Mild exercise plus levothyroxine ameliorate deficits of spatial navigation, anxiety profile, and hippocampal BDNF in hypothyroid male offspring rats.

PURPOSE: Levothyroxine (LEV) monotherapy cannot completely improve cognitive and behavioral impairments induced by hypothyroidism, whereas a combination therapy of exercise and LEV may ameliorate these deficits. This study aimed to determine the effects of mild-intensity forced exercise and LEV treatment on the anxiety profile and cognitive functions in male offspring of hypothyroid dams. METHOD: Twenty-four female rats (mothers) were randomly divided into sham (healthy) and hypothyroidism groups and then placed with male rats to mate. The presence of vaginal plaque confirmed pregnancy (gestational day, GD 0). 6-propyl-2-thiouracil (PTU, 100 ppm) was added to the drinking water of the hypothyroidism group from GD 6 to the 21st postnatal day (PND). The sham group received tap water. On PND 21, serum T4 levels of mothers, and 10 pups were measured to confirm hypothyroidism. Sixty-four male pups were left undisturbed for 30 days and then were divided into eight groups that received saline or LEV (50 µg/kg, i.p.) with or without forced mild-intensity exercise. After 14 days of interventions, anxiety-like behaviors, spatial learning and memory, and hippocampal brain-derived neurotrophic factor (BDNF) levels were evaluated. FINDING: A pre and postnatal PTU-induced model of hypothyroidism increased anxiety-like behaviors, impaired spatial learning and memory, and decreased hippocampal BDNF levels in male offspring rats. LEV alone increased BDNF levels and improved spatial learning. Exercise alone increased BDNF levels, improved spatial learning and memory, and decreased anxiety-like behaviors. Exercise plus LEV more effectively improved anxiety-like behaviors and spatial learning than exercise or LEV alone. CONCLUSION: Practically, these pre-clinical findings highlight the importance of the combination of exercise and LEV regimen in treating patients with hyperthyroidism.

Early elastic and viscoelastic corneal biomechanical changes after photorefractive keratectomy and small incision lenticule extraction.

PURPOSE: To compare early changes in the corneal biomechanical parameters after photorefractive keratectomy (PRK) and small incision lenticule extraction (SMILE) and their correlations with corneal shape parameters. METHODS: One hundred twenty four eyes received myopic PRK and SMILE for similar amounts of myopia. Corneal tomography with Pentacam HR, biomechanical parameters using Corvis ST, and Ocular Response Analyzer (ORA) were evaluated before and 2 weeks after surgery. The change in each parameter was compared between groups, while the difference in central corneal thickness and cornea-compensated intraocular pressure measured before and after surgery were considered as covariates. RESULTS: A significant reduction was seen in the corneal stiffness parameter at first applanation, and an increase in deformation amplitude ratio (DAR), and integrated inverse radius (IIR) in both groups after surgery (p < 0.001) Changes in DAR, and IIR were significantly greater in the SMILE than in the PRK group (p < 0.001) Corneal hysteresis (CH) and corneal resistance factor (CRF) decreased in both SMILE and PRK groups after surgery, (p < 0.001) with no statistically significant difference between groups (p > 0.05) Among new Corvis ST parameters, DAR showed a significant correlation with changes in Ambrosio relational thickness in both groups (p < 0.05). CONCLUSIONS: Both techniques caused significant changes in corneal biomechanics in the early postoperative period, with greater elastic changes in the SMILE group compared to the PRK group, likely due to lower tension in the SMILE cap and thinner residual stromal bed in SMILE. There were no differences in viscoelastic changes between them, so the lower CH may reflect the volume of tissue removed.

Gait asymmetrical evaluation of lower limb amputees using wearable inertial sensors.

