Corrigendum: Modeling the volume of tissue activated in deep brain stimulation and its clinical influence: a review.

[This corrects the article DOI: 10.3389/fnhum.2024.1333183.].

A Case of Crigler-Najjar Syndrome Type II During Pregnancy and Its Management.

Crigler-Najjar syndrome (CNS) is a genetic syndrome that results in increased levels of unconjugated bilirubin due to less or completely nonfunctional enzyme, uridine diphosphoglucoronyltransferase (UDPGT) in hepatocytes. When bilirubin metabolism is compromised, hyperbilirubinemia is caused, which results in increased levels of unconjugated and conjugated bilirubin in the bloodstream. CNS is an autosomal recessive disorder, usually noticeable as people get older. This disorder is divided into two types: CNS type I and CNS type II, which are caused by homozygous or compound heterozygous mutations in the UDP glucuronosyltransferase family 1 member A1 (UGT1A1) gene. The disorder affects all races and genders equally, with a prevalence of one per million births. CNS type I is more severe and has almost undetectable UDPGT expression activity, and affected individuals die before one year of age. Consanguineous marriages are a major risk factor as CNS is inherited in an autosomal recessive manner. Being rare, maternal CNS type II is yet to be completely understood in terms of its impact on the mother, her pregnancy, and the infant. We aim to present a case of a pregnant female with CNS type II and its clinical course. She was monitored closely during her pregnancy. The treatment protocol was followed as per previously reported cases and was managed on low, non-teratogenic doses of phenobarbitone. A successful outcome with the birth of a healthy infant having normal neurological development till six months follow-up was observed.

Modeling the volume of tissue activated in deep brain stimulation and its clinical influence: a review.

Deep brain stimulation (DBS) is a neuromodulatory therapy that has been FDA approved for the treatment of various disorders, including but not limited to, movement disorders (e.g., Parkinson's disease and essential tremor), epilepsy, and obsessive-compulsive disorder. Computational methods for estimating the volume of tissue activated (VTA), coupled with brain imaging techniques, form the basis of models that are being generated from retrospective clinical studies for predicting DBS patient outcomes. For instance, VTA models are used to generate target-and network-based probabilistic stimulation maps that play a crucial role in predicting DBS treatment outcomes. This review defines the methods for calculation of tissue activation (or modulation) including ones that use heuristic and clinically derived estimates and more computationally involved ones that rely on finite-element methods and biophysical axon models. We define model parameters and provide a comparison of commercial, open-source, and academic simulation platforms available for integrated neuroimaging and neural activation prediction. In addition, we review clinical studies that use these modeling methods as a function of disease. By describing the tissue-activation modeling methods and highlighting their application in clinical studies, we provide the neural engineering and clinical neuromodulation communities with perspectives that may influence the adoption of modeling methods for future DBS studies.

Revolutionizing Early-Stage Cervical Cancer Treatment: A Comprehensive Review of Radical Trachelectomy as a Minimally Invasive Approach.

This comprehensive review explores the transformative potential of radical trachelectomy as a minimally invasive approach to early-stage cervical cancer treatment. Cervical cancer, a significant global health concern, necessitates innovative strategies for effective intervention, particularly in its early stages. The review begins by providing a background on cervical cancer, emphasizing the pressing need for early-stage treatment options. The focal point is the meticulous examination of radical trachelectomy, a surgical technique that addresses the oncological aspects of treatment and preserves fertility. The conclusion encapsulates vital findings, highlighting this approach's dual benefits and challenges. Furthermore, the implications for clinical practice underscore the paradigm shift that radical trachelectomy brings, urging healthcare professionals to consider its integration into personalized treatment plans. The review concludes with a compelling call to action for further research, emphasizing the importance of refining surgical techniques and fostering interdisciplinary collaboration to ensure the seamless implementation of radical trachelectomy. Overall, this review sets the stage for a transformative shift in the approach to early-stage cervical cancer, presenting radical trachelectomy as a promising frontier in the quest for effective and patient-centered interventions.

Fetal Reduction by Potassium Chloride Infusion in Unruptured Heterotopic Pregnancy: A Comprehensive Review.

