Combined Treatment Research Articles

Efficacy and diabetes risk of moderate-intensity statin plus ezetimibe versus high-intensity statin after percutaneous coronary intervention

BackgroundsHigh-intensity statin is recommended for patients undergoing percutaneous coronary intervention (PCI), and ezetimibe is recommended to be added in patients not achieving low-density lipoprotein cholesterol (LDL-C) targets. Moderate-intensity statin plus ezetimibe can reduce LDL-C levels similar to high-intensity statin. The aim of this study is to examine the long-term efficacy and safety of moderate-intensity statin plus ezetimibe as the first-line strategy compared to high-intensity statin in patients undergoing PCI.MethodData was obtained from the Health Insurance Review and Assessment Service database of South Korea. Patients who underwent PCI from 2012 to 2017 were included. The primary efficacy endpoint was major adverse cardiac cerebrovascular events (MACCEs), a composite of all-cause death, revascularization, or ischemic stroke. The safety endpoint was new-onset diabetes mellitus (DM).ResultsA total of 45,501 patients received high-intensity statin (n = 38,340) or moderate-intensity statin plus ezetimibe (n = 7,161). Among propensity-score-matched 7,161 pairs, MACCEs occurred in 1,460 patients with high-intensity statin and 1,406 patients with moderate-intensity statin plus ezetimibe (33.8% vs. 31.9%, hazard ratio 0.96, 95% confidence interval 0.89–1.03, P = 0.27) at a median follow-up of 2.7 years. DM was newly diagnosed in 398 patients with high-intensity statin and 342 patients with moderate-intensity statin plus ezetimibe (12.5% vs. 10.7%; hazard ratio 0.84, 95% confidence interval 0.73–0.97, P = 0.02).ConclusionIn patients undergoing PCI, moderate-intensity statin plus ezetimibe demonstrated a similar risk of MACCEs but a lower risk of new-onset DM than high-intensity statin. Early combination treatment of moderate-intensity statin and ezetimibe may be a useful and safe lipid-lowering strategy after PCI.Graphical abstractCumulative incidence according to the first-line lipid-lowering strategy in patients undergoing percutaneous coronary intervention. Abbreviation: MACCE, major adverse cardiac cerebrovascular events; PCI, percutaneous coronary intervention.

Inferior Overall Survival After Haploidentical Donor Lymphocyte Infusions in Relapsed Myeloid Neoplasms.

Allogeneic hematopoietic stem cell transplantation (HSCT) effectively treats high-risk myeloid neoplasms, but relapses post-HSCT, particularly in acute myeloid leukemia (AML) and myelodysplastic neoplasms (MDS), pose significant challenges. Donor lymphocyte infusion (DLI) has been utilized, but its effectiveness, especially in haploidentical settings, remains insufficiently clarified, and graft-versus-host disease (GvHD) poses a substantial risk. In this retrospective cohort study, 57 patients with AML or MDS who received DLI after allogeneic HSCT at our center from 2002 to 2023 were analyzed. Herein, only preemptively or therapeutically applied DLI were included, and endpoints included overall survival (OS), progression-free survival (PFS), and GvHD incidence post-DLI. Median OS after DLI was 517 days, with a 1-year OS of 62.5%. Factors associated with longer OS included patient age, HLA-identical donor, post-HSCT treatment naivety, and preemptive DLI indication. Haploidentical DLI was associated with inferior OS compared to HLA-identical DLI; however, PFS and GvHD incidence post-DLI did not differ significantly. Our study findings indicate that OS rate is inferior in patients with relapsed AML or MDS treated with haploidentical DLI in comparison to those who received HLA-identical DLI. Given the limitations of haploidentical DLI, alternative strategies, such as higher cell doses or combination treatment approaches, warrant further investigation.

