Treatment Options Research Articles

Exploring Parent Treatment Decision-Making in Relapsed and Refractory Neuroblastoma: A Qualitative Study

Parents often become involved in making treatment decisions for their child with cancer when there is no standard treatment protocol, typically seen in poor-prognosis cancers. Advances in scientific medicine has led to more treatment options being available for children resulting in parents making repeated treatment decisions depending on their child’s response to treatment. The emotional turmoil of their child's cancer diagnosis can be exacerbated when combined with making decisions that have uncertain outcomes. This study aimed to identify, describe, explore, and explain how parents made repeated treatment decisions and the role of emotion in decision-making when their child had relapsed or refractory neuroblastoma, a poor-prognosis cancer.Data were collected using qualitative interviews between 2020-2022 with parents of children with relapsed or refractory neuroblastoma in the United Kingdom. Data were analysed using Reflexive Thematic Analysis.Eighteen parents who made between one to six treatment decisions participated. Decision-making incorporated four themes which enabled, influenced, and informed how parents made treatment decisions: 1) time as a structure within decision-making; 2) uncertainty and its relationships with treatment risk, side effects and outcomes; 3) parent oscillation of their cognitive and emotional adjustment; 4) parent responsibility and involvement in decision-making. Time was the central organising concept which structured and organised parent decision-making. We adopted Orlikowski and Yates’s (2002) temporal structures to characterise the experience of time and Stroebe and Schut’s (1999) dual-processing theory to explore the oscillation of parent adjustment of their situation cognitively and emotionally. A conceptual framework showed the interrelationships of these themes.

Samelisant (SUVN-G3031), A Histamine 3 Receptor Inverse Agonist: Results from The Phase 2 Double-Blind Randomized Placebo-Controlled Study for The Treatment of Excessive Daytime Sleepiness in Adult Patients with Narcolepsy

Narcolepsy is a rare, chronic neurological disorder characterized by a dysregulated sleep-wake cycle, with core clinical features including excessive daytime sleepiness (EDS), cataplexy, hypnopompic/hypnagogic hallucinations, and sleep paralysis. Several treatment options are available for the symptomatic management of narcolepsy, but they have limitations. Comorbidities of narcolepsy further limit the treatment choices. Blocking of histamine 3 (H3) receptors has been demonstrated to be a viable approach for the management of symptoms of narcolepsy. Samelisant (SUVN-G3031) is a new H3 receptor inverse agonist. The efficacy, safety, tolerability, and pharmacokinetics of Samelisant in narcolepsy patients were evaluated in a phase 2, double-blind, placebo-controlled study (ClinicalTrials.gov identifier: NCT04072380). Patients diagnosed with narcolepsy according to the International Classification of Sleep Disorders criteria and having an Epworth Sleepiness Scale (ESS) score of ≥12 and a mean Maintenance of Wakefulness Test (MWT) time of <12min across the 4 sessions at baseline were enrolled. The total study duration was up to 7 weeks, which included a screening period of 4 weeks, a treatment period of 2 weeks, and a safety follow-up 1 week after the last study drug administration. The primary efficacy measure was the change in total ESS score compared to placebo. Secondary and exploratory assessments included the Clinical Global Impression of Severity, MWT, Clinical Global Impression of Change, Patient Global Impression of Change and cataplexy rate. Safety assessments included monitoring adverse events (AEs) and laboratory assessments. Of the 426 patients screened, 190 were randomized. The safety and intention-to-treat population included 188 and 164 patients, respectively. A statistically significant treatment effect of Samelisant was observed on the primary endpoint, indicating improvements in EDS. The treatment's impact on EDS was also evident on the other patients' and clinicians' perspectives scales. The AEs reported in ≥5% patients in any treatment groups were insomnia, abnormal dreams, nausea, and hot flush. Global phase 3 studies and long-term safety and efficacy assessments of Samelisant are planned to reaffirm the current findings.

