Alternative Treatments Research Articles

Mitigating Acetaminophen-Induced Kidney Injury: The Protective Role of Grape Seed and Peanut Skin Extracts through the iNOS/CYP2E1 Pathway.

The rising number of acute kidney injury cases worldwide due to acetaminophen (APAP) emphasizes the critical need for effective prevention strategies to counteract APAP's detrimental effects. This study examined the kidney-protective capabilities of ethanolic extracts from grape seeds and peanut skins (GSEE and PSEE, respectively) in comparison with silymarin in rats that experienced an APAP overdose. The phenolic compounds in these extracts were measured by using high-performance liquid chromatography (HPLC). In the experiment, Sixty adult male albino rats were divided into five groups of 12. The Control group received 0.5 mL of saline via a gastric tube. Group II received acetaminophen (APAP, 640 mg/kg per day via a gastric tube) to induce renal injury, following Ucar et al. and Islam et al. Groups III, IV, and V received silymarin (50 mg/kg), grape seed extract (200 mg/kg), and peanut skin extract (200 mg/kg), respectively, along with 640 mg of APAP/kg per day for 21 days. Post APAP treatment, significant increases in serum urea and creatinine levels were noted, along with notable decreases in the percentage of body weight gain. Furthermore, there were increases in oxidative stress and inflammatory markers in the kidney tissues, including heightened mRNA expressions of renal iNOS and CYP2E1, which were confirmed through histological studies. The administration of GSEE, PSEE, and silymarin mitigated these adverse effects, likely due to their high phenolic content, which is recognized for its antioxidant and anti-inflammatory effects. GSEE, in particular, showed efficacy comparable to that of silymarin. Molecular docking studies revealed that APAP impeded critical enzymes essential for cellular antioxidant defense, whereas the bioactive compounds in the grape seed and peanut skin extracts effectively inhibited key enzymes and receptors involved in inflammation and oxidative stress. These findings suggest that GSEE and PSEE could serve as viable alternative treatments for kidney damage induced by APAP. Further research to isolate and identify these effective compounds is recommended.

Metabolite profiling, in vitro antioxidant and a-glucosidase inhibitory properties of Timonius ternifolius leaves

Abstract. Vivit MB, Batuyong RG, Damian AFT, Gaoat CA, Beltran KGD, Alejo AB, Calaramo MA, Ibana FV, Batuyong MAR. 2024. Metabolite profiling, in vitro antioxidant and a-glucosidase inhibitory properties of Timonius ternifolius leaves. Biodiversitas 25: 3027-3034. The genus Timonius (Rubiaceae) possesses different pharmacological properties. One understudied endemic species under this genus from the Philippines is the Timonius ternifolius (Bartl. ex DC.) Fern.-Vill. Hence, this study investigates the physicochemical properties and phytochemical constituents of the leaf ethanolic extract (EE) and subjected to solvent partitioning to yield the following subfractions: hexane (HE), ethyl acetate (EA), and methanol (ME) extracts, which were utilized for the in vitro antioxidant, a-glucosidase and a-amylase assays. Quantitative tests of T. ternifolius leaves revealed the following physicochemical properties: herbal tea-like odor, fibrous and fluffy appearance, 50.07% moisture content, 3.10% total ash content, and a slightly acidic pH value of 5.13. The liquid chromatography-mass spectrometry (LC-MS) analysis has identified eight putative compounds namely glabrolide, aloinoside B, 2-benzyl octanal, geumonoid, (±) gomisin M1, 25-O-Acetyl-7,8-didehydrocimigenol-3-O-a-D-xylopyranoside, lucialdehyde B, and kadsuric acid. The extracts' concentrations of flavonoids, phenols, and terpenoids were 1.23±0.19 mg QE/g, 20.77±0.77 mg GAE/g, and 6.07±0.53 mg/g, respectively. Antioxidant profiling among the subfractions showed EE exhibiting the highest at 59.15±2.08 µg/mL (IC50 value). Moreover, significant a-glucosidase inhibition was noted in the EE extract at 99.74%, EA at 99.71%, and ME at 99.45%. The results showed that T. ternifolius leaves are a promising lead source of pharmacologically active compounds with antioxidant and antidiabetic activities, expanding information on plant-derived alternative treatments and developing medicinal products.

