Single hole, high-flow, spinal cord peri-medullary arteriovenous fistula (PMAVF) in a child, treated with transarterial embolization: A case report.

Peri-medullary arteriovenous fistula (PMAVF) is a rare spinal vascular malformation that manifests as progressive neurologic deficits or hemorrhage in the spinal canal. We report a case of high-flow PMAVF in a child, with a single feeder artery and a large venous pouch, which was successfully treated with transarterial endovascular intervention. A 2-year-old boy was referred with a progressive 2-year history of myelopathy. The MRI revealed a large venous pouch at the midthoracic spinal cord with segmental surrounding edema. A spinal angiogram confirmed high-flow PMAVF with a single feeder artery from the anterior radiculomedullary artery, draining into the peri-medullary vein. The patient underwent transarterial embolization at the distal feeder artery, resulting in gradual motor strength improvement. PMAVF is classified as type IV spinal vascular malformation, usually presenting as a large, high-flow fistula with multiple feeders, although there was only one in this case. PMAVFs are intradural and may cause severe neurologic deficits due to mass effect, venous congestion, or hemorrhage, hence requiring prompt treatment. Treatment options for PMAVF include microsurgery, endovascular intervention, or a combination of the 2. Endovascular intervention with coil or liquid embolic material is considered first-line treatment for IVc PMAVF, and effective in type IVb with good clinical outcome. PMAVF is a rare spinal vascular malformation commonly manifesting as severe neurologic deficits but has the potential of favorable outcomes with endovascular therapy. This case demonstrates a unique angioarchitecture of high-flow PMAVF with a single feeder artery and large venous pouch, treated successfully with endovascular therapy.

Development of a reverse transcription loop-mediated isothermal amplification assay with novel quantitative pH biosensor readout method for SARS-CoV-2 detection.

Reverse transcription loop-mediated isothermal amplification (RT-LAMP) is a molecular amplification method that can detect SARS-CoV-2 in a shorter time than the current gold-standard molecular diagnostic reverse transcription-polymerase chain reaction (RT-PCR). However, previously developed RT-LAMP assays have mostly relied on highly subjective visual colorimetric interpretation. In this study, an RT-LAMP assay was developed with quantitative measurement of reaction pH using a novel portable pH biosensor compared to qualitative colorimetric interpretation and gel electrophoresis, with 57 clinical COVID-19 samples used for validation of the test. The LoD of the assay is 103 copies/µL. The highest sensitivity was found in the qualitative methods (93.75%), while the highest specificity and likelihood ratio was found in the pH sensor (87.5% and 6.72). On the sensor measurement, a significant difference (p < 0.0001) was observed between the average pH of the RT-PCR (+) COVID-19 (6.15 ± 0.27), while the average pH of the RT-PCR (-) samples (6.72 ± 0.22). Correlation analysis revealed a strong correlation (r = 0.78, p < 0.0001) between the Ct values obtained from RT-PCR with the biosensor pH readout. RT-LAMP with the quantitative pH sensor readout method has the potential to be further developed as an objective molecular assay for rapid and simple detection of SARS-CoV-2.

Association between glaucoma susceptibility with combined defects in mitochondrial oxidative phosphorylation and fatty acid beta oxidation.

Glaucoma is one of the leading causes of visual impairment and blindness worldwide, and is characterized by the progressive damage of retinal ganglion cells (RGCs) and the atrophy of the optic nerve head (ONH). The exact cause of RGC loss and optic nerve damage in glaucoma is not fully understood. The high energy demands of these cells imply a higher sensitivity to mitochondrial defects. Moreover, it has been postulated that the optic nerve is vulnerable towards damage from oxidative stress and mitochondrial dysfunction. To investigate this further, we conducted a pooled analysis of mitochondrial variants related to energy production, specifically focusing on oxidative phosphorylation (OXPHOS) and fatty acid ß-oxidation (FAO). Our findings revealed that patients carrying non-synonymous (NS) mitochondrial DNA (mtDNA) variants within the OXPHOS complexes had an almost two-fold increased risk of developing glaucoma. Regarding FAO, our results demonstrated that longer-chain acylcarnitines (AC) tended to decrease, while shorter-chain AC tended to increase in patients with glaucoma. Furthermore, we observed that the knocking down cpt1a (a key rate-limiting enzyme involved in FAO) in zebrafish induced a degenerative process in the optic nerve and RGC, which resembled the characteristics observed in glaucoma. In conclusion, our study provides evidence that genes encoding mitochondrial proteins involved in energy metabolisms, such as OXPHOS and FAO, are associated with glaucoma. These findings contribute to a better understanding of the molecular mechanisms underlying glaucoma pathogenesis and may offer potential targets for therapeutic interventions in the future.

