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Shedding of SARS-CoV-2 Virus in COVID-19 Patients and Neutralizing Antibody Level

Mikrobiyol Bul. 2022 Jul;56(3):416-431. doi: 10.5578/mb.20229704.

ABSTRACT

The coronavirus disease 2019 (COVID-19) turned into a pandemic shortly after emerging in December 2019, in the city of Wuhan, China. In this study, it was aimed to investigate the presence of severe acute respiratory system coronavirus-2 (SARS-CoV-2) RNA in various clinical samples and the scattering profile of the virus and the variation of anti-SARS-CoV-2 IgG and neutralizing antibody levels over time in infected patients during and after the period of COVID-19 disease. The study included COVID-19 patients from the community (CCP) (n= 47) (May-June 2020) and healthcare workers (HCWP) (n= 30) (November-December 2020). To investigate the presence of SARS-CoV-2 in clinical samples, oropharynx (OF), nasopharynx (NF), sputum, stool, blood and urine samples were taken from the CCP group on days 0, 3, 7, 14 and 28. For the detection of anti SARS-CoV-2 IgG and neutralizing antibodies serum samples were taken from the CCP group on days 0, 3, 7, 14, 28, 60, 90 and 120 and on days 14, 28, 60, 90, 120 and 150 from HCWP group. Virus RNA was detected by reverse transcription polymerase chain reaction (RT-PCR), anti SARS-CoV-2 IgG antibody levels by enzyme-linked immunosorbent assay (ELISA), neutralizing antibody levels (NAb) by cell culture neutralization and representative neutralization test (sVNT) methods. With the onset of the vaccination program in our country, 11 of the HCWP group patients had SARS-CoV-2 vaccine after the second month serum samples were taken, the remaining HCWP group patients did not get vaccinated during the study period. SARS-CoV-2 RNA was detected with the highest rates in NF (100%), stool (65.8%), sputum (45.7%), OF (41.3%), blood (5.3%), and urine (2.2%) samples, respectively. It was found that viral shedding continued for 14 days in respiratory tract samples and up to 60 days in stool samples, and no virus was detected in blood samples after the third day. It was observed that the viral load was highest at the time of diagnosis in both upper and lower respiratory tract samples, peaking on the seventh day in stool samples and following an irregular course throughout the disease. Anti-SARS-CoV-2 IgG antibody positivity was found in 41.4% of CCP group patients on the first day of diagnosis, and seroconversion was observed in all patients at the fourth month. During the study period, seropositivity was detected in only 82.1% of the patients in the HCWP group. It was observed that the IgG antibody levels peaked at the 7th day in the CCP group patients and at the third month in the HCWP group patients (S/Co: 9.6 and 2.8, respectively). Anti-SARS-CoV-2 IgG antibody levels detected in the CCP group were found to be significantly higher than the HCWP group (p<0.05). At the end of the first month, NAb was detected in all (100%) patients in the CCP group. It was found that NAb titers peaked (1/256) on the 28th day and showed a decreasing trend from the second month. NAb median titers were observed to peak earlier in the severe HCWP group (14 days in the severe group, 28 days in the mild group, p> 0.05). It was observed that 6 (26.1%) of HCWP group patients had low, 11 (47.8%) moderate, 6 (26.1%) high titers of representative NAb. The distribution of representative NAb levels by vaccine status was examined and no statistically significant difference was found (p= 0.400, p= 0.077 and p= 0.830, respectively). As a result; SARS-CoV-2 RNA was detected in many samples such as sputum, stool, blood and urine, and it was observed that viral shedding in stool samples could continue for months. Anti-SARS-CoV-2 IgG antibody positivity was observed in most of the patients in the fourth month, and it was found that the antibody titers decreased after the third month. It was determined that protective antibody levels continued in the fourth month. These findings are important in vaccination strategies and in the fight against the pandemic. However, considering the emergence of new mutant forms of the virus in today’s conditions where the pandemic continues, more detailed and comprehensive studies are needed for viral shedding and antibody titer studies.

