Folate fortification for spina bifida: preventing neural tube defects.

Neural tube defects (NTDs), such as spina bifida and anencephaly, are severe congenital anomalies affecting the development of the brain and spine. These conditions are often linked to folic acid deficiency during early pregnancy, a modifiable risk factor. While high-income countries have implemented mandatory folic acid fortification in staple foods, resulting in significant reductions in NTD prevalence, low- and middle-income countries (LMICs) continue to experience disproportionately high rates of these birth defects. Folic acid supplementation and fortification are proven interventions for preventing NTDs, but many LMICs face political, financial, and logistical barriers to implementing these programs. This paper highlights the importance of mandatory folic acid fortification as a cost-effective public health intervention and advocates for its expansion in LMICs. It reviews the successes of fortification programs in high-income countries, explores alternative food vehicles like rice for regions with different dietary staples, and discusses the potential of multi-nutrient fortification strategies. Additionally, this paper emphasizes the need for global collaboration, enhanced monitoring and evaluation, and public health education campaigns to ensure that women of reproductive age, especially in LMICs, receive adequate folic acid. By addressing these challenges, the global health community can significantly reduce the incidence of NTDs, improve maternal and child health, and promote health equity worldwide. The time to act is now, as the benefits of folic acid fortification far outweigh the costs of inaction.

Rathke's cleft cysts: from pathophysiology to management.

Rathke's cleft cysts (RCCs) are benign, non-neoplastic lesions located in the sellar and suprasellar regions of the brain, originating from remnants of Rathke's pouch, an embryonic precursor to the anterior pituitary gland. Although RCCs are frequently asymptomatic and discovered incidentally during imaging studies, they can present with a variety of symptoms, including headaches, visual disturbances, and endocrine dysfunction due to the compression of adjacent neural structures. The management of RCCs is particularly challenging, as the decision to pursue conservative monitoring or surgical intervention depends heavily on the cyst's size, growth potential, and the severity of symptoms. Transsphenoidal surgery is the primary treatment for symptomatic RCCs, offering effective relief from symptoms through decompression of the cyst. However, recurrence remains a significant issue, with rates reported up to 33%, prompting debates about the extent of cyst wall removal during surgery. Recent advancements in minimally invasive endoscopic techniques have improved surgical outcomes, yet the risk of postoperative complications such as hypopituitarism and cerebrospinal fluid leaks persists. Additionally, stereotactic radiosurgery has emerged as a potential alternative for patients with recurrent RCCs or those who are not suitable candidates for repeat surgery. Despite its promise, the long-term safety and efficacy of radiotherapy in RCC management require further investigation. This narrative review aims to provide a comprehensive overview of RCCs, integrating the latest research and clinical guidelines to discuss pathophysiology, clinical presentation, and management strategies, emphasizing the need for a personalized approach to treating this complex condition.

Arachnoid cysts and epilepsy: seizures and epileptogenesis.

Arachnoid cysts are sacs within the arachnoid membrane, filled with cerebrospinal fluid, and overwhelmingly asymptomatic; however, they can also lead to neurological symptoms such as epilepsy. The dependence of AC on epilepsy has been a subject of controversy because of studies with mixed results on whether AC contributes to seizure activity. This is a narrative review for the synthesis of available present research on the pathophysiological mechanisms of epilepsy, clinical presentation, and treatment options in patients with epilepsy and ACs. Some find no impactful association between ACs and seizures, while others point out the probable role of ACs in Epileptogenesis. Endoscopic fenestration and similar surgical interventions were found quite effective at reducing the frequency of seizures for selected patients, although not all of them achieve complete seizure control. Such a decision needs to be tailored on the basis of considerations such as localization and size of cysts and general health conditions. Future research should investigate the genetic and molecular basis of ACs and, based on large prospective long-term studies, define the AC-epilepsy relationship and refine treatment strategies in affected individuals.

Vein of galen malformations: for patients and caregivers.