Correlation of serum interleukin-6 levels and neutrophil-lymphocyte ratio in the severity of COVID-19.

Background: Interleukin-6 (IL-6) is a pro-inflammatory cytokine that is produced at varying levels in patients with coronavirus disease 2019 (COVID-19). The neutrophil-lymphocyte ratio (NLR) is one of the new inflammatory markers of COVID-19. This study aimed to evaluate the differences in IL-6 level and the NLR in mild and severe COVID-19 and assess their correlation with COVID-19 severity and the correlation of IL-6 and NLR in COVID-19. Methods: A total of 91 patients with COVID-19 were divided into mild (n = 57) and severe (n = 34) COVID-19 groups. IL-6 levels were measured using the electrochemiluminescence immunoassay method on Roche Cobas e411. The NLR was the ratio of the total neutrophil and lymphocyte counts from complete haematology on the Sysmex XS-800i. Data were analysed using the Kolmogorov-Smirnov, Mann-Whitney, receiver operating characteristic curve, chi-square and Spearman correlation tests. The statistical test was significant at p <0.05. Results: Serum IL-6 levels and NLR significantly differed in mild and severe COVID-19. The median (min-max) IL-6 levels for mild and severe COVID-19 were 3.59 (1.50-638.30) pg/mL and 28.82 (5.52-926.30) pg/mL, respectively (p <0.001). The median (min-max) NLR in mild and moderate COVID-19 was 2.18 (0.69-15.58) and 8.13 (2.24-30.90), respectively (p <0.001). The obtained cut-off values for IL-6 and NLR were >6.99 pg/mL and >4.18, with odds ratios of 29.29 and 26.19, respectively. A positive correlation was found between IL-6 and NLR and COVID-19 severity (r = 0.612; p <0.001). Conclusions: The results indicated that serum IL-6 levels and NLR are higher in severe COVID-19 than in mild COVID-19. Patients with IL-6 levels >6.99 pg/mL and NLR >4.18 are 29 and 26 times more likely to suffer from severe COVID-19, respectively. Serum IL-6 levels and NLR are strongly correlated with COVID-19 severity. Serum IL-6 levels correlate with NLR in COVID-19.

Sudomotor dysfunction in diabetic peripheral neuropathy (DPN) and its testing modalities: A literature review.

Long term consequences of diabetes mellitus (DM) may include multi-organ complications such as retinopathy, cardiovascular disease, neuronal, and kidney damage. One of the most prevalent complication is diabetic peripheral neuropathy (DPN), occurring in half of all diabetics, and is the main cause of disability globally with profound impact on a patient's quality of life. Small fiber neuropathy (SFN) can develop in the pre-diabetes stage preceding large fiber damage in DPN. Asymptomatic SFN is difficult to diagnose in early stages, with sudomotor dysfunction considered one of the earliest manifestations of autonomic neuropathy. Early detection is crucial as it can prevent potential cardiovascular events. Although punch skin biopsy is the gold-standard method for SFN diagnosis, implementation as routine screening is hindered due to its invasive, impractical, and time-consuming nature. Other sudomotor testing modalities, most of which evaluate the postganglionic cholinergic sympathetic nervous system, have been developed with varying sensitivity and specificity for SFN diagnosis. Here, we provide an overview on the general mechanism of DPN, the importance of sudomotor assessment for early detection of autonomic dysfunction in DPN, the benefits and disadvantages of current testing modalities, factors that may affect testing, and the importance of future discoveries on sudomotor testing for successful DPN diagnosis.

