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Apparent Young's modulus (AYM), which reflects the fundamental mechanical property of live cells measured by atomic force microscopy and is determined by substrate stiffness regulated cytoskeletal organization, has been investigated as potential indicators of cell fate in specific cell types. However, applying biophysical cues, such as modulating the substrate stiffness, to regulate AYM and thereby reflect and/or control stem cell lineage specificity for downstream applications, remains a primary challenge during in vitro stem cell expansion. Moreover, substrate stiffness could modulate cell heterogeneity in the single-cell stage and contribute to cell fate regulation, yet the indicative link between AYM and cell fate determination during in vitro dynamic cell expansion (from single-cell stage to multi-cell stage) has not been established.

Here, we show that the AYM of cells changed dynamically during passaging and proliferation on substrates with different stiffness. Moreover, the same change in substrat reflects and contributes to hESCs and their derived progenitor cells lineage specificity maintenance, through the underlying mechanistic pathways of stiffness-induced cytoskeletal organization and the downstream YAP signaling. These findings highlighted the potential of AYM as an indicator to select suitable substrate stiffness for stem cell specificity maintenance during in vitro expansion for regenerative applications.

In summary, this study suggests that optimal substrate stiffness regulated consistent AYM during passaging and proliferation reflects and contributes to hESCs and their derived progenitor cells lineage specificity maintenance, through the underlying mechanistic pathways of stiffness-induced cytoskeletal organization and the downstream YAP signaling. These findings highlighted the potential of AYM as an indicator to select suitable substrate stiffness for stem cell specificity maintenance during in vitro expansion for regenerative applications.The increasing intensity and frequency of droughts predicted for the Mediterranean basin with ongoing climate change will impact plant communities and ecosystem functioning. This study investigated the effect of severe recurrent droughts and the role of the neighbor plant identity on the growth and survival of three abundant and co-existing species of a typical Mediterranean shrubland. Two juvenile plants, either of the same species or in all possible combinations of the two woody species Quercus coccifera and Cistus albidus and the perennial grass species Brachypodium retusum were grown together in rhizotrons under controlled watering regimes for two years. Compared to a treatment with only one drought cycle, three successive droughts reduced the relative growth rates (RGR) of shoots and roots in B. retusum, but not in woody species, and increased the mortality of the woody species, but not that of the grass. The survival of C. albidus and of B. retusum, but not of Q. coccifera, increased when the neighbor individual was a different species than when it was the same species. Our data suggest that both species composition and frequency of drought events will impact the dynamics of plant communities in Mediterranean shrublands under ongoing climate change. The abundance of dehydration sensitive woody species will likely decrease under more frequent drought events at the expense of dehydration-tolerant grass species, resulting in potentially strong changes in the functioning of these ecosystems.Environmental DNA (eDNA) detection is a valuable conservation tool that can be used to identify and monitor imperiled or invasive species and wildlife pathogens. Batrachochytrium pathogens are of global conservation concern because they are a leading cause of amphibian decline. While eDNA techniques have been used to detect Batrachochytrium DNA in the environment, a systematic comparison of extraction methods across environmental samples is lacking. In this study, we first compared eDNA extraction methods and found that a soil extraction kit (Qiagen PowerSoil) was the most effective for detecting Batrachochytrium dendrobatidis in water samples. The PowerSoil extraction had a minimum detection level of 100 zoospores and had a two- to four-fold higher detection probability than other commonly used extraction methods (e.g., QIAamp extraction, DNeasy+Qiashredder extraction method, respectively). Next, we used this extraction method on field-collected water and sediment samples and were able to detect pathogen DNA in both. While field-collected water filters were equivalent to amphibian skin swab samples in detecting the presence of pathogen DNA, the seasonal patterns in pathogen quantity were different between skin swabs and water samples. Detection rate was lowest in sediment samples. We also found that detection probability increases with the volume of water filtered. Our results indicate that water filter eDNA samples can be accurate in detecting pathogen presence at the habitat scale but their utility for quantifying pathogen loads in the environment appears limited. We suggest that eDNA techniques be used for early warning detection to guide animal sampling efforts.

Primary care physicians frequently encounter patients with supraspinatus pathology and face a difficult task of managing this subset of patients using limited imaging resources. The purpose of this study was to develop a guidance that could help primary care physicians choose appropriate imaging tests judiciously for patients with suspected supraspinatus pathology.

The imaging reports of one hundred patients who underwent ultrasound and MRI for suspected supraspinatus tendinopathy were retrospectively assessed. The supraspinatus tendon was recorded as intact, partial tear (articular or bursal), or full-thickness tear (focal or complete width). The agreement between imaging modalities was then evaluated using factors such as pathology type and age.