This study presents an analysis and evaluation of gait asymmetry (GA) based on the temporal gait parameters identified using a portable gait event detection system, placed on the lateral side of the shank of both lower extremities of the participants. Assessment of GA was carried out with seven control subjects (CS), one transfemoral amputee (TFA) and one transtibial amputee (TTA) while walking at different speeds on overground (OG) and treadmill (TM). Gait cycle duration (GCD), stance phase duration (SPD), swing phase duration (SwPD), and the sub-phases of the gait cycle (GC) such as Loading-Response (LR), Foot-Flat (FF), and Push-Off (PO), Swing-1 (SW-1) and Swing-2 (SW-2) were evaluated. The results revealed that GCD showed less asymmetry as compared to other temporal parameters in both groups. A significant difference (p < 0.05) was observed between the groups for SPD and SwPD with lower limb amputees (LLA) having a longer stance and shorter swing phase for their intact side compared to their amputated side, resulting, large GA for TFA compared to CS and TTA. The findings could potentially contribute towards a better understanding of gait characteristics in LLA and provide a guide in the design and control of lower limb prosthetics/orthotics.

Optimizing graphene content in scaffolds for evenly distributed crumpled MoS2paper wads as anodes for high-performance Li-ion batteries.

Lithium-ion batteries (LIBs) have revolutionized portable electronics, yet their conventional graphite anodes face capacity limitations. Integrating graphene and 3D molybdenum disulfide (MoS2) offers a promising solution. Ensuring a uniform distribution of 3D MoS2nanostructures within a graphene matrix is crucial for optimizing battery performance and preventing issues like agglomeration and capacity degradation. This study focuses on synthesizing a uniformly distributed paper wad structure by optimizing a composite of reduced graphene oxide RGO@MoS2through structural and morphological analyses. Three composites with varying graphene content were synthesized, revealing that the optimized sample containing 30 mg RGO demonstrates beneficial synergy between MoS2and RGO. The interconnected RGO network enhances reactivity and conductivity, addressing MoS2aggregation. Experimental results exhibit an initially superior capacity of 911 mAh g-1, retained at 851 mAh g-1even after 100 cycles at 0.1 A g-1current density, showcasing improved rate efficiency and long-term stability. This research underscores the pivotal role of graphene content in customizing RGO@MoS2composites for enhanced LIB performance.

A methodological quality review of citations of randomized controlled trials of diabetes type2 in leading clinical practice guidelines and systematic reviews.

Objective: Evaluate methodological quality of type 2 diabetes RCTs conducted in Iran and cited in clinical practice guidelines and systematic reviews and meta-analyses. Methods: We conducted a descriptive methodological quality review, analyzing 286 Randomized Controlled Trials (RCTs) on diabetes mellitus published in Iran from July 2004 to 2021. We searched six databases systematically and evaluated eligible articles using the CONSORT 2010 checklist for abstracts. Two investigators assessed the data using a 17-item checklist derived from CONSORT. Additionally, we examined the citations of each RCT in 260 clinical practice guidelines, with a specific focus on the adequate reporting of outcomes. Results: Out of 6667 articles, 286 analyzed. Poor reporting and failure to meet criteria observed. Only 3.8% cited in guidelines. Reporting rates: primary outcomes (41.9%), randomization (61.8%), trial recruitment (12.6%), blinding (50.8%). 27.9% cited in systematic reviews, 50.34% in systematic reviews and meta-analyses, 26.57% in meta-analyses. 67.8% of papers cited in systematic reviews. Adherence highest for participants, objective, randomization, intervention, outcome; lowest for recruitment, trial design, funding source, harms, and reporting primary outcomes. Conclusions: Poor methodological reporting and adherence to CONSORT checklist in evaluated RCTs, especially in methodological sections. Improvements needed for reliable and applicable results in guidelines, reviews, and meta-analyses. Inadequate outcome reporting challenges researchers, clinicians, and policymakers, impacting evidence-based decision-making. Urgent improvements in RCT registration necessary.

The combination of Curcumin and Doxorubicin on targeting PI3K/AKT/mTOR signaling pathway: an in vitro and molecular docking study for inhibiting the survival of MDA-MB-231.

