Assessment of Neurology Residency Program Websites across North America during COVID-19.

With virtual interviews for residency applications, residency program websites have become increasingly important resources for applicants. We evaluated the comprehensiveness of US and Canadian neurology residency program website, comparing this to published rankings of the best neurology and neurosurgery hospitals (for US programs) and number of residency positions (for US and Canadian programs). US program websites were found to be largely more comprehensive than Canadian websites, more extensive websites were associated with better program rankings and fewer residency seats in the US, and US regional differences in comprehensiveness were present. We recommend standardized guidelines to increase website comprehensiveness across programs.

Disease-modifying therapies used to treat multiple sclerosis and the gut microbiome: a systematic review.

BACKGROUND: The gut microbiome may play a role in multiple sclerosis (MS). However, its relationship with the disease-modifying therapies (DMTs) remains unclear. We systematically reviewed the literature to examine the relationship between DMTs and the gut microbiota among persons with MS (pwMS). METHODS: MEDLINE, EMBASE, Web of Science, and Scopus were searched (01/2007-09/2022) for studies evaluating potential gut microbiota differences in diversity, taxonomic relative abundances, and functional capacity between DMT-exposed/unexposed pwMS or before/after DMT initiation. All US FDA-approved MS DMTs (1993-09/2022) and rituximab were included. RESULTS: Of the 410 studies, 11 were included, totalling 1243 pwMS. Of these, 821 were DMT exposed and 473 unexposed, including 51 assessed before/after DMT initiation. DMT use duration ranged from 14 days to > 6 months. No study found a difference in gut microbiota alpha-diversity between DMT exposed/unexposed (p > 0.05). One study observed a difference in beta-diversity between interferon-beta users/DMT non-users (weighted UniFrac, p = 0.006). All studies examined taxa-level differences, but most (6) combined different DMTs. Two or more studies reported eight genera (Actinomyces, Bacteroides, Clostridium sensu stricto 1, Haemophilus, Megasphaera, Pseudomonas, Ruminiclostridium 5, Turicibacter) and one species (Ruthenibacterium lactatiformans) differing in the same direction between DMT exposed/unexposed. DMT users had lower relative abundances of carbohydrate degradation and reductive tricarboxylic acid cycle I pathway than non-users (p < 0.05), but findings could not be attributed to a specific DMT. DISCUSSION: While DMT use (versus no use) was not associated with gut microbiota diversity differences, taxa-level differences were observed. Further work is warranted, as most studies were cross-sectional, few examined functionality, and DMTs were combined.

Parakinesia Brachialis Oscitans and Excessive yawning From Tumefactive Demyelination.

We present a case and video of a 31-year-old man with biopsy-confirmed tumefactive demyelination affecting the right internal capsule causing left hemiplegia, excessive yawning, and the curious but well-described phenomenon of parakinesia brachialis oscitans (PBO) with transient tonic elevation of his paralyzed arm while yawning. PBO is most commonly reported in ischemic stroke with internal capsule or pontomedullary brainstem lesions. Our case uniquely demonstrates this phenomenon in the case of tumefactive demyelination. We also highlight excessive yawning which has also been described in multiple sclerosis.

Sex, racial, and ethnic disparities in motor neuron disease: clinical trial enrolment.

