Biogenic synthesis, characterization, and in vitro biological investigation of silver oxide nanoparticles (AgONPs) using Rhynchosia capitata.

The current research aimed to study the green synthesis of silver oxide nanoparticles (AgONPs) using Rhynchosia capitata (RC) aqueous extract as a potent reducing and stabilizing agent. The obtained RC-AgONPs were characterized using UV, FT-IR, XRD, DLS, SEM, and EDX to investigate the morphology, size, and elemental composition. The size of the RC-AgONPs was found to be ~ 21.66 nm and an almost uniform distribution was executed by XRD analysis. In vitro studies were performed to reveal biological potential. The AgONPs exhibited efficient DPPH free radical scavenging potential (71.3%), reducing power (63.8 ± 1.77%), and total antioxidant capacity (88.5 ± 4.8%) to estimate their antioxidative power. Antibacterial and antifungal potentials were evaluated using the disc diffusion method against various bacterial and fungal strains, and the zones of inhibition (ZOI) were determined. A brine shrimp cytotoxicity assay was conducted to measure the cytotoxicity potential (LC50: 2.26 µg/mL). In addition, biocompatibility tests were performed to evaluate the biocompatible nature of RC-AgONPs using red blood cells, HEK, and VERO cell lines (< 200 µg/mL). An alpha-amylase inhibition assay was carried out with 67.6% inhibition. Moreover, In vitro, anticancer activity was performed against Hep-2 liver cancer cell lines, and an LC50 value of 45.94 µg/mL was achieved. Overall, the present study has demonstrated that the utilization of R. capitata extract for the biosynthesis of AgONPs offers a cost-effective, eco-friendly, and forthright alternative to traditional approaches for silver nanoparticle synthesis. The RC-AgONPs obtained exhibited significant bioactive properties, positioning them as promising candidates for diverse applications in the spheres of medicine and beyond.

Integrated Approach to Hydrogeochemical Assessment of Groundwater Quality in Major Industrial Zone of Punjab, Pakistan.

Groundwater contamination with arsenic (As) is a significant concern in Pakistan's Punjab Province. This study analyzed 69 groundwater samples from Faisalabad, Gujranwala, Lahore, and Multan to understand hydrogeochemistry, health impacts, contamination sources, and drinking suitability. Results revealed varying as concentrations across districts, with distinctive cation and anion orders. Faisalabad exhibited Na+ > Mg2+ > Ca2+ > K+ > Fe2+ for cations and SO42- > Cl- > HCO3- > NO3- > F- for anions. Gujranwala showed Na+ > Ca2+ > Mg2+ > K+ for cations and HCO3- > SO42- > Cl- > NO3- > F- for anions. In Lahore, demonstrated: Na+ > Ca2+ > Mg2+ > Fe > K+ for cations and HCO3- > SO42- > Cl- > NO3- > F- for anions. Multan indicated K+ > Ca2+ > Mg2+ > Na+ > Fe for cations and HCO3- > SO42- > Cl- > F- > NO3- ) for anions. Hydrochemical facies were identified as CaHCO3 and CaMgCl types. Principal Component Analysis (PCA), highlighted the influence of natural processes and human activities on groundwater pollution. Water Quality Index (WQI) result reveal that most samples met water quality standards. The carcinogenic risk values for children exceeded permissible limits in all districts, emphasizing a significant cancer risk. The study highlights the need for rigorous monitoring to mitigate (As) contamination and protect public health from associated hazards.

Trapped temporal horn: From theory to practice, a systematic review of current understanding and future perspectives.