Evidence to Support the Collaboration of SP1, MYC, and HIF1A and Their Association with microRNAs

This study provides evidence to support the concept proposed by Kimura et al. in 2023 that the inhibitors of SP1, MYC, and HIF1A should induce strong anticancer activity by reducing the expression of stem cell-related proteins. In LN229 and U87MG glioblastoma cells, either tetra-methyl-O-nordihydroguaiaretic acid (M4N) or tetra-acetyl-O-nordihydroguaiaretic acid (A4N) suppressed SP1 and only a few stem cell-related proteins and induced only a small amount of cell death; in contrast, the combination treatment of M4N with A4N greatly suppressed the expression of SP1, MYC, and HIF1A, as well as all of the stem cell-related proteins examined, and greatly induced cell death. The bioinformatic analysis showed that the proteins associated with SP1, MYC, and HIF1A were specifically involved in the regulation of transcription and that various microRNAs (miRNAs) that had been shown to induce either anti- or procancer activity were associated with SP1, MYC, and HIF1A, which suggested that the inhibition of SP1, MYC, and HIF1A could modulate the transcription of both coding and noncoding RNAs and affect cancers. These data overall supported our concept.

Drip irrigation and mulching reduce weed interference and improve water productivity of spring maize

Abstract Drip irrigation and mulching were tested to minimize unproductive water loss through evaporation and weed interference. A field experiment was conducted during spring season of 2020 and 2021 in split plot design with three replications. The study includes six treatment combinations of drip irrigation methods (surface drip and subsurface drip irrigation) and mulching (black plastic, paddy straw and no mulch) along with one conventional furrow irrigation without mulching (as control) in main plots. Four weed control treatments (atrazine 1000 g a.i./ha as pre-emergence, two hand weedings at 30 and 60 days after sowing [DAS], weed free and weedy for whole crop growth period) were kept in the subplots. The combination of drip irrigation and mulches significantly enhanced leaf area index and crop biomass at 60 DAS than furrow irrigation. Integration of subsurface drip irrigation with plastic mulching resulted in the lowest weed density and biomass among main plots. Drip irrigation coupled with plastic and straw mulching resulted in 86 and 50% reduction in weed density and biomass, respectively, as compared to no mulching. Integration of subsurface drip with paddy straw mulch and black plastic mulch resulted in 17.1 and 15.5% higher maize grain yield, respectively, as compared to furrow irrigation. The highest irrigation water productivity (3.58 kg/m3) was observed in combination of subsurface drip and paddy straw mulch followed by combination of subsurface drip and black plastic mulch (3.51 kg/m3). Overall, straw mulching in drip irrigation system proved economical in terms of maize productivity.

Effects of mulching on plant growth, viral diseases, earliness and fruit yield attributes of round gourd under variable sowing dates in North Indian plains

Abstract Round gourd is sensitive to low temperature (March), high temperature (May–June), high humidity (July–August), and whitefly-transmitted begomovirus diseases (July–September), thereby restricting its fruit availability period in North-Western Indian Plains. Mulches extend the growing season by modifying soil temperature and reducing the incidence of viral diseases. Therefore, the present study was conducted to investigate the effects of sowing time, mulching and their interaction on performance of round gourd crop so as to identify the best mulch at different sowing times. The field trials were conducted in a split-plot design during 2021 and 2022. The main plot consisted of six sowing dates, i.e., the first week of March (DS1), April (DS2), May (DS3), June (DS4), July (DS5) and August (DS6). The sub-plot comprised bare soil (BS) and three mulching treatments, viz., silver-black plastic mulch (SBPM), black plastic mulch (BPM) and paddy straw mulch (6 t/ha) (PSM). The BPM and SBPM increased the seasonal soil temperature over BS by 3.1–4.1°C and 2.1–3.1°C, respectively, whereas the PSM reduced the seasonal soil temperature by 2.3–3.5°C. The SBPM produced the best crop performance, followed by BPM and PSM in all sowing dates except DS5 in which the PSM outperformed BPM. The DS1 and DS2 were the best sowing times, and the crop performance gradually declined with each successive sowing time, except that the crop performed better in DS6 compared with DS5. The SBPM or BPM in DS2 and DS1 were the best treatment combinations for round gourd cultivation in the study area.

Occlusal and Cephalometric Outcomes of Cleft Orthognathic Surgery: A Retrospective Cohort Study.