OBJECTIVE: Motor neuron disease (MND) is a group of neurological diseases, the majority being amyotrophic lateral sclerosis (ALS), with varying clinical presentations across demographics. Clinical trial enrollment reflecting global disease burden improves understanding of diverse presentations and aids personalized therapy development. We assessed the sex, racial, and ethnic composition of MND/ALS clinical trial participants relative to global disease burdens. METHODS: We searched 'motor neuron disease OR amyotrophic lateral sclerosis' on ClinicalTrials.gov from 02/2000-04/2024. We extracted trial (start year, study site, sponsor location, phase, masking, intervention) and demographic data (sex, race, ethnicity) from randomized interventional studies. We obtained sex-based MND/ALS disease burden estimates from the Global Burden of Disease database. For females, we calculated pooled participation-to-prevalence ratio (PPR) with 95% confidence intervals (CIs), with PPR of 0.8-1.2 indicating adequate enrollment. We used Kruskal-Wallis tests to compare demographic groups across trial characteristics. RESULTS: Of 85 trials, females comprised 37.47% (n = 5011) of 13,372 participants; the pooled female PPR was 0.97 (95% CI: 0.77-1.16). Of 41 trials (9340 participants) reporting race, 121 (1.30%) participants were Black or African American, 16 (0.17%) American Indian or Alaskan Native, and 6 (0.06%) Native Hawaiian or Other Pacific Islander. 24 trials (595 participants) reported ethnicity, with a minority of Hispanic participants (n = 153; 2.57%). CONCLUSIONS: MND/ALS clinical trials had adequate female enrollment relative to global disease burdens. Race and ethnicity data were underreported. However, there were enrollment disparities of racial and ethnic groups. Increased trial leadership diversity, equitable enrollment policies, and addressing barriers to participation could improve enrollment diversity.

Synthesis of 9,10-bis-ketoenaminoanthryl and 9,10-bis-isoxazolylanthryl linked biscalix[4]arenes: atropisomers and molecular recognitions.

An efficient synthetic pathway for the synthesis of biscalix[4]arenes 5-10 using 1,3-dipolar cycloaddition reactions is reported. Biscalix[4]arene 10 is capable of forming a complex with methyl viologen because of favorable cation-π interactions and a proper cavity size to accommodate the guest. Moreover, biscalix[4]arenes 8a and 8b were found to be atropisomers at room temperature. These two conformers were unable to exchange at room temperature because of the restricted rotation of the C(9)-C(11) or C(10)-C(12) bonds of the ß-amino-α,ß-unsaturated ketones of anthracene.

A dataset of sea turtle occurrences around the Taiwan coast.

Background: We describe a dataset of sea turtle sightings around the coast of Taiwan and its islands (Hoh and Fong 2022). This data collection was initiated by TurtleSpot Taiwan, a citizen-science project that collects sea turtle sighting data. This dataset includes 3,515 sighting data dated from March 2010, except most of the data (n = 3,128; 89%) were collected between June 2017 to December 2021. Sightings were reported by citizen scientists to the Facebook Group of TurtleSpot Taiwan by providing occurrence information. We also requested photos and videos for species identification and to record any physical abnormality of the turtle, if observable. In addition to recording data often associated with an occurrence, TurtleSpot aims to identify each sea turtle up to the individual level using the Photo Identification (Photo ID) method. Hence, if photos of left facial scutes were available, the sighted individual can be identified and given a unique turtle ID. In total, 762 individuals were assigned a turtle ID, comprising 723 Greens (Cheloniamydas), 38 Hawksbills (Eretmochelysimbricata) and one Olive Ridley (Lepidochelysolivacea) turtle. This dataset is now publicly opened in Global Biodiversity Information Facility (GBIF) and available for download. It is hoped that the data may assist in future ecological studies and the development of conservation measures. New information: This dataset contains 3,515 occurrence records of sea turtles (Cheloniidae) and is currently the largest public dataset of sea turtle sighting records in Taiwan. Post-publication of this dataset to the GBIF platform demonstrated that the number of Green sea turtle Cheloniamydas records in Taiwan is one of the largest in the world (last accessed date: 15-10-2022). The data served as the foundation for understanding biogeography and sea turtle ecology in Taiwan's coastal waters.

Legacy Chemical Pollutants in House Dust of Homes of Pregnant African Americans in Atlanta.