Background: The Entrapped Temporal Horn (ETH) is characterized by localized enlargement of the temporal horn of the lateral ventricle of the brain. This study aimed to investigate the factors, development, prognosis, and effective treatment. Methods: Following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines, a systematic search was conducted in major research databases. The inclusion criteria included patients of all ages with TTH diagnosis in cohort studies, case series, and case reports. Results: Our study included 160 patients and 49 studies. The major causes of TTH were neoplastic lesions (42.3%), infections (22.3%), and cystic disease (13.08%). Of these cases, 71 were unrelated to cranial surgery, while 89 were unrelated to prior surgeries. Headache was the most common symptom (41.91%), followed by seizures (13.20%), drowsiness (12.50%) and memory loss (11.00%). Surgery was not required in 17 patients. Fenestration of the trapped temporal horn was performed in 24 patients, while VP/VA shunt surgeries were performed in the majority (57 patients) owing to favorable outcomes, lower revision rates, and extensive experience. However, TTH recurred in six of the 21 patients who underwent endoscopic ventriculocisternostomy. Tumors were the main cause, and isolated headache was the most frequent symptom. Ventriculoperitoneal shunts (VPS) are preferred because of their positive outcomes, lower revision rates, and wider expertise. Tumors near the trigonal area pose a higher risk. Conclusion: Although TTH remains a rare condition, VPS continues to be the most widely preferred procedure among surgeons.

In-silico analysis and transformation of OsMYB48 transcription factor driven by CaMV35S promoter in model plant - Nicotiana tabacum L. conferring abiotic stress tolerance.

Global crop yield has been affected by a number of abiotic stresses. Heat, salinity, and drought stress are at the top of the list as serious environmental growth-limiting factors. To enhance crop productivity, molecular approaches have been used to determine the key regulators affecting stress-related phenomena. MYB transcription factors (TF) have been reported as one of the promising defensive proteins against the unfavorable conditions that plants must face. Different roles of MYB TFs have been suggested such as regulation of cellular growth and differentiation, hormonal signaling, mediating abiotic stress responses, etc. To gain significant insights, a comprehensive in-silico analysis of OsMYB TF was carried out in comparison with 21 dicot MYB TFs and 10 monocot MYB TFs. Their chromosomal location, gene structure, protein domain, and motifs were analyzed. The phylogenetic relationship was also studied, which resulted in the classification of proteins into four basic groups: groups A, B, C, and D. The protein motif analysis identified several conserved sequences responsible for cellular activities. The gene structure analysis suggested that proteins that were present in the same class, showed similar intron-exon structures. Promoter analysis revealed major cis-acting elements that were found to be responsible for hormonal signaling and initiating a response to abiotic stress and light-induced mechanisms. The transformation of OsMYB TF into tobacco was carried out using the Agrobacterium-mediated transformation method, to further analyze the expression level of a gene in different plant parts, under stress conditions. To summarize, the current studies shed light on the evolution and role of OsMYB TF in plants. Future investigations should focus on elucidating the functional roles of MYB transcription factors in abiotic stress tolerance through targeted genetic modification and CRISPR/Cas9-mediated genome editing. The application of omics approaches and systems biology will be indispensable in delineating the regulatory networks orchestrated by MYB TFs, facilitating the development of crop genotypes with enhanced resilience to environmental stressors. Rigorous field validation of these genetically engineered or edited crops is imperative to ascertain their utility in promoting sustainable agricultural practices.

Surgical strategies in acute subdural hematoma: a meta-analysis of decompressive craniectomy vs. craniotomy.

OBJECTIVE: Acute subdural hematoma (ASDH) stands as a significant contributor to morbidity after severe traumatic brain injuries (TBI). The primary treatment approach for patients experiencing progressive neurological deficits or notable mass effects is the surgical removal of the hematoma, which can be achieved through craniotomy (CO) or decompressive craniectomy (DC). Nevertheless, the choice between these two procedures remains a subject of ongoing debate and controversy. MATERIALS AND METHODS: We conducted a comprehensive literature review, utilizing prominent online databases and manually searching references related to craniotomy and craniectomy for subdural hematoma evacuation up to November 2023. Our analysis focused on outcome variables such as the presence of residual subdural hematoma, the need for revision procedures, and overall clinical outcomes. RESULTS: We included a total of 11 comparative studies in our analysis, encompassing 4269 patients, with 2979 undergoing craniotomy and 1290 undergoing craniectomy, meeting the inclusion criteria. Patients who underwent craniectomy displayed significantly lower scores on the Glasgow Coma Scale (GCS) during their initial presentation. Following surgery, the DC group exhibited a significantly reduced rate of residual subdural (P = 0.009). Additionally, the likelihood of a poor outcome during follow-up was lower in the CO group. Likewise, the mortality rate was lower in the CO group compared to the craniectomy group (OR 0.63, 95% CI 0.41-0.98, I2 = 84%, P = 0.04). CONCLUSION: Our study found that CO was associated with more favorable outcomes in terms of mortality, reoperation rate, and functional outcome while DC was associated with less likelihood of residual subdural hematoma. Upon further investigation of patient characteristics who underwent into either of these interventions, it was very clear that patients in DC cohort have more serious and low pre-op characteristics than the CO group. Nonetheless, brain herniation and advanced age act as independent factor for predicting the outcome irrespective of the intervention.

