Long-term Use Research Articles

Review of Thymic Peptides and Hormones: From Their Properties to Clinical Application

Abstract Background The thymus is the main lymphoid organ that regulates the functions of the immune system, protecting against pathogens, tumors, antigens, and mediators of tissue damage. It produces a family of hormone-like peptides that can modulate physiological processes such as stimulation or suppression of immune responses, angiogenesis, and wound healing. Objective This review aims to comprehensively characterize the properties of thymic peptides and their clinical applications. Methodology This article discusses the structure, biological properties, mechanism of action, and therapeutic applications of the most important thymic hormones (thymosin alpha 1, thymosin beta-4, thymulin, and thymopoietin), as well as preparations that are purified thymic extracts. Results Thymic peptides and extracts act in multiple manners on the immune system: they stimulate the differentiation and maturation of T cells, regulate the activity of natural killer cells and dendritic cells, and induce the release of proinflammatory cytokines, and their immunomodulatory effects have been confirmed in numerous clinical studies. An important feature of thymus preparations is their therapeutic safety—even long-term use does not cause side effects. Conclusions A wide range of therapeutic uses, i.e., from defensive and immunomodulatory tasks to participation in tissue regeneration processes, has led to the use of thymic peptides in the treatment of neoplastic diseases, viral infections, autoimmune diseases or immunodeficiencies. Further investigation of the mechanisms of action of thymic peptides may contribute to the discovery of new therapeutic targets.

Patient and Parent/Caregiver Satisfaction with Efficacy and Cosmetic Elegance of Tapinarof Cream 1% Once Daily in a Long-term Extension Trial in Adults and Children Down to Age 2 Years with Atopic Dermatitis

Introduction: Patients with atopic dermatitis (AD) report low satisfaction with currently available topical therapies. Satisfaction and patient preference are closely linked to treatment adherence, and understanding preferences may contribute to improving the quality of AD care and adherence. In the pivotal 8-week, phase 3 ADORING 1 and 2 trials, tapinarof cream 1% (VTAMA®, Dermavant Sciences, Inc.) once daily (QD) demonstrated superior efficacy versus vehicle and was well tolerated in adults and children down to age 2 years with AD. We report Patient Satisfaction Questionnaire© (PSQ) results from ADORING 3, a 48-week, open-label extension trial. Methods: In ADORING 3, eligible patients from ADORING 1 and 2, from a 4-week maximal usage pharmacokinetics trial, and tapinarof-naive patients with mild AD, or moderate or severe AD, that did not meet inclusion criteria for ADORING 1 or 2, were followed for up to 48 weeks. The PSQ was completed at Week 48 or at early termination visit and assessed patient or parent/caregiver satisfaction with tapinarof efficacy, cosmetic elegance (look and feel of tapinarof cream), application ease, impact on daily life, and preference for tapinarof versus prior AD therapies. Patients aged ≥16 years self-completed the PSQ; parents/caregivers completed for children aged 2 to 15 years. Results: 505 patients or parents/caregivers completed the questionnaire. Respondents consistently reported high rates of satisfaction across all parameters. Most patients or parents/caregivers strongly agreed or agreed with PSQ questions assessing satisfaction with cosmetic elegance (91.5%), quick absorption (89.5%), application ease (97.6%), impact on daily life (94.3%), efficacy (92.3%), and confidence in tapinarof (92.7%). For patients or parents/caregivers who reported prior use of other topical therapies to treat AD, most strongly agreed or agreed that tapinarof was more effective (86.3%), easier to use (68.6%), and that they preferred tapinarof to prior topicals (88.0%). Compared with systemic drugs used previously for AD, most strongly agreed or agreed that tapinarof was more effective (84.6%), easier to use (77.6%), and that they preferred tapinarof to prior systemic drugs (85.9%). Conclusion: Patient or parent/caregiver satisfaction data from ADORING 3 showed a consistent and highly positive perception of long-term use of tapinarof cream across all parameters, including satisfaction with tapinarof efficacy, cosmetic elegance, application ease, impact on daily life, and preference for tapinarof compared with prior AD therapies. Satisfaction with tapinarof is likely to contribute to long-term adherence and improved outcomes for patients with AD.

