Time Points Research Articles

Mathematical modeling suggests heterogeneous replication of Mycobacterium tuberculosis in rabbits.

How quickly Mycobacterium tuberculosis ( Mtb ) replicates and dies in lungs of infected individuals is likely to determine the outcome of the infection - either control/clearance of the bacteria by the host immune response or progression to active disease, tuberculosis ( TB ). And yet, only a few studies, primarily in mice, rigorously estimated the rates of Mtb replication and death during an in vivo infection. We infected rabbits with a novel clinical isolate of Mtb carrying an unstable, "replication clock" plasmid and followed the dynamics of bacteria over time. Interestingly, previous methods developed to estimate Mtb replication and death rates using similar data for Mtb infection of mice failed to describe our novel data on Mtb dynamics in rabbits; we showed that heterogeneous dynamics of Mtb in semi-independent subpopulations in lungs of Mtb-infected rabbits may be one explanation of this failure of the method. Our results highlight potential differences in Mtb dynamics in different mammalian hosts and suggest ways to evaluate heterogeneity of Mtb replication and death rates in vivo.

Chronic Lithium Treatment Alters NMDA and AMPA Receptor Synaptic Availability and Dendritic Spine Organization in the Rat Hippocampus.

The mechanisms underlying the action of lithium (LiCl) in bipolar disorder (BD) are still far from being completely understood. Previous evidence has revealed that BD is characterized by glutamate hyperexcitability, suggesting that LiCl may act, at least partially, by toning down glutamatergic signaling abnormalities. In this study, taking advantage of western blot and confocal microscopy, we used a combination of integrative molecular and morphological approaches in rats exposed to repeated administration of LiCl at a therapeutic dose (between 0.6 and 1.2 mmol/l) and sacrificed at two different time points, i.e., 24 hours and 7 days after the last exposure. We report that repeated LiCl treatment activates multiple, parallel, but also converging forms of compensatory neuroplasticity related to glutamatergic signaling. More specifically, LiCl promoted a wave of neuroplasticity in the hippocampus, involving the synaptic recruitment of GluN2A-containing NMDA receptors, GluA1-containing AMPA receptors, and the neurotrophin BDNF that are indicative of a more plastic spine. The latter is evidenced by morphological analyses showing changes in dendritic spine morphology, such as increased length and head diameter of such spines. These changes may counteract the potentially negative extra-synaptic movements of GluN2B-containing NMDA receptors as well as the increase in the formation of GluA2-lacking Ca2+-permeable AMPA receptors. Our findings highlight a previously unknown cohesive picture of the glutamatergic implications of LiCl action that persist long after the end of its administration, revealing for the first time a profound and persistent reorganization of the glutamatergic postsynaptic density receptor composition and structure.

Histological and morphometrical evaluation of the urethral wall after bioresorbable stent implantation in male New Zealand White Rabbits: A preliminary study.

The aim of the study was the histological and morphometrical evaluation of the urethral wall at three time points after bioresorbable stent implantation in male New Zealand White Rabbits. The research was performed on 26 male New Zealand White rabbits aged 3-4 months and weighing 2.1-3.0 kg. Two models of bioresorbable sodium alginate-based stents were developed and implanted into the urethral lumen for one (T1), three (T3), and six weeks (T6). Sections of 5 µm thickness were cut from the urethra at intervals of 2 mm. The sliced sections were stained with hematoxylin-eosin (H&E), Van Gieson's (VG), Von Kossa, and Movat-Russell modified pentachrome (MOVAT) staining methods. The study provided valuable information for future models of urethral stents. The first model of the stent failed to fit the requirements due to inadequate mechanical properties. It curled up on itself losing the ability to adhere to the animals' urethra and was bioresorbed three weeks after implantation. The more rigid no. 2 stent was effective in widening the urethral lumen but did not biodegrade during the experiment. A comprehensive assessment of the second model's properties of biosorption and biointegration requires an extended observation of at least 12 months for an in depth morphological analysis. Stent migration is not likely to be caused solely by the mechanical properties of the urethra or urinary flow but mainly by muscle contraction of the organ wall.

Evaluation of Blood Lactate among Different Player Roles: A Pilot Study on Competitive Young Male Soccer Players.