Role of estrogen in sex differences in memory, emotion and neuropsychiatric disorders.

Estrogen regulates a wide range of neuronal functions in the brain, such as dendritic spine formation, remodeling of synaptic plasticity, cognition, neurotransmission, and neurodevelopment. Estrogen interacts with intracellular estrogen receptors (ERs) and membrane-bound ERs to produce its effect via genomic and non-genomic pathways. Any alterations in these pathways affect the number, size, and shape of dendritic spines in neurons associated with psychiatric diseases. Increasing evidence suggests that estrogen fluctuation causes changes in dendritic spine density, morphology, and synapse numbers of excitatory and inhibitory neurons differently in males and females. In this review, we discuss the role of estrogen hormone in rodents and humans based on sex differences. First, we explain estrogen role in learning and memory and show that a high estrogen level alleviates the deficits in learning and memory. Secondly, we point out that estrogen produces a striking difference in emotional memories in men and women, which leads them to display sex-specific differences in underlying neuronal signaling. Lastly, we discuss that fluctuations in estrogen levels in men and women are related to neuropsychiatric disorders, including schizophrenia, autism spectrum disorder (ASD), attention deficit hyperactivity disorder (ADHD), bipolar disorder (BPD), major depressive disorder (MDD), substance use disorder (SUD), and anxiety disorders.

Genome-Wide Bioinformatics Analysis of SWEET Gene Family and Expression Verification of Candidate PaSWEET Genes in Potentilla anserina.

Sugars act as the main energy sources in many fruit and vegetable crops. The biosynthesis and transportation of sugars are crucial and especially contribute to growth and development. SWEET is an important gene family that plays a vital role in plants' growth, development, and adaptation to various types of stresses (biotic and abiotic). Although SWEET genes have been identified in numerous plant species, there is no information on SWEETs in Potentilla anserina. In the present study, we performed a comprehensive genome-wide bioinformatics analysis and identified a total of 23 candidate PaSWEETs genes in the Potentilla anserina genome, which were randomly distributed on ten different chromosomes. The phylogenetic analysis, chromosomal location, gene structure, specific cis-elements, protein interaction network, and physiological characteristics of these genes were systematically examined. The identified results of the phylogenetic relationship with Arabidopsis thaliana revealed that these PaSWEET genes were divided into four clades (I, II, III, and IV). Moreover, tissue-specific gene expression through quantitative real-time polymerase chain reaction (qRT-PCR) validation exposed that the identified PaSWEETs were differentially expressed in various tissues (roots, stems, leaves, and flowers). Mainly, the relative fold gene expression in swollen and unswollen tubers effectively revealed that PaSWEETs (7, 9, and 12) were highly expressed (300-, 120-, and 100-fold) in swollen tubers. To further elucidate the function of PaSWEETs (7, 9, and 12), their subcellular location was confirmed by inserting them into tobacco leaves, and it was noted that these genes were present on the cell membrane. On the basis of the overall results, it is suggested that PaSWEETs (7, 9, and 12) are the candidate genes involved in swollen tuber formation in P. anserina. In crux, we speculated that our study provides a valuable theoretical base for further in-depth function analysis of the PaSWEET gene family and their role in tuber development and further enhancing the molecular breeding of Potentilla anserina.