Aberrant facial growth in individuals affected by orofacial clefts can result in maxillary retrusion and class III malocclusion, with a proportion requiring surgical correction at cessation of growth. This study aimed to evaluate occlusal and cephalometric outcomes of combined orthodontic-orthognathic treatment. Retrospective cohort study in a United Kingdom cleft center. Participants included twenty-seven patients (20 males, 7 females) with cleft (n = 16 UCLP :7 BCLP :4 ICP) who consecutively underwent combined surgical treatment for Class III malocclusion between January 2013 and December 2017. Records were collected pre-treatment (T0), pre-surgery (T1) and at debond (T2). Models were scored using the Peer Assessment Rating (PAR) index and cephalometric radiographs were traced and analyzed. Outcomes were assessed by an independent rater. Mean age at surgery was 21.4 years (SD 4.9). Le Fort 1 advancement (mean 6.1 mm, SD 4.0) was performed in all cases. Additional procedures included mandibular setback (n = 2), cortico-cancellous bone grafting (n = 6) and genioplasty (n = 1). Mean T0 PAR score was 44.8 (SD 11.7), reducing to 3.6 (SD 2.0) at T2, indicating a mean % PAR score reduction of 91.6% (SD 4.7). Class III skeletal profiles improved from a mean T0 ANB of -2.1º (SD 2.2), to 2.8º (SD 1.6) at T2. Mean T0 overjet was -3.3 mm (SD 2.3), increasing to 2.6 mm (SD 1.3) at T2. Cleft orthognathic surgery differs in complexity and approach to routine orthognathics, however, these results demonstrate that occlusal outcomes can still be comparable with non-cleft populations. Outcome data can be used for comparison with other centers providing cleft orthognathic treatment.

Carbon dot-based nanomaterials with enzyme-like activity for fluorescence imaging and potential combination withtherapy of cancer.

Carbon dot-based nanomaterials (o-CDs@Mn) were fabricated by assembling fluorescent o-CDs with enzyme-like activity and Mn nanoparticles with photothermal properties for realizing fluorescence imaging and combined therapy of cancer. Due to the inherent optical properties of o-CDs, o-CDs@Mn can be effectively used for bioimaging. In addition, o-CDs@Mn possess peroxidase-like (POD-like) and glutathione (GSH) degradation capabilities, which can effectively deplete excessive H2O2 and GSH in the tumor microenvironment (TME), generating ·OH and reduced GSSH for regulating the TME and triggering ROS-mediated apoptosis in cancer cells. More importantly, it is synergistically supplemented with fluorescence imaging and photothermal therapy (PTT), which realizes the integration of monitoring and combined treatment, providing a promising potential pathway for accurate and efficient cancer treatment.

Effects of pain neuroscience education combined with neuromuscular exercises on pain, functional disability and psychological factors in chronic low back pain: A study protocol for a single-blind randomized controlled trial.

Chronic low back pain (CLBP) is a prevalent health condition worldwide. Several therapeutic interventions aim to improve CLBP. Pain Neuroscience Education (PNE) helps patients better understand their pain from biological and physiological perspectives, which clinicians use to reduce pain and disability in patients with chronic musculoskeletal conditions. Neuromuscular exercises (NMS) are also treatments adopted in CLBP. This study will investigate whether PNE combined with an NMS program improves pain, functional and psychological outcomes more than NMS alone in patients with CLBP. In this single-blind randomized controlled trial, 60 patients (male and female; age range, 30-60 years) diagnosed with CLBP will be randomly assigned to one of the following groups: (1) PNE plus NMS (n = 30; 24 sessions of PNE plus NMS in a total of 8 weeks, 3 each week), and (2) NMS alone (n = 30; 24 sessions of NMS sessions in a total of 8 weeks, 3 each week). Outcome assessors will be blinded to the group allocation. The primary outcome will be pain. Secondary outcomes will be disability, fear-avoidance beliefs about work and physical activity, self-efficacy, exercise anxiety, and kinesiophobia. Outcomes will be assessed at baseline, after 8 weeks of intervention, and 6 months post-intervention. The findings of this RCT will help shed light on new treatment strategies to address the biopsychosocial dimensions of CLBP. The study protocol will be conducted in a clinical setting, offering the opportunity for future implementation in healthcare systems. Moreover, it will help clarify whether a combined treatment (PNE with NMS) is more effective than NMS alone for improving pain, functional and psychological outcomes in CLBP. Study registration: The study was prospectively registered in the Iranian Registry of Clinical Trials-IRCT20190427043384N2 (https://www.irct.ir/trial/69146). Registered on March 17, 2023.

