Category: Nevin Manimala

Nat Commun. 2023 Feb 25;14(1):1075. doi: 10.1038/s41467-023-36752-1.

ABSTRACT

Endosomal escape and subsequent cytosolic delivery of small interfering RNA (siRNA) therapeutics is believed to be highly inefficient. Since it has not been possible to quantify cytosolic amounts of delivered siRNA at therapeutic doses, determining delivery bottlenecks and total efficiency has been difficult. Here, we present a confocal microscopy-based method to quantify cytosolic delivery of fluorescently labeled siRNA during lipid-mediated delivery. This method enables detection and quantification of sub-nanomolar cytosolic siRNA release amounts from individual release events with measures of quantitation confidence for each event. Single-cell kinetics of siRNA-mediated knockdown in cells expressing destabilized eGFP unveiled a dose-response relationship with respect to knockdown induction, depth and duration in the range from several hundred to thousands of cytosolic siRNA molecules. Accurate quantification of cytosolic siRNA, and the establishment of the intracellular dose-response relationships, will aid the development and characterization of novel delivery strategies for nucleic acid therapeutics.

PMID:36841822 | DOI:10.1038/s41467-023-36752-1

Adv Simul (Lond). 2023 Feb 25;8(1):7. doi: 10.1186/s41077-023-00244-5.

ABSTRACT

Neonatal deaths are a major contributor to global under-5-year-old mortality. Training birth attendants can improve perinatal outcomes, but skills may fade over time. In this pilot study, we assessed skill decay of nursing students after remote video versus in-person resuscitation training in a low-resource setting. Filipino nursing students (n = 49) underwent traditional, in-person simulation-based Helping Babies Breathe (HBB) training in Mindanao, Philippines. Participants were then assigned to receive refresher training at 2-month intervals either in-person or via tele-simulation beginning at 2 months, 4 months, or 6 months after initial training. A knowledge examination and practical examination, also known as objective structured clinical examination B in the HBB curriculum, were administered before retraining to assess knowledge and skill retention at time of scheduled follow-up. Time to initiation of bag-mask ventilation (BMV) in seconds during simulated birth asphyxia was the primary outcome. Skill decay was evident at first follow-up, with average time to BMV increasing from 56.9 (range 15-87) s at initial post-training to 83.8 (range 32-128) s at 2 months and 90.2 (range 51-180) s at 4 months. At second follow-up of the 2-month group, students showed improved pre-training time to BMV (average 70.4; range 46-97 s). No statistical difference was observed between in-person and video-trained students in time to BMV. Because of COVID-19 restrictions, the 6-month follow-up was not completed. We conclude that remote video refresher training is a reasonable alternative to traditional in-person HBB training. Our study also suggests that refreshers may be needed more frequently than every 2 months to mitigate skill decay. Additional studies are necessary to assess the longitudinal impact of tele-simulation on clinical outcomes.

PMID:36841812 | DOI:10.1186/s41077-023-00244-5

Oncogenesis. 2023 Feb 25;12(1):10. doi: 10.1038/s41389-023-00456-4.

ABSTRACT

Head and neck paragangliomas (HNPGLs), rare chemoresistant tumors curable only with surgery, are strongly influenced by genetic predisposition, hence patients and relatives require lifetime follow-up with MRI and/or PET-CT because of de novo disease risk. This entails exposure to electromagnetic/ionizing radiation, costs, and organizational challenges, because patients and relatives are scattered far from reference centers. Simplified first-line screening strategies are needed. We employed flow injection analysis tandem mass spectrometry, as used in newborn metabolic screening, to compare the plasma metabolic profile of HNPGL patients (59 samples, 56 cases) and healthy controls (24 samples, 24 cases). Principal Component Analysis (PCA) and Partial Least Discriminant Analysis (PLS-DA) highlighted a distinctive HNPGL signature, likely reflecting the anaplerotic conversion of the TCA cycle to glutaminolysis and catabolism of branched amino acids, DNA damage and deoxyadenosine (dAdo) accumulation, impairment of fatty acid oxidation, switch towards the Warburg effect and proinflammatory lysophosphatidylcholines (LPCs) signaling. Statistical analysis of the metabolites that most impacted on PLS-DA was extended to 10 acoustic neuroma and 2 cholesteatoma patients, confirming significant differences relative to the HNPGL plasma metabolomic profile. The best confusion matrix from the ROC curve built on 2 metabolites, dAdo and C26:0-LPC, provided specificity of 94.29% and sensitivity of 89.29%, with positive and negative predictive values of 96.2% and 84.6%, respectively. Analysis of dAdo and C26:0-LPC levels in dried venous and capillary blood confirmed that dAdo, likely deriving from 2′-deoxy-ATP accumulated in HNPGL cells following endogenous genotoxic damage, efficiently discriminated HNPGL patients from healthy controls and acoustic neuroma/cholesteatoma patients on easily manageable dried blood spots.