Soccer match requires anaerobic and aerobic energetic metabolism. The aim of this pilot study was to investigate the changes in blood lactate concentration in young male soccer players in different playing roles at different time points after the soccer match. Following an initial screening of 134 young soccer athletes, 8 male athletes (average age of 15.5 ± 5 SD) were chosen for their characteristics similar to those of competitive athletes. Players were categorized as goalkeeper, central defender, central midfielder, and forward. Blood lactate concentrations were determined using a portable device at different times (10 min, 5 and 16 h) after the soccer match by a maximum effort test on a treadmill. The data were analyzed by one-way analysis of variance ANOVA, followed by Bonferroni's post-hoc test. The following results (mean ± SD) were obtained: VO2max (%) 60.33 ± 3.10; blood lactate (mM) end match (10 min) 2.17 ± 0.78, post-match-early (after 5 h) 2.2 ± 0.42, postmatch-late (16 h) 3.2 ± 0.84. ANOVA analysis indicated that the blood LA concentrations at end-match (10 min) and post-match-early (5 h) were statistically significative lower than those determined at post-match-late (16 h) (p < 0.05). These results suggest that aerobic mechanisms can also use LA as an energy source, contributing to the reduction of its blood concentration. This effect can be due to reduced maximal work during a soccer match and to the LA removal during exercise at reduced intensity. These data can provide indications for planning suitable training strategies for young male soccer players.

Multi-condition and multi-modal temporal profile inference during mouse embryonic development.

The emergence of single-cell time-series datasets enables modeling of changes in various types of cellular profiles over time. However, due to the disruptive nature of single-cell measurements, it is impossible to capture the full temporal trajectory of a particular cell. Furthermore, single-cell profiles can be collected at mismatched time points across different conditions (e.g., sex, batch, disease) and data modalities (e.g., scRNA-seq, scATAC-seq), which makes modeling challenging. Here we propose a joint modeling framework, Sunbear, for integrating multi-condition and multi-modal single-cell profiles across time. Sunbear can be used to impute single-cell temporal profile changes, align multi-dataset and multi-modal profiles across time, and extrapolate single-cell profiles in a missing modality. We applied Sunbear to reveal sex-biased transcription during mouse embryonic development and predict dynamic relationships between epigenetic priming and transcription for cells in which multi-modal profiles are unavailable. Sunbear thus enables the projection of single-cell time-series snapshots to multi-modal and multi-condition views of cellular trajectories.

Að þjóna sömu herrum en keppa þó: Sameiginlegt eignarhald á íslenskum hlutabréfamarkaði

Tilgangur þessarar greinar er að fjalla um og varpa ljósi á sameiginlegt eignarhald fyrirtækja á skráðum hlutabréfamarkaði á Íslandi og er það borið saman við umfang slíks eignarhalds í Bandaríkjunum. Nokkur umræða hefur verið um hversu fáir aðilar eiga stóra hluti í íslenskum fyrirtækjum sem eru í samkeppni við hvert annað og því er umfang þessa og þróun á íslenskum hlutabréfamarkaði greind. Sjónum er beint að þremur mörkuðum hér á landi þar sem tveir eða þrír keppinautar eru skráðir í Kauphöll Íslands. Það eru trygginga-, fjarskipta, og fasteignamarkaðir. Þá er umfang fjárfestinga lífeyrissjóða á íslenskum hlutabréfamarkaði greint á fjórum mismunandi tímapunktum; árin 2003, 2007, 2014 og 2016. Þótt erfitt sé að bera saman hlutabréfaeign milli tímabila sést að sameiginlegt eignarhald var mun minna fyrir efnahagshrunið árið 2008 en á árunum eftir hrun, bæði hjá öllum stærstu hluthöfum skráðra fyrirtækja og þá einkum lífeyrissjóðum. Um mitt ár 2016 var eign lífeyrissjóða í skráðum hlutafélögum í Kauphöll Íslands orðin umtalsverð eða um 50% af markaðsvirði allra skráðra félaga. Stærstu lífeyrissjóðirnir áttu hlut í nánast öllum hlutafélögum í kauphöllinni. Á þeim mörkuðum sem hér er fjallað um fara lífeyrissjóðirnir með yfir 45% eign í öllum skráðum fasteignafélögum, yfir 35% í öllum skráðum tryggingafélögum og yfir 50% í fjarskiptafyrirtækjum á markaði. Ekki liggur fyrir hvaða afleiðingar þetta sameiginlega eignarhald á íslenskum fyrirtækjum hefur á samkeppni og verð. Engar rannsóknir hafa enn verið gerðar á því. Bandarískar rannsóknir benda þó til þess að slíkt eignarhald hafi skaðleg áhrif á samkeppni. Í ljósi umfangs þess á Íslandi er ástæða til þess að greina áhrif þess hér og mun greinin því varpa betra ljósi á hvernig þróunin hefur verið á Íslandi síðustu tæpu tvo áratugi.

