Normal Function Research Articles

MicroRNA signatures in neuroplasticity, neuroinflammation and neurotransmission in association with depression.

Depression is a multifactorial disorder that occurs mainly on account of the dysregulation of neuroplasticity, neurotransmission and neuroinflammation in the brain. In addition to environmental /lifestyle factors, the pathogenesis of disease has been associated with genetic and epigenetic factors that affect the reprogramming of normal brain function. MicroRNA (miRNAs), a type of non-coding RNAs, are emerging as significant players that play a vital role in the regulation of gene expression and have been extensively explored in neurodegenerative disorders. Recent studies have also shown the role of gut microbiota that forms a complex bidirectional network with gut brain axis, impacting neuroinflammation in case of Parkinson's disease and depression. Translating targeted miRNA-based therapies for the treatment of neurological disorders including depression, into clinical practice remains challenging due to the ineffective delivery of the therapeutic molecules and off-target effects of the specific miRNAs. This review provides significant insights into how miRNAs are emerging as vital players in the development of depression, especially the ones involved in three important processes including neuroplasticity, neurotransmission and neuroinflammation. In this review, the current status of miRNAs as biomarkers for therapeutic interventions in the case of depression has been discussed along with an overview of future perspectives, like use of nanotechnology and gene editing, keeping in view other multifactorial disorders where such interventions by mimics and inhibitors have already reached clinical trials. The challenges for targeting the specific miRNAs for therapeutic outcomes have also been highlighted.

End Binding Proteins: Drivers of Cancer Progression.

Cancer, a complex and heterogeneous disease, continues to be a major global health concern. Despite advancements in diagnostics and therapeutics, the aggressive nature of certain cancers remain a significant challenge, necessitating a deeper understanding of the underlying molecular mechanisms driving their severity and progression. Cancer severity and progression depend on cellular properties such as cell migration, cell division, cell shape changes, and intracellular transport, all of which are driven by dynamic cellular microtubules. Dynamic properties of microtubules, in turn, are regulated by an array of proteins that influence their stability and growth. Among these regulators, End Binding (EB) proteins stand out as critical orchestrators of microtubule dynamics at their growing plus ends. Beyond their fundamental role in normal cellular functions, recent research has uncovered compelling evidence linking EB proteins to the pathogenesis of various diseases, including cancer progression. As the field of cancer research advances, the clinical implication of EB proteins role in cancer severity and aggressiveness become increasingly evident. This review aims to comprehensively explore the role of microtubule-associated EB proteins in influencing the severity and aggressiveness of cancer. We also discuss the potential significance of EB as a clinical biomarker for cancer diagnosis and prognosis and as a target for therapeutic intervention.

Retention of indoxyl sulfate in different genotypes of ABCC2 may explain variation in tacrolimus pharmacokinetics

Background Microbiota-derived toxins indoxyl sulfate and hippuric acid were previously reported to be associated with altered pharmacokinetics of the immunosuppressant tacrolimus in liver transplant recipients, and ABC transporter proteins are likely to be involved in the transport of such substances, but the in vivo role has not been elucidated. The aim of this study was to assess the retention of indoxyl sulfate and hippuric acid in the plasma of liver transplantation subjects carrying different genotypes of ABCB1 and ABCC2 (changes in transporter activity due to genetic variation), and to explore whether genetic variation is involved in altering the relationship between microbe-derived toxins and tacrolimus pharmacokinetics. Methods Liver transplantation subjects treated with the immunosuppressive regimen tacrolimus, corticosteroids, and mycophyolate mofetil were included and divided into normal renal function group and chronic kidney disease group. The plasma concentrations of indoxyl sulfate and hippuric acid in two groups of liver transplantation subjects carrying different genotypes of ABCB1 and ABCC2 were compared. For genotype carriers with significant differences, the Pearson Correlation Coefficient method was further used to investigate the correlation between plasma indoxyl sulfate level and tacrolimus dose-corrected trough concentration in patients with different renal function status. Results Carriers of the rs717620-24T variant exhibited high plasma indoxyl sulfate retention in patients with normal renal function, and furthermore, chronic kidney disease patients and patients with normal renal function exhibited indoxyl sulfate and tacrolimus in the ABCC2 normal function (β = −0.740, p = 0.020) and reduced function groups (β = −0.526, p = 0.005), respectively, showing a strong correlation with tacrolimus. Conclusion ABCC2 may be one of the pathways by which tacrolimus pharmacokinetics is altered by indoxyl sulfate.