A systematic proteomic profiling and pathway analysis of protein biomarkers in diabetic retinopathy with subsequent validation of the IL-6 upstream regulator.

Purpose: Diabetic retinopathy (DR) is a leading cause of irreversible blindness worldwide. Identifying risk factors associated with DR development and progression is crucial for improving treatment efficacy. Although proteomic changes in DR have been extensively studied, the results remain equivocal. Hence, this study aims to summarize and identify potential diagnostic or prognostic markers for DR. In addition, the upstream regulator responsible for protein deregulation of this disease was also validated. Methods: We systematically analyzed the current literature on proteomic profile changes in DR, followed by pathway analysis identification. To validate the protein level changes, ELISA was performed from serum samples collected from 27 patients with DR and 25 healthy controls. Results: Our analysis revealed that 1 candidate marker (afamin [AFM]) distinguished non-proliferative diabetic retinopathy (NPDR) from type 2 diabetic patients with no diabetic retinopathy/controls, 65 candidate markers distinguished proliferative diabetic retinopathy (PDR) from NPDR, 1 candidate marker (thyroid receptor-interacting protein 11 [TRIP11]) distinguished PDR from PDR-DME/DME, and 3 candidate markers for therapeutic evaluation of PDR. Our results pinpoint that inflammatory response, which IL-6 mainly modulated, is responsible for the changes of proteomic profiles identified in DR. This was also validated by ELISA analysis, indicating that IL-6 could be potentially useful for diagnosing DR. Conclusion: We report a comprehensive patient-based proteomic approach to identify potential biomarkers for DR diagnosis, prognosis, and treatment evaluation. Supplementary information: The online version contains supplementary material available at 10.1007/s40200-023-01204-6.

Delayed versus immediate intervention of ruptured brain arteriovenous malformations: A case report.

BACKGROUND: Brain arteriovenous malformations (bAVMs) remains one of the most prevalent causes of intracranial hemorrhage and stroke-like syndromes in the young adult population. Although it has been agreed upon that definitive treatment using either single or multi-modal approach is warranted for successful bAVM management, much debate still revolves regarding the optimal timing of definitive treatment. CASE SUMMARY: In this report, we present a case of delayed, definitive endovascular treatment for ruptured bAVM in a 21-year-old female, 3 mo post-ictus. The bAVM, with a left pericallosal feeding artery and cortical draining veins, was successfully obliterated through embolization using the Onyx 18. On follow-up the patient has recommenced her daily activities and experiences only mild occasional headaches with mild motor deficits. The report leads to our review on an important issue regarding the optimal timing of ruptured bAVM definitive management and bring forward the current evidence available on delayed vs immediate definitive bAVM intervention. We also highlight current issues that need to be addressed for clearer guidelines on definitive therapy initiation. CONCLUSION: Current treatment paradigms of ruptured bAVM remains elusive, with substantial heterogeneity in the current literature. A consensus on the definition of "acute" vs "delayed", management goal, follow-up length and outcome parameters are required to support formation of a clear paradigm.

Sequence analysis of SARS-CoV-2 Delta variant isolated from Makassar, South Sulawesi, Indonesia.

