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Wilkinson McClanahan opublikował 1 rok, 8 miesięcy temu
In the game of softball, the batter should possess the necessary skills to hit the ball toward various directions with high initial speed. However, because various factors influence each other, there are limitations to the range that can be controlled by the batter’s skill. This study was aimed at extracting the impact characteristics associated with the launch speed/direction and batted ball spin and clarifying the important skills required to improve the batter’s hitting performance. In our experiments, 20 female softball players, who are members of the Japan women’s national softball team, hit balls launched from a pitching machine. The movements of the ball and bat before, during, or after the impact were recorded using a motion capture system. Stepwise multiple regression analysis was performed to extract factors relating the side spin rate. The undercut angle (elevation angle between the bat’s trajectory and the common normal between the ball and bat ΔR2 = 0.560) and the horizontal bat angle (azimuth of bat’s long axis at ball impact ΔR2 = 0.299) were strongly associated with the side spin rate (total R2 = 0.893, p less then 0.001). The undercut angle in opposite-field hitting was significantly larger than that in pull-side hitting (p less then 0.001). The side spin rate was associated with the undercut angle because the bat’s distal (barrel) side inclined downward (-29.6 ± 8.7°) at impact. The ball exit velocity was higher when it was hit at a smaller undercut angle (R2 = 0.523, p less then 0.001). Therefore, it is deemed desirable to focus on maximizing the ball exit velocity rather than ball spin because the ball-bat impact characteristics vary inevitably depending on the launch direction. Meanwhile, the use of the ball delivery machine and the slower pitched ball are the limiting factors in the generalization of the findings.Collective cell migration is essential for embryonic development and homeostatic processes. During zebrafish development, the posterior lateral line primordium (pLLP) navigates along the embryo flank by collective cell migration. The chemokine receptors, Cxcr4b and Cxcr7b, as well as their cognate ligand, Cxcl12a, are essential for this process. We corroborate that knockdown of the zebrafish cd9 tetraspanin orthologue, cd9b, results in mild pLL abnormalities. Through generation of CRISPR and TALEN mutants, we show that cd9a and cd9b function partially redundantly in pLLP migration, which is delayed in the cd9b single and cd9a; cd9b double mutants. This delay led to a transient reduction in neuromast numbers. Loss of both Cd9a and Cd9b sensitized embryos to reduced Cxcr4b and Cxcl12a levels. Together these results provide evidence that Cd9 modulates collective cell migration of the pLLP during zebrafish development. One interpretation of these observations is that Cd9 contributes to more effective chemokine signalling.The Drosophila NMJ is a system of choice for investigating the mechanisms underlying the structural and functional modifications evoked during activity-dependent synaptic plasticity. Because fly genetics allows considerable versatility, many strategies can be employed to elicit this activity. Here, we compare three different stimulation methods for eliciting activity-dependent changes in structure and function at the Drosophila NMJ. We find that the method using patterned stimulations driven by a K+-rich solution creates robust structural modifications but reduces muscle viability, as assessed by resting potential and membrane resistance. We argue that, using this method, electrophysiological studies that consider the frequency of events, rather than their amplitude, are the only reliable studies. We contrast these results with the expression of CsChrimson channels and red-light stimulation at the NMJ, as well as with the expression of TRPA channels and temperature stimulation. With both these methods we observed reliable modifications of synaptic structures and consistent changes in electrophysiological properties. Indeed, we observed a rapid appearance of immature boutons that lack postsynaptic differentiation, and a potentiation of spontaneous neurotransmission frequency. Surprisingly, a patterned application of temperature changes alone is sufficient to provoke both structural and functional plasticity. In this context, temperature-dependent TRPA channel activation induces additional structural plasticity but no further increase in the frequency of spontaneous neurotransmission, suggesting an uncoupling of these mechanisms.Endoplasmic reticulum (ER) stress is associated with acute kidney injury (AKI) caused by various mechanisms, including antibiotics, non-steroidal anti-inflammatory drugs, cisplatin, and radiocontrast. Tunicamycin (TM) is a nucleoside antibiotic that induces ER stress and is a commonly used model of AKI. 4-phenylbutyrate (4-PBA) is a chemical chaperone and histone deacetylase (HDAC) inhibitor and has been shown to protect the kidney from ER stress, apoptosis, and structural damage in a tunicamycin model of AKI. The renal protection provided by 4-PBA is attributed to its ability to prevent misfolded protein aggregation and inhibit ER stress; however, the HDAC inhibitor effects of 4-PBA have not been examined in the TM-induced model of AKI. As such, the main objective of this study was to determine if histone hyperacetylation provides any protective effects against TM-mediated AKI. The FDA-approved HDAC inhibitor vorinostat was used, as it has no ER stress inhibitory effects and therefore the histone hyperacetylation properties alone could be investigated. In vitro work demonstrated that vorinostat inhibited histone deacetylation in cultured proximal tubular cells but did not prevent ER stress or protein aggregation induced by TM. Vorinostat induced a significant increase in cell death, and exacerbated TM-mediated total cell death and apoptotic cell death. Wild type male mice were treated with TM (0.5 mg/kg, intraperitoneal injection), with or without vorinostat (50 mg/kg/day) or 4-PBA (1 g/kg/day). Mice treated with 4-PBA or vorinostat exhibited similar levels of histone hyperacetylation. Expression of the pro-apoptotic protein CHOP was induced with TM, and not inhibited by vorinostat. Further, vorinostat did not prevent any renal damage or decline in renal function caused by tunicamycin. These data suggest that the protective mechanisms found by 4-PBA are primarily due to its molecular chaperone properties, and the HDAC inhibitors used did not provide any protection against renal injury caused by ER stress.
