Nevin Manimala

Ulus Travma Acil Cerrahi Derg. 2021 Jul;27(4):402-409. doi: 10.14744/tjtes.2020.76767.

ABSTRACT

BACKGROUND: The increase in free oxygen radicals and proinflammatory cytokines in the ischemia-reperfusion injury caused by acute mesenteric ischemia are the key responsibilities of intestinal histopathological alterations. It has been reported that Ficus carica and its various parts contain antioxidant and anti-inflammatory compounds recently. Thus, in the present study, we aimed to investigate how Ficus carica seed oil affects intestinal ischemia-reperfusion injury in a rat model.

METHODS: In this study, 50 male Wistar albino rats were randomly divided into five equal groups. Negative control (NC), sham-operated (Sham), ischemia and reperfusion (IR), 3 ml/kg/day Ficus carica seed oil (FC3), 6 ml/kg/day Ficus carica seed oil (FC6). IR, FC3 and FC6 groups underwent ischemia and reperfusion procedure for 45+120 min. Only abdominal midline laparotomy was performed in the Sham group for 165 minutes.

RESULTS: Tissue levels of TNFα and IL-1β, which were proinflammatory cytokines, were significantly reduced in the FC6 group than the IR group (p<0.05). In FC3 and FC6 groups, the tissue MPO and MDA enzyme levels were significantly lower than the IR group, but there was a significantly greater decrease in the FC6 group than the FC3 group (p<0.05). SOD and CAT enzymes and reduced glutathione levels of FC3 and FC6 groups were significantly lower than IR group (p<0.05); however, there was no statistically significant difference between the FC3 and FC6 groups. FC3 and FC6 groups were histopathologically graded statistically lower than the IR group, and the FC6 group showed a significant decrease than the FC3 group (p<0.05).

CONCLUSION: Oral administration of fig seed oil may reverse biochemical and histopathological findings resulting from ischemia-reperfusion injury in an experimental model of acute mesenteric ischemia in rats, probably because of its antioxidant and anti-inflammatory compounds.

PMID:34213002 | DOI:10.14744/tjtes.2020.76767

Ulus Travma Acil Cerrahi Derg. 2021 Jul;27(4):449-456. doi: 10.14744/tjtes.2020.49196.

ABSTRACT

BACKGROUND: The optimal timing of intervention for aneurysmatic subarachnoid hemorrhage is one of the historically controversial issues in neurosurgery. Although numerous studies investigated the subject, they had many limitations due to the nature of the disease. Early and ultra-early interventions have gained more and more supporters in recent decades. Nevertheless, the effects of the early and ultra-early intervention on the outcome of the disease are far from clarity.

METHODS: A single-center retrospective cohort study was carried out at Trakya University Medical Faculty Training and Practice Hospital. The study includes data on all patients admitted with an aneurysmal subarachnoid hemorrhage between January 1, 2001, and December 31, 2005. Patients were divided into two groups according to their WFNS grade status: Good (I-III) or poor (IV-V) grades. Patients are also classified according to their Glasgow Outcome Scale score: Unfavorable (1-2) or favorable (3-5) outcomes. Data were analyzed statistically, and the effects of the early and ultra-early intervention on the outcome were assessed.

RESULTS: A total of 580 patients were admitted in the study period. Among them, 494 were eligible for the study. The median age (interquartile range) was 55 (18) years. While 244 (49.4%) patients were women, 250 (50.6%) patients were men. Three hundred and fourteen (63.6%) patients were operated, and 25 patients (5.1%) were undergone endovascular treatment. The ultra-early intervention was achieved in 60 (12.1%) patients and 142 patients (28.7%, including the previous ultra-early intervention group) early intervention was achieved. A meaningful outcome difference was present between the poor-grade ultra-early treatment group and the rest (p=0.007). Analogously, a meaningful outcome difference was present between the poor-grade early treatment group and the rest (p<0.001).

CONCLUSION: This study supports the growing trend toward early or ultra-early intervention in aneurysmatic subarachnoid hemorrhage. Our findings showed that both early and ultra-early interventions have positive effects on the outcome in poor-grade aneurysmatic subarachnoid hemorrhage patients. Future studies with more homogenized and larger samples should be realized to clarify the optimal timing of intervention for aneurysmatic subarachnoid hemorrhage.