The interplay between toothbrush stiffness and charcoal-containing dentifrice on the development of enamel topography changes.

This study aimed to investigate the in vitro effect of a charcoal-containing dentifrice with different toothbrush stiffness on enamel. Four main groups were applied: distilled water, conventional fluoridated toothpaste (Colgate® Total® 12 Clean Mint Toothpaste), charcoal toothpaste (Colgate® Total® Charcoal Toothpaste) and whitening toothpaste (Colgate Total® Advanced Whitening Toothpaste). Three subgroups for each toothpaste were further included according to the toothbrush bristles' stiffness (soft, medium, and hard). Enamel specimens were subjected to 1,250 and 2,500 cycles of brushing using toothbrushing simulation machine. The average surface roughness change (ΔRa) in nanometer (nm) was measured to estimate the changes following the brushing simulation model. Two-way ANOVA and Tukey tests analyzed the data. The type of toothpaste and the bristles' stiffness were determinant factors in increasing the ΔRa value (P = < 0.05). Generally, charcoal and whitening toothpastes with medium and hard bristles yielded higher ΔRa than fluoridated toothpaste and smooth bristles. Following 1,250 cycles of brushing simulation, charcoal toothpaste did not increase the enamel roughness compared to the controls. However, in prolonged brushing via 2,500 cycles of brushing simulation, using bristles with soft stiffness revealed that charcoal toothpaste was associated with increased surface roughness (55.86 ± 41.18nm), which was statistically significant (P = 0.024) compared to the negative control. Using bristles with medium stiffness showed that the whitening (68.23 ± 48.58nm) and charcoal (73.62 ± 34.66nm) toothpastes significantly (P = < 0.05) increased the enamel roughness compared to the conventional toothpaste (36.53 ± 22.56nm). There was no significant difference among the groups when brushes with hard bristles were used, as all the groups revealed increased enamel roughness. The use of charcoal and whitening toothpastes increased enamel roughness, particularly with long-term use. The effect of bristle stiffness on enamel roughness was found to vary depending on the type of toothpaste used.

Can Talaromyces marneffei Infection Cause Acute Liver Failure? A Case Report

Introduction: Talaromyces marneffei is a pathogen that causes talaromycosis, a systemic fungal infection. Cases in which hepatic failure is the primary clinical presentation are exceedingly rare. Case Presentation: This report details the case of a 49-year-old male with no prior liver disease, presenting to the hospital with persistent symptoms, including a fever lasting over ten days, abdominal distension for five days, and jaundice for three days. The patient’s history included immune thrombocytopenia and prolonged glucocorticoid therapy. Physical examination revealed yellowing of the skin and sclera, abdominal distension, firmness of the abdominal wall, absence of abdominal tenderness, positive shifting dullness, and pitting edema in the lumbosacral region and bilateral lower extremities. An HIV antibody test was negative. The patient developed hepatic failure and received artificial liver support along with routine therapy. Despite these interventions, the patient was automatically discharged without improvement and subsequently passed away. Post-discharge, cultures from pleural and abdominal effusions identified Talaromyces marneffei. Conclusions: Talaromyces marneffei infection should be considered in the differential diagnosis of immunocompromised patients, particularly those with no history of liver disease but with long-term glucocorticoid or immunosuppressant use who present with acute liver failure. Early and aggressive investigation for the causative pathogen is essential to minimize diagnostic and treatment delays. Given the prolonged incubation period of Talaromyces marneffei, metagenomic next-generation sequencing may offer a more rapid approach for etiological diagnosis.

Peripheral immune signatures associated with the risk of hepatocarcinogenesis in cirrhotic Egyptian HCV patients before and after treatment with direct-acting antivirals.