The process of tumorigenesis is highly associated with the disruption of cell-cycle regulators and derangement of various signaling pathways, which end up with the inhibition of apoptosis and hyper-activation of survival pathways. The PI3K medicated AKT/mTOR pathway is the widely explained mechanism for cancer cell survival which causes the overexpression of MDM2 and downregulates the p53-BAX mediated apoptotic pathway. Curcumin (CUR), the phyto-compound, derived from Curcuma longa is currently being focused on for its anticancer activities against breast cancer cells, MDA-MB-231, not only because of its minimal cytotoxicity against healthy cells (HEK293) but also because it synergistically sensitizes the activity of Doxorubicin (DOXO) in lower doses, which can be a promising source for complementary drug development. This study aims to investigate the combinatorial effect of CUR and DOXO on PI3K/AKT/mTOR pathway proteins by sequential molecular docking analysis and MD simulation studies. The lower binding affinity of the sequentially docked protein-ligand complex proves the increasing binding affinity of CUR and DOXO in the combinatorial dose. The mRNA expressions of different genes of this pathway are observed and quantified using rt-qPCR, where the decreasing fold change (2-∆∆Ct) indicates the suppression of the AKT/mTOR pathway after co-treatment of CUR and DOXO against MDA-MB-231 cells. These in silico and in vitro findings can be a new horizon for further in vitro and clinical trials of breast cancer treatment. Supplementary Information: The online version contains supplementary material available at 10.1007/s40203-024-00231-2.

Relationship between fibrosis-4 score and microvascular complications in patients with type 2 diabetes mellitus.

BACKGROUND AND STUDY AIMS: Nonalcoholic fatty liver disease is the most prevalent chronic liver disease globally and is linked to augmented susceptibility to type 2 diabetes mellitus (DM), cardiovascular disease, and microvascular complications inherent to DM, such as nephropathy, neuropathy, and retinopathy. The fibrosis-4 (FIB-4) scoring system, a noninvasive tool, is useful for predicting the extent of liver fibrosis across diverse pathologies. This study aimed to assess the potential predictive role of FIB-4 scores in microvascular complications associated with diabetes. PATIENTS AND METHODS: The medical records of patients with type 2 DM admitted to our endocrinology clinic between February 2019 and December 2020 were retrospectively evaluated. Parameters including demographic attributes, fasting blood glucose, glycated hemoglobin, aspartate aminotransferase, alanine aminotransferase, thrombocyte levels, and microvascular complications were recorded. The FIB-4 score was computed, and patients were categorized based on these scores (<1.3 and ≥ 1.3). RESULTS: The analysis included 312 patients with a median age of 60 (50-68 years); 39.7 % were men. The median duration of diabetes was 10 years (5-20 years), and the median FIB-4 score was 0.93 (0.63-1.34). Neuropathy, nephropathy, and retinopathy were observed in 50.6 %, 31.4 %, and 34 % of the patients, respectively. Although the FIB-4 score did not differ significantly between patients with and without neuropathy or retinopathy, patients with nephropathy exhibited higher FIB-4 scores. Notably, patients with FIB-4 scores ≥ 1.3 demonstrated a significantly higher prevalence of nephropathy. Logistic regression analysis demonstrated that higher FIB-4 scores were significantly associated with an increased risk of nephropathy. CONCLUSION: The FIB-4 score is a cost-effective and straightforward tool with potential applicability in predicting nephropathy in individuals with type 2 DM.

Effect of 20 mph speed limits on traffic injuries in Edinburgh, UK: a natural experiment and modelling study.

INTRODUCTION: There is limited research evaluating 20 mph speed limit interventions, and long-term assessments are seldom conducted either globally or within the UK. This study evaluated the impact of the phased 20 mph speed limit implementation on road traffic collisions and casualties in the City of Edinburgh, UK over approximately 3 years post implementation. METHODS: We used four sets of complementary analyses for collision and casualty rates. First, we compared rates for road segments changing to 20 mph against those at 30 mph. Second, we compared rates for the seven implementation zones in the city against paired control zones. Third, we investigated citywide casualty rate trends using generalised additive model. Finally, we used simulation modelling to predict casualty rate changes based on changes in observed speeds. RESULTS: We found a 10% (95% CI -19% to 0%) greater reduction in casualties (8% for collisions) for streets that changed to 20 mph compared with those staying at 30 mph. However, the reduction was similar, 8% (95% CI -22% to 5%) for casualties (10% collisions), in streets that were already at 20 mph. In the implementation zones, we found a 20% (95% CI -22% to -8%) citywide reduction in casualties (22% for collisions) compared with control zones; this compared with a predicted 10% (95% CI -18% to -2%) reduction in injuries based on the changes in speed and traffic volume. Citywide casualties dropped 17% (95% CI 13% to 22%) 3 years post implementation, accounting for trend. CONCLUSION: Our results indicate that the introduction of 20 mph limits resulted in a reduction in collisions and casualties 3 years post implementation. However, the effect exceeded expectations from changes in speed alone, possibly due to a wider network effect.

