Genetic polymorphisms of ACE1, ACE2, and TMPRSS2 associated with COVID-19 severity: A systematic review with meta-analysis.

Novel coronavirus disease 2019 (COVID-19) poses a global threat, due to its fluctuating frequency and lethality. Published data revealed associations of COVID-19 susceptibility and severity with host genetic polymorphisms in renin-angiotensin-aldosterone system (RAAS)-related genes including angiotensin-converting enzyme (ACE)1, ACE2, and transmembrane protease (TMPRSS)2. However, the findings remain inconclusive. Accordingly, we aimed to clarify associations of genetic variants in those genes with COVID-19 susceptibility and severity using a systematic review with meta-analysis. From inception through 1 July 2021, a literature search was performed using PubMed, Scopus, Web of Science, and Cochrane Library databases. Allelic distributions for each polymorphism were calculated as pooled odds ratios (OR) with 95% confidence intervals (CI) to assess the strength of association. A total of 3333 COVID-19 patients and 5547 controls from 11 eligible studies were included. From a systematic review, ACE1 rs1799752, ACE1 rs4646994, ACE2 rs2285666, and TMPRSS2 rs12329760 were identified as common polymorphisms of RAAS-related genes. Meta-analysis showed a significant association between TMPRSS2 rs12329760 C-allele and an increased risk of developing severe COVID-19 (OR = 1.32, 95% CI: 1.01, 1.73). Likewise, additional meta-analyses uncovered that both ACE1 rs4646994 DD-genotype and ACE2 rs2285666 GG-genotype carriers had a significantly increased risk of developing severe COVID-19 (OR = 2.06, 95% CI: 1.45, 2.93; OR = 2.14, 95% CI: 1.26, 3.66; respectively). Genetic polymorphisms of ACE1 rs4646994 DD-genotype, ACE2 rs2285666 GG-genotype, and TMPRSS2 rs12329760 CC-genotype and C-allele may serve as predictive models of COVID-19 severity.

Cytokine Profiling and Intra-Articular Injection of Autologous Platelet-Rich Plasma in Knee Osteoarthritis.

Osteoarthritis (OA) is a degenerative joint disease leading to joint pain and stiffness. Due to lack of effective treatments, physical and psychological disabilities caused by OA have a detrimental impact on the patient's quality of life. Emerging evidence suggests that intra-articular injection of platelet-rich plasma (PRP) may provide favorable results since PRP comprises not only a high level of platelets but also a huge amount of cytokines, chemokines, and growth factors. However, the precise mechanism and standardization method remain uncertain. This study aimed to examine cytokine profiling in both PRP and platelet-poor plasma (PPP) of knee OA patients and to determine the effects of PRP on OA chondrocytes and knee OA patients. PRP contained a wide variety of cytokines, chemokines, growth factors, and autologous intra-articular PRP injection resulted in favorable outcomes in knee OA patients. Significant increases in levels of IL-1, IL-2, IL-7, IL-8, IL-9, IL-12, TNF-α, IL-17, PDGF-BB, bFGF, and MIP-1ß were detected in PRP compared to PPP (p < 0.001). An in vitro study showed a marked increase in proliferation in OA chondrocytes cultured with PRP, compared to PPP and fetal bovine serum (p < 0.001). In a clinical study, knee OA patients treated with PRP showed improvement of physical function and pain, assessed by physical performance, Western Ontario and McMaster Universities Arthritis Index and visual analog scale. Our findings from both in vitro and clinical studies suggest that intra-articular PRP injection in knee OA patients may be a potential therapeutic strategy for alleviating knee pain and delaying the need for surgery.

Circulating Levels of Interleukin-6 and Interleukin-10, But Not Tumor Necrosis Factor-Alpha, as Potential Biomarkers of Severity and Mortality for COVID-19: Systematic Review with Meta-analysis.