This comprehensive review explores the practice of fetal reduction through potassium chloride infusion in unruptured heterotopic pregnancies. Heterotopic pregnancies, characterized by the simultaneous occurrence of intrauterine and extrauterine gestations, present unique challenges in reproductive medicine. The review defines fetal reduction and underscores its significance in mitigating risks associated with heterotopic pregnancies, including the threat of rupture, maternal morbidity, and adverse outcomes. The analysis encompasses the background, methods, efficacy, ethical considerations, and future directions related to the procedure. Findings highlight the efficacy and safety of potassium chloride infusion, emphasizing the importance of proper patient selection and counseling. Implications for clinical practice underscore the procedure's viability in specific cases where the benefits outweigh the associated risks. The review concludes with recommendations for future studies, encouraging further research on procedural techniques, alternative methods, and the psychosocial impact on patients. This work is a foundation for advancing the management of unruptured heterotopic pregnancies, providing insights for clinicians and researchers to improve clinical outcomes and patient care.

Torsion in Uterus: An Obstetrical and Gynaecological Emergency.

Uterine torsion is defined as torsion of the uterus along its longitudinal axis greater than 45 degrees. It is observed in all age groups of the reproductive period, in all parity groups, and at all stages of pregnancy. Torsion from 60 degrees to 720 degrees has been described. It is not possible to clarify why it occurs, but numerous abnormalities have appeared with uterine torsion. It is a rare complication that can result in placental abruption and intrauterine foetal death. Pregnancy, giant fibroids, and ovarian cysts are among the most common causes. Vague clinical attributes make diagnosis challenging pre-operatively and can be missed on routine ultrasound. Being a rare life-threatening condition, it necessitates a high level of concern for diagnosis and prompt intervention to optimise results. This review will help the healthcare worker to understand the various presentation of uterine torsion and their management by appropriately and timely diagnosing it.

Leukodystrophy Imaging: Insights for Diagnostic Dilemmas.

Leukodystrophies, a group of rare demyelinating disorders, mainly affect the CNS. Clinical presentation of different types of leukodystrophies can be nonspecific, and thus, imaging techniques like MRI can be used for a more definitive diagnosis. These diseases are characterized as cerebral lesions with characteristic demyelinating patterns which can be used as differentiating tools. In this review, we talk about these MRI study findings for each leukodystrophy, associated genetics, blood work that can help in differentiation, emerging diagnostics, and a follow-up imaging strategy. The leukodystrophies discussed in this paper include X-linked adrenoleukodystrophy, metachromatic leukodystrophy, Krabbe's disease, Pelizaeus-Merzbacher disease, Alexander's disease, Canavan disease, and Aicardi-Goutières Syndrome.

Unraveling the Predictive Power: Placenta Growth Factor and Pregnancy-Associated Plasma Protein A in Pre-eclampsia.

This review provides a comprehensive exploration of the roles of placenta growth factor (PlGF) and pregnancy-associated plasma protein A (PAPP-A) in the context of pre-eclampsia, a pregnancy-related hypertensive disorder with significant implications for maternal and fetal health. The background elucidates the clinical significance of pre-eclampsia, highlighting its prevalence and impact. The review delves into the biological importance of PlGF and PAPP-A, emphasizing their critical roles in normal placental development and their dysregulation in pre-eclampsia. Notably, altered levels of these biomarkers emerge as potential diagnostic indicators, offering insights into the pathophysiology of the disorder. The exploration of pathophysiological mechanisms, including angiogenic imbalance and placental dysfunction, provides a nuanced understanding of pre-eclampsia's molecular landscape. The therapeutic implications of targeting PlGF and PAPP-A open avenues for future research, aiming at effective intervention strategies. The conclusion summarizes key findings, outlines implications for future research, and underscores the crucial role of PlGF and PAPP-A in understanding and managing pre-eclampsia, with the ultimate goal of improving outcomes for both mothers and infants.

Immature Teratoma: A Case Report of a Monster Tumor in the Pediatric Age Group.