Research with a focus on sleep posture has been conducted in association with sleep pathologies such as insomnia and positional obstructive sleep apnoea. Research examining the potential role sleep posture may have on waking spinal symptoms and quality of sleep is however limited. The aims of this research were to compare sleep posture and sleep quality in participants with and without waking spinal symptoms.
Fifty-three participants (36 female) were, based on symptoms, allocated to one of three groups; Control (n = 20, 16 female), Cervical (n = 13, 10 female) and Lumbar (n = 20, 10 female). Participants completed an online survey to collect general information and patient reported outcomes and were videoed over two consecutive nights to determine sleep posture using a validated classification system including intermediate sleep postures.
Participants in the symptomatic groups also reported a lower sleep quality than the Control group. Compared to Control group participants, those in the Cervical group al, participants with waking spinal symptoms spent more time in provocative sleep postures, and experienced poorer sleep quality.
Key populations (KP) are disproportionately infected with HIV and experience barriers to HIV care. KP include men who have sex with men (MSM), female sex workers (FSW), persons who inject drugs (PWID) and transgender people (TG). We implemented three different approaches to the delivery of community-based antiretroviral therapy for KP (KP-CBART) in Benue State Nigeria, including One Stop Shop clinics (OSS), community drop-in-centres (DIC), and outreach venues. OSS are community-based health facilities serving KP only. DIC are small facilities led by lay healthcare providers and supported by an outreach team. Outreach venues are places in the community served by the outreach team. We studied long-term attrition of KP and virological non-suppression.
This is a retrospective cohort study of KP living with HIV (KPLHIV) starting ART between 2016 and 2019 in 3 0SS, 2 DIC and 8 outreach venues. Attrition included lost to follow-up (LTFU) and death. A viral load >1000 copies/mL showed viral non-suppression. Su load test. Of those, 97.8% (n = 1654) were virally suppressed.
Although long-term retention in care is low, the virological suppression was optimal for KP on ART and retained in community-based ART care. However, viral load testing coverage was sub-optimal. Future research should explore the perspectives of clients on reasons for LTFU and how to adapt approach to CBART to meet individual client needs.
Although long-term retention in care is low, the virological suppression was optimal for KP on ART and retained in community-based ART care. However, viral load testing coverage was sub-optimal. Future research should explore the perspectives of clients on reasons for LTFU and how to adapt approach to CBART to meet individual client needs.Telemedicine can be used to conduct ophthalmological assessment of patients, facilitating patient access to specialist care. Since the teleophthalmology models require data collection support from other health professionals, the purpose of our study was to assess agreement between the nursing technician and the ophthalmologist in acquisition of health parameters that can be used for remote analysis as part of a telemedicine strategy. A cross-sectional study was conducted with 140 patients referred to an ophthalmological telediagnosis center by primary healthcare doctors. The health parameters evaluated were visual acuity (VA), objective ophthalmic measures acquired by autorefraction, keratometry, and intraocular pressure (IOP). Bland-Altman plots were used to analyze agreement between the nursing technician and the ophthalmologist. The Bland-Altman analysis showed a mean bias equal to zero for the VA measurements [95%-LoA -0.25-0.25], 0.01 [95%-LoA -0.86-0.88] for spherical equivalent (M), -0.08 [95%-LoA -1.1-0.95] for keratometry (K) and -0.23 [95%-LoA -4.4-4.00] for IOP. The measures had a high linear correlation (R [95%CI] 0.87 [0.82-0.91]; 0.97 [0.96-0.98]; 0.96 [0.95-0.97] and 0.88 [0.84-0.91] respectively). The results observed demonstrate that remote ophthalmological data collection by adequately trained health professionals is viable. This confirms the utility and safety of these solutions for scenarios in which access to ophthalmologists is limited.Cook Inlet, Alaska, is home to an endangered and declining population of 279 belugas (Delphinapterus leucas). Recovery efforts highlight a paucity of basic ecological knowledge, impeding the correct assessment of threats and the development of recovery actions. In particular, information on diet and foraging habitat is very limited for this population. Passive acoustic monitoring has proven to be an efficient approach to monitor beluga distribution and seasonal occurrence. Identifying acoustic foraging behavior could help address the current gap in information on diet and foraging habitat. To address this conservation challenge, eight belugas from a comparative, healthy population in Bristol Bay, Alaska, were instrumented with a multi-sensor tag (DTAG), a satellite tag, and a stomach temperature transmitter in August 2014 and May 2016. DTAG deployments provided 129.6 hours of data including foraging and social behavioral states. A total of 68 echolocation click trains ending in terminal buzzes were identifiedrun periods, with increased feeding occurrence at the peak of the Chinook and pink salmon runs.
A wide range of potentially modifiable risk factors, indicating that the onset of neurocognitive disorders can be delayed or prevented, have been identified. The region of Central and Eastern Europe has cultural, political and economic specifics that may influence the occurrence of risk factors and their link to the cognitive health of the population.
We aimed to systematically review population-based studies from Central and Eastern Europe to gather evidence on risk and protective factors for neurocognitive disorders.
We searched the electronic databases PubMed, Cochrane Database of Systematic Reviews, PsycINFO, Web of Science, and Embase. The search was performed on 26th of February 2020 and repeated at the end of the review process on 20th May 2021.