Comparative evaluation of the effects of deferiprone and/or resveratrol in alleviating iron overload-induced tongue injury in rats

Iron overload causes excessive iron deposition in extrahepatic organs, including the tongue. This study aims to compare the deferiprone and/or resveratrol treatments for the alleviation of iron overload-induced tongue injury in rats. Rats were divided into 6 groups: control group, iron-overloaded group, recovery group where rats were left to recover from iron overload, deferiprone-treated group, resveratrol-treated group, and combined deferiprone/resveratrol-treated group. Iron was administered for 4 weeks, while all treatment options were given for the subsequent 4 weeks. After 8 weeks, all rats were sacrificed; the serum iron profile was estimated, and the tongues were assessed by histopathological, tumour necrosis factor alpha (TNF-α) immunohistochemical, histomorphometric, and ultrastructural evaluations. Serum iron parameters were significantly increased in iron-overloaded rats and decreased to control levels only in the combined group. The iron-overloaded tongues demonstrated lost lingual papillae, coarse keratohyalin granules, vacuolated epithelial cells, degenerated muscle fibers, and congested blood vessels. Compared to the control rats, this group revealed a significant decrease in the epithelial layer thickness (550.7 vs. 763.4µm), papillae height (441.4 vs. 849.7µm), and myofiber diameter (58.5 vs. 98.6µm), and increased lamina propria thickness (305.1 vs. 176.8µm), fibrosis index (33.4 vs. 8.6%), and TNF-α immunoexpression (1.16 vs. 0.63 optical density). Additionally, the ultrastructure showed hyperkeratinized papillae, wide interpapillary spaces, flat fungiform papillae, and lost gustatory pores. All these parameters were improved in the recovery, deferiprone, and resveratrol groups to different degrees, while the combined deferiprone/resveratrol treatment was the best option.

Clinical and radiographic outcomes after subduro-peritoneal shunt insertion in adults

BackgroundSubdural collections consist amongst others of cerebrospinal, inflammatory, haemorrhagic or infective fluid. While these accumulations can be treated with conservative or surgical measures, such as burr hole evacuation or craniotomy, clinicians may resort to implantation of a subduro-peritoneal shunt, due to their high recurrence rates. While this treatment option is widely used in the pediatric population, its efficacy and safety in adults is scarcely reported. MethodsThis project is a retrospective case series of 25 adult patients, who underwent subduro-peritoneal shunt (SDPS) implantation between December 2008 and June 2021. The indications included symptomatic subdural collections following trauma, tumor resection or bone flap reimplantation. In general, adjustable valves were used. All patients received a pre- and postoperative computed tomography (CT) scan. We evaluated patients’ postoperative clinical outcomes as well as radiographic criteria, including midline shift, frontal horn width and collection volume. Additionally, we analyzed shunt-related complications. ResultsImpaired consciousness was the commonest presenting symptom. We report a significant reduction in volume and width of the subdural collection after SDP shunt implantation. Furthermore, the midline shift decreased significantly. While 60% (N=15) of the patients improved clinically, only 12% (N=3) deteriorated. Complications comprised infection in 12% (N=3) of patients and valve dysfunction in 1 patient. ConclusionsOur study shows that SDPS in adults is an effective treatment to eliminate or reduce subdural collections, that improves clinical outcomes in the majority of patients. Hence, it should be utilised more widely in this patient population. However, further studies are necessary to validate the treatment and identify eligible patients.

Management of pediatric thyroid carcinoma.

