Validity and Reliability of the European Foot and Ankle Society (EFAS) Score in Patients With Hallux Valgus in Singapore.

The European Foot and Ankle Society score is a popular tool for monitoring treatment outcomes of foot or ankle conditions. However, few studies have assessed its psychometric properties in patients with hallux valgus. We aimed to validate the European Foot and Ankle Society score in patients with hallux valgus in Singapore. This is a cohort study of 121 patients with operatively managed hallux valgus from a tertiary referral hospital, evaluated preoperatively and at 6 months postoperatively with the primary endpoint of restoring patients to premorbid status. Internal consistency was assessed via Cronbach's alpha. Construct validity was assessed through 7 a priori hypotheses by correlating the European Foot and Ankle Society score with other patient-reported outcomes measures. Structural validity was assessed via Confirmatory Factor Analysis, whereby a good fit was indicated when Comparative Fit Index >0.95, Tucker-Lewis Index >0.95, Root Mean Square Error of Approximation <0.06, and Standardized Root Mean Residuals <0.08. Among our subjects, the European Foot and Ankle Society score demonstrated reliability, reflected by a good internal consistency (Cronbach's alpha = 0.773). Six out of the 7 a priori hypotheses were fulfilled, indicating both convergent and divergent construct validity. Structural validity was confirmed with our European Foot and Ankle Society score model which showed good fit for a 1-factor structure (Confirmatory Factor Analysis = 0.998, Tucker-Lewis Index = 0.996, Root Mean Square Error of Approximation = 0.025 [90% CI: 0-0.111], Standardized Root Mean Residuals = 0.027). In conclusion, the European Foot and Ankle Society score was validated for monitoring treatment outcomes of patients with hallux valgus in Singapore.

TNFAIP3, a negative regulator of the TLR signaling pathway, is a potential predictive biomarker of response to antidepressant treatment in major depressive disorder.

Inflammation and abnormalities in Toll-like receptor (TLR) expression and activation have been linked to major depressive disorder (MDD). However, negative regulators of TLR pathways have not been previously investigated in this context. Here, we sought to investigate the association of depression severity, measured by the 17-item Hamilton Depression Rating Scale (HAMD-17), with mRNA expression levels of negative regulators of the TLR pathway, including SOCS1, TOLLIP, SIGIRR, MyD88s, NOD2 and TNFAIP3, in peripheral blood mononuclear cells (PBMCs) from 100 patients with MDD and 53 healthy controls, before and after treatment with antidepressants. Positive regulators of the TLR4 pathway, including Pellino 1, TRAF6 and IRAK1, were also investigated. Among all patients, MyD88s, and TNFAIP3 mRNAs were expressed at lower levels in PBMCs from patients with MDD. Multiple linear regression analyses revealed that TNFAIP3 mRNA expression before treatment was inversely correlated with severity of depression and effectively predicted improvement in HAMD-17 scores. Among 79 treatment-completers, only TNFAIP3 mRNA was significantly increased by treatment with antidepressants for 4 weeks. Treatment of human monocytes (THP-1) and mouse microglia (SIM-A9) cell lines with fluoxetine significantly increased TNFAIP3 mRNA expression and suppressed IL-6 levels. The suppressive effect of fluoxetine on IL-6 was attenuated by knockdown of TNFAIP3 expression. These findings suggest that both dysfunction of the negative regulatory system in patients with MDD and antidepressant treatment exert anti-inflammatory effects, at least in part through increased expression of the TNFAIP3 gene. They also indicate that modulating expression of the TNFAIP3 gene to rebalance TLR-mediated inflammatory signaling may be potential therapeutic strategy for treating MDD.

Relapses and recurrences of catatonia: 30-case analysis and literature review.

