Prebiotics in New-Born and Children's Health.

At present, prebiotics, like probiotics, are receiving more attention as a promising tool for health maintenance. Many studies have recognized the role of prebiotics in preventing and treating various illnesses including metabolic disorders, gastrointestinal disorders, and allergies. Naturally, prebiotics are introduced to the human body in the first few hours of life as the mother breastfeeds the newborn. Prebiotic human milk oligosaccharides (HMOs) are the third largest constituent of human breastmilk. Studies have proven that HMOs modulate an infant's microbial composition and assist in the development of the immune system. Due to some health conditions of the mother or beyond the recommended age for breastfeeding, infants are fed with formula. Few types of prebiotics have been incorporated into formula to yield similar beneficial impacts similar to breastfeeding. Synthetic HMOs have successfully mimicked the bifidogenic effects of breastmilk. However, studies on the effectiveness and safety of consumption of these synthetic HMOs are highly needed before massive commercial production. With the introduction of solid foods after breastfeeding or formula feeding, children are exposed to a range of prebiotics that contribute to further shaping and maturing their gut microbiomes and gastrointestinal function. Therefore, this review evaluates the functional role of prebiotic interventions in improving microbial compositions, allergies, and functional gastrointestinal disorders in children.

Comprehensive interrogation of human skeletal muscle reveals a dissociation between insulin resistance and mitochondrial capacity.

Insulin resistance and blunted mitochondrial capacity in skeletal muscle are often synonymous, however, this association remains controversial. The aim of this study was to perform an in-depth multifactorial comparison of skeletal muscle mitochondrial capacity between individuals who were lean and active (Active, n = 9), individuals with obesity (Obese, n = 9), and individuals with obesity, insulin resistance, and type 2 diabetes (T2D, n = 22). Mitochondrial capacity was assessed by ex vivo mitochondrial respiration with fatty-acid and glycolytic-supported protocols adjusted for mitochondrial content (mtDNA and citrate synthase activity). Supercomplex assembly was measured by Blue Native (BN)-PAGE and immunoblot. Tricarboxylic (TCA) cycle intermediates were assessed with targeted metabolomics. Exploratory transcriptomics and DNA methylation analyses were performed to uncover molecular differences affecting mitochondrial function among the three groups. We reveal no discernable differences in skeletal muscle mitochondrial content, mitochondrial capacity, supercomplex assembly, TCA cycle intermediates, and mitochondrial molecular profiles between obese individuals with and without T2D that had comparable levels of confounding factors (body mass index, age, and aerobic capacity). We highlight that lean, active individuals have greater mitochondrial content, mitochondrial capacity, supercomplex assembly, and TCA cycle intermediates. These phenotypical changes are reflected at the level of DNA methylation and gene transcription. The collective observation of comparable muscle mitochondrial capacity in individuals with obesity and T2D (vs. individuals without T2D) underscores a dissociation from skeletal muscle insulin resistance. Clinical trial number: NCT01911104.NEW & NOTEWORTHY Whether impaired mitochondrial capacity contributes to skeletal muscle insulin resistance is debated. Our multifactorial analysis shows no differences in skeletal muscle mitochondrial content, mitochondrial capacity, and mitochondrial molecular profiles between obese individuals with and without T2D that had comparable levels of confounding factors (BMI, age, aerobic capacity). We highlight that lean, active individuals have enhanced skeletal muscle mitochondrial capacity that is also reflected at the level of DNA methylation and gene transcription.

Multimodal monitoring: practical recommendations (dos and don'ts) in challenging situations and uncertainty.

With the advancements in modern medicine, new methods are being developed to monitor patients in the intensive care unit. Different modalities evaluate different aspects of the patient's physiology and clinical status. The complexity of these modalities often restricts their use to the realm of clinical research, thereby limiting their use in the real world. Understanding their salient features and their limitations can aid physicians in interpreting the concomitant information provided by multiple modalities to make informed decisions that may affect clinical care and outcomes. Here, we present a review of the commonly used methods in the neurological intensive care unit with practical recommendations for their use.

Source of nicotinamide governs its metabolic fate in cultured cells, mice, and humans.