PMID:36841802 | DOI:10.1038/s41389-023-00456-4

J Orthop Surg Res. 2023 Feb 25;18(1):140. doi: 10.1186/s13018-023-03636-5.

ABSTRACT

BACKGROUND: The purpose of this meta-analysis was to compare the efficacy and outcomes of bifocal bone transport (BFT) and trifocal bone transport (TFT) for the treatment of tibial bone defects caused by fracture-related infection (FRI).

METHODS: The literature searches of Cochrane Library, Embase, Google Scholar databases, PubMed/Medline, and Web of Science for literature published up to September 20, 2022, were performed. The quality of the included studies was evaluated according to the MINORS scale. Patients were divided into the BFT group and the TFT group, depending on the site of the osteotomy. The demographic data, defect size (DS), external fixation time (EFT), external fixation index (EFI), bone and functional results, complications, and autologous bone grafting (ABG) were extracted and analyzed using the Review Manager software (version 5.3).

RESULTS: Five studies included 484 patients with tibial bone defects treated by bone transport investigated in this meta-analysis, with a mean bone defect of 9.3 cm. There were statistical differences in DS (MD = – 2.38, 95% CI – 3.45 to – 1.32, P < 0.0001), EFT (MD = 103.44, 95% CI 60.11 to 146.77, P < 0.00001), and EFI (MD = 26.02, 95% CI 14.38 to 37.65, P < 0.00001) between BFT group and TFT group. There was no statistical difference in bone results (RR = 0.98, 95% CI 0.91 to 1.06, P = 0.67), functional results (RR = 0.94, 95% CI 0.82 to 1.07, P = 0.37), complications (OR = 1.57, 95% CI 0.59 to 4.14, P = 0.36), and ABG (RR = 1.2, 95% CI 0.78 to 1.84, P = 0.42) between two groups.

CONCLUSIONS: TFT was a feasible and practical method in the treatment of massive tibial bone defects caused by FRI to receive shorter EFT and satisfactory bone and functional results.

PMID:36841800 | DOI:10.1186/s13018-023-03636-5

Cancer Imaging. 2023 Feb 25;23(1):22. doi: 10.1186/s40644-023-00532-3.

ABSTRACT

BACKGROUND: We aimed to prospectively compare the diagnostic performance of gadoxetic acid-enhanced MRI (EOB-MRI) and contrast-enhanced Computed Tomography (CECT) for hepatocellular carcinoma (HCC) detection and liver transplant (LT) eligibility assessment in cirrhotic patients with explant histopathology correlation.

METHODS: In this prospective, single-institution ethics-approved study, 101 cirrhotic patients were enrolled consecutively from the pre-LT clinic with written informed consent. Patients underwent CECT and EOB-MRI alternately every 3 months until LT or study exclusion. Two blinded radiologists independently scored hepatic lesions on CECT and EOB-MRI utilizing the liver imaging reporting and data system (LI-RADS) version 2018. Liver explant histopathology was the reference standard. Pre-LT eligibility accuracies with EOB-MRI and CECT as per Milan criteria (MC) were assessed in reference to post-LT explant histopathology. Lesion-level and patient-level statistical analyses were performed.