Sensing potential of C6N8 for ammonia (NH3) and nitrogen triflouride (NF3): A DFT study.

The detection of toxic gases (NH3 and NF3) in regulating and monitoring air quality in the atmosphere has drawn a lot of attention. Herein, we explored a novel material (C6N8) for the detection of the important but toxic gases (NH3 and NF3). We investigated the interactions of the NH3 and NF3 with C6N8 through DFT at B3LYP, ωB97XD, and non-DFT M06-2X. Counterpoise interaction energy values (Eint. cp.) of NH3@C6N8 and NF3@C6N8 are -0.45 eV and -3.51 eV (for B3LYP), -0.42 eV and 2.11 eV (for ωB97XD) and -0.44 eV and -3.41eV (for M06-2X), respectively. Complexes having the most stable configurations were then subjected to further analyses including frontier molecular orbitals, H-L gap, and conductivity of complexes. An increase in the H-L gap in complexes (NH3@C6N8 and NF3@C6N8) is observed. The conductivity of NH3@C6N8 and NF3@C6N8 decreases as compared to C6N8. A considerable change in dipole moment was seen in C6N8 before and after complex formation. This is because of the shifting of charge between C6N8 and gases (NH3 and NF3). CHELPG and NBO charge analysis were used to evaluate the amount of charge transfer between C6N8 and gases. These analyses demonstrate that NH3 and NF3 withdraw electron density from C6N8. It was found that NH3 tends to be physically adsorbed on C6N8 while NF3 adsorbs chemically on C6N8. NCI and QTAIM analyses were performed to investigate the kind of interactions between the surface (C6N8) and gases (NH3 and NF3). Furthermore, the recovery time of NH3@C6N8 and NF3@C6N8 shows that C6N8 can be a better choice for sensing NH3 and NF3 gases.

Comparative analysis of exoscope-assisted spine surgery versus operating microscope: A systematic review.

Background: Limitations in the operative microscope (OM)'s mobility and suboptimal ergonomics created the opportunity for the development of the exoscope. This systematic review aims to evaluate the advantages and disadvantages of exoscopes and OMs in spine surgery. Methods: Following Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines, a systematic search was conducted in the major research databases. All studies evaluating the exoscopes and/or OMs in spinal procedures were included. Results: There were 602 patients included in the 16 studies, with 539 spine surgery patients, 19 vascular cases, 1 neural pathology case, 19 cranial cases, and 24 tumor pathologies. When examining surgical outcomes with the exoscope, results were mixed. Compared to the OM, exoscope usage resulted in longer operative times in 7 studies, comparable times in 3 studies, and shorter operative times in 3 studies. Two studies found similar lengths of stay (LOS) for both tools, two reported longer LOS with exoscopes, and one indicated shorter hospital LOS with exoscopes. One study reported higher exoscope-related blood loss (EBL), but four other studies consistently showed reduced EBL. In terms of image quality, illumination, dynamic range, depth perception, ergonomics and cost-effectiveness, the exoscope was consistently rated superior, while findings across studies were mixed regarding the optical zoom ratio and mean scope adjustment (MSA). The learning curve for exoscope use was consistently reported as shorter in all studies. Conclusion: Exoscopes present a viable alternative to OMs in spine surgery, offering multiple advantages, which supports their promising role in modern neurosurgical practice.

Frailty as a predictor of postoperative outcomes in neurosurgery: a systematic review.

