Nevin Manimala

J Neurol. 2022 May 3. doi: 10.1007/s00415-022-11135-6. Online ahead of print.

ABSTRACT

BACKGROUND: The understanding of fatal familial insomnia (FFI), a rare neurodegenerative autosomal dominant prion disease, has improved in recent years as more cases were reported. This work aimed to propose new diagnostic criteria for FFI with optimal sensitivity, specificity, and likelihood ratio.

METHODS: An international group of experts was established and 128 genetically confirmed FFI cases and 281 non-FFI prion disease controls are enrolled in the validation process. The new criteria were proposed based on the following steps with two-round expert consultation: (1) Validation of the 2018 FFI criteria. (2) Diagnostic item selection according to statistical analysis and expert consensus. (3) Validation of the new criteria.

RESULTS: The 2018 criteria for possible FFI had a sensitivity of 90.6%, a specificity of 83.3%, with a positive likelihood ratio (PLR) of 5.43, and a negative likelihood ratio (NLR) of 0.11; and the probable FFI criteria had a sensitivity of 83.6%, specificity of 92.9%, with a PLR of 11.77, and a NLR of 0.18. The new criteria included more specific and/or common clinical features, two exclusion items, and summarized a precise and flexible diagnostic hierarchy. The new criteria for possible FFI had therefore reached a better sensitivity and specificity (92.2% and 96.1%, respectively), a PLR of 23.64 and a NLR of 0.08, whereas the probable FFI criteria showed a sensitivity of 90.6%, a specificity of 98.2%, with a PLR of 50.33 and a NLR of 0.095.

CONCLUSIONS: We propose new clinical diagnostic criteria for FFI, for a better refining of the clinical hallmarks of the disease that ultimately would help an early recognition of FFI and a better differentiation from other prion diseases.

PMID:35501502 | DOI:10.1007/s00415-022-11135-6

Eur J Clin Pharmacol. 2022 May 3. doi: 10.1007/s00228-022-03329-8. Online ahead of print.

ABSTRACT

PURPOSE: To assess the feasibility and acceptance of the semi-automated meta-analysis (SAMA). The objectives are twofold, namely (1) to compare expert opinion on the quality of protocols, methods, and results of one conventional meta-analysis (CMA) and one SAMA and (2) to compare the time to execute the CMA and the SAMA.

METHODS: Experts evaluated the protocols and manuscripts/reports of the CMA and SAMA conducted independently on the safety of metronidazole in pregnancy. Expert opinion was collected using AMSTAR 2 checklist. Time spent was recorded using case report forms.

RESULTS: The overall scores of the opinion of all experts for protocols, methods, and results for SAMA (6.75) and CMA (6.87) were not statistically different (p = 0.88). The experts’ confidence in the results of each MA was 7.89 ± 1.17 and 8.11 ± 0.92, respectively. The time to completion was 14 working days for SAMA and 24.7 for CMA. MA tasks such as calculation of effect estimates, subgroup/sensitivity analysis, and publication bias investigation required no investment in time for SAMA.

CONCLUSION: In conclusion, our study demonstrated the feasibility of SAMA and suggests acceptance for risk assessment by an expert committee. Our results suggest that SAMA reduces the time required for a MA without altering expert confidence in the methodological and scientific rigor. As our study was limited to one example, the generalization of our results requires confirmation by other studies.

PMID:35501476 | DOI:10.1007/s00228-022-03329-8

Commun Biol. 2022 May 2;5(1):407. doi: 10.1038/s42003-022-03358-0.

