Evaluating the potential role of determinants of health on encephalocele patient outcomes - a combined retrospective study and systematic review.

INTRODUCTION: To evaluate the outcomes and demographics of encephalocele patients who were born and received treatment in our neonatal ICU and conduct a PRISMA literature review. METHODS: An Institutional Review Board (IRB)-approved retrospective cohort study was undertaken to investigate the results of treating encephalocele patients at Jackson Memorial Hospital (JMH) from 1998 to 2022. The study focused on assessing outcomes and the impact of maternal socioeconomic factors, such as religion, age, and education, along with the timing of diagnosis, in connection with a systematic review. RESULTS: A total of 20 encephalocele patients were identified (13 females and 7 males), with 15 having available medical records for review. Most of these cases involved occipital encephaloceles (73.3%). Maternal ages at the time of delivery ranged from 15 to 42 years, with a mean age of 27.3 years. The average gestational age at birth was 37 weeks. Ten cases had a prenatal diagnosis documented, occurring between 12 and 24.5 weeks of gestation. Three of the surviving patients had records of prenatal counseling that included discussions about termination. No infections were reported. Among the 15 cases, 11 patients (73.3%) were alive at the last follow-up, with a mean age at follow-up of 4.12 years, ranging from 6 weeks to 15 years post-birth. Hydrocephalus was noted in 26.7%. Only 1 mother had completed high school. Most mothers were either on Medicaid (9 patients) or uninsured (3 patients), with only 3 having commercial insurance. Religious affiliations varied among the mothers, with 14 out of 15 identifying with a particular religion. The systematic review identified 22 articles from various countries, with 11 articles meeting the inclusion criteria for qualitative analysis. These articles revealed potential maternal risk factors for encephaloceles, including low-nutrient diets, inadequate folic acid intake, young maternal age, advanced maternal age, low socioeconomic status, and limited educational attainment. CONCLUSIONS: In the twenty-first century, there is a positive trend in the survival rates of children born with encephalocele. However, maternal factors such as low socioeconomic status and limited educational attainment remain prominent, affecting their ability to access timely prenatal care and impacting follow-up medical care for these children.

The hippocampal code for space in Mongolian gerbils.

Large parts of our knowledge about the physiology of the hippocampus in the intact brain are derived from studies in rats and mice. While many of those findings fit well to the limited data available from humans and primates, there are also marked differences, for example, in hippocampal oscillation frequencies and in the persistence of theta oscillations. To test whether the distinct sensory specializations of the visual and auditory system of primates play a key role in explaining these differences, we recorded basic hippocampal physiological properties in Mongolian gerbils, a rodent species with high visual acuity, and good low-frequency hearing, similar to humans. We found that gerbils show only minor differences to rats regarding hippocampal place field activity, theta properties (frequency, persistence, phase precession, theta compression), and sharp wave ripple events. The only major difference between rats and gerbils was a considerably higher degree of head direction selectivity of gerbil place fields, which may be explained by their visual system being able to better resolve distant cues. Thus, differences in sensory specializations between rodent species only affect hippocampal circuit dynamics to a minor extent, which implies that differences to other mammalian lineages, such as bats and primates, cannot be solely explained by specialization in the auditory or visual system.

Signaling in the Auditory System: Implications in Hair Cell Regeneration and Hearing Function.

Ear is a sensitive organ involved in hearing and balance function. The complex signaling network in the auditory system plays a crucial role in maintaining normal physiological function of the ear. The inner ear comprises a variety of host signaling pathways working in synergy to deliver clear sensory messages. Any disruption, as minor as it can be, has the potential to affect this finely tuned system with temporary or permanent sequelae including vestibular deficits and hearing loss. Mutations linked to auditory symptoms, whether inherited or acquired, are being actively researched for ways to reverse, silence, or suppress them. In this article, we discuss recent advancements in understanding the pathways involved in auditory system signaling, from hair cell development through transmission to cortical centers. Our review discusses Notch and Wnt signaling, cell to cell communication through connexin and pannexin channels, and the detrimental effects of reactive oxygen species on the auditory system. There has been an increased interest in the auditory community to explore the signaling system in the ear for hair cell regeneration. Understanding signaling pathways in the auditory system will pave the way for the novel avenues to regenerate sensory hair cells and restore hearing function. J. Cell. Physiol. 232: 2710-2721, 2017. © 2016 Wiley Periodicals, Inc.