Although direct-acting antivirals (DAAs) have revolutionized the management of chronic HCV, the debatable association with hepatocellular carcinoma (HCC) occurrence/recurrence has raised major concerns about their long-term use, especially in cirrhotic cases. The role of epithelial tight junction proteins (TJPs) in hepatocarcinogenesis has been highlighted; however, the association of their expression in peripheral blood mononuclear cells (PBMCs) with HCC has rarely been reported. This study aimed to explore the role of peripheral claudin (Cldn)1 in liver pathogenesis and its crosstalk with soluble immune mediators in HCC prognosis. The study population included six independent subgroups: healthy controls, cirrhotic/non-cirrhotic treatment-naïve HCV patients, DAA-SVR patients, and anticancer treatment-naïve de novo HCC patients. The laboratory tests included serum levels of alpha-fetoprotein (AFP), albumin, liver transaminases, total bilirubin, and CBC profiling. The serum levels of soluble cluster of differentiation (sCD)163, IL-10, and IL-12 were estimated by corresponding ELISA kits, whereas the levels of Cldn1 and transforming growth factor (TGF)-β in PBMCs were quantified using quantitative PCR (qPCR). Serum sCD163, IL-10, and IL-12 levels were significantly higher in the HCC patient group than in the control and non-malignant patient groups (P < 0.0001). No significant difference was detected in the serum levels of the three markers between cirrhotic and non-cirrhotic patients, whereas their levels were significantly different between cirrhotic and non-cirrhotic patients (P < 0.0001). Similarly, the transcriptional levels of peripheral Cldn1 and TGF-β were significantly higher in patients with HCC and non-malignant cirrhosis than in patients without cirrhosis (P = 0.0185-<0.0001 and 0.0089-<0.0001, respectively). Logistic regression analysis revealed a significant association between all the abovementioned markers and HCC (P = 0.0303 to < 0.0001), which was further confirmed by the results of receiver operating characteristic (ROC) analysis, which revealed an area under the curve (AUC) value ranging from 0.883 to 0.996. The calculated cutoff values demonstrated remarkable prognostic capacity, with ranges of 88-99.41% and 82.14-97.92% and positive/negative predictive values ranging from 84.62 to 98.3% and 92-98%, respectively. The proposed HCC predictors are novel non-invasive HCC biomarkers that maintain their predictive power under different pathological conditions and circumvent the drawbacks of conventional prognostic markers in patients with mild cirrhosis and/or normal AFP, albumin, and/or platelet counts.

Divergence of nutrients, salt accumulation, bacterial community structure and diversity in soil after 8years of flood irrigation with surface water and groundwater.

Irrigation with saline groundwater has become necessary to overcome freshwater scarcity in the agricultural industry in arid areas. However, the effects of long-term saline groundwater irrigation on soil salinity and bacterial diversity have rarely been examined. In this study, a Lycium ruthenicum field was divided into two parts and subjected to flooding irrigation with saline groundwater (pH 7.81, total salinity 0.95g L-1) and surface water (pH 7.76, total salinity 0.36g L-1) for 8years. After 8years of irrigation, the soil salinity and salt ion content (i.e., Na+, Mg2+, K+, Ca2+, Cl- and CO32-) in the groundwater irrigation group were significantly greater than those in the surface water irrigation group (p < 0.001), with notable accumulation in the topsoil (0-5cm) (p < 0.01). The bacterial community structure differed between the surface water and groundwater irrigation groups. Salt-tolerant bacterial groups (e.g., Balneolaceae and Halomonadaceae) and species (e.g., the marine bacterium JK1007, the bacterium YC-LK-LKJ35, and Methylohalomonas lacus) dominated in the groundwater irrigation environment. Additionally, bacterial communities were associated primarily with soil salt ions (RV = 0.66, p < 0.001). The characteristic bacterial taxa in long-term groundwater irrigation soils were salt-tolerant species (e.g., the marine bacterium JK1007, the bacterium YC-LK-LKJ35, and Methylohalomonas lacus). These findings suggest that salinity is the key factor driving differences in bacterial community structure between long-term groundwater and surface water irrigation. The long-term use of surface water and groundwater for irrigation has different impacts on soil environments, with groundwater irrigation having a more pronounced negative effect. Highlights. The long-term effects of this practice on soil salt accumulation and bacterial diversity were examined. This study provides potential applications for sustainable land management in similar ecological contexts. Groundwater irrigation is characterized by saline-tolerant keystone species. Salinity filtering was used to determine the pattern of bacterial community construction.