Involvement of relaxin-family peptide-3 receptor (RXFP3) in the ventral dentate gyrus of the hippocampus in spatial and fear memory in rats.

The neuropeptide relaxin-3 and its cognate receptor, relaxin family peptide-3 receptors (RXFP3), have been implicated in modulating learning and memory processes, but their specific roles remain unclear. This study utilized behavioral and molecular approaches to investigate the effects of putatively reversible blockade of RXFP3 in the ventral dentate gyrus (vDG) of the hippocampus on spatial and fear memory formation in rats. Male Wistar rats received bilateral vDG cannula implantation and injections of the RXFP3 antagonist, R3(BΔ23-27)R/I5 (400 ng/0.5 µL per side), or vehicle at specific time points before acquisition, consolidation, or retrieval phases of the Morris water maze and passive avoidance learning tasks. RXFP3 inhibition impaired acquisition in the passive avoidance task but not the spatial learning task. However, both memory consolidation and retrieval were disrupted in both tasks following RXFP3 antagonism. Ventral hippocampal levels of the consolidation-related kinase p70-S6 kinase (p70S6K) were reduced RXFP3 blockade. These findings highlight a key role for ventral hippocampal RXFP3 signaling in the acquisition, consolidation, and retrieval of spatial and emotional memories, extending previous work implicating this neuropeptide system in hippocampal memory processing.

Regulation of immune responses to infection through interaction between stem cell-derived exosomes and toll-like receptors mediated by microRNA cargoes.

Infectious diseases are among the factors that account for a significant proportion of disease-related deaths worldwide. The primary treatment approach to combat microbial infections is the use of antibiotics. However, the widespread use of these drugs over the past two decades has led to the emergence of resistant microbial species, making the control of microbial infections a serious challenge. One of the most important solutions in the field of combating infectious diseases is the regulation of the host's defense system. Toll-like receptors (TLRs) play a crucial role in the first primary defense against pathogens by identifying harmful endogenous molecules released from dying cells and damaged tissues as well as invading microbial agents. Therefore, they play an important role in communicating and regulating innate and adaptive immunity. Of course, excessive activation of TLRs can lead to disruption of immune homeostasis and increase the risk of inflammatory reactions. Targeting TLR signaling pathways has emerged as a new therapeutic approach for infectious diseases based on host-directed therapy (HDT). In recent years, stem cell-derived exosomes have received significant attention as factors regulating the immune system. The regulation effects of exosomes on the immune system are based on the HDT strategy, which is due to their cargoes. In general, the mechanism of action of stem cell-derived exosomes in HDT is by regulating and modulating immunity, promoting tissue regeneration, and reducing host toxicity. One of their most important cargoes is microRNAs, which have been shown to play a significant role in regulating immunity through TLRs. This review investigates the therapeutic properties of stem cell-derived exosomes in combating infections through the interaction between exosomal microRNAs and Toll-like receptors.

An overview of neuro-ophthalmic disorders at Jenna Ophthalmic Center, Baghdad, Iraq (2021-2022).

Neuro-ophthalmic disorders are often documented individually for each illness, with little data available on their overall incidence and pattern. The overall incidence of neuro-ophthalmic illnesses in Iraq is still not recorded. This study aimed to evaluate the clinical, demographic, and etiological features of patients seeking consultation at an Iraqi neuro-ophthalmology clinic. A prospective cross-sectional observational research was conducted at the Janna Ophthalmic Center in Baghdad, Iraq. The center serves a diverse patient population from various governorates. All newly diagnosed patients with neuro-ophthalmic disorders who visited the neuro-ophthalmological clinic, regardless of gender or age group, were included. The neuro-ophthalmologist established a diagnosis for each case by reviewing the patient's medical history, doing physical examinations, administering specific tests, and, in certain cases, using neuroimaging methods. The duration of the study was extended from March 2021 to November 2022. Among the 6440 patients evaluated, 613 cases were confirmed at the neuro-ophthalmology clinic. Ischemic optic neuropathy (NAION, AION, and PION) was the most prevalent diagnosis, accounting for 17.61% of newly reported cases in the field of neuro-ophthalmology. This was followed by sixth nerve palsy. Diabetes mellitus affected 42.7% of the cases, followed by hypertension, which affected 39.3% of the participants. The incidence of neuro-ophthalmic diseases tended to be high. Ischemic optic neuropathy and sixth nerve palsy, traumatic/compressive optic neuropathy, and papilledema were the most common neuro-ophthalmic disorders reported.

