Tag: nevin manimala

Protein Pept Lett. 2022 Mar 14. doi: 10.2174/0929866529666220314105130. Online ahead of print.

ABSTRACT

BACKGROUND: A series of mutants of Rhizomucor miehei lipase (RML) screened through four rounds of directed evolution was studied as the research object. The hydrolysis activity of mutants to triglycerides was determined, and their genes were sequenced. Results showed that mutations in the propeptide can improve the activity of RML during the evolution. Two parts of propeptide (wild-type and mutant) and mature region were connected by molecular simulation technology.

METHODS: The spatial structure of the most positive mutants containing the mutations in the propeptide was mainly characterized by the increase in the opening angle of the lid structure in the mature region of RML, the enhancement of the hydrophobicity of the active center, and the triad of the active center shifted outward.

RESULTS: The three indexes above explain the mechanism of propeptide mutations on the activity change of the target protein. In addition, statistical analysis of all the mutants screened in directed evolution showed that: (1) most of the mutants with increased activity contained mutations of the propeptide; (2) In the later stage of directed evolution, the number of active mutants decreased gradually, and the mutations of inactivated protein mainly occurred in the mature region; and (3) In the last round of directed evolution, the mutations distributed in the propeptide improved the mutant activity further. The results show the propeptide down the evolutionary pressure of RML and delayed emergence of the evolutionary platform.

CONCLUSION: These findings reveal the role of propeptide in the evolution of RML and provide strategies for the molecular transformation of other lipases.

PMID:35289250 | DOI:10.2174/0929866529666220314105130

Recent Adv Inflamm Allergy Drug Discov. 2022 Mar 14. doi: 10.2174/2772270816666220314154951. Online ahead of print.

ABSTRACT

BACKGROUND AND AIM: Chronic Urticaria is an allergic disorder that affects about 0.5 to 5% of the population in different communities. The disease’s chronic course and long-term onset impose high economic and psychological costs on communities, adversely affecting individual and social life. Platelets play a role in various pathophysiological processes, including inflammation and immunology. Growing evidence suggests that platelets are actively involved in the pathogenesis of various inflammatory disorders, including inflammatory skin diseases. This study investigated the relationship between platelet and Immunoglobulin-E markers and chronic idiopathic urticaria.

MATERIALS AND METHODS: In the present case-control study, for the study population, patients with chronic idiopathic urticaria were referred to the Asthma and Allergy Clinic, and their caregivers were selected as the case and control groups, respectively. In this study, the mean platelet count (PLT), mean platelet volume (MPV), platelet distribution width (PDW), and Total IgE values were simultaneously measured in the case and control groups. After taking 5CCs of venous blood, a blood sample was sent to the laboratory for platelet and IgE marker measurements.

RESULTS: 100 patients and 100 healthy persons were studied in this study. The mean age in the case group was 34.95, and in the control group was 35.78 years. The results showed that the mean values of PLT, MPV, PDW, and Total IgE in the case group were 12.86, 9.83, 252190, and 147.05, respectively. The mean values of PLT, MPV, PDW, and Total IgE in the control group were 16.93, 7.53, 231410, and 15.29, respectively, which was statistically significant (P = 0.001). Moreover, Total IgE in the Autologous Serum Skin Test (ASST) positive group was higher than ASST negative group and was statistically significant (P = 0.001).

CONCLUSION: The study results indicate the possible role of platelets in urticaria and inflammation. MPV in patients with chronic urticaria was higher than in the control group. The present study showed no significant relationship between the severity of urticaria and platelet markers, but there was a significant relationship between the severity of urticaria and ASST. Moreover, the severity of urticaria was higher in the positive skin test group.

PMID:35289259 | DOI:10.2174/2772270816666220314154951

Am J Sports Med. 2022 Mar;50(3):618-629. doi: 10.1177/03635465211072554.

ABSTRACT

BACKGROUND: Autologous platelet-rich plasma (PRP) and bone marrow aspirate concentrate (BMC) are being used clinically as therapeutic agents for the treatment of knee osteoarthritis.

