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Abstract The indirect impact of the COVID-19 pandemic on clinical services in peripheral hospitals has not been fully described. We compared the impact of COVID-19 on Cerebral Vascular Accident (CVA) and ST-elevation myocardial infarction (STEMI) management and outcome in an Israeli peripheral hospital. We included 1029 CVA and 495 STEMI patients. Patients who arrived during (15/3/2020–15/4/2022) and before (1/1/2018–14/3/2020) the pandemic, were demographically comparable. During the pandemic, median time for CVA patients from arrival to imaging was longer (23 vs. 19 min, p = 0.001); timing from arrival to tissue Plasminogen Activator administration was similar (49 vs. 45 min, p = 0.61); transfer to another hospital was more common (20.3% vs. 14.4% p = 0.01) and median length of stay (LOS) was shorter (3 vs. 4 days, p

There are different diagnostic modalities to investigate atherosclerosis cervical artery disease in suspected stroke patients. We aimed to test the concordance of findings of the two most widely used diagnostic modalities in stroke patients: duplex ultrasound (DUS) and computerized tomographic angiography (CTA). A total of 100 stroke patients were retrospectively included in the study, all of them had DUS followed by CTA. Discrepancies of DUS compared to the CTA results in both the internal carotid and vertebral arteries were found in 44% of the patients. The patients with significant differences in diagnostic results were characterized by older age. Evaluation of the degree of carotid artery stenosis revealed vast differences in patients with 50–69% stenosis found by DUS, in which 45.5% of them had a different percentage of stenosis found by CTA. In studying the degree of stenosis of the vertebral artery, only 47.1% of the patients with more than 50% stenosis found by DUS had the same results with CTA, while the remaining revealed normal or less than 50% stenosis by CTA. The current study emphasizes that CTA is more accurate than DUS in the evaluation of stenosis of the cervical arteries including both the internal carotid and vertebral arteries.

AIM: To identify a link between optical coherence tomography(OCT), length of multiple sclerosis(MS)and the expanded disability status scale(EDSS).METHODS: In a prospective double blind study, 29 patients with a diagnosis of MS were compared with 29 healthy patients, matched by age and sex. All participants underwent an OCT study and neurological EDSS test on the same day.RESULTS: The mean EDSS score was 3.2 in the MS group vs 0.03 in the control group, and the duration of MS was 11.7y. The mean retinal nerve fiber layer(RNFL)thickness was significantly thinner in those with MS (PCONCLUSION: RNFL is thinner in MS patients than in the general population. MS duration has a direct statistically significant effect on RNFL thickness. There seems to be a tendency of a relationship between RNFL thinning and EDSS. OCT is suggested as a monitoring and evaluation tool of MS patients.

Radi Shahien, Abdalla BowirratDepartment of Neurology, Ziv Medical Center, Zfat, IsraelAbstract: We report a complication related to epidural analgesia for delivery in a 24-year-old woman who was admitted with mild pre-eclampsia and for induction of labor. At the first postpartum day she developed a postdural puncture headache, which was unresponsive to conservative measures. On the fifth day an epidural blood patch was done, and her headache subsided. Sixteen hours later she developed paralysis of the right facial nerve, which was treated with prednisone. Seven days later she complained of pain in the left arm and the posterior region of the shoulder. She was later admitted and diagnosed with partial brachial plexopathy.Keywords: facial nerve paralysis, partial brachial plexopathy, epidural blood patch