Phytoconstituents of Nymphaea rubra flowers and their anti-diabetic metabolic targets.

Nymphaea rubra (N. rubra) flowers are prevalent in subtropical regions for both dietary and traditional medicinal purposes, attributing to their beneficial properties in supporting overall health. This study first time provides descriptions of the antidiabetic and dyslipidemic properties employing STZ induced high fat diet fed diabetic rats and inhibition of α-amylase enzyme activity first by in vitro analyses, followed by a confirmatory in silico study to create a stronger biochemical rationale. Furthermore, in 3 T3-L1 cells, this extract promoted the suppression of adipogenesis. GC-MS investigation of the ethyl acetate fraction of ethanolic extract of N. rubra flowers revealed the presence of marker compounds of N. rubra, Nuciferine, and Apomorphine, which were the focus of molecular docking studies. The acquired concentrations of Nuciferine (22.39%) and 10, 11-dimethoxy-Apomorphine (1.47%) were detected. Together with other alkaloids identified by GC-MS analysis from this extract, mechanistically suggested that it might be caused by the synergistic impact of these bioactive chemicals. Molecular docking has been done to check the binding affinities of various isolated phytochemicals with HPAA, the dose-response effect of 100 mg/kg and 250 mg/kg of flower extract after 30 days showed a significant effect on body weight, food, water intake, serum insulin, FBG, OGTT, lipid profile, glycated haemoglobin, liver and kidney function test. Kidney histopathology results show a significant effect. These findings offer a strong foundation for the potential application of the ethyl acetate fraction of ethanolic extract from Nymphaea rubra flowers and its bioactive constituent in an in vivo system for the treatment and control of diabetes and its associated condition dyslipidemia.

Unilateral renal mucormycosis in a patient presenting with pyelonephritis and acute kidney failure: A case report.

Key Clinical Message: Unilateral renal mucormycosis is a rare infection that should be suspected in patients with recurrent renal infections presenting nonspecific clinical features that do not respond to conventional therapies, especially in impaired immune systems due to related risk factors. Moreover, histopathological examinations should be performed to confirm the diagnosis. For treatment, the preference is that the patient is hospitalized, and surgical intervention and rapid administration of intravenous antifungals for 2-3 weeks are the treatment choices. After discharge, the patient should be followed up with periodic blood urea nitrogen and creatinine levels and, if needed, an imaging modality such as a CT scan or sonography. Abstract: Renal mucormycosis (RM) is a rare form of mucormycosis infection and is more often in immunocompromised patients with risk factors. Unilateral renal involvement is infrequent in patients and is available as case reports. This condition usually presents with renal colic, fever and chills, and oliguria and has a high mortality rate. Herein, we report a case of unilateral renal mucormycosis presenting with pyelonephritis and acute kidney injury in a 32-year-old patient. The patient had numerous urological procedures in previous years due to nephrolithiasis state, which put him in an immunocompromised state. The histopathological examination of the pylocalyceal system revealed a collection of broad non-septated fungal hyphae branching at 90° accompanied by numerous neutrophils and necrotic tissue in favor of mucormycosis. He was successfully treated with 5 mg/kg/day Liposomal Amphotericin B for 3 weeks, discharged with good general condition, and remained asymptomatic for 3 months after discharge. The diagnosis of RM relies on solid clinical suspicion, which can be authenticated by histopathological examination, and the combination of antifungal therapy and surgical intervention can result in a good outcome.

Comparing the Performance of Popular Large Language Models on the National Board of Medical Examiners Sample Questions.