RESULTS: Sixty patients (49 men; age 33-72 years) underwent LT successfully. One hundred four non-treated HCC and 42 viable HCC in previously treated HCC were identified at explant histopathology. For LR-4/5 category lesions, EOB-MRI had a higher pooled sensitivity (86.7% versus 75.3%, p < 0.001) but lower specificity (84.6% versus 100%, p < 0.001) compared to CECT. EOB-MRI had a sensitivity twice that of CECT (65.9% versus 32.2%, p < 0.001) when all HCC identified at explant histopathology were included in the analysis instead of imaging visible lesions only. Disregarding the hepatobiliary phase resulted in a significant drop in EOB-MRI performance (86.7 to 72.8%, p < 0.001). EOB-MRI had significantly lower pooled sensitivity and specificity versus CECT in the LR5 category with lesion size < 2 cm (50% versus 79%, p = 0.002 and 88.9% versus 100%, p = 0.002). EOB-MRI had higher sensitivity (84.8% versus 75%, p < 0.037) compared to CECT for detecting < 2 cm viable HCC in treated lesions. Accuracies of LT eligibility assessment were comparable between EOB-MRI (90-91.7%, p = 0.156) and CECT (90-95%, p = 0.158).

CONCLUSION: EOB-MRI had superior sensitivity for HCC detection; however, with lower specificity compared to CECT in LR4/5 category lesions while it was inferior to CECT in the LR5 category under 2 cm. The accuracy for LT eligibility assessment based on MC was not significantly different between EOB-MRI and CECT.

TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03342677 , Registered: November 17, 2017.

PMID:36841796 | DOI:10.1186/s40644-023-00532-3

BMC Cardiovasc Disord. 2023 Feb 25;23(1):109. doi: 10.1186/s12872-023-03086-1.

ABSTRACT

BACKGROUND: Recent studies indicated that the prognosis of patients with gastrointestinal tumors is frequently influenced by its complications, notably myocardial injury. The main object is to investigate the occurrence and risk factors of myocardial injury in patients with gastrointestinal tumor.

METHODS: 1126 patients who received gastrointestinal tumor related surgery from May 2018 to June 2020 in the Sixth Affiliated Hospital of Sun Yat-sen University were retrospectively collected and divided into the non-myocardial injury group and the myocardial injury group (high-sensitive cardiac troponin I (hs-cTnI) ≥ 0.028 ng/ml). The occurrence and risk factors of myocardial injury in patients with gastrointestinal tumor are analyzed. The influence of myocardial injury on the ICU detention time in gastrointestinal tumor patients is also studied.

RESULTS: In total, 78 (6.93%) patients developed myocardial injuries. Compared with patients in the non-myocardial injury group, patients in the myocardial injury group have a higher prevalence of cardiovascular risk factors (including advanced age and higher smoking ratio), a higher prevalence of comorbidities (such as previous coronary artery disease, hypertension, atrium fibrillation and diabetes), and a higher rate of premedication (such as anticoagulation, β-blocker, Angiotensin-converting enzyme inhibitor/Angiotensin II receptor blocker, and diuretic) (all with P-value < 0.05). In addition, patients in the myocardial injury group also presented with a higher revised cardiac risk index (Lee index), higher neutrophil granulocyte ratio, lower hemoglobin, and higher likelihood of impaired cardiac structure and function (all with P-value < 0.05). There was a trend of statistical significance in the ICU detention time between the myocardial injury group and the non-myocardial injury group (1[1,3] vs. 2[1,10], P = 0.064). In this study, there were 7 patients presented with clinical symptoms in the myocardial injury group (chest discomfort in 4 cases, non-compressive precordial chest pain in 1 case, dyspnea in 2 cases). In the multivariate analysis, advanced age, increased Lee index score, increased neutrophil granulocyte ratio, decreased left ventricular ejection fraction (LVEF), increased interventricular septum were independent risk factors for myocardial injury.

CONCLUSION: In conclusion, advanced age, increased Lee index, increased neutrophil granulocyte ratio, decreased left ventricular ejection fraction, and increased ventricular septum were independent risk factors for preoperative myocardial injury in patients with gastrointestinal tumors. The proportion of clinical symptoms in gastrointestinal tumor patients with myocardial injury was low, indicating the necessity to closely monitor the cardiac status of individuals with gastrointestinal tumors.