Athafnafólk í opinberri stefnumótun á óvissutímum: Hvernig hugmyndin um notendastýrða persónulega aðstoð varð að veruleika á Íslandi

Þessi rannsókn leitast við að útskýra tímamótaákvörðun í þjónustu við fatlað fólk á Íslandi. Opinber stefnumótun hefur löngum einkennst af hægfara breytingum, sem gerast í smáum skrefum. Stundum bregður þó svo við að meiriháttar breytingar verða og stefnumál, sem verið hefur baráttumál hagsmunahópa um margra ára skeið, ná fram að ganga. Dagskrárkenningar leitast við að útskýra meiriháttar stefnubreytingar með því m.a. að beina athyglinni að því hvernig og hvers vegna tiltekin málefni koma til kasta stjórnvalda á hverju tíma. Bandaríski stjórnmálafræðingurinn, John W. Kingdon, setti fyrst fram kenningu sína um straumana þrjá og glugga tækifæranna fyrir rúmum 30 árum. Nýlegar rannsóknir evrópskra stjórnmálafræðinga halda því nú fram að nálgun Kingdons geti varpað ljósi á það hvernig það pólitíska kerfi sem stefnumótunin fer fram í virkar og hvernig hegðun og aðferðir þátttakenda í ferlinu hafa áhrif. Í þessari eigindlegu rannsókn er skoðað hvernig hugmyndin um notendastýrða persónulega aðstoð (NPA) varð að veruleika á Íslandi. Rannsóknin byggir á fyrirliggjandi gögnum og viðtölum við lykilfólk um þá framvindu mála sem leiddi til ákvörðunar um að innleiða NPA hér á landi. Rannsóknin lýsir því hvernig og undir hvaða kringumstæðum NPA komst á dagskrá stjórnvalda. Niðurstöðurnar sýna hvernig breytingar á verkaskiptingu milli ríkis og sveitarfélaga gáfu tækifæri fyrir nýja hugmyndafræði sem nýttist bæði notendum, viðskiptahagsmunum og pólitískum hagsmunum. Niðurstöðurnar benda til þess að þar hafi ekki aðeins verið réttur maður á réttum stað á réttum tíma, heldur varpa þær fræðilegu ljósi á það hvað einkennir athafnafólk í opinberri stefnumótun og hvernig og hvers vegna það skiptir máli á óvissutímum í stjórnmálum.

Exploring the Sport–Alcohol Relationship: A Longitudinal Qualitative Study of Student-Athlete Drinking Following the Transition out of University

The purpose of this study was to provide new knowledge about the temporal and contextual aspects of the alcohol–sport relationship. Eight U.K. student-athletes completed the Alcohol Use Disorders Identification Test in their final year at university, 18 months, and 30 months after graduation. They also completed semistructured interviews about their drinking motives, behaviors, and life circumstances. Results showed that participants reduced their alcohol consumption after leaving university, but despite the onset of some adult responsibilities, most were still drinking at hazardous levels. After university, drinking took place with old friends, new colleagues, and new sporting teammates. At all time points, social drinking motives were the most prevalent. Findings demonstrate a relationship between alcohol and sport that is cemented at university but continues beyond it. Targeted interventions to reduce the role of alcohol in the social experience of sport are needed to support long-term athlete health.

ENLARGEMENT OF CHOROIDAL NEOVASCULARIZATION BEFORE RECURRENCE AFTER PHOTODYNAMIC THERAPY FOR PACHYCHOROID NEOVASCULOPATHY.