The incidence of thyroid carcinoma is increasing among children and adolescents, particularly in female individuals. Children and adolescents require special considerations in management as the molecular genetics of pediatric thyroid tumors are inherently different from their adult counterparts. The increased risk of malignancy, nodal metastases, and pulmonary metastases in pediatric patients warrants pediatric-specific management recommendations and pediatric-specific multidisciplinary teams. This article highlights the molecular origins of pediatric thyroid carcinoma and the implications of tumor genetics for the course of disease and treatment considerations. We highlight specific surgical considerations to optimize outcomes while minimizing lifelong risks of vocal paralysis and hypoparathyroidism. The landscape of treatment options is rapidly evolving with development of sophisticated molecular approaches to understand the genetic landscape, and this review features updated recommendations and systemic treatment options for the management of pediatric thyroid malignancy. Pediatric thyroid carcinoma is a lifelong burden and the treatment tailored to optimize outcomes minimizes long-term risks of treatments, surgery, radiation and targeted systemic therapies. Multidisciplinary teams that treat pediatric thyroid carcinoma should focus surgical experience and use the most updated guidelines and treatments available, particularly considering the landscape of molecular genetics in pediatric thyroid carcinoma.

A novel near-infrared fluorescent probe for butyrylcholinesterase: Research for screening of natural anti-AD inhibitors

Elevated levels of butyrylcholinesterase (BuChE) have the potential to be predictive in the timely detection and diagnosis of Alzheimer's disease (AD). By inhibiting of BuChE activity can raise acetylcholine levels and intervene AD processes. Therefore, BuChE as an important factor in treatment AD has been given more and more attention in clinical studies. Given the facts above, in this study, for precise monitoring of BuChE level changes and screening for possible butyrylcholinesterase inhibitor (BuChEI) for AD diagnosis and therapy, a near-infrared (NIR) fluorescence probe (NFP-BuChE) was created. The probe exhibits excellent sensitivity and selectivity for BuChE. NFP-BuChE has been successfully applied to the detection of endogenous BuChE levels in live cells, and we successfully constructed a screening system for BuChEI on cells and a novel natural efficient BuChEI (matrine) was discovered and identified, which significantly reduced BuChE activity and thus alleviated AD symptoms. Most importantly, for the first time, we measured the changes of BuChE levels in zebrafish (0-4 days) after fertilization, various organs of zebrafish, and AD zebrafish modeled by different concentrations of AlCl3 by NFP-BuChE, and at the same time, we also validated the inhibitory effect of matrine on BuChE by NFP-BuChE in zebrafish. In addition, NFP-BuChE has also been successfully used to measure the changes of BuChE levels in the brains of AD mice. These findings imply that NFP-BuChE is a potentially useful molecular tool for screening possible natural BuChEI quickly and for monitoring changes in BuChE activity, and it is expected that more value will be explored in mice. In addition, matrine and its derivatives are promising options for future Alzheimer's disease treatments.

Exploring stereotactic radiosurgery for tremor using the Varian cone planning system

BackgroundStereotactic radiosurgery (SRS) is an effective treatment for essential tremor (ET) and Parkinsonian tremor (PT). However, current treatment methods can be time-consuming and expose patients to unnecessary radiation. This study investigates the use of the Varian TrueBeam system with FFF beam modes as a potential solution for these issues. MethodsWe recreated and evaluated treatment plans using the Varian TrueBeam and Eclipse Cone Planning system for ten patients previously treated for tremor cessation using a Novalis Tx linear accelerator with Brainlab planning system prescribed a maximum dose of 160 Gy. Analyses included beam-on delivery time, total MU, dose to brain and brainstem tissues, and confirmation of SRS cone accuracy. ResultsThe TrueBeam cone delivery system is highly accurate. Our results demonstrated a significant reduction in monitor units (MU) and treatment delivery time shortened to 17-26 min beam-on time for all-Varian plans compared to 39 min for non-Varian (iPlan) plans (p < 0.0001). Furthermore, the Varian plans showed improved or similar dose fall-off and radiation dose to brainstem normal tissue. ConclusionOur findings suggest that the Varian TrueBeam system offers a safe and effective option for SRS tremor treatment, providing similar or superior treatment parameters compared to other LINAC-based SRS treatments. The reduced treatment times and improved patient comfort offered by this system make it a promising solution for future tremor treatments.