Introduction: This study aimed to perform mutation and phylogenetic analyses of the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Delta variants and analyze the characteristic signs and symptoms of patients infected with SARS-CoV-2 Delta variant originated from Makassar during the Delta outbreak.Methods: We collected samples from patients who were infected with coronavirus disease 2019 (COVID-19) between June and October 2021. We selected the Quantitative Reverse Transcription-Polymerase Chain Reaction (PCR)-positive samples with a cycle threshold value of <30 for whole genome sequencing. Total viral ribonucleic acid (RNA) was isolated from 34 PCR-positive nasopharyngeal swab samples, and whole genome sequencing was performed using the Oxford Nanopore GridlON sequencer. Phylogenetic and maximum clade credibility analyses were performed using the Bayesian Markov chain Monte Carlo method. Results: It was found that 33 patients were infected with the SARS-CoV-2 Delta variant in this cohort study, among whom 63.6% (21) patients were female. According to the clinical data, 24 (72.7%), 7 (21.2%), and 2 (6.1%) patients had mild, moderate, and severe COVID-19 infections. Phylogenetic analysis based on the spike and RNA-dependent RNA polymerase (RdRp) genes showed that the collected samples were clustered in the main lineage of B.1.617.2 (Delta variant). The Delta variants had a high frequency of distinct mutations in the spike protein region, including T19R (94.12%), L452R (88.23%), T478K (91.17%), D614G (97%), P681R (97%), and D950 N (97%). Other unique mutations found in a smaller frequency in our samples were present in the N-terminal domain, including A27T (2.94%) and A222V (14.70%), and in the receptor-binding domain, including Q414K (5.88%), G446V (2.94%), and T470 N (2.94%). Conclusion: This study revealed the unique mutations in the S protein region of Delta variants. T19R, L452R, T478K/T478R, D614G, P681R, and D950 N were the most common substitutions in Makassar's Delta variant.

SF3B4 Frameshift Variants Represented a More Severe Clinical Manifestation in Nager Syndrome.

Nager syndrome (NS) is a rare disease marked with craniofacial and preaxial limb anomalies. In this report, we summarized the current evidence to determine a possible genotype-phenotype association among NS individuals. Twenty-four articles comprising of 84 NS (including 9 patients with a severe form of NS [Rodriguez syndrome]) patients were examined, of which 76% were caused by variants in SF3B4 (OMIM *605593, Splicing Factor 3B, Subunit 4). Within the SF3B4 gene, variants located in exon 3 commonly occurred (20%) from a total identified variant, while hotspot location was identified in exon 1 (12%), and primarily occurred as frameshift variants (64%). Thirty-five distinct pathogenic variants within SF3B4 gene were identified with two common sites, c.1A > G and c.1060dupC in exons 1 and 5, respectively. Although no significant genotype-phenotype association was found, it is notable that patients with frameshift SF3B4 variants and predicted to lead to nonsense-mediated RNA decay (NMD) of the transcripts tended to have a more severe clinical manifestation. Additionally, patients harboring variants in exons 2 and 3 displayed a higher proportion of cardiac malformations. Taken together, this article summarizes the pathogenic variants observed in SF3B4 and provides a possible genotype-phenotype relationship in this disease.

A systematic review on Treacher Collins syndrome: Correlation between molecular genetic findings and clinical severity.

Treacher Collins syndrome (TCS, OMIM: 154500) is a rare congenital craniofacial disorder that is caused by variants in the genes TCOF1, POLR1D, POLR1C, and POLR1B. Studies on the association between phenotypic variability and their relative variants are very limited. This systematic review summarized the 53 literatures from PubMed and Scopus to explore the potential TCS genotype-phenotype correlations with statistical analysis. Studies reporting both complete molecular genetics and clinical data were included. We identified that the molecular anomaly within TCOF1 (88.71%) accounted for most TCS cases. The only true hot spot for TCOF1 was detected in exon 24, with recurrent c.4369_4373delAAGAA variant is identified. While the hot spot for POLR1D, POLR1C, and POLR1B were identified in exons 3, 8, and 15, respectively. Our result suggested that the higher severity level was likely to be observed in Asian patients harboring TCOF1 variants rather than POLR1. Moreover, common 5-bp deletions tended to have a higher severity degree in comparison to any variants within exon 24 of TCOF1. In summary, this report suggested the relationship between genetic and clinical data in TCS. Our findings could be used as a reference for clinical diagnosis and further biological studies.

A Brief Analysis on Clinical Severity of Mandibulofacial Dysostosis Guion-Almeida Type.