Metabolic routing of nicotinamide (NAM) to NAD+ or 1-methylnicotinamide (MeNAM) has impacts on human health and aging. NAM is imported by cells or liberated from NAD+. The fate of 2H4-NAM in cultured cells, mice, and humans was determined by stable isotope tracing. 2H4-NAM is an NAD+ precursor via the salvage pathway in cultured A549 cells and human PBMCs and in A549 cell xenografts and PBMCs from 2H4-NAM-dosed mice and humans, respectively. 2H4-NAM is a MeNAM precursor in A549 cell cultures and xenografts, but not isolated PBMCs. NAM released from NAD+ is a poor MeNAM precursor. Additional A549 cell tracer studies yielded further mechanistic insight. NAMPT activators promote NAD+ synthesis and consumption. Surprisingly, NAM liberated from NAD+ in NAMPT activator-treated A549 cells is also routed toward MeNAM production. Metabolic fate mapping of the dual NAM sources across the translational spectrum (cells, mice, humans) illuminates a key regulatory node governing NAD+ and MeNAM synthesis.

CD8 Encephalitis: A Diagnostic Dilemma.

CD8+ encephalitis is a subacute encephalopathy associated with HIV infection. Pathophysiology is thought to be auto-reactive CD8+ cells attacking on HIV infected CD4+ cells and 'viral escape' phenomena (replication of CD8+ cells in CSF). We present a case of a 45-year-old man with well controlled HIV who developed CD8 encephalitis following Herpes simplex encephalitis. He had persistent encephalopathy for several weeks with status epilepticus and agitated delirium, and diagnosis remained elusive until a brain biopsy confirmed the diagnosis.

Bilateral Carotid-Cavernous Fistula: A Diagnostic and Therapeutic Challenge.

Carotid-cavernous fistula (CCF) is an aberrant communication between the main trunk or branches of carotid artery and the cavernous sinus. Most of the cases of CCF occur following head trauma, but congenital and spontaneous cases have been reported. We report an interesting case of bilateral CCF with no history of trauma, thus most likely spontaneous form. Since it is rare, it was a diagnostic challenge. The suspicion of this diagnosis was made due to clinical features of headache, signs of increased Intracranial Pressure (ICP) (nausea, vomiting, and worsening headaches during Valsalva), exophthalmos, periorbital edema, periorbital erythema, chemosis, and conjunctival injection in both eyes. It was diagnosed with a 4-vessel angiography (digital subtraction angiography) which is the gold standard and was managed successfully with endovascular coil embolization.

Spectrum of Hemorrhagic Encephalitis in COVID-19 Patients: A Case Series and Review.

Severe acute respiratory syndrome corona virus 2 (SARS-CoV-2) is an ongoing pandemic that has affected over 400 million people worldwide and caused nearly 6 million deaths. Hemorrhagic encephalitis is an uncommon but serious complication of COVID-19. The etiology of this disease is multifactorial, including secondary to severe hypoxemia, systemic inflammation, direct viral invasion, hypercoagulability, etc. The clinical spectrum of COVID-19-related hemorrhagic encephalitis is also varied, ranging from leukoencephalopathy with microhemorrhage, acute necrotizing hemorrhagic encephalitis (ANHE) involving the cortex, basal ganglia, rarely brain stem and cervical spine, hemorrhagic posterior reversible encephalopathy syndrome (PRES) to superimposed co-infection with other organisms. We report a case series of three young patients with different presentations of hemorrhagic encephalitis after COVID-19 infection and a review of the literature. One patient had self-limiting ANHE in the setting of mild COVID-19 systemic illness. The second patient had self-limiting leukoencephalopathy with microhemorrhages in the setting of severe systemic diseases and ARDS, and clinically improved with the resolution of systemic illness. Both patients were healthy and did not have any premorbid conditions. The third patient with poorly controlled diabetes and hypertension had severe systemic illness with neurological involvement including multiple ischemic strokes, basal meningitis, hemorrhagic encephalitis with pathological evidence of cerebral mucormycosis, and Epstein-Barr virus coinfection, and improved after antifungal therapy.

Predictors of No-Show in Neurology Clinics.