INTRODUCTION: Large language models (LLMs) have transformed various domains in medicine, aiding in complex tasks and clinical decision-making, with OpenAI's GPT-4, GPT-3.5, Google's Bard, and Anthropic's Claude among the most widely used. While GPT-4 has demonstrated superior performance in some studies, comprehensive comparisons among these models remain limited. Recognizing the significance of the National Board of Medical Examiners (NBME) exams in assessing the clinical knowledge of medical students, this study aims to compare the accuracy of popular LLMs on NBME clinical subject exam sample questions. METHODS: The questions used in this study were multiple-choice questions obtained from the official NBME website and are publicly available. Questions from the NBME subject exams in medicine, pediatrics, obstetrics and gynecology, clinical neurology, ambulatory care, family medicine, psychiatry, and surgery were used to query each LLM. The responses from GPT-4, GPT-3.5, Claude, and Bard were collected in October 2023. The response by each LLM was compared to the answer provided by the NBME and checked for accuracy. Statistical analysis was performed using one-way analysis of variance (ANOVA). RESULTS: A total of 163 questions were queried by each LLM. GPT-4 scored 163/163 (100%), GPT-3.5 scored 134/163 (82.2%), Bard scored 123/163 (75.5%), and Claude scored 138/163 (84.7%). The total performance of GPT-4 was statistically superior to that of GPT-3.5, Claude, and Bard by 17.8%, 15.3%, and 24.5%, respectively. The total performance of GPT-3.5, Claude, and Bard was not significantly different. GPT-4 significantly outperformed Bard in specific subjects, including medicine, pediatrics, family medicine, and ambulatory care, and GPT-3.5 in ambulatory care and family medicine. Across all LLMs, the surgery exam had the highest average score (18.25/20), while the family medicine exam had the lowest average score (3.75/5).  Conclusion: GPT-4's superior performance on NBME clinical subject exam sample questions underscores its potential in medical education and practice. While LLMs exhibit promise, discernment in their application is crucial, considering occasional inaccuracies. As technological advancements continue, regular reassessments and refinements are imperative to maintain their reliability and relevance in medicine.

Production and Evaluation of Ag85B:HspX:hFcγ1 Immunogenicity as an Fc Fusion Recombinant Multi-Stage Vaccine Candidate Against Mycobacterium tuberculosis.

An urgent need is to introduce an effective vaccine against Mycobacterium tuberculosis (M.tb) infection. In the present study, a multi-stage M.tb immunodominant Fcγ1 fusion protein (Ag85B:HspX:hFcγ1) was designed and produced, and the immunogenicity of purified protein was evaluated. This recombinant fusion protein was produced in the Pichia pastoris expression system. The HiTrap-rPA column affinity chromatography purified and confirmed the fusion protein using ELISA and Western blotting methods. The co-localisation assay was used to confirm its proper folding and function. IFN-γ, IL-12, IL-4, and TGF-ß expression in C57BL/6 mice then evaluated the immunogenicity of the construct in the presence and absence of BCG. After expression optimisation, medium-scale production and the Western blotting test confirmed suitable production of Ag85B:HspX:hFcγ1. The co-localisation results on antigen-presenting cells (APCs) showed that Ag85B:HspX:hFcγ1 properly folded and bound to hFcγRI. This strong co-localisation with its receptor can confirm inducing proper Th1 responses. The in vivo immunisation assay showed no difference in the expression of IL-4 but a substantial increase in the expression of IFN-γ and IL-12 (P ≤ 0.02) and a moderate increase in TGF-ß (P = 0.05). In vivo immunisation assay revealed that Th1-inducing pathways have been stimulated, as IFN-γ and IL-12 strongly, and TGF-ß expression moderately increased in Ag85B:HspX:hFcγ1 group and Ag85B:HspX:hFcγ1+BCG. Furthermore, the production of IFN-γ from splenocytes in the Ag85B:HspX:hFcγ1 group was enormously higher than in other treatments. Therefore, this Fc fusion protein can make a selective multi-stage delivery system for inducing appropriate Th1 responses and is used as a subunit vaccine alone or in combination with others.

Regulation of Hypoxia Dependent Reprogramming of Cancer Metabolism: Role of HIF-1 and Its Potential Therapeutic Implications in Leukemia.