PMID:34212997 | DOI:10.14744/tjtes.2020.49196

Ulus Travma Acil Cerrahi Derg. 2021 Jul;27(4):410-420. doi: 10.14744/tjtes.2020.18552.

ABSTRACT

BACKGROUND: Organ failures that develop due to acute pancreatitis (AP), some laboratory values and the anthropometric characteristics of the patients have been shown to play a role in the prognosis AP and have been increasingly used to investigate the prognosis of the disease although classification systems, such as Ranson’s criteria, are still used habitually. In this stud, we aimed to investigate the relationship of the organ failures observed during the course of AP, the biochemical parameters and the anthropometric characteristics of the patients and compare using Ranson’s and Atlanta Classifica-tion (AC) systems.

METHODS: Laboratory values, anthropometric data, including the waist circumference and body mass index, Systemic inflammatory response syndrome (SIRS) and organ failures developed during the course of the disease, were investigated prospectively in 153 AP patients and the Ranson and Modified Atlanta Classifications (MAC) were made.

RESULTS: A relationship was observed between the organ failures that were established in the course of the disease (lung, liver, kidney, heart and MOF (multiple organ failure)) and higher Ranson’s and MAC scores (p<0.05). Among the patients included in this study, 13 (8.4%) had multiple organ failure and 17 (11.1%) had SIRS. Exitus occurred in 10 patients (6.5%). A statistically significant relationship was found with organ failure, multiple organ failure and SIRS; and ensuing exitus (p<0.05). While no relationship was observed between the waist circumference, body mass index, Ranson’s score, there was a significant relationship between the MAC and the waist circumference (p<0.01). Among the laboratory values, high urea and ALT values showed a relationship with the Ranson and MAC (p<0.001), while between the CRP values tested at the 0 time point and the 48th hour, only the CRP value at the 48th hour had a relationship with Ranson’s score (p<0.05). Organ failure, MOF, and SIRS showed a correlation with both the severity scores and the mortality rate. In addition, a significant corre-lation was observed between the cholesterol, triglycerides and the CRP level at the time of hospitalisa-tion and mortality. On the contrary, no significant relationship was observed with the other laboratory results, including calcium, lipase and hematocrit.

CONCLUSION: In conclusion, to determine the severity and prognosis of acute pancreatitis, and ex-pect the organ failures that may occur in severe pancreatitis, the body mass index, waist circumference and laboratory values, including cholesterol, triglycerides, ALT, and CRP may supply important prog-nostic data besides the conventional disease severity scoring methods.

PMID:34212994 | DOI:10.14744/tjtes.2020.18552

Ulus Travma Acil Cerrahi Derg. 2021 Jul;27(4):427-433. doi: 10.14744/tjtes.2020.04788.

ABSTRACT

BACKGROUND: In this study, we aimed to evaluate the outcomes of patients transported by Helicopter Emergency Medical Services in East Azerbaijan Province.

METHODS: This retrospective cross-sectional study was conducted on patients transported by the HEMS centre of Tabriz from August 2014 to March 2017. Records of the centre were used to collect data. Statistical analysis was performed by SPSS software version 20; the statistical significance level was considered below 0.05.

RESULTS: In this study, 268 patients were transferred to Tabriz hospitals by 167 missions performed. The mean age of patients was 34.26±19.43, and 173 (65%) patients were male. The most common reason for call-out was the need for professional care (91.4%). The target of the majority of missions was on countryside routes. The mean distance of destinations was about 99.13±35.9 Kms, with a mean transference time of 54.68±14.17 minutes, while the mean estimated ground route time was 86.38±26.26 minutes. The most prevalent diagnosis was trauma; The Glasgow Coma Scale (GCS) and vital signs of the majority of patients were above 13 and stable, respectively. About 98 percent of patients received fluid therapy, and 71 percent were immobilized, and only 6 percent needed intubation. Also, 28 percent of patients needed Intensive Care Unit (ICU), 56 percent of whom passed away later.

CONCLUSION: Our results suggest that Tabriz HEMS missions have reduced the patient transport time and also made the mortality rate closer to international standards.

PMID:34212990 | DOI:10.14744/tjtes.2020.04788

Chem Soc Rev. 2021 Jul 2. doi: 10.1039/d0cs01065k. Online ahead of print.