Indispensable Role of Ion Channels and Transporters in the Auditory System.

Ear is a complex system where appropriate ionic composition is essential for maintaining the tissue homeostasis and hearing function. Ion transporters and channels present in the auditory system plays a crucial role in maintaining proper ionic composition in the ear. The extracellular fluid, called endolymph, found in the cochlea of the mammalian inner ear is particularly unique due to its electrochemical properties. At an endocochlear potential of about +80 mV, signaling initiated by acoustic stimuli at the level of the hair cells is dependent on the unusually high potassium (K+ ) concentration of endolymph. There are ion channels and transporters that exists in the ear to ensure that K+ is continually being cycled into the stria media endolymph. This review is focused on the discussion of the molecular and genetic basis of previously and newly recognized ion channels and transporters that support sensory hair cell excitation based on recent knock-in and knock-out studies of these channels. This article also addresses the molecular and genetic defects and the pathophysiology behind Meniere's disease as well as how the dysregulation of these ion transporters can result in severe defects in hearing or even deafness. Understanding the role of ion channels and transporters in the auditory system will facilitate in designing effective treatment modalities against ear disorders including Meniere's disease and hearing loss. J. Cell. Physiol. 232: 743-758, 2017. © 2016 Wiley Periodicals, Inc.

Neurotransmitters: The Critical Modulators Regulating Gut-Brain Axis.

Neurotransmitters, including catecholamines and serotonin, play a crucial role in maintaining homeostasis in the human body. Studies on these neurotransmitters mainly revolved around their role in the "fight or flight" response, transmitting signals across a chemical synapse and modulating blood flow throughout the body. However, recent research has demonstrated that neurotransmitters can play a significant role in the gastrointestinal (GI) physiology. Norepinephrine (NE), epinephrine (E), dopamine (DA), and serotonin have recently been a topic of interest because of their roles in the gut physiology and their potential roles in GI and central nervous system pathophysiology. These neurotransmitters are able to regulate and control not only blood flow, but also affect gut motility, nutrient absorption, GI innate immune system, and the microbiome. Furthermore, in pathological states, such as inflammatory bowel disease (IBD) and Parkinson's disease, the levels of these neurotransmitters are dysregulated, therefore causing a variety of GI symptoms. Research in this field has shown that exogenous manipulation of catecholamine serum concentrations can help in decreasing symptomology and/or disease progression. In this review article, we discuss the current state-of-the-art research and literature regarding the role of neurotransmitters in regulation of normal GI physiology, their impact on several disease processes, and novel work focused on the use of exogenous hormones and/or psychotropic medications to improve disease symptomology. J. Cell. Physiol. 232: 2359-2372, 2017. © 2016 Wiley Periodicals, Inc.

Autologous Fat Injection for Treatment of Velopharyngeal Insufficiency.

