Category: Nevin Manimala

PeerJ. 2022 Jan 4;10:e12568. doi: 10.7717/peerj.12568. eCollection 2022.

ABSTRACT

BACKGROUND: Malignant mesothelioma (MM) is a rare and highly aggressive cancer. Despite advances in multidisciplinary treatments for cancer, the prognosis for MM remains poor with no effective diagnostic biomarkers currently available. The aim of this study was to identify plasma metabolic biomarkers for better MM diagnosis and prognosis by use of a MM cell line-derived xenograft (CDX) model.

METHODS: The MM CDX model was confirmed by hematoxylin and eosin staining and immunohistochemistry. Twenty female nude mice were randomly divided into two groups, 10 for the MM CDX model and 10 controls. Plasma samples were collected two weeks after tumor cell implantation. Gas chromatography-mass spectrometry analysis was conducted. Both univariate and multivariate statistics were used to select potential metabolic biomarkers. Hierarchical clustering analysis, metabolic pathway analysis, and receiver operating characteristic (ROC) analysis were performed. Additionally, bioinformatics analysis was used to investigate differential genes between tumor and normal tissues, and survival-associated genes.

RESULTS: The MM CDX model was successfully established. With VIP > 1.0 and P-value < 0.05, a total of 23 differential metabolites were annotated, in which isoleucine, 5-dihydrocortisol, and indole-3-acetamide had the highest diagnostic values based on ROC analysis. These were mainly enriched in pathways for starch and sucrose metabolism, pentose and glucuronate interconversions, galactose metabolism, steroid hormone biosynthesis, as well as phenylalanine, tyrosine and tryptophan biosynthesis. Further, down-regulation was observed for amino acids, especially isoleucine, which is consistent with up-regulation of amino acid transporter genes SLC7A5 and SLC1A3 in MM. Overall survival was also negatively associated with SLC1A5, SLC7A5, and SLC1A3.

CONCLUSION: We found several altered plasma metabolites in the MM CDX model. The importance of specific metabolic pathways, for example amino acid metabolism, is herein highlighted, although further investigation is warranted.

PMID:35036082 | PMC:PMC8740518 | DOI:10.7717/peerj.12568

J Nutr Metab. 2022 Jan 7;2022:2661912. doi: 10.1155/2022/2661912. eCollection 2022.

ABSTRACT

Loss of appetite (LOA) may have a negative impact on a patient’s well-being owing to loss of nutrition and associated conditions. The current study assessed the effects of an appetite-stimulating medication containing multivitamins, lysine, and zinc in Indian patients with a history of LOA. Using an investigator-initiated, single-center, open-label, single-arm design, we evaluated the effectiveness and safety of the appetite-stimulating medication (15 mL) in 50 male or female patients (18-55 years old) attending the outpatient department, with a confirmed diagnosis of LOA after two weeks of therapy and assessed the change in Council on Nutrition Appetite Questionnaire (CNAQ) score and safety of the medication after two weeks of treatment. CNAQ scores were presented as mean (standard deviation (SD)). The mean age of patients was 42.1 years, with the majority (66%) being males. At weeks 1 and 2, a statistically significant improvement was observed in the mean CNAQ scores of 25.48 (5.10) and 25.48 (4.29), respectively, vs. baseline (22.08 (2.76); P ≤ 0.0001 both). Majority of the patients had CNAQ appetite scores of 17-28 at baseline (94%), week 1 (66%), and week 2 (78%) of treatment. For patients with acute and chronic illness, a statistically significant improvement was observed in the mean CNAQ score at week 1 (26.75 (3.69), P = 0.0256; 25.24 (5.33), P = 0.0004) and at week 2 (26.63 (3.46), P = 0.0027; 25.26 (4.43), P ≤ 0.0001) from baseline (21.88 (3.31) and 22.12 (2.69), respectively). No serious adverse events were reported during the study. The study findings suggest that appetite-stimulating medication containing multivitamins, lysine, and zinc could be a suitable treatment option for the management of LOA with no significant safety concerns.