We developed and applied a method for measuring selected persistent organic pollutants (POPs) (i.e., polybrominated diphenyl ethers (PBDEs), organochlorine pesticides, and polychlorinated biphenyls (PCBs)) in dust collected from pregnant African Americans (AAs) in Atlanta using isotope dilution gas chromatography-tandem mass spectrometry. Limits of quantification were ranged from 0.10 to 2.50 ng/g dust. NIST standard reference material measurements demonstrated the robustness of our method. Our accuracies ranged from 82 to 108%, relative standard deviations ranged from 2 to 16%, and extraction recoveries ranged from 76 to 102%. We measured POPs in dust collected from 34 homes of pregnant AAs participating in the Atlanta AA birth cohort study who were enrolled from 2016 to 2019. Concentrations of POPs were detected in all samples with the frequencies of detection ranging from 8 to 100%. Concentrations of PBDE congeners 99 and 47, p,p'-DDT, and PCB153 were detected at some of the highest concentrations with geometric means of 1270, 730, 63.4 and 240 ng/g, respectively. The ratio of DDT/DDE was quite large (~2.7) indicating that p,p'-DDT remains intact in homes for long periods of time. These data demonstrate that care should be taken to remediate POPs in indoor dust, especially in vulnerable, disparate segments of the population.

Substituent effects on the iodine-catalyzed thermal cyclization of 3,4-diphenylbuta-1,3-dienyl isocyanates: mechanistic studies.

The thermal cyclization of 3,4-diphenylbuta-1,3-dienyl isocyanates 1, generated in situ from the corresponding azides, was investigated using iodine as a catalyst. Diphenylpyridinones 2, phenylnaphthalenes 3, and indenes 4 were produced via intramolecular ring closure. The nature of the substituents on the phenyl rings was found to be crucial to the distribution of cyclized products 2-4. The mechanism of the reaction is also discussed.

Celecoxib enhances radiosensitivity in medulloblastoma-derived CD133-positive cells.

OBJECTS: Cyclooxygenase-2 (COX-2), the enzyme that converts arachidonic acid to prostaglandins, is overexpressed in a variety of tumors, including medulloblastoma (MB). CD133, a transmembrane glycoprotein, has been suggested as a marker for cancer stem cells in brain tumors. The aim of the present study was to investigate the role of celecoxib, a selective COX-2 inhibitor, in enhancing the effects of ionizing radiotherapy (IR) on medulloblastoma-derived CD133-positive cells (MB-CD133(+)). MATERIALS AND METHODS: MB-CD133(+) were isolated from two medulloblastoma cell lines (Daoy and UW228). Then, they were treated with celecoxib in different concentrations, and cell viability was assessed. The assays of cell survival, soft agar, radiosensitivity, colony formation, and apoptotic activity in MB-CD133(+) treated with celecoxib alone, radiation alone, or celecoxib combined with radiation were further evaluated. RESULTS: MB-CD133(+) showed the self-renew ability to form sphere bodies in vitro and regenerate tumors in vivo. The levels of COX-2 mRNA and protein in MB-CD133(+) were significantly higher than those in MB-CD133(-). The treatment of 30 µM celecoxib could effectively inhibit the abilities of cell proliferation and colony formation and increase IR-induced apoptosis in treated MB-CD133(+). Furthermore, in vivo study demonstrated that celecoxib significantly enhanced radiosensitivity in MB-CD133(+)-transplanted grafts. Notably, xenotransplantation analysis demonstrated that the treatment of celecoxib could further suppress the expressions of angiogenic and stemness-related genes in treated MB-CD133(+) grafts of SCID mice. CONCLUSIONS: Celecoxib presents the potential of radiosensitizing effect in MB-derived cancer stem cells. Therefore, it should be warranted in future trials to enhance the radiotherapeutic effects in MB patients.

Characteristics of Frequent Attenders Compared with Non-Frequent Attenders in Primary Care: Study of Remote Communities in Taiwan.