INTRODUCTION: Baseline frailty status has been utilized to predict a wide range of outcomes and guide preoperative decision making in neurosurgery. This systematic review aims to analyze existing literature on the utilization of frailty as a predictor of neurosurgical outcomes. EVIDENCE ACQUISITION: We conducted a systematic review following PRISMA guidelines. Studies that utilized baseline frailty status to predict outcomes after a neurosurgical intervention were included in this systematic review. Studies that utilized sarcopenia as the sole measure of frailty were excluded. PubMed, EMBASE, and Cochrane library was searched from inception to March 1st, 2023, to identify relevant articles. EVIDENCE SYNTHESIS: Overall, 244 studies met the inclusion criteria. The 11-factor modified frailty index (mFI-11) was the most utilized frailty measure (N.=91, 37.2%) followed by the five-factor modified Frailty Index (mFI-5) (N.=80, 32.7%). Spine surgery was the most common subspecialty (N.=131, 53.7%), followed by intracranial tumor resection (N.=57, 23.3%), and post-operative complications were the most reported outcome (N.=130, 53.2%) in neurosurgical frailty studies. The USA and the Bowers author group published the greatest number of articles within the study period (N.=176, 72.1% and N.=37, 15.2%, respectively). CONCLUSIONS: Frailty literature has grown exponentially over the years and has been incorporated into neurosurgical decision making. Although a wide range of frailty indices exist, their utility may vary according to their ability to be incorporated in the outpatient clinical setting.

Current stage of preclinical and clinical development of guggulsterone in cancers: Challenges and promises.

Throughout human history, the utilization of medicinal herbs has been recognized as a crucial defense against various ailments, including cancer. Natural products with potential anticancer properties, capable of inducing apoptosis in cancer cells, have garnered substantial attention. One such agent under investigation is guggulsterone (GS), a phytosterol derived from the gum resin of the Commiphora mukul tree. This review aims to provide a comprehensive summary of recent studies elucidating the anticancer molecular mechanisms and molecular targets of GS, guiding future research and potential applications as an adjuvant drug in cancer therapy. Recent in vivo and in vitro studies have explored the biological activities of the active ingredients in Commiphora mukul. Specifically, GS emerges as a potential cancer chemopreventive and therapeutic agent. The investigations delve into the impact of GS on constitutively activated survival pathways, including Janus kinase/signal transducer and activator of transcription (JAK/STAT), nuclear factor-kappa B (NF-kB), and PI3-kinase/AKT signaling pathways. These pathways regulate antiapoptotic and proinflammatory genes, exerting control over growth and inflammatory responses. The findings highlight the potential of GS in disrupting survival pathways crucial for cancer cell viability. The inhibition of JAK/STAT, NF-kB, and PI3-kinase/AKT signaling pathways positions GS as a promising candidate for cancer therapy. The review synthesizes evidence from diverse studies, underscoring the multifaceted biological activities of GS in cancer prevention and treatment. To advance our understanding, future clinical and translational studies are imperative to determine effective doses in humans. Additionally, there is a need for the development of new pharmaceutical forms of GS to optimize therapeutic effects. This comprehensive review provides a foundation for ongoing research, offering insights into the potential of GS as a valuable addition to the armamentarium against cancer.

Advancements in the treatment of geographic atrophy: focus on pegcetacoplan in age-related macular degeneration.

Geographic atrophy (GA) is a progressive form of age-related macular degeneration characterized by the degeneration of retinal pigment epithelial cells and photoreceptor death. The dysregulation of the complement cascade has been implicated in GA progression. This review provides a comprehensive overview of the pathophysiology of age-related macular degeneration and GA, discusses current therapeutic options, and focuses on the recent breakthrough drug, pegcetacoplan (SYFOVRE). Pegcetacoplan is a complement inhibitor that selectively targets the C3 complement protein, effectively modulating complement activation. Clinical trials, including the OAKS and DERBY studies, have demonstrated the efficacy of SYFOVRE in reducing the growth of GA lesions compared to placebo. The FDA approval of SYFOVRE as the first and only definitive therapy for GA marks a significant milestone in the management of this debilitating condition. The review also explores potential future treatment strategies, including immune-modulating agents and ocular gene therapy. While SYFOVRE offers new hope for GA patients, further research is needed to evaluate its long-term benefits, safety profile, and optimal treatment regimens.

Exploring the Role of Simulation Training in Improving Surgical Skills Among Residents: A Narrative Review.

