Endoplasmic reticulum stress in the intestinal epithelium initiates purine metabolite synthesis and promotes Th17 cell differentiation in the gut.

Intestinal IL-17-producing T helper (Th17) cells are dependent on adherent microbes in the gut for their development. However, how microbial adherence to intestinal epithelial cells (IECs) promotes Th17 cell differentiation remains enigmatic. Here, we found that Th17 cell-inducing gut bacteria generated an unfolded protein response (UPR) in IECs. Furthermore, subtilase cytotoxin expression or genetic removal of X-box binding protein 1 (Xbp1) in IECs caused a UPR and increased Th17 cells, even in antibiotic-treated or germ-free conditions. Mechanistically, UPR activation in IECs enhanced their production of both reactive oxygen species (ROS) and purine metabolites. Treating mice with N-acetyl-cysteine or allopurinol to reduce ROS production and xanthine, respectively, decreased Th17 cells that were associated with an elevated UPR. Th17-related genes also correlated with ER stress and the UPR in humans with inflammatory bowel disease. Overall, we identify a mechanism of intestinal Th17 cell differentiation that emerges from an IEC-associated UPR.

Recent trends of refractive surgery rate and detailed analysis of subjects with refractive surgery: The 2008-2015 Korean National Health and Nutrition Examination Survey.

The present study was conducted to investigate recent trends of refractive surgery rates and analyze subjects undergoing refractive surgery using large-scale population studies over the past 8 years. We used the dataset of the Korean National Health and Nutrition Examination Surveys, a nationwide population-based cross-sectional study which were performed from 2008 to 2015. Of the 21,415 participants aged 20 to 49 years, 1,621 had refractive surgeries. Seventy three percent of them were females and 81% of them were aged under 40 years old. Over the past 8 years, cumulative prevalence of refractive surgery rate increased more than 10%. Although young (< 40 years, odds ratio (OR) 0.31, P<0.001) women (OR 1.86, P<0.001) living in urban areas (OR 0.51, P<0.001) with high educational attainment (OR 2.67, P<0.001) and income levels (OR 3.16, P<0.001) accounted for a high proportion in refractive surgery group through all survey years, subgroup analyses revealed that gaps between genders (ORs 3.8 in 2008-2009, 2.1 in 2010-2012, and 1.5 in 2013-2015), educational level (ORs 3.0, 2.5, and 2.1, respectively), and highest/lowest quartiles of household income (ORs 5.2, 2.6, and 2.4, respectively) were decreasing over time. Overall, our study suggests that refractive surgery has reached an age where the majority accepts it, and indeed more and diverse people are undergoing refractive surgeries.

A screen of kinase inhibitors reveals a potential role of Chk1 in regulating Hydra head regeneration and maintenance.

The cnidarian Hydra possesses remarkable regenerative capabilities which allow it to regrow lost or damaged body parts in a matter of days. Given that many key regulators of regeneration and development are evolutionarily conserved, Hydra is a valuable model system for studying the fundamental molecular mechanisms underlying these processes. In the past, kinase inhibitors have been useful tools for determining the role of conserved signaling pathways in Hydra regeneration and patterning. Here, we present a systematic screen of a commercially available panel of kinase inhibitors for their effects on Hydra regeneration. Isolated Hydra gastric segments were exposed to 5 µM of each kinase inhibitor and regeneration of the head and foot regions were scored over a period of 96 hours. Of the 80 kinase inhibitors tested, 28 compounds resulted in abnormal regeneration. We directed our focus to the checkpoint kinase 1 (Chk1) inhibitor, SB 218078, considering the role of Chk1 in G2 checkpoint regulation and the importance of G2-paused cells in Hydra regeneration. We found that Hydra exposed to SB 218078 were unable to regenerate the head and maintain head-specific structures. Furthermore, SB 218078-treated Hydra displayed a reduction in the relative proportion of epithelial cells; however, no differences were seen for interstitial stem cells or their derivatives. Lastly, exposure to SB 218078 appeared to have no impact on the level of mitosis or apoptosis. Overall, our study demonstrates the feasibility of kinase inhibitor screens for studying Hydra regeneration processes and highlights the possible role for Hydra Chk1 in head regeneration and maintenance.

Clinical Characteristics of Uveitis in Patients with Psoriasis in Korea: A Retrospective Multicenter Case Series.