Relationship Between Body Weight and Leukopenia in Non-Kidney Solid Organ Transplant Recipients With Normal Renal Function Who Are Receiving Valganciclovir for CMV Prophylaxis.

Cytomegalovirus (CMV) disease causes significant morbidity among solid organ transplant (SOT) recipients. To prevent CMV disease, eligible recipients are frequently started on valganciclovir (VGC) prophylaxis post-transplant. Leukopenia has been documented as a primary adverse events of the drug (1). This study's primary aim was to determine whether a patient's weight at the start of VGC prophylaxis was associated with the development of leukopenia. This was a single center, retrospective cohort study that included adults > 18 years of age, who had received an organ transplant (heart, liver, or lung) at an academic transplant center from January 1, 2018 through December 31, 2022. A creatinine clearance of > 60mL/min was required. All 294 included patients received 900mg/day of VGC for CMV prophylaxis, without dose adjustment. Fifty-two percent of the patients developed leukopenia while receiving VGC prophylaxis. The mean weight at initiation of VGC was higher in patients who did not develop leukopenia (97.9kg) compared to those who did (90.7kg; p = 0.0112). It was found that with each 1kg increase in body weight, the likelihood of developing leukopenia decreased by 1.7% (p = 0.004, odds ratio = 0.983, 95% confidence interval [CI], 0.972-0.994). Patients with a baseline body-mass index (BMI) > 25 had a longer median freedom time from leukopenia after initiation of VGC as compared to the group with baseline BMI < 25 (log-rank p = 0.035). These data suggest that in SOT recipients with normal renal function, receiving a fixed dose of VGC resulted in a significant, inverse relationship between body weight and the development of leukopenia.

Analysis of the correlations and inconsistencies between spirometry and impulse oscillometry in the diagnosis of small-airway dysfunction

ObjectiveCurrently, there has been no gold standard for diagnosing small airway dysfunction (SAdf). This study aimed to evaluate the correlation between small airway parameters derived from spirometry and oscillometry in hospitalized patients, assessing the potential of oscillometry as an alternative diagnostic tool for SAdf. Additionally, this study explored the inconsistencies and influencing factors related to spirometry and oscillometry in diagnosing SAdf, conducting a preliminary assessment of these factors.MethodsA retrospective study was conducted involving data collection from patients who underwent both spirometry and oscillometry between June 1, 2022, and September 1, 2023, at Chengdu Third People’s Hospital was conducted. Initially, 1,771 patients were considered, with 1,446 meeting the inclusion and exclusion criteria. The clinical characteristics and correlations between small airway parameters from the two methods were analyzed based on different lung function data groups. Besides, this study explored the inconsistency between the two pulmonary function tests in diagnosing SAdf in hospitalized patients. Multivariate logistic regression was employed to investigate the factors contributing to these inconsistencies.ResultsSignificant correlations were identified between parameters (reactance area [AX], resonant frequency [Fres], reactance at 5 Hz [X5], difference between resistance at 5 Hz and R20 [R5-R20]) and the forced expiratory flow (FEF) metrics (FEF25%-75%, FEF50%, and FEF75%). Among these, AX showed the strongest correlation, regardless of the severity of forced vital capacity (FVC), forced expiratory volume in one second (FEV1), and the FEV1/FVC ratio. Diagnostic inconsistencies were influenced by factors such as sex, body mass index (BMI), and sputum production. Females, individuals with a high BMI, and those with less sputum were linked to oscillometry-only SAdf, while males, individuals with alow BMI, and those with more sputum were linked to spirometry-only SAdf.ConclusionIn hospitalized patients, oscillometry could serve as an effective alternative or complement to spirometry for diagnosing SAdf. A greater degree of lung function impairment was correlated with small airway parameters between the two tests. The oscillometry might detect SAdf more sensitively in patients with normal pulmonary function as measured by spirometry. Ultimately, we recommend the combined use of spirometry and oscillometry in hospitalized patients based on its comprehensive assessment of small airway function and potential in timely intervention.