PURPOSE: Cytokine storm, an uncontrolled overproduction of inflammatory cytokines contributing to an aberrant systemic inflammatory response, is a major pathological feature of acute respiratory distress syndromes being severe manifestations of COVID-19, thus highlighting its potential as a biomarker and therapeutic target for COVID-19. We aimed to determine associations of circulating levels of inflammatory cytokines with severity and mortality of COVID-19 by systematic review and meta-analysis. METHODS: A comprehensive literature search in electronic databases consisting of PubMed, Scopus, and Cochrane Library and in a hand searching of reference lists from inception to July 31, 2020, was performed using the following search terms: COVID-19, interleukin (IL)-6, IL-10, and tumor necrosis factor-alpha (TNF-α). Mean difference (MD) from individual studies was pooled using a random-effects model. Quality assessment, publication bias, meta-regression, subgroup, and sensitivity analyses were performed. RESULTS: A total of 6212 COVID-19 patients from 24 eligible studies were included. Compared with non-severe COVID-19 patients, systemic levels of IL-6 and IL-10, but not TNF-α, were significantly elevated in severe COVID-19 patients (MD = 18.63, 95% CI: 10.91, 26.35, P < 0.00001; MD = 2.61, 95% CI: 2.00, 2.32, P < 0.00001; respectively). For COVID-19 mortality, circulating levels of IL-6, IL-10, and TNF-α were found to be significantly increased in non-survivors when compared with survivors (MD = 57.82, 95% CI: 10.04, 105.59, P = 0.02; MD = 4.94, 95% CI: 3.89, 6.00, P < 0.00001; MD = 5.60, 95% CI: 4.03, 7.17, P < 0.00001; respectively). CONCLUSION: Circulating levels of IL-6 and IL-10 might have great potential as biomarkers for the disease severity and mortality in COVID-19 patients.

The Effects of Andrographolide on the Enhancement of Chondrogenesis and Osteogenesis in Human Suprapatellar Fat Pad Derived Mesenchymal Stem Cells.

Andrographolide is a labdane diterpenoid herb, which is isolated from the leaves of Andrographis paniculata, and widely used for its potential medical properties. However, there are no reports on the effects of andrographolide on the human suprapatellar fat pad of osteoarthritis patients. In the present study, our goal was to evaluate the innovative effects of andrographolide on viability and Tri-lineage differentiation of human mesenchymal stem cells from suprapatellar fat pad tissues. The results revealed that andrographolide had no cytotoxic effects when the concentration was less than 12.5 µM. Interestingly, andrographolide had significantly enhanced, dose dependent, osteogenesis and chondrogenesis as evidenced by a significantly intensified stain for Alizarin Red S, Toluidine Blue and Alcian Blue. Moreover, andrographolide can upregulate the expression of genes related to osteogenic and chondrogenic differentiation, including Runx2, OPN, Sox9, and Aggrecan in mesenchymal stem cells from human suprapatellar fat pad tissues. In contrast, andrographolide suppressed adipogenic differentiation as evidenced by significantly diminished Oil Red O staining and expression levels for adipogenic-specific genes for PPAR-γ2 and LPL. These findings confirm that andrographolide can specifically enhance osteogenesis and chondrogenesis of mesenchymal stem cells from human suprapatellar fat pad tissues. It has potential as a therapeutic agent derived from natural sources for regenerative medicine.

Elevated serum heat shock protein 70 and liver stiffness reflect hepatic dysfunction and severity in postoperative biliary atresia.

BACKGROUND: Biliary atresia (BA) is a severe chronic liver disease characterized by progressive obstructive cholangiopathy of biliary tract. Heat shock protein 70 (HSP70) is involved in protecting cells against a wide variety of stress and plays a protective role in tissue damage. The purpose of this study was to investigate serum HSP70 and liver stiffness in BA and determine the association of serum HSP70, liver stiffness, and outcome parameters in post-Kasai BA patients. METHODS: One hundred post-Kasai BA patients and 40 controls were enrolled. Serum HSP70 levels were analyzed using enzyme-linked immunosorbent assay. Liver stiffness values were assessed by transient elastography. RESULTS: BA patients had significantly higher serum HSP70 and liver stiffness values than controls. Serum HSP70 and liver stiffness values were markedly elevated in BA patients with jaundice compared to those without jaundice (P < 0.001). Furthermore, serum HSP70 was more elevated in BA children with portal hypertension than those without portal hypertension (35.1 ± 2.1 vs. 27.9 ± 2.5 ng/mL, P < 0.001). Moreover, serum HSP70 was positively correlated with serum aspartate aminotransferase (r = 0.491, P < 0.001), alanine aminotransferase (r = 0.448, P < 0.001), total bilirubin (r = 0.303, P = 0.002), alkaline phosphatase (r = 0.414, P < 0.001), and liver stiffness values (r = 0.455, P < 0.001). There was a negative correlation between serum HSP70 and serum albumin (r = -0.434, P = 0.001). CONCLUSION: Serum HSP70 and liver stiffness values were higher in BA patients than controls. The increased serum HSP70 was correlated with hepatic dysfunction in BA. Consequently, serum HSP70 and liver stiffness could serve as non-invasive parameters reflecting the severity in post-Kasai BA.