Analyzing the Role of Different Molybdenum doses and Rhizobium Inoculation in Optimizing Nutrient Absorption and Yield in Vegetable Cowpea [Vigna unguiculata (L.) Walp.] cv. AVCP 1

Legumes, along with cereals, can be considered a main plant source of energy and quality proteins. A versatile legume crop, cowpeas offer economic, agronomic, environmental, and nutritional advantages. Cowpeas have a high total protein level and a relatively low fat content, making them nutritionally similar to other pulses. The study aimed to evaluate the effects of different rates of ammonium molybdate and Rhizobium inoculation on the yield and nutrient uptake of vegetable cowpea. There were 12 treatment combinations comprising six concentrations of molybdenum i.e. M0:control, M1: soil application of molybdenum @ 200 g ha-1, M2: soil application of molybdenum @ 300 g ha-1, M3: seed treatment of molybdenum 25 g ha-1 seeds, M4: seed treatment of molybdenum 50 g ha-1 seeds and M5: seed treatment of molybdenum 6 ml kg-1 seeds and two levels of Rhizobium i.e. R0: without Rhizobium seed treatment, R1: with Rhizobium (10 ml kg-1 seed) seed treatment in a Randomized Block Design (Factorial) with three replications. Results indicated that the application of ammonium molybdate and Rhizobium inoculation significantly improved total cowpea yield. The highest yield was observed with the treatment combination of 300 g ha⁻¹ ammonium molybdate (M₂) and Rhizobium inoculation (R₁). Nutrient analysis revealed that phosphorus, potassium and iron content in cowpea pods significantly increased with ammonium molybdate and Rhizobium treatments. The highest phosphorus and potassium contents were recorded with M₂ treatment, while the maximum iron content was found in M₃ treatment. Rhizobium treated seeds (R₁) also enhanced phosphorus, potassium and iron content in the pods. In terms of nutrient uptake, the highest nitrogen and phosphorus uptake were observed with the combined M₂R₁ treatment. Similarly, the highest potassium uptake in pods and total potassium uptake were recorded with M₂R₁ treatment, respectively. The interaction between ammonium molybdate and Rhizobium inoculation showed significant effects on nitrogen, phosphorus and potassium uptake, highlighting the importance of these treatments in enhancing cowpea nutrient absorption and yield. The use of biofertilizers can be highly successful in restoring agricultural soil, and this study highlights the possibility of combining Rhizobium inoculation with ammonium molybdate treatment to maximize nutrient uptake and enhance cowpea yield in sustainable agriculture production.

Groundnut (Arachis hypogaea L.) Response to Nitrogen Fertilizer and Earthing Up Practices in the Tigray Region of Ethiopia

To increase groundnut yields, integrated agronomic techniques must be implemented. The current study focuses on using starter nitrogen fertilizer in conjunction with earthing up for groundnut cultivation. Three replications and a factorial combination were used in the complete randomized block design of the experiment. Two types of earthing up (no earthing up and earthing up) and four levels of nitrogen fertilizer (0, 15, 30, and 45 kg ha-1) were used in the treatment combinations. For each of the Hamedo 1 and Hamedo 2 experimental sites, two undisturbed and two disturbed composite soil samples were collected at a depth of 20 cm before sowing. The data analysis showed that neither the combination application of N fertilizer and earthing up nor the individual independent applications of N fertilizer and earthing up had a significant effect on groundnut flowering and maturity. Groundnut plant height, number of branches per plant, number of pods per plant, number of seeds per plant, seed weight per plant, and haulm yields were not significantly affected by earthing up alone or by the co-application of nitrogen fertilizer and earthing up. On the other hand, the exclusive use of nitrogen fertilizer significantly affected groundnut plant height, the number of branches per plant, the number of pods per plant, the number of seeds per plant, seed weight per plant, and haulm yield. Applying 45 kg ha-1 of nitrogen fertilizer to the Hamedo 1 and Hamedo 2 trial sites enhanced the haulm yield by 70.53% and 78.76%, respectively, compared to the unfertilized plots. Individual applications of nitrogen fertilizer, earthing up, or a combination of both had a significant effect on groundnut pod and kernel yields. In comparison to plots that received a combined application of 45 kg ha-1 of nitrogen fertilizer and earthing up, the Hamedo 1 and Hamedo 2 trial sites exhibited increases in pod yields of 57.73% and 55.97%, respectively, when earthing up was combined with 15 kg ha-1 of nitrogen fertilizer. In the same way, applying 15 kg ha-1 of nitrogen fertilizer to the earthing-up soil in the Hamedo 1 and Hamedo 2 experimental sites boosted the kernel yields by 70.05% and 75.43%, respectively, in comparison to soil earthing-up plots that received 45 kg ha-1 nitrogen. The findings of the economic and agronomic analyses showed that applying nitrogen fertilizer and earthing up together greatly increases groundnut yields and revenues. Therefore, to increase groundnut yields and receive more financial advantages, farmers can consider the combined application of 15 kg ha-1 of nitrogen fertilizer and earthing-up.

