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Nevin Manimala Statistics

Possibility of new lymphatic pathway creation through neo-lymphangiogenesis induced by subdermal dissection

Lymphology. 2021;54(3):154-163.

ABSTRACT

Surgical intervention and subsequent wound healing process are known to induce neo-lymphangiogenesis, but few studies have been reported to utilize this mechanism for lymphedema treatment. The aim of this study was to evaluate feasibility of subdermal dissection for neo-lymphangiogenesis induction (SDN) to treat lower extremity lymphedema (LEL). Medical records of secondary LEL patients who had undergone ICG lymphography and SDN procedure were reviewed. SDN was performed by dissecting fat tissues just below the dermis from the most proximal area showing dermal backflow through abdominal-toaxillary lymphatic pathways. Perioperative lymphedematous conditions were evaluated with lymphedema quality of life score (LeQOLiS) and LEL index. Seventeen female patients were included. SDN could be performed in 10 minutes on average without postoperative complication. Postoperative ICG lymphography showed new lymphatic pathways in 6 (35.3%) cases. Postoperative LeQOLiS ranged from 9 to 66, which was statistically lower than preoperative LeQOLiS (32.9 ± 19.2 vs. 36.6 ± 19.3, p = 0.048), whereas there was no statistically significant difference between pre- and post-operative LEL index (275.2 ± 23.3 vs. 270.5 ± 20.8, P = 0.073). Subdermal dissection, although its probability is not high, has a potential to induce neo-lymphangiogenesis. Further studies are required to improve and demonstrate efficacy of the procedure for new lymphatic pathway creation.

PMID:34929076

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Nevin Manimala Statistics

Evaluation of the American College of Surgeons National Surgical Quality Improvement Program Risk Calculator to Predict Outcomes after Hysterectomies

Int J Gynaecol Obstet. 2021 Dec 20. doi: 10.1002/ijgo.14075. Online ahead of print.

ABSTRACT

OBJECTIVE: To evaluate the American College of Surgeons surgical risk calculator’s reliability in predicting outcomes in hysterectomies.

METHODS: This is a prospective cohort study at a large community-based hospital. 21 preoperative and postoperative criteria were abstracted from the electronic medical record and entered into the online ACS calculator to determine a risk score. Logistical regression was used to determine the association between risk score and actual outcome. The prediction capability was analyzed with c-statistic, Hosmer-Lemeshow and Brier score.

RESULTS: 634 hysterectomies were performed during the study period from January to April 2019. Patients were predominantly 55 years old, white (53%) and overweight (BMI 30). Predicted perioperative adverse events were significantly higher than actual adverse events across all domains. 54/634 (8.5%) patients experienced postoperative urinary tract infection. C-statistic for return to operating room, renal failure, and readmission were 0.607 (95% C-statistic index [CI] 0.370-0.845), 0.882 (95% CI 0.802-0.962), 0.637 (95% CI 0.524-0.750) respectively. Brier scores approached one in all categorical domains.

CONCLUSION: The ACS surgical risk calculator holds the promise of predicting postoperative complications or length of stay for patients undergoing hysterectomy. Further adjustment to this tool is required before it can be advocated for use in the clinical setting.

PMID:34929052 | DOI:10.1002/ijgo.14075

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Nevin Manimala Statistics

Assessment of tear film osmolarity using the IPen® Vet osmometer in Pug and Shih-Tzu dogs with and without keratoconjunctivitis sicca

Vet Ophthalmol. 2021 Dec 20. doi: 10.1111/vop.12966. Online ahead of print.

ABSTRACT

OBJECTIVE: To establish tear film osmolarity (TFO) values in Pugs and Shih-Tzus, with and without keratoconjunctivitis sicca (KCS).

ANIMALS STUDIED: A total of 82 adult dogs were evaluated.

PROCEDURE: The inclusion criteria for the healthy group was a Schirmer tear test (STT-1) ≥15 mm/min with no clinical signs of KCS, whereas those with KCS had clinical signs and a STT-1 ≤10 mm/min. All animals underwent complete ophthalmological evaluation prior to STT-1 and TFO. Student’s t tests were used to compare STT-1 and TFO in KCS and healthy eyes as well as possible differences in TFO between breeds. In addition, a linear regression to model the relationship between the two variables (STT-1 and TFO) was performed. A P-value ≤ 0.05 was considered statistically significant.