A Water-Based Chitosan-Maleimide Precursor for Bioconjugation: An Example of a Rapid Pathway for an In Situ Injectable Adhesive Gel.

Chitosan conjugated with maleimide (CS-Mal) as a potential precursor for bioconjugation and the example of the application in in situ injectable adhesive gel is proposed. The homogeneous reaction in water/dimethyl sulfoxide (DMSO) (1:1) followed by dialysis in HCl (10 × 10-3 m) is a good condition to obtain CS-Mal. When SH-PEG-SH is applied as the crosslinker, the gel can be obtained in a few seconds without any by-products at room temperature. The gel formation and properties are controllable by simply varying the concentration and the molecular weight of CS, the Mal substitution degree, and the temperature. The gel is injectable and shows adhesive property for soft tissue. Moreover, the gel shows not only biocompatibility to SAOS2 cells but also antimicrobial activity against both gram-negative and gram-positive bacteria. CS-Mal is useful not only for bioconjugation of CS but also for development of biomaterials.

Elevated serum periostin is associated with liver stiffness and clinical outcome in biliary atresia.

OBJECTIVE: To analyze serum periostin and liver stiffness in postoperative biliary atresia (BA). METHODS: A total of 60 BA patients and 14 controls were enrolled. Serum periostin levels were analyzed by ELISA. Liver stiffness measurement was determined by transient elastography. RESULTS: Biliary atresia patients had significantly higher periostin and liver stiffness values than controls. Serum periostin levels were remarkably increased in BA patients with jaundice compared to those without jaundice. Moreover, serum periostin was correlated with liver stiffness. CONCLUSIONS: Serum periostin was associated with liver stiffness in BA. Thus, serum periostin has potential as a parameter reflecting the severity in BA.

Serum autotaxin levels correlate with hepatic dysfunction and severity in postoperative biliary atresia.

OBJECTIVE: To investigate correlation of serum autotaxin and disease severity in biliary atresia (BA). METHODS: Eighty postoperative BA patients and 15 controls were recruited. Serum autotaxin levels were determined by enzyme-linked immunosorbent assay. RESULTS: BA patients had greater serum autotaxin and liver stiffness than controls. Serum autotaxin and liver stiffness were markedly elevated in BA patients with jaundice compared to those without jaundice. Furthermore, serum autotaxin was correlated with liver stiffness and biochemical parameters in BA. CONCLUSIONS: Elevated serum autotaxin was correlated with hepatic dysfunction in BA. Accordingly, serum autotaxin is a promising biomarker reflecting the severity in BA.

Elevated serum IL-34 is correlated with disease severity in patients with biliary atresia following Kasai portoenterostomy.

BACKGROUND: Biliary atresia (BA) is a severe congenital disorder with progressive obstructive cholangiopathy in young children. The inflammatory process has been recognized as one of the pathological mechanisms driving bile duct injury. Since interleukin-34 (IL-34) has been reportedly linked to several pathological liver disorders, including inflammation, the current study aimed to analyze circulating IL-34 and the association of circulating IL-34 with hepatic deterioration and clinical outcomes in post-Kasai BA children. METHODS: Circulating IL-34 levels were analyzed in 89 post-Kasai BA subjects and 45 healthy individuals using an ELISA. Liver stiffness (hardness) was measured by ultrasound elastography. RESULTS: Circulating IL-34 was substantially higher in BA children than in control individuals, particularly those with unfavorable outcomes including hepatic dysfunction, jaundice, and portal hypertension. In BA group, circulating IL-34 was positively correlated with liver stiffness (r = 0.515, p < 0.001), AST (r = 0.403, p < 0.001), ALT (r = 0.279, p = 0.008), total bilirubin (r = 0.224, p = 0.03), ALP (r = 0.255, p = 0.016), and serum IL-6 (r = 0.590, p < 0.001) but inversely correlated with albumin (r = -0.417, p < 0.001). Kaplan-Meier survival analysis showed that higher circulating IL-34 levels were significantly associated with reduced survival rates in BA subjects (p = 0.002). CONCLUSION: Higher circulating IL-34 values were directly associated with hepatic impairment and the BA severity, implicating thatserum IL-34 could be applied as a noninvasive marker for the monitoring of the severity in BA subjects following Kasai portoenterostomy and therapeutic efficacy.