Eradication of proliferative verrucous leukoplakia with toll-like receptor 7 agonist (topical imiquimod): a case report

Proliferative verrucous leukoplakia (PVL) is an aggressive and distinct type of oral precancerous lesion characterized by warty surfaced white plaque diffusely involving oral mucosa. Surgical excision is the treatment of choice. However, PVL has persistent and recurrent growth patterns, requiring multiple surgical procedures. Surgical intervention is especially challenging if PVL extends between teeth limiting access. These interproximally located lesions have a high propensity to undergo malignant transformation. We report a case of a 53-year-old man with recurrent PVL diffusely covering the maxillary and mandibular gingiva. Despite complete surgical excisions, PVL recurred, and a focal area in the interproximal mandibular gingiva progressed to invasive squamous cell carcinoma requiring marginal resection. The remaining PVL areas were treated with topical imiquimod (toll-like receptor 7 agonist) for six months, resulting in complete clinical and histological resolution. Topical agents can cover a larger surface area and penetrate in between interproximal areas. Importantly, it allows for maximal local exposure with minimal systemic toxicity, essential for long-term treatment and prophylactic use of the agent to prevent relapse.

Intracerebral haemorrhage - mechanisms, diagnosis and prospects for treatment and prevention.

Intracerebral haemorrhage (ICH) is a devastating condition associated with high mortality and substantial residual disability among survivors. Effective treatments for the acute stages of ICH are limited. However, promising findings from randomized trials of therapeutic strategies, including acute care bundles that target anticoagulation therapies, blood pressure control and other physiological parameters, and trials of minimally invasive neurosurgical procedures have led to renewed optimism that patient outcomes can be improved. Currently ongoing areas of research for acute treatment include anti-inflammatory and haemostatic treatments. The implementation of effective secondary prevention strategies requires an understanding of the aetiology of ICH, which involves vascular and brain parenchymal imaging; the use of neuroimaging markers of cerebral small vessel disease improves classification with prognostic relevance. Other data underline the importance of preventing not only recurrent ICH but also ischaemic stroke and cardiovascular events in survivors of ICH. Ongoing and planned randomized controlled trials will assess the efficacy of prevention strategies, including antiplatelet agents, oral anticoagulants or left atrial appendage occlusion (in patients with concomitant atrial fibrillation), and optimal management of long-term blood pressure and statin use. Together, these advances herald a new era of improved understanding and effective interventions to reduce the burden of ICH.

A case of penicillin-resistant group B Streptococcus isolated from a patient in the UK.

In England, group B streptococci (GBS; Streptococcus agalactiae) are considered universally susceptible to penicillin. Reports from Africa, Asia, North America and a few European countries have described GBS isolates with penicillin MICs above the epidemiological cut-off (0.125 mg/L). Our aim was to characterize a penicillin-resistant GBS (PRGBS) isolate recovered in 2016 from a patient treated with long-term antimicrobials in the UK. Antibiotic susceptibility of a referred isolate from a discharging sinus overlying a chronic prosthetic joint infection was determined using gradient strip testing for seven antibiotics. Illumina short read sequencing was carried out using a HiSeq 2500 platform to determine MLST, capsular type, to detect mutations in the pbp genes, and to compare the isolate with contemporaneous GBS isolates circulating in the UK. The GBS isolate belonged to capsular type Ia and MLST 144. We observed resistance to penicillin (MIC = 1 mg/L) and tetracycline (32 mg/L) with susceptibility to linezolid (1 mg/L), erythromycin (0.064 mg/L), clindamycin (0.064 mg/L), teicoplanin (0.064 mg/L) and vancomycin (0.25 mg/L). Deduced amino acid sequences revealed substitutions and non-synonymous changes in PBP2x and PBP2b. Genomic analysis of contemporaneous cases (n = 34) from across the UK identified single nucleotide polymorphism (SNP) variation ranged from 153-6596 SNPs. We confirm the first identification of a PRGBS isolate amongst referrals to the UK's national reference laboratory. Substitutions in pbp1a, pbp2a, pbp2x and pbp2b were identified that likely developed in the face of long-term beta-lactam antibiotic use.

Postoperative pain management using high-dose oral acetaminophen for enhanced recovery after colorectal cancer surgery.