Vein of Galen malformations (VOGMs), also known as Vein of Galen Aneurysmal Malformations (VGAMs), are rare and complex cerebrovascular anomalies that pose significant diagnostic and therapeutic challenges. These malformations result from abnormal arteriovenous shunts during embryonic development, leading to a range of severe clinical manifestations, including high-output cardiac failure and hydrocephalus. Advances in prenatal imaging, particularly fetal MRI, have improved early detection, allowing for timely intervention. Endovascular techniques, especially transarterial embolization, have become the primary treatment modality, often preferred over surgical approaches due to their effectiveness and lower risk. However, challenges remain, particularly in managing these malformations in neonates and infants, where the risk of complications is high. Gamma Knife radiosurgery offers a non-invasive alternative for select cases, though its effects are gradual and may carry delayed risks. Despite advancements, the management of VOGMs continues to require a multidisciplinary approach, with ongoing research focused on improving outcomes through a better understanding of the genetic and molecular underpinnings of the disease. Future directions include the integration of genetic studies into clinical practice and the refinement of treatment strategies to optimize outcomes for this complex condition.

A call for clinical trials in glioblastoma multiforme for interleukin 4, interleukin 6, interleukin 13 and CD40.

Glioblastoma multiforme (GBM) is one of the most aggressive and deadly forms of brain cancer, which has a very complex tumor microenvironment (TME) promoting tumor growth, immune evasion, and resistance to therapy. The main players within this environment are represented by cytokines such as Interleukin-4, Interleukin-6, and Interleukin-13, along with the costimulatory molecule CD40. The paper draws back the curtain on the complex interactions played out by these molecules in contributing to the formation of a TME within GBM. IL-4 and IL-13 induce an immunosuppressive environment through the polarization of tumor-associated macrophages (TAMs) into a pro-tumoral M2 phenotype. In contrast, IL-6 takes part in the activation of the JAK-STAT3 pathway, enhancing survival and proliferation of tumor cells. In this context, CD40 either induces anti-tumor immunity through APC activation or facilitates tumors by angiogenesis and survival pathways. The synergistic actions of these molecules create feedback loops that keep up the malignancy of GBM and present a big problem for therapy. Knowledge of these interactions opens new ways for the development of multi-targeted therapeutic strategies at the other end. This may result in the interruption of the tumor-supportive environment in GBM, reducing tumor growth and improving patient outcomes by targeting IL-4, IL-6, IL-13, and CD40 simultaneously.

Ethics of deep brain stimulation for neuropsychiatric disorders.

Deep Brain Stimulation (DBS) has emerged as a revolutionary neurosurgical technique with significant implications for the treatment of various neuropsychiatric disorders. Initially developed for movement disorders like Parkinson's disease, DBS has expanded to psychiatric conditions such as obsessive-compulsive disorder, depression, anorexia nervosa, dystonia, essential tremor, and Tourette's syndrome. This paper explores the clinical efficacy and ethical considerations of DBS in treating these disorders. While DBS has shown substantial promise in alleviating symptoms and improving quality of life, it raises ethical challenges, including issues of informed consent, patient selection, long-term management, and equitable access to treatment. The irreversible nature of DBS, potential adverse effects, and the high cost of the procedure necessitate a rigorous ethical framework to guide its application. The ongoing evolution of neuromodulation requires continuous ethical analysis and the development of guidelines to ensure that DBS is used responsibly and equitably across different patient populations. This paper underscores the need for a balanced approach that integrates clinical efficacy with ethical considerations to optimize patient outcomes and ensure sustainable practice.

Rapid Tetra-Primer Amplification Refractory Mutation System-Polymerase Chain Reaction Protocol for Detection of Y132F Mutation in Fluconazole Resistant Candida parapsilosis.