In this study, we aim to identify predictors of a no-show in neurology clinics at our institution. We conducted a retrospective review of neurology clinics from July 2013 through September 2018. We compared odds ratio of patients who missed appointments (no-show) to those who were present at appointments (show) in terms of age, lead-time, subspecialty, race, gender, quarter of the year, insurance type, and distance from hospital. There were 60,012 (84%) show and 11,166 (16%) no-show patients. With each day increase in lead time, odds of no-show increased by a factor of 1.0019 (p < 0.0001). Odds of no-show were higher in younger (p ≤ 0.0001, OR = 0.49) compared to older (age ≥ 60) patients and in women (p < 0.001, OR = 1.1352) compared to men. They were higher in Black/African American (p < 0.0001, OR = 1.4712) and lower in Asian (p = 0.03, OR = 0.6871) and American Indian/Alaskan Native (p = 0.055, OR = 0.6318) as compared to White/Caucasian. Patients with Medicare (p < 0.0001, OR = 1.5127) and Medicaid (p < 0.0001, OR = 1.3354) had higher odds of no-show compared to other insurance. Young age, female, Black/African American, long lead time to clinic appointments, Medicaid/Medicare insurance, and certain subspecialties (resident and stroke clinics) are associated with high odds of no show. Possible suggested interventions include better communication and flexible appointments for the high-risk groups as well as utilizing telemedicine.

Autoimmune encephalitis and seizures, cerebrospinal fluid, imaging, and EEG findings: a case series.

Antibody-mediated encephalitides constitute a group of inflammatory brain diseases characterized by prominent neuropsychiatric symptoms and are associated with antibodies against neuronal cell-surface proteins, ion channels, or receptors. The diagnosis and management of autoimmune encephalitis include evaluation of the clinical presentation, brain imaging, cerebrospinal fluid (CSF) findings, antibody detection, and electroencephalography (EEG) findings. This is a retrospective study of adults 18 years or older with autoimmune encephalitis due to antibodies against membrane surface antigens as well as anti-glutamic acid decarboxylase (anti-GAD) antibodies. The electronic medical record was reviewed for demographic data, clinical data, laboratory results, EEG, and imaging findings. Antibody screening was requested for 341 patients between May 2014 and December 2019. Antibody screening was positive in 37 patients presenting with seizures and/or encephalopathy. Of these, 10 patients tested positive for antibodies against neuronal surface antigens or anti-GAD antibodies-2 patients had anti-GAD antibody encephalitis, 5 had anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis, and 3 had anti-leucine-rich glioma-inactivated 1 (anti-LGI1) encephalitis. Demographics, clinical presentation, EEG, imaging, and CSF findings are reported. Autoimmune encephalitides are a diverse group of disorders with a few common clinical features and MRI findings. MRI, EEG, and CSF findings can be normal or show nonspecific findings in autoimmune encephalitis. Therefore, early diagnosis of these disorders requires a high level of suspicion to avoid delaying the diagnosis. Carefully looking for diagnostic clinical features (e.g., faciobrachial dystonic seizures in anti-LGI1 encephalitis), significant findings in MRI (e.g., limbic encephalitis), and some EEG patterns (e.g., extreme delta brush and generalized rhythmic delta activity in anti-NMDAR encephalitis) may help in early diagnosis.

Trends in Demographics of Neurology House Staff in the United States.

Background The lack of an adequate number of neurologists is a worldwide problem. As populations age, the prevalence of neurological disorders will likely increase, thereby increasing the demand for neurologists. In addition to the growing demand, inadequate diversity in the neurology healthcare workforce still exists. The purpose of this study is to examine the demographic characteristics of neurology residents and fellows. Methodology This cross-sectional study used data from the following publicly available databases: Accreditation Council for Graduate Medical Education, Association of American Medical Colleges, and the United States Census Bureau. Trends (from 2007 to 2018) in demographic characteristics were assessed using the slope and the associated p-value of a simple linear regression model, with the year as the independent variable. All p-values of <0.05 were considered significant. Results From 2007 through 2018, the percentage of US medical school graduates in neurology residency decreased from 58% to 55% (slope = -0.25; p = 0.0004), while the percentage of international medical graduates (IMGs) decreased from 36% to 32% (slope = -0.29; p = 0.0141) and doctor of osteopathy (DO) graduates increased from 6% to 13% (slope = 0.58; p < 0.0001). Although the percentage of female neurology residents increased from 39.5% in 2007 to 43.1% in 2018 (slope = 0.03; p = 0.8659), female physicians were underrepresented in vascular neurology fellowship (34% in 2018). Collectively, the percentage of underrepresented minorities in neurology residencies was low and increased only slightly over time (from 8% in 2011 to 9% in 2018; slope = 0.17; p = 0.0788). In 2018, the proportion of underrepresented minorities was smaller in neurology fellowships (5.5% neurophysiology, 12.5% epilepsy, 10.4% neuromuscular, and 12.4% vascular) compared to the population as a whole (31.3%). Conclusions IMGs still play an important role in filling a significant portion of the neurology residencies and fellowships. DO graduates have slowly increased in neurology residencies and fellowships. Members of several racial/ethnic minority groups and women are underrepresented in neurology house staff and efforts need to be taken to increase diversity.