ABSTRACT

Epithelial-mesenchymal Transition (EMT) is a multi-step process that involves cytoskeletal rearrangement. Here, developing and using an image quantification tool, Statistical Parametrization of Cell Cytoskeleton (SPOCC), we have identified an intermediate EMT state with a specific cytoskeletal signature. We have been able to partition EMT into two steps: (1) initial formation of transverse arcs and dorsal stress fibers and (2) their subsequent conversion to ventral stress fibers with a concurrent alignment of fibers. Using the Orientational Order Parameter (OOP) as a figure of merit, we have been able to track EMT progression in live cells as well as characterize and quantify their cytoskeletal response to drugs. SPOCC has improved throughput and is non-destructive, making it a viable candidate for studying a broad range of biological processes. Further, owing to the increased stiffness (and by inference invasiveness) of the intermediate EMT phenotype compared to mesenchymal cells, our work can be instrumental in aiding the search for future treatment strategies that combat metastasis by specifically targeting the fiber alignment process.

PMID:35501466 | DOI:10.1038/s42003-022-03358-0

Environ Sci Pollut Res Int. 2022 May 2. doi: 10.1007/s11356-022-20531-4. Online ahead of print.

ABSTRACT

Multi-criteria decision-making (MCDM) is an important means for evaluating resources and environment, and sensitivity analysis can enhance understand the robustness of evaluation results. Spatial visualization has been used in sensitivity analysis of MCDM, but the sensitivity results are still generally summarized by presenting traditional statistical measurements that omit the spatial information. To address this issue, this paper proposed a novel spatially measurement approach of sensitivity analysis by introducing the spatial barycenter model (SBM), which overcame the limitations of existing statistical methods and provided the spatial directivity of uncertainty for the MCDM results. According to our proposed method and its application in farmland quality evaluation (FQE) in an arid area of China, the mean of the absolute average change rate (MACR) and the SBM were applied to test the sensitivity of farmland quality to different evaluation factors from both numerical and spatial perspectives. From the numerical perspective, the soil organic matter and irrigation capacity were the most sensitive factors determined by the MACR. From the spatial perspective, the ≥10 °C accumulated temperature (AT) and precipitation were the most sensitive factors measured by the SBM. Based on the SBM, the spatial configuration of farmland quality index was most sensitive to increase of AT in a northwesterly direction. Calculating the SBM is computationally inexpensive and provides a straightforward indication of spatial direction for the changes of FQE results with changes of parameters. This means it can provide improved understandings and new insights into the comprehensive measurement of sensitivity analysis and agricultural production layout.

PMID:35501443 | DOI:10.1007/s11356-022-20531-4

Environ Sci Pollut Res Int. 2022 May 2. doi: 10.1007/s11356-022-20442-4. Online ahead of print.

ABSTRACT

Climate change and health are inextricably linked, especially the role of ambient temperature. This study aimed to analyze the non-communicable disease (NCD) burden attributable to low temperature globally, regionally, and temporally using data from the Global Burden of Disease (GBD) study 2019. Globally, in 2019, low temperature was responsible for 5.42% DALY and 7.18% death of NCDs, representing the age-standardized disability-adjusted life years (DALY) and death rates (per 100,000 population) of 359.6 (95% uncertainty intervals (UI): 306.09, 416.88) and 21.36 (95% UI:18.26, 24.74). Ischemic heart disease was the first leading cause of DALY and death resulting from low temperature, followed by stroke. However, age-standardized DALY and death rates attributable to low temperature have exhibited wide variability across regions, with the highest in Central Asia and Eastern Europe and the lowest in Caribbean and Western sub-Saharan Africa. During the study period (1990-2019), there has been a significant decrease in the burden of NCDs attributable to low temperature, but progress has been uneven across countries, whereas nations exhibiting high sociodemographic index (SDI) declined more significantly compared with low SDI nations. Notably, three nations, including Uzbekistan, Tajikistan, and Lesotho, had the maximum NCDs burden attributed to low temperature and displayed an upward trend. In conclusion, ambient low temperature contributes to substantial NCD burden with notable geographical variations.

PMID:35501439 | DOI:10.1007/s11356-022-20442-4

Clin Implant Dent Relat Res. 2022 May 2. doi: 10.1111/cid.13094. Online ahead of print.

