Nevin Manimala

Bioengineered. 2022 Mar;13(3):6908-6918. doi: 10.1080/21655979.2022.2026709.

ABSTRACT

Ischemic stroke is one of the leading causes of morbidity and mortality in humans. Cerebral ischemia-reperfusion (CIR) injury serves as a leading cause of stroke. Schisandra chinensis is a well-known Chinese traditional medicine. In this study, we explored the role of Gomisin J (GJ), a compound of S. chinensis, in CIR using a middle cerebral artery occlusion/reperfusion rat model and the possible mechanisms. We identified that GJ reduced neurological scores, cerebral infarction, and water content in the I/R rat brain. Importantly, GJ rescued I/R treatment-reduced neuron survival in the hippocampus, inhibited apoptosis of ischemic tissues in I/R rats, increased B-cell lymphoma-extra-large (Bcl-XL) expression, and reduced the levels of cleaved caspase-3, Bax, cyclooxygenase-2, nuclear factor kappa-B, and nitric oxide in I/R rat brain tissues. Furthermore, GJ treatment enhanced nuclear factor E2 related factor 2 (Nrf2) translocation, heme oxygenase-1 (HO-1) expression, superoxide dismutase and glutathione peroxidase activities, and glutathione level. Overall, GJ treatment GJ attenuates CIR injury by inducing anti-apoptotic, antioxidant, and anti-inflammatory effects in vivo.

PMID:35235758 | DOI:10.1080/21655979.2022.2026709

J Clin Psychiatry. 2022 Mar 1;83(2):21m14274. doi: 10.4088/JCP.21m14274.

ABSTRACT

Objective: Measurement-based care (MBC) improves patient outcomes. However, there has been minimal focus on MBC for psychotic disorders. This study examines the use of patient-reported outcome measures (PROMs) in the Veterans Health Administration (VHA) to characterize their use among Veterans with psychotic disorders and to inform candidate measures for psychosis-related MBC.

Methods: Data on Veterans with and without ICD-10 psychotic disorders and at least 1 PROM during fiscal years (FYs) 2016-2019 (FY16-FY19) were collected. The sample included 3,935,504 PROM administrations among 1,192,897 Veterans. Included PROMs spanned multiple symptom and non-symptom domains. Percentages of total PROM administrations were calculated by aggregating across time and diagnosis. Facility-level statistics were also calculated. Absolute change in the percentage of unique Veterans administered a particular and repeated PROMs over time were calculated.

Results: The core PROMs for VHA MBC (Patient Health Questionnaire-9 [PHQ-9], General Anxiety Disorder-7 Scale, PTSD Checklist-5, and Brief Addiction Monitor) accounted for the majority of PROMs for Veterans with (88.18%) and without (92.56%) psychotic disorders. The PHQ-9 accounted for the largest proportion (psychotic disorder: 45.89%; other diagnosis: 46.70%). The absolute changes in percentages of repeated PROM administration were similar over time across groups.

Conclusions: The use of PROMs in VHA mental health care increased during FY16-FY19 for Veterans with and without psychosis. The rates of PROM use were similar for both groups, and PROM use predominately consisted of the core measures. While the similar rates of PROM administration are encouraging, these findings highlight the need for psychosis-specific measures to tailor MBC for Veterans with these diagnoses.

PMID:35235719 | DOI:10.4088/JCP.21m14274

Ecol Lett. 2022 Mar 2. doi: 10.1111/ele.13982. Online ahead of print.

ABSTRACT

Life-history strategies differ with respect to investment in current versus ‘future’ reproduction, but when is this future? Under the novel ‘temporality in reproductive investment hypothesis’, we postulate variation should exist in the time frame over which reproductive costs are paid. Slow-paced individuals should pay reproductive costs over short (e.g. inter-annual) time scales to prevent reproductive costs accumulating, whereas fast-paced individuals should allow costs to accumulate (i.e. senescence). Using Fourier transforms, we quantify adjustments in clutch size with age, across four populations of blue tits (Cyanistes caeruleus). Fast populations had more prevalent and stronger long-term changes in reproductive investment, whereas slower populations had more prevalent short-term adjustments. Inter-annual environmental variation partly accounted for short-, but not long-term changes in reproductive investment. Our study reveals individuals differ in when they pay the cost of reproduction and that failure to partition this variation across different temporal scales and environments could underestimate reproductive trade-offs.