To investigate predictors of recurrent exudation in choroidal neovascularization (CNV) of pachychoroid neovasculopathy after photodynamic therapy (PDT). Consecutive, treatment-naïve, symptomatic patients with pachychoroid neovasculopathy with subfoveal retinal fluid treated with PDT and followed for 18 months were studied retrospectively. Choroidal neovascularization areas were calculated from optical coherence tomography angiography images obtained at various time points after the initial PDT. In 52 eyes, the subfoveal retinal fluid resolved completely three months after PDT; in 23 (44%) eyes, exudation recurred during the 18-month follow-up period. In 29 eyes with no recurrence, the mean baseline square root of the CNV area of 1.91 mm (95% CI, 0.27) decreased significantly ( P = 0.006) to 1.47 mm (95% CI, 0.16) at three months after PDT and decreased further until 12 months after PDT (mean, 1.26 mm; 95% CI, P < 0.001) and was maintained thereafter. In 23 eyes with a recurrence, the square root of the CNV area enlarged significantly ( P = 0.028) from 1.43 mm (95% CI, 0.21) at examination three months before the recurrence to 1.73 mm (95% CI, 0.18) at recurrence. Choroidal neovascularization enlargement during the follow-up period after PDT for pachychoroid neovasculopathy may predict recurrence.

Longitudinal effects of prenatal alcohol exposure on visual neurodevelopment over infancy.

Prenatal alcohol exposure (PAE) affects neurodevelopment in over 59 million individuals globally. Prior studies using dichotomous categorization of alcohol use and comorbid substance exposures provide limited knowledge of how prenatal alcohol specifically impacts early human neurodevelopment. In this longitudinal cohort study from Cape Town, South Africa, PAE is measured continuously-characterizing timing, dose, and drinking patterns (i.e., binge drinking). High-density electroencephalography (EEG) during a visual-evoked potential (VEP) task was collected from infants aged 8 to 52 weeks with prenatal exposure exclusively to alcohol and matched on sociodemographic factors to infants with no substance exposure in utero. First trimester alcohol exposure related to altered timing of the P1 VEP component over the first 6 months postnatally, and first trimester binge drinking exposure altered timing of the P1 VEP components such that increased exposure was associated with longer VEP latencies while increasing age was related to shorter VEP latencies (n = 108). These results suggest alcohol exposure in the first trimester may alter visual neurodevelopmental timing in early infancy. Exploratory individual-difference analysis across infants with and without PAE tested the relation between VEP latencies and myelination for a subsample of infants with usable magnetic resonance imaging (MRI) T1w and T2w scans collected at the same time point as EEG (n = 47). Decreased MRI T1w/T2w ratios (an indicator of myelin) in the primary visual cortex (n = 47) were linked to longer P1 VEP latencies. Results from these two sets of analyses suggest that prenatal alcohol and postnatal myelination may both separately impact VEP latency over infancy. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Variables predicting clinical remission among adults with severe asthma treated with biologic agents.

Background. Although biologic agents promise a short- to medium-term remission in asthma, it is unclear whether they can fundamentally alter disease course and achieve long-term remission. We aimed to investigate the clinical remission success of biologics in patients with severe asthma and the factors associated with remission. Methods. Adults followed-up due to severe asthma who were treated with mepolizumab or omalizumab were included in the study. Sociodemographic and clinical characteristics were reviewed. Subjects with and without clinical remission at 12 and 36 months were identified. Comparisons between the groups were made with univariate and multivariable analyses. Results. Seventy-four patients were included in the study. The mean age of subjects was 51.85 (standard deviation: 11.43) years, and 50 (67.57%) were females. The 12- and 36-month remission rates were 72.97% and 51.79%, respectively. Patients with and without remission were similar in terms of age and gender distribution. FEV1% predicted (p = 0.009) and FEV1/FVC ratio (p = 0.039) were significantly higher in those with remission at 12 months compared to those without. FEV1 (p less than 0.001), FEV1% predicted (p less than 0.001) and FEV1/FVC ratio (p = 0.004) were significantly higher in those with remission at 36 months compared to those without. Multivariable logistic regression revealed that higher FEV1% predicted was the only factor independently associated with remission for both time points. Conclusions. Omalizumab and mepolizumab provide significant clinical remission rates in severe asthma. FEV1% predicted is a variable that can independently predict clinical remission among severe asthmatics receiving biologic agents.

EgPDE-Net: Building Continuous Neural Networks for Time Series Prediction With Exogenous Variables.