The role of simulation in medical education is crucial to the development of surgeons' skills. Surgical simulation can be used to improve surgical skills in a secure and risk-free environment. Animal models, simulated patients, virtual reality, and mannequins are some types of surgical simulation. As a result, feedback encourages students to reflect on their strengths and weaknesses, enabling them to focus on improvement. Healthcare simulation is a strong educational instrument, and the main goal of this is to give the students an opportunity to do a practical application of what they have learned through theory. Before taking it to the patients, they will already have certain tools they have previously acquired during the practice. This makes it easier for students to identify the knowledge gaps that they must fill to improve patient outcomes. Moreover, simulation brings a wonderful opportunity for students to acquire skills, gain confidence, and experience success before working with real patients, especially when their clinical exposure is limited. The use of simulation to teach technical skills to surgical trainees has become more prevalent. The cost of setting up a simulation lab ranges from $100,000 to $300,000. There are several ways to evaluate the effectiveness of simulation-based surgical training. Repetitive surgical simulation training can improve speed and fluidity in general surgical skills in comparison to conventional training. Few previous studies compared learners who received structured simulation training to a group of trainees who did not receive any simulation training in single-center randomized control research. Significantly faster and less time-consuming skill proficiency was noticeable in simulated trainees. Despite being anxious in the operating room for the first time, simulated trainees completed the surgery on time, demonstrating the effectiveness of surgical simulation training. Traditional surgical training involves senior-surgeon supervision in the operating room. In simulation-based training, the trainees have full control over clinical scenarios and settings; however, guidance and assessment are also crucial. Simulators allow users to practice tasks under conditions resembling real-life scenarios. Simulators can be compared with traditional surgical training methods for different reasons. For example, intraoperative bleeding may occasionally show up not only visibly on the screen but also by shaking the trocars erratically. Without haptics, training on virtual simulators can cause one's pulling and pushing forces, which are frequently greater than what the tissue needs, to be distorted. A good method of simulation training is using virtual reality simulators with haptics and simulated patients. The availability of these facilities is limited, though, and a typical session might include an exercise involving stacking sugar cubes and box trainers. The degree of expertise or competency is one area that needs clarification as medical education transitions to a competency-based paradigm. The article aims to provide an overview of simulation, methods of simulation training, and the key role and importance of surgical simulation in improving skills in surgical residents.

Use of National Institute for Health and Care Excellence head injury guidelines among patients with delayed presentation after head trauma can lead to missed traumatic brain injury: a 5-year institutional review.

Introduction: In 2014, traumatic brain injury (TBI) caused 3 million ER visits, hospitalizations, and deaths in the US. The National Institute for Health and Care Excellence (NICE) guidelines, initially generated using data from patients presenting within 24 h of head trauma, are used to determine the need for head computed tomography (CT) scan in patients after 24 h. The authors wanted to determine the proportion of CT scans for head trauma performed at our center in late presenters (>24 h after head trauma), the incidence of intracranial pathology in early (24 h) versus late (>24 h) presenters, and the sensitivity of the NICE guidelines for TBI in these two subpopulations. Methods: A retrospective chart review was conducted at a tertiary care center in Karachi. All people (>16) who had a head CT for head trauma from 2010 to 2015 were included. Age, sex, primary diagnosis, comorbid disorders, mechanism-of-injury, duration (in hours) from head trauma to presentation, site, and extent of injury (injury severity scale), hospital stay, number and details of surgical procedures, CT scan findings, other injuries, and mortality were recorded. Means were compared using the Independent Sample t-test, while categorical variables were compared using χ2. Multivariate logistic regression analyses were used to identify TBI predictors. Results: The authors found 2009 eligible patients; seven were excluded due to incomplete medical records. The final statistical analysis comprised 2002 head trauma patients. Overall, 52% of early and late presenters had severe injuries, and 2.3% died. 32.2% of patients with head trauma had CT after 24 h. Early presenters were 46.7% traumatized, while late presenters were 63%. The NICE guidelines were 93% sensitive for early presenters and 83% for late presenters with traumatic intracranial injury. Conclusion: Patients coming to the emergency department after 24 h of head trauma are a large proportion of the overall head trauma population. The NICE guidelines for late-presenting head injuries are less sensitive and may overlook intracranial injuries if imaging is not performed.