PMID:36841792 | DOI:10.1186/s12872-023-03086-1

Arch Public Health. 2023 Feb 25;81(1):31. doi: 10.1186/s13690-023-01038-x.

ABSTRACT

BACKGROUND: Community drug retail outlets (CDROs) are among the initial healthcare facilities where pharmacists play a crucial role in preventing and managing noncommunicable diseases (NCDs). Therefore, this study assessed pharmacists’ level of involvement and barriers in the provision of health promotion for noncommunicable diseases at CDROs in Northwest Ethiopia.

METHODS: A community-based multicenter cross-sectional study was conducted among community pharmacists in Northwest Ethiopia from April to June 2022. Data was collected using a self-administered structured questionnaire, and analyzed using the Statistical Package for Social Science (SPSS) version 26. The level of involvement mean score difference among pharmacists was investigated using an independent samples t-test and a one-way ANOVA. Logistic regression analysis was used to examine the association between pharmacists’ level of involvement and other variables. A p-value < 0.05 at a 95% confidence interval (CI) was considered statistically significant.

RESULTS: A total of 285 (94.4%) participants participated in the study out of 302 approached samples. Overall, more than half (58.9%) of the participants showed a high level of involvement in health promotion. Pharmacists who had a degree and/or above (AOR = 0.03, 95% CI: 0.01-0.63; p < 0.001) and served a lower number of clients per day (AOR = 0.19, 95% CI: 0.04-94; p = 0.042) were less likely to have low involvement in health promotion services. Pharmacists who worked fewer hours per day (AOR = 3.65, 95% CI: 1.79-7.48; p = 0.005) were more likely to have low involvement. Lack of an appropriate area in the CDROs (52.1%) and lack of coordination with other healthcare providers (43.6%) were the most reported barriers to the provision of health promotion.

CONCLUSION: Most pharmacists were found to have a high level of involvement in health promotion activities. A lack of an appropriate area in the CDROs and a lack of coordination with other healthcare providers were among the most reported barriers. Pharmacists might benefit from training to increase their educational backgrounds, and barriers could be addressed to enhance the pharmacist involvement.

PMID:36841787 | DOI:10.1186/s13690-023-01038-x

BMC Nurs. 2023 Feb 25;22(1):53. doi: 10.1186/s12912-023-01207-x.

ABSTRACT

BACKGROUND: The COVID-19 pandemic reinforced the need to invest in nursing practice environments and health institutions were led to implement several changes. In this sense, this study aimed to analyze the impact of the changes that occurred in nursing practice environments between the first and fourth critical periods of the pandemic.

METHODS: Quantitative, observational study, conducted in a University Hospital, with the participation of 713 registered nurses. Data were collected through a questionnaire with sociodemographic and professional characterization and the Scale for the Environments Evaluation of Professional Nursing Practice, applied at two different points in time: from 1 to 30 June 2020 and from 15 August to 15 September 2021. Data were processed using descriptive and inferential statistics.

RESULTS: Overall, the pandemic had a positive impact on nursing practice environments. However, the Process component remained favourable to quality of care, while the Structure and Outcome components only moderately favourable. Nurses working in Medicine Department services showed lower scores in several dimensions of the Structure, Process and Outcome components. On the other hand, nurses working in areas caring for patients with COVID-19 showed higher scores in several dimensions of the Structure, Process and Outcome components.

CONCLUSIONS: The pandemic had a positive impact on various dimensions of nursing practice environments, which denotes that regardless of the adversities and moments of crisis that may arise, investment in work environments will have positive repercussions. However, more investment is needed in Medicine Department services, which have historically been characterised by high workloads and structural conditions that make it difficult to promote positive and sustainable workplaces.

PMID:36841780 | DOI:10.1186/s12912-023-01207-x

BMC Oral Health. 2023 Feb 25;23(1):127. doi: 10.1186/s12903-023-02832-3.

ABSTRACT

OBJECTIVE: This systematic review (SR) with meta-analysis aimed to evaluate the frequency of micronuclei in the oral mucosa exfoliated cells after cone-beam computed tomography (CBCT) examination.