Effect of nanocomposite cementitious capillary crystalline waterproofing material on self-healing properties of cementitious composites

There are limited studies about the effect of nanocomposite cementitious capillary crystalline waterproofing material (CCCW) on the self-healing properties of cementitious materials in different environments. Compressive strength recovery ratio(CSRR) test, electrochemical impedance spectroscopy (EIS) test, and macroscopic cracks healing observation test were adopted to study the self-healing properties of pure mortar specimens, mortar specimens mixed with CCCW, and nanocomposite CCCW respectively under three kinds of curing conditions. The self-healing mechanism of nanocomposite CCCW was analyzed using thermogravimetric analysis and differential scanning calorimetry (TG-DSC), mercury intrusion porosimetry (MIP), and scanning electronic microscope and energy dispersive spectroscopy (SEM-EDS) techniques. It was found that the curing condition significantly influenced self-healing performance, with touching water curing condition having the highest impact, followed by soaking water curing condition and natural curing condition. Nanocomposite CCCW promoted the healing performance of damaged specimens and significantly increased the CSRR. Under touching water curing condition, the CSRRs of the mortar groups with 3% nano-SiO2, 3% nano-CaCO3, and 2% nano-MgO were 26.1%, 11.5%, and 8.6%, respectively, higher than the CSRR of the single-doped CCCW group. After 28 days of touching water curing, change in charge transfer resistance before and after specimen healing (∆Rct) of the groups with 3% dosage of nano-SiO2, 3% dosage of nano-CaCO3, and 2% dosage of nano-MgO were 5.2, 1.8, and 2.7 times, respectively, higher than that of the single-doped CCCW mortar group. Throughout the healing process, the addition of the three nanocomposite CCCWs accelerated the hydration reaction to generate C-S-H gel, CaCO3, Aft, etc., improved the internal pore structure, reduced the size of the most probable pore diameter (MPPD) of the mortar specimens, and ultimately promoted the self-healing properties of the cementitious materials.

How Does Nerve Mechanical Interface Treatment Impact Pre-Surgical Carpal Tunnel Syndrome Patients? A Randomized Controlled Trial.

Carpal tunnel syndrome (CTS) presents a high burden on the healthcare system. However, no alternative treatments are provided during the waiting period. In addition, the incidence of severe patients with comorbidities is underestimated. The aim of this study was to determine whether nerve mechanical interface treatment improves the symptoms, function, and quality of life in pre-surgical CTS patients. A randomized controlled trial and intention-to-treat analysis were carried out. Forty-two patients with an electrodiagnosis of carpal tunnel syndrome, included on the surgery waiting list of a public healthcare system, were analyzed. The intervention group (n = 20) received a 45 min session/per week of instrument-assisted manual therapy (diacutaneous fibrolysis) for 3 weeks. The Boston Carpal Tunnel Questionnaire (BCTQ) was the primary outcome. The symptoms, mechanical threshold, grip strength, mechanosensitivity of the median nerve, quality of life, and patient satisfaction were included as secondary outcomes. The control group (n = 22) remained on the waiting list. The intervention seems to be beneficial for the BCTQ score (function and symptoms scale), pain, and mechanosensitivity after treatment, at the 3 and 6 months follow-up (p < 0.05). Kinesiophobia was improved at 6 months (p = 0.043; η2 = 0.10) and the mechanical threshold at the 3-month follow-up (p = 0.048; η2 = 0.10). No differences were identified for grip strength. At 6 months, the intervention group patients were satisfied (100%), as opposed to the controls, who felt that they had experienced a worsening of their condition (50.1%). Nerve mechanical interface treatment improved the symptoms, function, and quality of life in pre-surgical CTS patients. One hundred percent of the treated patients, characterized as moderate and severe CTS with associated comorbidities, were satisfied.

Nanocarriers for the treatment of glioblastoma multiforme: A succinct review of conventional and repositioned drugs in the last decade.

Glioblastoma multiforme is a very combative and threatening type of cancer. The standard course of treatment involves excising the tumor surgically, then administering chemotherapy and radiation therapy. Because of the presence of the blood-brain barrier and the unique characteristics of the tumor microenvironment, chemotherapy is extremely difficult and has a high incidence of relapse. With their capacity to precisely target and transport therapeutic medications to the tumor while overcoming the challenges provided by invasive and infiltrative gliomas, nanocarriers offer a potentially beneficial treatment option for gliomas. Drug repositioning or, in other words, finding novel therapeutic uses for medications that have received approval for previous uses has also recently emerged to provide alternative treatments for many diseases, with glioblastoma being among them. In this article, our goal is to shed light on the pathogenesis of glioma and summarize the proposed treatment approaches in the last decade, highlighting how combining repositioned drugs and nanocarriers technology can reduce drug resistance and improve therapeutic efficacy in primary glioma.