PURPOSE/HYPOTHESIS: The purpose of this study was to compare the efficacy of BMC and PRP on pain and function in patients with knee osteoarthritis up to 24 months after injection. It was hypothesized that patients receiving BMC would have better sustained outcomes than those receiving PRP.

STUDY DESIGN: Randomized controlled trial; Level of evidence, 2.

METHODS: A total of 90 participants aged between 18 and 80 years with symptomatic knee osteoarthritis (Kellgren-Lawrence grades 1-3) were randomized into 2 study groups: PRP and BMC. Both groups completed the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) and subjective International Knee Documentation Committee (IKDC) questionnaire before and 1, 3, 6, 9, 12, 18, and 24 months after a single intra-articular injection of leukocyte-rich PRP or BMC. A linear mixed-effects model was performed to quantify the effects over time and the difference between the groups. This model has the random effect for time to assess the extent in which the change over time differs from one person to another.

RESULTS: An overall 84 patients completed questionnaires from baseline to 12 months; however, 17 patients (n = 9; PRP group) were lost to follow-up at 18 months and 25 (n = 13; PRP group) at 24 months. There were no statistically significant differences in IKDC (P = .909; 95% CI, -6.26 to 7.03) or WOMAC (P = .789; 95% CI, -6.26 to 4.77) scores over time between the groups. Both groups had significantly improved IKDC (P < .001; 95% CI, 0.275-0.596) and WOMAC (P = .001; 95% CI, -0.41 to -0.13) scores from baseline to 24 months after the injection. These improvements plateaued at 3 months and were sustained for 24 months after the injection, with no difference between PRP and BMC at any time point.

CONCLUSIONS: For the treatment of osteoarthritis, PRP and BMC performed similarly out to 24 months. BMC was not superior to PRP.

REGISTRATION: NCT03289416 (ClincalTrials.gov identifier).

PMID:35289231 | DOI:10.1177/03635465211072554

Nutr Health. 2022 Mar 15:2601060221086113. doi: 10.1177/02601060221086113. Online ahead of print.

ABSTRACT

Background: Increasing water and decreasing sugar-sweetened beverage (SSB) consumption in preschoolers provide a strategy to reduce lifelong obesity risks. Aim: To determine feasibility/acceptability and examine preliminary findings of an innovative intervention for preschooler parents to promote fruit-infused water (FIW) to decrease SSB intake. Methods: Fourteen parents of preschoolers completed a pre-intervention survey, attended a presentation with a FIW demonstration/taste-testing, received pitchers/strainers, cutting boards, and FIW recipes/instructions, and received 8 supportive text messages over one month. Feasibility/acceptability was determined from analyzing parents’ responses about participating. Descriptive statistics were conducted to analyze pre-/post-intervention survey data. Results: Three themes emerged: “Healthy Option Alternative”; “Feasible to Make FIW at Home”; and “Benefits for Parents”. Preliminary findings from ten parents completing both pre-/post-intervention surveys indicated a decrease in preschoolers’ total SSB amount/kcal intake, and an increase in parent self-efficacy and FIW knowledge/consumption. Conclusion: Preliminary findings provide valuable feasibility/acceptability information to guide a larger future study.

PMID:35289221 | DOI:10.1177/02601060221086113

Am J Sports Med. 2022 Mar;50(3):778-787. doi: 10.1177/03635465211067806.

ABSTRACT

BACKGROUND: The deltoid ligament (DL) is an important stabilizer of the ankle. DL injury of varying severity can occur alone or with syndesmotic injury and fibular fracture. Limited diagnostic tools are available to assess DL injury quantitatively.

PURPOSE: To establish an arthroscopic quantitative assessment of DL injury and to compare its performance with that of external rotation stress (ERS) and gravity stress (GS) radiography.

STUDY DESIGN: Controlled laboratory study.