Postoperative pain management is important for enhanced recovery. High-dose oral acetaminophen is effective; however, the safety of its long-term use has not been established in gastrointestinal surgeries. This study aimed to investigate drug-induced liver injury (DILI) in patients with colorectal cancer using high-dose acetaminophen. One hundred sixty-eight consecutive colorectal cancer using high-dose oral acetaminophen (3600mg/day between postoperative day 1 and 7) were enrolled. One hundred forty-nine patients (88.7%) completed the administration of high-dose oral acetaminophen. DILI occurred in 58 patients (34.5%), and the cumulative incidence rates were 20.4% and 37.9% on postoperative 6 and 7, respectively. The severity of liver injury was grade 1 in all cases and returned to normal without treatment. Patients with DILI had a higher frequency of dyslipidemia (44.8% vs. 23.6%, P = 0.0047) and M1 staging (10.3% vs. 1.0%, P = 0.0036). A multivariate analysis showed that the presence of dyslipidemia (OR 2.61, P = 0.0067) and M1 stage (OR 12.4, P = 0.0053) were independent risk factors for DILI. The long-term use of high-dose oral acetaminophen in colorectal cancer patients enrolled in enhanced recovery protocols is feasible. Moreover, the presence of dyslipidemia and M status are risk factors for DILI.

A mobile electrical stimulator for therapeutic modulation of the vestibular system — design, safety, and functionality

Low-intensity noisy galvanic vestibular stimulation (nGVS) is a promising non-invasive treatment for enhancing vestibular perceptual performance and postural control in patients with chronic vestibular hypofunction. However, this approach has so far been studied mainly under laboratory conditions. Evidence indicates that continuous application of nGVS in daily life is necessary for it to be effective. To address this need, we have developed a mobile nGVS stimulator and conducted a series of pilot studies to evaluate its safety, tolerability, functionality, and therapeutic effects. The device is a lightweight, compact, and portable AC stimulator featuring a user-friendly interface for the individualized adjustment of nGVS parameters. It includes an integrated motion sensor that automatically activates stimulation during body movement and deactivates it during inactivity, optimizing its practical use in real-world settings. The stimulator adheres to strict safety standards and, in initial long-term use, has exhibited only mild side effects (e.g., skin irritation and headaches), likely attributable to the current electrode placement, which requires further optimization. As expected, the device consistently elicits known vestibular sensorimotor reflex responses in healthy individuals. Importantly, further pilot studies in healthy participants demonstrate that the device can reliably replicate known facilitating effects on vestibular perception and postural control. Together, these findings suggest that this mobile stimulation device can facilitate the translation of nGVS into therapeutic everyday use.

Evaluation of the Awareness and Knowledge Levels of Dentists Regarding Bisphosphonates and Bisphosphonate-Related Jaw Necrosis

Bisphosphonates are used in the treatment of osteoporosis, bone metastases, and metabolic bone diseases. Long-term use of bisphosphonates increases the risk of osteonecrosis in patients undergoing dental surgery. This study aimed to evaluate dentists’ knowledge about bisphosphonates and bisphosphonate-related osteonecrosis of the jaw (BRONJ) and their treatment approaches in patients using oral and intravenous bisphosphonates. In this study, a 25-question questionnaire was applied to dentists working in different institutions regarding their knowledge and experience about bisphosphonates and BRONJ, and treatment approaches for different surgical procedures in patients using bisphosphonates. The obtained data were statistically analyzed and evaluated. In total, 90.5% of the dentists identified osteoporosis, 79.8% identified bone metastases, 52.4% identified osteitis deformans, and 39.3% identified multiple myeloma as conditions in which bisphosphonates are used, thus answering correctly in a significant proportion. When participants were asked about treatment options according to the stages of BRONJ, participation in the “I’m not sure” option increased as the stages progressed, indicating that dentists were not sufficiently familiar with the treatments for different stages of BRONJ. In total, 88.5% of the participants stated that when they see an exposed bone area in patients they examine, they consider bisphosphonate use as a possible cause. There was a statistically significant difference between dentists with and without prior BRONJ experience regarding their ages (P=0.039) and years of practice (P=0.001). There was a statistically significant difference between dentists with and without BRONJ experience regarding whether they inquired about bisphosphonate use (P=0.001). It was found that dentists have serious deficiencies in knowledge regarding bisphosphonates, their side effects, and treatment approaches for patients using bisphosphonates. Increasing dentists’ knowledge and awareness of this issue would help reduce the risk of developing BRONJ.