A Comprehensive Review of Ocular Manifestations in Systemic Diseases.

Ocular manifestations often serve as critical indicators of underlying systemic diseases, providing valuable diagnostic and prognostic information. This comprehensive review aims to elucidate the complex interplay between ocular symptoms and systemic conditions, emphasising the importance of early recognition and interdisciplinary collaboration in patient management. The review encompasses various systemic diseases, including cardiovascular, autoimmune, infectious, neurological, endocrine, hematologic, genetic, dermatologic, gastrointestinal, hepatic, renal, and connective tissue disorders, highlighting their specific ocular manifestations. Diagnostic approaches, including ophthalmologic examination techniques, imaging modalities, and laboratory tests, are discussed to enhance diagnostic accuracy. Furthermore, the review outlines current management and treatment strategies, emphasising the need for a multidisciplinary approach to care. Emerging therapies and future research directions are also explored, underscoring the necessity of continued innovation in this field. This review aims to improve clinical practices, promote integrative healthcare, and ultimately enhance patient outcomes by providing a detailed overview of ocular manifestations in systemic diseases.

Irradiated tumor cell-released microparticles enhance the therapeutic efficacy of PD-1 inhibitors by promoting M1-TAMs polarization in NSCLC brain metastases

Brain metastases (BMs) are the most common sites of metastasis in patients with non-small cell lung cancer (NSCLC). However, BMs are not responsive to immunotherapy because of the blood-brain barrier. This is because intracranial immune cells such as M2 tumor-associated macrophages (TAMs) accumulate, creating an immunosuppressive tumor microenvironment. In this study, we focused on irradiated tumor cell-released microparticles (RT-MPs) that can cross the blood-brain barrier and influence the intracranial immune microenvironment. Using animal models of BMs, we observed that RT-MPs could penetrate the blood-brain barrier and be swallowed by TAMs. Then the microenvironment of TAMs is shifted from the M2 phenotype to the M1 phenotype, thereby modulating the interactions between TAMs and tumor cells. Single-cell sequencing analysis demonstrated that TAMs, after internalizing RT-MPs, active chemokine signaling pathways and secrete more chemokines, such as CCL5, CXCL2, CXCL1, CCL3, CCL4, and CCL22, attracting more CD4+ T cells and CD8+ T cells, improving immune-mediated killing, and enhancing subsequent combination anti-PD-1 therapy. These findings provide a preclinical foundation for exploring alternative treatments for patients with immunoresistant NSCLC BMs.

Using a PH-adjusted Semi-rigid Agarose Gel with Ion Exchange Resin for Poultice Desalination: Preliminary Experimentation and Case Studies

ABSTRACT Many highly unstable, actively crumbling and/or spalling objects cannot withstand desalination by repeated immersion in water baths. Alternative poultice treatments can be more difficult to monitor and less effective at removing soluble salts. Historically, objects too fragile to undergo desalination have been stored in climate-controlled enclosures, which can present maintenance challenges and often prevent examination or display. This paper presents a review of recent gel-based desalination approaches and brief experiments on an innovative method to remove soluble salts from extremely fragile porous materials using a pH-adjusted agarose gel mixed with an ion exchange resin. A pilot application led to experimental modifications and the development of the treatment protocol used in this case study. Process and results are described along with suggestions for further research.

Challenges in designing a randomized, double-blind noninferiority trial for treatment of acne: The SD-ACNE trial.