We included 25 papers in a narrative synthesis of the evidence describing cardiovascular risk factors (n = 7), social factors (n = 5), oxidative stress (n = 2), vitamins (n = 2), genetic factors (n = 2) and other areas (n = 7). We found that there was a good body of evidence on the association between neurocognitive disorders and the history of cardiovascular disease while there were gaps in research of genetic and social risk factors.
We conclude that the epidemiological evidence from this region is insufficient and population-based prospectively followed cohorts should be established to allow the development of preventive strategies at national levels.
We conclude that the epidemiological evidence from this region is insufficient and population-based prospectively followed cohorts should be established to allow the development of preventive strategies at national levels.Evidence-based teaching practices are associated with improved student academic performance. However, these practices encompass a wide range of activities and determining which type, intensity or duration of activity is effective at improving student exam performance has been elusive. To address this shortcoming, we used a previously validated classroom observation tool, Practical Observation Rubric to Assess Active Learning (PORTAAL) to measure the presence, intensity, and duration of evidence-based teaching practices in a retrospective study of upper and lower division biology courses. We determined the cognitive challenge of exams by categorizing all exam questions obtained from the courses using Bloom’s Taxonomy of Cognitive Domains. We used structural equation modeling to correlate the PORTAAL practices with exam performance while controlling for cognitive challenge of exams, students’ GPA at start of the term, and students’ demographic factors. Small group activities, randomly calling on students or grots’ learning by incorporating these evidence-based teaching practices.Lung cancer is the leading cause of cancer-related deaths. While the recent use of immune checkpoint inhibitors significantly improves patient outcomes, responsiveness remains restricted to a small proportion of patients. Conventional dendritic cells (DCs) play a major role in anticancer immunity. In mice, two subpopulations of DCs are found in the lung DC2s (CD11b+Sirpα+) and DC1s (CD103+XCR1+), the latest specializing in the promotion of anticancer immune responses. However, the impact of lung cancer on DC populations and the consequent influence on the anticancer immune response remain poorly understood. To address this, DC populations were studied in murine models of Lewis Lung Carcinoma (LLC) and melanoma-induced lung metastasis (B16F10). We report that direct exposure to live or dead cancer cells impacts the capacity of DCs to differentiate into CD103+ DC1s, leading to profound alterations in CD103+ DC1 proportions in the lung. In addition, we observed the accumulation of CD103loCD11b+ DCs, which express DC2 markers IRF4 and Sirpα, high levels of T-cell inhibitory molecules PD-L1/2 and the regulatory molecule CD200. Finally, DC1s were injected in combination with an immune checkpoint inhibitor (anti-PD-1) in the B16F10 model of resistance to the anti-PD-1 immune checkpoint therapy; the co-injection restored sensitivity to immunotherapy. Thus, we demonstrate that lung tumor development leads to the accumulation of CD103loCD11b+ DCs with a regulatory potential combined with a reduced proportion of highly-specialized antitumor CD103+ DC1s, which could promote cancer growth. Additionally, promoting an anticancer DC signature could be an interesting therapeutic avenue to increase the efficacy of existing immune checkpoint inhibitors.Metaheuristic optimization algorithms are one of the most effective methods for solving complex engineering problems. However, the performance of a metaheuristic algorithm is related to its exploration ability and exploitation ability. Therefore, to further improve the African vultures optimization algorithm (AVOA), a new metaheuristic algorithm, an improved African vultures optimization algorithm based on tent chaotic mapping and time-varying mechanism (TAVOA), is proposed. First, a tent chaotic map is introduced for population initialization. Second, the individual’s historical optimal position is recorded and applied to individual location updating. Third, a time-varying mechanism is designed to balance the exploration ability and exploitation ability. To verify the effectiveness and efficiency of TAVOA, TAVOA is tested on 23 basic benchmark functions, 28 CEC 2013 benchmark functions and 3 common real-world engineering design problems, and compared with AVOA and 5 other state-of-the-art metaheuristic optimization algorithms. According to the results of the Wilcoxon rank-sum test with 5%, among the 23 basic benchmark functions, the performance of TAVOA has significantly better than that of AVOA on 13 functions. Among the 28 CEC 2013 benchmark functions, the performance of TAVOA on 9 functions is significantly better than AVOA, and on 17 functions is similar to AVOA. Besides, compared with the six metaheuristic optimization algorithms, TAVOA also shows good performance in real-world engineering design problems.
To conduct a cross-sectional nationwide study examining how exclusion of nursing home COVID-19 cases influences the association between county level social distancing behavior and COVID-19 cases throughout the US during the early phase of the pandemic (February 2020-May 2020).
Using county-level COVID-19 data and social distancing metrics from tracked mobile devices, we investigated the impact social distancing had on a county’s total COVID-19 cases (cases/100,000 people) between when the first COVID-19 case was confirmed in a county and May 31st, 2020 when most statewide social distancing measures were lifted, representing the pandemic’s exponential growth phase. We created a mixed-effects negative binomial model to assess how implementation of social distancing measures when they were most stringent (March 2020-May 2020) influenced total COVID-19 cases while controlling for social distancing and COVID-19 related covariates in two scenarios (1) when COVID-19 nursing home cases are not excluded from total phones leaving home 163.84 cases/100,000 people (95% CI 121.81, 205.86), 45% of mobile phones leaving home 432.79 cases/100,000 people (95% CI 256.91, 608.66)) and when they were excluded (25% of mobile phones leaving home 149.58 cases/100,000 people (95% CI 111.90, 187.26), 45% of mobile phones leaving home 405.38 cases/100,000 people (95% CI 243.14, 567.62)).