METHODS: In total, 24 cadaveric lower extremities were divided into 4 groups: group 1 consisted of intact DL, group 2 of superficial DL disruption, group 3 of deep DL disruption, and group 4 of complete DL (superficial and deep) disruption. All specimens underwent sequential sectioning of syndesmotic ligaments, and medial clear space (MCS) was measured with ankle arthroscopy, ERS radiography, and GS radiography at different stages of syndesmotic sectioning.

RESULTS: For noninjured deltoid (group 1) and injured deltoid (groups 2-4), area under the receiver operating characteristic curve (AUC) of measurement of MCS was 0.939 for arthroscopy, 0.932 for ERS radiography, and 0.874 for GS radiography, with a significant difference between arthroscopy and GS radiography (P = .014). For incomplete deltoid injury (groups 1-3) and complete deltoid injury (group 4), the AUC of MCS was 0.811 for arthroscopy, 0.656 for ERS radiography, and 0.721 for GS radiography, with a significant difference between arthroscopy and ERS radiography (P < .001) and between arthroscopy and GS radiography (P = .035). For all stages of syndesmotic sectioning, cutoff values of arthroscopic MCS with intact fibula were ≤2.5 mm for intact DL, between 2.5 and 3.5 mm for partial DL injury (superficial or deep), and ≥3.5 mm for complete DL injury. Arthroscopy was unable to detect a difference between superficial deltoid injury (group 2) and deep deltoid injury (group 3) in partial DL injury, with a measured MCS between 2.5 and 3.5 mm. The intraclass correlation coefficient of interrater reliability was 0.975 for arthroscopy, 0.917 for ERS radiography, and 0.811 for GS radiography.

CONCLUSION: Arthroscopic MCS measurement can differentiate intact DL, partial DL injury, and complete DL injury. Compared with ERS and GS radiography, arthroscopic MCS measurement has greater accuracy with excellent interrater reliability.

CLINICAL RELEVANCE: For patients with suspected DL injury, arthroscopic MCS is useful for determining deltoid lesion severity based on defined cutoff values for consideration in preoperative planning to improve surgical outcomes.

PMID:35289224 | DOI:10.1177/03635465211067806

Korean J Radiol. 2022 Mar 8. doi: 10.3348/kjr.2021.0786. Online ahead of print.

ABSTRACT

OBJECTIVE: To compare the therapeutic outcomes of laparoscopic hepatic resection (LHR) and laparoscopic radiofrequency ablation (LRFA) for single subcapsular hepatocellular carcinoma (HCC).

MATERIALS AND METHODS: We screened 244 consecutive patients who had received either LHR or LRFA between January 2014 and December 2016. The feasibility of LRFA in patients who underwent LHR was retrospectively assessed by two interventional radiologists. Finally, 60 LRFA-feasible patients who had received LHR and 29 patients who had received LRFA as the first treatment for a solitary subcapsular HCC between 1 cm and 3 cm were finally included. We compared the therapeutic outcomes, including local tumor progression (LTP), recurrence-free survival (RFS), and overall survival (OS) between the two groups before and after propensity score (PS) matching. Multivariable Cox proportional hazard regression was also used to evaluate the difference in OS and RFS between the two groups for all 89 patients.

RESULTS: PS matching yielded 23 patients in each group. The cumulative LTP and OS rates were not significantly different between the LHR and LRFA groups after PS matching (p = 0.900 and 0.003, respectively). The 5-year LTP rates were 4.6% and 4.4%, respectively, and OS rates were 100% and 90.7%, respectively. The RFS rate was higher in LHR group without statistical significance (p = 0.070), with 5-year rates of 78.3% and 45.3%, respectively. OS was not significantly different between the LHR (reference) and LRFA groups in multivariable analyses, with a hazard ratio (HR) of 1.33 (95% confidence interval, 0.12-1.54) (p = 0.818). RFS was higher in LHR (reference) than in LRFA without statistical significance in multivariable analysis, with an HR of 2.01 (0.87-4.66) (p = 0.102).