There is an emerging fluconazole resistance in Candida parapsilosis in recent years. The leading mechanism causing azole resistance in C. parapsilosis is the Y132F codon alteration in the ERG11 gene which encodes the target enzyme of azole drugs. In this study, we evaluated the sensitivity, compatibility, and specificity of a novel tetra-primer amplification refractory mutation system-polymerase chain reaction (T-ARMS-PCR) method for rapid detection of the Y132F mutation in fluconazole nonsusceptible C. parapsilosis. Antifungal susceptibility tests for detection of fluconazole resistance were performed by broth microdilution according to the CLSI guidelines. All susceptible and nonsusceptible C. parapsilosis isolates were analyzed for ERG11 mutations with Sanger sequencing. T-ARMS-PCR was fully concordant with the Sanger sequencing (100% of sensitivity and specificity) for detection of Y132F mutations. T-ARMS-PCR method could be a rapid, simple, accurate, and economical assay in the early detection of the most common cause of fluconazole resistance in C. parapsilosis isolates. In routine laboratories with high C. parapsilosis isolation rates, performing the T-ARMS-PCR for early detection of the most common reason of fluconazole resistance in C. parapsilosis, could be a life-saving approach for directing antifungal therapy before obtaining the definitive antifungal susceptibility tests results.

COVID-19-associated mucormycosis: a systematic review and meta-analysis of 958 cases.

BACKGROUND: Mucormycosis, a rare fungal infection, has shown an increase in the number of reported cases during the COVID-19 pandemic. OBJECTIVES: To provide a comprehensive insight into the characteristics of COVID-19-associated mucormycosis, through a systematic review and meta-analysis. METHODS OF DATA SYNTHESIS: Demographic information and clinical features were documented for each patient. Logistic regression analysis was used to predict the risk of mortality. DATA SOURCES: PubMed, Scopus, Web of Science, Cochrane, CINAHL, Ovid MEDLINE, and FungiSCOPE. STUDY ELIGIBILITY CRITERIA: Studies reporting individual-level information in patients with adult COVID-19-associated mucormycosis (CAM) between 1 January 2020 and 28 December 2022. PARTICIPANTS: Adults who developed mucormycosis during or after COVID-19. INTERVENTIONS: Patients with and without individual clinical variables were compared. ASSESSMENT OF RISK OF BIAS: Quality assessment was performed based on the National Institutes of Health quality assessment tool for case series studies. RESULTS: Nine hundred fifty-eight individual cases reported from 45 countries were eligible. 88.1% (844/958) were reported from low- or middle-income countries. Corticosteroid use for COVID-19 (78.5%, 619/789) and diabetes (77.9%, 738/948) were common. Diabetic ketoacidosis (p < 0.001), history of malignancy (p < 0.001), underlying pulmonary (p 0.017), or renal disease (p < 0.001), obesity (p < 0.001), hypertension (p 0.040), age (>65 years) (p 0.001), Aspergillus coinfection (p 0.037), and tocilizumab use during COVID-19 (p 0.018) increased the mortality. CAM occurred on an average of 22 days after COVID-19 and 8 days after hospitalization. Diagnosis of mucormycosis in patients with Aspergillus coinfection and pulmonary mucormycosis was made on average 15.4 days (range, 0-35 days) and 14.0 days (range, 0-53 days) after hospitalization, respectively. Cutaneous mucormycosis accounted for <1% of the cases. The overall mortality rate was 38.9% (303/780). CONCLUSION: Mortality of CAM was high, and most reports were from low- or middle-income countries. We detected novel risk factors for CAM, such as older age, specific comorbidities, Aspergillus coinfection, and tocilizumab use, in addition to the previously identified factors.

Investigation of the computer experiences and attitudes of pre-service mathematics teachers: new evidence from Turkey.

This study aimed to investigate the experiences of pre-service mathematics (PSM) teachers with computers and their attitudes toward them. The Computer Attitude Scale, Computer Competency Survey, and Computer Use Information Form were administered to 180 Turkish PSM teachers. Results revealed that most PSM teachers used computers at home and at Internet cafes, and that their competency was generally intermediate and upper level. The study concludes that PSM teachers' attitudes about computers differ according to their years of study, computer ownership, level of computer competency, frequency of computer use, computer experience, and whether they had attended a computer-aided instruction course. However, computer attitudes were not affected by gender.