Exclusion of nursing home COVID-19 cases from total COVID-19 case counts has little impact when estimating the relationship between county-level social distancing and preventing COVID-19 cases with additional research needed to see whether this finding is also observed for COVID-19 growth rates and mortality.
Exclusion of nursing home COVID-19 cases from total COVID-19 case counts has little impact when estimating the relationship between county-level social distancing and preventing COVID-19 cases with additional research needed to see whether this finding is also observed for COVID-19 growth rates and mortality.Thrombolytic and fibrinolytic therapies are effective treatments to dissolve blood clots in stroke therapy. Thrombolytic drugs activate plasminogen to its cleaved form plasmin, a proteolytic enzyme that breaks the crosslinks between fibrin molecules. The FDA-approved human tissue plasminogen activator Reteplase (rPA) is a non-glycosylated protein produced in E. coli. rPA is a deletion mutant of the wild-type Alteplase that benefits from an extended plasma half-life, reduced fibrin specificity and the ability to better penetrate into blood clots. Different methods have been proposed to improve the production of rPA. Here we show for the first time the transient expression in Nicotiana benthamiana of rPA fused to the immunoglobulin fragment crystallizable (Fc) domain on an IgG1, a strategy commonly used to improve the stability of therapeutic proteins. Despite our success on the expression and purification of dimeric rPA-Fc fusions, protein instability results in high amounts of Fc-derived degradation products. We hypothesize that the „Y”- shape of dimeric Fc fusions cause steric hindrance between protein domains and leads to physical instability. Indeed, mutations of critical residues in the Fc dimerization interface allowed the expression of fully stable rPA monomeric Fc-fusions. The ability of rPA-Fc to convert plasminogen into plasmin was demonstrated by plasminogen zymography and clot lysis assay shows that rPA-Fc is able to dissolve blood clots ex vivo. Finally, we addressed concerns with the plant-specific glycosylation by modulating rPA-Fc glycosylation towards serum-like structures including α2,6-sialylated and α1,6-core fucosylated N-glycans completely devoid of plant core fucose and xylose residues.
Recorded serum 25(OH)D in survey data varies with observed and unobserved respondent characteristics. The aim of this study was to expose latent population sub-groups and examine variation across groups regarding relationships between serum 25(OH)D and observable characteristics.
This study explored the role of unobserved heterogeneity on associations between surveyed 25(OH)D and various factors using a sample (n = 2,641) extracted from the Saudi Health Interview Survey (2013). Linear regression and finite mixture models (FMM) were estimated and compared. The number of latent classes in the FMM was chosen based on BIC score.
Three latent classes were identified. Class I (39.82%), class II (41.03%), and class III (19.15%) with mean 25(OH)D levels of 22.79, 34.88, and 57.45 ng/ml respectively. Distinct patterns of associations with nutrition, behaviour and socio-demographic variables were recorded across classes that were not revealed in pooled linear regression.
FMM has the potential to provide additional insights on the relationship between 25(OH)D levels and observable characteristics. It should be more widely considered as a method of investigation in this area.
FMM has the potential to provide additional insights on the relationship between 25(OH)D levels and observable characteristics. It should be more widely considered as a method of investigation in this area.Durian (Durio zibethinus L.) is a major economic crop native to Southeast Asian countries, including Thailand. Accordingly, understanding durian fruit ripening is an important factor in its market worldwide, owing to the fact that it is a climacteric fruit with a strikingly limited shelf life. However, knowledge regarding the molecular regulation of durian fruit ripening is still limited. Herein, we focused on cytochrome P450, a large enzyme family that regulates many biosynthetic pathways of plant metabolites and phytohormones. Deep mining of the durian genome and transcriptome libraries led to the identification of all P450s that are potentially involved in durian fruit ripening. Gene expression validation by RT-qPCR showed a high correlation with the transcriptome libraries at five fruit ripening stages. In addition to aril-specific and ripening-associated expression patterns, putative P450s that are potentially involved in phytohormone metabolism were selected for further study. Accordingly, the expression of CYP72, CYP83, CYP88, CYP94, CYP707, and CYP714 was significantly modulated by external treatment with ripening regulators, suggesting possible crosstalk between phytohormones during the regulation of fruit ripening. Interestingly, the expression levels of CYP88, CYP94, and CYP707, which are possibly involved in gibberellin, jasmonic acid, and abscisic acid biosynthesis, respectively, were significantly different between fast- and slow-post-harvest ripening cultivars, strongly implying important roles of these hormones in fruit ripening. Taken together, these phytohormone-associated P450s are potentially considered additional molecular regulators controlling ripening processes, besides ethylene and auxin, and are economically important biological traits.Similar to psychostimulants, the peripheral administration of menthol promotes mouse motor activity, and the neurotransmitter dopamine has been suggested to be involved in this effect. The present study aimed to elucidate the effects of l-menthol on parts of the central nervous system that are involved in motor effects. The subcutaneous administration of l-menthol significantly increased the number of c-Fos-like immunoreactive nuclei in the dorsal striatum of the mice, and motor activity was promoted. It also