PMID:35036004 | PMC:PMC8759923 | DOI:10.1155/2022/2661912

Int J Nephrol. 2022 Jan 6;2022:1148378. doi: 10.1155/2022/1148378. eCollection 2022.

ABSTRACT

BACKGROUND: There is very little published data on outcomes of COVID-19 among chronic kidney disease (CKD) patients. We compared the outcomes of COVID-19 in a tertiary care renal hospital among CKD V patients on hemodialysis (HD), peritoneal dialysis (PD), and dialysis initiation, in terms of duration of hospitalization, in-patient mortality, and 30-day mortality.

METHODS: A total of 436 CKD V patients, on either HD, PD, or dialysis initiation, with COVID-19 who were admitted at the National Kidney and Transplant Institute (NKTI) from March 13, 2020, to August 31, 2020, were included. Kaplan-Meier survival analysis was performed. Comparison of probability of mortality by group was performed using Log-Rank test. p values ≤0.05 were considered statistically significant.

RESULTS: Among 436 CKD V patients, 298 (68%) were on HD, 103 (24%) were on PD, and 35 (8%) required dialysis initiation. Overall in-hospital mortality was 34%; 38% were on HD, 20% on PD, and 37% on dialysis initiation. Total 30-day mortality was 27%; 32% were on HD, 26% on PD, and 16% on dialysis initiation. Median follow-up was 24 days. Among the 137 deaths recorded, total median time to death was 10 days; 8.5 days, 15.5 days, and 9 days for HD, PD, and dialysis initiation groups, respectively. Probability of mortality was significantly higher in HD patients versus PD patients (p < 0.00001) and in the dialysis initiation group compared to PD patients (p=0.0234). Mortality probability, however, was not significantly different in HD patients versus the dialysis initiation group (p=0.63).

CONCLUSION: Among CKD V patients diagnosed with COVID-19 at the NKTI, those on HD and on dialysis initiation had significantly higher in-hospital and 30-day mortality, compared to patients on PD.

PMID:35036007 | PMC:PMC8758287 | DOI:10.1155/2022/1148378

Scars Burn Heal. 2022 Jan 10;8:20595131211049043. doi: 10.1177/20595131211049043. eCollection 2022 Jan-Dec.

ABSTRACT

BACKGROUND: Keloids are fibrous lesions formed at the site of trauma due to types I and III collagen irregular production. The presence of thymidylate synthase (TS) is a must for DNA synthesis and repairs causing cell death. 5-fluorouracil (5-FU) is a fluorinated pyrimidine analogue acting as an anti-metabolic agent that inhibits thymidylate synthase and interferes with ribo-nucleic acid (RNA) synthesis.

OBJECTIVES: we aimed to evaluate the level of thymidylate synthase in post burn keloid patients before and after intralesional injection of 5-fluorouracil.

METHODS: The study included 20 keloid patients and 20 healthy subjects as a control. Serum TS was estimated using commercially available enzyme-linked immunosorbent assay (ELISA) kits before and after treatment with 5-fluorouracil.

RESULTS: There was a statistically significant difference in TS levels before and after 5-FU treatment (p < 0.05). Also, results have shown that 5-FU injection has good satisfactory results in treatment of keloid causing reduction in scar volume and symptoms improvement (90% of the patients improved). On the other hand, there was no statistically significant difference in TS levels and the outcomes of the treatment.

CONCLUSION: Our findings suggest that intralesional 5-FU injection in keloid has very satisfactory results. However, thymidylate synthase enzyme has a minimal role in evaluating the treatment of keloid, so further studies are required to elaborate the relation between this enzyme and keloid scars.

PMID:35035999 | PMC:PMC8753068 | DOI:10.1177/20595131211049043

J Ophthalmol. 2022 Jan 7;2022:1703806. doi: 10.1155/2022/1703806. eCollection 2022.