There was agreement between modalities in 48/100 patients (Kappa statistic = 0.30). The consistency varied with type of pathology intact tendons by ultrasound had 55.8% agreement with MRI, partial sided bursal tears 50%, partial sided articular tears 25%, and in younger patients and in patients with suspected full supraspinatus tears, based on clinical exam, with MRI as an option for further evaluation to quantify supraspinatus muscle atrophy. These patient selection recommendations will help promote mindful utilization of scarce resources.To examine antimicrobial management of brain abscess and prioritize future trials. Self-administered, Internet-based survey of practices for treatment of community-acquired bacterial brain abscess among infectious diseases (ID) specialists in France, Sweden, Australia, and Denmark during November 2019. Respondents were also asked to rank future randomized controlled trials (RCTs) from 1 (high priority) to 6 (low priority). 310 ID specialists (45% female) from France (35%), Sweden (29%), Australia (25%), and Denmark (11%) participated in the survey, primarily from university hospitals (69%) with an on-site neurosurgical department (61%). Preferred empiric intravenous (IV) antimicrobials were cefotaxime (154/273, 56%) or ceftriaxone (68/273, 25%) combined with metronidazole for a median of 4 weeks (IQR 4-6), 4 weeks (IQR 2-4), and 6 weeks (IQR 4-6) for aspirated, excised, and conservatively treated patients, respectively. Early transition to oral antimicrobials (i.e., less then 4 weeks of IV antimicrobials) was used by 134/269 (50%), whereas consolidation therapy with oral antimicrobials after a standard IV regimen (i.e., 4-8 weeks) was used by 123/264 (47%). Median prioritization scores for future RCTs were as follows 1 (IQR 1-2) for an early transition to oral antimicrobials and duration of therapy, 3 (IQR 2-4) for comparisons of antimicrobial regimens, use of adjunctive dexamethasone, and neurosurgical aspiration versus excision, and 4 (IQR 3-5) for intracavitary antimicrobial instillation and drainage, and for prophylactic anti-epileptic therapy. Willingness to include patients into RCTs reflected prioritization scores. Duration of intravenous antimicrobial treatment and use of oral antimicrobials varies substantially among ID specialists. RCTs are needed to define optimal treatment of brain abscess.We describe excessive buccal saliva (EBS) prevalence in patients with Parkinson's Disease (PD) and controls of the COPARK study, its changes between "ON" and OFF" conditions and over time, its impact on Health-related Quality of life (HRQoL), and factors associated with this condition. We studied 671 ambulatory PD patients and 177 age/sex-matched controls. We defined "sialorrhea" as UPDRS item #6 (salivation) = 1 or 2; and "drooling" as item #6 = 3 or 4. SCOPA-Aut drooling score (item #2) was also available in a subset (45%) of the cohort. HRQoL was assessed by the PDQ-39 and SF-36 scales. Twenty-four months' follow-up data were available in 401/671 patients. EBS as assessed by UPDRS was present in 38% of PD patients in the "ON" condition ("Sialorrhea" 35%; "drooling" 3%). click here There were also more PD patients reporting "drooling" than controls according to the SCOPA-Aut (49% vs 19%, p  less then  0.01). UPDRS salivation score was worse in the "OFF" vs "ON" condition in PD patients with motor fluctuations (0.90 ± 0.94 vs 0.54 ± 0.79, p  less then  0.01). UPDRS salivation score worsened after ~ 24 months of follow-up (0.47 ± 0.70 vs 0.64 ± 0.81, p  less then  0.01). Worse PDQ-39 scores were observed in PD patients with EBS in bivariate but not in multivariate analyses. EBS was directly related to PD duration and severity, male gender, dysphagia, hypomimia, and autonomic dysfunction (logistic regression). EBS was more frequent in PD patients than controls, worsened in the "OFF" condition and after ~ 24 months of follow-up, moderately affected HRQoL, and was correlated with indices of bradykinesia, dysphagia, and autonomic dysfunction.We report the two youngest cases of hepatocellular carcinoma (HCC) in non-alcoholic fatty liver disease (NAFLD) among our 119 NAFLD-HCC patients. A 36-year-old man was referred to our hospital due to a 5 cm in diameter liver tumor with elevation of α-fetoprotein and des-γ-carboxy prothrombin found at his annual health check. He had no symptoms other than 20 kg weight loss. He has been morbidly obese since he was a child. At the time of the diagnosis of NAFLD-HCC, blood chemistry showed FIB4-index 0.52, α-fetoprotein 11.1 ng/mL and des-γ-carboxy prothrombin 361 mAU/mL. He underwent curative operation. The non-cancerous lesion showed steatohepatitis with mild fibrosis. A 41-year-old man was diagnosed as having a huge liver tumor (15 cm in diameter) during medical examination for 10 kg weight loss. He had no clinical symptoms except weight loss. He has been morbidly obese since childhood. NAFLD was diagnosed at age 20. At the time of the HCC diagnosis, blood chemistry showed FIB4-index 1.42, α-fetoprotein 1974 ng/mL, and des-γ-carboxy prothrombin 82,602 mAU/mL. He underwent curative operation. We have to be aware that HCC can develop in young NAFLD patients without advanced fibrosis. Concerning tumor markers, elevation of des-γ-carboxy prothrombin was more sensitive than α-fetoprotein.

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