A Metabolomic Signature of Glucagon Action in Healthy Individuals With Overweight/Obesity.

CONTEXT: Glucagon is produced and released from the pancreatic alpha-cell to regulate glucose levels during periods of fasting. The main target for glucagon action is the liver, where it activates gluconeogenesis and glycogen breakdown; however, glucagon is postulated to have other roles within the body. OBJECTIVE: We sought to identify the circulating metabolites that would serve as markers of glucagon action in humans. METHODS: In this study (NCT03139305), we performed a continuous 72-hour glucagon infusion in healthy individuals with overweight/obesity. Participants were randomized to receive glucagon 12.5 ng/kg/min (GCG 12.5), glucagon 25 ng/kg/min (GCG 25), or a placebo control. A comprehensive metabolomics analysis was then performed from plasma isolated at several time points during the infusion to identify markers of glucagon activity. RESULTS: Glucagon (GCG 12.5 and GCG 25) resulted in significant changes in the plasma metabolome as soon as 4 hours following infusion. Pathways involved in amino acid metabolism were among the most affected. Rapid and sustained reduction of a broad panel of amino acids was observed. Additionally, time-dependent changes in free fatty acids and diacylglycerol and triglyceride species were observed. CONCLUSION: These results define a distinct signature of glucagon action that is broader than the known changes in glucose levels. In particular, the robust changes in amino acid levels may prove useful to monitor changes induced by glucagon in the context of additional glucagon-like peptide-1 or gastric inhibitory polypeptide treatment, as these agents also elicit changes in glucose levels.

Criteria for Emergency Brain MRI During Stroke-Alert.

OBJECTIVES: Intravenous (IV) tissue plasminogen activator (tPA) should be given to patients with acute ischemic stroke (AIS) and avoided in stroke mimics (SM). Select use of emergency brain magnetic resonance imaging (eMRI-brain) in stroke-alerts aids diagnosis, but accepted utilization criteria for eMRI-brain do not currently exist. We developed criteria for eMRI-brain and report the yield of eMRI-brain in stroke-alert patients. MATERIALS AND METHODS: We developed three history-based criteria for performing eMRI-brain during stroke-alerts: (1) history of previous similar deficits, (2) change in consciousness at onset of symptoms, (3) symptom presentation consistent with migraine aura. We then performed a retrospective chart review of patients who presented as a stroke-alert over a 5-year period and determined how these criteria affected administration of IV tPA to AIS and SM patients. RESULTS: Among 3,512 stroke-alerts, 230 (8.1%) patients met our criteria for eMRI-brain exams: 217 (92.6%) had SM and 17 (7.4%) had AIS. Our IV tPA decision-making analysis showed that based on eMRI-brain IV tPA was less frequently administered to SM patients (PCC-0.841, p=0.036) with less failures to administer IV tPA to patients with AIS (PCC -0.907, p-value=0.013, Pearson correlation coefficient). No patients became ineligible for IV tPA due to MRI-related time delays. CONCLUSIONS: Our history based criteria for performing eMRI-brain during stroke-alerts show a high yield of stroke mimics. Selective eMRI-brain improves decision-making accuracy regarding IV tPA administration.

Cost-Effectiveness of Emergent MRI during Stroke Alert to Diagnose Stroke Mimics: Single-Center Experience.