PMID:35235709 | DOI:10.1111/ele.13982

Alzheimers Dement. 2022 Mar 2. doi: 10.1002/alz.12615. Online ahead of print.

ABSTRACT

This perspective is a companion to a recent editorial on the use of Bayesian analysis in clinical research. We aim to introduce and highlight the relevance and advantages that Bayesian inference offers to clinical trials using the data on the amyloid antibody aducanumab presented at a Food and Drug Administration hearing in November 2020 as an applied example. We apply Bayesian analysis of model plausibility and effect sizes based on simulated data of the two phase 3 trials of aducanumab in prodromal and mild dementia stages of Alzheimer’s disease (AD). Bayesian analysis can quantify evidence in favor of, or against, the presence of an effect (i.e., provide evidence of absence), as well as assess the strength of the effect. This is in contrast to the binary conclusions provided by frequentist tests.

PMID:35235700 | DOI:10.1002/alz.12615

Math Med Biol. 2022 Mar 2:dqac001. doi: 10.1093/imammb/dqac001. Online ahead of print.

ABSTRACT

Mycobacterium tuberculosis (TB) infection can involve all immune system components and can result in different disease outcomes. The antibiotic TB drugs require strict adherence to prevent both disease relapse and mutation of drug- and multidrug-resistant strains. To overcome the constraints of pathogen-directed therapy, host-directed therapy has attracted more attention in recent years as an adjunct therapy to enhance host immunity to fight against this intractable pathogen. The goal of this paper is to investigate in-host TB models to provide insights into therapy development. Focusing on therapy-targeting parameters, the parameter regions for different disease outcomes are identified from an established ODE model. Interestingly, the ODE model also demonstrates that the immune responses can both benefit and impede disease progression, depending on the number of bacteria engulfed and released by macrophages. We then develop two Itô SDE models, which consider the impact of demographic variations at the cellular level and environmental variations during therapies along with demographic variations. The SDE model with demographic variation suggests that stochastic fluctuations at the cellular level have significant influences on (1) the T-cell population in all parameter regions, (2) the bacterial population when parameters located in the region with multiple disease outcomes and (3) the uninfected macrophage population in the parameter region representing active disease. Further, considering environmental variations from therapies, the second SDE model suggests that disease progression can slow down if therapies (1) can have fast return rates and (2) can bring parameter values into the disease clearance regions.

PMID:35235658 | DOI:10.1093/imammb/dqac001

J Clin Endocrinol Metab. 2022 Mar 2:dgac104. doi: 10.1210/clinem/dgac104. Online ahead of print.

ABSTRACT

CONTEXT: PLIN1 encodes Perilipin-1 which coats lipid droplets in adipocytes and is involved in droplet formation, triglyceride storage and lipolysis. Rare PLIN1 frameshift variants that extend the translated protein have been described to cause lipodystrophy.

OBJECTIVE: To test whether PLIN1 protein-truncating variants cause lipodystrophy in a large population-based cohort.

DESIGN: We identified individuals with PLIN1 PTVs in individuals with exome data in UK Biobank. We performed gene-burden testing for individuals with PLIN1 PTVs. We replicated the associations using data from the T2D Knowledge portal. We performed a phenome-wide association study using publicly available association statistics.

SETTING: A population-based cohort and a T2D case/control study.

PARTICIPANTS: 362,791 individuals in UK Biobank and 43,125 individuals in the T2D Knowledge portal.Main Outcome Measures: Twenty-two diseases and traits relevant to lipodystrophy.