Cell-Penetrating Peptide Enhances Tafazzin Gene Therapy in Mouse Model of Barth Syndrome

Barth Syndrome (BTHS) is an early onset, lethal X-linked disorder caused by a mutation in tafazzin (TAFAZZIN), a mitochondrial acyltransferase that remodels monolysocardiolipin (MLCL) to mature cardiolipin (CL) and is essential for normal mitochondrial, cardiac, and skeletal muscle function. Current gene therapies in preclinical development require high levels of transduction. We tested whether TAFAZZIN gene therapy could be enhanced with the addition of a cell-penetrating peptide, penetratin (Antp). We found that TAFAZZIN-Antp was more effective than TAFAZZIN at preventing the development of pathological cardiac hypertrophy and heart failure. These findings indicate that a cell-penetrating peptide enhances gene therapy for BTHS.

Production of [18F]DPA-714, [18F]fallypride and [18F]LBT-999 using iMiDEV, a fully automated microfluidic platform: towards clinical radiopharmaceutical production

BackgroundPositron emission tomography is widely used to study biological processes without disrupting normal physiological functions. Traditional radiotracer synthesis and industrial market is focused on producing large batches of 18F-labelled tracers, especially [18F]FDG. Accessibility to smaller quantity of diverse radiopharmaceuticals is a key to enable a more personalised approach in nuclear medicine. A novel microfluidic module, iMiDEV™, has earlier been shown to be a versatile labelling platform as it has been used in the production of Na[18F]F and various 11C- and 68 Ga-labelled tracers. In the current study our aim was to utilise iMiDEV™ in the synthesis of fluorine-18-labelled radiotracers, specifically [18F]DPA-714, [18F]LBT-999 and [18F]fallypride.Results[18F]DPA-714, [18F]LBT-999 and [18F]fallypride have been produced in up to 24%, 12% and 11% radiochemical yield, respectively, using the microfluidics based iMiDEV™ labelling platform. Activity yields at the end of synthesis were 3.6 GBq, 2.1 GBq and 2.3 GBq, respectively. All individual synthesis steps were studied for efficient activity transfer and labelling and the optimised synthesis sequence was fully automated.ConclusionIn this paper, we have demonstrated fully automated production of different 18F-tracers of clinical relevance with moderate to good yields using microfluidic iMiDEV™ platform. Our work is a step towards more personalised, dose-on-demand manufacturing of PET radiopharmaceuticals.

Impaired liver function: effect on paclitaxel toxicity, dose modifications and overall survival

BackgroundThe anticancer drug paclitaxel is primarily metabolized in the liver. Previous studies have indicated a correlation between impaired liver function and paclitaxel toxicity, which may indicate dose reduction. Since the evidence is limited, the aim of this study was to investigate the effect of impaired liver function on the hematological toxicity of paclitaxel, dose modifications and overall survival (OS).MethodsFor this single-center retrospective observational study, patients treated with paclitaxel for breast, esophageal and ovarian cancer at the University Medical Centre Utrecht between 2011 and 2022 were identified from the Utrecht Patient Oriented Database (UPOD). Based on regression analysis, the risk of developing Grade 3/4 hematological toxicity was compared between patients with normal and impaired (based on the NCI criteria for bilirubin and ASAT (aspartate aminotransferase) concentrations) liver function. Additionally, differences in the occurrence of toxicity-related dose modifications and OS were evaluated between the two groups.ResultsA total of 569 patients were included. Breast cancer patients who were receiving advanced treatment and had mildly impaired liver function (ASAT ≤ 2x ULN, bilirubin ≤ ULN) had an increased risk of developing grade 3/4 neutropenia (HR = 4.39, 95% CI 1.20-16.02; p = 0.03). In addition, patients with impaired liver function treated according to the advanced ovarian cancer regimen had an increased risk of developing grade 3/4 leukopenia (HR = 12.64, 95% CI 2.12–75.22, p = 0.01) and dose modification (treatment discontinuation) (HR = 3.91, 95% CI 1.74–8.79, p < 0.01). Impaired liver function was also associated with decreased OS in inoperable esophageal and advanced ovarian cancer patients (HR = 7.65, 95% CI 2.54–23.1, p < 0.01 and HR = 2.98, 95% CI 1.36–6.54, p < 0.01, respectively). The risk of developing grade 3/4 hematological toxicity during lower-dose paclitaxel treatment protocols was not significantly different in patients with impaired liver function.ConclusionsThis study revealed that patients with impaired liver function treated with paclitaxel for breast and ovarian cancer in an advanced setting are at greater risk of developing hematological toxicity than patients with normal liver function at the start of therapy. Furthermore, in patients with ovarian (advanced) or inoperable esophageal cancer, impaired liver function is associated with decreased OS. Within these groups of patients, it is important to weigh the risk of upfront paclitaxel dose modifications versus an adaptive strategy.