Objective The aim of this article was to assess the role of emergent magnetic resonance imaging (MRI) for stroke mimics during a stoke alert (within 45 minutes) in reducing direct cost of management and duration of inpatient stay. Methods We did a retrospective chart review of all the patients who received emergent MRI brain during a stroke alert to help make decision about intravenous tissue-type plasminogen activator (IV tPA) administration from January 2013 to December 2015. Using the patient financial resource data and with the help of billing department, we calculated the approximate money saved in taking care of the patients who may have received IV tPA if emergent MRI brain was not available to diagnose stroke mimics as they presented with acute neurologic deficit within IV tPA time window. Results Ninety seven out of 1,104 stroke alert patients received emergent MRI. Of these only 17 (17.5%) were diagnosed with acute ischemic stroke (AIS), and 80 (82.5%) as stroke mimics. By doing emergent MRI for suspected stroke mimics, our study showed an approximate total saving of $1,005,720 to $1,384,560, that is, $12,571 to $17,307 per patient in medical expenditure. Discussion We suggest modification of stroke pathway from current algorithm "CT+CTA≥IV-tPA/neurointervention≥MRI" to "MRI+MRA≥IV-tPA/neurointervention" for possible stroke mimics, which can reduce the cost, radiation exposure, and duration of hospital stay for stroke mimics. Conclusion Emergent MRI is a cost-effective tool to evaluate IV-tPA eligibility for suspected stroke mimics during a stroke alert.

Immunosuppression in chronic autoimmune neurological disorders during the COVID-19 pandemic.

OBJECTIVE: To study the risk of acquiring Corona Virus Disease 2019 (COVID-19) and its outcomes in patients on immunosuppressive therapy (IST) for chronic autoimmune neuromuscular disorders (aNMD) and multiple sclerosis (MS). METHODS: We used TriNetX, a global health collaborative clinical research platform collecting real-time electronic medical records data, which has one of the largest known global COVID-19 database. We included patients with chronic autoimmune neuromuscular disorders (aNMD) [myasthenia gravis (MG), inflammatory myositis, and chronic inflammatory neuropathies (CIN)] and MS, based on the International Classification of Disease-10 (ICD-10) coding for one year before January 20th, 2020. We examined the use of IST, rate of COVID- 19, hospitalization, intubation, and mortality among the patients with aNMD and MS. RESULTS: A total of 33,451 patients with aNMD and 42,899 patients with MS were included. Among them, 111 (0.33%) patients with aNMD and 115 patients (0.27%) with MS had COVID-19. About one third of them required hospitalization. IST did not appear to have a significant impact on overall infection risk in either group; however, risk of hospitalization for immunosuppressed patients with aNMD was higher (Odds ratio 2.86, p-value 0.011). CONCLUSIONS: IST use does not appear to make patients with aNMD and MS more vulnerable to COVID-19. IST may be continued during the pandemic, as previously suggested by expert opinion guidelines. However, it is important to consider individualizing immunotherapy regimens in some cases. Additional physician reported registry-based data is needed to further confirm these findings.

Isolated primary neurolymphomatosis with cranial multineuritis: a case presentation.

BACKGROUND: Isolated primary neurolymphomatosis (NL) of cranial multineuritis is a very rare condition that refers to the lymphomatous invasion of cranial nerves only. There are sparse cases of isolated cranial nerves NL reported worldwide. CASE PRESENTATION: We present magnetic resonance imaging (MRI) and cerebrospinal fluid (CSF) findings of a 63-year-old female patient suffering from isolated neurolymphomatosis of cranial multineuritis with a wide constellation of syndromes including binocular diplopia, left facial paralysis and pain, syncope episodes, and progressive dysphagia. A contrasted MRI brain showed multiple cranial nerves enhancement. Extensive workup for infectious, autoimmune, neoplastic, paraneoplastic, or inflammatory etiologies had been unrevealing except CSF cytology revealed large atypical monotypic B cells that were suspicious for non-Hodgkin lymphoma on the third large volume tap. The decision of biopsy was deferred after the risks and benefits discussion. Following the four cycles of empiric methotrexate-based induction chemotherapy, the patient's symptoms resolved, and a complete radiographic response was achieved without whole-brain radiation or autologous hematopoietic cell transplantation. In the latest follow-up, she is independent with her daily activities and remains in clinical and radiographic remission more than 3 years since initial chemotherapy. CONCLUSION: Isolated NL of cranial nerves can present diagnostic and management pitfalls for the neurologist, neurosurgeons, and oncologists. Since current diagnostic modalities have modest sensitivity and a pathological diagnosis is often difficult, empiric treatment once other possibilities are ruled out can carry a good prognosis.

