Image-based cell/colony analyses offer promising solutions to compensate for the lack of quality control (QC) tools for noninvasive monitoring of cultured cells, a regulatory challenge in regenerative medicine. Here, the feasibility of two image analysis algorithms, optical flow and normalised cross-correlation, to noninvasively measure cell/colony motion in human primary oral keratinocytes for screening the proliferative capacity of cells in the early phases of cell culture were examined. We applied our software to movies converted from 96 consecutive time-lapse phase-contrast images of an oral keratinocyte culture. After segmenting the growing colonies, two indices were calculated based on each algorithm. The correlation between each index of the colonies and their proliferative capacity was evaluated. The software was able to assess cell/colony motion noninvasively, and each index reflected the observed cell kinetics. A positive linear correlation was found between cell/colony motion and proliferative capacity, indicating that both algorithms are potential tools for QC.

Magnetic resonance spectroscopy quantitatively monitors biomarkers of neuron-myelin coupling (N-acetylaspartate (NAA)), and inflammation (total creatine (tCr), total choline (tCho), myo-inositol (mI)) in the brain.

Patients with Multiple Sclerosis (PwMS) display altered lipoproteins levels and function, which seem to affect disease risk and progress. Whether disease-modifying therapies affect the lipoprotein profile in PwMS has scarcely been studied.

Although Toxoplasma gondii infection in immune-competent individuals is usually asymptomatic or causes a mild flu-like illness, it may become severe and can occasionally be fatal in immune-compromised people, such as AIDS patients or pregnant women.

Assessing changes suffered by the cornea as keratoconus progresses has proven to be vital for this disease diagnosis and treatment. This study determines the corneal biometric profile in eyes considered as affected by keratoconus (KC) showing severe visual limitation, by means of in vivo 3D modelling techniques. This observational case series study evaluated new objective indices in 50 healthy and 30 KC corneas, following a validated protocol created by our research group, which has been previously used for diagnosis and characterization of KC in asymptomatic (preclinical) and mild visually impaired eyes. Results show a statistically significant reduction of corneal volume and an increase of total corneal area in the severe KC group, being anterior and posterior corneal surfaces minimum thickness points the best correlated parameters, although with no discrimination between groups. Receiving operator curves were used to determine sensitivity and specificity of selected indices, being anterior and posterior apex deviations the ones which reached the highest area under the curve, both with very high sensitivity (96.7% and 90%, respectively) and specificity (94.0% and 99.9%, respectively). The results suggest that once severe visual loss appears, anterior corneal topography should be considered for a more accurate diagnosis of clinical KC, being anterior apex deviation the key metric discriminant. This study can be a useful tool for KC classification, helping doctors in diagnosing severe cases of the disease, and can help to characterize corneal changes that appear when severe KC is developed and how they relate with vision deterioration.

The distal cholangiocarcinoma (dCCA) is associated with many factors: genes, environment, infection, etc. The current changes in biliary flora are thought to be involved in the formation of many gastrointestinal tract (GIT) diseases, like colon adenocarcinoma. Therefore we want to investigate whether the dCCA has a certain correlation with biliary microecology, and to detect specific strains.

Bacteria in biofilms are encased in an extracellular polymeric matrix that limits exposure of microbial cells to lethal doses of antimicrobial agents, leading to resistance. In Pseudomonas aeruginosa, biofilm formation is regulated by cell-to-cell communication, called quorum sensing. Quorum sensing facilitates a variety of bacterial physiological functions such as swarming motility and protease, pyoverdine, and pyocyanin productions. Peptide mix from the marine mollusc, Olivancillaria hiatula, has been studied for its antibiofilm activity against Pseudomonas aeruginosa. Microscopy and microtiter plate-based assays were used to evaluate biofilm inhibitory activities. Effect of the peptide mix on quorum sensing-mediated processes was also evaluated. Peptide mix proved to be a good antibiofilm agent, requiring less than 39 μg/mL to inhibit 50% biofilm formation. Micrographs obtained confirmed biofilm inhibition at 1/2 MIC whereas 2.5 mg/mL was required to degrade preformed biofilm. There was a marked attenuation in quorum sensing-mediated phenotypes as well. At 1/2 MIC of peptide, the expression of pyocyanin, pyoverdine, and protease was inhibited by 60%, 72%, and 54%, respectively. Additionally, swarming motility was repressed by peptide in a dose-dependent manner. These results suggest that the peptide mix from Olivancillaria hiatula probably inhibits biofilm formation by interfering with cell-to-cell communication in Pseudomonas aeruginosa.