Non-Pharmacological Spine Pain Management in Clinical Practice Guidelines: A Systematic Review Using AGREE II and AGREE-REX Tools

OBJECTIVE: To summarize the content and critically appraise the quality and applicability of recent clinical practice guidelines (CPGs) for non-pharmacological, non-surgical management of spine pain. DESIGN: Systematic review of CPGs. LITERATURE SEARCH: Six databases and seven guideline clearinghouses. STUDY SELECTION CRITERIA: Included de novo CPGs for non-pharmacological, non-surgical management of spine pain designed for any primary healthcare providers, published in English, Arabic, French, or traditional Chinese within the past 12 years. DATA SYNTHESIS: Five reviewers independently appraised the guidelines using AGREE II and AGREE REX. Inter-rater agreements were calculated for each domain and the total score of these tools using the intraclass correlation coefficient (ICC [2,1]) with absolute agreement. RESULTS: We included 30 CPGs, primarily (90%) developed in Western countries, which contained 404 recommendations. High-quality CPGs consistently recommended exercise therapy and multimodal care, encompassing a combination of exercises, mobilization/manipulation, education, alternative medicine, and cognitive-behavioral treatments. Generally, CPGs did not recommend assistive (e.g., coresets and orthosis) devices or electro/thermotherapies (e.g., therapeutic ultrasound, and transcutaneous electrical nerve stimulation). Approximately half of the CPGs demonstrated good methodological quality according to AGREE II, while the rest were of poor quality. On the AGREE-REX assessment, one-third of the recommendations were of excellent quality. CONCLUSION: Although recent guidelines frequently recommended exercise therapy and multimodal care for the management of spine pain, their recommendations often overlooked demographics and comorbidities. Despite methodological improvements, most CPGs lacked simple clinical applicability and considerations of knowledge users’ values.

Evidence-Base Update of Psychosocial and Combination Treatments for Child and Adolescent Depression

ABSTRACT Objective This evidence-based update (EBU) builds on three previous reviews (1998, 2008, 2017) sponsored by the Society of Clinical Child and Adolescent Psychology with the aim of evaluating the empirical support for psychosocial interventions for depression in youth. Method In the current review period (2014–2022), 25 randomized controlled trials (RCT) were identified: four in children and 21 in adolescents. Descriptive effect sizes and number-needed-to-treat (NNT) ratios were calculated for primary outcomes. Results were integrated with prior reviews, and cumulative evidence used to classify treatments as well-established, probably efficacious, possibly efficacious, or experimental. Published secondary analyses of predictors, moderators, and mediators were examined. Results For adolescents, cognitive behavioral therapy (CBT), interpersonal psychotherapy (IPT-A), CBT in combination with antidepressant medication, and collaborative care programs were all classified as well-established. The evidence was considerably weaker for children, with no treatments achieving well-established or probably efficacious status. New developments include greater exploration of parent- and family-mediated treatment models and increasing evidence on technology-assisted interventions. Data on predictors, moderators, and mediators continued to be focused on adolescent depression samples and drawn from a limited number of RCT datasets. Conclusion Since the prior EBU, there has been incremental progress in youth depression treatment research. There is an urgent need to: (a) develop innovative approaches to substantially improve on the modest effects seen in most RCTs, (b) expand the evidence base for children and other underserved groups, (c) craft evidence-based guidelines for choosing between interventions when multiple efficacious treatments do exist, and (d) address issues of treatment effectiveness and scalability to ameliorate the wide prevalence and high impact of depression in youth.