Radi Shahien1, Vetaly Vieksler1, Abdalla Bowirrat11Department of Neurology and Neurophysiology, Ziv Medical Center, Safed, IsraelAbstract: Meningitis is usually produced by an infectious agent, but there are multiple noninfectious causes. Drug-induced aseptic meningitis (DIAM) is an important entity and has been reported as an uncommon adverse reaction with numerous agents. Thus, DIAM constitutes a diagnostic and patient management challenge. We present a patient with three episodes of aseptic meningitis due to amoxicillin, and then review the literature on this rare idiosyncratic event which may occur after local or systemic drug administration. A 77-year-old man was admitted to our hospital with fever, headache, and neck stiffness. Seven days before admission he had a dental and gingival inflammation. He was treated with two oral doses of 500 mg daily of amoxicillin for one week. The seventh day he awoke with the complaints that prompted hospital admittance. Amoxicillin was stopped 1 day before his admission. From his history we knew of two similar episodes: The first episode was after a dental procedure 3 months before this incident. He had received a 1-week course of postprocedure amoxicillin of 500 mg daily and had similar headache, fever, and chills during the entire course of treatment. He wasn’t admitted to the hospital, because he stopped taking amoxicillin and he felt spontaneous pain relief after taking symptomatic pain treatment. The second episodes was 6 months after his first admission, he had been admitted to our hospital with the same symptoms. Amoxicillin was stopped and changed with intravenous (IV) ceftriaxone (CTRX) for 10 days due to suspected partial untreated meningitis. The patient improved rapidly within 2 days and was discharged from the hospital. On the basis of these three confirmed episodes of meningitis after recurrent exposure to amoxicillin, with repetitive negative testing for viral, bacterial, and mycobacterial micro-organisms, we diagnosed aseptic meningitis induced by amoxicillin. To our knowledge, this is the seventh well documented publication of such a severe side effect of a commonly used antibiotic.Keywords: drug induced aseptic meningitis, viral meningitis, meningoencephalitis, amoxicillin

Radi Shahien, Abdalla BowirratDepartment of Neurology, Ziv Medical Center, Safed, IsraelBackground: Neurologic involvement in Behçet’s disease (BD), also known as neuro-Behcet’s disease (NBD), is one of the most devastating manifestations of the disease. The etiology of BD remains obscure and speculative. NBD usually occurs 1–10 years after the first symptom of BD has occurred, and its incidence is 18% (range of 4%–49%).Objective: This study was conducted to describe the clinical and prognostic aspects of neurologic involvement in BD among patients attending a multidisciplinary hospital clinic.Methods: Eighty patients with BD were diagnosed according to the International Study Group Criteria for BD at our hospital. Sixteen patients (20%, including 11 men and five women) had evidence of and fulfilled the diagnostic criteria for NBD. These patients underwent laboratory and imaging investigations, including human leukocyte antigen-typing, lumbar puncture, electroencephalographic studies, and computed tomography scanning.Results: Fourteen of the 16 patients received high-dose steroids, and four of these 14 patients were treated with a combination of steroids and cytotoxic agents. Relief was observed in 14 of 16 patients (87.5%). The remaining two patients were untreated males who suffered severe brainstem lesions, and later died.Conclusion: In contrast with previous reports of a poor prognosis with NBD, our study shows that early aggressive intervention with corticosteroids and cytotoxic agents may ameliorate the prognosis in these patients, and can diminish and stabilize the negative effect of neurologic involvement.Keywords: neuro-Behçet’s disease, neurologic involvement, aphthous ulceration, genital ulceration, iridocyclitis

Hepatocyte Nuclear Factor 4α (HNF4α), a master regulator of hepatocyte differentiation, is regulated by two promoters (P1 and P2) which drive the expression of different isoforms. P1-HNF4α is the major isoform in the adult liver while P2-HNF4α is thought to be expressed only in fetal liver and liver cancer. Here, we show that P2-HNF4α is indeed expressed in the normal adult liver at Zeitgeber time (ZT)9 and ZT21. Using exon swap mice that express only P2-HNF4α we show that this isoform orchestrates a distinct transcriptome and metabolome via unique chromatin and protein-protein interactions, including with different clock proteins at different times of the day leading to subtle differences in circadian gene regulation. Furthermore, deletion of the Clock gene alters the circadian oscillation of P2- (but not P1-)HNF4α RNA, revealing a complex feedback loop between the HNF4α isoforms and the hepatic clock. Finally, we demonstrate that while P1-HNF4α drives gluconeogenesis, P2-HNF4α drives ketogenesis and is required for elevated levels of ketone bodies in female mice. Taken together, we propose that the highly conserved two-promoter structure of the Hnf4a gene is an evolutionarily conserved mechanism to maintain the balance between gluconeogenesis and ketogenesis in the liver in a circadian fashion., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2023 Deans, Deol, Titova, Radi, Vuong, Evans, Pan, Fahrmann, Yang, Hammock, Fiehn, Fekry, Eckel-Mahan and Sladek.)