ABSTRACT

COVID-19 has resulted in huge numbers of infections and deaths worldwide and brought the most severe disruptions to societies and economies since the Great Depression. Massive experimental and computational research effort to understand and characterize the disease and rapidly develop diagnostics, vaccines, and drugs has emerged in response to this devastating pandemic and more than 130 000 COVID-19-related research papers have been published in peer-reviewed journals or deposited in preprint servers. Much of the research effort has focused on the discovery of novel drug candidates or repurposing of existing drugs against COVID-19, and many such projects have been either exclusively computational or computer-aided experimental studies. Herein, we provide an expert overview of the key computational methods and their applications for the discovery of COVID-19 small-molecule therapeutics that have been reported in the research literature. We further outline that, after the first year the COVID-19 pandemic, it appears that drug repurposing has not produced rapid and global solutions. However, several known drugs have been used in the clinic to cure COVID-19 patients, and a few repurposed drugs continue to be considered in clinical trials, along with several novel clinical candidates. We posit that truly impactful computational tools must deliver actionable, experimentally testable hypotheses enabling the discovery of novel drugs and drug combinations, and that open science and rapid sharing of research results are critical to accelerate the development of novel, much needed therapeutics for COVID-19.

PMID:34212944 | DOI:10.1039/d0cs01065k

Sci Rep. 2021 Jul 1;11(1):13654. doi: 10.1038/s41598-021-93096-w.

ABSTRACT

Prediction models for population-based screening need, for global usage, to be resource-driven, involving predictors that are affordably resourced. Here, we report the development and validation of three resource-driven risk models to identify people with type 2 diabetes (T2DM) at risk of stage 3 CKD defined by a decline in estimated glomerular filtration rate (eGFR) to below 60 mL/min/1.73m². The observational study cohort used for model development consisted of data from a primary care dataset of 20,510 multi-ethnic individuals with T2DM from London, UK (2007-2018). Discrimination and calibration of the resulting prediction models developed using cox regression were assessed using the c-statistic and calibration slope, respectively. Models were internally validated using tenfold cross-validation and externally validated on 13,346 primary care individuals from Wales, UK. The simplest model was simplified into a risk score to enable implementation in community-based medicine. The derived full model included demographic, laboratory parameters, medication-use, cardiovascular disease history (CVD) and sight threatening retinopathy status (STDR). Two less resource-intense models were developed by excluding CVD and STDR in the second model and HbA1c and HDL in the third model. All three 5-year risk models had good internal discrimination and calibration (optimism adjusted C-statistics were each 0.85 and calibration slopes 0.999-1.002). In Wales, models achieved excellent discrimination(c-statistics ranged 0.82-0.83). Calibration slopes at 5-years suggested models over-predicted risks, however were successfully updated to accommodate reduced incidence of stage 3 CKD in Wales, which improved their alignment with the observed rates in Wales (E/O ratios near to 1). The risk score demonstrated similar model performance compared to direct evaluation of the cox model. These resource-driven risk prediction models may enable universal screening for Stage 3 CKD to enable targeted early optimisation of risk factors for CKD.

PMID:34211028 | DOI:10.1038/s41598-021-93096-w

Sci Rep. 2021 Jul 1;11(1):13712. doi: 10.1038/s41598-021-92699-7.

ABSTRACT

We present mathematical simulations of shapes of red blood cells (RBCs) and their cytoskeleton when they are subjected to linear strain. The cell surface is described by a previously reported quartic equation in three dimensional (3D) Cartesian space. Using recently available functions in Mathematica to triangularize the surfaces we computed four types of curvature of the membrane. We also mapped changes in mesh-triangle area and curvatures as the RBCs were distorted. The highly deformable red blood cell (erythrocyte; RBC) responds to mechanically imposed shape changes with enhanced glycolytic flux and cation transport. Such morphological changes are produced experimentally by suspending the cells in a gelatin gel, which is then elongated or compressed in a custom apparatus inside an NMR spectrometer. A key observation is the extent to which the maximum and minimum Principal Curvatures are localized symmetrically in patches at the poles or equators and distributed in rings around the main axis of the strained RBC. Changes on the nanometre to micro-meter scale of curvature, suggest activation of only a subset of the intrinsic mechanosensitive cation channels, Piezo1, during experiments carried out with controlled distortions, which persist for many hours. This finding is relevant to a proposal for non-uniform distribution of Piezo1 molecules around the RBC membrane. However, if the curvature that gates Piezo1 is at a very fine length scale, then membrane tension will determine local curvature; so, curvatures as computed here (in contrast to much finer surface irregularities) may not influence Piezo1 activity. Nevertheless, our analytical methods can be extended address these new mechanistic proposals. The geometrical reorganization of the simulated cytoskeleton informs ideas about the mechanism of concerted metabolic and cation-flux responses of the RBC to mechanically imposed shape changes.