Excessive use of antibiotics has led to development of antibiotic resistance and other antibiotic-associated complications. Dermatologists prescribe more antibiotics per clinician than any other major specialty, with much of this use for acne. Alternative acne treatments are available but are used much less often than antibiotics, at least partially because dermatologists feel that they are less effective. Spironolactone, a hormonal therapy with antiandrogen effects that can address the hormonal pathogenesis of acne, may represent a therapeutic alternative to oral antibiotics for women with acne. However, the comparative effects of spironolactone and oral antibiotics in the treatment of acne have not been definitively studied. The Spironolactone versus Doxycycline for Acne: A Comparative Effectiveness, Noninferiority Evaluation (SD-ACNE) trial aims to answer whether spironolactone, in addition to standard topical therapy, is noninferior to doxycycline (an oral antibiotic) for women with acne. Several interesting challenges arose in the development of this study, including determining acceptability of the comparative regimens to participating dermatologists, identifying data to support a noninferiority margin, and establishing a process for unblinding participants after they completed the study while maintaining the blind for study investigators. We present the scientific and clinical rationale for the decisions made in the design of the trial, including input from key stakeholders through a Delphi consensus process. The Spironolactone versus Doxycycline for Acne: A Comparative Effectiveness, Noninferiority Evaluation trial (NCT04582383) is being conducted at a range of community and academic sites in the United States. To maximize external validity and inform clinical practice, the study is designed with broad eligibility criteria and no prohibition of use of topical medications. Participants in the trial will be randomized to receive either spironolactone 100 mg/day or doxycycline hyclate 100 mg/day for 16 weeks. The primary outcome is the absolute decrease in inflammatory lesion count, and we have established a noninferiority margin of four inflammatory lesions. Secondary outcomes include the percentage of participants achieving Investigator Global Assessment success, change in quality of life, and microbiome changes and diversity. The Spironolactone versus Doxycycline for Acne: A Comparative Effectiveness, Noninferiority Evaluation trial will have substantial implications for the treatment of acne and antibiotic stewardship. In addition, this study will provide important information on the effect of these systemic agents on the development of changes to the microbiome and antibiotic resistance in a healthy population of patients.

Attitudes toward incarceration, neuronormalization and psychological treatment for violent offenders

ABSTRACT Incarceration is a popular method of dealing with violent offenders. However, incarceration does not rehabilitate many violent offenders and often increases recidivism, which suggests a need for different interventions. Because public opinion has an important influence on the criminal justice system, we compared attitudes toward two alternative interventions and incarceration. These alternative interventions were brain-based treatments (i.e. neuronormalization) and psychological therapies. In two experiments, participants were randomly assigned to one of these three interventions and answered questions about their use with violent offenders in general and two severely violent cases: a domestic violence homicide offender and a child sex offender. For violent offenders in general, participants were more positive toward neuronormalization and psychological therapies than incarceration. However, when evaluating the two severely violent cases, participants were most positive toward incarceration. These findings highlight that people were generally amenable to alternative treatments for violent offenders, but these attitudes flipped in favor of incarceration when confronted with serious individual cases of violence. Our findings suggest that disseminating evidence for the effectiveness of alternative treatments may eventually lead to positive attitudes and policy change. Doing so could simultaneously lead to lower rates of incarceration and recidivism and create safer communities.

STRUCTURAL ANALYSIS OF THE CAUSATIVE-HOLISTIC MODEL OF HEALTH

Within this study, the necessity of a causative-holistic approach to health, viewed through philosophical and spiritual contexts, is substantiated. The author focuses on the structural analysis of the health model, based on the conducted research on the understanding of the phenomenon of health by ancient philosophers, medieval thinkers, and contemporary scientists. The article acknowledges the importance of spirituality in health and defines it as a causal factor that sets parameters for the development of physical health. The research offers a detailed description of the structure of holistic health, which includes unity, duality, and trinity, forming the foundation on the tripartite model “spirit-soul-body,” which has shaped the understanding of holistic health since medieval times and remains unchanged. Based on the metaphysical system proposed by the German mystic Jacob Böhme, the author substantiates the septenary structure of the spirit, reflecting in the septenary manifestation of the human being, and should have its analogy in the physical body and social dimension of the human being. A decenary model of health is also proven, appearing in the connection of the septenary «earthly human» with the triple metasystem complex, reflecting the spiritual aspect of holistic human. This decenary model forms a new causative-holistic view on human health and can be the basis for changing the medical paradigm, which should be based on primary spiritual factors of health for the preservation and improvement of both physical health and the health of the metasystem complex human-collective-society-planet.