Functional Neuroanatomy of the Normal and Pathological Basal Ganglia.

The term "basal ganglia" refers to a group of interconnected subcortical nuclei engaged in motor planning and movement initiation, executive functions, behaviors, and emotions. Dopamine released from the substantia nigra is the underlying driving force keeping the basal ganglia network under proper equilibrium and, indeed, reduction of dopamine levels triggers basal ganglia dysfunction, setting the groundwork for several movement disorders. The canonical basal ganglia model has been instrumental for most of our current understanding of the normal and pathological functioning of this subcortical network. This model explains how cortical information flows through the basal ganglia nuclei back to the cortex by going through two pathways with opposing effects that together lead to the proper execution of a given movement. The basal ganglia model has paved the way for the standard clinical management of Parkinson's disease, where pharmacological and neurosurgical treatments in place collectively afford an impressive symptomatic alleviation. Although much of the model has remained, the canonical model has been enriched with new arrivals gathered from evidence provided in the last three decades. Here, we sought to provide a comprehensive review of the basal ganglia network, with emphasis on structure, connectivity patterns, and basic operational principles, both in normal and pathological conditions.

Low Expression of FAM96B is Associated with Poor Prognosis in Hepatocellular Carcinoma.

Recently, studies on FAM96B functions mainly focused on its role in maintaining the normal physiological function of cells. However, the clinical implications of FAM96B in hepatocellular carcinoma (HCC) are still unclear. FAM96B mRNA expression was detected in human HCC tissues and the matched nontumorous tissues by quantitative real-time reverse transcription (qRT-PCR) and then validated in The Cancer Genome Atlas (TCGA) database. Immunohistochemistry assay (IHC) was performed on all 137 cases of HCC samples to examine the protein level of FAM96B. Subsequently, the associations between FAM96B expression and clinicopathological parameters and prognosis were further analyzed. The mRNA level of FAM96B was found to be significantly lower in HCC tissues compared to non-tumorous tissues, as observed in both the local hospital and TCGA database.Immunohistochemistry assay analysis revealed a decrease in FAM96B expression in 78 out of 137 cases, which was significantly associated with larger tumor size, higher Barcelona clinic liver cancer or Child stage, and early distant metastasis. Patients with low FAM96B levels tended to have an unfavorable disease-free and overall survival. Moreover, FAM96B was identified as an independent predictor of patient prognosis in both univariate and multivariate survival analyses. Mechanistically, FAM96B was found to inhibit cancer progression by inducing apoptosis in liver cancer cells and inhibiting their growth. Our findings provide the first evidence suggesting the involvement of FAM96B in the progression of HCC. Additionally, FAM96B could potentially serve as a marker for tumor recurrence and prognosis in HCC patients.

