Individual and community-level determinants of quality antenatal care in six South Asian countries.

Maternal health is a global public health concern. The paucity of antenatal care (ANC) during pregnancy is directly associated with maternal mortality. This study assessed the individual and community-level determinants of quality  ANC in six South-Asian countries. Data were obtained from a Demographic health survey of six South-Asian countries. This study included a sample of 180,567 (weighted) women aged 15-49 who had given birth in the preceding three years prior to the survey. The quality of ANC was determined by assessing whether a woman had received blood pressure monitoring, urine and blood sample screening, and iron supplements at any ANC visits. Frequency, percentage distribution, and inferential analysis (multilevel mixed-effects model) were conducted. The proportion of quality antenatal care utilization in South Asia was 66.9%. The multilevel analysis showed that women aged 35-49 years (AOR = 1.16; 95% CI = 1.09-1.24), higher education (AOR = 2.84; 95% CI = 2.69-2.99), middle wealth status (AOR = 1.55; 95% CI = 1.49-1.62), richest wealth status (AOR = 3.21; 95% CI = 3.04-3.39), unwanted pregnancy (AOR = 0.92; 95% CI = 0.89-0.95) and 2-4 birth order (AOR = 0.86; 95% CI = 0.83-0.89) were among the individual-level factors that were significantly associated with quality ANC utilization. In addition, rural residence (AOR = 0.77; 95% CI = 0.74-0.8), and big problem - distance to health facility (AOR = 0.63; 95% CI: 0.53-0.76) were the among community level factors there were also significantly associated with use of quality ANC. Meanwhile, women who lived in India (AOR: 22.57; 95% CI: 20.32-25.08) and Maldives (AOR: 33.33; 95% CI: 31.06-35.76) had higher odds of quality ANC than those lived in Afghanistan. Educational status, wealth status, pregnancy wantedness, sex of household head, birth order, place of residence, and distance to health facility were associated with quality ANC. Improving educational status, improving wealth status, reducing the distance to health facilities, and providing rural area-friendly interventions are important to increase the quality of ANC in South Asia.

Evaluation of the binding interactions between Plasmodium falciparum Kelch-13 mutant recombinant proteins with artemisinin.

Malaria, an ancient mosquito-borne illness caused by Plasmodium parasites, is mostly treated with Artemisinin Combination Therapy (ACT). However, Single Nucleotide Polymorphisms (SNPs) mutations in the P. falciparum Kelch 13 (PfK13) protein have been associated with artemisinin resistance (ART-R). Therefore, this study aims to generate PfK13 recombinant proteins incorporating of two specific SNPs mutations, PfK13-V494I and PfK13-N537I, and subsequently analyze their binding interactions with artemisinin (ART). The recombinant proteins of PfK13 mutations and the Wild Type (WT) variant were expressed utilizing a standard protein expression protocol with modifications and subsequently purified via IMAC and confirmed with SDS-PAGE analysis and Orbitrap tandem mass spectrometry. The binding interactions between PfK13-V494I and PfK13-N537I propeller domain proteins ART were assessed through Isothermal Titration Calorimetry (ITC) and subsequently validated using fluorescence spectrometry. The protein concentrations obtained were 0.3 mg/ml for PfK13-WT, 0.18 mg/ml for PfK13-V494I, and 0.28 mg/ml for PfK13-N537I. Results obtained for binding interaction revealed an increased fluorescence intensity in the mutants PfK13-N537I (83 a.u.) and PfK13-V494I (143 a.u.) compared to PfK13-WT (33 a.u.), indicating increased exposure of surface proteins because of the looser binding between PfK13 protein mutants with ART. This shows that the PfK13 mutations may induce alterations in the binding interaction with ART, potentially leading to reduced effectiveness of ART and ultimately contributing to ART-R. However, this study only elucidated one facet of the contributing factors that could serve as potential indicators for ART-R and further investigation should be pursued in the future to comprehensively explore this complex mechanism of ART-R.

Date palm transcriptome analysis provides new insights on changes in response to high salt stress of colonized roots with the endophytic fungus Piriformospora indica.