increased the extracellular dopamine level in the dorsal striatum of the mice. These observations indicated that after subcutaneous administration, l-menthol enhances dopamine-mediated neurotransmission, and activates neuronal activity in the dorsal striatum, thereby promoting motor activity in mice.The size distribution of marine microplastics provides a fundamental data source for understanding the dispersal, break down, and biotic impacts of the microplastics in the ocean. The observed size distribution at the sea surface generally shows, from large to small sizes, a gradual increase followed by a rapid decrease. This decrease has led to the hypothesis that the smallest fragments are selectively removed by sinking or biological uptake. Here we propose a new model of size distribution, focusing on the fragmentation of marine plastics. The model is inspired by ideas from statistical mechanics. In this model, the original large plastic piece is broken into smaller pieces once by the application of „energy” or work by waves or other processes, under two assumptions, one that fragmentation into smaller pieces requires larger energy and the other that the occurrence probability of the „energy” exponentially decreases toward larger energy values. Our formula well reproduces observed size distributions over wide size ranges from micro- to mesoplastics. According to this model, the smallest fragments are fewer because large „energy” required to produce such small fragments occurs more rarely.Disease-related effects on hepatic metabolism can alter the composition of chemicals in the circulation and subsequently in breath. The presence of disease related alterations in exhaled volatile organic compounds could therefore provide a basis for non-invasive biomarkers of hepatic disease. This study examined the feasibility of using global volatolomic profiles from breath analysis in combination with supervised machine learning to develop signature pattern-based biomarkers for cirrhosis. Breath samples were analyzed using thermal desorption-gas chromatography-field asymmetric ion mobility spectroscopy to generate breathomic profiles. A standardized collection protocol and analysis pipeline was used to collect samples from 35 persons with cirrhosis, 4 with non-cirrhotic portal hypertension, and 11 healthy participants. Molecular features of interest were identified to determine their ability to classify cirrhosis or portal hypertension. A molecular feature score was derived that increased with the stage of cirrhosis and had an AUC of 0.78 for detection. Chromatographic breath profiles were utilized to generate machine learning-based classifiers. Algorithmic models could discriminate presence or stage of cirrhosis with a sensitivity of 88-92% and specificity of 75%. These results demonstrate the feasibility of volatolomic profiling to classify clinical phenotypes using global breath output. These studies will pave the way for the development of non-invasive biomarkers of liver disease based on volatolomic signatures found in breath.Social behaviors are foundational to society and quality of life while social behavior extremes are core symptoms in a variety of psychopathologies and developmental disabilities. Oxytocin (OXT) is a neuroactive hormone that regulates social behaviors through its receptor (OXTR), with all previously identified social behavior effects attributed to the central nervous system, which has developmental origins in the neural tube. However, OXTR are also present in neural crest-derived tissue including sensory ganglia of the peripheral nervous system. Avil encodes for the actin-binding protein ADVILLIN, is expressed in neural crest-derived cells, and was therefore used as a target in this study to knock out OXTR expression in neural-crest derived cells. Here, we tested if OXTRs specifically expressed in Avil positive neural crest-derived cells are necessary for species-typical adult social behaviors using a Cre-LoxP strategy. Genetically modified male and female mice lacking OXTR in Avil expressing cells (OXTRAvil KO) were tested for sociability and preference for social novelty. Males were also tested for resident intruder aggression. OXTRAvil KO males and females had reduced sociability compared to OXTRAvil WT controls. Additionally, OXTRAvil KO males had increased aggressive behaviors compared to controls. These data indicate that OXTRs in cells of neural crest origin are important regulators of typical social behaviors in C57BL/6J adult male and female mice and point to needed directions of future research.
To assess the response of serum triglycerides (TG) to continuous insulin infusion (CII) in adults with hypertriglyceridemia-associated acute pancreatitis (HTGP).
Retrospective analysis of TG response to standardized CII therapy in 77 adults admitted to intensive care with TG >1000 mg/dL and HTGP.
Participants had initial TG 3869.0 [2713.5, 5443.5] mg/dL and were 39.3 ± 9.7 years old, 66.2% males, 58.4% Hispanic, BMI 30.2 [27.0, 34.8] kg/m2, 74.0% with diabetes mellitus (DM) and 50.6% with excess alcohol use. TG-goal, defined as ≤1,000 ± 100 mg/dL, was achieved in 95%. Among the 73 TG-goal achievers (responders), 53.4% reached TG-goal in <36 hours after CII initiation (rapid responders). When compared to slow responders taking≥36 hours, rapid responders had lower initial TG (2862.0 [1965.0, 4519.0] vs 4814.5 [3368.8, 6900.0] mg/dL), BMI (29.4 [25.9, 32.8] vs 31.9 [28.2, 38.3] kg/m2), DM prevalence (56.4 vs 94.1%), and reached TG-50% (half of respective initial TG) faster (12.0 [6.0, 17.0] vs 18.5 [ to reach TG-goal. These baseline parameters and rate of decline to TG-50% may be real-time indicators to initiate and adjust the CII for quicker response.Fragile X syndrome results from the loss of expression of the Fragile X Mental Retardation Protein (FMRP). FMRP and RNA helicase Moloney Leukemia virus 10 (MOV10) are important Argonaute (AGO) cofactors for miRNA-mediated translation regulation. We previously showed that MOV10 