Insights into the molecular underlying mechanisms and therapeutic potential of endoplasmic reticulum stress in sensorineural hearing loss

Sensorineural hearing loss (SNHL) is characterized by a compromised cochlear perception of sound waves. Major risk factors for SNHL include genetic mutations, exposure to noise, ototoxic medications, and the aging process. Previous research has demonstrated that inflammation, oxidative stress, apoptosis, and autophagy, which are detrimental to inner ear cells, contribute to the pathogenesis of SNHL; however, the precise mechanisms remain inadequately understood. The endoplasmic reticulum (ER) plays a key role in various cellular processes, including protein synthesis, folding, lipid synthesis, cellular calcium and redox homeostasis, and its homeostatic balance is essential to maintain normal cellular function. Accumulation of unfolded or misfolded proteins in the ER leads to endoplasmic reticulum stress (ERS) and activates the unfolded protein response (UPR) signaling pathway. The adaptive UPR has the potential to reestablish protein homeostasis, whereas the maladaptive UPR, associated with inflammation, oxidative stress, apoptosis, and autophagy, can lead to cellular damage and death. Recent evidence increasingly supports the notion that ERS-mediated cellular damage responses play a crucial role in the initiation and progression of various SNHLs. This article reviews the research advancements on ERS in SNHL, with the aim of elucidating molecular biological mechanisms underlying ERS in SNHL and providing novel insights for the treatment.

Unlocking the epigenetic code: new insights into triple-negative breast cancer

Triple-negative breast cancer (TNBC) is a highly aggressive and clinically challenging subtype of breast cancer, lacking the expression of estrogen receptor (ER), progesterone receptor (PR), and HER2/neu. The absence of these receptors limits therapeutic options necessitating the exploration of novel treatment strategies. Epigenetic modifications, which include DNA methylation, histone modifications, and microRNA (miRNA) regulation, play a pivotal role in TNBC pathogenesis and represent promising therapeutic targets. This review delves into the therapeutic potential of epigenetic interventions in TNBC, with a focus on DNA methylation, histone modifications, and miRNA therapeutics. We examine the role of DNA methylation in gene silencing within TNBC and the development of DNA methylation inhibitors designed to reactivate silenced tumor suppressor genes. Histone modifications, through histone deacetylation and acetylation in particular, are critical in regulating gene expression. We explore the efficacy of histone deacetylase inhibitors (HDACi), which have shown promise in reversing aberrant histone deacetylation patterns, thereby restoring normal gene function, and suppressing tumor growth. Furthermore, the review highlights the dual role of miRNAs in TNBC as both oncogenes and tumor suppressors and discusses the therapeutic potential of miRNA mimics and inhibitors in modulating these regulatory molecules to inhibit cancer progression. By integrating these epigenetic therapies, we propose a multifaceted approach to target the underlying epigenetic mechanisms that drive TNBC progression. The synergistic use of DNA methylation inhibitors, HDACi, and the miRNA-based therapies offers a promising avenue for personalized treatment strategies, aiming to enhance the clinical outcome for patients with TNBC.

Bifidobacterium longum JBLC-141 alleviates hypobaric hypoxia-induced intestinal barrier damage by attenuating inflammatory responses and oxidative stress

Hypobaric hypoxia exposure occurs at high altitudes, including plateaus, and affects normal intestinal function and microbiota composition. Exposure induces an intestinal inflammatory response and oxidative stress injury, ultimately disrupting intestinal homeostasis and causing barrier damage. Thus, due to its anti-inflammatory, antioxidative, and intestinal microbiota-regulating properties, Bifidobacterium longum is a potentially effective probiotic intervention to protect the intestinal barrier during low-pressure hypoxia on plateaus. However, its mechanism of action is not fully defined. In this study, we investigate the mechanism by which B. longum intervenes in intestinal barrier damage caused by plateau low-pressure hypoxia. To this end, an in vivo model is established by exposing rats to a simulated low-pressure hypoxic plateau environment. The experimental rats were subsequently supplemented with a B. longum strain (JBLC-141) extracted from the feces of healthy adults in Bama, Guangxi. B. longum JBLC-141 mitigates the effects of plateau low-pressure hypoxia on the rat intestinal barrier. This is achieved by activating the intestinal Kelch-like ECH-associated protein 1 (KEAP1)/nuclear factor erythroid 2-related factor 2 (NRF2) pathway, alleviating plateau hypoxia-induced intestinal oxidative stress injury. B. longum JBLC-141 also attenuates the inflammatory response and upregulates the expression of the tight junction proteins claudin-1, occludin, and zonula occludens-1. Furthermore, it reduces intestinal permeability, effectively ameliorating and repairing the barrier histological damage induced by the plateau low-pressure hypoxic environment. In addition, B. longum JBLC-141 positively regulates the intestinal microbiota, increasing the relative abundance of beneficial bacteria while reducing that of pathogenic bacteria and maintaining intestinal flora homeostasis in rats.