Salinity is a significant threat that causes considerable yield losses in date palm. The root endophytic fungus Piriformospora indica has proven effective in providing salt stress tolerance to host plants. However, the underlying molecular mechanism facilitating the date palm's response to P. indica inoculation, and its involvement in the salt stress tolerance, remains unknown. In this study, the colonization of P. indica on date palm seedlings exposed to saline conditions was observed through confocal microscopy, and its impact on gene expressions was evaluated using the transcriptomic analysis. Our findings show that P. indica colonization reinforced the cortical cells, prevented them from plasmolysis and cell death under salinity. The RNAseq analysis produced clean reads ranging from 62,040,451 to 3,652,095 across the treatment groups, successfully assembling into 30,600 annotated genes. Out of them, the number of differentially expressed genes (DEGs) varied across the treatments: i.e., 2523, 2031, and 1936 DEGs were upregulated, while 2323, 959, and 3546 were downregulated in Salt, Fungi, and Fungi+Salt groups, respectively. Furthermore, principal component analysis based on transcriptome profiles revealed discrete clustering of samples from different treatment groups. KEGG and GO pathways enrichment analysis highlighted variation in the number and types of enriched pathways among the treatments. Our study indicated variations in gene expression related to plant hormone biosynthesis and signal transduction (auxin, abscisic acid, gibberellin, and ethylene), ABC transporters, sodium/hydrogen exchanger, cation HKT transporter, transcription factors such as WRKY and MYBs, and the plant immune system (lipoxygenase and jasmonate) of the date palm seedlings. By characterizing the transcriptome of date palm roots under salt stress and with colonization of P. indica, the present findings provide valuable perspectives on the molecular mechanisms responsible for inducing salinity stress tolerance in plants.

Cutaneous Squamous Cell Carcinoma on the Eyebrow of a Woman: A Rare Case Report.

The exact incidence of cutaneous squamous cell carcinoma (CSCC) or nonmelanoma skin cancer is unknown, and it is believed that the rate of occurrence is increasing with the growing elderly population and sun exposure, and it is more prevalent in males than in females. In this article, we describe the case of an 81-year-old woman who presented with a lesion on the right upper eyebrow. The patient had been consulting a dermatologist and undergoing treatment for three months. However, the lesion did not show any signs of improvement, and the dermatologist speculated that it might be a common wound that was healing slowly because of her diabetes. Imaging revealed an ulcerating skin lesion on the right upper eyebrow without connection to the deeper structures. Surgical intervention was chosen with the patient's consent. This rare case of CSCC on a woman's eyebrow showed that skin cancer can occur in unusual locations and in people without risk factors.

Unraveling mitochondrial dysfunction: comprehensive perspectives on its impact on neurodegenerative diseases.

Neurodegenerative diseases represent a significant challenge to modern medicine, with their complex etiology and progressive nature posing hurdles to effective treatment strategies. Among the various contributing factors, mitochondrial dysfunction has emerged as a pivotal player in the pathogenesis of several neurodegenerative disorders. This review paper provides a comprehensive overview of how mitochondrial impairment contributes to the development of neurodegenerative diseases including Alzheimer's disease, Parkinson's disease, Huntington's disease, and amyotrophic lateral sclerosis, driven by bioenergetic defects, biogenesis impairment, alterations in mitochondrial dynamics (such as fusion or fission), disruptions in calcium buffering, lipid metabolism dysregulation and mitophagy dysfunction. It also covers current therapeutic interventions targeting mitochondrial dysfunction in these diseases.

The impact of extracorporeal support on antimicrobial pharmacokinetics in critically ill neonatal and paediatric patients: A systematic review.

Infections represent a major risk for critically ill neonatal and paediatric patients requiring extracorporeal life-saving support such as extracorporeal membrane oxygenation (ECMO) and/or continuous renal replacement therapies (CRRT). Patient outcomes rely on achieving target antimicrobial concentrations. In critically ill adults on extracorporeal support, suboptimal antimicrobial concentrations have been shown to be common. Our objective was to systematically review antimicrobial pharmacokinetic studies in critically ill term neonatal and paediatric patients receiving ECMO and/or CRRT and compare them to similar cohorts of patients not receiving ECMO or CRRT. Studies published between 1990 and 2022 were identified through systematic searches in PUBMED, Embase, Web of Science, Medline, Google Scholar and CINAHL. Studies were included which provided antimicrobial pharmacokinetic parameters (volume of distribution and clearance) in the neonatal and paediatric patients receiving ECMO and/or CRRT. Studies were excluded if no antimicrobial pharmacokinetic parameters were described or could be calculated. Forty-four pharmacokinetic studies were identified describing 737 patients, with neonatal patients recruited in 70% of the ECMO studies and <1% of the CRRT studies. Of all the studies, 50% were case reports or case series. The pharmacokinetics were altered for gentamicin, daptomycin, ceftolozane, micafungin, voriconazole, cefepime, fluconazole, piperacillin, and vancomycin, although considerable patient variability was described. Significant gaps remain in our understanding of the pharmacokinetic alterations in neonatal and paediatric patients receiving ECMO and CRRT support.