Cartilage oligomeric matrix protein as a potential biomarker for knee osteoarthritis.

Aims: This study aimed to determine the expression and clinical significance of a cartilage protein, cartilage oligomeric matrix protein (COMP), in knee osteoarthritis (OA) patients. Methods: A total of 270 knee OA patients and 93 healthy controls were recruited. COMP messenger RNA (mRNA) and protein levels in serum, synovial fluid, synovial tissue, and fibroblast-like synoviocytes (FLSs) of knee OA patients were determined using enzyme-linked immunosorbent assay, real-time polymerase chain reaction, and immunohistochemistry. Results: COMP protein levels were significantly elevated in serum and synovial fluid of knee OA patients, especially those in the advanced stages of the disease. Serum COMP was significantly correlated with radiological severity as well as measures of body composition, physical performance, knee pain, and disability. Receiver operating characteristic curve analysis unveiled a diagnostic value of serum COMP as a biomarker of knee OA (41.64 ng/ml, area under the curve (AUC) = 1.00), with a sensitivity of 99.6% and a specificity of 100.0%. Further analysis uncovered that COMP mRNA expression was markedly upregulated in the inflamed synovium of knee OA, consistent with immunohistochemical staining revealing localization of COMP protein in the lining and sub-lining layers of knee OA inflamed synovium. Most notably, relative COMP mRNA expression in knee OA synovium was positively associated with its protein levels in serum and synovial fluid of knee OA patients. In human knee OA FLSs activated with tumour necrosis factor-alpha, COMP mRNA expression was considerably up-regulated in a time-dependent manner. Conclusion: All results indicate that COMP might serve as a supportive diagnostic marker for knee OA in conjunction with the standard diagnostic methods.

Correlation of connective tissue growth factor with liver stiffness measured by transient elastography in biliary atresia.

AIM: Biliary atresia (BA) is a neonatal liver disease defined as chronic progressive fibrotic obliteration of extrahepatic bile ducts. The objective of this study was to determine the association of serum connective tissue growth factor (CTGF) with clinical outcome and liver stiffness measurement. METHODS: Eighty-two BA patients post-Kasai operation and 28 healthy controls were recruited. BA patients were categorized into two groups based on their portal hypertension (PH) status. Serum CTGF levels were determined by enzyme-linked immunosorbent assay. Liver stiffness scores were measured by transient elastography. RESULTS: BA patients had greater CTGF levels (905.9 ± 57.7 vs 238.3 ± 23.5 pg/mL, P < 0.001) and higher liver stiffness values than controls (28.2 ± 2.6 vs 5.0 ± 0.5 kPa, P < 0.001). Serum CTGF levels were remarkably elevated in BA patients with PH compared to those without PH (1092.4 ± 73.9 vs 582.6 ± 45.7 pg/mL, P < 0.001). Furthermore, BA patients with PH had significantly higher liver stiffness values compared to those without PH (37.3 ± 3.0 vs 10.6 ± 1.1 kPa, P < 0.001). Additionally, serum CTGF was positively correlated with liver stiffness (r = 0.875, P < 0.001) and total bilirubin (r = 0.462, P < 0.001). There was an inverse correlation between serum CTGF and serum albumin (r = -0.579, P < 0.001). CONCLUSION: High serum CTGF was associated with a poor outcome in BA patients. Accordingly, serum CTGF and transient elastography may serve as non-invasive biomarkers reflecting the disease severity in postoperative BA patients.

Interleukin-1 family cytokines in liver cell death: a new therapeutic target for liver diseases.

INTRODUCTION: Liver cell death represents a basic biological process regulating the progression of liver diseases via distinct mechanisms. Accumulating evidence has uncovered participation of interleukin (IL)-1 family cytokines in liver cell death. Upon activation of cell death induced by hepatotoxic stimuli, IL1 family cytokines released by hepatic dead cells stimulate recruitment of immune cells, which in turn influence inflammation and subsequent liver injury, thus highlighting their potential as therapeutic targets in liver diseases. Enhancing our comprehension of mechanisms underlying IL1 family cytokine signaling in cell death responses could pave the way for novel therapeutic interventions aimed at addressing liver cell death-related liver pathologies. AREAS COVERED: This review summarizes the recent findings reported in preclinical and clinical studies on mechanisms of liver cell death, alongside participation of IL1 family members consisting of IL1α, ILß, IL18, and IL33 in liver cell death and their significant implications in liver diseases. EXPERT OPINION: Discovery of new and innovative therapeutic approaches for liver diseases will need close cooperation between fundamental and clinical scientists to better understand the multi-step processes behind IL1 family cytokines' contributions to liver cell death.

