Nevin Manimala

Proteomics Clin Appl. 2022 Apr 24:e2100049. doi: 10.1002/prca.202100049. Online ahead of print.

ABSTRACT

PURPOSE: The study aim is a comparative proteome-based analysis of different autologous bone entities (alveolar bone (AB), iliac cortical bone (IC) and iliac spongiosa (IS)) used for alveolar onlay grafting.

EXPERIMENTAL DESIGN: Site-matched bone samples of AB, IC and IS were harvested during alveolar onlay grafting. Proteins were extracted using a detergent-based (sodium dodecyl sulfate) strategy and trypsinized. Proteome analysis was performed using liquid chromatography – tandem mass spectrometry (LC-MS/MS). MaxQuant was used for peptide-to-spectrum matching, peak detection, and quantitation. Linear models for microarray analysis (LIMMA) were used to detect differentially abundant peptides and proteins.

RESULTS: 1730 different proteins were identified across the 15 samples at a false discovery rate of 1 %. Partial least-squares discriminant analysis approved segregation of AB, IC and IS protein profiles. LIMMA statistics highlighted 66 proteins that were more abundant in AB then in IC (vs. 92 proteins were enriched in IC over AB). Gene ontology enrichment analysis revealed a matrisomal vs. an immune-related proteome fingerprint in AB vs IC.

CONCLUSION AND CLINICAL RELEVANCE: This pilot study demonstrates an ECM protein-related proteome fingerprint in AB and an immune-related proteome fingerprint in IS and IC. This article is protected by copyright. All rights reserved.

PMID:35462455 | DOI:10.1002/prca.202100049

J Basic Microbiol. 2022 Apr 24. doi: 10.1002/jobm.202200116. Online ahead of print.

ABSTRACT

Actinomycetes isolated from the Arctic sediment were evaluated for the production of the enzyme L-asparaginase, an enzyme used to treat acute lymphoblastic leukemia. The most potent strain Streptomyces koyangensis SK4 was selected for L-asparaginase enzyme production by submerged fermentation. The effect of various fermentation parameters on enzyme production was analyzed statistically using the Plackett Burman design and response surface method. Effects of eight parameters including temperature, pH, incubation time, inoculum size, agitation speed, the concentration of starch, L-asparagine and yeast extract were studied on L-asparaginase production by the Arctic isolate Streptomyces koyangensis SK4. Factors such as temperature, pH, incubation time, agitation speed and L-asparagine concentration were found to be important factors influencing the L-asparaginase production. Maximum enzyme activity of 136 IU/ml was obtained at 20°C on the seventh day of incubation in the Asparagine dextrose broth maintained at pH-7.5, agitation speed-125 rpm and L-asparagine concentration of 7.5 g/L. The statistical optimization method described in this study proved effective for increasing the L-asparaginase production by Arctic actinomycetes. This article is protected by copyright. All rights reserved.

PMID:35462434 | DOI:10.1002/jobm.202200116

Acta Cytol. 2022 Apr 22:1-7. doi: 10.1159/000524053. Online ahead of print.

ABSTRACT

OBJECTIVE: Morphological indicators of chromosomal instability (CI), including multipolar mitoses, chromatin bridges (CB), strings, nuclear buds (NB), micronuclei (MN), and deoxyribonucleic acid (DNA) ploidy analysis help in prognostication of breast carcinoma. The present study was done to evaluate CI in breast carcinoma and correlate with DNA ploidy and tumor grade.

STUDY DESIGN: Fifty cases of carcinoma breast diagnosed by fine-needle aspiration cytology were included. Robinson’s grading method was used on smears to grade breast carcinoma. To assess the morphological features of CI, the best May-Grünwald Giemsa stained smear was chosen. At least 1,000 epithelial cells on oil immersion magnification (×100 objective) were counted. DNA ploidy on the aspirates was done by flow cytometry.

RESULTS: All the patients were female, diagnosed as infiltrating ductal carcinoma on cytology. Eight tumors were grade I, 32 were grade II, and 10 were grade III. MN was seen in 48 cases, NB in 45, and CB in 12 cases. Mean MN, NB, and CB scores in aneuploid (24) cases were 9.96 ± 8.42, 5.29 ± 4.71, and 1.08 ± 1.84 while 6.19 ± 6.67, 1.92 ± 1.79, and 0.11 ± 0.33 were seen in diploid (26) cases. Statistically significant positive correlation was observed between CI and DNA ploidy.