ABSTRACT

PURPOSE: To analyze ocular manifestations, visual field (VF) pattern, and VF test performance in traumatic brain injury (TBI) and stroke patients.

METHODS: This retrospective, cross-sectional study included 118 patients (236 eyes) with TBI and stroke who had undergone VF testing by standard automated perimetry with the central 24-2 threshold test. Clinical features including best-corrected visual acuity (BCVA), intraocular pressure (IOP), ocular manifestations, and VF test results including VF defect pattern, reliability, and global indices were analyzed and compared between the TBI and stroke patients.

RESULTS: In TBI patients, ocular manifestations included strabismus (11.1%), cataract (4.2%), and glaucoma suspect (2.8%), whereas in stroke patients, cataract (15.2%), strabismus (8.5%), diabetic retinopathy (4.9%), extraocular movement (EOM) limitation (3.0%), glaucoma suspect (3.0%), nystagmus (2.4%), drusen (1.2%), and vitreous hemorrhage (1.2%) were found. The VF test results showed that 47 eyes (85.5%) in TBI and 86 (65.2%) in stroke had VF defect; in TBI, the scattered pattern was the most common (56.4%), followed by homonymous hemianopsia (14.5%), homonymous quadrantanopia (10.9%), and total defect (3.6%), whereas in stroke, homonymous hemianopsia was the most common (31.8%), followed by scattered pattern (16.7%), homonymous quadrantanopia (12.1%), and total defect (4.5%). Only 15 eyes (27.3%) in TBI and 32 (24.2%) in stroke showed reliable VF indices. The mean deviation (MD) was -10.5 ± 7.1 dB in TBI and -9.5 ± 6.8 dB in stroke, and the pattern standard deviation (PSD) was 4.9 ± 3.3 dB in TBI and 6.1 ± 3.9 dB in stroke, without statistically significant differences between the two groups.

CONCLUSION: Various ocular manifestations were found, and a considerable proportion of patients were experiencing VF defects and showed unreliable VF test performance. Our findings suggest that accurate evaluation and rehabilitation of visual function should be a matter of greater concern and emphasis in the management of TBI and stroke patients, besides systemic diseases.

PMID:35036002 | PMC:PMC8759901 | DOI:10.1155/2022/1703806

Clin Kidney J. 2021 Jul 6;15(1):136-144. doi: 10.1093/ckj/sfab117. eCollection 2022 Jan.

ABSTRACT

BACKGROUND: Calcific uraemic arteriolopathy (CUA; calciphylaxis) is a rare disease seen predominantly in patients receiving dialysis. Calciphylaxis is characterized by poorly healing or non-healing wounds, and is associated with mortality, substantial morbidity related to infection and typically severe pain. In an open-label Phase 2 clinical trial, SNF472, a selective inhibitor of vascular calcification, was well-tolerated and associated with improvement in wound healing, reduction of wound-related pain and improvement in wound-related quality of life (QoL). Those results informed the design of the CALCIPHYX trial, an ongoing, randomized, placebo-controlled, Phase 3 trial of SNF472 for treatment of calciphylaxis.

METHODS: In CALCIPHYX, 66 patients receiving haemodialysis who have an ulcerated calciphylaxis lesion will be randomized 1:1 to double-blind SNF472 (7 mg/kg intravenously) or placebo three times weekly for 12 weeks (Part 1), then receive open-label SNF472 for 12 weeks (Part 2). All patients will receive stable background care, which may include pain medications and sodium thiosulphate, in accordance with the clinical practices of each site. A statistically significant difference between the SNF472 and placebo groups for improvement of either primary endpoint at Week 12 will demonstrate efficacy of SNF472: change in Bates-Jensen Wound Assessment Tool-CUA (a quantitative wound assessment tool for evaluating calciphylaxis lesions) or change in pain visual analogue scale score. Additional endpoints will address wound-related QoL, qualitative changes in wounds, wound size, analgesic use and safety.