IMPLANTATION OF CHONDROFILLER LIQUID® AS A SCAFFOLD MATERIAL FOR THE TREATMENT OF CHONDRAL LESIONS OF THE KNEE JOINT

Introduction: Trauma, sports, or the normal aging degenerative process may damage the articular cartilage. Surgical methods that are most often used to manage cartilage defects include autologous chondrocyte implantation, mosaicplasty, microfractures, perforations, and joint arthroplasty in cases of severe damage. Another approach is to use collagen gel for cartilage defect reconstruction. Its biocompatibility, high tensile strength, and minimal invasiveness make it an attractive solution. ChondroFiller gel is a two-component collagen implant that could be used in the treatment of traumatic or degenerative chondral lesions. After application, it forms a protective cover for the damaged chondral area and provides structural support for the stem cells that migrate to its collagen matrix. Thus, with ChondroFiller, we aim to restore articular cartilage, prevent further degenerative processes, and return to normal joint function. In this research, we have investigated the application of ChondroFiller during knee arthroscopy to treat knee articular cartilage lesions. Methods: The clinical study was conducted at the University Hospital - Pleven Clinic of Orthopedics and Traumatology between 2012 and 2023. Seventeen patients (ten males and seven females) with a mean age of 31 years underwent knee chondroplasty with ChondroFiller gel, and their data was analyzed. Knee function was assessed using the Lysholm scale and IKDC score. The follow-up period was twelve months. Results: Statistical analysis has shown a significant difference between pre-operative Lysholm and pre-operative IKDC score and 3rd month, 6th and 12 months. Significant difference is detected between the 3rd month and 6th and 12th months Lysholm and IKDC scores (p &lt; 0.05). No statistical difference was found between 6 and 12 month (p &gt; 0.05). Conclusion: Restoring joint congruity is challenging. Overall, we have found encouraging results by employing ChondroFiller to restore articular cartilage. We believe that Chondrofiller provides an excellent surgical solution to younger patients with chondral defects less than 2cm2. In our opinion, further research in the field of collagen implants is needed to discover long-term effect.

Psk1 virulence gene-induced pulmonary and systemic tuberculosis in a young woman with normal immune function: A case report

BACKGROUND Tuberculosis is a chronic infectious disease and an important public health problem. Despite progress in controlling tuberculosis, the incidence of tuberculosis in China is still very high, with 895000 new cases annually. This case report describes the investigation of a case of severe disseminated tuberculosis in a young adult with normal immune function, conducted to ascertain why a Mycobacterium tuberculosis (M. tuberculosis ) strain caused such severe disease. CASE SUMMARY A previously healthy 28-year-old woman presented to our hospital with a 1-month history of fever and fatigue. She was diagnosed with severe disseminated pulmonary tuberculosis, spinal tuberculosis with paravertebral abscesses, and tuberculous meningitis. M. tuberculosis was isolated from bronchoalveolar lavage fluid. She was treated with standard antituberculous therapy and underwent debridement, bone graft, and internal fixation surgery for spinal tuberculosis. She responded to therapy and regained her ability to walk following the surgery. We analysed the whole-genome sequence of the strain and designated it BLM-A21. Additional M. tuberculosis genomes were selected from the Virulence Factor Database (http://www.mgc.ac.cn/cgi-bin/VFs/genus.cgi?Genus=Mycobacterium ) for comparison. An evolutionary tree of the BLM-A21 strain was built using PhyML maximum likelihood software. Further gene analysis revealed that, except for the pks1 gene, BLM-A21 had similar virulence genes to the CDC 1551 and H37Rv strains, which have lower dissemination. CONCLUSION We speculate that the pks1 virulence gene in BLM-A21 may be the key virulence gene responsible for the widespread dissemination of M. tuberculosis infection in this previously healthy adult with normal immune function.

