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Nevin Manimala Statistics

Discovery of a rapidly evolving yeast defense factor, KTD1, against the secreted killer toxin K28

Proc Natl Acad Sci U S A. 2023 Feb 21;120(8):e2217194120. doi: 10.1073/pnas.2217194120. Epub 2023 Feb 17.

ABSTRACT

Secreted protein toxins are widely used weapons in conflicts between organisms. Elucidating how organisms genetically adapt to defend themselves against these toxins is fundamental to understanding the coevolutionary dynamics of competing organisms. Within yeast communities, “killer” toxins are secreted to kill nearby sensitive yeast, providing a fitness advantage in competitive growth environments. Natural yeast isolates vary in their sensitivity to these toxins, but to date, no polymorphic genetic factors contributing to defense have been identified. We investigated the variation in resistance to the killer toxin K28 across diverse natural isolates of the Saccharomyces cerevisiae population. Using large-scale linkage mapping, we discovered a novel defense factor, which we named KTD1. We identified many KTD1 alleles, which provided different levels of K28 resistance. KTD1 is a member of the DUP240 gene family of unknown function, which is rapidly evolving in a region spanning its two encoded transmembrane helices. We found that this domain is critical to KTD1‘s protective ability. Our findings implicate KTD1 as a key polymorphic factor in the defense against K28 toxin.

PMID:36800387 | DOI:10.1073/pnas.2217194120

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Nevin Manimala Statistics

Endoscopic Lavage for the Treatment of Multiple Shunt Failures in Children

Turk Neurosurg. 2022 Dec 28. doi: 10.5137/1019-5149.JTN.42640-22.3. Online ahead of print.

ABSTRACT

AIM: To compare the efficacy of neuroendoscopic lavage (NEL) and shunt revision (SR) in the treatment of multiple shunt failures in children with hydrocephalus.

MATERIAL AND METHODS: The data of 56 pediatric patients who underwent surgeries for the treatment of shunt failure were retrospectively reviewed. Patients were divided into 2 groups as simple SR (Group A) and NEL+SR (Group B). Demographic characteristics, co-morbidities, surgical interventions, cerebrospinal fluid (CSF) analyzes, and complications were recorded and statistically compared for both groups.

RESULTS: Among the 56 patients, 51 of them presented with shunt dysfunction due to infectious debris or clots at different times. 28 of 51 patients (54.9%) were female and 23 (45%) were male. The mean age was 7.3 months. Simple SR was performed in 30 cases (Group A), and NEL and simultaneous SR were performed in 21 patients (Group B). The risk of shunt dysfunction was significantly lower in Group B (p 0.05).The risk of infection was high in Group A, but this was not statistically significant (p 0.05).

CONCLUSION: Simultaneously endoscopic lavage and shunt revision is an effective method in the treatment of shunt dysfunction in children. It is also superior to simple shunt revision for the risk of shunt dysfunction. More clinical studies are needed to verify this outcome.

PMID:36799283 | DOI:10.5137/1019-5149.JTN.42640-22.3

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Unilateral Dynamic Stabilization in Recurrent Lumbar Disc Herniation

Turk Neurosurg. 2022 Dec 28. doi: 10.5137/1019-5149.JTN.42533-22.2. Online ahead of print.

ABSTRACT

AIM: To evaluate the effectiveness and outcomes of unilateral dynamic stabilization surgical treatment in patients with recurrent lumbar disc herniation (RLDH).

MATERIAL AND METHODS: Patients requiring an operation due to RLDH at the L4-5 level were included in the study.They divided into the following two groups: SD group who had only revision discectomy (n = 20) and DDgroup who had unilateral dynamic rod stabilization with discectomy (n = 20). Low back and leg pain were evaluated with the visual analog scale (VAS), and functional results were evaluated with the Oswestry disability index (ODI). The VAS scores were evaluated in two different regions as VAS Low Back (VASLB) and VAS Leg (VASL). The results of each patient were evaluated preoperatively and at 1 and 12 months postoperatively. The anterior disc height (ADH), posterior disc height (PDH), and segmental angle (SA) were measured on the sagittal computed tomography (CT) scans of each patient’s lumbar spine. Modified Pfirrmann grades in the operated and adjacent segments on lumbar magnetic resonance imaging (MRİ) were assessed preoperatively and at 12 months postoperatively.