Potential of bioregulatory therapy in the treatment of patients with rhinitis medicamentosa

Chronic rhinitis is a common condition characterized by inflammation of the mucous membrane of the nose. It can lead to troublesome symptoms like itching, runny nose, nasal congestion, sneezing and irritation. Rhinitis can significantly lower the quality of life, have a detrimental effect on productivity and negatively affect social communications. Therefore, it is important to diagnose and treat this disease in due time. There are two main types of rhinitis: allergic rhinitis and non-allergic rhinitis. Non-allergic rhinitis refers to patients who have nasal symptoms, but skin tests do not show any allergic reactions. In this case, additional tests are necessary before making an accurate diagnosis. In turn, several subgroups of non-allergic rhinitis can be distinguished according to the causes and mechanisms of its development. The article discusses the features of the treatment of rhinitis medicamentosa. The use of different drugs can cause nasal symptoms, including nasal congestion. Rhinitis medicamentosa can be divided into two subgroups: rhinitis caused by adverse effects of systemic drugs and rhinitis due to overuse of antioedemic nasal therapy. Topically active vasoconstrictors are used to relieve nasal congestion caused by various reasons. However, the long-term use of such drugs can lead to the development of rhinitis medicamentosa and other adverse reactions. There are several hypotheses as to why rhinitis medicamentosa occurs. They include activation of beta-adrenergic receptors, the decreased production of presynaptic endogenous norepinephrine, and the development of tachyphylaxis. The overuse of topical nasal decongestants can bring on vicious cycle: the more frequently the patients use the drugs, the more likely thery are to get increased adverse effects. It is important to understand the potential risks and limitations of using topical nasal decongestants. If symptoms of nasal congestion or other adverse effects develop, it is necessary to consult a doctor to adjust the treatment.

Choroidal and retinal alteration after long-term use of tadalafil: a prospective non-randomized clinical trial.

The purpose of this study is to investigate choroidal and retinal vascular features in patients taking PDE5is by measuring dynamic vascular alterations and neurostructural features of the retina before and after oral tadalafil administration. The current clinical research involved 22 patients treated with tadalafil 20 mg on alternate days (OAD) after nerve-sparing robotic radical prostatectomy (NS-RARP) for prostate cancer. Patients underwent SD-OCT to assess ganglion cell complex (GCC), retinal nerve fiber layer (RNFL), and subfoveal choroidal thickness (SFCT), as well as OCTA to assess superficial capillary plexus (SCP), deep capillary plexus (DCP), choriocapillaris (CC), foveal avascular zone (FAZ), and radial peripapillary capillary thickness (RPC). All patients were evaluated at baseline (t0), and 3 (t1) and 6 (t2) months after the use of oral tadalafil. A statistically significant reduction in DCP and CC vessel density was found at t2 compared to baseline. According to the SFCT parameter, a statistically significant increase was observed from t0 to t1, and from t1 to t2. GCC parameter increased at t2 compared to baseline in a statistically significant way. No statistically significant differences were recorded between t0, t1 and t2 for the SCP, RPC, FAZ area, RNFL parameter. Retinal and optic disc toxicity may be detected using modifications of capillary vessel density. Further studies are needed to detect the possible progression or regression of ocular or systemic vascular complications in long-term follow-up.