Identification of kinase inhibitors as potential host-directed therapies for intracellular bacteria

The emergence of antimicrobial resistance has created an urgent need for alternative treatments against bacterial pathogens. Here, we investigated kinase inhibitors as potential host-directed therapies (HDTs) against intracellular bacteria, specifically Salmonella Typhimurium (Stm) and Mycobacterium tuberculosis (Mtb). We screened 827 ATP-competitive kinase inhibitors with known target profiles from two Published Kinase Inhibitor Sets (PKIS1 and PKIS2) using intracellular infection models for Stm and Mtb, based on human cell lines and primary macrophages. Additionally, the in vivo safety and efficacy of the compounds were assessed using zebrafish embryo infection models. Our screen identified 11 hit compounds for Stm and 17 hit compounds for Mtb that were effective against intracellular bacteria and non-toxic for host cells. Further experiments were conducted to prioritize Stm hit compounds that were able to clear the intracellular infection in primary human macrophages. From these, two structurally related Stm hit compounds, GSK1379738A and GSK1379760A, exhibited significant activity against Stm in infected zebrafish embryos. In addition, we identified compounds that were active against intracellular Mtb, including morpholino-imidazo/triazolo-pyrimidinones that target PIK3CB, as well as 2-aminobenzimidazoles targeting ABL1. Overall, this study provided insights into kinase targets acting at the host–pathogen interface and identified several kinase inhibitors as potential HDTs.

Infantile hemangiomas: a dermatologist's perspective.

Infantile hemangioma (IH), the most common vascular tumor in pediatrics, is thought to arise from aberrant stem cell responses to stimuli such as hypoxia. This review explores the diverse manifestations, complications, and management strategies for IH, emphasizing the importance of a multidisciplinary approach. The epidemiology and risk factors associated with IH, including connections to prematurity, low birth weight, and family background, are discussed. The intricate pathogenesis involving hemangioma stem cells, KIAA1429, hypoxia, and the renin-angiotensin system is examined. The natural history and clinical features, as well as extracutaneous involvements such as hepatic IH, PHACES syndrome, and LUMBAR syndrome, are detailed. Complications such as ulceration, functional impairment, hypothyroidism, and cosmetic concerns are highlighted. The differential diagnosis and diagnostic modalities, including colorimeters, high-frequency ultrasonography, and imaging techniques, are discussed. Management approaches, including the use of propranolol, atenolol, corticosteroids, alternative systemic treatments, topical therapy, laser therapy, and surgery, are comprehensively reviewed. The evolving landscape of IH management is underscored, with ongoing research exploring alternative treatments and individualized approaches based on IH characteristics.

A Case study of polypharmacy-induced serotonin syndrome in a cancer patient.

Polypharmacy in cancer care can be complex and detrimental, particularly among younger patients, who can be easily overlooked. This report showcases a 54-year-old woman with cancer, treated for dapsone-induced methemoglobinemia with methylene blue (MB), subsequently developing serotonin syndrome (SS) due to concurrent serotonin-active medications. This case highlights the critical impact of polypharmacy, emphasizing the necessity for acute care providers to diligently assess medication interactions, especially in emergencies. It underscores the importance of considering alternative treatments and the vigilant monitoring of symptoms indicative of adverse drug interactions to ensure patient safety and optimize outcomes in complex therapeutic scenarios.

Haploidentical versus Cord Blood Transplantation in Pediatric AML. A Retrospective Outcome Analysis on Behalf of the Pediatric Subcommittee of GETH (Grupo Español de Trasplante Hematopoyético)

Haploidentical stem cell transplantation (Haplo-SCT) and cord blood transplantation (CBT) are both effective alternative treatments in patients suffering from acute myeloid leukemia (AML) and lacking a matched HLA donor. In the last years, many centers have abandoned CBT procedures mostly due to concern about poorer immune recovery compared with Haplo-SCT. We conducted a retrospective multicenter study comparing the outcomes using both alternative approaches in AML. A total of 122 transplants (86 Haplo-SCTs and 36 CBTs) from 12 Spanish centers were collected from 2007 to 2021. Median age at hematopoietic stem cell transplantation (HSCT) was 7 years (0.4-20). Thirty-nine patients (31.9%) showed positive minimal residual disease (MRD) at HSCT and a previous HSCT was performed in 37 patients (30.3%). The median infused cellularity was 14.4 × 106/kg CD34+ cells (6.0-22.07) for Haplo-SCT and 4.74 × 105/kg CD34+ cells (0.8-9.4) for CBT. Median time to neutrophil engraftment was 14 days (7-44) for Haplo-SCT and 17 days (8-29) for CBT (P = .03). The median time to platelet engraftment was 14 days (6-70) for Haplo-SCT and 43 days (10-151) for CBT (P < .001). Graft rejection was observed in 13 Haplo-SCTs (15%) and in 6 CBTs (16%). The cumulative incidence of acute graft versus host disease (GvHD) grades II-IV was 54% and 51% for Haplo-SCT and CBT, respectively (P = .50). The cumulative incidence of severe acute GvHD (grades III-IV) was 22% for Haplo-SCT and 25% for CBT (P = .90). There was a tendency to a higher risk of chronic GvHD in the Haplo-SCT group being the cumulative incidence of 30% for Haplo-SCT and 12% for CBT (P = .09). The cumulative incidence of relapse was 28% and 20% for Haplo-SCT and CBT, respectively (P = .60). We did not observe statistically significant differences in outcome measures between Haplo-SCT and CBT procedures: 5-year overall survival (OS) was 64% versus 57% (P = .50), 5-year disease-free survival (DFS) 58% versus 57% (P = .80), GvHD-free and relapse-free survival (GFRFS) 41% versus 54% (P = .30), and cumulative incidence of transplant-related mortality (TRM) 14% versus 15% (P = .80), respectively. In the multivariate analysis, MRD positivity and a disease status >CR1 at the time of HSCT were significantly associated with poorer outcomes (P < .05). In conclusion, our study supports that both haploidentical and cord blood transplantation show comparable outcomes in pediatric AML patients. We obtained comparable survival rates, although CBT showed a trend to lower rates of chronic GvHD and higher GFRFS, demonstrating that it should still be considered a valuable option, particularly for pediatric patients.