RESULTS: STT-1 results were significantly lower (p = 0.0001) in the KCS group (4.46 ± 1.74) compared with the control group (18.80 ± 2.02). Mean TFO results were significantly higher in the KCS group (353.02 ± 16.58 mOsm/L) (p < 0.0001) compared with the control group (315.27 ± 6.15 mOsm/L). The formula Y = 365.059-2.625 * X significantly predicts (p < 0.001) the value of the variable Y (TFO mOsm/L) as a function of the variable X (STT-1 mm/min), with a coefficient of determination of 0.71.

CONCLUSIONS: The results revealed differences in TFO and STT-1 between KCS and healthy dogs. Additionally, STT-1 and TFO values were correlated with the aim to use STT-1 values to predict TFO values in brachycephalic breeds.

PMID:34929058 | DOI:10.1111/vop.12966

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Nevin Manimala Statistics

Latent Semantic Structure of the WMS-III Verbal Paired-Associates

Arch Clin Neuropsychol. 2021 Dec 20:acab093. doi: 10.1093/arclin/acab093. Online ahead of print.

ABSTRACT

OBJECTIVE: To investigate the factor structure of the verbal paired-associates (VPA) subtest in the WMS-III using a theoretically driven model of semantic processing previously found to be well-fitting for the WMS-IV version of the test.

METHOD: Archival data were used from 267 heterogeneous neurosciences patients and 223 seizure disorder patients who completed the WMS-III as part of a standard neuropsychological evaluation. Confirmatory factor analysis was used to test theoretically driven models for VPA based on principles of semantic processing. Four nested models of different complexities were examined and compared for goodness-of-fit using chi-squared difference testing. Measurement invariance testing was conducted across heterogeneous neuroscience and seizure disorder samples to test generality of the factor model.

RESULTS: After removing items with limited variability (very easy or very hard; 12 of 40 items), a four-factor model was found to be best-fitting in the present patient samples. The four factors were “recreational”, “functional”, “material”, and “symbolic”, each representing semantic knowledge associated with the function of the target word referent. This model subsequently met the criteria for the strict measurement invariance, showing good overall fit when factor loadings, thresholds, and residuals were held to equality across samples.

CONCLUSIONS: The results of this study provide further evidence that “arbitrary” associations between word pairs in VPA items have an underlying semantic structure, challenging the idea that unrelated hard-pairs are semantic-free. These results suggest that a semantic-structure model may be implemented as an alternative scoring in future editions of the WMS to facilitate interpretation.

PMID:34929041 | DOI:10.1093/arclin/acab093

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Nevin Manimala Statistics

Apolipoprotein E deficiency correlates to oxidative stress in gestational diabetes mellitus

Int J Gynaecol Obstet. 2021 Dec 20. doi: 10.1002/ijgo.14076. Online ahead of print.

ABSTRACT

OBJECTIVE: To address the relationship between Apolipoprotein E (ApoE and oxidative stress in gestational diabetes mellitus (GDM).

METHODS: 50 pregnant women diagnosed with GDM and normal pregnant women were recruited separately and their blood and placental tissue were collected. Western blot assay, qRT-PCR assay and ELISA were used to detect the expression levels of ApoE and other oxidative stress factors in these samples. ApoE-/- mice with a C57BL/6J background were used to evaluate the relationship between ApoE deficiency and oxidative stress during GDM.

RESULTS: Serum and placental ApoE were both down-regulated in GDM patients (serum: 45.25 ± 19.27 μg/mL for GDM and 96.34 ± 24.05 μg/mL for control; placental: 14.49 ± 6.52 ng/mg tissue for GDM and 48.76 ±13.59 ng/mg tissue for control). There was a statistical correlation between placental ApoE level and oxidative stress in GDM (r = -0.4904 with MDA, -0.4258 with NO, 0.4476 with SOD, 0.6316 with GSH). ApoE deficiency exacerbated blood glucose, insulin anomaly and oxidative stress in placenta in GDM mouse models. Placental Apo E deficiency correlates to oxidative stress in GDM.

CONCLUSION: In conclusion, we innovatively revealed the relationship between ApoE and GDM oxidative stress among GDM patients in this study.

PMID:34929050 | DOI:10.1002/ijgo.14076

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Nevin Manimala Statistics

Mycobacterium tuberculosis-specific T cell responses are impaired during late pregnancy with elevated biomarkers of tuberculosis risk postpartum

J Infect Dis. 2021 Dec 20:jiab614. doi: 10.1093/infdis/jiab614. Online ahead of print.

ABSTRACT

BACKGROUND: Pregnancy is a risk factor for progression from latent tuberculosis infection (LTBI) to symptomatic tuberculosis (TB). However, how pregnancy influences T cell responses to M. tuberculosis (Mtb) is unknown.