Research progress of the SLFN family in malignant tumors

The Schlafen (SLFN) gene family has emerged as a critical subject of study in recent years, given its involvement in an array of cellular functions such as proliferation, differentiation, immune responses, viral infection inhibition, and DNA replication. Additionally, SLFN genes are linked to chemosensitivity, playing a pivotal role in treating malignant tumors. Human SLFNs comprise three domains: the N-terminal, middle (M), and C-terminal. The N- and C-terminal domains demonstrate nuclease and helicase/ATPase activities, respectively. Meanwhile, the M-domain likely functions as a linker that connects the enzymatic domains of the N- and C-terminals and may engage in interactions with other proteins. This paper aims to present a comprehensive overview of the SLFN family’s structure and sequence, examine its significance in various tumors, and explore its connection with immune infiltrating cells and immune checkpoints. The objective is to assess the potential of SLFNs as vital targets in cancer therapy and propose novel strategies for combined treatment approaches.

Bacterial isolates and antibiotic sensitivity in canine bacterial keratitis in Korea.

To analyze bacterial isolates associated with canine bacterial keratitis and their antibiotic susceptibility patterns in Korea, focusing on multidrug resistance (MDR) and identifying effective antibiotic combinations for clinical treatment. A total of 146 dogs diagnosed with suspected bacterial keratitis between October 2022 and October 2023 in Korea, with 157 eye samples collected for analysis. Eye samples were cultured to isolate bacteria, and antibiotic susceptibility testing was performed using the minimum inhibitory concentration (MIC) method. Bacterial identification was conducted using Matrix-Assisted Laser Desorption/Ionization Time-of-Flight (MALDI-TOF). The study assessed the efficacy of individual antibiotics and combination therapies. Bacteria were isolated in 55.4% of the samples. The most common genera were Staphylococcus species (48.5%, 48/99), Streptococcus species (13.1%, 13/99), Pseudomonas species (9.1%, 9/99), and Escherichia coli (9.1%, 9/99). Amikacin (84.8%) showed the highest antibiotic susceptibility, while doxycycline exhibited the lowest (17.2%). The most effective antibiotic combinations were amikacin-moxifloxacin (93%). MDR isolates accounted for 52.5% (52/99) of the total bacterial samples. Staphylococcus species were the most common isolates, with 52.5% showing MDR, underscoring the need to curb antibiotic misuse. While antibiotics like amikacin demonstrated high susceptibility rates, their use should be reserved for resistant infections to prevent further resistance development. Rather than focusing solely on finding effective combinations of antibiotics, it is crucial to consider alternative treatment strategies that offer more sustainable solutions. Rather than relying on antibiotic combinations, attention should shift to sustainable alternatives to treat bacterial keratitis and reduce antibiotic dependence in clinical practice.

Foliar Application of Methyl Jasmonate and Chitosan Improve Growth, Yield, and Quality of Guar (Cyamopsis tetragonoloba L.) Under Water-Deficit Stress