Comparative impact of conventional and alternative gut health management programs on plasma and tibia attributes in broiler chickens raised in commercial and research settings

Plasma and tibia attributes were investigated in broiler chickens raised on three gut health management programs in commercial farms (study 1) and research station settings (study 2). The programs were: 1) conventional antibiotics (CON), 2) raised without medically important antimicrobials (RWMIA), and 3) raised without antibiotics (RWA). Birds had free access to feed and water from placement to harvest; samples of blood and left tibia were collected on d 28 in both studies and further samples were taken on d 41 in study 2. In both studies, there were no program differences (P &gt; 0.05) on plasma metabolites with exception of enzyme concentrations with notably higher levels of circulating plasma alkaline phosphatase (ALP) in birds reared on the RWA program (P ≤ 0.04). Differences were observed among programs for tibia length in both studies (P &lt; 0.05). Birds reared on RWMIA exhibited significantly (P = 0.016) higher tibia ash than CON on d 41. Observed differences in the plasma enzyme concentrations, tibia length, and ash concentration suggest altered metabolism which could be linked to gut health management programs and their ability to support gut integrity and function in the absence of antibiotics.

Hyperglycemia from Diabetes Potentiates Uncarboxylated Osteocalcin-Stimulated Insulin Secretion in Rat INS-1 Pancreatic β-Cells.

Uncarboxylated osteocalcin (ucOC) is a hormone secreted by osteoblasts that strengthens bone during mineralization and is a biomarker for ongoing bone formation. It also regulates glucose homeostasis by stimulating insulin secretion from pancreatic β-cells. However, its effect on β-cells under hyperglycemic diabetic conditions is unclear. The objective of this study was to investigate ucOC's effect on insulin secretion in β-cells maintained under high glucose conditions. We hypothesized that hyperglycemia potentiates insulin secretion in response to ucOC stimulation. Using INS-1 cells, we performed insulin secretion experiments, intracellular calcium recordings, and RT-qPCR to determine ucOC's effect on glucose-stimulated insulin secretion (GSIS)-related genes. The results reveal that ucOC significantly increased insulin secretion under hyperglycemic conditions compared to lower glucose levels. High glucose conditions also potentiated the effect of ucOC on calcium signals, which enhanced insulin secretion. The increase in intracellular calcium was due to an influx from the extracellular space via voltage-dependent calcium channels (VDCCs). Interestingly, the treatment of cells with NPS-2143, a GPRC6A blocker, failed to abolish the calcium signals. Uncarboxylated osteocalcin upregulated the expression of GSIS-related genes under high glucose conditions (450 mg/dL) compared to cells under standard culture conditions (200 mg/dL). In conclusion, hyperglycemia potentiates ucOC-induced insulin secretion in β-cells by opening VDCCs and upregulating GSIS genes. These findings provide a better understanding of ucOC's mechanism in the diabetic state and could lead to alternative treatments to stimulate insulin secretion.

Hypnotics on Obstructive Sleep Apnea Severity and Endotypes: A Systematic Review and Meta-Analysis.