RESULTS: Altogether, 40 patients (17 women and 23 men; mean age, 47.9 years) were enrolled. There was no statistically significant difference in the VASLB scores between the two groups (P = 0.42). The decrease in VASL scores was statistically significant between groups (P 0.05). A statistically significant decrease in ODI scores was also observed (P 0.05). When ADH and PDH obtained preoperatively and postoperatively were compared for the SD group, the differences were not statistically significant. Significant differences were found for ADH and PDH obtained preoperatively and postoperatively in the DD group (P 0.05). However, for SA, the difference was not significant between the two groups (P = 0.28).

CONCLUSION: Unilateral dynamic stabilization for RLDH leads to fewer surgical complications and provides sufficient stability by preserving segmental movements.

PMID:36799282 | DOI:10.5137/1019-5149.JTN.42533-22.2

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Contribution of Multilevel Transformainal Lumbar Interbody Fusion Surgery to Restoration of Lumbar Lordosis in Patients with Degenerative Spine: Comparison of Long and Short Level Fusion

Turk Neurosurg. 2022 Nov 30. doi: 10.5137/1019-5149.JTN.41633-22.3. Online ahead of print.

ABSTRACT

AIM: The present study aimed to investigate the effect of multi-level TLIF (Transforaminal lumbar interbody fusion) procedures in degenerative spine conditions on the restoration of sagittal balance.

MATERIAL AND METHODS: In this retrospective study we compared the radiological results of patients treated with three or fewer segment fusion assigned as the short-level group (n: 23) and patient with more than three segment fusion as assigned to the long-level group (n: 24) in who underwent lumbar fusion using a multilevel TLIF procedure diagnosed with degenerative spine. The spinopelvic parameter (pelvic incidence (PI), pelvic tilt (PT), sacral slope (SS)), and sagittal spinal balance parameters (lumbar lordosis (LL), distal lumbar lordosis(DLL), thoracolumbar kyphosis (TLK), thoracic kyphosis (TK), T1 spinopelvic inclination (T1SPI), T9 spinopelvic inclination (T9SPI), T1 pelvic angle (TPA) and sagittal vertical axis (SVA)) were measured from lateral spinal radiograph pre and postoperatively.

RESULTS: The study included 47 patients who met the inclusion criteria, with a mean age of 60.4 ± 12.2 years. The mean follow-up time of our patients was 18.3 ± 11 months. Thirty-five (74.5%) patients were women and 12 (25.5%) were men. There was a significant difference in the postoperative LL, DLL, and TK measurements in both groups compared with the preoperative period. There were no statistical differences in the pre- and postoperative PT, PI, SS, TPA, and T1SPI between the groups.

CONCLUSION: Multilevel TLIF procedure regardless of long or short level fusion can be used to correct sagittal alignment which improved the LL, DLL, and SVA. However, long level fusion group had improved the SVA better than short level.

PMID:36799280 | DOI:10.5137/1019-5149.JTN.41633-22.3

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Relationship of Public Interest in Cardiopulmonary Resuscitation with Cardiac Arrest Epidemiology and National Socioeconomic Indicators: Exploratory Infodemiology Study

Prehosp Disaster Med. 2023 Feb 17:1-5. doi: 10.1017/S1049023X23000183. Online ahead of print.

ABSTRACT

STUDY OBJECTIVE: Web-based big data analytics provides a great opportunity to measure public interest in cardiac arrest (CA) and cardiopulmonary resuscitation (CPR). This study aimed to examine associations of online interest in CPR and CA with epidemiological characteristics of out-of-hospital CA (OHCA) and national socioeconomic indicators in a set of European countries.

METHODS: Country-level online search popularity data for CPR and CA topics measured in relative search volume (RSV) with Google Trends (GT), published OHCA epidemiological indicators, and World Bank’s socioeconomic statistics of 28 European countries for the year 2017 were analyzed for correlation using Spearman’s rank correlation coefficient (r S ).

RESULTS: Whereas OHCA incidence, bystander CPR rate, and hospital survival did not correlate with RSV for CPR or CA, the rate of return of spontaneous circulation (ROSC) demonstrated a positive correlation with RSV for CPR (r S = 0.388; P = .042). Further, RSV for CPR positively correlated with countries’ gross domestic product and health expenditure (r S = 0.939 and 0.566; P ≤.002) and negatively correlated with mortality caused by road traffic injury (r S = -0.412; P = .029).

CONCLUSION: For the sample of European countries, public interest in CPR or CA showed no relationship with real bystander CPR rates and therefore could not be recommended as a proxy of community readiness to attempt resuscitation. The association of RSV for CPR with the rate of ROSC and countries’ socioeconomic characteristics suggests it could be used for identifying geographies with poor performance of prehospital systems in terms of managing CA, in particular where effective epidemiological surveillance for CA may be unavailable.