PURPOSE: To describe the clinical characteristics and treatment outcomes of uveitis in patients with psoriasis in Korea. METHODS: The medical records of 20 patients (27 eyes) with psoriatic uveitis in two tertiary hospitals were retrospectively reviewed. We analyzed data about patient demographics, uveitis types, laterality, onset of disease, human leukocyte antigen (HLA) types, intraocular pressure, visual acuity, comorbidities, and medical treatments and outcomes for uveitis and psoriasis. RESULTS: The cohort comprised 11 males and nine females (age of onset, 50.1 ± 13.2 years) and the mean follow-up period was 3.9 ± 4.0 years. Types of uveitis included anterior (85%), intermediate (10%), and panuveitis (5%). A total of 13 (65%) cases presented with unilateral involvement and 12 out of 18 patients (66.7%) were positive for HLA-B27. The average intraocular pressure of affected eyes was 11.6 ± 3.6 at the first visit and 13.8 ± 3.6 mmHg at the final visit. The average logarithm of the minimum angle of resolution visual acuity of affected eyes at the initial examination was 0.16 ± 0.52 and 0.27 ± 0.71 at the last examination. Most common comorbidity (13 patients, 65%) was psoriatic arthritis (PsA). All cases underwent topical corticosteroid treatment; however, 11 (55%) required systemic corticosteroid and immunosuppressants for the treatment of uveitis. Notable deterioration in visual outcome was found in two cases (10%) due to severe intraocular inflammation and its complications (uveitic glaucoma and bullous keratopathy). Recurrent uveitis was observed in 57.9% of patients. Patients with PsA tended to have higher positive rate of HLA-B27 (83.3%). However, there was no significant correlation between visual prognosis and location of psoriatic uveitis, presence of PsA, and HLA-B27 positivity. CONCLUSIONS: Psoriatic uveitis in Koreans usually presents with anterior uveitis with unilateral involvement. PsA was the most common comorbidity. In majority of patients, visual outcomes are satisfactory with appropriate topical or systemic immunosuppressive treatment.

ELF-MF occupational exposure in die-casting and electroplating workers in Korea.

A 24-h exposure assessment was performed in two groups of blue-collar workers from a die-casting plant and an electroplating plant to investigate levels of exposure to extremely low-frequency magnetic fields (ELF-MFs), using an EMDEX Lite (Enertech, USA) dosimeter. ELF-MF exposure of workers from the die-casting plant (arithmetic M ± SD 0.649 ± 1.343 µT) is higher than in electroplating workers (0.138 ± 0.045 µT). Higher ELF-MF exposure occurred among workers living in the same building as their workplace compared with that among other workers. This study suggests that ELF-MF exposure levels should be taken into consideration when providing dormitories for workers to minimize levels of residential ELF-MF exposure due to emissions from industrial plants. The study recommends that blue-collar workers should be made aware of measures to minimize their exposure to environmental agents such as ELF-MFs and electromagnetic fields during work, such as maintaining a safe distance between machines and avoiding undesirable behavior with equipment.

Natural Course of Ophthalmoplegia after Iatrogenic Ophthalmic Artery Occlusion Caused by Cosmetic Filler Injections.

BACKGROUND: Besides the devastating complication of blindness, paralysis of the eye muscles, namely ophthalmoplegia, may occur after cosmetic facial filler injection. However, little is known of the clinical characteristics and prognosis of such complications. This study was performed to investigate the natural course of ophthalmoplegia and development of sensory strabismus secondary to blindness after iatrogenic occlusion of the ophthalmic artery and its branches resulting from cosmetic facial filler injection. METHODS: A retrospective study of 21 patients with occlusion of the ophthalmic artery and its branches after cosmetic facial filler injection was performed. The clinical characteristics and prognosis of ophthalmoplegia after cosmetic filler injection were evaluated. At the final examination, development of sensory strabismus defined as deviation of the eye secondary to unilateral vision loss was evaluated. RESULTS: At initial presentation, ophthalmoplegia was found in 15 of 21 patients (71 percent) and was significantly associated with the presence of anterior segment ischemia (p = 0.017). Among patients with ophthalmoplegia at initial presentation, ocular motility recovered completely in 77 percent and incomplete recovery was found in 23 percent. At the final examination, sensory strabismus developed in 42 percent after an average follow-up of 2.5 years. CONCLUSIONS: Ophthalmoplegia frequently occurs after iatrogenic occlusion of the ophthalmic artery and its branches caused by cosmetic facial filler injection. Ocular motility recovers spontaneously in most patients. However, as most patients are blind, sensory strabismus may develop in nearly half of patients during follow-up that requires strabismus surgery. CLINICAL QUESTION/LEVEL OF EVIDENCE: Risk, IV.