BACKGROUND: Management of velopharyngeal insufficiency (VPI) has traditionally involved surgical repair to improve speech. Posterior pharyngeal augmentation using injectable synthetic materials has been advocated. However, outcomes have been equivocal. More recently, autologous fat injection (AFI) has been advocated for correction of mild to moderate VPI. However, long-term efficacy and safety of this procedure remain unsettled. METHODS: A systematic review of the literature was performed. Available studies that reported outcomes of autologous fat velopharyngeal injection for treatment of documented VPI were included. Preclinical animal studies were excluded. Study characteristics, patient demographics, treatment details including fat harvest site, volume injected, and outcome measures were evaluated. RESULTS: Fifteen studies met inclusion criteria, yielding 251 patients who underwent AFI. There was high variability in terms of indications for procedure and reporting of outcomes. Majority of studies required velopharyngeal gap closure of at least 50% in order to undergo AFI. Most common etiology of VPI was secondary to cleft palate. Some studies included patients with velocardiofacial syndromes. Improvements in speech and nasalance were reported in a majority of patients. Major complications were rare. Only 1 patient with graft hypertrophy resulting in obstructive sleep apnea was reported. CONCLUSION: Autologous fat injection offers a minimally invasive approach to the treatment of VPI. Current literature is limited to small noncomparative studies. These appear to suggest efficacy and safety in mild to moderate patients with VPI. Future prospective studies with standardized technique and objective outcomes are required to definitively establish its safety and efficacy, as well as define patient selection criteria.

Molecular Structure and Regulation of P2X Receptors With a Special Emphasis on the Role of P2X2 in the Auditory System.

The P2X purinergic receptors are cation-selective channels gated by extracellular adenosine 5'-triphosphate (ATP). These purinergic receptors are found in virtually all mammalian cell types and facilitate a number of important physiological processes. Within the past few years, the characterization of crystal structures of the zebrafish P2X4 receptor in its closed and open states has provided critical insights into the mechanisms of ligand binding and channel activation. Understanding of this gating mechanism has facilitated to design and interpret new modeling and structure-function experiments to better elucidate how different agonists and antagonists can affect the receptor with differing levels of potency. This review summarizes the current knowledge on the structure, activation, allosteric modulators, function, and location of the different P2X receptors. Moreover, an emphasis on the P2X2 receptors has been placed in respect to its role in the auditory system. In particular, the discovery of three missense mutations in P2X2 receptors could become important areas of study in the field of gene therapy to treat progressive and noise-induced hearing loss. J. Cell. Physiol. 231: 1656-1670, 2016. © 2015 Wiley Periodicals, Inc.

Intricate Functions of Matrix Metalloproteinases in Physiological and Pathological Conditions.

Matrix metalloproteinases (MMPs) are a diverse group of proteolytic enzymes and play an important role in the degradation and remodeling of the extracellular matrix (ECM). In normal physiological conditions, MMPs are usually minimally expressed. Despite their low expression, MMPs have been implicated in many cellular processes ranging from embryological development to apoptosis. The activity of MMPs is controlled at three different stages: (1) transcription; (2) zymogen activation; and (3) inhibition of active forms by tissue inhibitor metalloproteinases (TIMPs). They can collectively degrade any component of ECM and basement membrane, and their excessive activity has been linked to numerous pathologies mainly including, but not limited to, tumor invasion and metastasis. The lack of information about several MMPs and the steady stream of new discoveries suggest that there is much more to be studied in this field. In particular, there is a need for controlling their expression in disease states. Various studies over the past 30 years have found that each MMP has a specific mode of activation, action, and inhibition. Drugs specifically targeting individual MMPs could revolutionize the treatment of a great number of health conditions and tremendously reduce their burden. In this review article, we have summarized the recent advances in understanding the role of MMPs in physiological and pathological conditions. J. Cell. Physiol. 231: 2599-2621, 2016. © 2016 Wiley Periodicals, Inc.

Newer treatment paradigm improves outcomes in the most common neurosurgical disease of the elderly: a literature review of middle meningeal artery embolization for chronic subdural hematoma.