CONCLUSIONS: Morphological evaluation of CI by light microscopy on routinely stained breast aspirates is feasible, although a meticulous search is required. Cytomorphological features of CI and ploidy have a positive correlation with increasing tumor grade.

PMID:35462374 | DOI:10.1159/000524053

Am J Nephrol. 2022 Apr 22:1-9. doi: 10.1159/000523961. Online ahead of print.

ABSTRACT

BACKGROUND: Desidustat, an oral hypoxia-inducible factor prolyl hydroxylase inhibitor, is being developed to treat anemia in patients with chronic kidney disease (CKD) without dialysis dependency.

METHODS: In total, 588 patients with a clinical diagnosis of anemia due to CKD without dialysis need and with baseline hemoglobin of 7.0-10.0 g/dL (inclusive) were randomized in a 1:1 ratio to receive either desidustat 100 mg oral tablets thrice a week for 24 weeks or biosimilar darbepoetin subcutaneous injection 0.75 μg/kg once in 2 weeks for 24 weeks. The primary outcome was the change from baseline in hemoglobin to evaluation period of Weeks 16-24. Key secondary outcomes included the number of patients with hemoglobin response, changes in the hepcidin levels, changes in the vascular endothelial growth factor (VEGF) levels, and changes in the lipid and lipoprotein profiles.

RESULTS: Hemoglobin change from baseline to Weeks 16-24 was 1.95 g/dL in the desidustat group and 1.83 g/dL in the darbepoetin group (difference: 0.11 g/dL; 95% CI: -0.12, 0.34), which met prespecified non-inferiority margin (-0.75 g/dL). The hemoglobin responders were significantly higher (p = 0.0181) in the desidustat group (196 [77.78%]) compared to the darbepoetin group (176 [68.48%]). The difference of change in hepcidin from baseline to Week 12 and Week 24 (p = 0.0032 at Week 12, p = 0.0016 at Week 24) and the difference of change in low-density lipoprotein from baseline to Week 24 (p value = 0.0269) between the two groups was statistically significant. The difference of change from baseline in VEGF to Weeks 12 and 24 between the two groups was not statistically significant.

CONCLUSION: Desidustat is non-inferior to darbepoetin in the treatment of anemia due to non-dialysis dependent CKD and it is well-tolerated.

PMID:35462372 | DOI:10.1159/000523961

Fetal Diagn Ther. 2022 Apr 22. doi: 10.1159/000521421. Online ahead of print.

ABSTRACT

INTRODUCTION: The methodological quality of fetal brain charts has not been critically appraised yet.

MATERIAL AND METHODS: MEDLINE, EMBASE, CINAHL and the Web of Science databases were searched electronically up to December 31, 2020. The primary outcome was to evaluate the methodology of the studies assessing the growth of fetal brain structures throughout gestation. A list of 28 methodological quality criteria divided into three domains according to “study design”, “statistical and reporting methods”, and “specific relevant neurosonography aspects” was developed in order to assess the methodological appropriateness of the included studies. The overall quality score was defined as the sum of low risk of bias marks, with the range of possible scores being 0-28. This quality assessment was applied to each individual study reporting reference ranges for fetal brain structures.

RESULTS: Sixty studies were included in the systematic review. The overall mean quality score of the studies included in this review was 51.3%. When focusing on each of the assessed domains, the mean quality score was 53.7% for “study design”, 54.2% for “statistical and reporting methods” and 38.6% for “specific relevant neurosonography aspects”. The sample size calculation, the correlation with a postnatal imaging evaluation and the whole fetal brain assessment were the items at the highest risk of bias for each domain assessed, respectively. The subgroup analysis according to different anatomical location showed the lowest quality score for ventricular and periventricular structures and the highest for cortical structures.