Femoral Head Avascular Necrosis Due to Brucella Infection: A Case Report.

Brucellosis remains a widespread disease in endemic regions worldwide and is not adequately controlled. It is a common zoonotic disease worldwide, a systemic infection, and a major health problem in endemic countries. Femoral head avascular necrosis (FHAVN) as a consequence of brucellosis is exceedingly unusual and has seldom been recorded. The case reports a 21-year-old female patient was hospitalized due to severe pain in both lower limbs, particularly in the anterior portion of the hip joint, accompanied by a low-grade fever persisting for six months. Movement of the right hip was painful, and the patient limped at the beginning of walking after a few steps. Rheumatoid factor and antinuclear antibody test results were negative. The right hip joint was aspirated, and a small quantity of fluid was sent for Gram staining and culture. Synovial joint fluid culture confirmed Brucella abortus infection after four weeks. The source of infection in the present case was the consumption of raw milk. Based on laboratory tests and radiographic images, FHAVN was diagnosed. Owing to misdiagnosis, she had not received standard treatment for brucellosis in the previous months. The patient was diagnosed early, and she was in the third stage. After the patient received medical treatment, the left and right hip joints partly recovered. The right hip joint required replacement; however, the patient refused. Attending physicians should consider brucellosis as an alternative to arthritis for hip joint pain in Brucella-endemic locations. Medication-based therapy may be effective for early avascular necrosis, emphasizing the need for early diagnosis and treatment.

Mitochondrial Deoxyribonucleic Acid Copy Number Elevation As a Predictor for Extended Survival and Favorable Outcomes in High-Grade Brain Tumor Patients: A Malaysian Study.

BACKGROUND:  Investigating the role of mitochondrial DNA (mtDNA) alterations and their impact on brain tumor progression remains a significant focus in cancer research. The research aimed to explore the specific contributions of mtDNA copy number changes and their correlations with patient survival, large mtDNA deletions, and TFAM mutations in brain tumor patients. METHODS:  A total of 41 patients with confirmed brain tumors underwent DNA extraction from both tumor tissues and blood samples. The relative mtDNA copy number in comparison to the nuclear genome was quantified using quantitative real-time polymerase chain reaction (qRT-PCR). Long-range PCR assessed largescale mtDNA deletions, and Sanger sequencing was applied to detect exon 4 TFAM mutations. RESULTS:  Analysis revealed significantly increased mtDNA copy numbers in brain tumor tissues (80.5%) compared to matched blood samples (P < .001). Median delta Ct (∆Ct) values were 7.35 in cancerous tissues and 11.81 in blood (P <.001), with median relative mtDNA content of 0.0123 and 0.0006, respectively (P <.001). Patients with higher mtDNA copy numbers experienced longer overall survival periods (P=.045) and notably favorable outcomes, particularly in high-grade tumor cases (P=.016). Furthermore, a singlenucleotide deletion was identified in exon 4 of TFAM in a patient with glioblastoma IV, while no large-scale mtDNA deletions were found in brain tumor patients. CONCLUSION:  Our study strongly supports the role of increased mtDNA copy numbers as a reliable predictor for improved survival and positive outcomes in high-grade brain tumor patients.

A bitter flavonoid gum from Dorema aucheri accelerate wound healing in rats: Involvement of Bax/HSP 70 and hydroxyprolin mechanisms.