Immature teratoma is a rare type of germ cell tumor containing embryonic tissues that may be malignant. It usually occurs in young women and affects the ovaries. Teratomas exhibit benign clinical behavior, but they can return as teratomas or with malignant components, and in a small subset of individuals, the prognosis may be deadly. We will discuss a case of a 9-year-old female child who presented with pain and a huge lump in the lower abdomen that was suggestive of an ovarian dermoid cyst or a germ cell tumor on computed tomography (CT) abdomen pelvis and underwent exploratory laparotomy and debulking surgery. Histopathology results indicated that she had a grade 3 immature teratoma. Postoperatively, the patient received 3 cycles of bleomycin, etoposide, and cisplatin (BEP) as adjuvant chemotherapy with a good response. She is currently under regular follow-up and has no evidence of recurrence or metastasis. This case illustrates the importance of early diagnosis and treatment of immature teratoma, which can be cured with surgery and chemotherapy. It also highlights the challenges of managing such a large tumor in a pediatric patient.

Placental Abruption Complicated by the Couvelaire Uterus: A High-Risk Obstetric Case at 30 Weeks Gestation.

Placental abruption, a rare but life-threatening obstetric emergency, presents substantial risks to maternal and fetal well-being. This case report documents the clinical journey of a 35-year-old woman with multiple risk factors who presented at 30 weeks gestation with symptoms suggestive of placental abruption, including colicky lower abdominal pain and vaginal bleeding. Notably, her late initiation of prenatal care and a history of pregnancy-induced hypertension added complexity to the clinical picture. The case revealed a Couvelaire uterus, an uncommon and challenging complication of placental abruption, further emphasizing the need for early recognition and swift intervention. A multidisciplinary approach played a pivotal role in managing this high-risk obstetric case. Imaging and laboratory tests facilitated diagnosis and assessment, guiding surgical intervention and post-operative care. Despite the severity of the condition, the patient experienced a positive outcome for herself and her fetus, highlighting the critical importance of timely and comprehensive medical care. This case report contributes to medical knowledge by shedding light on the rare Couvelaire uterus. It underscores the significance of early diagnosis, coordinated healthcare teams, and patient education in mitigating risks associated with placental abruption. Ultimately, it reinforces the vital role of healthcare providers in safeguarding the lives of expectant mothers and their infants in obstetric emergencies.

Radiotherapy Versus Chemotherapy in Locally Advanced Cervical Cancer.

Eighty percent of women who have cervical cancer present at such an alarmingly advanced stage leading to high morbidity and mortality. Due to a lack of public awareness and inadequate infrastructure for screening and early identification in resource-poor countries like India, this tardy presentation is anticipated to continue in the future. Standard management for locally advanced squamous cell cervical cancer is radiotherapy. To increase responses and survival, neoadjuvant chemotherapy (NACT) was introduced to the arsenal. Recent studies from India have shown encouraging results for women getting concomitant chemo-radiation for locally advanced cervical cancer. However, toxicities are still a major problem. The approximated five-year actuarial survival rate with NACT is roughly 45% (95% confidence interval, 37-53%) with a median survival rate of 56 months. Compared to radiotherapy alone, patients receiving chemo-radiation are said to have a considerably better survival rate. Vomiting and nausea are the adverse effects that occur most frequently. Renal dysfunction and myelosuppression can also happen. However, there is evidence of effective tumor control. We will talk about a 55-year-old, para 5 elderly lady who had white discharge coming from her vagina and a cervical mass that bled when touched. She underwent NACT for six weekly cycles, followed by definitive chemo-radiation, and she responded favorably to this management strategy, indicating that the addition of chemotherapy is yet another cause for optimism in the management of cancer of the cervix.

Precision medicine in neurosurgery: The evolving role of theranostics.

Theranostics in neurosurgery is a rapidly advancing field of precision medicine that combines diagnostic and therapeutic modalities to optimize patient outcomes. This approach has the potential to provide real-time feedback during therapy and diagnose a condition while simultaneously providing treatment. One such form of theranostics is focused ultrasound, which has been found to be effective in inducing neuroablation and neuromodulation and improving the efficacy of chemotherapy drugs by disrupting the blood-brain barrier. Targeted radionuclide therapy, which pairs positron emission tomography tracers with therapeutic effects and imaging modalities, is another promising form of theranostics for neurosurgery. Automated pathology analysis is yet another form of theranostics that can provide real-time feedback during the surgical resection of tumors. Electrical stimulation has also shown promise in optimizing therapies for patients with cerebral palsy. Overall, theranostics is a cost-effective way to optimize medical care for patients in neurosurgery. It is a relatively new field, but the advancements made so far show great promise for improving patient outcomes.

