LTBI and healthy lungs in macaques are enriched in genes involved in tumor necrosis factor alpha, cholesterol and transforming growth factor beta signaling. In contrast, MCs clusters found in PTB express transcriptional signatures associated with interferon gamma, oxidative phosphorylation, and MYC signaling. Additionally, MC deficiency in the mouse model showed improved control of Mtb infection that coincided with reduced accumulation of lung myeloid cells and diminished inflammation at chronic stages. Thus, these collective results provide novel evidence for the pathological contribution of MCs during Mtb infection and may represent a novel target for host directive therapy for TB.