PMID:35960235 | DOI:10.5578/mb.20229704

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The effect of bone particle size on the histomorphometric and clinical outcomes following lateral ridge augmentation procedures. A randomized double blinded controlled trial

J Periodontol. 2022 Aug 12. doi: 10.1002/JPER.22-0212. Online ahead of print.

ABSTRACT

BACKGROUND: The aim of this randomized clinical trial was to clinically and histologically compare the amount and quality of bone gained after lateral ridge augmentation (LRA) procedures performed using small (250-1000μm) versus large (1000-2000μm) particle size cortico-cancellous bone allografts at 6 months following surgical intervention.

MATERIALS AND METHODS: 22 patients, each presenting with ridge width less than 5mm were enrolled. Patients were randomly allocated to small (SP) and large particle (LP) size graft. The gain in ridge width at the level of the crest and 4mm apical to the crest was assessed via a standardized procedure before grafting and at time of implant placement, using a surgical caliper and a novel digital technique using cone beam computed tomography (CBCT). Six months following the procedure, trephine bone cores were taken from 19 augmented sites out of 17 patients (14/19 sites were in the posterior mandible) who completed the study for clinical, histologic and histomorphometric analysis.

RESULTS: 17 patients (19 sites) completed the study. LP size graft resulted in greater ridge width gain at the level of the crest (LP, 5.1 ± 1.7; SP, 3.7 ± 1.3 mm; p = 0.0642) and 4mm apical to the crest (LP, 5.9 ± 2.2; SP, 5.1 ± 1.8 mm; p = 0.4480) compared with the SP. No statistical significance for the bone density at the time of implant placement (p = 1.00) was found. Vital bone formation was more extensive in the SP compared with the LP 41.0 ± 10.1% vs 31.4 ± 14.8%, respectively (p = 0.05).

CONCLUSION: The results of the present article show a trend of higher ridge gain using LP during bone augmentation procedure. Future research with bigger sample size should confirm the results of the present article. This article is protected by copyright. All rights reserved.

PMID:35959712 | DOI:10.1002/JPER.22-0212

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Smartphone Application-Assisted Home Blood Pressure Monitoring Compared With Office and Ambulatory Blood Pressure Monitoring in Patients With Hypertension: the AMUSE-BP Study

Hypertension. 2022 Aug 12:101161HYPERTENSIONAHA12219685. doi: 10.1161/HYPERTENSIONAHA.122.19685. Online ahead of print.

ABSTRACT

BACKGROUND: The development of automated, smartphone application (app)-assisted home blood pressure monitoring (HBPM) allows for standardized measurement of blood pressure (BP) at home. The aim of this study was to evaluate the (diagnostic) agreement between app-assisted HBPM, automated office BP (OBP), and the reference standard 24-hour ambulatory BP monitoring (ABPM).

METHODS: In this open randomized 5-way cross-over study, patients diagnosed with hypertension were randomized to one of 10 clusters, each containing 5 BP measurement methods (ABPM, HBPM, attended OBP, unattended OBP, and unattended 30-minute BP) in different order.

RESULTS: In total, 113 patients were included. The average 24-hour ABPM was 126±11/73±8 mm Hg compared with 141±14/82±10 mm Hg with app-assisted HBPM, 134±13/80±9 mm Hg with unattended 30-minute BP, 137±16/81±11 mm Hg with attended OBP, and 135±15/81±10 mm Hg with unattended OBP monitoring. Diagnostic agreement between app-assisted HBPM and 24-hour ABPM for diagnosing sustained (OBP >140/90 mm Hg and ABPM ≥130/80 mm Hg or HBPM ≥135/85 mm Hg), white-coat (OBP ≥140/90 mm Hg and ABPM <130/80 mm Hg or HBPM <135/85 mm Hg), and masked hypertension (OBP <140/90 mm Hg and ABPM ≥130/80 mm Hg or HBPM ≥135/85 mm Hg) was fair-to-moderate (κ statistics ranging from 0.34 to 0.40). App-assisted HBPM had high sensitivities (78%-91%) and negative predictive values (90%-97%) for diagnosing sustained and masked hypertension.