functionally associates with FMRP. Here we quantify the effect of reduced MOV10 and FMRP expression on dendritic morphology. Murine neurons with reduced MOV10 and FMRP phenocopied Dicer1 KO neurons which exhibit impaired dendritic maturation Hong J (2013), leading us to hypothesize that MOV10 and FMRP regulate DICER expression. In cells and tissues expressing reduced MOV10 or no FMRP, DICER expression was significantly reduced. Moreover, the Dicer1 mRNA is a Cross-Linking Immunoprecipitation (CLIP) target of FMRP Darnell JC (2011), MOV10 Skariah G (2017) and AGO2 Kenny PJ (2020). MOV10 and FMRP modulate expression of DICER1 mRNA through its 3’untranslated region (UTR) and introduction of a DICER1 transgene restores normal neurite outgrowth in the Mov10 KO neuroblastoma Neuro2A cell line and branching in MOV10 heterozygote neurons. Moreover, we observe a global reduction in AGO2-associated microRNAs isolated from Fmr1 KO brain. We conclude that the MOV10-FMRP-AGO2 complex regulates DICER expression, revealing a novel mechanism for regulation of miRNA production required for normal neuronal morphology.Aiming at these problems of image colorization algorithms based on deep learning, such as color bleeding and insufficient color, this paper converts the study of image colorization to the optimization of image semantic segmentation, and proposes a fully automatic image colorization model based on semantic segmentation technology. Firstly, we use the encoder as the local feature extraction network and use VGG-16 as the global feature extraction network. These two parts do not interfere with each other, but they share the low-level feature. Then, the first fusion module is constructed to merge local features and global features, and the fusion results are input into semantic segmentation network and color prediction network respectively. Finally, the color prediction network obtains the semantic segmentation information of the image through the second fusion module, and predicts the chrominance of the image based on it. Through several sets of experiments, it is proved that the performance of our model becomes stronger and stronger under the nourishment of the data. Even in some complex scenes, our model can predict reasonable colors and color correctly, and the output effect is very real and natural.A variety of mitigation strategies have been employed against the Covid-19 pandemic. Social distancing is still one of the main methods to reduce spread, but it entails a high toll on personal freedom and economic life. Alternative mitigation strategies that do not come with the same problems but are effective at preventing disease spread are therefore needed. Repetitive mass-testing using PCR assays for viral RNA has been suggested, but as a stand-alone strategy this would be prohibitively resource intensive. Here, we suggest a strategy that aims at targeting the limited resources available for viral RNA testing to subgroups that are more likely than the average population to yield a positive test result. Importantly, these pre-selected subgroups include symptom-free people. By testing everyone in these subgroups, in addition to symptomatic cases, large fractions of pre- and asymptomatic people can be identified, which is only possible by testing-based mitigation. We call this strategy smart testing (ST). In principle, pre-selected subgroups can be found in different ways, but for the purpose of this study we analyze a pre-selection procedure based on cheap and fast virus antigen tests. We quantify the potential reduction of the epidemic reproduction number by such a two-stage ST strategy. In addition to a scenario where such a strategy is available to the whole population, we analyze local applications, e.g. in a country, company, or school, where the tested subgroups are also in exchange with the untested population. Our results suggest that a two-stage ST strategy can be effective to curb pandemic spread, at costs that are clearly outweighed by the economic benefit. It is technically and logistically feasible to employ such a strategy, and our model predicts that it is even effective when applied only within local groups. We therefore recommend adding two-stage ST to the portfolio of available mitigation strategies, which allow easing social distancing measures without compromising public health.
To examine the association between metabolic syndrome (MetS) and successful aging among community-dwelling older adults.
Adults aged ≥ 65 years who participated in the senior health checkup program at National Taiwan University Hospital during 2011-2013 were recruited (N = 467 at baseline). The participants were followed after 4 years and 6 years. MetS was assessed at baseline. Successful aging was evaluated at baseline, 4-year follow-up, and 6-year follow-up. We adopted an extended definition of successful aging, which was defined as three major domains physiological, psychological, and sociological and economic domains. Generalized linear mixed models were used to assess the association between MetS and successful aging adjusting for time (follow-up years), age, sex, years of education, alcohol consumption and MetS×time interaction term.
The mean age of the study population was 72.9 (SD 5.5) years. The absence of baseline MetS had a positive effect on the probability of successful aging over six years. The absences of abdominal obesity, hyperglycemia, reduced high-density lipoprotein cholesterol, and hypertension were associated with the physiological successful aging. The absence of hypertension was the most significant predictor of physiological successful aging [aOR (95% CI) = 2.76 (1.67-4.58), p<0.001]. Significant increased trend was found in the overall and physiological successful aging across MetS status (No MetS, pre MetS, MetS; Ptrend <0.001).
We found that MetS is a risk factor of successful aging among community-dwelling older adults. Public health policy should aim at avoidance of MetS in order to facilitate successful aging in older population.