Neurostimulation for Spinal Lesions: Enhancing Recovery and Axonal Regeneration.

Spinal neurostimulation is a promising approach for treating spinal lesions and has implications in various neurological disorders. It promotes axonal regeneration and neuronal plasticity to reestablish disrupted signal transduction pathways following spinal injuries or degeneration. This paper reviews the current technology and its differing utilities in various types of neurostimulation, including invasive and noninvasive methods. The paper also explores the efficacy of spinal compression and decompression therapy, with a primary focus on degenerative spinal disorders. Moreover, the potential of spinal neurostimulation in therapies for motor disorders, such as Parkinson's disease and demyelinating disorders, is discussed. Finally, the paper examines the changing guidelines of use for spinal neurostimulation following surgical tumor resection. The review suggests that spinal neurostimulation is a promising therapy for axonal regeneration in spinal lesions. This paper concludes that future research should focus on the long-term effects and safety of these existing technologies, optimizing the use of spinal neurostimulation to enhance recovery and exploring its potential for other neurological disorders.

Ligand-Gated Ion Channels: Prognostic and Therapeutic Implications for Gliomas.

Gliomas are common primary brain malignancies that remain difficult to treat due to their overall aggressiveness and heterogeneity. Although a variety of therapeutic strategies have been employed for the treatment of gliomas, there is increasing evidence that suggests ligand-gated ion channels (LGICs) can serve as a valuable biomarker and diagnostic tool in the pathogenesis of gliomas. Various LGICs, including P2X, SYT16, and PANX2, have the potential to become altered in the pathogenesis of glioma, which can disrupt the homeostatic activity of neurons, microglia, and astrocytes, further exacerbating the symptoms and progression of glioma. Consequently, LGICs, including purinoceptors, glutamate-gated receptors, and Cys-loop receptors, have been targeted in clinical trials for their potential therapeutic benefit in the diagnosis and treatment of gliomas. In this review, we discuss the role of LGICs in the pathogenesis of glioma, including genetic factors and the effect of altered LGIC activity on the biological functioning of neuronal cells. Additionally, we discuss current and emerging investigations regarding the use of LGICs as a clinical target and potential therapeutic for gliomas.

CSF Dynamics: Implications for Hydrocephalus and Glymphatic Clearance.

Beyond its neuroprotective role, CSF functions to rid the brain of toxic waste products through glymphatic clearance. Disturbances in the circulation of CSF and glymphatic exchange are common among those experiencing HCP syndrome, which often results from SAH. Normally, the secretion of CSF follows a two-step process, including filtration of plasma followed by the introduction of ions, bicarbonate, and water. Arachnoid granulations are the main site of CSF absorption, although there are other influencing factors that affect this process. The pathway through which CSF is through to flow is from its site of secretion, at the choroid plexus, to its site of absorption. However, the CSF flow dynamics are influenced by the cardiovascular system and interactions between CSF and CNS anatomy. One, two, and three-dimensional models are currently methods researchers use to predict and describe CSF flow, both under normal and pathological conditions. They are, however, not without their limitations. "Rest-of-body" models, which consider whole-body compartments, may be more effective for understanding the disruption to CSF flow due to hemorrhages and hydrocephalus. Specifically, SAH is thought to prevent CSF flow into the basal cistern and paravascular spaces. It is also more subject to backflow, caused by the presence of coagulation cascade products. In regard to the fluid dynamics of CSF, scar tissue, red blood cells, and protein content resulting from SAH may contribute to increased viscosity, decreased vessel diameter, and increased vessel resistance. Outside of its direct influence on CSF flow, SAH may result in one or both forms of hydrocephalus, including noncommunicating (obstructive) and communicating (nonobstructive) HCP. Imaging modalities such as PC-MRI, Time-SLIP, and CFD model, a mathematical model relying on PC-MRI data, are commonly used to better understand CSF flow. While PC-MRI utilizes phase shift data to ultimately determine CSF speed and flow, Time-SLIP compares signals generated by CSF to background signals to characterizes complex fluid dynamics. Currently, there are gaps in sufficient CSF flow models and imaging modalities. A prospective area of study includes generation of models that consider "rest-of-body" compartments and elements like arterial pulse waves, respiratory waves, posture, and jugular venous posture. Going forward, imaging modalities should work to focus more on patients in nature in order to appropriately assess how CSF flow is disrupted in SAH and HCP.