ABSTRACT

AIM: The study aimed to evaluate the effect of implant-supported prosthesis in completely edentulous participants in terms of osseoperception ability, neural activity, and stereognostic ability in comparison to removable prosthetic options.

MATERIALS AND METHODS: A total sample of 18 patients, irrespective of gender and age were allocated into three groups according to the three-treatment protocol (upper and lower complete denture, upper complete denture opposing lower implant-retained overdenture, implant-supported fixed prosthesis in both arches). Four weeks after completion of the treatment procedure active tactile sensibility (ATS) was checked by using varying thicknesses (12, 40, 80, 100, 200 μ) of articulating foils and papers. Functional magnetic resonance imaging (fMRI) was performed to record neurophysiological activity in cerebral cortex in all the participants. Various forms of test pieces (heat cure acrylic resin) were used to evaluate stereognostic ability. Data regarding the neurophysiological activity were analyzed by using Krushkal-Wallis test and p ≤ 0.05 was considered to be statistically significant. Data from stereognostic ability test procedure and ATS were compared by using chi-squared test and p ≤ 0.05 was considered to be statistically significant.

RESULTS: Statistically significant difference was found in between the articulating foils in terms of true negative responses as the foil thickness increased in participants wearing complete denture in both the arches (p = 0.004) and implant-supported fixed prosthesis in both the arches (p = 0.010). Participants in implant-supported fixed prosthesis group showed significantly more activation in primary motor cortex (right side), somatosensory cortex (left side), angular gyrus (both sides), temporal lobe (left) compared to other groups. No significant difference found in thalamus and premotor cortex region in between the participants of different groups. No statistically significant difference found in between the groups in terms of true responses identifying correct shapes. Mean number of correct responses in stereognostic ability test were 4.16 (83.33%), 3.5 (70%), 3.83 (76.66%) for participants of complete denture group, upper complete denture opposing lower implant retained overdenture group, and implant-supported fixed prosthesis group, respectively.

CONCLUSION: Primary motor cortex, somatosensory cortex, and other regions of brain were diffusely activated in participants wearing implant-supported fixed prosthesis in both the arches. Less number of false responses were recorded in participants of implant-supported fixed prosthesis group and upper complete denture opposing lower implant-retained overdenture group in ATS test compared to participants wearing complete denture in both the arches.

PMID:35500283 | DOI:10.1111/cid.13094

Ann Intern Med. 2022 May 3. doi: 10.7326/M21-2973. Online ahead of print.

ABSTRACT

BACKGROUND: The real-world protection provided by SARS-CoV-2 messenger RNA (mRNA) vaccines to kidney transplant recipients (KTRs) remains uncertain.

OBJECTIVE: To study the association between mRNA vaccination and SARS-CoV-2 infection rate in KTRs.

DESIGN: Retrospective observational cohort study.

SETTING: The Czech Republic (17 February to 16 May 2021).

PATIENTS: 2101 KTRs followed in the Department of Nephrology at the Institute for Clinical and Experimental Medicine.

MEASUREMENTS: Positive result for SARS-CoV-2 on polymerase chain reaction test and vaccination status of KTRs.

RESULTS: The incidence rate in the vaccinated group was 0.474 per 1000 person-days (33 cases in 69 672 days at risk). The incidence rate in the unvaccinated group was 1.370 per 1000 person-days (79 cases in 57 658 days at risk). The unadjusted incidence rate ratio (IRR; incidence rate of vaccinated/incidence rate of unvaccinated) for KTRs was 0.346 (95% CI, 0.227 to 0.514). The multivariable adjusted IRR for KTRs was 0.544 (CI, 0.324 to 0.876).

LIMITATION: Retrospective observational design, uneven follow-up of patient groups, and different exposition to SARS-CoV-2 stemming from strong temporal trends and differences in clinical and probably behavioral characteristics.

CONCLUSION: Vaccination of KTRs is associated with lower risk for SARS-CoV-2 infection.