Metabolic reprogramming occurs to meet cancer cells' high energy demand. Its function is essential to the survival of malignancies. Comparing cancer cells to non-malignant cells has revealed that cancer cells have altered metabolism. Several pathways, particularly mTOR, Akt, PI3K, and HIF-1 (hypoxia-inducible factor-1) modulate the metabolism of cancer. Among other aspects of cancer biology, gene expression in metabolism, survival, invasion, proliferation, and angiogenesis of cells are controlled by HIF-1, a vital controller of cellular responsiveness to hypoxia. This article examines various cancer cell metabolisms, metabolic alterations that can take place in cancer cells, metabolic pathways, and molecular aspects of metabolic alteration in cancer cells placing special attention on the consequences of hypoxia-inducible factor and summarising some of their novel targets in the treatment of cancer including leukemia. A brief description of HIF-1α's role and target in a few common types of hematological malignancies (leukemia) is also elucidated in the present article.

Social media-related nightmare - a potential explanation for poor sleep quality and low affective well-being in the social media era?

Research has posited that social media use during the day may be reflected in nighttime dreams. Nevertheless, no prior studies have explored frightening, unpleasant dreams arising from social media use. This study introduces the construct of the social media-related nightmare by (a) developing and validating a scale capturing negative-valenced dreams with themes of helplessness, loss of control, inhibition, victimization, and making mistakes in social media, and (b) examining relationships between social media use, social media-related nightmares, sleep quality, and affective well-being. A convenience sample of 595 Iranian adult social media users (Mage = 27.45, SDage = 11.42) reported on social media-related nightmare, social media use integration, anxiety, peace of mind, sleep quality, and nightmare distress. The Social Media-Related Nightmare Scale (SMNS) demonstrated a unidimensional structure with sound psychometric properties. The most common nightmares involved the inability to log in to social media and the disruption of relationships with other users. Social media use intensity predicted frequency of social media-related nightmares. These nightmares were correlated with increased anxiety, lower peace of mind, poor sleep quality, and nightmare distress. Importantly, social media-related nightmares mediated the relationship between social media use intensity and low affective well-being (i.e., anxiety and peace of mind), poor sleeping, and nightmare distress. The findings suggest that social media-related nightmares could be a potential pathway through which social media engagement may lead to affective distress and sleep difficulties.

CTLA-4 Blockade of Natural Killer Cells Increases Cytotoxicity against Acute Lymphoid Leukaemia Cells Neda.

OBJECTIVE: There is interest in using cytotoxic T lymphocyte antigen-4 (CTLA-4) immunotherapy to treat blood cancers. Unfortunately, patients with acute lymphoblastic leukaemia (ALL) frequently exhibit resistance to treatment and natural killer (NK) cell exhaustion. This study aims to increase the cytotoxic potency of natural killer cells by using CTLA-4 to block the Nalm-6 leukaemia cell line. MATERIALS AND METHODS: In this experimental study, NK cells were purified from the peripheral blood mononuclear cells (PBMCs) of 10 healthy people and assessed by flow cytometry for purity and viability. The purified cells were activated overnight at 37°C and 5% CO2 with interleukin-15 (IL-15, 10 ng/ml) followed by evaluation of expressions of CTLA-4, activating and inhibitory receptors, and the release of interferon gamma (IFN-γ) and granzyme B (GZM B). CTLA-4 expression on NK cells from recurrent ALL patients was also evaluated. Finally, the cytotoxic activity of NK cells was assessed after the CTLA-4 blockade. RESULTS: The purity of the isolated cells was 96.58 ± 2.57%. Isolated NK cells activated with IL-15 resulted in significantly higher CTLA-4 expression (8.75%, P<0.05). Similarly, CTLA-4 expression on the surface of NK cells from patients with ALL was higher (7.46%) compared to healthy individuals (1.46%, P<0.05). IL-15 reduced NKG2A expression (P<0.01), and increased expressions of NKP30 (P<0.05) and NKP46 (P<0.01). The activated NK cells released more IFN-γ (P<0.5) and GZM B (P<0.01) compared to unactivated NK cells. Blockade of CTLA-4 enhanced the NK cell killing potential against Nalm-6 cells (56.3%, P<0.05); however, IFN-γ and GZM B levels were not statistically different between the blocked and non-blocked groups. CONCLUSION: Our findings suggest that CTLA-4 blockage of Nalm-6 cells causes an increase in antitumour activity of NK cells against these cells. Our study also provides evidence for the potential of cancer immunotherapy treatment using blocking anti-CTLA-4 mAbs.