Epilepsy Surgery in Children versus Adults.

Epilepsy is one of the most common chronic neurological disorder affecting 6-7 per 1000 worldwide. Nearly one-third of patients with newly diagnosed epilepsy continue to have recurrent seizures despite adequate trial of more than two anti-seizure drugs : drug-resistant epilepsy (DRE). Children with DRE often experience cognitive and psychosocial co-morbidities requiring more urgent and aggressive treatment than adults. Epilepsy surgery can result in seizure-freedom in approximately two-third of children with improvement in cognitive development and quality of life. Understanding fundamental differences in etiology, co-morbidity, and neural plasticity between children and adults is critical for appropriate selection of surgical candidates, appropriate presurgical evaluation and surgical approach, and improved overall outcome.

Comparison of Cerebrospinal Fluid Cytokine Levels in Children of Enteroviral Meningitis With Versus Without Pleocytosis.

In viral meningitis, proinflammatory cytokines were detected at higher levels in the cerebrospinal fluid (CSF) and might play an important role in the inflammatory process. Our goal was to compare the cytokine profiles in the CSF of children of enteroviral meningitis (EVM) with versus without CSF pleocytosis. In total, 158 patients were enrolled in this prospective cohort study and were classified as EVM (group-A, n = 101), nonenteroviral aseptic meningitis (group-B, n = 27), and control (group-C, n = 30) groups. Of the 101 children with EVM, 71 had CSF pleocytosis (group-A1) and 30 had CSF nonpleocytosis (group-A2). Fifteen cytokines/chemokines in the CSF were measured simultaneously by immunoassay. Significant differences were found in interleukin (IL)-2, IL-6, and IL-8 levels in the CSF across the 3 groups, with the highest levels in group-A, followed by group-B and group-C. The levels of IL-1ß, IL-2, IL-6, IL8, IL-10, interferon-γ, and tumor necrosis factor-α were significantly higher in the CSF of group-A1 than in that of group-A2. Group-A2 was significantly younger than group-A1 (3.4 ± 2.8 years versus 5.5 ± 3.2 years, P = 0.016). Significant differences between CSF pleocytosis and nonpleocytosis in EVM appear to be associated with distinct levels of CSF cytokines.

Three children of meningoencephalitis with Kikuchi necrotizing lymphadenitis.

BACKGROUND: Kikuchi necrotizing lymphadenitis (KNL) is a rare and benign cause of lymphadenopathy, most often cervical. The etiology of KNL remains unknown. Central nervous system (CNS) involvement, such as in meningoencephalitis, is a very rare clinical manifestation of KNL, especially in children. CASE REPORTS: A 12-year-old boy presented with unilateral cervical lymphadenopathy and fever. Histopathological findings led to the diagnosis of KNL. He revisited due to severe headache and vomiting one week later. Cerebrospinal fluid (CSF) analysis demonstrated pleocytosis (lymphocytic 57%), high protein (312 mg/dL) and low CSF/serum glucose ratio (52/121 mg/dL.) The next day, he had a seizure. Brain MRI revealed increased signal involving posterior area of both hemisphere. Another 17-year-old boy presented with headache for 7 days and behavioral and personality changes. He had a history of cervical lymphadenopathy two weeks ago. CSF analysis demonstrated lymphocytosis, high protein and low glucose ratio. MRI revealed the involvement of right cerebellum and posterior brainstem. A biopsy of one cervical lymphadenopathy demonstrated the findings of KNL. A 15-year-old girl presented with fever, headache, and cervical pain lasting 10 days. CSF analysis demonstrated pleocytosis (lymphocytic 95%), high protein and low CSF/serum glucose ratio. Histopathological findings of lymph node were suggestive of KNL. Above three patients were undertaken the steroid therapy and recovered fully without neurological dysfunction. CONCLUSIONS: Recognition of CNS involvement in KNL may help evaluate the patients of acute meningitis/encephalitis with regional lymphadenopathy, thereby avoiding unnecessary treatment.

A neonate with Joubert syndrome presenting with symptoms of Horner syndrome.