Effect of betahistine on pro-inflammatory cytokine expression in autoimmune inner ear disease and Meniere's disease patients.

Betahistine is a partial H1 receptor agonist and a potent H3 receptor antagonist commonly used for the treatment of MD and peripheral vertigo. The aim of this study was to investigate the impact of betahistine on the salt induced cytokine expression profiles of AIED and MD patients. Peripheral blood mononuclear cells (PBMCs) were obtained from 24 patients with autoimmune inner ear disease (AIED) or Meniere's disease (MD) during an acute exacerbation of hearing loss. These PBMCs were cultured with 80 mM NaCl or a combination of 80 mM NaCl and betahistine and IL-1β and IL-6 expression were measured by real time PCR and ELISA. In most patients, IL-1β expression in response to NaCl exceeded the unstimulated condition and this expression was abrogated by the addition of betahistine, which was statistically significant at p = .004. mRNA expression of IL-1β was not reduced when samples were treated with both salt and betahistine compared to samples treated with salt alone, inferring the mechanism of betahistine-mediated IL-1β suppression is post-translational. Similarly, IL-6 cellular release was augmented with salt exposure and reduced with co-culture of betahistine. Unlike IL-1 however, betahistine appeared to reduce IL-6 mRNA expression. We observe that betahistine abrogates salt-induced IL-1β expression, suggesting an additional treatment option for AIED and MD patients with inflammatory mediated disease. Level 4.

Virtual Reality Therapy for Chronic Pain: A Scoping Review on Indications, Mechanisms of Action, and Effectiveness

Background: The application of virtual reality (VR) technology as a nonpharmacologic treatment option for chronic pain has been increasingly studied. However, the mechanisms underlying this treatment modality's potential positive effects and appropriate indications are not well understood or summarized in the literature. Objectives: This scoping review aims to better understand the chronic pain populations best indicated for head-mounted display-based VR interventions, explore their efficacy on pain score reduction, and characterize the mechanisms of action underlying their efficacy. Methods: PubMed database systematic searches were conducted including articles from January 2010 to August 2023 with primary qualifying criteria including but not limited to use of head-mounted display VR and adequate VR treatment dosage. Mechanisms of action(s) were deduced via an exploratory approach whereby characteristics of VR treatment interventions were analyzed and categorized. Results: Fourteen studies met qualifying criteria, representing a total treatment group of 327. Study data extracted were solely relative to VR treatment group participants. VR intervention mechanisms of action were best characterized via 2 broad but distinct categories: addressing kinesiophobia and psychobehavioral modulation. Three studies investigating chronic neck pain used addressing kinesiophobia as a mechanism of action and demonstrated a significant improvement [weighted average numerical rating scale (NRS): 4.6 at baseline, 2.5 post-intervention, and 2.5 3 months post-intervention]. Six studies investigated chronic low back pain, for which 5 studies, representing 99% of the subgroup, used psychobehavioral modulation. Each demonstrated significant reduction in pain (weighted average NRS: 5.1 baseline and 3.2 post-intervention). Conclusion: This large-scale within-group analysis review proposes 2 broad mechanisms of action underlying the efficacy of VR interventions for chronic pain indications. VR interventions addressing kinesiophobia seem to be significantly effective in nontraumatic chronic neck pain patients. Psychobehavioral VR interventions demonstrate significant efficacy in the chronic low back pain population. Studies with interventions targeting nonspecific chronic pain populations did not show significant results.