CONCLUSIONS: This study showed a considerable (diagnostic) disagreement between app-assisted HBPM and ABPM. App-assisted HBPM had high sensitivity in the diagnosis of sustained and masked hypertension and may, therefore, be used as complementary to, but not a replacement of, ABPM.

PMID:35959685 | DOI:10.1161/HYPERTENSIONAHA.122.19685

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Maintaining a National Acute Kidney Injury Risk Prediction Model to Support Local Quality Benchmarking

Circ Cardiovasc Qual Outcomes. 2022 Aug 12:101161CIRCOUTCOMES121008635. doi: 10.1161/CIRCOUTCOMES.121.008635. Online ahead of print.

ABSTRACT

BACKGROUND: The utility of quality dashboards to inform decision-making and improve clinical outcomes is tightly linked to the accuracy of the information they provide and, in turn, accuracy of underlying prediction models. Despite recognition of the need to update prediction models to maintain accuracy over time, there is limited guidance on updating strategies. We compare predefined and surveillance-based updating strategies applied to a model supporting quality evaluations among US veterans.

METHODS: We evaluated the performance of a US Department of Veterans Affairs-specific model for postcardiac catheterization acute kidney injury using routinely collected observational data over the 6 years following model development (n=90 295 procedures in 2013-2019). Predicted probabilities were generated from the original model, an annually retrained model, and a surveillance-based approach that monitored performance to inform the timing and method of updates. We evaluated how updating the national model impacted regional quality profiles. We compared observed-to-expected outcome ratios, where values above and below 1 indicated more and fewer adverse outcomes than expected, respectively.

RESULTS: The original model overpredicted risk at the national level (observed-to-expected outcome ratio, 0.75 [0.74-0.77]). Annual retraining updated the model 5×; surveillance-based updating retrained once and recalibrated twice. While both strategies improved performance, the surveillance-based approach provided superior calibration (observed-to-expected outcome ratio, 1.01 [0.99-1.03] versus 0.94 [0.92-0.96]). Overprediction by the original model led to optimistic quality assessments, incorrectly indicating most of the US Department of Veterans Affairs’ 18 regions observed fewer acute kidney injury events than predicted. Both updating strategies revealed 16 regions performed as expected and 2 regions increasingly underperformed, having more acute kidney injury events than predicted.

CONCLUSIONS: Miscalibrated clinical prediction models provide inaccurate pictures of performance across clinical units, and degrading calibration further complicates our understanding of quality. Updating strategies tailored to health system needs and capacity should be incorporated into model implementation plans to promote the utility and longevity of quality reporting tools.

PMID:35959674 | DOI:10.1161/CIRCOUTCOMES.121.008635

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Inventory of the situation of mental disorders and their care in Algeria

East Mediterr Health J. 2022 Jul 31;28(7):532-538. doi: 10.26719/emhj.22.054.

ABSTRACT

BACKGROUND: Algeria has undertaken several actions and devoted various resources to improve mental health services in the prevention and management of mental disorders. Indeed, the increase in mental disorders and the demand for care make mental health a major social issue.

AIMS: To present an inventory of the mental disorders in Algeria, describe the state of mental health structures and resources as well as the current state of psychiatry as the main device of treatment and support.

METHODS: We carried out a descriptive analysis of the data generated from national surveys on the state of health of Algerians, as well as those obtained from various reports and censuses of the population and hospital statistics.

RESULTS: The few surveys that have been carried out to date have all highlighted the increasing prevalence of mental disorders and the increased demand for mental health care. However, the coverage of mental disorders and the supply of care remain insufficient and unevenly distributed, at the level of reception structures, human resources and, above all, legislation.

CONCLUSION: This analysis showed that despite the efforts made in terms of structures, resources and legislation, mental health in Algeria deserves more attention in public health policies.