Guar (Cyamopsis tetragonoloba L.), a summer legume, is becoming increasingly important as an industrial crop due to its high gum and viscosity content. This study investigated the effects of methyl jasmonate (MeJA), chitosan (CH), and their combination on the growth, yield, and quality of guar under irrigation regimes. A greenhouse experiment was conducted using a factorial design to evaluate the effect of foliar spraying with MeJA (5, 25, and 50 µM), CH (100, 150, and 200 mg/L), their combination (25 µM MeJA + 150 mg/L CH), and control on two commercial guar varieties (RGC-986 and BR-2017) under different irrigation regimes (100%, 70%, and 40% field capacity). The results showed that the exogenous application of MeJA and CH, individually and in combination, significantly enhanced various morphological traits and yield components in guar, including plant height, pod characteristics, seed yield, and root development. Additionally, the combination treatments improved seed quality parameters, such as gum percentage and viscosity content. Leaf analysis revealed increased levels of total phenolic content, total flavonoid, and anthocyanin contents. The BR-2017 variety showed superior performance in most morphological and qualitative traits, demonstrating greater resistance to irrigation regimes. It maintained yield and quality characteristics under water-deficit conditions, particularly when treated with 25 µM MeJA and 150 mg/L CH. The highest gum percentage (33.67%) and viscosity (4768.5 cP) were observed in the RGC-986 variety, along with enhanced levels of secondary metabolites. This study provides new insights into how MeJA, CH, and their combination can improve the yield and quality of guar under water deficit stress conditions. The results suggest that the use of these elicitors, especially in combination, represents an innovative strategy for improving guar production and quality, with potential variety-specific responses to water-deficit stress.

Injectable nanocomposite hydrogel with cascade drug release for treatment of uveal melanoma

Uveal melanoma (UM) is the most common malignant intraocular tumor with the trait of distant metastases. Currently, the standard clinical therapy results in suboptimal outcomes due to ineffective inhibition of tumor metastasis. Thus, developing novel therapeutic modalities for UM remains a critical priority. Herein, we have developed an injectable nanocomposite hydrogel (HA-DOX/LAP gel) through integrating hyaluronic acid-based drug-loaded nanoparticles into an alginate-dopamine gel, delivering the chemotherapeutic drugs, lapatinib and doxorubicin for combinational treatment of UM. HA-DOX/LAP gel is fabricated in situ by a simple injection of the mixed precursor solution into tumor sites and maintains in vivo for more than 21 days. The entrapped drug-loaded nanoparticles can gradually release from HA-DOX/LAP gel, enhancing tumor targeting and penetration, and synchronously releasing lapatinib and doxorubicin into the acidic intracellular environment to synergistically destroy UM cells. In vivo anti-tumor studies conducted in MuM-2B tumor models demonstrated that HA-DOX/LAP gel significantly impedes tumor growth, diminishes postoperative recurrence, and prolongs overall survivals of UM tumor-bearing mice through only single injection. Remarkably, the escaped drug-loaded nanoparticles effectively reduce the risk of tumor metastases. Our findings provide new insights for the development of multifunctional nanocomposite-incorporating combination therapy against UM by targeting tumor recurrence and metastases.

Neurotrophic and synaptic effects of GnRH and/or GH upon motor function after spinal cord injury in rats

Thoracic spinal cord injury (SCI) profoundly impairs motor and sensory functions, significantly reducing life quality without currently available effective treatments for neuroprotection or full functional regeneration. This study investigated the neurotrophic and synaptic recovery potential of gonadotropin-releasing hormone (GnRH) and growth hormone (GH) treatments in ovariectomized rats subjected to thoracic SCI. Employing a multidisciplinary approach, we evaluated the effects of these hormones upon gene expression of classical neurotrophins (NGF, BDNF, and NT3) as well as indicative markers of synaptic function (Nlgn1, Nxn1, SNAP25, SYP, and syntaxin-1), together with morphological assessments of myelin sheath integrity (Klüver-Barrera staining and MBP immunoreactivity) and synaptogenic proteins (PSD95, SYP) by immunohystochemistry (IHC) , and also on the neuromotor functional recovery of hindlimbs in the lesioned animals. Results demonstrated that chronic administration of GnRH and GH induced notable upregulation in the expression of several neurotrophic and synaptogenic activity genes. Additionally, the treatment showed a significant impact on the restoration of functional synaptic markers and myelin integrity. Intriguingly, while individual GnRH application induced certain recovery benefits, the combined treatment with GH appeared to inhibit neuromotor recovery, suggesting a complex interplay in hormonal regulation post-SCI. GnRH and GH are bioactive and participate in modulating neurotrophic responses and synaptic restoration under neural damage conditions, offering insights into novel therapeutic approaches for SCI. However, the intricate effects of combined hormonal treatment accentuate the necessity for further investigation that conduce to optimal and novel therapeutic strategies for patients with spinal cord lesions.