While exogenous variables have a major impact on performance improvement in time series analysis, interseries correlation and time dependence among them are rarely considered in the present continuous methods. The dynamical systems of multivariate time series could be modeled with complex unknown partial differential equations (PDEs) which play a prominent role in many disciplines of science and engineering. In this article, we propose a continuous-time model for arbitrary-step prediction to learn an unknown PDE system in multivariate time series whose governing equations are parameterized by self-attention and gated recurrent neural networks. The proposed model, exogenous-guided PDE network (EgPDE-Net), takes account of the relationships among the exogenous variables and their effects on the target series. Importantly, the model can be reduced into a regularized ordinary differential equation (ODE) problem with specially designed regularization guidance, which makes the PDE problem tractable to obtain numerical solutions and feasible to predict multiple future values of the target series at arbitrary time points. Extensive experiments demonstrate that our proposed model could achieve competitive accuracy over strong baselines: on average, it outperforms the best baseline by reducing 9.85% on RMSE and 13.98% on MAE for arbitrary-step prediction.

Intraoperative landmark-based genicular nerve block versus periarticular infiltration for postoperative analgesia in total knee arthroplasty: a randomized non-inferiority trial

IntroductionGenicular nerve blocks (GNBs) are an emerging technique that have been used as a part of multimodal analgesia for total knee arthroplasty. The efficacy of intraoperative landmark-based GNBs, a recently...

Preventing evolutionary rescue in cancer.

First-line cancer treatment frequently fails due to initially rare therapeutic resistance. An important clinical question is then how to schedule subsequent treatments to maximize the probability of tumour eradication. Here, we provide a theoretical solution to this problem by using mathematical analysis and extensive stochastic simulations within the framework of evolutionary rescue theory to determine how best to exploit the vulnerability of small tumours to stochastic extinction. Whereas standard clinical practice is to wait for evidence of relapse, we confirm a recent hypothesis that the optimal time to switch to a second treatment is when the tumour is close to its minimum size before relapse, when it is likely undetectable. This optimum can lie slightly before or slightly after the nadir, depending on tumour parameters. Given that this exact time point may be difficult to determine in practice, we study windows of high extinction probability that lie around the optimal switching point, showing that switching after the relapse has begun is typically better than switching too early. We further reveal how treatment dose and tumour demographic and evolutionary parameters influence the predicted clinical outcome, and we determine how best to schedule drugs of unequal efficacy. Our work establishes a foundation for further experimental and clinical investigation of this evolutionarily-informed "extinction therapy" strategy.

Age-matched analysis of axial length growth in myopic children wearing defocus incorporated multiple segments spectacle lenses

Background/aimsDefocus incorporated multiple segments (DIMS) spectacle lenses are known to be able to inhibit axial length (AL) growth in myopic children compared with single vision (SV) spectacle lenses. However, it...

Prediction of visual field progression with serial optic disc photographs using deep learning

AimWe tested the hypothesis that visual field (VF) progression can be predicted with a deep learning model based on longitudinal pairs of optic disc photographs (ODP) acquired at earlier time...

MASH Resolution Index: development and validation of a non-invasive score to detect histological resolution of MASH

BackgroundDynamic changes in non-invasive tests, such as changes in alanine aminotransferase (ALT) and MRI proton-density-fat-fraction (MRI-PDFF), may help to detect metabolic dysfunction-associated steatohepatitis (MASH) resolution, but a combination of non-invasive...

Evaluation of infrared thermography, arterial Doppler ultrasound, and Doppler echocardiography in healthy adult dogs exposed to a single session of Whole-body vibration at different frequencies