PMID:35959669 | DOI:10.26719/emhj.22.054

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Understanding the reasons for refusal of polio vaccine by families in Quetta Block, Pakistan

East Mediterr Health J. 2022 Jul 31;28(7):498-505. doi: 10.26719/emhj.22.052.

ABSTRACT

BACKGROUND: Global polio eradication is a goal yet to be achieved in countries like Pakistan. In recent years, the Polio Eradication Initiative has been making steady progress with good campaign coverage and low numbers of polio cases. However, in 2019 Pakistan reported 146 cases compared to 12 in 2018. A major factor cited for this regression was a surge in vaccine refusals by parents and caretakers.

AIMS: To assess the reasons for the refusal of polio vaccination in Quetta Block, Balochistan.

METHODS: The study was conducted using data acquired from 2 polio vaccination campaigns over 3 months in 2019. The data were collected in Quetta Block, a highly endemic zone having continuous transmission of the polio virus over several years. The data were analysed using the statistical software, SPSS, version 20. We used descriptive statistics to demonstrate the characteristics of the study population. Categorical variables were measured as frequencies and percentages.

RESULTS: Refusal rates were almost 8.6% for the polio campaign of April and 8.1% for June 2019. Misconceptions about vaccines made up 56.4% of reasons for refusals, followed by religion 16%.

CONCLUSION: Misconceptions about the vaccine are the main driving force behind vaccine refusals in the study setting. Efficient strategies are required to address misconceptions in this red zone of poliovirus transmission in Balochistan.

PMID:35959665 | DOI:10.26719/emhj.22.052

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Comprehensive two-dimensional gas chromatography with mass spectrometry: an advanced bioanalytical technique for clinical metabolomics studies

Analyst. 2022 Aug 12. doi: 10.1039/d2an00584k. Online ahead of print.

ABSTRACT

The detection of human-derived metabolites as potential diagnostic biomarkers of genetic disorders, metabolic diseases, systemic diseases, and infectious diseases has been much studied in recent years, especially as technical capabilities improve, and statistical procedures are increasingly able to tease critical chemical attributes from complex data sets. Given the complex distribution of human biological matrices, the characterization and/or identification of these chemical entities is technically challenging, and is often confounded by incomplete chromatographic resolution or insufficient discriminatory power of the mass spectrometry (MS) domain. Recently, comprehensive two-dimensional gas chromatography (GC×GC) has evolved into a mature higher separation order technique that offers unprecedented resolving power, which in turn can greatly advantage clinical metabolomics studies via the expansion of metabolite coverage. In this contribution, the current state of knowledge in the development of GC×GC coupled to MS as a high-resolution bioanalytical technique for the analysis of clinical metabolites is reviewed. Selected recent applications (years 2012 to 2021) that emphasize improved GC×GC-MS strategies for clinical human metabolites’ detection, identification, and quantitative analysis are described. In addition, we share our perspectives on current challenges and potential future directions of GC×GC in clinical applications.

PMID:35959641 | DOI:10.1039/d2an00584k

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Predicting the anticancer activity of 2-alkoxycarbonylallyl esters against MDA-MB-231 breast cancer – QSAR, Machine Learning and Molecular Docking

Curr Drug Discov Technol. 2022 Aug 11. doi: 10.2174/1570163819666220811094019. Online ahead of print.

ABSTRACT

BACKGROUND: The continuous increase in mortality of breast cancer and other forms of cancer due to the failure of current drugs, resistance, and associated side effects calls for the development of novel and potent drug candidates.

METHODS: In this study, we used the QSAR and extreme learning machine models in predicting the bioactivities of some 2-alkoxycarbonylallyl esters as potentials drug candidates against MDA-MB-231 breast cancer. The lead candidates were docked at the active site of a carbonic anhydrase target.