BACKGROUND: Dorema aucheri gum (DAG) is a bitter flavonoid gum widely used for numerous medicinal purposes including wound recovery. The present work investigates the acute toxicity and wound-healing effects of DAG in excisional skin injury in rats. MATERIALS AND METHODS: Sprague Dawley rats (24) were clustered into four groups, each rat had a full-thickness excisional dorsal neck injury (2.00 cm) and addressed with 0.2 mL of the following treatments for 15 days: Group A (vehicle), rats addressed with normal saline; Group B, rats received intrasite gel; C and D, rats addressed with 250 and 500 mg/kg of DAG, respectively. RESULTS: The results revealed the absence of any toxic signs in rats who received oral dosages of 2 and 5 g/kg of DAG. Wound healing was significantly accelerated following DAG treatments indicated by smaller open areas and higher wound contraction percentages compared to vehicle rats. Histological evaluation revealed higher fibroblast formation, collagen deposition, and noticeably lower inflammatory cell infiltration in granulated skin tissues of DAG-addressed rats compared to vehicle rats. DAG treatment caused significant modulation of immunohistochemical proteins (decreased Bax and increased HSP 70) and inflammatory mediators (reduced TNF-α, IL-6, and magnified IL-10), which were significantly varied compared to vehicle rats. Moreover, topical DAG treatment led to significant upregulation of the hydroxyproline (HDX) (collagen) and antioxidant content. At the same time, decreased the lipid peroxidation (MDA) levels in healed tissues obtained from DAG-treated rats. CONCLUSION: The present wound contraction by DAG might be linked with the modulatory effect of its phytochemicals (polysaccharides, flavonoids, and phenolic) on the cellular mechanisms, which justify their folkloric use and provokes further investigation as therapeutic drug additives for wound contraction.

A Review on the Mechanisms, Applications, and Clinical Trials of Advanced Technologies in the Transdermal Drug Delivery System.

Transdermal Drug Delivery Systems (TDDS) have emerged as a promising method for administering therapeutic agents due to their non-invasive nature and patient-friendly approach. However, the effectiveness of this system is limited to drugs with specific physicochemical properties that allow for transdermal delivery as the skin acts as a barrier. To address this limitation, researchers have been exploring alternative approaches to improve drug delivery through the stratum corneum, ensuring consistent drug distribution at controlled rates. Thirdgeneration delivery systems have been developed to facilitate the delivery of various drugs across the skin barrier by disrupting the stratum corneum while protecting deeper skin tissues from injury. This review has explored various approaches that have gained popularity in enhancing drug delivery through TDDS, including microneedle-mediated, nanoparticle-enabled, thermal ablation-enhanced, and electroporation-driven delivery systems. It has discussed the mechanisms of drug delivery and potential applications for different types of drugs and detailed the clinical studies. This review has also highlighted the significant advancements in TDDS, offering valuable insights into both the pharmaceutical field and biomedical applications. The continued exploration and refinement of these delivery systems, particularly with the incorporation of Internet-of-Things (IoT) technology, Artificial Intelligence (AI), and machine learning, hold promise for expanding the scope of therapeutic interventions.

The Effect of Periodontitis on Fibroblast Growth Factor 23 Levels in Predialysis Chronic Kidney Disease Patients.

Introduction Chronic kidney disease (CKD) is known to cause an increase in fibroblast growth factor 23 (FGF23). Periodontitis, a condition recognized as a risk factor for CKD, is also potentially associated with the increment of FGF23. This study aims to compare FGF23 levels in CKD patients with and without periodontitis and non-CKD patients with and without periodontitis. Correlation with serum phosphate, calcium, and intact parathyroid hormone (iPTH) was assessed. Additionally, associations between FGF23, calcium, phosphate, iPTH, creatinine, urea, plaque score, and bleeding score with periodontitis in CKD patients were determined. Method A total of 124 participants were categorized into four groups: CKD patients with periodontitis (n=31), CKD patients without periodontitis (n=32), periodontitis patients without CKD (n=32), and healthy population (n=29). The selected CKD patients include those from stages 3 and 4 (predialysis) patients. Serum levels of FGF23, calcium, phosphate, iPTH, creatinine, and urea were analyzed. Oral examinations were conducted to determine the presence and absence of periodontitis and assess plaque and bleeding scores. Result A significantly higher level of FGF23 was found in CKD compared to non-CKD groups; however, no difference was observed with the presence of periodontitis in both CKD and non-CKD. There was no significant correlation found between FGF23 and serum calcium, phosphate, or iPTH concerning periodontal status. Apart from the bleeding score, there was no association between FGF23, calcium, phosphate, iPTH, creatinine, urea, and plaque score with the presence of periodontitis in CKD patients. Conclusion The presence of periodontitis was not associated with higher FGF23 levels in CKD patients. Changes in FGF23, calcium, phosphate, iPTH, creatinine, urea, and plaque score could not be attributed to the presence of periodontitis in CKD patients.

Malaysian Medical Students' Career Intention (MMSCI): a cross-sectional study.