Abstract 4117180: Hyperkalemia-Related Hospitalization Associated with Short-Term vs. Long-Term Outpatient SZC Therapy Among RAASi Users: The GALVANIZE Outcome study

Introduction: Patients receiving renin-angiotensin-aldosterone system inhibitors (RAASi) are at increased risk of developing hyperkalemia (HK). Sodium zirconium cyclosilicate (SZC) is used to treat HK, but the impact of duration of SZC on healthcare resource utilization (HRU) in RAASi users is unknown. The GALVANIZE Outcome study compared HK-related HRU among RAASi users between long-term and short-term SZC users. Methods: Adults with ≥1 outpatient prescription for SZC (index date) and ≥1 RAASi prescription spanning the index date were identified from a large US insurance claims database (7/2018-12/2022) and were stratified based on duration of SZC use. Long-term SZC users (&gt;90 days) and short-term SZC users (≤30 days) were exactly and propensity score matched on key baseline characteristics. Rates of HK-related hospitalizations or emergency department (ED) visits, HK-related ED visits, and HK-related hospitalizations were compared during follow-up from index to the earliest of 6 months post-index, end of data availability, other potassium binder use, or re-initiation of SZC post-discontinuation. Results: Among 1,586 matched pairs, the mean age was 65.5 years, 41.0% of patients were female, and most patients had any stage chronic kidney disease (91.9%), hypertension (90.8%), and diabetes (73.4%). Also, 30.0% of patients had heart failure. The most used RAASi therapies at index were angiotensin-converting enzyme inhibitors (57.3%) and angiotensin-receptor blockers (56.3%). Patients with long-term SZC use had a 44% lower rate of HK-related hospitalizations or ED visits, a 41% lower rate of HK-related hospitalizations and a 52% lower rate of HK-related ED visits than patients with short-term SZC use during follow-up (all p&lt;0.01; Figure 1). Conclusions: Among patients with RAASi and SZC therapy use, long-term SZC use was associated with significantly lower rates of HK-related HRU compared to matched patients with short-term SZC use. Funding: AstraZeneca

The phospho-tau cascade, basal forebrain neurodegeneration, and dementia in Alzheimer's disease: Anti-neurodegenerative benefits of acetylcholinesterase inhibitors.

A conundrum in Alzheimer's disease (AD) is why the long-term use of acetylcholinesterase (AChE) inhibitors, intended for treatment of dementia, results in slowing neurodegeneration in the cholinergic basal forebrain, hippocampus, and cortex. The phospho-tau cascade hypothesis presented here attempts to answer that question by unifying three hallmark features of AD into a specific sequence of events. It is proposed that the hyperphosphorylation of tau protein leads to the AD-associated deficit of nerve growth factor (NGF), then to atrophy of the cholinergic basal forebrain and dementia. Because the release of pro-nerve growth factor (pro-NGF) is activity-dependent and is controlled by basal forebrain projections to the hippocampus and cortex, our hypothesis is that AChE inhibitors act by increasing acetylcholine-dependent pro-NGF release and, thus, augmenting the availability of mature NGF and improving basal forebrain survival. If correct, improved central nervous system-selective AChE inhibitor therapy started prophylactically, before AD-associated basal forebrain atrophy and cognitive impairment onset, has the potential to delay not only the onset of dementia but also its rate of advancement. The phospho-tau hypothesis thus suggests that preventing hyperphosphorylation of tau protein, early should be a high priority as a strategy to help reduce dementia and its associated widespread social and economic suffering.

Game of Life With Your Companion Robot: Exploring the Sustainable Future for Long-Term Human-Robot Interaction

Reducing electronic waste is one of the key topics in Sustainable Interaction Design. However, research regarding the sustainable future of the long-term use of robots is limited. Our study employs a game-based workshop to investigate the factors influencing potential users’ sustainability choices in long-term human-robot interactions. We developed a board game called “Game of Life with Your Companion Robot” to help participants situate themselves in the context of cohabiting with companion robots of their choice. Through five workshops with seventeen participants, we explore (a) the factors mentioned by participants that influence their sustainability choices in long-term human-robot interactions, and (b) the connections between how participants frame their companion robots and their sustainability choices. We use four sustainable criteria to evaluate participants’ choices. Our findings show that different framings of robots can result in different sustainable outcomes.