MiR-124 in Neuroblastoma: Mechanistic Insights, Biomarker Potential, and Therapeutic Prospects

: Neuroblastoma, a malignancy predominantly affecting young children, originates from neural crest cells in the sympathetic nervous system. It primarily appears in the adrenal gland but can also affect nerve tissues in regions, such as the chest, neck, abdomen, and pelvis. Despite advancements in treatment, high-risk neuroblastoma patients often face poor prognoses, underscoring the need for ongoing research. This review paper examines the numerous factors responsible for neuroblastoma, emphasizing the importance of approaching the disorder with more strategic therapeutic methods. MicroRNAs, particularly miR-124, play critical roles in gene regulation and cancer pathogenesis. Abundant in the brain, miR-124 functions as a tumor suppressor by inhibiting cell growth, migration, and invasion and is often dysregulated in neuroblastoma. This study investigates the molecular functions of miR-124 in neuroblastoma, its potential as a biomarker, and its application in targeted therapy. MiR-124 regulates key pathways in neuroblastoma, including PI3K/AKT, TGF-β, and p53 signaling, impacting cell proliferation, apoptosis, and metastasis. The study also explores the promise of miR-124 as a biomarker for neuroblastoma through liquid biopsy, enabling non-invasive diagnosis and disease monitoring. Therapeutic strategies targeting miR-124 pathways show potential for overcoming chemotherapy resistance and improving treatment efficacy. The research underscores the significance of miR-124 in neuroblastoma, aiming to enhance early diagnosis, identify specific drug targets, and expand treatment options, ultimately improving patient outcomes.

Understanding the Relationship between the Ketogenic Diet and the Heart: A Novel Therapeutic Potential for Cardiovascular Health.

Obesity and cardiovascular diseases are major health problems worldwide, and weight loss is used as a treatment strategy to enhance various aspects. While there are many weight loss methods, one of the most effective is through a dietary approach. The ketogenic diet (KD), which is characterized by low carbohydrates and high levels of fat and/or protein, is used in obese patients as it is a promising treatment option for weight loss as well as for controlling the risk factors for cardiovascular diseases, as seen in its effects on cardio-metabolic outcomes, particularly in obesity, heart failure, and hypertension. In this review, we summarize the clinical evidence of the efficacy and safety of the KD in controlling risk factors for cardiovascular diseases and discuss the possible mechanisms of action based on recent evidence in understanding the influence of the KD at the cellular and molecular levels.

Deep infections after low-velocity ballistic tibia fractures are frequently polymicrobial and recalcitrant.

To identify risk factors for developing a fracture-related infection in operatively treated ballistic tibia fractures and to report the microbiologic results of intraoperative cultures. Retrospective review. Level 1 trauma center. One hundred thirty-three adults with operatively treated low-velocity ballistic tibia fractures, from 2011 to 2021. One dose of prophylactic cefazolin or equivalent as well as perioperative prophylaxis. Deep infection rate. The deep infection rate was 12% (16/134) with no significant difference in injury characteristics, index surgical characteristics, or time to antibiotics between the groups (P > 0.05). Patients who were slightly older (35.5 vs. 27 median years, P = 0.005) and with higher median body mass indexes (BMIs) (30.09 vs. 24.51, P = 0.021) developed a deep infection. 56.3% of patients presented with signs of infection within the first 100 days after injury. Nine patients had polymicrobial infections. There were 29 isolated organisms, 69% were uncovered by first-generation cephalosporin prophylaxis (anaerobes, gram-negative rods, Enterococcus, methicillin resistant Staphylococcus Aureus [MRSA]), and 50% of patients developed recalcitrant infection and required a second reoperation where 6 organisms were isolated, half of which were not covered by first-generation prophylaxis (Enterococcus, Staphylococcus Aureus MRSA). We found a deep infection rate of 12% among ballistic tibia fractures receiving standard-of-care antibiotic prophylaxis. Increased age and body mass index were associated with deep infections. Half became recalcitrant requiring a second reoperation. 66.7% of isolated organisms were not covered by first-generation cephalosporin prophylaxis. Consideration should be given to treatment options such as broader prophylaxis or local antibiotic treatment. IV.

Lecanemab Planning: Blueprint for Safe and Effective Management of Complex Therapies.