We found that MetS is a risk factor of successful aging among community-dwelling older adults. Public health policy should aim at avoidance of MetS in order to facilitate successful aging in older population.Health varies by U.S. region of residence. Despite regional heterogeneity in the outbreak of COVID-19, regional differences in physical distancing behaviors over time are relatively unknown. This study examines regional variation in physical distancing trends during the COVID-19 pandemic and investigates variation by race and socioeconomic status (SES) within regions. Data from the 2015-2019 five-year American Community Survey were matched with anonymized location pings data from over 20 million mobile devices (SafeGraph, Inc.) at the Census block group level. We visually present trends in the stay-at-home proportion by Census region, race, and SES throughout 2020 and conduct regression analyses to examine these patterns. From March to December, the stay-at-home proportion was highest in the Northeast (0.25 in March to 0.35 in December) and lowest in the South (0.24 to 0.30). Across all regions, the stay-at-home proportion was higher in block groups with a higher percentage of Blacks, as Blacks disproportionately live in urban areas where stay-at-home rates were higher (0.009 [CI 0.008, 0.009]). In the South, West, and Midwest, higher-SES block groups stayed home at the lowest rates pre-pandemic; however, this trend reversed throughout March before converging in the months following. In the Northeast, lower-SES block groups stayed home at comparable rates to higher-SES block groups during the height of the pandemic but diverged in the months following. Differences in physical distancing behaviors exist across U.S. regions, with a pronounced Southern and rural disadvantage. Results can be used to guide reopening and COVID-19 mitigation plans.Transcription factors are regulatory proteins known to modulate gene expression. These are the critical component of signaling pathways and help in mitigating various developmental and stress responses. Among them, bZIP, BBR, and BZR transcription factor families are well known to play a crucial role in regulating growth, development, and defense responses. However, limited data is available on these transcription factors in Triticum aestivum. In this study, bZIP, BBR, and BZR sequences from Brachypodium distachyon, Oryza sativa, Oryza barthii, Oryza brachyantha, T. aestivum, Triticum urartu, Sorghum bicolor, Zea mays were retrieved, and dendrograms were constructed to analyze the evolutionary relatedness among them. The sequences clustered into one group indicated a degree of evolutionary correlation highlighting the common lineage of cereal grains. This analysis also exhibited that these genes were highly conserved among studied monocots emphasizing their common ancestry. Furthermore, these transcription factor genes were evaluated for envisaging conserved motifs, gene structure, and subcellular localization in T. aestivum. This comprehensive computational analysis has provided an insight into transcription factor evolution that can also be useful in developing approaches for future functional characterization of these genes in T. aestivum. Furthermore, the data generated can be beneficial in future for genetic manipulation of economically important plants.Chlamydia pneumoniae (Cpn) is a gram-negative intracellular pathogen that causes a variety of pulmonary diseases, and there is growing evidence that it may play a role in Alzheimer’s disease (AD) pathogenesis. Cpn can interact functionally with host histones, altering the host’s epigenetic regulatory system by introducing bacterial products into the host tissue and inducing a persistent inflammatory response. Because Cpn is difficult to propagate, isolate, and detect, a modified LPS-like neuroinflammation model was established using lyophilized cell free supernatant (CFS) obtained from infected cell cultures, and the effects of CFS were compared to LPS. The neuroprotective effects of Trichostatin A (TSA), givinostat, and RG108, which are effective on epigenetic mechanisms, and the antibiotic rifampin, were studied in this newly introduced model and in the presence of amyloid beta (Aβ) 1-42. The neuroprotective effects of the drugs, as well as the effects of CFS and LPS, were evaluated in Aβ-induced neurotoxicity using a real-time cell analysis system, total ROS, and apoptotic impact. TSA, RG108, givinostat, and rifampin all demonstrated neuroprotective effects in both this novel model and Aβ-induced neurotoxicity. The findings are expected to provide early evidence on neuroprotective actions against Cpn-induced neuroinflammation and Aβ-induced neurotoxicity, which could represent a new treatment option for AD, for which there are currently few treatment options.
The Hereditary Spastic Paraplegias (HSP) are a group of genetic diseases that lead to slow deterioration of locomotion. Clinical scales seem to have low sensitivity in detecting disease progression, making the search for additional biomarkers a paramount task. This study aims to evaluate the role of evoked potentials (EPs) as disease biomarkers of HSPs.
A single center cross-sectional case-control study was performed, in which 18 individuals with genetic diagnosis of HSP and 21 healthy controls were evaluated. Motor evoked potentials (MEP) obtained with transcranial magnetic stimulation and somatosensory evoked potentials (SSEP) were performed in lower (LL) and upper limbs (UL).