A Narrative Review of Breastfeeding and Its Correlation With Breast Cancer: Current Understanding and Outcomes.

Breastfeeding has been extensively studied in relation to breast cancer risk. The results of the reviewed studies consistently show a decreased risk of breast cancer associated with breastfeeding, especially for 12 months or longer. This protective effect is attributed to hormonal, immunological, and physiological changes during lactation. Breastfeeding also appears to have a greater impact on reducing breast cancer risk in premenopausal women and specific breast cancer subtypes. Encouraging breastfeeding has dual benefits: benefiting infants and reducing breast cancer risk long-term. Healthcare professionals should provide evidence-based guidance on breastfeeding initiation, duration, and exclusivity, while public health policies should support breastfeeding by creating enabling environments. This review examines the existing literature and analyzes the correlation between breastfeeding and breast cancer risk.

Differential regulation of hippocampal transcriptome by circulating estrogen.

Estrogen (E2) modulates the synaptic structure and plasticity in the hippocampus. Previous studies showed that E2 fluctuations during various phases of the menstrual cycle produce subtle neurosynaptic changes that impact women's behavior, emotion, and cognitive functions. In this study, we explored the transcriptome of the hippocampus via RNA-seq (RNA-sequencing) between proestrus (PE) and diestrus (DE) stages in young female rats to determine the effect of E2 of PE and DE stages on hippocampal gene expression. We identified 238 genes (at 1.5-fold-change selection criteria, FDR adjusted p-value < 0.05) as differentially expressed genes (DEGs) that responded to E2 between PE and DE stages. Functional analysis based on Gene Ontology (GO) revealed that a higher E2 level corresponded to an increase in gene transcription among most of the DEGs, suggesting biological mechanisms operating differentially in the hippocampus of female rats between PE and DE stages in the estrus cycle; while analysis with Kyoto Encyclopedia of Genes and Genomes database (KEGG) found that the DEGs involving neuroactive ligand-receptor interaction, antigen processing, cell adhesion molecules, and presentation were upregulated in PE stage, whereas DEGs in pathways relating to bile secretion, coagulation cascades, osteoclast differentiation, cysteine and methionine metabolism were upregulated in DE stage of the estrus cycle. The high-fold expression of DEGs was confirmed by a follow-up quantitative real-time PCR. Our findings in this current study have provided fundamental information for further dissection of neuro-molecular mechanisms in the hippocampus in response to E2 fluctuation and its relationship with disorders.

A quantum mechanical investigation of nanocone oxide as a drug carrier for zidovudine: AIDS drug.

Traditionally, nanocones as a drug delivery material allow controlled drug delivery close to the target area while reducing the toxicity and generic accumulation associated with traditional intravenous injection methods. In the current study, density functional theory (DFT) is employed to investigate the therapeutic potential of carbon nanocone oxide (ONC) as a carrier with zidovudine drug for the treatment of human immunodeficiency virus (HIV). The electronic ground state and excited state were studied to evaluate the drug carrier potential of ONC and Zidovudine-ONC complex. The Frontier Molecular Orbitals (FMOs) and Molecular Electrostatic Potential (MEPs) revealed that the ONC carrier acts as a donor and zidovudine as an acceptor. The FMOs confirmed the interaction between drug and carrier stabilization energy by calculating chemical hardness, material softness, electronegativity, Ionization energy and electron affinity. The natural bond analysis (NBO), non-covalent interaction (NCI) and electron localization function (ELF) revealed the charge transfer between zidovudine and ONC. The density of state (DOS) and Charge Deposition analysis (CDA) provided the charge transfer. To study the excited state of zidovudine, transition density matrix (TDM), UV(Ultra-visible), IR (infrared), Raman, and NMR (Nuclear Magnetic Resonance) spectra of ONC and zidovudine-ONC complex have been plotted. The spectra showed a significant red shift in the zidovudine-ONC complex. Photoinduced electron studies (PET) showed fluorescence quenching because of the interaction between the drug and the carrier and provided a graphical explanation of the distinct excited state. All the results show that the ONC carrier has therapeutic potential as a zidovudine carrier for the treatment of Human Immunodeficiency Virus (HIV).