Frequent attenders (FAs) have an impact on the medical resources and the quality of care. In Taiwan, the characteristics of FAs remain unclear in primary care. Outpatient data were screened from a central clinic within six surrounding fishing villages in northeastern Taiwan in 2017. FAs were defined as those who made >18 visits in one year, and those who made ≤18 visits were defined as non-frequent attenders (NFAs). Data of FAs and NFAs were collected and compared. The major diagnoses were reported using International Classifications of Diseases, Tenth Edition (ICD-10) codes. A total of 1586 subjects and 9077 visits were enrolled, including 119 FAs and 1467 NFAs. FAs had a more advanced age compared to NFAs. Both FAs and NFAs had more visits in summer. FAs had consumed high prescriptions and related costs. FAs also had higher therapeutic and first visit costs than NFAs. Comparing with age- sex-matched NFAs, FAs were positively associated with musculoskeletal diseases (M00-M99), hematological diseases (D50-D89), endocrine diseases (E00-E90), and mental disorders (F00-F99). Large-scale local datasets and suitable definitions of FAs for Taiwanese subjects are needed.

Relationship between central corneal thickness, refractive error, corneal curvature, anterior chamber depth and axial length.

BACKGROUND: To determine the relationship between central corneal thickness (CCT), refractive error, corneal curvature, anterior chamber depth and axial length in normal Taiwanese Chinese adults. METHODS: Five hundred normal Taiwanese Chinese patients aged 40-80 years were recruited for the study. Measurement procedures included CCT, refractive error, corneal curvature, anterior chamber depth and axial length. Exclusion criteria were previous ocular surgery, glaucoma, trauma history, external eye disease, and previous contact lens use. The relationships among parameters were tested using Pearson's correlation and linear regression analysis. RESULTS: The median CCT was 555 +/- 27 mum for males and 553 +/- 30 mum for females. Eyes with more myopic refractive error tended to have greater axial length (r = -0.645, p < 0.001). Eyes with axial elongation tended to have flatter cornea (r = -0.502, p < 0.001) and deeper anterior chamber (r = 0.651, p < 0.001). There were no significant correlations between the CCT and refractive error (r = -0.034, p = 0.445), corneal curvature (r = 0.013, p = 0.770), anterior chamber depth (r = 0.023, p = 0.614) and axial length (r = -0.053, p = 0.223). CONCLUSION: CCT was not associated with refractive error, corneal curvature, anterior chamber depth and axial length. CCT is an independent factor unrelated to other ocular parameters.

The Primary Care of Immigrant Workers and Their Associated Characteristics within A Taiwanese Fishing Community.

In Taiwan, immigrant workers play an important role in fisheries but they are easily ignored by society. The health problems and associated characteristics of immigrant workers in fisheries remain unclear. Descriptive and retrospective analyses were performed. Outpatient data were collected from a primary care clinic for six fishing villages in North Eastern Taiwan between 1 August 2016 and 31 July 2017. The data of immigrant workers was recorded and compared with that of natives. A total of 241 immigrant workers and 1342 natives were enrolled. Compared with the natives, the immigrant workers had a significantly younger age, male predominance, and fewer mean visits per year. The immigrant worker's visits tended to be more highly focused during the third quarter of the year. Immigrant workers paid more registration fees and self-payment, but they paid less on diagnosis fees, oral medication, laboratory exams and had reduced total costs. The top five diagnoses for immigrant workers were respiratory diseases (38.3%), trauma (15.2%), musculoskeletal diseases (11.2%), skin-related diseases (9.5%), and digestive diseases (9.1%). Immigrant workers were positively correlated with infectious/parasitic diseases, and negatively correlated with medical consults and endocrine/metabolic diseases. Immigrant workers were also positively associated with registration fees and self-payment, but negatively correlated with diagnosis fees and total costs (all p < 0.05). The distribution of skin diseases and trauma were affected by age and sex as opposed to ethnic group. Immigrant status' health issues should be given more attention.

Behcet's disease with uveitis in Taiwan.