OBJECTIVE: Relieving catatonia helps identify the underlying etiology and its treatment. However, catatonia may reemerge after some time, but there are few data on the relapses and recurrences of catatonia. We aimed to investigate the characteristics of patients with relapses or recurrences of catatonia as well as the efficacy of the lorazepam-diazepam protocol on them. METHODS: Patients with catatonia who had more than one episode of catatonia and were treated with the lorazepam-diazepam protocol were identified. Their medical charts were reviewed, and interview was conducted. RESULTS: Thirty patients were identified. Nineteen (63.3%) were diagnosed with schizophrenia, five (16.7%) with major depressive disorder, two (6.7%) with bipolar disorder, and four (13.3%) with general medical conditions. In the 68 relapses and relapses the lorazepam-diazepam protocol was used, full response was reported in 54 (79.4%) of them. Twelve of 19 (63.2%) patients with schizophrenia were treated with clozapine. Twenty (66.7%) out of 30 patients were maintained on oral lorazepam by the time of discharge. Literature review showed similar prevalence of schizophrenia in patients with more than one episode of catatonia, and a wide variety of treatment options. CONCLUSION: The lorazepam-diazepam protocol was mostly effective in managing relapses and recurrences of catatonia. Maintenance clozapine and oral lorazepam were beneficial in a significant number of patients.

Consensus statements and guideline for the diagnosis and management of plantar fasciitis in Singapore.

Introduction: Plantar fasciitis (PF) is a common cause of heel pain among the general population. The lack of standard practice guideline in Singapore presents challenges in education and clinical practice for this painful condition. These consensus statements and guideline were developed to streamline and improve the management of PF, covering key aspects such as diagnosis, investigations, risk factors, treatment modalities, monitoring and return to work/play. Method: A multidisciplinary expert panel consisting of 6 sports physicians, 2 orthopaedic surgeons, 2 podiatrists and 1 physiotherapist from SingHealth Duke-NUS Sport & Exercise Medicine Centre (SDSC) was convened based on their clinical and academic experience with PF. The Grading of Recommen-dations, Assessment, Development and Evaluations (GRADE) approach was used to evaluate the quality of the evidence and subsequently prepare a set of clinical recommen-dations pertaining to the manage-ment of PF. A modified Delphi process was used to reach consensus. Results: Eighteen consensus statements were developed to cover key components of PF management, from initial diagnosis to treatment modalities and finally, clinical progression. They were subsequently consolidated under a proposed treatment pathway guideline for PF. Conclusion: The SDSC consensus statements and guideline provide concise recommendations for the management of PF in Singapore.

Dissection of the Candida albicans Cdc4 protein reveals the involvement of domains in morphogenesis and cell flocculation.

BACKGROUND: CDC4, which encodes an F-box protein that is a member of the Skp1-Cdc53/Cul1-F-box (SCF) ubiquitin E3 ligase, was initially identified in the budding yeast Saccharomyces cerevisiae as an essential gene for progression through G1-S transition of the cell cycle. Although Candida albicans CDC4 (CaCDC4) can release the mitotic defect caused by the loss of CDC4 in S. cerevisiae, CaCDC4 is nonessential and suppresses filamentation. RESULTS: To further elucidate the function of CaCDC4, a C. albicans strain, with one CaCDC4 allele deleted and the other under the repressible C. albicans MET3 promoter (CaMET3p) control, was made before introducing cassettes capable of doxycycline (Dox)-induced expression of various C. albicans Cdc4 (CaCdc4) domains. Cells from each strain could express a specific CaCdc4 domain under Dox-induced, but CaMET3-CaCDC4 repressed conditions. Cells expressing domains without either the F-box or WD40-repeat exhibited filamentation and flocculation similarly to those lacking CaCDC4 expression, indicating the functional essentiality of the F-box and WD40-repeat. Notably, cells expressing the N-terminal 85-amino acid truncated CaCdc4 partially reverse the filament-to-yeast and weaken the ability to flocculate compared to those expressing the full-length CaCdc4, suggesting that N-terminal 85-amino acid of CaCdc4 regulates both morphogenesis and flocculation. CONCLUSIONS: The F-box and the WD40-repeat of CaCdc4 are essential in inhibiting yeast-to-filament transition and flocculation. The N-terminal region (1-85) of CaCdc4 also has a positive role for its function, lost of which impairs both the ability to flocculate and to reverse filamentous growth in C. albicans.