METHODS: We performed language-independent computer-assisted data searches using PubMed databases, Cochrane, Embase, Web of Science all databases, and Google Scholar. The literature on micronucleus (MN) frequency of clinical trials before and after CBCT examination was included. The frequency of MN in exfoliated cells of the human oral mucosa was the primary outcome of the study. All statistical analyses were performed with R (version 4.1.0), RStudio (version 2022.02.2 + 485) software, and Meta packages (version 5.2-0). Two reviewers independently assessed the quality of the included studies by the EPHPP (Effective Public Health Practice Project) Modified scale with minor modifications. The heterogeneity of the data was analyzed using I² statistics, in which I² > 50% was considered substantial heterogeneity.

RESULTS: A total of 559 articles were selected through the search strategy. After screening titles and abstracts, nine full-text manuscripts were assessed for eligibility, and six observational studies were included in the meta-analysis. The present study showed a significant increase in MN frequency of human oral mucosal exfoliated cells 10 days after CBCT examination compared to baseline (SMD = – 0.56, 95%-CI = – 0.99 ~ – 0.13, p = 0.01). Because of the high heterogeneity among the studies (I² = 72%), after removing one study that was the main source of heterogeneity, excluding the study (I² = 47%), the common-effect model was chosen, and the meta-analysis also showed that the frequency of MN in human oral mucosa exfoliated cells increased significantly 10 days after CBCT examination (SMD = – 0.35, 95%-CI = – 0.59 ~ – 0.11, p = 0.004).

CONCLUSION: This review suggested that CBCT examination increases the frequency of micronuclei in oral mucosal exfoliated cells.

PMID:36841769 | DOI:10.1186/s12903-023-02832-3

BMC Oral Health. 2023 Feb 25;23(1):126. doi: 10.1186/s12903-023-02831-4.

ABSTRACT

BACKGROUND: A novel injectable mixture termed treated dentin matrix hydrogel (TDMH) has been introduced for restoring dentin defect in DPC. However, no study evaluated its physiological biodegradation. Therefore, the present study aimed to assess scaffold homogeneity, mechanical properties and biodegradability in vitro and in vivo and the regenerated dentin induced by TDMH as a novel pulp capping agent in human permanent teeth.

METHODS: Three TDMH discs were weighted, and dry/wet ratios were calculated in four slices from each disc to evaluate homogeneity. Hydrogel discs were also analyzed in triplicate to measure the compressive strength using a universal testing machine. The in vitro degradation behavior of hydrogel in PBS at 37 °C for 2 months was also investigated by monitoring the percent weight change. Moreover, 20 intact fully erupted premolars were included for assessment of TDMH in vivo biodegradation when used as a novel injectable pulp capping agent. The capped teeth were divided into four equal groups according to extraction interval after 2-, 8-, 12- and 16-weeks, stained with hematoxylin-eosin for histological and histomorphometric evaluation. Statistical analysis was performed using F test (ANOVA) and post hoc test (p = 0.05).

RESULTS: No statistical differences among hydrogel slices were detected with (p = 0.192) according to homogeneity. TDMH compression modulus was (30.45 ± 1.11 kPa). Hydrogel retained its shape well up to 4 weeks and after 8 weeks completely degraded. Histological analysis after 16 weeks showed a significant reduction in TDMH area and a simultaneous significant increase in the new dentin area. The mean values of TDMH were 58.8% ± 5.9 and 9.8% ± 3.3 at 2 and 16 weeks, while the new dentin occupied 9.5% ± 2.8 at 2 weeks and 82.9% ± 3.8 at 16 weeks.

CONCLUSIONS: TDMH was homogenous and exhibited significant stability and almost completely recovered after excessive compression. TDMH generally maintained their bulk geometry throughout 7 weeks. The in vivo response to TDMH was characterized by extensive degradation of the hydrogel and dentin matrix particles and abundant formation of new dentin. The degradation rate of TDMH matched the rate of new dentin formation.

TRIAL REGISTRATION: PACTR201901866476410: 30/1/2019.

PMID:36841767 | DOI:10.1186/s12903-023-02831-4