CONCLUSIONS: This randomized, placebo-controlled Phase 3 clinical trial will examine the efficacy and safety of SNF472 in patients who have ulcerated calciphylaxis lesions. Patient recruitment is ongoing.

PMID:35035944 | PMC:PMC8757410 | DOI:10.1093/ckj/sfab117

F1000Res. 2021 Dec 13;10:1275. doi: 10.12688/f1000research.73754.1. eCollection 2021.

ABSTRACT

Background: The biomaterials engineering goal is to manufacture a biocompatible scaffold that adequately supports or improves tissue regeneration after implantation of the biomaterial in the injured area. Many requirements are demanded for a biomaterial, such as biocompatibility, elasticity, degradation time, and a very important factor is its cost of importation or synthesis, making its application inaccessible to some countries. Studies about biomaterials market show that Polylactic acid (PLLA) is one of the most used polymers, but expensive to produce. It becomes important to prove the biocompatibility of the new PLLA and to find strategies to produce biocompatible biopolymers at an acceptable production cost. Methods: In this work, the polylactic acid biomaterial was synthesized by ring-opening polymerization. The polymer was submitted to initial in vivo biocompatibility studies in 12 New Zealand female rabbits, assigned to two groups: (1) Lesion and PLLA group (n = 6), (2) Lesion No PLLA group (n = 6). Each group was divided into two subgroups at six and nine months post-surgical time. Before euthanasia clinical and biochemical studies were performed and after that tomographic (CT), histological (Hematoxylin and Eosin and Masson’s trichrome) and histomorphometric analyses were performed to evaluate the injury site and prove biocompatibility. The final cost of this polymer was analyzed. Results: The statistical studies of hemogram and hepatocyte enzymes, showed that there were no significant differences between the groups for any of the times studied, in any of the variables considered and the results of CT and histology showed that there was an important process of neoregeneration. The cost analysis showed the biopolymer synthesis is between R$3,06 – R$5,49 cheaper than the import cost. Conclusions: It was possible to synthesize the PLLA biopolymer by cyclic ring opening, which proved to be biocompatible, potential osteoregenerative and cheaper than other imported biopolymers.

PMID:35035900 | PMC:PMC8729025 | DOI:10.12688/f1000research.73754.1

Clin Kidney J. 2021 Jul 6;15(1):51-59. doi: 10.1093/ckj/sfab119. eCollection 2022 Jan.

ABSTRACT

INTRODUCTION: Acute tubulointerstitial nephritis (ATIN) is a common cause of acute kidney injury with various etiologies. It has been shown that autoimmune-related ATIN (AI-ATIN) has a higher recurrence rate and a greater likelihood of developing into chronic kidney disease compared with drug-induced ATIN, yet misdiagnosis at renal biopsy is not uncommon.

METHODS: Patients who were clinicopathologically diagnosed as ATIN from January 2006 to December 2015 in Peking University First Hospital were enrolled. Clinical, pathological and follow-up data were collected. Serum samples on the day of renal biopsy were collected and tested for anti-C-reactive protein (CRP) antibodies. CRP and its linear peptides were used as coating antigens to detect antibodies. Statistical analysis was used to assess the diagnostic value of the antibodies.

RESULTS: Altogether 146 patients were enrolled. The receiver operating characteristic-area under the curve of the anti-CRP antibody for the identification of late-onset AI-ATIN was 0.750 (95% confidence interval 0.641-0.860, P < 0.001) and the positivity was associated with ATIN relapse (adjusted hazard ratio = 4.321, 95% confidence interval 2.402-7.775, P < 0.001). Antibodies detected by CRP linear peptide 6 (PT6) were superior with regard to differentiating patients with AI-ATIN, while antibodies detected by peptide 17 (PT17) could predict ATIN relapse. Antibodies detected by these two peptides were positively correlated with the severity of tubular dysfunction and pathological injury.

CONCLUSIONS: Serum anti-CRP antibody could be used to differentiate late-onset AI-ATIN and predict relapse of ATIN at the time of renal biopsy. The CRP linear peptides PT6 and PT17 could be used as coating antigens to detect anti-CRP antibodies, which may provide more information for the clinical assessment of ATIN.