CONCLUSION: There was no significant difference in therapeutic outcomes between LHR and LRFA for single subcapsular HCCs measuring 1-3 cm. The difference in RFS should be further evaluated in a larger study.

PMID:35289151 | DOI:10.3348/kjr.2021.0786

J Korean Med Sci. 2022 Mar 14;37(10):e77. doi: 10.3346/jkms.2022.37.e77.

ABSTRACT

BACKGROUND: Herein, we aimed to evaluate the maternal mortality ratio and perinatal mortality rate for different perinatal medical care service areas (PMCSAs), which were established by considering their geographical accessibility to maternal-fetal intensive care units (MFICUs) and neonatal intensive care units (NICUs), and to compare the PMCSAs according to their accessibility to these perinatal care services.

METHODS: Based on the 70 hospital service areas (HSAs) across the country confirmed through the Dartmouth Atlas methodology analysis and gathering of expert opinions, the PMCSAs were designated by merging HSAs without MFICUs and NICUs to the nearest HSA that contained MFICUs and NICUs, based on which MFICU and NICU could be reached within the shortest amount of time from population-weighted centroids in HSAs. PMCSAs where 30% or more of the population could not access MFICUs and NICUs within 60 minutes were identified using the service module ArcGIS and were defined as having access vulnerability.

RESULTS: Thirty-three of 70 HSAs in the country did not contain MFICUs and NICUs, and 39 PMCSAs were finally derived by merging 70 HSAs. Ten of 39 PMCSAs (25.6%) were classified as having access vulnerability to MFICUs and NICUs. The national maternal mortality ratio was 9.42, with the highest ratio seen in the region of Wonju (25.86) and the lowest in Goyang (2.79). The national perinatal mortality rate was 2.86, with the highest and lowest rates observed in the Gunsan (4.04) and Sejong (1.99) regions, respectively. The perinatal mortality rates for areas vulnerable and invulnerable to maternal and neonatal healthcare accessibility were 2.97 and 2.92, respectively, but there was no statistically significant difference in this rate (P = 0.789). The maternal mortality ratio for areas vulnerable and invulnerable to maternal and neonatal healthcare accessibility were 14.28 and 9.48, respectively; this ratio was significantly higher in areas vulnerable to accessibility (P = 0.022).

CONCLUSION: Of the PMCSAs across the country, 25.6% (10/39) were deemed to be vulnerable to MFICU and NICU accessibility. There was no difference in the perinatal mortality rate between the vulnerable and invulnerable areas, but the maternal mortality ratio in vulnerable areas was significantly higher than that in invulnerable areas.

PMID:35289138 | DOI:10.3346/jkms.2022.37.e77

J Pathol Clin Res. 2022 Mar 14. doi: 10.1002/cjp2.266. Online ahead of print.

ABSTRACT

The tumor microenvironment (TME) is a critical regulator of the development of malignant lymphoma. Therapeutics targeting the TME, especially immune checkpoint molecules, are changing the treatment strategy for lymphoma. However, the overall response to these therapeutics for diffuse large B-cell lymphoma (DLBCL) is modest and new targets of immunotherapy are needed. To find critical immune checkpoint molecules for DLBCL, we explored the prognostic impact of immune checkpoint molecules and their ligands using publicly available datasets of gene expression profiles. In silico analysis of three independent datasets (GSE117556, GSE10846, and GSE181063) revealed that DLBCL expressing CD24 had a poor prognosis and had a high frequency of MYC aberrations. Moreover, gene set enrichment analysis showed that the ‘MYC-targets-hallmark’ (false discovery rate [FDR] = 0.024) and ‘inflammatory-response-hallmark’ (FDR = 0.001) were enriched in CD24-high and CD24-low DLBCL, respectively. In addition, the expression of cell-specific markers of various immune cells was higher in CD24-low DLBCL than in CD24-high DLBCL. CIBERSORT analysis of the datasets showed fewer macrophages in CD24-high DLBCL than in CD24-low DLBCL. Additionally, immunohistochemical analysis of 335 cases of DLBCL showed that few TME cells were found in CD24-high DLBCL, although statistical differences were not observed. These data indicate that CD24 expression suppresses immune cell components of the TME in DLBCL, suggesting that CD24 may be a target for cancer immunotherapy in aggressive large B-cell lymphoma.