X-Linked Gusher Disease DFNX2 in Children, a Rare Inner Ear Dysplasia with Mixed Hearing and Vestibular Loss.

Conductive hearing losses are typically present in disorders of the external/middle ear. However, there is a rare group of inner ear conditions called third windows that can also generate a conductive hearing loss. This is due to an abnormal connection between the middle and the inner ear or between the inner ear and the cranial cavity. X-linked gusher disorder is an extremely rare congenital inner ear dysplastic syndrome with an abnormal connection due to a characteristic incomplete cochlear partition type III and an incomplete internal auditory meatus fundus. The disorder is inherited in an X-linked fashion due to the mutation of the POU3F4 gene. We present two siblings diagnosed with the condition and their long-term follow-ups. They both presented audiovestibular symptoms and showed progressive mixed losses and bilateral vestibular weakness. They were treated with cochlear implant, digital amplification and with vestibular rehabilitation. Significant others around them were involved in their journey with the medical team, and in both, a very favourable outcome was achieved. This is the first time that we have reported evolving audiovestibular function with vestibular quantification in X-linked gusher disorder and emphasize on the multidisciplinary holistic approach to manage these children effectively.

Negative Chronotropic Cardiovascular Changes in Lumbar Spine Surgery: A Potential Spinal-Cardiac Reflex?

Cardiovascular changes following lumbar spine surgery in a prone position are exceedingly rare. Over the past 20 years, a total of six cases have been published where patients experienced varying degrees of bradycardia, hypotension, and asystole, which could be attributed to intraoperative dural manipulation. As such, there is emerging evidence for a potential neural-mediated spinal-cardiac reflex. The authors report their experience of negative chronotropy during an elective lumbar spine surgery that coincided with dural manipulation and review the available literature. A 34-year-old male presented with a long-standing history of lower back pain recently deteriorating to bilaterally radiating leg pain, with restricted left leg raise, and numbness at the left L5 dermatomal territory. The patient was an athletic police officer with no comorbidities or past medical history. Magnetic resonance imaging lumbosacral spine revealed spinal stenosis most pronounced at L4/L5 and disc bulges at L3/L4 and L5/S1. The patient opted for lumbar decompression surgery. After an unremarkable comprehensive preoperative workup, including cardiac evaluation (electrocardiogram, echocardiogram), the patient was induced general anesthesia in a prone position. A lumbar incision was made from L2 to S1. When the left L4 nerve root was retracted while removing the prolapsed disc at L4/L5, the anesthetist cautioned the surgeon of bradycardia (34 beats per minute [bpm]), and the surgery was immediately stopped. The heart rate improved to 60 bpm within 30 seconds. When the root was later retracted again, a second episode of bradycardia occurred for 4 minutes with heart rate declining to 48 bpm. The surgery was stopped, and after 4 minutes, the anesthetist administered 600 µg of atropine. The heart rate then rose to 73 bpm within 1 minute. Other potential causes for bradycardia were excluded. The total blood loss was estimated to be 100 mL. He remains well at his 6-month follow-up and has returned to work as normal. Akin to previously published cases, each episode of bradycardia coincided with dural manipulation, which may indicate a possible reflex between the spinal dura mater and the cardiovascular system. Such a rare adverse event may occur even in seemingly healthy, young individuals, and anesthetists should caution the operating surgeon of bradycardias to exclude operative manipulation of the dura as the cause. While this phenomenon is only reported in a handful of lumbar spine surgery cases, it provides evidence for a potential spinal-cardiac physiological reflex in the lumbar spine that may be neural mediated and should be investigated further.