Lorazepam-diazepam protocol for catatonia in schizophrenia: a 21-case analysis.

OBJECTIVES: Catatonia is a unique clinical phenomenon characterized by concurrent motor, emotional, vegetative and behavioral signs. Benzodiazepines (BZD) and electroconvulsive therapy (ECT) can rapidly relieve catatonic signs. The lorazepam-diazepam protocol presented here has been proven to relieve catatonia in schizophrenia within a day. METHODS: From July 2002 to August 2011, schizophrenic patients requiring psychiatric intervention for catatonia in Kaohsiung Chang Gung Memorial Hospital were studied by medical chart review. The study used the Bush-Francis Catatonia Rating Scale (BFCRS). Patients receiving the lorazepam-diazepam protocol were identified. RESULTS: The survey included 21 patients (eight males and 13 females) with a mean age of 30.3 ± 12.6 years. Mean duration of schizophrenia was 4.7 ± 5.6 years. Thirteen (61.9%) patients responded within 2 h, 18 (85.7%) responded within one day, and all became catatonia-free within a week. Mean BFCRS score was 9.9 ± 3.0 before treatment. Patients that responded with a single intramuscular lorazepam injection had mean BFCRS score of 8.9 ± 2.8, significantly lower than the mean score (11.6 ± 2.5) of the rest of the patients (p = 0.034). CONCLUSIONS: The lorazepam-diazepam protocol can rapidly relieve retarded catatonia in schizophrenia. Most patients became catatonia-free within one day but some may require up to a week. ECT should be considered if the protocol fails.

Oxygenated Cembranoids from the Soft Coral Sinularia flexibilis.

Chemical examination of the Taiwanese soft coral Sinularia flexibilis led to the isolation of five cembrane-based diterpenoids 1-5, including two new metabolites, 11-acetylsinuflexolide (1) and 11-acetyldihydrosinuflexolide (2). The structures of the new metabolites were determined based on extensive spectroscopic analysis, particularly mass spectrometry and 2D NMR (1H-1H COSY, HMQC, HMBC, and NOESY) spectroscopy. Metabolites 1, 3 and 4 exhibited moderate to weak cytotoxicity to human tumor cell lines, HeLa, HEp-2, MCF-7 and MDA-MB-231.

Orexin/hypocretin and major psychiatric disorders.

Orexin A and B, also known as hypocretin 1 and 2, are excitory neuropeptides synthesized in the perifornical and lateral hypothalamic areas. Following their discovery in 1998, orexins are now known to be involved in feeding, sleep, stress response, and reward processing. Most importantly, orexin deficiency has been linked to narcolepsy, a neurological sleep-wake disorder. Patients with narcolepsy also present overlapping symptoms with psychiatric disorders, such as anxiety and depressed mood, and even hallucinations, which often lead to misdiagnosis in the initial assessment. In this article, we aim to review studies of the orexin system associated with the three major psychiatric disorders: schizophrenia, major depressive disorder (MDD), and bipolar disorder. In addition to animal and clinical reports, studies of the orexin system in treatment, symptoms and side effects would also be reviewed. Thus far, relatively robust evidence suggests a connection of the orexin system with MDD. Findings of orexin involvement in schizophrenia are inconsistent and only studies in bipolar disorder are limited. While the orexin system might not be firmly associated with diagnosis, it may be useful to target specific symptom within the diagnosis or treatment, such as insomnia, weight gain and polydipsia.

Isobaric Tags for Relative and Absolute Quantitation Identification of Blood Proteins Relevant to Paroxetine Response in Patients With Major Depressive Disorder.