RESULTS: The QSAR model of choice satisfied the recommended values and was statistically significant. The R2pred (0.6572) was credence to the predictability of the model. The extreme learning machine ELM-Sig model showed excellent performance superiority over other models against MDA-MB-231 breast cancer. Compound 22 with a docking score of 4.67 kcal mol-1 displayed better inhibition of the carbonic anhydrase protein, interacting through its carbonyl bonds.

CONCLUSION: The extreme learning machine’s ELM-Sig model showed excellent performance superiority over other models and should be exploited in the search for novel anticancer drugs.

PMID:35959613 | DOI:10.2174/1570163819666220811094019

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Mechanical analysis of the impact of the morphology of the iris and ciliary body on the central vault after posterior chamber phakic intraocular lens implantation

Zhonghua Yan Ke Za Zhi. 2022 Aug 11;58(8):615-623. doi: 10.3760/cma.j.cn112142-20220214-00060.

ABSTRACT

Objective: To investigate the impact of the iris and ciliary body morphology on the central vault after phakic posterior chamber intraocular lens (pIOL) implantation. Methods: This research was based on the retrospective analysis of 123 patients (123 eyes) who underwent pIOL implantation in the Department of Ophthalmology, Affiliated Hospital of Qingdao University between June 2018 and June 2020. The anterior segment structure was observed with an ultrasound biomicroscope before surgery, and all morphological parameters of the iris and ciliary body were measured manually using the ImageJ software, including iris span (IS), iris convexity (IC), iris-ciliary body contact distance (ICCD) and iris-lens contact distance (ILCD). The ICCD was divided into Q1, Q2 and Q3 groups according to the equidistant distance of 0.36 mm. The lens thickness was measured with the IOLMaster. The horizontal corneal diameter and anterior chamber depth were measured using the Pentacam. The central vaults were measured by optical coherence tomography at 1 week, 3 months and 1 year after surgery. The relationships between vault values and preoperative parameters of the anterior segment were evaluated using the Pearson correlation analysis, Spearman correlation analysis, and multiple linear regression. The repeated measures ANOVA was applied to identify changes of vault values over time. Results: The mean values of the vaults at 1 week, 3 months and 1 year after surgery were (723±265) μm, (642±255) μm and (613±280) μm, respectively. The difference among them was statistically significant (F=50.143, P<0.001). The vaults continued to decline within 1 year after pIOL implantation, and the total decline was (122±86) μm. The vaults declined by (69±98) μm from postoperative 1 week to 3 months and by (52±54) μm from postoperative 3 months to 1 year. The regression formula showed that the pIOL size and ILCD were positively related with the vault, while the LT, IS and IC were negatively related with the vault at 1 week postoperatively (adjusted R²=0.404, P<0.001). The pIOL size and ILCD were positively related with the vault, while the IS and IC were negatively related with the vault at 3 months postoperatively (adjusted R²=0.342, P<0.001). The pIOL size was positively related with the vault, while the IS and IC were negatively related with the vault at 1 year postoperatively (adjusted R²=0.661, P<0.001). The vault values were higher in group Q3 compared to group Q1 at every timepoint, and the vault value was higher in group Q2 compared to Q1 at 1 year postoperatively. Conclusions: In the early postoperative period, eyes with a larger pIOL, shorter iris span, longer contact distance between the iris and ciliary body, and longer contact distance between the iris and lens were associated with a higher rate of excessive vaults. Meanwhile, eyes with a thicker lens and larger iris reverse convexity were more likely to obtain insufficient vaults. Within one year after surgery, the pIOL size, IS, IC and ICCD continued to impact on the vault. The ICCD, ILCD and IC can reflect the posterior chamber volume and change the haptic location and force, thus affecting the vault.

PMID:35959606 | DOI:10.3760/cma.j.cn112142-20220214-00060

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Therapeutic effect of amniotic membrane-fibrin sealant cement on severe ocular surface alkali burn in rabbits

Zhonghua Yan Ke Za Zhi. 2022 Aug 11;58(8):606-614. doi: 10.3760/cma.j.cn112142-20220310-00103.