RESULTS: The 735 individuals with PLIN1 protein-truncating variants had a favourable metabolic profile. These individuals had increased HDL cholesterol (0.12mmol/L, 95% CI: 0.09, 0.14, P=2×10 -18), reduced triglycerides (-0.22 mmol/L 95% CI: -0.29, -0.14, P=3×10 -11), reduced waist hip ratio (-0.02, 95% CI: -0.02, -0.01, P=9×10 -12) and reduced systolic blood pressure (-1.67 mmHg, -3.25, -0.09, P=0.05). These associations were consistent in the smaller T2D knowledge portal cohort. In UK Biobank, PLIN1 PTVs were associated with reduced risk of myocardial infarction (OR=0.59, 95% CI: 0.35, 0.93, P=0.02) and hypertension (OR=0.85, 95% CI: 0.73, 0.98, P=0.03), but not Type 2 diabetes (OR=0.99 95% CI: 0.63,1.51, P=0.99).

CONCLUSION: Our study suggests that PLIN1 haploinsufficiency causes a favourable metabolic profile and may protect against cardiovascular disease.

PMID:35235652 | DOI:10.1210/clinem/dgac104

Cereb Cortex. 2022 Mar 2:bhac081. doi: 10.1093/cercor/bhac081. Online ahead of print.

ABSTRACT

Neuropsychological disturbances in the sense of limb ownership provide unique opportunities to study the neurocognitive basis of body ownership. Previous small sample studies that showed discrete cortical lesions cannot explain why multisensory, affective, and cognitive manipulations alter disownership symptoms. We tested the novel hypothesis that disturbances in the sense of limb ownership would be associated not only with discrete cortical lesions but also with disconnections of white-matter tracts supporting specific functional networks. We drew on an advanced lesion-analysis and Bayesian statistics approach in 49 right-hemisphere patients (23 with and 26 without limb disownership). Our results reveal that disturbances in the sense of ownership are associated with lesions in the supramarginal gyrus and disconnections of a fronto-insular-parietal network, involving the frontal-insular and frontal inferior longitudinal tracts, confirming previous disconnection hypotheses. Together with previous behavioral and neuroanatomical results, these findings lead us to propose that the sense of body ownership involves the convergence of bottom-up, multisensory integration, and top-down monitoring of sensory salience based on contextual demands.

PMID:35235644 | DOI:10.1093/cercor/bhac081

Int J Oral Maxillofac Implants. 2022 Jan-Feb;37(1):159-170. doi: 10.11607/jomi.9107.

ABSTRACT

PURPOSE: The goal of this study was to assess the effect of a liquid platelet-rich fibrin (PRF)-coated implant surface (double acid-etched) on osseointegration, analyzing the stability and the possibility of shortening the rehabilitation period.

MATERIALS AND METHODS: Initially, the blood was centrifuged to obtain the liquid PRF (2,000 revolutions per minute [rpm], 10 minutes), dividing a sample to be analyzed by Luminex, and another was applied onto the implant surface. Fifteen patients (30 implants) were divided into two groups (control and liquid PRF). Following the recommendation provided by the manufacturer, within a controlled torque at a maximum of 34 N.mm, the implant was placed. All patients had 1 year of follow-up.

RESULTS: Eleven analytes were identified for the sample characterization (IP-10, eotaxin, RANTES, macrophage inflammatory protein 1-beta [MIP-1β], VEGF, PDGF-BB, bFGF, IFN-γ, interleukin [IL]-5, IL-10, and IL-15). Regarding clinical evaluation, for control and liquid PRF groups, respectively, (1) the mean torque for implant placement was 26.67 and 27.27 N.mm; (2) the initial stability (implant stability quotient [ISQ]) was 64.87 (SD ± 6.01) and 67.36 (SD ± 7.21); (3) the final ISQ was 67.67 (SD ± 6.13) and 70.14 (SD ± 6.40); (4) it took an average 73 and 71 days to reestablish the masticatory function; (5) the survival rate was 93.3% and 86.6%; and (6) the marginal bone loss was up to 1.0 mm after 1 year (control)-for two patients, it was between 1.0 and 2.0 mm, and for another two subjects, it was up to 1 mm (liquid PRF). No statistical significance was observed for all parameters analyzed (P > .05).