BACKGROUND: In recent years, there have been many instances of negative sentiments expressed by and resignations observed from doctors working in the Ministry of Health (MOH), Malaysia. However, little is known about the perspectives of medical students and their career intentions. This study aims to determine the current Malaysian medical students' career intentions immediately after graduation and upon completing the 2 years of housemanship and to establish the factors influencing these intentions. METHODS: This was a cross-sectional study of 859 Malaysian medical students from 21 medical schools who voluntarily completed a self-administered online questionnaire that was disseminated by representatives from medical schools nationwide and social media platforms of a national medical student society. RESULTS: 37.8% of the respondents were optimistic about a career with the Ministry of Health (MOH), Malaysia in the future. Most of the respondents (91.2%) plan to join and complete the MOH Housemanship programme as soon as possible after graduation, with the majority of them (66.2%) planning to complete it in their state of origin. After 2 years of Housemanship programme, only more than half of the respondents (63.1%) plan to continue their careers in MOH. Slightly more than a quarter (27.1%) of the total respondents plan to emigrate to practise medicine, with 80.7% of them planning to return to Malaysia to practise medicine after some years or after completing specialisation training. Combining the career intentions of Malaysian medical students immediately after graduation and upon completion of the 2 years housemanship programme, only a slight majority (57.5%) of the respondents plan to continue their career in MOH eventually. Most of the respondents (85.0%) intend to specialise. CONCLUSION: A concerning number of Malaysian medical students plan to leave the Ministry of Health workforce, the main healthcare provider in Malaysia, in the future. Urgent government interventions are needed to address the underlying factors contributing to the potential exodus of future doctors to prevent further straining of the already overburdened healthcare system, posing a significant threat to public well-being. An annual national study to track medical students' career intentions is recommended to gather crucial data for the human resources for health planning in Malaysia.

Recombinant C-Terminal Catalytic Domain of Rat L-Gulono Lactone Oxidase Produced in Bacterial Cells Is Enzymatically Active.

The L-gulonolactone oxidase enzyme (GULO) catalyzes the last step of L-ascorbic acid (vitamin C) biosynthesis. This enzymatic activity is lost in primates. The full-length rat GULO has been previously produced in plants and demonstrated to be active. In this study, we compared the activity of two variants of GULO produced in Escheriachia coli cells, full-length rat GULO (fGULO) and its C-terminal catalytic domain (cGULO). The expression and purification of the recombinant proteins were optimized, and their biological activity was confirmed by two methods, the GULO activity assay in the protein extracts and the 'in-gel' staining for GULO activity. Both variants of recombinant GULO were biologically active in both assays. However, cGULO is more promising than fGULO for ascorbic acid production because it is more efficiently produced by bacteria. Furthermore, the optimal activities of the fGULO and cGULO recombinant proteins were observed at pH 7 and 6.5, and at temperatures of 40 and 30 °C, respectively. Kinetic studies revealed that at low substrate concentrations, Km values for fGULO and cGULO were 53.5 ± 5 and 42 ± 6.3 µM, respectively.

Integrating Clinical and Neuroimaging Markers to Predict the Onset of Posthemorrhagic Ventricular Dilatation in Preterm Neonates.

BACKGROUND: Posthemorrhagic ventricular dilatation (PHVD) is a major complication of intraventricular hemorrhage (IVH); it is associated with high risks of cerebral palsy and cognitive deficits compared with infants without PHVD. This study aims to explore the early perinatal risk factors-associated with the risk of progressive PHVD. METHODS: Neonates ≤29 weeks gestational age (GA) with Grade II-III IVH and periventricular hemorrhagic infarct (PVHI) between 2015 and 2021 were retrospectively reviewed. All cranial ultrasounds done within 14 days postnatal age (PNA) were assessed for grade of IVH, anterior horn width (AHW), ventricular index (VI), and thalamo-occipital index (TOD). The outcome was defined as death of any cause or VI and/or AHW and/or TOD ≥ moderate-risk zone based on an ultrasound done beyond two weeks PNA. RESULTS: A total of 146 infants with a mean GA of 26 ± 1.8 weeks, birth weight 900 ± 234 g were included, 46% were females. The primary outcome occurred in 56 (39%) infants; among them 17 (30%) and 11 (20%) needed ventricular reservoir and shunt insertion, respectively. The risk factors present within 14 days PNA that significantly increased the odds of developing PHVD were hemodynamically significant patent ductus arteriosus (odds ratio [OR] 6.1, 95% confidence interval [CI] 1.9 to 22), culture-proven sepsis (OR 5.4, 95% CI 1.8 to 18), Grade III IVH (OR 4.6, 95% CI 1.1 to 22), PVHI (OR 3.0, 95% CI 0.9 to 10), and VI (OR 2.1, 95% CI 1.6 to 2.9). CONCLUSIONS: Clinical predictors such as significant ductus arteriosus and bacterial septicemia, along with risk levels of AHW and VI measured with early cranial ultrasounds, are potential predictors of subsequent onset of PHVD.