Vitamin D and autophagy in knee osteoarthritis: A review.

Knee osteoarthritis (KOA), the highly prevalent degenerative disease affecting the joint, perpetually devastates the health of the elderly. Of various mechanisms known to participate in KOA etiology, apoptosis of chondrocytes is widely regarded as the primary cause of cartilage degradation. It has been suggested that the induction of autophagy in chondrocytes could potentially prolong the progression of KOA by modulating intracellular metabolic processes, which may be helpful for ameliorating chondrocyte apoptosis and eventual cartilage degeneration. Autophagy, a physiological process characterized by intracellular self-degradation, has been reportedly implicated in various pathologic conditions including KOA. Interestingly, vitamin D has been shown to regulate autophagy in human chondrocytes through multiple pathways, specifically AMPK/mTOR signaling pathway. This observation underscores the potential of vitamin D as a novel approach for restoring the functionality and survivability of chondrocytes in KOA. Supporting vitamin D's clinical significance, previous studies have demonstrated its substantial involvement in the symptoms and irregular joint morphology observed in KOA patients, strengthening potential therapeutic efficacy of vitamin D in treatment of KOA. Herein, the purpose of this review was to determine the mechanisms underlying the multi-processes of vitamin D implicated in autophagy in several cells including chondrocytes, which would bring unique insights into KOA pathogenesis.

Effect of galectin-3 on synovial inflammation in knee osteoarthritis via stimulating phosphatidylinositol-3-kinase/Akt pathway.

Galectin-3 (Gal-3), a glycan-binding protein responsible for inflammation, has been reportedly implicated in inflammatory arthritis. This study aimed to determine clinical and pathological effects of Gal-3 on inflammation in knee osteoarthritis (OA). Gal-3 mRNA and protein levels in synoviocytes, synovium, synovial fluid, and plasma of knee OA patients were determined using real-time polymerase chain reaction, immunohistochemistry, and enzyme-linked immunosorbent assay. Signaling mechanism underlying inflammatory effect of Gal-3 was further elucidated in human knee OA synoviocytes. Clinical study uncovered significant increases in plasma and synovial fluid Gal-3 levels in knee OA patients, particularly those with advanced-stage. In knee OA patients, plasma Gal-3 was significantly associated with radiographic severity and indicators of body composition, physical performance, and knee pain and disability. In the inflamed synovium of knee OA patients, further analysis depicted a marked up-regulation of Gal-3 mRNA expression, consistent with immunohistochemical analysis showing localization of Gal-3 protein in the lining and sublining layers of the inflamed synovium. An in vitro study unveiled that aberrant Gal-3 mRNA expression was regulated by tumor necrosis factor (TNF)-α in knee OA synoviocytes. Gal-3 significantly enhanced production of NO and IL-6, up-regulated mRNA expressions of IL-6, NF-κB, and MMP-13, and down-regulated mRNA expressions of ACAN and SOX-9 via stimulating Akt phosphorylation in knee OA synoviocytes. Gal-3 exerted an inflammatory action, which might emerge as a possible mediator of synovitis and cartilage degeneration in knee OA.

Economic cost of patients with trisomy 13, 18, and 21 in a tertiary hospital in Thailand.

The purpose of this study was to determine direct and indirect costs of patients with trisomy (T) 13, 18, and 21 in Thailand. Direct medical costs were obtained from Siriraj Informatics and Data Innovation Center (SiData+), Faculty of Medicine, Siriraj Hospital, and indirect costs were estimated using a human capital approach. About 241 patients with T21 had outpatient care visits and 124 patients received inpatient care. For T13 and T18, five and seven patients were analyzed for outpatient and inpatient cares, respectively. For patients with T13, T18, and T21 receiving outpatient care, total annual mean direct medical costs ranged from 183.2 USD to 655.2 USD. For inpatient care, average yearly direct medical costs varied between 2,507 USD to 14,790 USD. The mean and median increased with age. In outpatient care, costs associated with drugs and medical devices were a major factor for both T13 and T21 patients, whereas laboratory costs were substantial for T18 patients. For inpatient care, costs of drug and medical devices were the greatest for T13 patients, while service fee and operation costs were the highest for T18 and T21 patients, respectively. For outpatient care, adult patients with congenital heart disease (CHD) had significantly higher mean annual direct medical costs than those without CHD. However, all adult and pediatric patients with CHD receiving inpatient care had significantly higher costs. Patients with T13, T18, and T21 had relative lifetime costs of 22,715 USD, 11,924 USD, and 1,022,830 USD, respectively.