Chronic subdural hematoma (cSDH) is one of the most prevalent neurosurgical diseases, especially in the elderly. Yet, its incidence is predicted to increase further, paralleling the growth of the geriatric population. While surgical evacuation is technically straightforward, it is associated with significant morbidity and mortality. In fact, 30% of patients are expected to have hematoma recurrence and to need repeat surgical evacuation, and 20% of patients are expected to lose independence and require long-term care. A pathophysiology more complex than originally presumed explains the disappointing results observed for decades. At its core, the formation of microcapillaries and anastomotic channels with the middle meningeal artery (MMA) perpetuates a constant cycle resulting in persistence of hematoma. The rationale behind MMA embolization is simple: to stop cSDH at its source. Over the last few years, this "newer" option has been heavily studied. It has shown tremendous potential in decreasing hematoma recurrence and improving neurological outcomes. Whether combined with surgical evacuation or performed as the only treatment, the scientific evidence to its benefits is unequivocal. Here, we aimed to review cSDH in the elderly and discuss its more recent treatment options with an emphasis on MMA embolization.

Industry payments to academic neurosurgeons in 2021: an open payments cross-sectional analysis.

OBJECTIVE: The Open Payments Program (OPP) was a database started in 2013 by the US government to report payments made by the medical device and pharmaceutical industry to physicians. Neurosurgery is a technologically advanced field that relies heavily on the latest innovations for complex treatment of its patient population. This study sought to explore the financial relationship between academic neurosurgeons and the industry. METHODS: OPP data were reviewed for the year 2021 of all faculty neurosurgeons affiliated with a neurosurgery residency program. Trends related to general payments, research payments, associated research funding, ownership and investment interest, name of the companies making payments, monetary amount of payments per company, and number of payments per company were analyzed. RESULTS: Industry payments to 1151 US academic neurosurgeons were reviewed. These neurosurgeons received $121.4 million in payments. Three hundred thirty-two companies made 18,466 payments. The average payment per neurosurgeon was approximately six-fold higher than that of all other physicians. Vascular and spine subspecialties received the highest payments. A higher proportion of research money was allocated to the Pacific division, while all other categories (including total amount) were higher in the Eastern US. Most financial contributions were made by a small number of companies. CONCLUSIONS: Neurosurgery has been rated by many as a field fueled by research, innovation, and technology. In 2021, academic neurosurgeons had a strong relationship with the medical device and pharmaceutical industry as reflected in the OPP data. While the true impact on patient care cannot be directly measured, the advancement of the field relies heavily on these collaborations.

Middle meningeal artery embolization following surgical evacuation of symptomatic chronic subdural hematoma improves outcomes, interim results of a prospective randomized trial.

BACKGROUND: Outcomes after surgical treatment of chronic subdural hematoma (cSDH) remain undesirable in a significant proportion of patients. We aimed to show the role of middle meningeal artery (MMA) embolization and to demonstrate its benefits. METHODS: Thirty-five patients with symptomatic cSDH were enrolled in a prospective randomized trial following evacuation surgery. Participants were randomized to embolization or control group (expectant management following surgical evacuation without embolization). Patients were followed throughout their hospitalization and outpatient follow-ups. The main goals of this planned interim analysis were to assess neurological outcome and resource utilization. RESULTS: The groups were comparable in terms of sex, age and follow-up retention rates. Side(s) of intervention(s) and hematoma size were similar. There was no statistical difference in neurological examination improvement at discharge, but at follow-up, we observed a decline in neurologic exam in the control group (p = 0.03). Control group participants required more re-interventions (p = 0.02) and were followed in clinic and during related readmissions for longer (p = 0.02). The number of imaging studies obtained in relation to the disease management was higher in the control group (p = 0.01). CONCLUSIONS: Our results suggest a beneficial role for the addition of MMA embolization to surgical intervention in the treatment of symptomatic chronic subdural hematoma. Neurological outcomes were significantly better in the embolization group. This contributed to less need for follow-up, re-interventions, and imaging studies.

The Risk of Peripheral Nerve Tumor Biopsy in Suspected Benign Etiologies.