Unraveling nitrogen loss in paddy soils: A study of anaerobic nitrogen transformation in response to various irrigation practice.

Soil nitrogen (N) transformation processes, encompassing denitrification, anaerobic ammonium oxidation (anammox), and anaerobic ammonium oxidation coupled with iron reduction (Feammox), constitute the primary mechanisms of soil dinitrogen (N2) loss. Despite the significance of these processes, there is a notable gap in research regarding the assessment of managed fertilization and irrigation impacts on anaerobic N transformations in paddy soil, crucial for achieving sustainable soil fertility management. This study addressed the gap by investigating the contributions of soil denitrification, anammox, and Feammox to N2 loss in paddy soil across varying soil depths, employing different fertilization and irrigation practices by utilizing N stable isotope technique for comprehensive insights. The results showed that anaerobic N transformation processes decreased with increasing soil depth under alternate wetting and drying (AWD) irrigation, but increased with the increasing soil depth under conventional continuous flooding (CF) irrigation. The denitrification and anammox rates varied from 0.41 to 2.12 mg N kg-1 d-1 and 0.062-0.394 mg N kg-1 d-1, respectively, which accounted for 84.3-88.1% and 11.8-15.7% of the total soil N2 loss. Significant correlations were found among denitrification rate and anammox rate (r = 0.986, p < 0.01), Fe (Ⅲ) reduction rate and denitrification rate (r = 0.527, p < 0.05), and Fe(Ⅲ) reduction rate and anammox rate (r = 0.622, p < 0.05). Moreover, nitrogen loss was more pronounced in the surface layer of the paddy soil compared to the deep layer. The study revealed that denitrification predominantly contributed to N loss in the surface soil, while Feammox emerged as a significant N loss pathway at depths ranging from 20 to 40 cm, accounting for up to 26.1% of the N loss. It was concluded that fertilization, irrigation, and soil depth significantly influenced anaerobic N transformation processes. In addition, the CF irrigation practice is best option to reduce N loss under managed fertilization. Furthermore, the role of microbial communities and their response to varying soil depths, fertilization practices, and irrigation methods could enhance our understanding on nitrogen loss pathways should be explored in future study.

Etiologies Associated With Elevated Liver Enzymes After Renal Transplant.

OBJECTIVES: One of the most important causes of morbidity and mortality in renal transplant recipients is liver disease. Liver dysfunction is shown in 7% to 67% of kidney transplant recipients. Liver insufficiency accounts for death in up to 28% of kidney transplant recipients. We stratified various etiological factors responsible for elevated liver enzymes in kidney transplant recipients. MATERIALS AND METHODS: We enrolled all patients who fulfilled inclusion criteria. The principal investigator obtained and recorded demographic and clinical information via a standardized form. We reviewed clinical records of kidney recipients with hepatotoxicity during the course of illness, and we analyzed data with SPSS statistical software (version 22). Descriptive statistics were used for continuous and categorical variables. RESULTS: All recipients of living related renal transplants from January 2015 to December 2016 were included in the study (n = 496). We excluded 64 patients with positive serology for hepatitis B or hepatitis C before transplant. Of the remaining 432 patients, 74 (17.1%) had deranged liver enzymes. Forty-one patients (55.4%) had deranged liver enzymes 3 to 4 years after transplant, whereas 23 patients (31.1%) had deranged liver enzymes 4 years after transplant. Liver parenchymal biopsy was performed in 17 patients (23%) to evaluate the etiology. The most common cause of deranged liver enzymes was sepsis, which was seen in 21 patients (28.4%), followed by viral hepatitis, ie, cytomegalovirus hepatitis in 7 (9.5%) and hepatitis C in 6 (8.1%) patients. Other causes included antituberculosis treatment-induced liver injury, autoimmune hepatitis, sinusoidal obstruction syndrome, and nonalcoholic steatohepatitis, observed in 4 patients each (5.4%). CONCLUSION: The most common cause of deranged liver enzymes in patients who received living related renal transplants in our population was sepsis, which can have a substantial effect on graft survival.