PMID:35289116 | DOI:10.1002/cjp2.266

CPT Pharmacometrics Syst Pharmacol. 2022 Mar 14. doi: 10.1002/psp4.12784. Online ahead of print.

ABSTRACT

The relationship between SARS-CoV-2 viral load reduction and disease symptom resolution remains largely undefined for COVID-19. While vaccine-derived immunity takes time to develop, neutralizing monoclonal antibodies offer immediate, passive immunity to patients with COVID-19. Bamlanivimab and etesevimab are two potent neutralizing monoclonal antibodies directed to the receptor binding domain (RBD) of the spike (S) protein of SARS-CoV-2. This study aims to describe the relationship between viral load and resolution of 8 common COVID-19-related symptoms in patients following treatment with neutralizing monoclonal antibodies (bamlanivimab alone or bamlanivimab and etesevimab together), in a Phase 2 clinical trial. Corresponding pharmacokinetics (PK), viral load and COVID-19-related symptom data were modelled using Nonlinear Mixed Effects Modeling (NONMEM) to describe the time-course of 8 COVID-19-related symptoms in an ordered categorical manner (none, mild, moderate, severe), following administration of bamlanivimab or bamlanivimab and etesevimab together to participants with COVID-19. The PK/PD models characterized the exposure-viral load-symptom time course of the 8 pre-selected COVID-19-related symptoms. Baseline viral load (BVL), change in viral load from baseline (ΔVL) and time since the onset of symptoms, demonstrated statistically significant effects on symptom score probabilities. Higher BVL generally indicated an increased probability of symptom severity. The severity of symptoms decreased over time, partially driven by the decrease in viral load. The effect of increasing time resulting in decreased severity of symptoms was over and above the effect of decreasing viral load. Administration of bamlanivimab alone or together with etesevimab results in a faster time to resolution of COVID-19-related symptoms compared to placebo.

PMID:35289125 | DOI:10.1002/psp4.12784

Thorac Cancer. 2022 Mar 15. doi: 10.1111/1759-7714.14384. Online ahead of print.

ABSTRACT

PURPOSE: A previous study demonstrated that intracranial tumor volume had some correlation with gastrointestinal cancer patients’ outcome. The aim of this study was to analyze patients with esophageal carcinoma (EC) and brain metastases to investigate if intracranial tumor volume would be a predictor of these patients’ survival.

METHODS: A total of 52 patients with brain metastases from esophageal squamous cell carcinoma or esophageal adenocarcinoma were retrospectively reviewed. Patients without images of brain metastases in the hospital information system were eliminated.

RESULTS: The median follow-up time duration was 8.4 months (interquartile range 4.0-15.2). The median overall survival (OS) from time of brain metastases diagnosis was 8.0 months for all cases. Median OS of patients with small and large cumulative intracranial tumor volume (CITV) (<6.65 cm³ , ≥6.65 cm³ ) was 11.23 and 7.4 months, respectively. Median OS of patients with large and small largest intracranial tumor volume (LITV) (≥7.75 cm³ , <7.75 cm³ ) was 6.4 and 10.6 months, respectively. Univariate analysis demonstrated that CITV (hazard ratio [HR] 1.255, 95% confidence interval [CI] 0.673-2.342, p = 0.475) or LITV (HR 1.037, 95% CI 0.570-1.887, p = 0.904) was not significantly associated with improved OS. Multivariate analysis demonstrated that CITV and LITV were not significantly associated with improved OS.

CONCLUSION: EC patients with small intracranial tumor volume may have longer OS than those with large intracranial tumor volume, but this difference did not reach statistical difference. Future studies with a larger sample size may validate the correlation of intracranial tumor volume and patient survival.

PMID:35289101 | DOI:10.1111/1759-7714.14384