METHODS: We measured Mtb-specific cytokines, T-cell memory markers, and overall CD4+ and CD8+ T-cell activation by flow cytometry from 49 women (18 with and 31 without HIV) who became pregnant while enrolled in a randomized controlled trial of pre-exposure prophylaxis for HIV prevention. We analyzed these data using COMPASS, an established statistical method for evaluating overall antigen-specific T cell responses.

RESULTS: Pregnant women with latent TB infection demonstrated significantly diminished Mtb-specific CD4+ cytokine responses in the third trimester (COMPASS score (PFS) 0.07) compared before (PFS 0.15), during (PFS 0.13 and 0.16), and after pregnancy (PFS 0.14; p = 0.0084, Kruskal-Wallis test). Paradoxically, Mtb-specific CD8+ cytokines and nonspecifically activated T-cells increased during late pregnancy. Nonspecific T-cell activation, a validated biomarker for progression from LTBI to TB disease, was increased in LTBI+ women postpartum, compared with LTBI- women.

CONCLUSIONS: Pregnancy-related functional T-cell changes were most pronounced during late pregnancy. Mtb-specific T-cell changes during pregnancy and postpartum, increases in immune activation may contribute to increased risk for TB progression in the postpartum period.

PMID:34929030 | DOI:10.1093/infdis/jiab614

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Nevin Manimala Statistics

Effects of Class II elastics during growth on the functional occlusal plane according to skeletal pattern and extraction vs nonextraction

Angle Orthod. 2021 Dec 20. doi: 10.2319/051521-381.1. Online ahead of print.

ABSTRACT

OBJECTIVES: To investigate the effect of Class II intermaxillary elastics on the functional occlusal plane (FOP) of growing patients.

MATERIALS AND METHODS: A total of 50 participants aged 11 to 16 years were selected from a university clinic archive >1-year after treatment and after undergoing 6 months of Class II elastic wear, taking pretreatment (T0) and posttreatment (T1) lateral cephalometric radiographs, and consenting to participate at recall (T2). Participants were divided into 3 groups according to skeletal pattern or into 2 groups according to treatment with extraction (E) or nonextraction (NE). Angular changes of FOP relative to the Sella-Nasion (SN), mandibular plane (MP), and Frankfort horizontal (FH) were compared within and between groups.

RESULTS: A statistically significant reduction of FOP-SN/FH, but not of FOP-MP, was found from T0-T1-T2 when all patients were grouped together. FOP-SN/MP/FH was significantly the largest in the patients with a hyperdivergent skeletal pattern, but lowest in the patients with a hypodivergent skeletal pattern at T0, T1, and T2 (P < .032). FOP-MP at T0-T2 was statistically larger in group E than in group NE (P < .02). No differences were found for FOP changes (change before treatment minus after treatment and change after treatment minus 1 year after treatment) between different skeletal patterns (P > .433) and treatment groups (P > .193).

CONCLUSIONS: Use of Class II elastics during the growth period was not found to show adverse effects on FOP rotation. Neither skeletal pattern nor treatment modality differed in the response to Class II elastics with regard to FOP changes. Individual patient growth pattern must be taken into consideration when treatment planning the use of Class II elastics. Orthodontists should take into account individual skeletal and growth patterns while using Class II elastics.

PMID:34929025 | DOI:10.2319/051521-381.1

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Nevin Manimala Statistics

Video-based quantification of human movement frequency using pose estimation: A pilot study

PLoS One. 2021 Dec 20;16(12):e0261450. doi: 10.1371/journal.pone.0261450. eCollection 2021.

ABSTRACT

Assessment of repetitive movements (e.g., finger tapping) is a hallmark of motor examinations in several neurologic populations. These assessments are traditionally performed by a human rater via visual inspection; however, advances in computer vision offer potential for remote, quantitative assessment using simple video recordings. Here, we evaluated a pose estimation approach for measurement of human movement frequency from smartphone videos. Ten healthy young participants provided videos of themselves performing five repetitive movement tasks (finger tapping, hand open/close, hand pronation/supination, toe tapping, leg agility) at four target frequencies (1-4 Hz). We assessed the ability of a workflow that incorporated OpenPose (a freely available whole-body pose estimation algorithm) to estimate movement frequencies by comparing against manual frame-by-frame (i.e., ground-truth) measurements for all tasks and target frequencies using repeated measures ANOVA, Pearson’s correlations, and intraclass correlations. Our workflow produced largely accurate estimates of movement frequencies; only the hand open/close task showed a significant difference in the frequencies estimated by pose estimation and manual measurement (while statistically significant, these differences were small in magnitude). All other tasks and frequencies showed no significant differences between pose estimation and manual measurement. Pose estimation-based detections of individual events (e.g., finger taps, hand closures) showed strong correlations (all r>0.99) with manual detections for all tasks and frequencies. In summary, our pose estimation-based workflow accurately tracked repetitive movements in healthy adults across a range of tasks and movement frequencies. Future work will test this approach as a fast, quantitative, video-based approach to assessment of repetitive movements in clinical populations.