OBJECTIVE: Genetic variants in EFTUD2 were proven to influence variable phenotypic expressivity in mandibulofacial dysostosis Guion-Almeida type (MFDGA) or mandibulofacial dysostosis with microcephaly (MFDM). Yet, the association between the severity of clinical findings with variants within the EFTUD2 gene has not been established. Thus, we aim to elucidate a possible genotype-phenotype correlation in MFDM. METHODS: Forty articles comprising 156 patients were evaluated. The genotype-phenotype correlation was analyzed using a chi-square or Fisher's exact test. RESULTS: The proportion of patients with MFDM was higher in Caucasian relative to Asian populations. Although, in general, there was no apparent genotype-phenotype correlation in patients with MFDM, Asians tended to have more severe clinical manifestations than Caucasians. In addition, cardiac abnormality presented in patients with intronic variants located in canonical splice sites was a predisposing factor in affecting MFDM severity. CONCLUSION: Altogether, this article provides the pathogenic variants observed in EFTUD2 and possible genotype-phenotype relationships in this disease.

Point-of-Care Saliva Osmolarity Testing for the Screening of Hydration in Older Adults With Hypertension.

OBJECTIVES: Older adults have an elevated risk of dehydration, a state with proven detrimental cognitive and physical effects. Furthermore, the use of diuretics by hypertensive patients further compounds this risk. This prospective study investigated the diagnostic accuracy of point-of-care (POC) salivary osmolarity (SOSM) measurement for the detection of dehydration in hypertensive adults with and without diuretic pharmacotherapy. DESIGN: Prospective diagnostic accuracy study. SETTING: Home visits to patients recruited from 4 community health centers in West Sulawesi, Indonesia. PARTICIPANTS: A total of 148 hypertensive older adults (57 men, 91 women). The mean ages of male and female patients were 69.4 ± 11.4 and 68.1 ± 7.8 years, respectively. METHODS: Hypertensive adults were divided into 2 groups based on the presence of diuretics in their pharmacotherapeutic regimen. First-morning mid-stream urine samples were used to perform urine specific gravity (USG) testing. Same-day SOSM measurements were obtained using a POC saliva testing system. RESULTS: Both USG (P = .0002) and SOSM (P < .0001) were significantly elevated in hypertensive patients with diuretic pharmacotherapy. At a USG threshold of ≥1.030, 86% of diuretic users were classified as dehydrated compared with 55% of non-using participants. A strong correlation was observed between USG and SOSM measurements (r = 0.78, P < .0001). Using a USG threshold of ≥1.030 as a hydration classifier, an SOSM threshold of ≥93 mOsm had a sensitivity of 78.6% and a specificity of 91.1% for detecting dehydration. CONCLUSIONS AND IMPLICATIONS: Hypertensive patients on diuretics have significantly higher first-morning USG and SOSM values, indicating a higher likelihood of dehydration relative to those on other classes of antihypertensive medication. POC SOSM assessment correlates strongly with first-morning USG assessment, and represents a rapid and noninvasive alternative to urinary hydration assessment that may be applicable for routine use in populations with elevated risk of dehydration.

Full-genome sequencing and mutation analysis of SARS-CoV-2 isolated from Makassar, South Sulawesi, Indonesia.

Introduction: A global surge in SARS-CoV-2 cases is occurring due to the emergence of new disease variants, and requires continuous adjustment of public health measures. This study aims to continuously monitor and mitigate the impact of SARS-CoV-2 through genomic surveillance, to determine the emergence of variants and their impact on public health. Methods: Data were collected from 50 full-genome sequences of SARS-CoV-2 isolates from Makassar, South Sulawesi, Indonesia. Mutation and phylogenetic analysis was performed of SARS-CoV-2 from Makassar, South Sulawesi, Indonesia. Results: Phylogenetic analysis showed that two samples (4%) were of the B.1.319 lineage, while the others (96%) were of the B.1.466.2 lineage. Mutation analysis of the spike (S) protein region showed that the most common mutation was D614G (found in 100% of the sequenced isolates), followed by N439K (98%) and P681R (76%). Several mutations were also identified in other genomes with a high frequency, including P323L (nsp12), Q57H (ns3-orf3a), and T205I (nucleoprotein). Conclusion: Our findings highlight the importance of continuous genomic surveillance to identify new viral mutations and variants with possible impacts on public health.

The prevalence of anxiety symptoms and disorders among ophthalmic disease patients.