Joubert syndrome (JS) is characterized by the "molar tooth sign" (MTS) with cerebellar vermis agenesis, episodic hyperpnea, abnormal eye movements, and hypotonia. Ocular and oculomotor abnormalities have been observed; however, Horner syndrome (HS) has not been documented in children with JS. We present the case of a 2-month-old boy having ocular abnormalities with bilateral nystagmus, left-dominant bilateral ptosis, and unilateral miosis and enophthalmos of the left eye, which were compatible with HS. Brain magnetic resonance imaging (MRI) revealed the presence of the MTS. Neck MRI showed no definite lesion or mass around the cervical sympathetic chain. His global development was delayed. He underwent ophthalmologic surgery, and showed some improvement in his ptosis. To the best of our knowledge, the association of HS with JS has not yet been described. We suggest that early neuroimaging should be considered for neonates or young infants with diverse eye abnormalities to evaluate the underlying etiology.

Neurocognitive function in children after anterior temporal lobectomy with amygdalohippocampectomy.

BACKGROUND: We assessed the postoperative neurocognitive function after temporal lobectomy in children with temporal lobe epilepsy. METHODS: This was a retrospective analysis of the data of 20 patients with Engel's class I or II outcomes after anterior temporal lobectomy with amygdalohippocampectomy between 2005 and 2008. Twenty children underwent resection of either dominant (n = 8) or nondominant (n = 12) temporal lobes, and their median age at surgery was 12.8 ± 3.2 years. We serially assessed intelligence and memory function as measured by the Korean-Wechsler Scales of Intelligence and Rey-Kim Memory test both before and after surgery. RESULTS: Intelligence quotient (IQ) and memory quotient scores remained stable during a 3.6-year median follow-up in these children after the surgery. There was no decrease of IQ or memory quotient scores in either the dominant or non-dominant hemisphere groups. Later onset of epilepsy, a shorter epilepsy duration, a smaller number of antiepileptic drugs, and postoperative seizure-free outcomes were significant good predictors of the postoperative IQ. CONCLUSION: Temporal lobectomy in children did not provoke a significant decline in intelligence or memory function. Early surgical treatment in children with intractable seizures of temporal lobe origin may result in better neurocognitive outcomes.

Melkersson-Rosenthal syndrome with Hashimoto thyroiditis in a 9-year-old girl: an autoimmune disorder.

BACKGROUND: Melkersson-Rosenthal syndrome (MRS) is a rare disorder of unknown cause. The classical triad of MRS is orofacial edema, recurrent facial paralysis, and a fissured tongue. PATIENT: We present a 9-year-old girl with a recurrent peripheral facial paralysis. She experienced the first episode of a peripheral facial paralysis on the same side without orofacial swelling and lingua plicata 1 year ago. She was diagnosed with Hashimoto thyroiditis 9 months earlier, as confirmed by an endocrinologic investigation. RESULTS: While the patient was hospitalized with recurrent facial paralysis, we found that serum levels of free thyroxine (1.3 ng/dL) and thyrotropin (0.4 uIU/mL) were within normal range, but the level of antithyroperoxidase antibodies (772.0 IU/mL) was very increased. She had been taking an oral prednisolone orally for 2 weeks. At the 1-month follow-up, the patient's symptoms had completely disappeared. DISCUSSION: The possible correlation between MRS and autoimmune disorders has been documented in only one report, which described an adult with autoimmune thyroiditis (Hashimoto thyroiditis) and MRS. We suggest that the co-occurrence of MRS and Hashimoto thyroiditis is not coincidental but linked to autoimmunity.

Outcomes of epilepsy surgery in childhood-onset epileptic encephalopathy.

PURPOSE: to evaluate the outcomes and role of epilepsy surgery in children with intractable epileptic encephalopathy (EE). METHODS: ninety-five children (64 boys, 31 girls) with intractable EE were treated by epilepsy surgery at Severance Children's Hospital from 2003 to 2008. Surgical treatments included lobar resection, hemispherotomy and corpus callosotomy (CC). Seventy-six children were Lennox-Gastaut syndrome (LGS), and 19 had West syndrome. RESULTS: of the 76 patients with LGS, CC was performed in 37 patients (48.7%), lobar resection in 29 (38.2%) and hemispherotomy in 10 (13.2%). Of the 19 patients with West syndrome, respective surgery was performed in 15 patients (78.9%) and CC in 4 (21.1%). Of the patients receiving respective surgery, Engel's class I outcomes were achieved for 24 of 39 (61.5%) of LGS patients, and for 9 of 15 (60.0%) of West syndrome. Malformations of cortical development were commonly observed, appearing in 73.5% (36/49). In neuropsychiatric tests, 19 of 27 with LGS demonstrated improvement in postoperative cognitive function. More significant intellectual improvement correlated well with shorter epilepsy duration, good seizure outcomes, and decreased number of antiepileptic drugs. CONCLUSIONS: epilepsy surgery should be considered in treating childhood intractable EE with expectation of improvement of both seizure and cognitive outcomes, even in cases of LGS.