Approximately 6.9 million American individuals have Alzheimer dementia and 50% have mild disease. Lecanemab, an approved antiamyloid antibody, is associated with modest reduction in functional decline in patients with mild dementia or mild cognitive impairment. In Clarity-AD, 239 (26.6%) of patients experienced amyloid-related imaging abnormalities (ARIAs) overall (i.e., ARIAs associated with hemorrhages or edema). The complexity of treatment and risks of adverse events necessitate a multidisciplinary collaborative approach. With limited treatment options, lecanemab approval generated significant interest among clinicians, patients, and families. Lecanemab treatment requires biweekly infusions along with ongoing imaging tests, laboratory monitoring, patient assessment, drug interaction screening, and cognitive function monitoring. Processes to support patient selection, access, and safety are important given the monitoring requirements and total cost of care. The planning process for lecanemab can serve as a blueprint to support safe and effective management of therapeutic innovation in neurology and other areas.

(E, E)-farnesol and myristic acid-loaded lipid nanoparticles overcome colistin resistance in Acinetobacter baumannii

The rise of colistin-resistant Acinetobacter baumannii has severely limited treatment options for infections caused by this pathogen. While terpene alcohols and fatty acids have shown potential to enhance colistin’s efficacy, but their high lipophilicity limits their clinical application. To address this, we developed water-dispersible lipid nanoparticles (LNPs) in two sizes (40 nm and 130 nm), loaded with these compounds to act as colistin adjuvants. Among eleven LNP formulations, six significantly reduced colistin’s minimum inhibitory concentration (MIC) by 16- to 64-fold. The most effective, featuring (E,E)-farnesol and myristic acid, were further examined for bactericidal activity, membrane disruption, cytotoxicity, and in vivo efficacy in Galleria mellonella larvae. Time-kill studies demonstrated that at an adjuvant concentration of 60 mg/L, these LNPs eradicated bacteria when combined with 4 mg/L free colistin for resistant isolates (MIC = 128 mg/L) and 0.06 mg/L for susceptible isolates (MIC = 0.5 mg/L), without regrowth. Myristic acid-loaded LNPs combined with free colistin at 1/8 MIC resulted in a 4.2-fold higher mortality rate than the combination with (E,E)-farnesol-loaded LNPs in resistant strains. This result was correlated with a 45-fold faster increase in inner membrane permeability, measured by propidium iodide (PI) uptake, in the presence of myristic acid-loaded LNPs compared with a 13-fold faster increase with (E,E)-farnesol-loaded LNPs. DiSC3(5) assays revealed that LNPs alone depolarised the bacterial inner membrane, with enhanced effects when combined with colistin at 1/8 MIC, a result not observed with colistin alone at this concentration. As with PI uptake, this inner membrane depolarising effect was more pronounced with myristic acid-loaded LNPs than with (E,E)-farnesol-loaded LNPs in resistant strains, suggesting that the colistin adjuvant effect of these lipophilic compounds is due to their ability to help colistin destabilise the bacterial inner membrane. Cytotoxicity assays demonstrated no adverse effects on bone marrow macrophages after 6 h of exposure, although some toxicity was observed after 24 h. No mortality was observed in Galleria mellonella larvae over 7 days following three consecutive days of treatment with colistin and LNPs. Notably, the combination of (E,E)-farnesol-loaded LNPs and colistin significantly improved the survival of Galleria infected with A.baumannii. These results suggest that lipophilic-adjuvant-loaded LNPs may offer a promising strategy to enhance colistin efficacy and combat antibiotic-resistant A. baumannii infections.

The Roles of Endogenous D2R Dopamine and μ-opioid Receptors of the Brain in Alcohol use Disorder.

Alcohol use disorder (AUD) affects millions of people worldwide. It is characterized by a strong physiological and psychological craving to consume large amounts of alcohol despite adverse consequences. Alcohol use disorder carries a large health and economic burden on society. Despite its prevalence, AUD is still severely undertreated. The precise molecular mechanisms of how alcohol addiction forms are yet unknown. However, previous studies on animal models show that along with the μ-opioid receptors, the D2R dopamine receptors may also be involved in alcohol craving and reward pathways. Currently, there is a limited number of treatment strategies for alcohol use disorder, which include several medications and therapy. By understanding the limitations of current treatment options and exploring new potential targets, it could be possible to find more effective ways of treating AUD in the future.