Background: Progressive and irreversible vision loss has been shown to place a patient at risk of mental health problems such as anxiety. However, the reported prevalence of anxiety symptoms and disorders among eye disease patients vary across studies. Thus, this study aims to clarify the estimated prevalence of anxiety symptoms and disorders among ophthalmic disease patients. Methods: Relevant studies on the prevalence of anxiety symptoms and disorders among eye disease patients were collected through international databases, PubMed, Scopus, and Web of Science. A random-effects model was used to determine the pooled prevalence of anxiety symptoms and disorders among ophthalmic disease patients. Results: The 95 included studies yielded a pooled prevalence of 31.2% patients with anxiety symptoms and 19.0% with anxiety disorders among subjects with ophthalmic disease. Pediatric patients were more anxious (58.6%) than adults (29%). Anxiety symptoms were most prevalent in uveitis (53.5%), followed by dry eye disease (DED, 37.2%), retinitis pigmentosa (RP, 36.5%), diabetic retinopathy (DR, 31.3%), glaucoma (30.7%), myopia (24.7%), age-related macular degeneration (AMD, 21.6%), and cataract (21.2%) patients. Anxiety disorders were most prevalent in thyroid eye disease (TED, 28.9%), followed by glaucoma (22.2%) and DED (11.4%). When compared with healthy controls, there was a twofold increase on the prevalence of anxiety symptoms (OR = 1.912, 95% CI 1.463-2.5, p < 0.001) and anxiety disorders (OR = 2.281, 95% CI 1.168-4.454, p = 0.016). Conclusion: Anxiety symptoms and disorders are common problems associated with ophthalmic disease patients. Thus, comprehensive and appropriate treatments are necessary for treating anxiety symptoms and disorders among ophthalmic disease patients.

Benefits and challenges in the implementation of virtual laboratory simulations (vLABs) for medical biochemistry in Indonesia.

The pandemic caused major shifts in the delivery of education worldwide. In the teaching of medical biochemistry, the greatest impact was towards the delivery of traditional laboratory simulations. In this study, we highlight the benefits and barriers encountered in the use of virtual laboratories (vLABs) to substitute traditional laboratory practicals. The subjects were a class of 271 medical students at the Faculty of Medicine, Hasanuddin University, all freshman undergoing the Biomedicine Block. The study assessed the use of a commercial vLAB on antibodies and blood typing procedures, which were implemented using our four-step model of vLAB implementation. Collected data include the lecturer-assigned pre- and post-test result, built-in vLAB assessment result of the student first and best attempts, a student perception questionnaire based on a 5-point Likert scale, and an open ended questionnaire regarding student perceptions of the advantages and disadvantages of the vLAB. We observed a remarkable increase of lecturer assigned pre- and post-test scores and built-in first and best attempt scores (p < 0.0001, Wilcoxon signed rank test). A majority of students reported increased motivation when using the vLABs, and favored the ability of mastery through repetition. However, technical and language barriers were highlighted by students during the vLAB implementation. We demonstrate a successful implementation of commercial vLABs in a cohort of non-native English speakers using our four-step approach. Implementation requires strong support from faculty to address technical and language barriers that arise during use of vLABs.

Nanotheranostics: A powerful next-generation solution to tackle hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is an epidemic burden and remains highly prevalent worldwide. The significant mortality rates of HCC are largely due to the tendency of late diagnosis and the multifaceted, complex nature of treatment. Meanwhile, current therapeutic modalities such as liver resection and transplantation are only effective for resolving early-stage HCC. Hence, alternative approaches are required to improve detection and enhance the efficacy of current treatment options. Nanotheranostic platforms, which utilize biocompatible nanoparticles to perform both diagnostics and targeted delivery, has been considered a potential approach for cancer management in the past few decades. Advancement of nanomaterials and biomedical engineering techniques has led to rapid expansion of the nanotheranostics field, allowing for more sensitive and specific diagnosis, real-time monitoring of drug delivery, and enhanced treatment efficacies across various malignancies. The focus of this review is on the applications of nanotheranostics for HCC. The review first explores the current epidemiology and the commonly encountered obstacles in HCC diagnosis and treatment. It then presents the current technological and functional advancements in nanotheranostic technology for cancer in general, and then specifically explores the use of nanotheranostic modalities as a promising option to address the key challenges present in HCC management.