Objectives: Isobaric tags for relative and absolute quantitation (iTRAQ) is a proteomic investigation that could be utilized for rapid identification and quantification of proteins, which we would use to identify differentially expressed proteins in treatment responsive patients with major depressive disorder (MDD). Methods: Six treatment responsive patients of MDD were recruited, and their peripheral blood mononuclear cell (PBMC) were collected before and after 4 weeks of paroxetine treatment. iTRAQ and Mascot search engine were used to detect differentially expressed proteins, which were then validated by Western blot. Results: Two thousand one hundred and fifty three proteins were screened, and seven proteins showed differences of more than two-fold and 62 proteins with a differences of less than two-fold. Six proteins with commercially available antibodies were identified, and were validated by Western blot in 10 paroxetine responsive MDD patients. Putative hydroxypyruvate isomerase (HYI), eukaryotic translation initiation factor 4H (eIF4H), and RNA binding motif 8A (RBM8A) had statistically significant differences before and after treatment in the validation. Data are available via ProteomeXchange with identifier PXD028947. Conclusions: By using iTRAQ and Western blot, we were able to identify HYI, eIF4H, and RAM8a to be the potential predictors of paroxetine treatment response in patients with MDD. This finding could help establish future individualized medicine.

Corrigendum: Isobaric Tags for Relative and Absolute Quantitation Identification of Blood Proteins Relevant to Paroxetine Response in Patients With Major Depressive Disorder.

[This corrects the article DOI: 10.3389/fpsyt.2022.577857.].

Validity and Reliability of the American Orthopaedic Foot and Ankle Society Score for the English-Literate Singapore Population With Hallux Valgus.

BACKGROUND: This study aimed to evaluate the reliability and validity of the American Orthopaedic Foot and Ankle Society Metatarsophalangeal-Interphalangeal (AOFAS MTP-IP) score in patients with hallux valgus in Singapore. METHOD: A total of 121 English-literate patients with hallux valgus identified between October 2017 and May 2020 were analyzed. Reliability was assessed via Cronbach α. Construct validity was evaluated through 20 a priori hypotheses by correlating the AOFAS MTP-IP score for hallux and lesser toes with other patient-reported outcome measures (PROMs). Standardized response means (SRMs) were calculated to evaluate responsiveness at 6 months postoperative. Structural validity was evaluated via confirmatory factor analysis (CFA) whereby a good fit was indicated when comparative fit index (CFI) is >0.95, Tucker-Lewis index (TLI) is >0.95 and standardized root mean residual (SRMR) is <0.08. RESULTS: The AOFAS MTP-IP score demonstrated reliability with a Cronbach α of 0.837. Convergent construct validity was confirmed when all a priori hypotheses were fulfilled. Structural validity was established with our AOFAS MTP-IP score model that displayed good fit for a 1-factor structure (CFI = 0.988, TLI = 0.960, SRMR = 0.034). Responsiveness of the AOFAS MTP-IP score for hallux was demonstrated by an SRM score of 1.28. CONCLUSION: The AOFAS MTP-IP score displayed adequate reliability and validity among English-literate patients in Singapore with an operatively managed hallux valgus. LEVEL OF EVIDENCE: Level III: Retrospective cohort study.

SIGIRR and TNFAIP3 Are Differentially Expressed in Both PBMC and TNF-α Secreting Cells of Patients With Major Depressive Disorder.

Background: Major depressive disorder (MDD) is associated with the activation of the immune/inflammatory system. TNF-α is associated with MDD and poor treatment response. Toll-like receptors (TLR) are responsible in innate immune response, and is associated with MDD and antidepressant response. Some negative regulators of TLR pathway such as SOCS1, TOLLIP, SIGIRR, TNFAIP3, and MyD88s, are reported to be differentially expressed in the peripheral blood samples of patients of MDD. Methods: We recruited patients with MDD and healthy controls, collect their demographic data, and measured their mRNA levels of negative TLR regulators, using peripheral blood mononuclear cells (PBMC) and isolated TNF-α secreting cells. Clinical symptoms were evaluated using Halmiton Depression Rating Scale (Ham-D). Some patients were evaluated again after 4 weeks of antidepressant treatment. Results: Forty-seven patients with MDD and 52 healthy controls were recruited. Between the PBMC samples of 37 MDD patients and 42 controls, mRNA levels of SOCS1, SIGIRR, TNFAIP3, and MyD88s were significantly different. Between TNF-α secreting cells of 10 MDD patients and 10 controls, mRNA levels of SIGIRR and TNFAIP3 were significantly different. Change of Ham-D score only correlated significantly with TOLLIP mRNA level after treatment. Conclusion: SIGIRR and TNFAIP3, two negative regulators of TLR immune response pathways, were differentially expressed in both PBMC and TNF-α secreting cells of patients with MDD as compared to healthy controls. The negative regulations of innate immune response could contribute to the underlying mechanism of MDD.