PMID:35035936 | PMC:PMC8757425 | DOI:10.1093/ckj/sfab119

F1000Res. 2021 Nov 1;10:1101. doi: 10.12688/f1000research.73657.1. eCollection 2021.

ABSTRACT

Background: Our objective was to estimate the frequency of anisometropia at various educational stages, from pre-school to 9th school year, studying its association with gender, study cycle and area of residence. Methods: 749 children and adolescents (from 3 to 16 years old) participated in this study, 46.7% girls and 42.7% living in a rural environment. The refraction was performed with a paediatric, open field autorefractometer (PlusOptix), without cycloplegic and under binocular conditions. Results: The frequency rate of anisometropia in the studied sample was 6.1%, varying from 2.9% in pre-school education to 9.4% in the 3rd study cycle. Myopic anisometropia was the most frequent and hyperopic and astigmatic anisometropia showed identical proportions of occurrence. No statistical evidence was found to state that the occurrence of anisometropia differs between genders or between areas of residence. Regarding the school cycle, a significant association was found with spherical equivalent anisometropia, with an increase in its frequency with school progress (p=0,012), with myopic anisometropia being the main contributor to this variation. Conclusions: The increase in workload for near tasks has been identified as a risk factor for the increase in myopia. This fact may be related to the increase in anisometropia with the educational stage, found in this study. The high rate of anisometropia found in adolescents (9.4%) as well as the progressive increase in this rate throughout school progress (from 2.9% to 9.4%) suggests the need to extend the detection strategies of this condition to beyond childhood.

PMID:35035896 | PMC:PMC8729023 | DOI:10.12688/f1000research.73657.1

Ther Adv Endocrinol Metab. 2022 Jan 10;13:20420188211066699. doi: 10.1177/20420188211066699. eCollection 2022.

ABSTRACT

BACKGROUND: Insulin resistance (IR) is common in women with polycystic ovary syndrome (PCOS). Metabolic syndrome (MS) involves IR, arterial hypertension, dyslipidemia, and visceral fat accumulation. Therefore, fatness indices and blood lipid ratios can be considered as screening markers for MS. Our study aimed to evaluate the predictive potential of selected indirect metabolic risk parameters to identify MS in PCOS.

METHODS: This cross-sectional study involved 596 women aged 18-40 years, including 404 PCOS patients diagnosed according to the Rotterdam criteria and 192 eumenorrheic controls (CON). Anthropometric and blood pressure measurements were taken, and blood samples were collected to assess glucose metabolism, lipid parameters, and selected hormone levels. Body mass index (BMI), waist-to-height ratio (WHtR), homeostasis model assessment for insulin resistance index (HOMA-IR), visceral adiposity index (VAI), lipid accumulation product (LAP), non-high-density lipoprotein cholesterol (non-HDL-C), and triglycerides-to-HDL cholesterol ratio (TG/HDL-C) were calculated. MS was assessed using the International Diabetes Federation (IDF) and the American Heart Association/National Heart, Lung, and Blood Institute (AHA/NHLBI) criteria.

RESULTS: MS prevalence was significantly higher in PCOS versus CON. Patients with both MS and PCOS had more unfavorable anthropometric, hormonal, and metabolic profiles versus those with neither MS nor PCOS and versus CON with MS. LAP, TG/HDL-C, VAI, and WHtR were the best markers and strongest indicators of MS in PCOS, and their cut-off values could be useful for early MS detection. MS risk in PCOS increased with elevated levels of these markers and was the highest when TG/HDL-C was used.

CONCLUSIONS: LAP, TG/HDL-C, VAI, and WHtR are representative markers for MS assessment in PCOS. Their predictive power makes them excellent screening tools for internists and enables acquiring accurate diagnoses using fewer MS markers.

PMID:35035875 | PMC:PMC8755932 | DOI:10.1177/20420188211066699