Low arousal threshold and poor muscle responsiveness are common determinants of obstructive sleep apnea (OSA). Hypnotics were hypothesized as an alternative OSA treatment via raising the arousal threshold and possibly genioglossus responsiveness. Effect of common hypnotics on arousal threshold, OSA severity and genioglossus responsiveness. We searched MEDLINE, EMBASE, CENTRAL and ClinicalTrials.gov for randomized clinical trials, and ran meta-analyses to determine the effect of oral hypnotics on arousal threshold, OSA severity and genioglossus responsiveness. GRADE was used to rate the quality of evidence (QoE). The association between post-treatment AHI and arousal threshold percent reductions was explored in individual patient data (IPD) metanalyses (overall sample and low arousal threshold subgroups). Based on our analysis (27 studies; 25 for AHI, 11 for arousal threshold, 4 for genioglossus responsiveness), hypnotics minimally raised arousal threshold (mean difference [95% CI]: 2.7 [1.5, 3.8] cmH2O epiglottic pressure swings; moderate QoE), but did not change OSA severity (1.4 [3.5, 0.7] events/h; moderate QoE). IPD meta-analysis (N=114) showed no association between changes in arousal threshold and AHI, independent of low arousal threshold subgrouping. However, people with very-low arousal threshold or those who exhibited 0-25% arousal threshold increase from placebo experienced the greatest-yet still modest-post-treatment AHI reductions (10%). Hypnotics did not affect genioglossus responsiveness (high QoE). Further research testing or clinical use of hypnotics as OSA alternative treatments should be discouraged, unless in the presence of comorbid insomnia or as part of combination therapy in individuals with very-low arousal threshold.

Clinical Outcome Using Different Catheter Interventional Treatment Modalities in High-Risk Pulmonary Artery Embolism.

For patients with high-risk pulmonary artery embolism (PE), catheter-directed therapies pose a viable alternative treatment option to systemic thrombolysis or anticoagulation. Right now, there are multiple devices available which have been proven to be safe and effective in lower-risk settings. There is, however, little data comparing their efficacies in high-risk PE. We performed a retrospective, single-center study on patients with high-risk PE undergoing catheter interventional treatment. Patients receiving large-bore catheter thrombectomy were compared to patients receiving alternative treatment forms. Of the 20 patients included, 9 received large-bore thrombectomy, and 11 received alternative interventional treatments. While the baseline characteristics were comparable between the two groups, periprocedural and in-hospital mortality tended to be significantly lower with large-bore thrombectomy when compared to other treatment forms (0 vs. 55% and 33 vs. 82%, p = 0.07 and 0.01, respectively). In this small, retrospective study, large-bore thrombectomy was associated with lower mortality as compared to alternative treatment forms. Future prospective research is needed to corroborate these findings.

Acute effects of fast, slow, and graded Suryanamaskar on cardiorespiratory and cardiac autonomic functions

BackgroundSuryanamaskar (SN) is a popular yogic practice due to its health benefits and fitness promises. This study aims to assess the acute effects of different paces of SN on cardiorespiratory responses and heart rate variability (HRV). MethodsIn this self-as-control comparative study, seventeen male yoga practitioners performed three rounds of SN at fast (FSN), slow (SSN), and graded (GSN) pace in a randomly allocated sequence. Cardiorespiratory responses and HRV kinetics were continuously monitored using a metabolic gas analyzer and heart rate sensor, respectively, and were analyzed by repeated-measures ANOVA and paired t-test. ResultsFSN involved the highest VO2, followed by GSN and SSN. Average HR (AHR) was significantly greater during FSN compared to SSN (p < 0.01; d = 0.81) and GSN (p < 0.05; d = 0.39). GSN demanded significantly higher (p < 0.05; d = 0.41) stroke volume compared to FSN. VO2, AHR, and energy expenditure (EE) showed a gradual increase across rounds in FSN and SSN, whereas in GSN those significantly reduced. SSN showed significantly lesser EE, fat% utilization, and METS as compared to FSN (p < 0.001) and GSN (p < 0.01). SSN also showed significantly reduced LF power (p < 0.01; d = 0.67), LF/HF ratio, and higher HF power than GSN and FSN. ConclusionFSN is more metabolically demanding compared to the other two paces. SSN is more effective in bringing a state of parasympathetic dominance and GSN brings progressive relaxation. The results provide insights into the acute HRV and cardio-metabolic responses to different SN paces suggesting its potential as a complementary therapy and to promote holistic health and well-being.