PMID:34211012 | DOI:10.1038/s41598-021-92699-7

NPJ Genom Med. 2021 Jul 1;6(1):55. doi: 10.1038/s41525-021-00220-w.

ABSTRACT

Among children, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections are typically mild. Here, we describe the case of a 3.5-year-old girl with an unusually severe presentation of coronavirus disease (COVID-19). The child had an autoinflammatory disorder of unknown etiology, which had been treated using prednisolone and methotrexate, and her parents were half cousins of Turkish descent. After 5 days of nonspecific viral infection symptoms, tonic-clonic seizures occurred followed by acute cardiac insufficiency, multi-organ insufficiency, and ultimate death. Trio exome sequencing identified a homozygous splice-variant in the gene TBK1, and a homozygous missense variant in the gene TNFRSF13B. Heterozygous deleterious variants in the TBK1 gene have been associated with severe COVID-19, and the variant in the TNFRSF13B gene has been associated with common variable immunodeficiency (CVID). We suggest that the identified variants, the autoinflammatory disorder and its treatment, or a combination of these factors probably predisposed to lethal COVID-19 in the present case.

PMID:34210994 | DOI:10.1038/s41525-021-00220-w

NPJ Breast Cancer. 2021 Jul 1;7(1):84. doi: 10.1038/s41523-021-00291-z.

ABSTRACT

While tumor infiltration by CD8⁺ T cells is now widely accepted to predict outcomes, the clinical significance of intratumoral B cells is less clear. We hypothesized that spatial distribution rather than density of B cells within tumors may provide prognostic significance. We developed statistical techniques (fractal dimension differences and a box-counting method ‘occupancy’) to analyze the spatial distribution of tumor-infiltrating lymphocytes (TILs) in human triple-negative breast cancer (TNBC). Our results indicate that B cells in good outcome tumors (no recurrence within 5 years) are spatially dispersed, while B cells in poor outcome tumors (recurrence within 3 years) are more confined. While most TILs are located within the stroma, increased numbers of spatially dispersed lymphocytes within cancer cell islands are associated with a good prognosis. B cells and T cells often form lymphocyte clusters (LCs) identified via density-based clustering. LCs consist either of T cells only or heterotypic mixtures of B and T cells. Pure B cell LCs were negligible in number. Compared to tertiary lymphoid structures (TLS), LCs have fewer lymphocytes at lower densities. Both types of LCs are more abundant and more spatially dispersed in good outcomes compared to poor outcome tumors. Heterotypic LCs in good outcome tumors are smaller and more numerous compared to poor outcome. Heterotypic LCs are also closer to cancer islands in a good outcome, with LC size decreasing as they get closer to cancer cell islands. These results illuminate the significance of the spatial distribution of B cells and LCs within tumors.

PMID:34210991 | DOI:10.1038/s41523-021-00291-z

NPJ Sci Learn. 2021 Jul 1;6(1):14. doi: 10.1038/s41539-021-00093-9.

ABSTRACT

Knowing when the brain learns is crucial for both the comprehension of memory formation and consolidation and for developing new training and neurorehabilitation strategies in healthy and patient populations. Recently, a rapid form of offline learning developing during short rest periods has been shown to account for most of procedural learning, leading to the hypothesis that the brain mainly learns during rest between practice periods. Nonetheless, procedural learning has several subcomponents not disentangled in previous studies investigating learning dynamics, such as acquiring the statistical regularities of the task, or else the high-order rules that regulate its organization. Here we analyzed 506 behavioral sessions of implicit visuomotor deterministic and probabilistic sequence learning tasks, allowing the distinction between general skill learning, statistical learning, and high-order rule learning. Our results show that the temporal dynamics of apparently simultaneous learning processes differ. While high-order rule learning is acquired offline, statistical learning is evidenced online. These findings open new avenues on the short-scale temporal dynamics of learning and memory consolidation and reveal a fundamental distinction between statistical and high-order rule learning, the former benefiting from online evidence accumulation and the latter requiring short rest periods for rapid consolidation.

PMID:34210989 | DOI:10.1038/s41539-021-00093-9