Risk of renal dysfunction in patients with dengue fever: a case-control study

Dengue fever, a mosquito-borne infection, is typically caused by the Dengue virus, leading to various illnesses, including dengue fever and severe dengue fever. This study aims to investigate the outcome of dengue fever severity as renal dysfunction in patients. For this case-control study, blood samples of the patients (N=66), including 31 D-W (Dengue without warning signs), 20 D+W (Dengue with warning signs), and 15 SDF (Severe dengue fever), as well as controls (N=45) of same age groups, were obtained. The renal parameters were determined and statistically analyzed using a one-way ANOVA and chi-square/Fisher exact test. The intergroup comparison showed that phosphorous, calcium, and sodium presented a marked decrease (P &lt; 0.001) in dengue patient groups compared to controls. However, a significant increase (P &lt; 0.05) in chloride was indicated in dengue patient groups. Moreover, a prominent potassium reduction (P = 0.036) was observed in the dengue subjects group compared to controls. Among the renal parameters, creatinine presented a significant elevation (P &lt; 0.002) while uric acid was significantly (P = 0.004) dropped in dengue patients groups as compared to controls. This study's results suggest that dengue infection's severity may be associated with aberrant electrolyte imbalance and renal impairment. This study indicates that dengue affects normal kidney functions and harms the patients' health. Keywords: electrolytes; renal profile; dengue fever; severe dengue fever

Do Individuals with Misophonia Experience Challenges with TheirAuditory Binaural Interaction and Integration Skills?

Background and Aim: Misophonia is a condition marked by heightened sensitivity and intense emotional and physiological responses to particular sounds that may not spark the same reactions in others. This study is the first of its kind to assess binaural integration and binaural interaction in misophonia. Methods: Thirty misophonia and 30 control participants were considered in the age range of 18 to 30 years. All the participants had hearing sensitivity within normal limits and normal middle ear function. Individuals with a history of otological complaints, noise exposure, ototoxic medications, tinnitus, hyperacusis, diabetes, or hypertension were excluded from the study. Misophonia severity was assessed using the Misophonia Assessment Questionnaire (MAQ). Binaural integration was assessed using Dichotic Consonant Vowel (DCV) test, and binaural interaction was assessed using Masking Level Difference (MLD). Results: The statistical analysis of the independent t-test for DCV and Mann Whitney U test for MLD showed no significant difference between misophonia and the control group for both MLD and DCV. Conclusion: The results suggest that there is no significant difference in DCV and MLD scores between the control and misophonia groups.Keywords: Misophonia; binaural integration; binaural interaction; dichotic consonant vowel; masking level difference

Flapless extraction of impacted mandibular third molars: A contemporary surgical approach

The aim of this review is to evaluate the clinical outcomes of flapless extraction of impacted mandibular third molars compared to traditional flap-based techniques, with a focus on patient satisfaction, complication rates, and overall surgical efficiency. The extraction of impacted mandibular third molars (wisdom teeth) is a common procedure in oral and maxillofacial surgery, traditionally performed using a flap-based technique. While this method provides clear access to the impacted tooth, it is often associated with significant postoperative morbidity, such as pain, swelling, and extended recovery time. Recent innovations have introduced flapless extraction as a minimally invasive alternative, aiming to minimize tissue trauma and preserve periosteal integrity. This technique, however, presents its own set of challenges, including limited visibility and technical demands.This review analyzes the current literature on flapless extraction techniques, drawing from retrospective studies, randomized controlled trials, and clinical case reports. The data include comparisons of postoperative outcomes between flapless and traditional methods, emphasizing factors such as operative time, postoperative discomfort, and the frequency of complications. Findings indicate that flapless extraction generally results in reduced postoperative pain, swelling, and faster recovery times compared to traditional flap-based techniques. Patients who undergo flapless extraction report higher satisfaction due to less postoperative discomfort and a quicker return to normal function. However, the technique poses challenges in cases of deeply impacted teeth, where the lack of a flap may hinder complete access and increase the risk of complications. Flapless extraction represents a promising evolution in the surgical removal of impacted mandibular third molars, offering several advantages over traditional methods, particularly in reducing postoperative morbidity. However, the technique requires precise surgical skill and is not suitable for all cases. Careful case selection is crucial, and continued research is needed to further validate its efficacy and safety in complex scenarios.