PMID:36799185 | DOI:10.1017/S1049023X23000183

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Meningiomas of the Cerebellopontine Angle: Tips and Pearls for Safe Surgical Resection

Turk Neurosurg. 2022 Sep 27. doi: 10.5137/1019-5149.JTN.41657-22.2. Online ahead of print.

ABSTRACT

AIM: To present our series of cerebellopontine angle (CPA) meningiomas and to provide some innovative surgical steps for safe removal of these tumors.

MATERIAL AND METHODS: The clinical, radiological and surgical characteristics of 32 patients with meningioma in the CPA were retrospectively analyzed. Statistical analysis was performed to determine the factors that affect the incidence of complication.

RESULTS: The mean age was 49.5 years and 87.5% of patients were male. 87.5% of patients had WHO grade I meningioma and the others had WHO grade II tumors. The mean tumor volume was 33.98 ml and 65.6% of the patients underwent gross total resection. Preoperative tumor size/extension and extent of resection were related with the development of complications.

CONCLUSION: CPA meningiomas are challeging tumors for a safe removal. Tumor size and extent of resection are important risk factors for the development of postoperative complications.

PMID:36799278 | DOI:10.5137/1019-5149.JTN.41657-22.2

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Use of time‑density curves of dynamic contrast‑enhanced computed tomography for determination of the histological therapeutic effects of neoadjuvant chemotherapy for pancreatic ductal adenocarcinoma

Oncol Rep. 2023 Mar;49(3):61. doi: 10.3892/or.2023.8498. Epub 2023 Feb 17.

ABSTRACT

The present study aimed to investigate the histological changes caused by neoadjuvant chemotherapy (NAC) for pancreatic ductal adenocarcinoma (PDAC), and to demonstrate the use of time‑density curves (TDCs) of dynamic contrast‑enhanced computed tomography (CECT) for determination of the histological therapeutic effects of NAC for PDAC. A total of 96 patients with PDAC were examined; 46 underwent NAC (NAC group) and 50 did not undergo NAC (non‑NAC group). Based on histological therapeutic effect and using the area of residual tumor (ART) grading system, the NAC group was divided into low‑responders and high‑responders. Histological analysis was used to evaluate the densities of cancer cells, cancer‑associated fibroblasts (CAFs), microvessels and stromal collagen fibers in the NAC and non‑NAC groups. Radiological analysis was used to evaluate the TDCs of three slopes of the NAC group, namely slopes between the non‑contrast and arterial phases (δ1 and δ1′), between the arterial and portal phases (δ2 and δ2′), and between the portal and equilibrium phases (δ3 and δ3′). δ1‑δ3 were before NAC, whereas δ1’‑δ3′ were after NAC. Changes in δ1, δ2 and δ3 before and after NAC were denoted as δδ1 (=δ1’‑δ1), δδ2 (=δ2’‑δ2) and δδ3 (=δ3’‑δ3). ART grading system, histological examination and radiological examination data were also statistically analyzed. Histological examination revealed a significant decrease in cancer cells and CAFs, and a significant increase in stromal collagen fibers due to NAC (P<0.01). Radiological examination revealed that δ1′ was significantly higher than δ1 in low‑responders (P<0.05), whereas δ2′ was significantly lower than δ2 in high‑responders (P<0.01). δδ2 was significantly lower and δδ3 was significantly higher in high‑responders than in low‑responders (P<0.01 and P<0.05, respectively). Receiver operating characteristic curve showed that δδ2 and δδ3 were effective indicators of the histological therapeutic effect of NAC. In conclusion, the TDC of dynamic CECT may be useful for determining the histological therapeutic effect of NAC for PDAC.

PMID:36799183 | DOI:10.3892/or.2023.8498

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Causal association between atopic eczema and inflammatory bowel disease: A two-sample bidirectional Mendelian randomization study of the East Asian population

J Dermatol. 2023 Mar;50(3):327-336. doi: 10.1111/1346-8138.16642. Epub 2022 Nov 22.