Central motor conduction time in lower limbs (CMCT-LL) was prolonged in HSP subjects, with marked reductions in MEP-LL amplitudes when compared to the control group (p<0.001 for both comparisons). CMCT-UL was 3.59ms (95% CI 0.73 to 6.46; p = 0.015) prolonged and MEP-UL amplitudes were reduced (p = 0.008) in the HSP group. SSE should address if SSEP is a sensitive disease progression biomarker for HSP.Hypertension is becoming increasingly prevalent among the elderly. Family caregivers play an important role in caring for elderly people and empowering them to care for themselves. This study’s goal was to see how social support training for family caregivers affected changes in hypertension, total cholesterol, and high-density lipoprotein (HDL), and how such support led to the prevention of hypertension behaviors among the elderly in rural areas. This was a quasi-experimental study with 268 elderly people at risk of hypertension and their caregivers. Sixty seven pairs of elderly people and their caregivers were assigned to the intervention and control groups. Baseline data were collected in November 2020. The intervention group received the Social Support Family Caregiver Training Program (SSFCTP), while the control group received a regular program from the local health authority. The activity lasted 12 weeks, with home visits and telephone check-ups along the way, and data collection took place after the prs in providing social support, boosting confidence, and encouraging participation in caring, monitoring, and assisting the elderly in controlling blood pressure and other health issues.Fraud is a pervasive problem and can occur as fabrication, falsification, plagiarism, or theft. The scientific community is not exempt from this universal problem and several studies have recently been caught manipulating or fabricating data. Current measures to prevent and deter scientific misconduct come in the form of the peer-review process and on-site clinical trial auditors. As recent advances in high-throughput omics technologies have moved biology into the realm of big-data, fraud detection methods must be updated for sophisticated computational fraud. In the financial sector, machine learning and digit-frequencies are successfully used to detect fraud. Drawing from these sources, we develop methods of fabrication detection in biomedical research and show that machine learning can be used to detect fraud in large-scale omic experiments. Using the gene copy-number data as input, machine learning models correctly predicted fraud with 58-100% accuracy. With digit frequency as input features, the models detected fraud with 82%-100% accuracy. All of the data and analysis scripts used in this project are available at https//github.com/MSBradshaw/FakeData.When successful, the operation of local and international networks of crop seed distribution or „seed systems” ensures farmer access to seed and impacts rural livelihoods and food security. Farmers are both consumers and producers in seed systems and benefit from access to global markets. However, phytosanitary measures and seed purity tests are also needed to maintain seed quality and prevent the spread of costly weeds, pests and diseases, in some countries regulatory controls have been in place since the 1800s. Nevertheless, seed contaminants are internationally implicated in between 7% and 37% of the invasive plant species and many of the agricultural pests and diseases. We assess biosecurity risk across international seed trade networks of forage crops using models of contaminant spread that integrate network connectivity and trade volume. To stochastically model hypothetical contaminants through global seed trade networks, realistic dispersal probabilities were estimated from quarantine weed seed detectinetwork position, the number of trading connections and trade volume. Risk mitigation measures could involve the use of more comprehensive lists of regulated species, comprehensive inspection protocols, or the addition of field surveillance at farms where seed is planted.Stable isotope analyses, particularly of carbon (δ13C) and nitrogen (δ15N), are used to investigate ecological relationships among species. For marine predators, research has shown the main factors influencing their intra-specific and intra-individual isotopic variation are geographical movements and changes in the composition of diet over time. However, as the differences seen may be the result of changes in the prey items consumed, a change in feeding location or the combination of both, knowledge of the temporal and spatial consistency in the isotopic values of prey becomes crucial for making accurate inferences about predator diets. This study used an abundant marine predator, the Australasian gannet (Morus serrator), as prey sampler to investigate the annual variation in fish and squid prey isotope values over a four-year period (2012-2015) and the geographic variation between two sites with contrasting oceanographic conditions. Significant inter-annual variation was observed in δ13C and/or δ15N values of five of the eight prey species analysed. The strongest inter-annual variation in both δ13C and δ15N values occurred in 2015, which coincided with a strong El Niño-Southern Oscillation (ENSO). This may suggest a temporal fluctuation in the geographic source of prey or the origin of their nutrients. These results suggest that it is important to consider the potential significant differences in isotopic values within the prey assemblages that predators consume. This is important to improve the interpretation of marine predator isotope results when determining the influence of environmental variability on their diets.
Fixation of humeral shaft fractures with a plate and screws can endanger the neurovascular structure if proper care is not taken. No studies to our knowledge have studied the risk of iatrogenic radial nerve and/or profunda brachii artery (RNPBA) injury from each screw hole of a 4.5 mm narrow dynamic compression plate (narrow DCP). The purpose of this study is to evaluate the risk of RNPBA injury in anterolateral humeral plating with a 4.5 mm narrow DCP.
18 humeri of 9 fresh-frozen cadavers in the supine position were exposed via the anterolateral approach with 45 degrees of arm abduction. A hypothetical fracture line was marked at the midpoint of each humerus. A precontoured ten-hole 4.5mm narrow DCP was applied to the anterolateral surface of the humerus using the fracture line to position the center of the plate. All screw holes were drilled and screws inserted. The cadaver was then turned over to the prone position with 45 degrees of arm abduction, and the RNPBA exposed. The holes through in which 100% of the screw had contact with or penetrated the RNPBA were identified as dangerous screw holes, while lesser percentages of contact were defined as risky.
The relative distance ratios of the entire humeral length from the lateral epicondyle of the humerus to the 4th, 3rd, 2nd and 1st proximal holes were 0.64, 0.60, 0.56 and 0.52, respectively. The most dangerous screw hole was the 2nd proximal, in which all 18 screws had contacted or penetrated the nerve, followed by the risky 1st (12/18), 3rd (8/18) and 4th (2/18) holes.
In humeral shaft plating with the 4.5mm narrow DCP using the anterolateral approach, the 2nd proximal screw hole carries the highest risk of iatrogenic radial nerve and/or profunda brachii artery injury.
In humeral shaft plating with the 4.5mm narrow DCP using the anterolateral approach, the 2nd proximal screw hole carries the highest risk of iatrogenic radial nerve and/or profunda brachii artery injury.There is growing recognition of the burden of depression in people living with HIV/AIDS (PLWHA), associated with negative behavioural and clinical outcomes. Unfortunately, most HIV care providers in sub-Saharan Africa do not routinely provide mental health services to address this problem. This article describes the process of developing a model for integrating the management of depression in HIV care in Uganda. Theory of Change (ToC) methodology was used to guide the process of developing the model. Three successive ToC workshops were held with a multi-disciplinary group of 38 stakeholders within Wakiso district, in the Central region of Uganda. The first 2 workshops were for generating practical ideas for a feasible and acceptable model of integrating the management of depression in HIV care at all levels of care within the district healthcare system; while the third and final workshop was for consensus building. Following meaningful brainstorming and discussions, the stakeholders suggested improved mental wellbeing among PLWHA as the ultimate outcome of the program.