This study aimed to evaluate the infrared thermography, arterial Doppler ultrasound, and Doppler echocardiography in healthy adult dogs exposed to a single Whole-body vibration (WBV) at different frequencies. Sixteen (16) healthy crossbreed dogs males of ages 1 to 5 years, weighing 16.3 to 24.5 kg were enrolled in the study. The dogs were exposed to a single WBV session at frequencies of 30 Hz (5 min), 40 Hz (5 min), and 50 Hz (5 min) with intervals between each frequency exposure of 10 min. The cutaneous temperature, arterial Doppler ultrasound, and Doppler echocardiography were evaluated 10 min before the WBV session, between each frequency, and 1 min after the last frequency. The cutaneous temperature of the regions of the superficial gluteal muscle and biceps femoris muscle of both hind limbs was obtained with an infrared camera. Resistive indexes of carotid and femoral arteries were determined using Doppler ultrasound, and Doppler echocardiography was used to assess the end-systolic volume and end-diastolic volume, heart rate, aortic blood flow velocity, and pulmonary artery flow velocity. Clinical parameters, complete blood count, and serum biochemical (alanine aminotransferase, creatinine, and creatine phosphokinase) were evaluated 10 min before and 60 min after the end of the WBV session. Statistically significant differences were not found in any of the variables among the time points. In conclusion, the protocol of increasing vibration frequencies (30, 40, and 50 Hz) at short-period WBV can be considered appropriate since no change occurred in the parameters evaluated.

Predictors of response in PROMIS-global in a chronic low back pain specialty clinic: STarTBack and chronic overlapping pain conditions.

Tools, such as the STarTBack Screening Tool (SBT), have been developed to identify risks of progressing to chronic disability in low back pain (LBP) patients in the primary care population. However, less is known about predictors of change in function after treatment in the specialty care population. We pursued a retrospective observational cohort study involving LBP patients seen in a multidisciplinary specialty clinic to assess which features can predict change in function at follow-up. The SBT was administered at initial visit, and a variety of patient characteristics were available in the chart including the presence of chronic overlapping pain conditions (COPCs). Patient Reported Outcomes Measurement Information System-10 (PROMIS-10) global physical health (PH) and global mental health (MH) were measured at baseline and at pragmatic time points during follow-up. Linear regression was used to estimate adjusted associations between available features and changes in PROMIS scores. 241patients were followed for a mean of 17.0 ± 7.5months. Mean baseline pain was 6.7 (SD 2.1), PROMIS-10 global MH score was 44.8 (SD 9.3), and PH score was 39.4 (SD 8.6). 29.7% were low-risk on the SBT, 41.8% were medium-risk, and 28.5% were high-risk. Mean change in MH and PH scores from baseline to the follow-up questionnaire were 0.86 (SD 8.11) and 2.39 (SD 7.52), respectively. Compared to low-risk patients, high-risk patients had a mean 4.35points greater improvement in their MH score (p= 0.004) and a mean 3.54points greater improvement in PH score (p= 0.006). Fewer COPCs also predicted greater improvement in MH and PH. SBT and the presence of COPC, which can be assessed at initial presentation to a specialty clinic, can predict change in PROMIS following treatment. Effort is needed to identify other factors that can help predict change in function after treatment in the specialty care setting.

Trehalose Improved 20-min Cycling Time-Trial Performance After 100-min Cycling in Amateur Cyclists.

Carbohydrate (CHO) supplementation during endurance exercise can improve performance. However, it is unclear whether low glycemic index (GI) CHO leads to differential ergogenic and metabolic effects compared with a standard high GI CHO. This study investigated the ergogenic and metabolic effects of CHO supplementation with distinct GIs, namely, (a)trehalose (30g/hr), (b)isomaltulose (30g/hr), (c)maltodextrin (60g/hr), and (d)placebo (water). In this double-blind, crossover, counterbalanced, placebo-controlled study, 13 male cyclists cycled a total of 100min at varied exercise intensity (i.e.,10-min stages at 1.5, 2.0, and 2.5W/kg; repeated three times plus two 5-min stages at 1.0W/kg before and after the protocol), followed by a 20-min time trial on four separated occasions. Blood glucose and lactate (every 20min), heart rate, and ratings of perceived exertion were collected throughout, and muscle biopsies were taken before and immediately after exercise. The results showed that trehalose improved time-trial performance compared with placebo (total work done 302 ± 39 vs. 287 ± 48kJ; p = .01), with no other differences between sessions (all p ≥ .07). Throughout the 100-min protocol, blood glucose was higher with maltodextrin compared with the other supplements at all time points (all p < .05). Heart rate, ratings of perceived exertion, muscle glycogen content, blood glucose, and lactate were not different between conditions when considering the 20-min time trial (all p > .05). Trehalose supplementation throughout endurance exercise improved cycling performance and appears to be an appropriate CHO source for exercise tasks up to 2hr. No ergogenic superiority between the different types of CHO was established.