CONCLUSIONS: Most previously published studies reporting fetal brain charts suffers from poor methodology and are at high risk of biases, mostly when focusing on neurosonography issues. Further prospective longitudinal studies aiming at constructing specific growth charts for fetal brain structures should follow rigorous methodology to minimize the risk of biases, guarantee higher levels of reproducibility and improve the standard of care.

PMID:35462359 | DOI:10.1159/000521421

J Environ Manage. 2022 Apr 21;314:115102. doi: 10.1016/j.jenvman.2022.115102. Online ahead of print.

ABSTRACT

A systems analysis perspective related to soil science is necessary to achieve many of the sustainability targets articulated by the United Nations Sustainable Development Goals (SDGs). The System of Environmental-Economic Accounting – Ecosystem Accounting (SEEA-EA) framework is the international statistical standard for quantifying both the contributions that ecosystems make to the economy, and the impacts of economic activity on ecosystems. However, due to the difficulty of obtaining empirical data on ecosystem service flows, in many cases such quantification is informed by ecosystem service models. Previous research on the Mitchell catchment, Queensland Australia provided a novel opportunity to quantify the implications of using a model of hillslope erosion and sediment delivery in isolation (as represented in one of the most frequently used ecosystem service models – InVEST), by comparing such estimates against multiple lines of local empirical data, and a more comprehensive representation of locally important erosion and deposition processes through a sediment budget model. Estimates of the magnitude of hillslope erosion modelled using an approach similar to InVEST and the calibrated sediment budget differed by an order of magnitude. If an uncalibrated InVEST-type model was used to inform the relative distribution of erosion magnitude, findings suggest the incorrect erosion process would be identified as the dominant contributor to suspended sediment loads. However, the sediment budget model could only be calibrated using data on sediment sources and sinks that had been collected through sustained research effort in the catchment. A comparable level of research investment may not be available to inform ecosystem service assessments elsewhere. Findings for the Mitchell catchment demonstrate that practitioners should exercise caution when using model-derived estimates of the sediment retention ecosystem service, which have not been calibrated and validated against locally collected empirical data, to inform an ecosystem account and progress towards achieving the SDGs.

PMID:35462256 | DOI:10.1016/j.jenvman.2022.115102

Int J Pediatr Otorhinolaryngol. 2022 Apr 14;157:111133. doi: 10.1016/j.ijporl.2022.111133. Online ahead of print.

ABSTRACT

OBJECTIVE: Repair of pediatric mandibular fractures (PMFs) can be challenging due to the lack of permanent dentition for immobilization, and the presence of unerupted teeth and growth plates in the mandible limiting the space for fixation. Interdental splinting (IDS) has been advocated to provide temporary fixation without the need for mandibular plating; however, there is sparse description of the surgical methodology, and data on long term outcomes are even more limited. The aim of this study is to present our technique and outcomes using a novel technique for IDS repair of pediatric mandible fractures.

STUDY DESIGN: Observational retrospective chart review.

SETTING: Tertiary care pediatric hospital.

SUBJECTS AND METHODS: Pediatric patients requiring operative repair for mandibular fracture at our tertiary care institution between 2004 and 2021 were included. Patients over 18 years of age, those who died due to associated injuries, or those who underwent non-IDS repairs were excluded. Subjects with at least 3 months of follow-up were assessed for efficacy of surgical repair and short-term adverse outcomes, and at least 1 year for long-term adverse events. Descriptive statistics were obtained.

RESULTS: Twenty-three children were included in the study with an average age of 7.4 years (range 2-17 years). Fifty-two percent (52.2%) were female. The most common fracture site was the condyle, occurring in 16 children (70%). The indication for operative repair in all cases was malocclusion. The average duration of maxillomandibular fixation (MMF) with the novel IDS was 21 days (range 12-42 days). The average length of follow up was 1.6 years (range 3 months-11 years). All children had restored, functional occlusion at follow up with none requiring further orthodontic or dental intervention. Three children of the total cohort (13.0%) had prolonged hospitalization beyond 48 h for poor oral intake. Five children (21.7%) experienced minor long-term complications including persistent temporomandibular joint pain (n = 1, 4.3%), infection (n = 2, 8.7%), hypertrophic scar (n = 1, 4.3%) and exposure of hardware (n = 1, 4.3%).