BACKGROUND: Peripheral nerve sheath tumors (PNSTs) are tumors with unique clinical and imaging features that present to a variety of physicians. These lesions are often referred for biopsy, which can put nerve fascicles at risk. Preoperative biopsy may cause distortion of normal anatomic planes, making definitive resection difficult. OBJECTIVE: To evaluate the neurological risks of preoperative biopsy in benign PNSTs. METHODS: Surgical cases collected retrospectively using a prospectively established database of PNSTs treated by a single surgeon between 1997 and 2019. Patients were dichotomized depending on preoperative biopsy. The effects of biopsy were assessed via history and physical examination both pre- and postdefinitive resection. RESULTS: A total of 151 cases were included. Only 23.2% (35) of patients underwent preoperative biopsy, but 42.9% of these experienced new or worsening neurological examination immediately following biopsy. After definitive resection, the rate of neurological deficit was significantly different between the 2 groups with 60% of biopsy patients and 19% of those patients not biopsied experiencing decline in examination (F = 25.72, P < .001). Odds ratio for any postoperative deficit for biopsy was 6.40 (CI [2.8, 14.55], P < .001). Univariate logistic regression of neurological deficit with patient age, sex, tumor type, and biopsy status showed that only biopsy was associated with the occurrence of any postoperative deficit. CONCLUSION: Biopsy of benign PNSTs is associated with a high rate of neurological deficit both immediately following the procedure and after definitive resection. Careful selection is imperative prior to proceeding with biopsy of nerve sheath tumors exhibiting benign features given the unacceptably high rate of neurological decline.

Laser Interstitial Thermal Therapy as a Primary Treatment for Deep Inaccessible Gliomas.

BACKGROUND: Treatment strategies for deep intracranial gliomas remain limited to stereotactic biopsy in many cases due to the morbidity of aggressive surgical resection. Since no cytoreductive therapy is offered, outcomes have been demonstrably poor compared to patients who are able to undergo primary surgical resection. OBJECTIVE: To present our practice, in an effort to reduce morbidity and still offer cytoreductive treatment, of offering the possibility of laser interstitial thermal therapy (LITT) for the primary treatment of intracranial deep gliomas that would be otherwise unamenable for resection. METHODS: From 2010 to 2017, 74 patients were identified from a single surgeon at a single tertiary care referral center who had been treated with LITT. We conducted an exploratory cohort study on patients (n = 6) who have undergone contemporaneous biopsy and laser ablation for the treatment of deep gliomas with a mean tumor volume of 10.9 cc (range 4.2-52 cc). RESULTS: In our cohort, mean extent of ablation (EOA) was 98.5% on postoperative MRI; mean progression-free survival was 14.3 mo, and 5 patients (83%) remained alive at mean follow-up time of 19.7 mo without any complications. Additionally, there was a negative linear relationship between preoperative lesion size and EOA (P < .04) when analyzed with previously reported series. CONCLUSION: Although our series is small, we suggest that LITT can be a safe alternative cytoreductive therapy for deep surgically inaccessible gliomas. Given the known benefit of near gross total resection for high-grade gliomas, we believe LITT may improve survival for these patients and complement adjuvant treatments if patients are appropriately selected.

Otopathogenic Staphylococcus aureus Invades Human Middle Ear Epithelial Cells Primarily through Cholesterol Dependent Pathway.

Chronic suppurative otitis media (CSOM) is one of the most common infectious diseases of the middle ear especially affecting children, leading to delay in language development and communication. Although Staphylococcus aureus is the most common pathogen associated with CSOM, its interaction with middle ear epithelial cells is not well known. In the present study, we observed that otopathogenic S. aureus has the ability to invade human middle ear epithelial cells (HMEECs) in a dose and time dependent manner. Scanning electron microscopy demonstrated time dependent increase in the number of S. aureus on the surface of HMEECs. We observed that otopathogenic S. aureus primarily employs a cholesterol dependent pathway to colonize HMEECs. In agreement with these findings, confocal microscopy showed that S. aureus colocalized with lipid rafts in HMEECs. The results of the present study provide new insights into the pathogenesis of S. aureus induced CSOM. The availability of in vitro cell culture model will pave the way to develop novel effective treatment modalities for CSOM beyond antibiotic therapy.