Malignant Recurrence of Benign Odontogenic Tumors (A Single Center Cross-Sectional Study).

BACKGROUND: Despite their rarity, malignant odontogenic tumors (MOT) represent an important group of oral lesions characterized by their variable clinical presentations and sometimes unexpected biological behavior. OBJECTIVES: The purpose of this retrospective cross-sectional study was to evaluate the number, types, and frequency of MOT and to investigate the relative rate of malignant transformation in recurrent odontogenic tumors (OT). METHODOLOGY: The records of patients diagnosed with OT in the hospital of the Faculty of Dentistry, Cairo University, were reviewed over 10 years (2013-2022). The OT were investigated for frequency, age, gender, site, and recurrence. The data were recorded and then analyzed using SPSS software version 25. RESULTS: Among 5543 oral excisions, 357 cases of them were OT, including 336 benign (94.1%) and 21 malignant neoplasms (5.9%). Among the odontogenic malignancies, 18 lesions (85.7%) appeared de novo, and 3 lesions (14.3%) developed as recurrent of previously classified benign tumors. A high incidence was observed in the middle and old age groups (90.4%) with a median age being 42. Slight male predilection (1.3:1) was noticed. The mandible was the highly affected site but all recurrent cases were diagnosed in the maxilla as ghost cell odontogenic carcinoma (n = 2, 66.6%) and primary intraosseous carcinoma (n = 1, 33.3%). CONCLUSION: Retrospective analysis of the relative frequency of MOT and the documentation of the unusual recurrence of benign OT as a malignancy enhances our understanding of OT behavior and the need for appropriate therapy and clinical follow-up.

Wide-range and high-accuracy wireless sensor with self-humidity compensation for real-time ammonia monitoring.

Real-time and accurate biomarker detection is highly desired in point-of-care diagnosis, food freshness monitoring, and hazardous leakage warning. However, achieving such an objective with existing technologies is still challenging. Herein, we demonstrate a wireless inductor-capacitor (LC) chemical sensor based on platinum-doped partially deprotonated-polypyrrole (Pt-PPy+ and PPy0) for real-time and accurate ammonia (NH3) detection. With the chemically wide-range tunability of PPy in conductivity to modulate the impedance, the LC sensor exhibits an up-to-180% improvement in return loss (S11). The Pt-PPy+ and PPy0 shows the p-type semiconductor nature with greatly-manifested adsorption-charge transfer dynamics toward NH3, leading to an unprecedented NH3 sensing range. The S11 and frequency of the Pt-PPy+ and PPy0-based sensor exhibit discriminative response behaviors to humidity and NH3, enabling the without-external-calibration compensation and accurate NH3 detection. A portable system combining the proposed wireless chemical sensor and a handheld instrument is validated, which aids in rationalizing strategies for individuals toward various scenarios.

Assessing the efficacy of tocotrienol-rich fraction vitamin E in obese children with non-alcoholic fatty liver disease: a single-blind, randomized clinical trial.