Gross saponins of Tribulus terrestris attenuate rheumatoid arthritis by promoting apoptosis of fibroblast-like synoviocytes and reducing inflammation by inhibiting MAPK signalling pathway.

Among the numerous treatment options for rheumatoid arthritis (RA), the promotion of synoviocyte apoptosis and inhibition of inflammation are considered the most effective. However, the potential pro-apoptotic effects of gross saponins of Tribulus terrestris (GSTT), which are natural saponins derived from the herb Tribulus terrestris L., on rheumatoid arthritis fibroblast-like synoviocytes (RA-FLSs) and their essential molecular mechanisms remain unclear. The aim of the present study was to investigate the influence of different concentrations of GSTT on RA-FLSs using various assays, including cell counting kit-8 (CCK-8), reverse transcription polymerase chain reaction (RT-PCR), enzyme-linked immunosorbent assay (ELISA), flow cytometry, terminal deoxynucleotidyl transferase dUTP nick end labelling (TUNEL) and western blot analysis. These assessments were conducted to evaluate the cell viability, changes in the levels of inflammatory cytokines, apoptosis rates and alterations in protein expression related to this process. In vivo, arthritis clinical score, haematoxylin and eosin (HE) staining and ELISA were used to assess paw inflammation, histopathology and serum inflammatory cytokine changes. Our findings demonstrated that GSTT substantially promotes the apoptosis of RA-FLSs and reduces pro-inflammatory cytokine levels. GSTT also reduced the Bcl-2/Bax ratio and inhibited JNK and p38 phosphorylation. Furthermore, GSTT exhibits positive effects on RA by improving clinical scores, reducing synovial inflammatory infiltration and lowering serum pro-inflammatory cytokine levels. Therefore, by promoting the apoptosis of RA-FLSs and suppressing inflammation through the inhibition of the MAPK signalling pathway, GSTT is a promising therapeutic intervention for RA.

A novel digital intervention for improving cognitive impairment in patients with chronic schizophrenia: A randomized clinical trial

BackgroundThere is an unmet need for stand-alone digital therapeutics for cognitive impairment in schizophrenia. This study aimed to evaluate the efficacy and acceptability of a novel digital therapeutic, IBT-SC02, for cognitive impairment in stable schizophrenia patients. MethodsA randomized, parallel-group trial was conducted at the Sichuan Province Institute of Mental Health, China. Participants aged 18–50 diagnosed with schizophrenia were randomized to either the IBT-SC02 intervention or a wait-list control. The primary outcome was cognitive performance measured using the MATRICS Consensus Cognitive Battery (MCCB) composite score. ResultsA total of 80 patients were randomized (40 intervention, 40 control). The dropout rate was 5 %. The intervention group exhibited significant improvements in the MCCB composite score compared to the control, though the improvement lessened after excluding data collected by unmasked raters. Post-hoc analyses revealed that participants in the intervention group improved in four out of the seven MCCB domains (speed of processing, verbal learning, visual learning and reasoning and problem solving). No adverse events were reported. ConclusionsThese results suggest that IBT-SC02, a fully automated digital therapeutic, improved cognitive performance in patients with stable schizophrenia and can potentially be a treatment option for patients without access to trained professionals.

Newer treatment paradigm improves outcomes in the most common neurosurgical disease of the elderly: a literature review of middle meningeal artery embolization for chronic subdural hematoma.