Association of long non-coding RNA genes (&lt;i&gt;H19&lt;/i&gt;, &lt;i&gt;MEG3&lt;/i&gt;, &lt;i&gt;MALAT1&lt;/i&gt;, &lt;i&gt;Linc00305&lt;/i&gt;, &lt;i&gt;Linc00261&lt;/i&gt;, &lt;i&gt;Linc02227&lt;/i&gt;, and &lt;i&gt;CDKN2B-AS1&lt;/i&gt;) polymorphic loci with chronic obstructive pulmonary disease

Chronic obstructive pulmonary disease (COPD) is a chronic lung disease resulting from dynamic, cumulative gene-environment interactions that cause lung tissue injury, alteration of its normal function and acceleration of cellular senescence. Long non-coding RNAs (lncRNAs) function as critical epigenetic regulators of various aspects of cellular senescence. The objective of the present study is to identify the association between polymorphic variants of H19 (rs3741219), MEG3 (rs7158663), MALAT1 (rs619586), LINC00305 (rs2850711), LINC00261 (rs6048205), CDKN2B-AS1 (rs4977574), and LINC02227 (rs2149954) lncRNAs genes with COPD. DNA samples from COPD patients (N = 703) and healthy individuals (N = 655) were studied in this study and polymorphic loci were analyzed by real–time PCR. Association with COPD was established with H19 (rs3741219), MEG3 (rs7158663), LINC02227 (rs2149954), MALAT1 (rs619586) and CDKN2B-AS1 (rs4977574). Polygenic analysis has allowed to identify informative gene-gene combinations that include polymorphic variants of the studied lncRNAs genes and genes encoding molecules of signaling cascades associated with cellular senescence and apoptosis. Multiple regression and ROC-analysis revealed a COPD risk predictive model, which included gene–gene combinations of lncRNAs genes and smoking index (P = 4.01 x 10-48, AUC = 0.87).

Impact of Laboratory-Measured Euthyroid Hashimoto's Thyroiditis on Reproductive Hormone Profile in Women with Obesity.

Introduction: Hashimoto's thyroiditis is a common endocrinological disorder that often coexists with obesity. Thyroid hormones interact with the regulation of sex steroids, and thyroid autoimmunity has a negative impact on female fertility. There are studies showing when euthyroid state is achieved with hormone replacement therapy (HRT), the reproductive hormone profile is improved but they usually compare the reproductive hormones before and after HRT in the same individuals. Studies comparing patients with Hashimoto's thyroiditis in an euthyroid state receiving HRT with individuals having normal thyroid function are limited. Here, it was aimed to search the impact of euthyroid Hashimoto's thyroiditis on reproductive hormone profile in women living with obesity. Materials and Methods: Sixty-one randomly selected female patients with Hashimoto's thyroiditis were included as the case group and 60 patients without Hashimoto's thyroiditis were included as the control group, from our obesity center. The case group included patients who had menstrual cycles and were euthyroid under l-thyroxine treatment for at least 6 months. Data on weight, height, body mass index (BMI), waist circumference (WC), free thyroxine (fT4), thyroid stimulating hormone (TSH), thyroid peroxidase antibody (anti-TPO), cortisol, insulin, prolactin (PRL), follicular stimulating hormone (FSH), luteinizing hormone (LH), estradiol (E2), progesterone (prog), testosterone (T), and dehydroepiandrosterone sulfate (DHEAS) levels, l-thyroxine treatment dosage (for case group), and accompanying diseases were recorded. The results were evaluated using SPSS. Results: A total of 121 patients were included in the study. Mean age was 41.8 ± 8.5 years in case and 38.6 ± 8.9 years in control group. There was no significant difference in weight, height, BMI, WC, or accompanying diseases between Hashimoto's thyroiditis and control group. fT4, anti-TPO, cortisol levels were higher in Hashimoto's thyroiditis group when compared with control group, but there was no significant difference for TSH, insulin, FSH, LH, E2, prog, T, DHEAS, or PRL. Conclusion: In women living with obesity, it is important to screen for Hashimoto's thyroiditis and achieve euthyroidism through effective LT4 treatment to promote a healthy reproductive system and improve fertility rates.