CONCLUSION: PMFs resulting in malocclusion are safely and effectively managed with operative repair utilizing a customizable IDS, with few observed short- and long-term complications.

PMID:35462217 | DOI:10.1016/j.ijporl.2022.111133

J Mol Graph Model. 2022 Apr 19;114:108199. doi: 10.1016/j.jmgm.2022.108199. Online ahead of print.

ABSTRACT

In this study, two approaches were applied to enhance the conformational search from molecular dynamics simulations to determine the transition states of a potential energy surface topology. The main focus is on the augmented dynamics using the swarm particle intelligence and Tsallis statistics molecular dynamics simulations of the phase transition from folding to unfolding state of a peptide in an explicit solvent environment. The transition between nodes is modelled as a random walk in a dynamic graph describing a set of basins in a free energy landscape and their pairwise relations. In this study, a dynamic graph neural networks approach is used to model the dynamic information of each free energy state as the graph evolves by observing the sequential information of edges, the time intervals between edges, and information flow. In addition, a multi-digraph approach is suggested to determine the discrete pathways of the conformation transitions between the states in that free energy surface. Besides, the role of water in the thermal and chemical denaturation of the protein is studied. This study supports the idea that the folding process is characterised by a reaction in water resulting in a reduction of the iceberg formation. Whereas unfolding by another reaction in which equilibrium is shifted towards creating iceberg states in water. In this study, the dipole-dipole correlations between the peptide and solvent are described based on an information-theoretic measure, such as local transfer entropy, to explain the role of waters in the folding/unfolding mechanism.

PMID:35462186 | DOI:10.1016/j.jmgm.2022.108199

Zhonghua Wei Chang Wai Ke Za Zhi. 2022 Apr 25;25(4):342-347. doi: 10.3760/cma.j.cn441530-20220217-00051.

ABSTRACT

Objective: To analyze the association of No.11p posterior lymph node metastasis with clinicopathological features and its prognostic significance in gastric cancer. Methods: A single-center retrospective cohort study was conducted. Clinicopathological data of patients with primary gastric cancers undergoing No.11p posterior lymph node dissection from January 2016 to December 2020 were retrieved from the Database of Gastric Cancer, West China Hospital, Sichuan University. Case inclusion criteria: (1) gastric cancer proved by pathology; (2) radical resection with intraoperative No.11p posterior lymph node dissection; (3) operations performed by the same surgical team; (4) no previous history of other malignant tumors and no concurrent malignant tumors. Those with stump gastric cancer, history of gastrectomy, neoadjuvant chemotherapy, incomplete clinicopathological data and lost to follow-up were excluded. During the operation, the upper edge of the pancreas was retracted forward to expose the area between the upper edge of the pancreas and the splenic vessels. The proximal segment of the splenic artery was skeletonized to remove lymphatic tissue anterior and superior to the splenic artery for No.11p lymph node dissection. For patients with lymphadenopathy in the area between the splenic artery and the splenic vein, dissection was performed. The enlarged lymph nodes were labeled with titanium clips and named as No.11p posterior lymph node. Pathological examination was performed separately after the specimen was isolated. Statistical analysis was performed using R software. Results: A total of 127 gastric cancer patients, who underwent No.11p posterior lymph nodes dissection were included in this study, of which 120 patients without No.11p posterior lymph nodes metastasis (No.11p posterior lymph nodes negative) and 7 patients with No.11p posterior lymph nodes metastasis (No.11p posterior lymph nodes positive). A total of 8 metastatic No.11p posterior lymph nodes were detected in 7 patients, metastasis rate and with a ratio of 5.5% (7/127) and 6.8% (8/127), respectively. In the subgroup analysis of T3-4 stage patients, the metastasis rate and ratio of No.11p posterior lymph nodes were 9.0% (7/78) and 10.7% (8/75), respectively. Compared to negative cases, patients with No.11p posterior lymph nodes metastasis had larger tumor (P=0.002), higher proportion of Borrmann type Ⅲ and Ⅳ tumors (P=0.005), more metastatic lymph nodes (P<0.001), more advanced T stage (P=0.043), N stage (P=0.004) and TNM stage (P=0.015). In survival analysis, patients with No.11p posterior lymph node metastasis had a significantly worse prognosis than those without metastasis after adjusting for TNM stage (hazard ratio=3.009, 95% confidence interval: 1.824-4.964, P<0.001). Conclusions: The No.11p posterior lymph node metastasis in gastric cancer is associated with worse prognosis. For patients of T3-4 stage gastric cancer, No.11p posterior lymph node dissection should be emphasized during radical operation.