Chronic subdural hematoma (cSDH) is one of the most prevalent neurosurgical diseases, especially in the elderly. Yet, its incidence is predicted to increase further, paralleling the growth of the geriatric population. While surgical evacuation is technically straightforward, it is associated with significant morbidity and mortality. In fact, 30% of patients are expected to have hematoma recurrence and to need repeat surgical evacuation, and 20% of patients are expected to lose independence and require long-term care. A pathophysiology more complex than originally presumed explains the disappointing results observed for decades. At its core, the formation of microcapillaries and anastomotic channels with the middle meningeal artery (MMA) perpetuates a constant cycle resulting in persistence of hematoma. The rationale behind MMA embolization is simple: to stop cSDH at its source. Over the last few years, this "newer" option has been heavily studied. It has shown tremendous potential in decreasing hematoma recurrence and improving neurological outcomes. Whether combined with surgical evacuation or performed as the only treatment, the scientific evidence to its benefits is unequivocal. Here, we aimed to review cSDH in the elderly and discuss its more recent treatment options with an emphasis on MMA embolization.

Lycium barbarum leaf flavonoids ameliorate high fructose induced insulin resistance in mice by regulating blood glucose and gut microbiota composition

Insulin resistance is an increasingly severe public health issue worldwide, affecting millions and significantly raising the risk of diabetes and cardiovascular diseases. Despite this, current treatment options remain limited, which has heightened interest in exploring interventions based on natural compounds. This study investigates the potential of Lycium barbarum leaf flavonoids (LBLF) to improve insulin resistance induced by high fructose in mice, with a focus on the mechanisms related to blood glucose regulation and gut microbiota composition. Research results show that, compared to the high fructose model group, treatment with metformin hydrochloride and rutin reduced fasting blood glucose levels by 32.06% and 18.94%, respectively. LBLF treatment at various doses decreased fasting blood glucose levels by 12.29%, 19.02%, and 32.98%, and insulin levels by 26.50%, 11.04%, and 28.23%, respectively, demonstrating its effective ability to regulate blood glucose levels. It was also found that LBLF effectively regulated lipid disorders, significantly reduced oxidative stress in the liver, and protected liver function. Liver transcriptomic analysis suggests that LBLF may improve insulin resistance by regulating gene expression in the MAPK and retinol metabolism signaling pathways. Additionally, gut microbiota diversity analysis revealed that LBLF treatment reduced the Firmicutes/Bacteroidetes (F/B) ratio, which is associated with obesity and metabolic disorders, thereby optimizing the gut microbiota structure disrupted by high fructose intake. These results highlight the therapeutic potential of LBLF in managing insulin resistance and associated metabolic disorders, providing a theoretical basis for further research into its broader applications.

Gene expression alterations in hypoxic A549 lung cancer cell line.

Human non-small cell lung cancer (NSCLC)is a very common disease with limited treatment options. Hypoxia is a characteristic feature of solid tumors associated with the resistance of cancer cells to radiotherapy and chemotherapy. Therefore, the expression changes in cancer-resistance genes may be biomarkers of hypoxia with value in targeted therapy. The aim of the present study was to examine the effect of hypoxia on gene expression and the changes that occur in relation to drug resistance in a human NSCLC cell line (A549). A549 cells were exposed to 72-h hypoxic episodes (<1% oxygen) for a total of 10 episodes (acute). The alterations in gene expression were examined using PCR array technology after 10 episodes of acute hypoxia and compared with normoxic cells. The chemoresistance of hypoxic cells toward doxorubicin was measured using a MTT cell proliferation assay. A549 cells were affected by acute hypoxia leading to induced doxorubicin chemoresistance. Evident changes in the gene expression level were identified following episodes of acute hypoxia. The most important changes occurred in the estrogen receptor 1 (ESR1) and Finkel-Biskis-Jinkins osteosarcoma (FOS) pathways and in different nucleic transcription factors such as aryl hydrocarbon receptor and cyclin-dependent kinase inhibitor. The present study showed that exposing cells to prolonged periods of hypoxia results in different gene expression changes. There was induction of chemo-resistance due to acute hypoxia. ESR1 and c-FOS are proposed as a potential hypoxia genes in lung cancer.