BACKGROUND: Behcet's disease is a multisystemic inflammatory disease which may lead to blindness. The purpose of this study was to describe and compare the clinical features and visual outcome of Behcet's uveitis in Taiwan. METHODS: The medical charts of 227 consecutive patients (414 eyes) with Behcet's uveitis who were seen in the Uveitis Clinic of Taipei Veterans General Hospital were reviewed: 96 patients (group A) between 1984 and 1993 and 131 (group B) between 1994 and 2003. RESULTS: The male-to-female ratio was 1.6. The mean age at the time of uveitis onset was 30.8 years. Males were most affected in the 3rd and 4th decades and females in the 2nd to 5th decades. There were more skin and gastrointestinal lesions in males, and less skin and genital lesions in group B. HLA-B51 antigen was found in 35.7% of patients. Treatment with cyclosporin, azathioprine and methotrexate was more frequent in group B. Uveitis occurred bilaterally in 83.9% of patients. At the first visit, potential visual acuity (VA) was 0.1 or less in 24.7% of eyes in males and 11.4% in females. The mean time from presentation to loss of useful vision (> 0.1) was 51 months in 19.1% of eyes. Kaplan-Meier survival analysis estimated the risks of losing useful vision at 5, 10 and 15 years as being 22.6%, 43.0% and 58.5%, respectively. VA at the first and last visits were better and VA deterioration slower in group B. CONCLUSION: Visual outcome is poorer in males than in females and has improved in the recent decade, but still a significant proportion of patients lose their vision quickly. The number of new patients has not decreased.

Characterization and functional correlation of multiple imaging modalities with focal choroidal excavation.

BACKGROUND: To investigate the clinical manifestations and imaging features of near-infrared autofluorescence (NIA), infrared reflectance (IR), fundus autofluorescence (FAF), indocyanine green angiography (ICGA) and fluorescein angiography (FAG) in the detection of patients with focal choroidal excavation (FCE) identified by cross-sectional spectral-domain optical coherence tomography (SD-OCT). METHODS: This retrospective cross-sectional study included 12 eyes of 10 Taiwanese patients with FCE diagnosed by SD-OCT. The areas and depths of FCE in serial cross-sectional and en-face OCT were compared in different imaging modalities. NIA, IR, FAF, ICGA and FAG images were obtained. Best corrected visual acuity, subjective distortion area in the Amsler grid and history of maculopathies were also recorded. RESULTS: In areas where the choroid started to excavate as shown in SD-OCT, hypo-autofluorescence in NIA was noted. The area of hypo-fluorescence in NIA of all the FCE lesions showed good correlation with the size. The area of FCE was associated with complications such as choroidal neovascularization and central serous chorioretinopathy (p = 0.014, d.f = 1) and the volume (NIA area × Depth measured by SD-OCT × 1/3) was associated with subjective distortion strongly (p = 0.051, Spearman's correlation = 0.600). CONCLUSION: Among all image modalities, NIA was the most sensitive tool in area measurement of FCE and peripheral lesion detection. Also, the volume of FCE was associated with subjective distortion and the area was related to complications. Recording the area and volume of FCE could play an important role in monitoring complications.

Cyano Group Removal from Cyano-Promoted Aza-Diels-Alder Adducts: Synthesis and Structure-Activity Relationship of Phenanthroindolizidines and Phenanthroquinolizidines.

Phenanthroindolizidines and phenanthroquinolizidines were concisely synthesized by the reductive decyanization of cyano-promoted intramolecular aza-Diels-Alder cycloadducts followed by aryl-aryl coupling. Cyano groups were removed from α-aminoacrylonitriles via treatment with sodium borohydride in 2-propanol in almost quantitative yields; a possible mechanism was proposed and examined using D-labeling experiments. A systematic study of the effects of the phenanthrene substitution pattern on the anticancer activity against three human cancer cell lines was discussed.

Electrophysiological changes in lipaemia retinalis.

PURPOSE: To report the electrophysiologic findings in a patient with lipaemia retinalis. DESIGN: Observational case report. METHODS: An 11-year-old girl with diabetes had hyperlipidemia and presented for ophthalmologic consultation. Fundus examinations revealed milky discoloration of retinal vessels in both eyes. Laboratory testing disclosed hyperglycemia and markedly elevated level of triglycerides and cholesterol. Although the visual acuity was not affected, the electroretinograms showed decrease amplitudes of a- and b-wave in both cone and rod responses. RESULTS: After correction of blood sugar and lipids with insulin and diet control, the lipaemia retinalis resolved, and the impaired ERG response reversed within 1 week. CONCLUSIONS: Lipaemia retinalis usually resolves rapidly without visual impairment after correction of hyperlipidemia. The reversible deficits of electroretinogram response in lipaemia retinalis are reported for the first time. High level of triglycerides or cholesterol or both may impair retinal function. The mechanism of an impaired electroretinogram remained speculative.