The combination of venetoclax and quercetin exerts a cytotoxic effect on acute myeloid leukemia

Venetoclax is a BH3 mimetic that was recently approved for the treatment of acute myeloid leukemia (AML) treatment. However, the effect of venetoclax on AML remains limited, and a novel strategy is required. Here, we demonstrate for the first time that the cytotoxic effect of venetoclax drastically increased when by combined with the naturally occurring flavonoid quercetin. Combined treatment with venetoclax and quercetin caused most of AML KG-1 cells to exhibit a condensed morphology. Cell cycle analysis revealed that the combination strongly induced cell death. Caspase inhibitor blocked this cell death, and the combination induced poly (ADP-ribose) polymerase (PARP) cleavage, indicating that apoptosis was the primary mechanism. These effects were also observed in another AML cell line Kasumi-1 but not in chronic myeloid leukemia (CML) K562 cells. Public data analysis demonstrated that B-cell/CLL lymphoma 2 (Bcl-2) expression is increased in AML cells compared to other malignant tumors, and the survival and the growth of AML cell line depends on Bcl-2. We found that quercetin increased Bcl-2-associated X protein (Bax) expression in KG-1. Our study provides a novel function for quercetin and presents a promising strategy for AML treatment using venetoclax.

Transmission Dynamics of Typhoid Fever Outbreak: A Mathematical Modelling and Optimal Control Approach

In this paper, we propose and analyze a deterministic mathematical model for the control of typhoid fever. This model incorporates five effective control strategies, including vaccination, booster vaccination, personal hygiene, treatment, and bacteria sterilization, in order to effectively stop the spread of the disease in the population. The model consists of seven compartments, each representing a different stage in the disease’s progression: vaccinated, susceptible, carrier, infected, recovered, booster vaccinated, and bacterial. Using the next-generation matrix approach, we calculated the reproduction number , which measures the disease’s potential for spreading. Our stability analysis, using the Routh-Hurwitz criteria, revealed that the disease-free equilibrium point is locally asymptotically stable when is less than 1, among other conditions. This means that typhoid can be completely eradicated if the rate of secondary infection is kept below a certain threshold. Further sensitivity analyses were conducted to determine the key parameters that impact . Based on our findings, we formulated an optimal control problem and utilized Pontryagin’s Maximum Principle to determine the most effective strategy for controlling and eliminating the disease. Our results show that a combination of vaccination, booster vaccination, personal hygiene, treatment, and bacteria sterilization is the most optimal approach. With our comprehensive model and effective control strategies, we are one step closer to wiping out typhoid fever for good.

Optimizing the treatment of patients with intrinsic temporomandibular joint disorders

Temporomandibular joint (TMJ) dysfunctions are conditions in which there is a disruption in the anatomical and functional relationship between the various structures of the joint, including the articular disc, intra-articular ligaments, mandibular head and capsule. These disorders have a negative impact on the patient’s quality of life, resulting in limitations in masticatory function and articulation. The multifactorial nature of this pathology emphasizes the need for an individualized and comprehensive approach to the treatment of each patient. In most cases, treatment includes both surgical and orthopedic methods. Currently, combined treatment approaches aimed at synergistic effects are being actively developed to maximize therapeutic Results.The purpose of this study. To evaluate the efficacy of the combination of treatment with a repositioning mouthguard and the use of the hydraulic articular disk repositioning method in patients with internal TMJ disorders combined with dental row end defects.Materials and methods. The study included 6 patients with TMJ dysfunction and end defects of the dentition. The study was conducted between September 2023 and May 2024. As part of the study, each patient underwent cone beam computed tomography (CBCT) to evaluate the bony structures of the TMJ and ultrasound (US) to evaluate the soft tissue structures of this joint.Results. The CBCT data showed that the mean posterior temporomandibular joint displacement before treatment was 1.67, while this value increased to 3.02 after treatment. The US results showed a significant decrease in the mean value of mandibular head displacement after treatment ranging from 0.21 to 0.03, indicating a positive effect of treatment. In addition, there was a decrease in the difference in the size of the anterior and posterior parts of the articular disc, confirming the elimination of its displacement.Conclusion. The treatment combination of using a repositioning mouth guard with the hydraulic repositioning method brought about a synergistic effect on the restoration of TMJ function.