A neuromuscular-based analysis of the open payments program.

INTRODUCTION: In August 2013, the Centers for Medicare and Medicaid Services (CMS) Open Payments Program (OPP) made eligible payment information publicly available. Data about industry payments to neuromuscular neurologists are lacking. METHOD: Financial relationships were investigated between industry and US neuromuscular neurologists from January 2014 through December 2018 using the CMS OPP database. RESULTS: The total annual payments increased more than 6-fold during the study period. The top 10% of physician-beneficiaries collected 80% to 90% of total industry payments except in 2014. In 2018, the most common drugs associated with payments to neuromuscular neurologists were nusinersen, vortioxetine, eteplirsen, alglucosidase alpha, edaravone, and intravenous immunoglobulin. DISCUSSION: A substantial increase in the annual payments to neuromuscular physicians during the study period is likely due to the development of new treatments, including gene therapy.

Industry payments to hospitalist physicians: a 5-year analysis of the Open Payments programme from 2014 to 2018.

We analysed Open Payments programme data (https://openpaymentsdata.cms.gov) on industry-to-physician payments to hospitalists for the years 2014 to 2018. Payments to hospitalists increased by 106.5% from 2014 to 2018 with food and beverage (38.5%) and compensation for services other than consulting (24.3%) being the highest-paid categories. Industry payment to hospitalists was highly skewed with top 10 hospitalists receiving more than 30% of the total payments during the study period. The most common drugs associated with payments were anticoagulant medications (apixaban and rivaroxaban). Industry seems to be spending a significant amount of money to increase awareness of medications among hospitalists. Identification of these trends and potential motives of industry spending is critical to address any potential physician bias.

COVID-19 and stroke, a case series and review of literature.

BACKGROUND: Corona Virus Disease 2019 (COVID-19) cases continue to increase around the World. Typical symptoms include fever and respiratory illness but a constellation of multisystem involvement including central nervous system (CNS) and peripheral nervous system (PNS) have been reported with COVID-19. Acute ischemic strokes (AIS) have also been reported as a complication. METHODOLOGY: We analyzed patient characteristics, clinical outcomes, laboratory results and imaging results of four patients with COVID-19 who had AIS. RESULTS: All four patients were =< 60 years, had hypoxemic respiratory failure secondary to pneumonia, elevated D-dimer and inflammatory markers. CONCLUSION: Ischemic strokes are known complications in patients with severe COVID-19.

Resident Education During COVID-19 Pandemic: Effectiveness of Virtual Electroencephalogram Learning.

Objective To explore effectiveness of alternative methods of neurology resident electroencephalogram (EEG) learning during COVID-19 pandemic due to social distancing requirements which caused disruption of traditional in-person teaching. Methods Virtual EEG learning was instituted using Zoom platform. Residents participated in live, interactive virtual sessions for eight weeks. A pre-test and post-test were administered and a survey was performed at the end of the project. Results Based on pre-test and post-test results, there was a significant improvement on average resident test scores. On the survey, 100% agreed (81.8% strongly agreed, 18.2% agreed) that virtual EEG sessions provided a conducive learning environment with easy access while preserving effective communication with the instructor. When compared to traditional EEG reading, 100% agreed (81.8% strongly agreed and 18.2% agreed) that virtual sessions were more accessible, 72.7% agreed (54.5% strongly agreed, 18.2% agreed) that they were more interactive; 81.9% (45.5% strongly agreed, 36.4% agreed) felt more engaged and 90.9% agreed (81.8% strongly agreed, 9.1% agreed) that they were able to attend more sessions. Hundred percent residents (72.7% strongly agreed, 27.3% agreed) felt more confident in their EEG reading and all (81.8% strongly agreed and 18.2% agreed) would sign up for more virtual learning courses. Conclusions Virtual EEG education is an efficient method of resident education with improved ease of access while maintaining interactive discussion leading to increased confidence in learners. It should be considered even after resolution of the need for social distancing and its applications in other fields of learning should be further explored.