Polymorphisms of the dopamine metabolic and signaling pathways are associated with susceptibility to motor levodopa-induced complications (MLIC) in Parkinson's disease: a systematic review and meta-analysis.

BACKGROUND: Dopamine replacement therapy remains the gold standard for symptomatic management of Parkinson's disease worldwide. However, most patients will develop debilitating motor levodopa-induced complications (MLIC) in the form of levodopa-induced dyskinesia (LID) and/or motor fluctuations (MF). This study aimed to conduct a systematic review and meta-analysis on the pharmacogenetic association between LID and MF with common genetic variants of the dopamine metabolic and signaling pathways. METHODS: A meta-analysis was conducted according to the PRISMA guidelines. Extracted studies include case-control studies evaluating the association between SLC6A3/DAT rs28363170 and rs393795; COMT rs4680 and rs4633; MAO-B rs1799836, BDNF rs6265, DRD1 rs4532, DRD2 rs1800497, DRD3 rs6280, and DRD5 rs6283 polymorphisms; and the overall risk of MLIC and its subtypes LID or MF. Genotypic frequency were tested for deviation from the Hardy-Weinberg equilibrium (HWE), and the genetic association was examined using the allelic (a vs. A), recessive (aa vs. Aa + AA), dominant (aa + Aa vs. AA), overdominant (Aa vs. aa + AA), homozygous (aa vs. AA), and heterozygous (Aa vs. AA and aa vs. aA) models. RESULTS: Fourteen studies were included in the meta-analysis. A significant association was found between COMT rs46809 polymorphisms with LID but not MF, with the association observable in Asians but not Caucasians. In Asians, the COMT rs4633 was significantly associated with the occurrence of both LID and MF. The MAO-B rs1799836 was associated with both MF and LID. Among all the dopamine receptor genes analyzed, only DRD2 exhibited an association with LID. No association was observed between the SLC6AT/DAT and BDNF genes with either LID or MF. CONCLUSION: Strong associations were observed between polymorphisms of genes regulating dopamine metabolism with the occurrence of LID and/or MF. The MAO-B rs1799836 may be potential for use as a general pharmacogenetic marker of MLIC, while the COMT rs4680 and rs4633 may be used as markers of LID in Asian ethnicities.

Serum IL-6/IL-10 ratio as a biomarker for the diagnosis and severity assessment of primary-open angle glaucoma.

OBJECTIVE: To assess the performance of serum cytokine IL-6 and IL-6/IL-10 ratio as biomarkers for the diagnosis of primary open-angle glaucoma (POAG) and for determining its progression. METHODS: In this study, 20 POAG patients and 21 healthy individuals from the Indonesian population were enrolled. The serum concentration of IL-6 and IL-10 were quantified. Comparative analysis was performed in addition to assessment of the diagnostic performance of cytokines using receiver-operating-curve (ROC) analysis. RESULTS: POAG patients had a higher IL-6 (p < 0.0001) and IL-6/IL-10 ratio (p < 0.0001) than controls. Among the POAG subjects, advanced-stage patients exhibited a higher IL-6/IL-10 ratio than those in the early-moderate stage (p = 0.001; p = 0.006). The ROC curve analysis showed that both IL-6 level and IL-6/IL-10 ratio exhibited an excellent capability of diagnosing POAG (cut-off of 20.5 pg/mL (100% sensitivity and 94% specificity) and 4.4 (88% sensitivity and 94% specificity), respectively). Serum IL-6/IL-10 ratio displayed a better performance than IL-6 in discriminating POAG severity with cut-off of at least 6.6 (sensitivity of 86% and specificity of 90%) and 9.1 (sensitivity of 89% and specificity of 78%) classified according to C/D ratio and MD of VF, respectively. CONCLUSION: The balance between IL-6 and IL-10 serum levels is potentially useful in discriminating POAG severity.