Recent advancements in nanoparticle based drug delivery for gastrointestinal disorders.

INTRODUCTION: The emergent field of nanoparticles has presented a wealth of opportunities for improving the treatment of human diseases. Recent advances have allowed for promising developments in drug delivery, diagnostics, and therapeutics. Modified delivery systems allow improved drug delivery over traditional pH, microbe, or receptor dependent models, while antibody association allows for more advanced imaging modalities. Nanoparticles have potential clinical application in the field of gastroenterology as they offer several advantages compared to the conventional treatment systems including target drug delivery, enhanced treatment efficacy, and reduced side effects. AREAS COVERED: The aim of this review article is to summarize the recent advancements in developing nanoparticle technologies to treat gastrointestinal diseases. We have covered the application of nanoparticles in various gastrointestinal disorders including inflammatory bowel disease and colorectal cancer. We also have discussed how the gut microbiota affects the nanoparticle based drug delivery in the gastrointestinal tract. EXPERT OPINION: Nanoparticles based drug delivery offers a great platform for targeted drug delivery for gastrointestinal disorders. However, it is influenced by the presence of microbiota, drug interaction with nanoparticles, and cytotoxicity of nanoparticles. With the advancements in nanoparticle technology, it may be possible to overcome these barriers leading to efficient drug delivery for gastrointestinal disorders based on nanoparticle platform.

Recent Advancements in the Regeneration of Auditory Hair Cells and Hearing Restoration.

Neurosensory responses of hearing and balance are mediated by receptors in specialized neuroepithelial sensory cells. Any disruption of the biochemical and molecular pathways that facilitate these responses can result in severe deficits, including hearing loss and vestibular dysfunction. Hearing is affected by both environmental and genetic factors, with impairment of auditory function being the most common neurosensory disorder affecting 1 in 500 newborns, as well as having an impact on the majority of elderly population. Damage to auditory sensory cells is not reversible, and if sufficient damage and cell death have taken place, the resultant deficit may lead to permanent deafness. Cochlear implants are considered to be one of the most successful and consistent treatments for deaf patients, but only offer limited recovery at the expense of loss of residual hearing. Recently there has been an increased interest in the auditory research community to explore the regeneration of mammalian auditory hair cells and restoration of their function. In this review article, we examine a variety of recent therapies, including genetic, stem cell and molecular therapies as well as discussing progress being made in genome editing strategies as applied to the restoration of hearing function.

Zika Virus: An Emerging Global Health Threat.

Zika virus (ZIKV) is an emerging healthcare threat. The presence of the mosquito Aedes species across South and Central America in combination with complementary climates have incited an epidemic of locally transmitted cases of ZIKV infection in Brazil. As one of the most significant current public health concerns in the Americas, ZIKV epidemic has been a cause of alarm due to its known and unknown complications. At this point, there has been a clear association between ZIKV infection and severe clinical manifestations in both adults and neonates, including but not limited to neurological deficits such as Guillain-Barré syndrome (GBS) and microcephaly, respectively. The gravity of the fetal anomalies linked to ZIKV vertical transmission from the mother has prompted a discussion on whether to include ZIKV as a formal member of the TORCH [Toxoplasma gondii, other, rubella virus, cytomegalovirus (CMV), and herpes] family of pathogens known to breach placental barriers and cause congenital disease in the fetus. The mechanisms of these complex phenotypes have yet to be fully described. As such, diagnostic tools are limited and no effective modalities are available to treat ZIKV. This article will review the recent advancements in understanding the pathogenesis of ZIKV infection as well as diagnostic tests available to detect the infection. Due to the increase in incidence of ZIKV infections, there is an immediate need to develop new diagnostic tools and novel preventive as well as therapeutic modalities based on understanding the molecular mechanisms underlying the disease.