Effect of nutrition on the nutritional status in preterm infants with very low birth weight

Introduction. Postnatal growth retardation in premature infants with very low birth weight (VLBW) remains an unresolved problem. There are different approaches regarding the duration of use of breast milk fortifiers during breastfeeding and specialized formulas during formula feeding, as well as the timing of the appointment of complementary feeding. Objective: to evaluate the physical development and component body composition in VLBW infants, depending on nutritional support over the first year of life. Materials and methods. The study included ninety three VLBW premature infants of 2 to 11 months postnatal age (PNA). The main (1st) group included infants (n = 74) who received dietary correction depending on the nutritional status, while no such intervention was performed in the (2nd) comparison group (n = 19). Up to 64 weeks of postconceptional age (PCA), weight, body length, and head circumference were assessed using INTERGROWTH-21st international growth standards, then in the software “WHO Anthro (2009)”. Fat and fat-free (lean) mass were determined using the air plethysmography method (PEA POD, LMi, USA). Results. The analysis of the nutritional status revealed a moderate deviation, not exceeding 1 sigma, decrease in indices (Z-scores) of anthropometric indices in infants of the 1st and 2nd groups by PNA of 2–3 months. Further in infants of the 1st group on the background of prolonged use of fortified nutrition (breast milk fortifier or specialized formulas for preterm infants) and timely introduction of complementary foods, nutritional deficiencies throughout the first year of life in general were not revealed. In the 2nd group of infants without additional correction of nutrition by 4–5 months of age, the development of mild nutritional deficiency was noted by 6–7 months of age. By 6–7 months of age, it turned into moderate nutritional deficiency, which persisted until 8–9 months of age and then turned into mild nutritional deficiency. Analysis of the component body composition showed that during the observation period, the fat-free body mass (FFM) gain in infants in the 1st group was 3.40 kg, in Group 2 infants — 2.2 kg. At the same time, % body fat mass (FM) in infants in groups 1 and 2 had no significant differences (%FM 1 = 19.3 [15.3–22.5], %FM 2 = 19.9 [16.7–24.6], p = 0.769) and did not exceed the values characteristic of preterm infants. Conclusion. A comprehensive assessment of the nutritional status of VLBW infants during the first year of life allowed us to eva­luate the positive impact of long-term use of fortified diets and timely introduction of certain complementary foods. Optimization of nutrition made it possible to prevent the development of nutritional deficiency, which can have a significant positive impact on their further growth, development, and health status.

Phyto-pharmaceuticals as a safe and potential alternative in management of psoriasis: a review.

Psoriasis is a chronic autoimmune skin disease with a worldwide prevalence of 1-3 % results from uncontrolled proliferation of keratinocytes and affects millions of people. While there are various treatment options available, some of them may come with potential side effects and limitations. Recent research has shown that using bioactive compounds that originate from natural sources with a lower risk of side effects are relatively useful in safe management psoriasis. Bioactive compounds are molecules that are naturally available with potential therapeutic efficacy. Someof bioactive compounds that have shown promising results in the management of psoriasis include curcumin, resveratrol, quercetin, epigallocatechin-3-gallate, etc., possess anti-inflammatory, antioxidant, immunomodulatory, and anti-proliferative properties, with capabilities to suppress overall pathogenesis of psoriasis. Moreover, these bioactive compounds are generally considered as safe andare well-tolerated, making them potential options for long-term use in the management of various conditions linked with psoriasis. In addition, these natural products may also offer a more holistic approach to treat the disease, which is appealing to many patients. This review explores the bioactive compounds in mitigation of psoriasis either innative or incorporated within novel drug delivery. Moreover, recent clinical findings in relation to natural product usage have been also explored.

Platelet-rich plasma and topical minoxidil 5% in the treatment of severe alopecia areata: Report of two cases

Alopecia areata (AA) is an autoimmune non-scarring hair loss that can affect any hair-baring body area. Corticosteroids are considered first-line treatment, but their long-term use may lead to undesirable side effects. Platelet-rich plasma (PRP) is an autologous product, which includes concentrated platelets that secrete growth factors stimulating hair follicle proliferation. Topical minoxidil has been used for mild cases of AA and other types of alopecia. We report two cases of severe multifocal AA, treated successfully with the combination of topical minoxidil 5% and intralesional PRP. PRP was injected once monthly for a total of six visits. Patients were advised to use 5% topical minoxidil twice daily. Trichoscopy was performed and evaluation of the severity of hair loss was done with Severity of Alopecia Tool (SALT). One month after the final PRP procedure, patients showed significant hair regrowth. Further controlled trials with more subjects are needed to validate the reported results.