Hepatocyte nuclear factor 4-alpha (HNF4α) drives a complex array of transcriptional programs across multiple organs. Beyond its previously documented function in the liver, HNF4α has crucial roles in the kidney, intestine, and pancreas. In the intestine, a multitude of functions have been attributed to HNF4 and its accessory transcription factors, including but not limited to, intestinal maturation, differentiation, regeneration, and stem cell renewal. Functional redundancy between HNF4α and its intestine-restricted paralog HNF4γ, and co-regulation with other transcription factors drive these functions. Dysregulated expression of HNF4 results in a wide range of disease manifestations, including the development of a chronic inflammatory state in the intestine. In this review, we focus on the multiple molecular mechanisms of HNF4 in the intestine and explore translational opportunities. We aim to introduce new perspectives in understanding intestinal genetics and the complexity of gastrointestinal disorders through the lens of HNF4 transcription factors., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Vemuri, Radi, Sladek and Verzi.)

In the more than 30 years since the purification and cloning of Hepatocyte Nuclear Factor 4 (HNF4α), considerable insight into its role in liver function has been gleaned from its target genes and mouse experiments. HNF4α plays a key role in lipid and glucose metabolism and intersects with not just diabetes and circadian rhythms but also with liver cancer, although much remains to be elucidated about those interactions. Similarly, while we are beginning to elucidate the role of the isoforms expressed from its two promoters, we know little about the alternatively spliced variants in other portions of the protein and their impact on the 1000-plus HNF4α target genes. This review will address how HNF4α came to be called the master regulator of liver-specific gene expression with a focus on its role in basic metabolism, the contributions of the various isoforms and the intriguing intersection with the circadian clock., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Radi, Vemuri, Martinez-Lomeli and Sladek.)

Inflammatory bowel disease (IBD) is a multifactorial disease with increasing incidence in the U.S. suggesting that environmental factors, including diet, are involved. It has been suggested that excessive consumption of linoleic acid (LA, C18:2 omega-6), which must be obtained from the diet, may promote the development of IBD in humans. To demonstrate a causal link between LA and IBD, we show that a high fat diet (HFD) based on soybean oil (SO), which is comprised of ~55% LA, increases susceptibility to colitis in several models, including IBD-susceptible IL10 knockout mice. This effect was not observed with low-LA HFDs derived from genetically modified soybean oil or olive oil. The conventional SO HFD causes classical IBD symptoms including immune dysfunction, increased intestinal epithelial barrier permeability, and disruption of the balance of isoforms from the IBD susceptibility gene Hepatocyte Nuclear Factor 4α (HNF4α). The SO HFD causes gut dysbiosis, including increased abundance of an endogenous adherent invasive Escherichia coli (AIEC), which can use LA as a carbon source. Metabolomic analysis shows that in the mouse gut, even in the absence of bacteria, the presence of soybean oil increases levels of LA, oxylipins and prostaglandins. Many compounds in the endocannabinoid system, which are protective against IBD, are decreased by SO both in vivo and in vitro . These results indicate that a high LA diet increases susceptibility to colitis via microbial and host-initiated pathways involving alterations in the balance of bioactive metabolites of omega-6 and omega-3 polyunsaturated fatty acids, as well as HNF4α isoforms.