Identifying Underlying Issues Related to the Inactive Excipients of Transfersomes based Drug Delivery System.

Transfersomes are bilayer vesicles composed of phospholipid and edge activators, which are mostly surfactant. Transfersomes based drug delivery system has gained a lot of interest of the pharmaceutical researchers for their ability to improve drug penetration and permeation through the skin. Transdermal drug delivery via transfersomes has the potential to overcome the challenge of low systemic availability. However, this complex vesicular system has different issues to consider for developing a successful transdermal delivery system. One of the major ingredients, phospholipid, has versatile sources and variable effect on the vesicle size and drug entrapment in transfersomes. The other one, termed as edge activators or surfactant, has some crucial consideration of skin damage and toxicity depending upon its type and concentration. A complex interaction between type and concentration of phospholipid and surfactant was observed, which affect the physicochemical properties of transfersomes. This review focuses on the practical factors related to these two major ingredients, such as phospholipid and surfactant. The origin, purity, desired concentration, the susceptibility of degradation, etc. are the important factors for selecting phospholipid. Regarding surfactants, the major aspects are type and desired concentration. A successful development of transfersomes based drug delivery system depends on the proper considerations of these factors and practical aspects.

Filgrastim-Associated Pneumonitis in Cancer Patient Undergoing Hematopoietic Stem Cell (HSC) Mobilization for Autologous-HSC Transplantation.

Filgrastim is a granulocyte-colony stimulating factors (G-CSF) used for multiple indications in cancer patients. We present a case of a 65-year-old man with non-Hodgkin's lymphoma who was undergoing mobilization of hemopoietic stem cells for autologous-hematopoietic stem cell transplantation (auto-HSCT) with filgrastim who developed dyspnea and non-productive cough. Chest imaging showed left lower lobe consolidation, new ground-glass opacities and small right-sided pleural effusion. Bronchoscopy with bronchoalveolar lavage (BAL) and infectious evaluation were completely negative. He was admitted for further evaluation and management. Antibiotics weren't started immediately given the clinical stability, multiple probable causes of fever and the intent of not confounding future thoracentesis results with antibiotic use. Thoracentesis occurred draining serous exudative pleural fluid; with follow-up chest imaging demonstrating no re-accumulation. His symptoms resolved and he was discharged in stable condition. The symptoms were hypothesized to be the probable adverse effects of filgrastim. We suggest close monitoring of pulmonary toxicities while administering this drug to patients to minimize such complications.

Potential of Tribological Properties of Metal Nanomaterials in Biomedical Applications.

Metallic nanomaterials show tremendous applications in biomedical devices due to compatible integration into the most of the biological systems as they are nano- structured. Metallic nanomaterials are capable of mimicking all the three major antioxidant enzymes such as catalase (CAT), peroxidase and oxidase, to control the level of reactive oxygen species (ROS) inside the cell as an alternative strategy over conventional one which has biological toxicity and have several adverse effects, if accumulation takes places during the treatment. This anti-oxidant property of metallic nanomaterials demonstrates as a promising candidate for its biomedical application in disease conditions where the excessive level of ROS causes damage to DNA, lipids and protein in several conditions such as diabetes, cancer and neurodegenerative diseases. Tribology is the study of interacting surfaces in motion and the measurement of properties such as friction, wear-tear and abrasion. While designing nano-scale biomedical devices, the consideration of tribology is particularly important because the high surface area ratio enhances problems with friction and wear-tear which can further affects its function as well as longevity.