Anthryl-1,2,4-oxadiazole-substituted calix[4]arenes as highly selective fluorescent chemodosimeters for Fe(3+).

Fluorescent chemosensors 1 and 2, with 1,2,4-oxadiazoles as the binding ligands and anthracene as the fluorophore, were synthesized through sequential 1,3-dipolar cycloaddition reactions of 25,27-dioxyacetonitrilecalix[4]arenes 8 and 11. The fluorescence of 1 was severely quenched by both Fe(3+) and Cu(2+) , whereas that of 2 was selectively quenched only by Fe(3+) . Control compound 4 was also selectively quenched by Fe(3+) , which implied the importance of anthryl-1,2,4-oxadiazole core; furthermore, it was shown to give various oxidation products such as oxanthrone 13, anthraquinone 14, and imidazolyl oxanthrone 15. In addition to product separation and identification, the fluorescent quenching mechanism of these 9-anthryl-1,2,4-oxadiazolyl derivatives by Fe(3+) is also discussed. Furthermore, it should be noted that the oxadiazole-substituted anthracene 4 and calix[4]arene 2 are Fe(3+) -selective fluorescent chemodosimeters without the interference by Cu(2+) .

Postpartum endogenous Candida endophthalmitis.

Candida albicans is the most common pathogen causing intraocular fungal infection. Postpartum endogenous Candida endophthalmitis, however, is extremely rare. We report the case of a 33-year-old postpartum woman who presented with a 5-day history of decreased vision and had a positive blood culture for C. albicans. Fundus examination showed vitreous haze and multiple pre-retinal whitish lesions with indistinct borders. Systemic investigations revealed acute renal failure and cardiomegaly. After treatment with intravenous antifungal therapy, vitrectomy, and intravitreal injection of antimycotics, systemic and intraocular infections were eradicated successfully.

A modified liquid chromatography/tandem mass spectrometry method for predominant disaccharide units of urinary glycosaminoglycans in patients with mucopolysaccharidoses.

BACKGROUND: The identification of acid mucopolysaccharide by the liquid chromatography/tandem mass spectrometry method (LC-MS/MS) of the predominant disaccharide units of glycosaminoglycans (GAGs) (chondroitin sulfate, CS; dermatan sulfate, DS; heparan sulfate, HS) after methanolysis is validated and applicable for mucopolysaccharidosis (MPS) type determination. METHODS: A total of 76 urine samples were collected and analyzed, from nine MPS I patients, 13 MPS II patients, seven MPS III patients, eight MPS VI patients, and 39 normal controls. Urinary GAG was first precipitated by the Alcian blue method followed by a treatment of 3 N HCl methanol. The protonated species of the methylated disaccharide products were detected by using a multiple reaction monitoring experiment. Internal standards, [2H6] CS, [2H6] DS and [2H6] HS, were prepared in-house by deuteriomethanolysis of CS, DS and HS. RESULTS: One particular disaccharide for each GAG was selected, in which the parent ion and its daughter ion after collision were m/z 426.1 → 236.2 for DS (m/z 432 → 239 for dimers derived from [2H6] CS and [2H6] DS) and m/z 384.2 → 161.9 for HS (m/z 390.4 → 162.5 for the [2H6] HS dimer). The quantities of DS and HS were determined, which varied from one MPS type to the other. The results can be used to evaluate the severity of MPS subgroups, as well as urinary GAG amelioration at follow-up after enzyme replacement therapy (ERT). CONCLUSIONS: The modified LC-MS/MS method for MPS type determination is specific, sensitive, validated, accurate, and applicable for simultaneous quantifications of urinary DS and HS. This method can help to make correct diagnosis of MPS patients and evaluate the effectiveness of ERT.