Brain-derived neurotrophic factor and mental disorders.

Brain-derived neurotrophic factor (BDNF) is a neurotrophin that modulates neuroplasticity in the brain, and is one of the most widely investigated molecule in psychiatric disorders. The researches of BDNF emcompassed the advance of investigative techniques of past decades. BDNF researches ranged from protein quantilization, to RNA expression measurements, to DNA sequencing, and lately but not lastly, epigenetic studies. In this review, we will briefly address findings on BDNF protein levels, mRNA expression, Val66Met polymorphism, and epigenetic modifications, in schizophrenia, major depressive disorder (MDD), and bipolar disorder.

Abnormal Brain-Derived Neurotrophic Factor Exon IX Promoter Methylation, Protein, and mRNA Levels in Patients with Major Depressive Disorder.

Brain-derived neurotrophic factor (BDNF) exon IX promoter methylation levels, serum BDNF protein levels, and serum mRNA levels were investigated in patients with major depressive disorder (MDD) and healthy controls. Over two years, 51 patients with MDD and 62 healthy controls were recruited. Peripheral blood was drawn from all participants to analyze the BDNF exon IX promoter methylation levels as well as serum BDNF protein and mRNA levels, at baseline and after four weeks of antidepressant treatment. Methylation sequential analysis showed that patients with MDD (n = 39) had a higher methylation level at CpG site 217 and lower methylation levels at CpG site 327 and CpG site 362. Drug responders (n = 25) had a higher methylation level at CpG site 24 and CpG site 324 than the non-responders (n = 11). Patients with MDD had a lower serum BDNF protein and mRNA levels than the healthy controls. In conclusion, these results showed that BDNF exon IX promoter methylation levels, serum BDNF protein level, and serum BDNF mRNA level could contribute to the pathophysiology of a major depressive disorder.

Antidepressant treatment increased serum miR-183 and miR-212 levels in patients with major depressive disorder.

Major depressive disorder (MDD) had been associated with brain-derived neurotrophic factor (BDNF). Studies had shown that patients with MDD were associated with lower BDNF protein levels, which could be reversed by antidepressant treatment. BDNF expression had also been affected by a number of microRNAs (miRNA). BDNF and miRNA in MDD had been investigated widely in the recent years, but the relationships between miRNAs and antidepressants were less studied. From November 2015 to October 2017, inpatients diagnosed with MDD were recruited. Serum miR-16, miR-30, miR-34, miR-128, miR-132, miR-134, miR-182, miR-183, miR-185, miR-212 levels were measured before and after four weeks of antidepressant treatment of either selective serotonin reuptake inhibitor (SSRI) or serotonin-norepinephrine reuptake inhibitor (SNRI). Thirty-three patients with MDD were recruited. After treatment, miR-183 and miR-212 levels increased significantly. In patients treated with SSRI (n = 13), miR-16 levels increased significantly after treatment. Therefore, miR-183 and miR-212 levels increased significantly after four weeks of antidepressant treatment. In the SSRI group, significantly increased miR-16 levels were found, but not in SNRI group, suggesting that different types of antidepressants might affect different sets of miRNAs.

Acute Q fever hepatitis in patients with and without underlying hepatitis B or C virus infection.