BACKGROUND: Childhood obesity is a growing concern, and non-alcoholic fatty liver disease (NAFLD) is a significant consequence. Currently, there are no approved drugs to treat NAFLD in children. However, a recent study explored the potential of vitamin E enriched with tocotrienol (TRF) as a powerful antioxidant for NAFLD. The aims of the present study were to investigate the effectiveness and safety of TRF in managing children with obesity and NAFLD. METHODS: A total of 29 patients aged 10 to 18 received a daily oral dose of 50 mg TRF for six months (January 2020 to February 2022), and all had fatty liver disease were detected by ultrasonography and abnormally high alanine transaminase levels (at least two-fold higher than the upper limits for their respective genders). Various parameters, including biochemical markers, FibroScan, LiverFASt, DNA damage, and cytokine expression, were monitored. RESULTS: APO-A1 and AST levels decreased significantly from 1.39 ± 0.3 to 1.22 ± 0.2 g/L (P = 0.002) and from 30 ± 12 to 22 ± 10 g/L (P = 0.038), respectively, in the TRF group post-intervention. Hepatic steatosis was significantly reduced in the placebo group from 309.38 ± 53.60 db/m to 277.62 ± 39.55 db/m (p = 0.048), but not in the TRF group. Comet assay analysis showed a significant reduction in the DNA damage parameters in the TRF group in the post-intervention period compared to the baseline, with tail length decreasing from 28.34 ± 10.9 to 21.69 ± 9.84; (p = 0.049) and with tail DNA (%) decreasing from 54.13 ± 22.1to 46.23 ± 17.9; (p = 0.043). Pro-inflammatory cytokine expression levels were significantly lower in the TRF group compared to baseline levels for IL-6 (2.10 6.3 to 0.7 1.0 pg/mL; p = 0.047 pg/mL) and TNF-1 (1.73 5.5 pg/mL to 0.7 0.5 pg/mL; p = 0.045). CONCLUSION: The study provides evidence that TRF supplementation may offer a risk-free treatment option for children with obesity and NAFLD. The antioxidant and anti-inflammatory properties of TRF offer a promising adjuvant therapy for NAFLD treatment. In combination with lifestyle modifications such as exercise and calorie restriction, TRF could play an essential role in the prevention of NAFLD in the future. However, further studies are needed to explore the long-term effects of TRF supplementation on NAFLD in children. TRIAL REGISTRATION: The study has been registered with the International Clinical Trial Registry under reference number (NCT05905185) retrospective registration on (15/06/2023).

Narrative review on the evolving role of HER2/neu targeting in uterine serous cancers.

Background and Objective: Serous endometrial cancers (ECs) are an aggressive histotype of ECs which are disproportionately responsible for 40% of cancer-specific mortality rates despite constituting only 5-10% of all uterine cancers in incidence. In recent times, it has become increasingly evident that about 20-40% of uterine serous cancers (USCs) have molecular alterations in ERBB2 pathway with human epidermal growth factor receptor 2 (HER2/neu) amplification or overexpression. We summarise the evidence on genetic and molecular alterations in HER2/neu pathway in USC with a focus on testing criteria, targeting agents and resistance mechanisms. Methods: We conducted a database search of PubMed/Medline up to 28th February 2023 for articles published in the English language using pre-defined search terms. One hundred and seventy-one relevant articles were subsequently reviewed for eligibility and inclusion in the review. Key Content and Findings: The Cancer Genome Atlas (TCGA) classification is a significant development in the molecular profiling of ECs with a positive impact on the treatment of these tumors including USCs. Testing criteria for HER2/neu in USC with immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) has evolved in more than a decade with progress made towards EC specific testing guidelines. The findings of a recent phase III study have led to the development of practice changing guidelines towards improving patient outcomes. Conclusions: Molecular aberration in the HER2/neu pathway contributes to the aggressive behaviour of USC. Considering the clinical benefit conferred by HER2/neu targeted therapy, HER2/neu testing is recommended for all cases of serous EC in advanced and recurrent settings. Trastuzumab in combination with platinum and taxanes based chemotherapy is the recommended treatment option for patients with advanced or recurrent serous cancers who test positive to HER2/neu. Clinical trials on targeted therapy are ongoing and future research should focus on selection of patients who will derive the most benefit from such therapy.

Ultrafast Optical Control of Exciton Diffusion in WSe2/Graphene Heterostructures Revealed by Heterodyne Transient Grating Spectroscopy.

Using heterodyne transient grating spectroscopy, we observe a significant enhancement of exciton diffusion in a monolayer WSe2 stacked on graphene. The diffusion dynamics can be optically tuned within a few picoseconds by altering the photoexcited carrier density in graphene. The effective diffusion constant in initial picoseconds in the WSe2/graphene heterostructure is (40.3 ± 4.5) cm2 s-1, representing a substantial improvement over (2.1 ± 0.8) cm2 s-1, typical for an isolated WSe2 monolayer. This enhancement can be understood in terms of a transient screening of impurities, charge traps, and defect states in WSe2 by photoexcited charge carriers in graphene. Furthermore, diffusion within WSe2 is affected by interlayer interactions, such as charge transfer, varying with the incident excitation fluence. These findings underscore the dynamical nature of screening and diffusion processes in heterostructures of 2D semiconductors and graphene and provide insights for future applications of these systems in ultrafast optoelectronic devices.