PMID:34929012 | DOI:10.1371/journal.pone.0261450

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Nevin Manimala Statistics

The pigtail macaque (Macaca nemestrina) model of COVID-19 reproduces diverse clinical outcomes and reveals new and complex signatures of disease

PLoS Pathog. 2021 Dec 20;17(12):e1010162. doi: 10.1371/journal.ppat.1010162. Online ahead of print.

ABSTRACT

The novel coronavirus SARS-CoV-2, the causative agent of COVID-19 disease, has killed over five million people worldwide as of December 2021 with infections rising again due to the emergence of highly transmissible variants. Animal models that faithfully recapitulate human disease are critical for assessing SARS-CoV-2 viral and immune dynamics, for understanding mechanisms of disease, and for testing vaccines and therapeutics. Pigtail macaques (PTM, Macaca nemestrina) demonstrate a rapid and severe disease course when infected with simian immunodeficiency virus (SIV), including the development of severe cardiovascular symptoms that are pertinent to COVID-19 manifestations in humans. We thus proposed this species may likewise exhibit severe COVID-19 disease upon infection with SARS-CoV-2. Here, we extensively studied a cohort of SARS-CoV-2-infected PTM euthanized either 6- or 21-days after respiratory viral challenge. We show that PTM demonstrate largely mild-to-moderate COVID-19 disease. Pulmonary infiltrates were dominated by T cells, including CD4+ T cells that upregulate CD8 and express cytotoxic molecules, as well as virus-targeting T cells that were predominantly CD4+. We also noted increases in inflammatory and coagulation markers in blood, pulmonary pathologic lesions, and the development of neutralizing antibodies. Together, our data demonstrate that SARS-CoV-2 infection of PTM recapitulates important features of COVID-19 and reveals new immune and viral dynamics and thus may serve as a useful animal model for studying pathogenesis and testing vaccines and therapeutics.

PMID:34929014 | DOI:10.1371/journal.ppat.1010162

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Nevin Manimala Statistics

Dynamics of latent HIV under clonal expansion

PLoS Pathog. 2021 Dec 20;17(12):e1010165. doi: 10.1371/journal.ppat.1010165. Online ahead of print.

ABSTRACT

The HIV latent reservoir exhibits slow decay on antiretroviral therapy (ART), impacted by homeostatic proliferation and activation. How these processes contribute to the total dynamic while also producing the observed profile of sampled latent clone sizes is unclear. An agent-based model was developed that tracks individual latent clones, incorporating homeostatic proliferation of cells and activation of clones. The model was calibrated to produce observed latent reservoir dynamics as well as observed clonal size profiles. Simulations were compared to previously published latent HIV integration data from 5 adults and 3 children. The model simulations reproduced reservoir dynamics as well as generating residual plasma viremia levels (pVL) consistent with observations on ART. Over 382 Latin Hypercube Sample simulations, the median latent reservoir grew by only 0.3 log10 over the 10 years prior to ART initiation, after which time it decreased with a half-life of 15 years, despite number of clones decreasing at a faster rate. Activation produced a maximum size of genetically intact clones of around one million cells. The individual simulation that best reproduced the sampled clone profile, produced a reservoir that decayed with a 13.9 year half-life and where pVL, produced mainly from proliferation, decayed with a half-life of 10.8 years. These slow decay rates were achieved with mean cell life-spans of only 14.2 months, due to expansion of the reservoir through proliferation and activation. Although the reservoir decayed on ART, a number of clones increased in size more than 4,000-fold. While small sampled clones may have expanded through proliferation, the large sizes exclusively arose from activation. Simulations where homeostatic proliferation contributed more to pVL than activation, produced pVL that was less variable over time and exhibited fewer viral blips. While homeostatic proliferation adds to the latent reservoir, activation can both add and remove latent cells. Latent activation can produce large clones, where these may have been seeded much earlier than when first sampled. Elimination of the reservoir is complicated by expanding clones whose dynamic differ considerably to that of the entire reservoir.

PMID:34929000 | DOI:10.1371/journal.ppat.1010165