PRIMARY FUNDING SOURCE: The Ministry of Health of the Czech Republic.

PMID:35500256 | DOI:10.7326/M21-2973

Genet Epidemiol. 2022 May 2. doi: 10.1002/gepi.22452. Online ahead of print.

NO ABSTRACT

PMID:35500225 | DOI:10.1002/gepi.22452

Prehosp Emerg Care. 2022 May 2:1-7. doi: 10.1080/10903127.2022.2072551. Online ahead of print.

ABSTRACT

Objective: The “Stop the Bleed” campaign was created to educate laypeople about bleeding control and make bleeding control kits available in public locations. Unfortunately, previous research has indicated that up to half of all laypeople cannot effectively apply a tourniquet. The purpose of this study was to determine if laypeople could apply tourniquets more effectively with just-in-time training using combined audio-written instructions versus written-only instructions.Methods: We conducted a prospective randomized study comparing the application of a tourniquet using a simulated bleeding arm. Participants were laypeople 18 years and older and excluded those with any previous tourniquet experience or training. Participants were randomized to just-in-time training using either audio-written or written-only instructions. Time in seconds to tourniquet application and the effectiveness of the tourniquet application was recorded. Effective application was defined as stopping the flow or significantly slowing the flow to a slow drip. Ineffective tourniquet placement was defined as not significantly changing the flow. Statistical analysis was performed using Fisher’s exact, t-test, and linear regression.Results: Eighty-two participants were included; 40 were in the audio-written instructions group, and 58.5% were male. The audio-written group’s effective application rate was 92.5% and that of the written-only group was 76.2%. A significantly higher rate of ineffective tourniquet application was noted for the written-only group, (23.8%), versus the audio-written group (7.5%), p=.04. Regardless of the type of instructions used, time to effective application of the tourniquet decreased as participant age increased (p = 0.02, 95%CI (-1.24, -0.13). There was no relationship between age and effective tourniquet application (p = 0.06). Time for tourniquet placement was not different between the audio-written (mean 100.4 seconds) and written-only (mean 106.1 seconds) groups (p = 0.58).Conclusion: This study suggests that combined audio-written instructions decrease the rate of ineffective tourniquet application by laypeople compared with written-only instructions. Further studies are needed to assess if audio instructions and just-in-time training can further maximize effective tourniquet application.

PMID:35500205 | DOI:10.1080/10903127.2022.2072551

J Clin Lab Anal. 2022 May 2:e24471. doi: 10.1002/jcla.24471. Online ahead of print.

ABSTRACT

BACKGROUND: Nowadays, neonatal screening has become an essential part of routine newborn care in the world. This is a non-invasive evaluation that evaluated inborn errors of metabolisms (IEMs) using tandem mass spectrometry (LC-MS/MS) for the evaluation of the baby’s risk of certain metabolic disorders.

METHODS: This retrospective study was conducted on 39987 Iranian newborns who were referred to Nilou Medical Laboratory, Tehran, Iran, for newborn screening programs of IEMs. We incorporated second-tier tests and secondary biomarkers to improve positive predictive value (PPV).

RESULTS: Statistical data were recorded via call interviewing in 6-8 months after their screening tests. The overall prevalence of IEM was 1:975. The mean age of all participants was 3.9 ± 1.1 days; 5.1% of participants were over 13 days and 7.7% were preterm or underweight. A total of 11384 (29.4%) of the cases were born in a consanguineous family. The type of delivery was the cesarean section in 8332 (51.3%) valid cases. The neonatal screening results had an overall negative predictive value (NPV) of 100% and the overall PPV of 40.2%. The false-positive rate was 0.15%.

CONCLUSION: This study showed a high incidence of metabolic disease due to a high rate of consanguineous marriages in Iran and indicated that incorporation of second-tier tests and secondary biomarkers improves PPV of neonatal screening programs.

PMID:35500172 | DOI:10.1002/jcla.24471