Temporal lobe epilepsy surgery in children versus adults: from etiologies to outcomes.

Temporal lobe epilepsy (TLE) is the most common type of medically intractable epilepsy in adults and children, and mesial temporal sclerosis is the most common underlying cause of TLE. Unlike in the case of adults, TLE in infants and young children often has etiologies other than mesial temporal sclerosis, such as tumors, cortical dysplasia, trauma, and vascular malformations. Differences in seizure semiology have also been reported. Motor manifestations are prominent in infants and young children, but they become less obvious with increasing age. Further, automatisms tend to become increasingly complex with age. However, in childhood and especially in adolescence, the clinical manifestations are similar to those of the adult population. Selective amygdalohippocampectomy can lead to excellent postoperative seizure outcome in adults, but favorable results have been seen in children as well. Anterior temporal lobectomy may prove to be a more successful surgery than amygdalohippocampectomy in children with intractable TLE. The presence of a focal brain lesion on magnetic resonance imaging is one of the most reliable independent predictors of a good postoperative seizure outcome. Seizure-free status is the most important predictor of improved psychosocial outcome with advanced quality of life and a lower proportion of disability among adults and children. Since the brain is more plastic during infancy and early childhood, recovery is promoted. In contrast, long epilepsy duration is an important risk factor for surgically refractory seizures. Therefore, patients with medically intractable TLE should undergo surgery as early as possible.

X-linked recessive myotubular myopathy with MTM1 mutations.

X-linked recessive myotubular myopathy (XLMTM) is a severe congenital muscle disorder caused by mutations in the MTM1 gene and characterized by severe hypotonia and generalized muscle weakness in affected males. It is generally a fatal disorder during the neonatal period and early infancy. The diagnosis is based on typical histopathological findings on muscle biopsy, combined with suggestive clinical features. We experienced a case of a newborn who required intubation and ventilator care because of profound hypotonia and respiratory difficulty. The preliminary diagnosis at the time of request for retrieval was hypoxic ischemic encephalopathy, but the infant was clinically reevaluated for generalized weakness and muscle atrophy. Muscle biopsies showed variability in fiber size and centrally located nuclei in nearly all the fibers. We detected an MTM1 gene mutation of c.1261-1C>A in the intron 10 region, and diagnosed the neonate with myotubular myopathy. The same mutation was detected in his mother.

Moyamoya syndrome occurred in a girl with an inactive systemic lupus erythematosus.

We report the case of a 17-year-old Korean girl with systemic lupus erythematosus (SLE) who presented with sudden weakness of the right-sided extremities and dysarthria. Oral prednisolone was being taken to control SLE. Results of clinical and laboratory examinations did not show any evidence of antiphospholipid syndrome or thromboembolic disease nor SLE activity. Cerebral angiography showed stenosis of the left internal carotid artery and right anterior cerebral artery with accompanying collateral circulation (moyamoya vessels). After the patient underwent bypass surgery on the left side, she recovered from the neurological problems and did not experience any additional ischemic attack during the 14-month follow-up period. This case represents an unusual association between moyamoya syndrome and inactive SLE (inactive for a relatively long interval of 2 years) in a young girl.

Expression of neuronal antigens and related ventral and dorsal proteins in the normal spinal cord and a surgically induced open neural tube defect of the spine in chick embryos: an immunohistochemical study.

OBJECTIVE: The aims of this study were to elucidate the processes of neuronal differentiation and ventrodorsal patterning in the spinal cord of the chick embryo from embryonic day (E) 3 to E17 and to study the effect of a prenatal spinal open neural tube defect (ONTD) on these processes. METHOD: Expression patterns of neuronal antigens (neuronal nuclear antigen, neurofilament-associated protein (NAP), and synaptophysin) and related ventral markers [sonic hedgehog, paired box gene (PAX)6, and islet-1], and dorsal markers (bone morphogenetic protein, Notch homolog 1, and PAX7) were investigated in the normal spinal cord and in a surgically induced spinal ONTD in chick embryos. Four normal and ONTD chick embryos were used for each antigen group. RESULT & CONCLUSION: There were no differences in the expression of neuronal and ventrodorsal markers between the control and ONTD groups. NAP and synaptophysin were useful for identifying dorsal structures in the distorted anatomy of the ONTD chicks.