Effect of vitamin D supplementation on circulating level of autophagosome protein LC3A, inflammation, and physical performance in knee osteoarthritis.

Aberrant autophagic activity is observed in osteoarthritic joints. Vitamin D was shown to alleviate not only osteoarthritis severity, but also autophagy process. However, the influence of vitamin D on autophagy in knee osteoarthritis (KOA) remains ambiguous. This study aimed to determine the effect of vitamin D2 on serum levels of autophagosome protein LC3A in patients with KOA and whether LC3A levels were correlated with serum 25-hydroxyvitamin D (25(OH)D) and clinical outcomes of patients with KOA. A total of 165 patients with KOA and 25 healthy controls were recruited. Vitamin D2 (ergocalciferol) was administered to patients with KOA at a weekly dosage of 40,000 IU. Serum LC3A, knee pain and functional scores, muscle strength, physical performance, and biochemical parameters were examined before and after 6 months of vitamin D2 supplementation. Serum LC3A levels were significantly higher in patients with KOA than healthy controls. In patients with KOA, vitamin D2 supplementation significantly decreased serum LC3A levels. Furthermore, baseline levels of serum LC3A were significantly associated with radiographic severity, pain and functional scores, total cholesterol, hs-CRP, IL-6, protein carbonyl, and serum 25(OH)D. After adjusting for established confounders, independent relationships among serum LC3A and radiographic severity, pain and functional scores, total cholesterol, hs-CRP, IL-6, protein carbonyl, and serum 25(OH)D were also observed. Vitamin D2 supplementation was shown to not only decrease serum levels of LC3A, inflammatory markers, as well as oxidative stress, but also improve muscle strength and physical performance in patients with KOA.

Economic evaluation of prenatal screening for fetal aneuploidies in Thailand.

Historically, there has been a lack of cost-effectiveness data regarding the inclusion of universal non-invasive prenatal testing (NIPT) for trisomy 21, 18, and 13 in the benefit package of the Universal Health Coverage (UHC) in Thailand. Therefore, this study aimed to perform the cost-benefit analysis of prenatal screening tests and calculate the budget impact that would result from the implementation of a universal NIPT program. A decision-tree model was employed to evaluate cost and benefit of different prenatal chromosomal abnormalities screenings: 1) first-trimester screening (FTS), 2) NIPT, and 3) definitive diagnostic (amniocentesis). The comparison was made between these screenings and no screening in three groups of pregnant women: all ages, < 35 years, and ≥ 35 years. The analysis was conducted from societal and governmental perspectives. The costs comprised direct medical, direct non-medical, and indirect costs, while the benefit was cost-avoidance associated with caring for children with trisomy and the loss of productivity for caregivers. Parameter uncertainties were evaluated through one-way and probabilistic sensitivity analyses. From a governmental perspective, all three methods were found to be cost-beneficial. Among them, FTS was identified as the most cost-beneficial, especially for pregnant women aged ≥ 35 years. From a societal perspective, the definitive diagnostic test was not cost-effective, but the other two screening tests were. The most sensitive parameters for FTS and NIPT strategies were the productivity loss of caregivers and the incidence of trisomy 21. Our study suggested that NIPT was the most cost-effective strategy in Thailand, if the cost was reduced to 47 USD. This evidence-based information can serve as a crucial resource for policymakers when making informed decisions regarding the allocation of resources for prenatal care in Thailand and similar context.

Host genetic polymorphisms involved in long-term symptoms of COVID-19.