ABSTRACT

Objective To prepare a biologically active amniotic membrane powder and explore its preservation conditions, and to evaluate the efficacy of the amniotic membrane (AM)-fibrin sealant (FS) cement made from the amniotic powder on the rabbit severe ocular surface alkali burn model. Methods Experimental research. Fresh AM was air-dried, cooled with liquid nitrogen, ground into amniotic powder and sterilized by radiation. The expression of transformed growth factor, nerve growth factor receptor (NGFR), hepatocyte growth factor (HGF), epidermal growth factor (EGF) and basic fibroblast growth factor (bFGF) after preparation and 10, 20 and 30 days after storage at room temperature, 4 ℃ and -20 ℃ was tested and compared with that in the fresh AM. The AM-FS cement containing different concentrations of amniotic powder and no amniotic powder was diluted. Rabbit corneal epithelial cells were cultured for 72 hours. The effects of different concentrations of amniotic powder on epithelial cell growth were observed by light microscopy, and the amniotic powder concentration with the largest absorbance value at 450 nm was selected for subsequent animal experiments. Thirty-two right eyes of 32 rabbits as the severe ocular surface alkali burn model were divided using the random counting method into the AM-FS cement group, fresh AM transplantation group, FS group and antibiotic control group (8 rabbits each group) and given different interventions. After weekly observation of corneal repair, hematoxylin and eosin staining, immunohistochemical staining of monocyte chemotaxis protein 1 (MCP-1)and vascular endothelial growth factor (VEGF) were performed and detected by light microscopy at 28 days. The logFC values of the growth factor or receptor expression difference ratio were corrected by BH; the data were analyzed by t-test and analysis of variance. Results: The expression of TGF in the amniotic membrane powder compared with the fresh amniotic membrane group (logFC=-0.11), and the expression of NGFR (HGF, EGF, bFGF) was higher than that of the fresh amniotic membrane group (logFC=-2.07, 0.72, 0.46, 2.62; P<0.05); the expression of HGF, bFGF and EGF in amniotic membrane powder stored for 10 days and 20 days were no lower than fresh amniotic membrane; at 30 days, the expression of growth factors or receptors except HGF and bFGF were decreased, and HGF, bFGF and EGF were no less than 4 ℃ and -20 ℃.The maximum A value was obtained for 0.25 mg/ml of the amniotic membrane powder after 72 hours of the CEC culture 0.98±0.05. The corneal recovery was better in the AM-FS and fresh amniotic membrane transplant groups, with corneal turbidity scores of 3.75±0.46 and 3.50±0.46, respectively, on 28 days, lower than antibiotics (4.29±0.45) (t=2.480, 3.629; P=0.019, 0.001). The corneal neovascular area in the antibiotic control group was compared with the other three groups (t=4.040, 4.339, 2.820; all P<0.001); the corneal neovascular area in the AM-FS group was (9.88±0.20) and (18.96±0.18) mm2 at 7 and 28 days. The corneal neovascularization area at 7 and 28 days in the fresh AM group [(9.54±0.22) and (18.08±0.96) mm2] was smaller than the AM-FS group (t=3.085, 3.017, P=0.005, 0.005). Despite the tiny statistical difference (0.34, 0.88), there was no clinical difference. Hematoxylin and eosin staining showed corneal structures were intact in the AM-FS and fresh AM groups, the epithelial arrangement became normal, and the corneal healing was superior to the FS and antibiotic control groups. Immunohistochemistry showed that the positive expression of VEGF in the fresh AM group was weaker than that in the remaining three groups. MCP-1 was expressed to a similar extent in the AM-FS and fresh AM groups. Conclusions: The active cytokine had high expression and stable properties at room temperature. The AM-FS cement containing 0.25 mg/ml amniotic powder can promote the repair of corneal epithelium, reduce inflammatory reaction and corneal neovascularization after alkali burning in rabbit eyes.

PMID:35959605 | DOI:10.3760/cma.j.cn112142-20220310-00103