BACKGROUND: Although hepatitis is one of the major presentations of acute Q fever, the possible influence of viral hepatitis in Q fever has, to our knowledge, never been investigated. It is an important issue in regions where Q fever hepatitis and viral hepatitis are prevalent, such as Taiwan. We conducted a study to investigate the possible influence of viral hepatitis in cases of acute Q fever hepatitis. METHODS: Cases of acute Q fever confirmed by serologic examination were included in the study. All patients who were found to be positive for Q fever were tested for hepatitis B surface antigen and antibody to hepatitis C virus, and those with positive results had their viral loads determined. Demographic data, clinical manifestations, results of laboratory and imaging examinations, and responses to treatment were recorded retrospectively from charts. RESULTS: A total of 58 patients with acute Q fever hepatitis were studied, of whom 16 (27.6%) had viral hepatitis (hepatitis B virus infection in 12 and hepatitis C virus infection in 4). Patients with and patients without viral hepatitis did not differ with regard to clinical manifestations and responses to treatment, except that chills (100% vs. 73.8%; P=.02) and nausea and/or vomiting (18.8% vs. 2.4%; P=.03) were significantly more common among patients with viral hepatitis. The change in hepatitis B and C virus loads between the acute and convalescent phase was <1.0 log(10). CONCLUSIONS: The clinical manifestations of acute Q fever hepatitis differ little in patients with and patients without underlying viral hepatitis, and replication of hepatitis virus is not influenced by acute Q fever hepatitis.

Clonorchiasis-associated perforated eosinophilic cholecystitis.

Clonorchiasis, a disease caused by infection with Clonorchis sinensis, is endemic in the Far East. Cholelithiasis, pyogenic cholangitis, cholecystitis, and biliary tract obstruction are common complications of chronic infection. Although cholecystitis caused by clonorchiasis is common, it is rarely reported as resulting from eosinophilic infiltration. We report a rare case of clonorchiasis-associated perforated eosinophilic cholecystitis and review the relevant literature.

Eosinophilic meningitis caused by Angiostrongylus cantonensis after ingestion of raw frogs.

Angiostrongylus cantonensis is the most common cause of eosinophilic meningitis in humans after ingestion of raw or inadequately cooked intermediate hosts or food contaminated with infective third-stage larvae. Frogs are known to be a paratenic host of A. cantonensis, but have never been reported as the infectious source of human angiostrongyliasis in Taiwan. We report the first case of eosinophilic meningitis caused by A. cantonensis after ingestion of raw frogs (Rana plancyi).

Increased serum brain-derived neurotrophic factor in male schizophrenic patients with metabolic syndrome.

Increased prevalence of metabolic syndrome was found in patients with schizophrenia. Brain-derived neurotrophic factor (BDNF) was involved in energy metabolism and the pathophysiology of schizophrenia, but differently in males and females. We aimed to investigate the serum BDNF levels in patients with schizophrenia with and without metabolic syndrome.Patients with schizophrenia were recruited. Their demographic data were collected. Metabolic profiles and serum BDNF levels were measured. Clinical symptoms were evaluated with Positive and Negative Syndrome Scale. Metabolic syndrome was determined with the criteria provided by Ministry of Health and Welfare of Taiwan. Framingham Risk Score (FRS) for estimate of 10-year risk for coronary heart disease was provided by National Institutes of Health.Of the 81 participants, 40.7% had metabolic syndrome. Those with metabolic syndrome had higher FRS. Using analysis of covariance adjusted for age and body mass index, male patients with schizophrenia with metabolic syndrome had higher serum BDNF levels than those without (4.6 ±â€Š4.7 vs 3.3 ±â€Š3.8 ng/mL, P = .022). No statistical difference was found between female patients with and without metabolic syndrome.Significant differences of serum BDNF levels were found between male patients with schizophrenia with and without metabolic syndrome, but not in females. This finding suggested the gender difference behind the mechanism of BDNF in metabolic syndrome in schizophrenia.