Host genetic polymorphisms are recognized as a critical determinant of diversity in clinical symptoms of Coronavirus disease 2019 (COVID-19). Accordingly, this study aimed to determine possible associations between single nucleotide polymorphisms (SNPs) in 37 candidate genetic variants and clinical consequences of COVID-19 - especially long-term symptoms, Long COVID. A total of 260 COVID-19 patients, divided into mild (n = 239) and severe (n = 21) and further categorized based on the presence of Long COVID (no, n = 211; yes, n = 49), were recruited. Genotyping of selected polymorphisms responsible for viral entry, immune response, and inflammation was performed using MassARRAY system. Out of 37 SNPs, 9 including leucine zipper transcription factor like-1 (LZTFL1) rs10490770 C allele, LZTFL1 rs11385942 dupA allele, nicotinamide adenine dinucleotide synthetase-1 (NADSYN1) rs12785878 TT genotype, plexin A-4 (PLXNA4) rs1424597 AA genotype, LZTFL1 rs17713054 A allele, interleukin-10 (IL10) rs1800896 TC genotype and C allele, angiotensin converting enzyme-2 (ACE2) rs2285666 T allele, and plasmanylethanolamine desaturase-1 (PEDS1) rs6020298 GG genotype and G allele were significantly associated with an increased risk of developing Long COVID, whereas interleukin-10 receptor subunit beta (IL10RB) rs8178562 GG genotype was significantly associated with a reduced risk of Long COVID. Kaplan-Meier curve displayed that the above gene polymorphisms were significantly associated with cumulative rate of Long COVID occurrence. Polymorphisms in LZTFL1 rs10490770, LZTFL1 rs11385942, LZTFL1 rs17713054, NADSYN1 rs12785878, PLXNA4 rs1424597, IL10 rs1800896, ACE2 rs2285666, PEDS1 rs6020298, and IL10RB rs8178562 appear to be genetic factors involved in development of Long COVID.

Efficacy of anti-tuberculosis drugs for the treatment of latent tuberculosis infection: a systematic review and network meta-analysis.

Despite the availability of three network meta-analyses (NMA) examining the efficacy, treatment completion, and adverse events associated with all latent tuberculosis infection (LTBI) treatments, there is currently no evidence to support the notion that the benefits of these treatments outweigh the potential risks. This NMA aimed to conduct a comprehensive comparison and update of the efficacy, treatment completion rates and adverse events associated with recommended treatment options for LTBI for individuals with confirmed LTBI, as outlined in the 2020 World Health Organization (WHO) Consolidated Guidelines for TB preventive treatment. A comprehensive search of the MEDLINE and Scopus databases was conducted until April 2023. The NMA was applied to estimate the risk difference and corresponding 95% confidence interval (CI) using a combination of direct and indirect evidence. The risk-benefit assessment was employed to evaluate the feasibility of the extra benefits in relation to the extra risks. The primary outcomes of interest in this study were active TB disease, completion rates, and adverse events. The meta-analysis incorporated data from 15 studies, which collectively demonstrated that the administration of a placebo resulted in a significant increase in the risk of developing TB disease by 1.279%, compared to the daily intake of isoniazid for 6 months (6H). Furthermore, treatment completion rates were significantly higher when using isoniazid plus rifapentine weekly for 3 months (3HP) and rifampicin daily for 4 months (4R), as compared to 6H. Considering adverse events, the combination of 3HP, 4R, and isoniazid administered daily for 9 months (referred to as 9H) significantly decreased adverse events by 4.53% in comparison to 6H. The risk-benefit assessment showed that alternative treatment regimens (9H, 4R, 3HR and 3HP) had a lower incidence of adverse events, while demonstrating a higher efficacy in preventing TB, as compared to 6H. This review indicates that there were no significant differences observed among various active treatment options in terms of their efficacy in preventing active TB. Moreover, completion rates were higher in 3HP and 4R, and a reduction in adverse events was observed in 3HP, 4R, and 9H.

Plasma and synovial fluid connective tissue growth factor levels are correlated with disease severity in patients with knee osteoarthritis.

BACKGROUND: Connective tissue growth factor (CTGF) has been implicated in development of osteoarthritis (OA). OBJECTIVE: To determine the correlation between plasma and synovial fluid CTGF levels and the severity in knee osteoarthritis patients. METHODS: A total of 100 subjects were recruited into this study (75 OA patients and 25 controls). CTGF concentrations in plasma and synovial fluid were analyzed by enzyme-linked immunosorbent assay. RESULTS: Plasma and synovial fluid CTGF concentrations were correlated with radiographic severity. There was a positive correlation between plasma and synovial fluid CTGF levels. CONCLUSION: CTGF could be useful for monitoring the severity and progression of OA.