ABSTRACT

Observation studies have postulated that atopic eczema is associated with a risk of inflammatory bowel disease in the East Asian population; however, this association does not obviate the biases resulting from confounding effects and reverse causation. This study aimed to determine whether this association is causal in the East Asian population using a bidirectional two-sample Mendelian randomization design. Independent genetic variants obtained from public genome-wide association studies for atopic eczema (4296 cases, 163 807 controls) were extracted to estimate the causal effects on inflammatory bowel disease (2824 cases, 3719 controls) and its two main conditions: Crohn’s disease (1690 cases, 3719 controls) and ulcerative colitis (1134 cases, 3719 controls). Atopic eczema was found to be strongly associated with inflammatory bowel disease (odds ratio [95% confidence interval]: 1.520 [1.179, 1.959]; p = 0.001), but not vice versa. Subtype analyses revealed that atopic eczema is significantly associated with Crohn’s disease (1.650 [1.293, 2.106]; p = 0.000) but not with ulcerative colitis. Both Crohn’s disease and ulcerative colitis were found to be causally related to atopic eczema; Crohn’s disease could reduce the risk of atopic eczema (0.866 [0.807, 0.930]; p = 0.000) while ulcerative colitis could increase the risk of atopic eczema (1.112 [1.021, 1.212]; p = 0.015). In conclusion, this study revealed that statistically causal relationships are present between atopic eczema and inflammatory bowel disease in the East Asian population. These findings are significant for guiding the treatment of atopic eczema and inflammatory bowel disease in clinical practice.

PMID:36799178 | DOI:10.1111/1346-8138.16642

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Oral contraceptives (OCs) in combination with metformin versus OCs alone on metabolism in non-obese polycystic ovary syndrome(PCOS): a meta-analysis and systematic review of randomized controlled trials(RCTs)

Clin Endocrinol (Oxf). 2023 Feb 17. doi: 10.1111/cen.14895. Online ahead of print.

ABSTRACT

BACKGROUND: To compare OCs(oral contraceptives) + metformin and OCs alone for metabolic effects in non-obese PCOS patients.

METHODS: The search was performed in PubMed, EMBASE, the Cochrane Library, and clinicaltrials.gov for all published studies up to April 30, 2022 and was limited to English language articles. All randomized controlled trials (RCTs) comparing OCs + metformin and OCs alone for reproductive-age women with PCOS were included. Data were processed using Revman 5.3 software.

RESULTS: Of 396 studies identified, 14 RCTs were included for analysis comprising 707 women. OCs+metformin significantly modified fasting glucose[MD=-0.21(95%CI=-0.31,-0.12),p<0.00001]and fasting insulin[MD= -2.54(95%CI=-4.04,-1.04),p=0.0009] at study completion compared with OCs alone in non-obese PCOS subjects. There was no statistic difference in the homeostasis model assessment of insulin resistance (HOMA-IR), high density lipoprotein (HDL), low density lipoprotein (LDL), total cholesterol or triglycerides at study end between the two groups.

CONCLUSIONS: Metformin, via its positive effects on insulin clearance, in combination with OCs, improved glucose metabolism and offered a good treatment alternative in non-obese women with PCOS. This article is protected by copyright. All rights reserved.

PMID:36799083 | DOI:10.1111/cen.14895

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Is local review of positron emission tomography scans sufficient in diffuse large B-cell lymphoma clinical trials? A CALGB 50303 analysis

Cancer Med. 2023 Feb 17. doi: 10.1002/cam4.5628. Online ahead of print.

ABSTRACT

BACKGROUND: Quantitative methods of Fluorodeoxyglucose Positron Emission Tomography (FDG-PET) interpretation, including the percent change in FDG uptake from baseline (ΔSUV), are under investigation in lymphoma to overcome challenges associated with visual scoring systems (VSS) such as the Deauville 5-point scale (5-PS).

METHODS: In CALGB 50303, patients with DLBCL received frontline R-CHOP or DA-EPOCH-R, and although there were no significant associations between interim PET responses assessed centrally after cycle 2 (iPET) using 5-PS with progression-free survival (PFS) or overall survival (OS), there were significant associations between central determinations of iPET ∆SUV with PFS/OS. In this patient cohort, we retrospectively compared local vs central iPET readings and evaluated associations between local imaging data and survival outcomes.

RESULTS: Agreement between local and central review was moderate (kappa = 0.53) for VSS and high (kappa = 0.81) for ∆SUV categories (<66% vs. ≥66%). ∆SUV ≥66% at iPET was significantly associated with PFS (p = 0.03) and OS (p = 0.002), but VSS was not. Associations with PFS/OS when applying local review vs central review were comparable.

CONCLUSIONS: These data suggest that local PET interpretation for response determination may be acceptable in clinical trials. Our findings also highlight limitations of VSS and call for incorporation of more objective measures of response assessment in clinical trials.

PMID:36799072 | DOI:10.1002/cam4.5628