CONCLUSION: Within the limitations of this study, the results indicated that there was no statistical significance when liquid PRF was applied on the implant surface, for all parameters.

PMID:35235635 | DOI:10.11607/jomi.9107

Int J Oral Maxillofac Implants. 2022 Jan-Feb;37(1):153-158. doi: 10.11607/jomi.9087.

ABSTRACT

PURPOSE: Strains transferred to the supporting simulated bone structure by implant-supported full-arch fixed dental prostheses (FAFDPs) were analyzed by digital image correlation (DIC).

MATERIALS AND METHODS: Polyurethane models were made using 3.75 × 11-mm implants and divided into the following groups with different implant numbers and design: EH5 (five implants/external hexagon), MT5 (five implants/internal taper), EH4 (four implants/external hexagon), and MT4 (four implants/internal taper). Both qualitative and quantitative (one-way analysis of variance [ANOVA] statistical comparison) analyses were performed by the DIC method after the application of a 250-N load in the central fossa of the mandibular first molar. Different regions of interest were selected in the polyurethane model for comparison between groups.

RESULTS: Compressive strains were found in the cervical region of the models, and tensile strains were found in the apical region of the models. Significant differences were found in the different analyzed regions of interest for the different number of supporting implants and implant designs (P < .05).

CONCLUSION: Groups with five implants showed more regions with less strain concentration compared to groups with four implants, but strain distribution was similar between groups. The different tested implant designs showed similar strain concentration and distribution to the supporting structures.

PMID:35235634 | DOI:10.11607/jomi.9087

Int J Oral Maxillofac Implants. 2022 Jan-Feb;37(1):135-142. doi: 10.11607/jomi.9064.

ABSTRACT

PURPOSE: Primary stability is the most important prognostic index for predicting osseointegration. It is generally thought that to achieve high primary stability, it is necessary to insert an implant with a high insertion torque (IT). To date, it has not yet been determined whether IT and implant stability quotient (ISQ) values are correlated. The primary aim of the study was to determine the correlation between IT and ISQ values at the time of implant insertion (T0); at 2 months, the time of healing (T1); and at 6 (T2) and 12 months (T3) after loading. The secondary aims were to determine the influence of different macroscopic implant designs and of a different insertion arch on this correlation; and to assess whether implants inserted with a high IT, that is, > 50 Ncm, had higher levels of implant stability at 2-, 6-, and 12-month follow-ups.

MATERIALS AND METHODS: STROBE guidelines were followed. Partially or monoedentulous patients were randomly assigned to receive taper thread on straight-body implants with microthreads (group A) or without microthreads (group B). At implant insertion, IT and ISQ values were recorded. At 2-, 6-, and 12-month follow-ups, the ISQ values were recorded. A spring-style torque wrench was used to assess the IT. The Osstell device was used to determine the ISQ values. Descriptive statistics, Pearson correlation, and t test were used. P was set at ≤ .005.

RESULTS: Two hundred fifty subjects were assessed; 142 were included. Two hundred sixty-eight implants were inserted (group A, 137 implants; group B, 131 implants). No subject dropped out, and no implant failed. A statistically significant correlation between ISQ and IT was determined at the time of implant insertion (T0; P = .000). The implant morphology and arch did not influence the correlation. An IT > 50 did not determine a higher secondary stability.

CONCLUSION: There is a strong correlation between IT and primary stability, but IT is not correlated with the secondary stability. A different implant macroscopic design and a different arch of insertion did not influence this correlation. Moreover, implants inserted with IT > 50 Ncm do not result in greater secondary stability.

PMID:35235632 | DOI:10.11607/jomi.9064