PMID:35461203 | DOI:10.3760/cma.j.cn441530-20220217-00051

Zhonghua Wei Chang Wai Ke Za Zhi. 2022 Apr 25;25(4):336-341. doi: 10.3760/cma.j.cn441530-20210520-00214.

ABSTRACT

Objective: To investigate the safety and efficacy of pelvic peritoneal reconstruction and its effect on anal function in laparoscopy-assisted anterior resection of low and middle rectal cancer. Methods: A prospective cohort study was conducted. Consecutive patients with low and middle rectal cancer who underwent laparoscopy-assisted transabdominal anterior resection at Naval Military Medical University Changhai Hospital from February 2020 to February 2021 were enrolled. Inclusion criteria: (1) the distance from tumor to the anal verge ≤10 cm; (2) laparoscopy-assisted transabdominal anterior resection of rectal cancer; (3) complete clinical data; (4) rectal adenocarcinoma diagnosed by postoperative pathology. Exclusion criteria: (1) emergency surgery; (2) patients with a history of anal dysfunction or anal surgery; (3) preoperative diagnosis of distant (liver, lung) metastasis; (4) intestinal obstruction; (5) conversion to open surgery for various reasons. The pelvic floor was reconstructed using SXMD1B405 (Stratafix helical PGA-PCL, Ethicon). The first needle was sutured from the left anterior wall of the neorectum to the right. Insertion of the needle was continued to suture the root of the sigmoid mesentery while the Hemo-lok was used to fix the suture. The second needle was started from the beginning of the first needle, after 3-4 needles, a drainage tube was inserted through the left lower abdominal trocar to the presacral space. Then, the left peritoneal incision of the descending colon was sutured, after which Hemo-lok fixation was performed. The operative time, perioperative complications, postoperative Wexner anal function score and low anterior resection syndrome (LARS) score were compared between the study group and the control group. Three to six months after the operation, pelvic MRI was performed to observe and compare the pelvic floor anatomical structure of the two groups. Results: A total of 230 patients were enrolled, including 58 who underwent pelvic floor peritoneum reconstruction as the study group and 172 who did not undergo pelvic floor peritoneum reconstruction as the control group. There were no significant differences in general data between the two groups (all P>0.05). The operation time of the study group was longer than that of control group [(177.5±33.0) minutes vs. (148.7±45.5) minutes, P<0.001]. There was no significant difference in the incidence of perioperative complications (including anastomotic leakage, anastomotic bleeding, postoperative pneumonia, urinary tract infection, deep vein thrombosis, and intestinal obstruction) between the two groups (all P>0.05). Eight cases had anastomotic leakage, of whom 2 cases (3.4%) in the study group were discharged after conservative treatment, 5 cases (2.9%) of other 6 cases (3.5%) in the control group were discharged after the secondary surgical treatment. The Wexner score and LARS score were 3.1±2.8 and 23.0 (16.0-28.0) in the study group, which were lower than those in the control group [4.7±3.4 and 27.0 (18.0-32.0)], and the differences were statistically significant (t=-3.018, P=0.003 and Z=-2.257, P=0.024). Severe LARS was 16.5% (7/45) in study group and 35.5% (50/141) in control group, and the difference was no significant differences (Z=4.373, P=0.373). Pelvic MRI examination 3 to 6 months after surgery showed that the incidence of intestinal accumulation in the pelvic floor was 9.1% (3/33) in study group and 46.4% (64/138) in control group (χ(2)=15.537, P<0.001). Conclusion: Pelvic peritoneal reconstruction using stratafix in laparoscopic anterior resection of middle and low rectal cancer is safe and feasible, which may reduce the probability of the secondary operation in patients with anastomotic leakage and significantly improve postoperative anal function.

PMID:35461202 | DOI:10.3760/cma.j.cn441530-20210520-00214