The detection of significant moments can support the care of individuals with dementia by making visible what is most meaningful to them and maintaining a sense of interpersonal connection. We present a novel intelligent assistive technology (IAT) for the detection of significant moments based on patterns of physiological signal changes in individuals with dementia and their caregivers. The parameters of the IAT are tailored to each individual's idiosyncratic physiological response patterns through an iterative process of incorporating subjective feedback on videos extracted from candidate significant moments identified through the IAT algorithm. The IAT was tested on three dyads (individual with dementia and their primary caregiver) during an eight-week movement program. Upon completion of the program, the IAT identified distinct, personal characteristics of physiological responsiveness in each participant. Tailored algorithms could detect moments of significance experienced by either member of the dyad with an agreement with subjective reports of 70%. These moments were constituted by both physical and emotional significances (e.g., experiences of pain or anxiety) and interpersonal significance (e.g., moments of heighted connection). We provide a freely available MATLAB toolbox with the IAT software in hopes that the assistive technology community can benefit from and contribute to these tools for understanding the subjective experiences of individuals with dementia.

The study aimed to investigate resting levels of several selected growth and metabolic hormones in a group of 24 endurance-trained adolescents (aged 13-19 years) compared with 24 untrained age- and sex-matched controls, and to investigate if increased cardiac dimensions were related to these hormones at rest with emphasis on insulin-like growth factor-1 (IGF-1).

Cells with high ploidy content are common in mammalian extraembryonic and adult tissues. Cell-to-cell fusion generates polyploid cells during mammalian development and tissue regeneration. However, whether increased ploidy can be occasionally tolerated in embryonic lineages still remains largely unknown. Here, we show that pluripotent, fusion-derived tetraploid cells, when injected in a recipient mouse blastocyst, can generate diploid cells upon ploidy reduction. The generated diploid cells form part of the adult tissues in mouse chimeras. Parental chromosomes in pluripotent tetraploid cells are segregated through tripolar mitosis both randomly and nonrandomly and without aneuploidy. Tetraploid-derived diploid cells show a differentiated phenotype. Overall, we discovered an unexpected process of controlled genome reduction in pluripotent tetraploid cells. This mechanism can ultimately generate diploid cells during mouse embryo development and should also be considered for cell fusion-mediated tissue regeneration approaches.

Tc toxins use a syringe-like mechanism to penetrate the membrane and translocate toxic enzymes into the host cytosol. They are composed of three components: TcA, TcB, and TcC. Low-resolution structures of TcAs from different bacteria suggest a considerable difference in their architecture and possibly in their mechanism of action. Here, we present high-resolution structures of five TcAs from insect and human pathogens, which show a similar overall composition and domain organization. Essential structural features, including a trefoil protein knot, are present in all TcAs, suggesting a common mechanism of action. All TcAs form functional pores and can be combined with TcB-TcC subunits from other species to form active chimeric holotoxins. We identified a conserved ionic pair that stabilizes the shell, likely operating as a strong latch that only springs open after destabilization of other regions. Our results provide new insights into the architecture and mechanism of the Tc toxin family.

PIP3-dependent Rac exchanger 1 (P-Rex1) is activated downstream of G protein-coupled receptors to promote neutrophil migration and metastasis. The structure of more than half of the enzyme and its regulatory G protein binding site are unknown. Our 3.2 Å cryo-EM structure of the P-Rex1-Gβγ complex reveals that the carboxyl-terminal half of P-Rex1 adopts a complex fold most similar to those of Legionella phosphoinositide phosphatases. Although catalytically inert, the domain coalesces with a DEP domain and two PDZ domains to form an extensive docking site for Gβγ. Hydrogen-deuterium exchange mass spectrometry suggests that Gβγ binding induces allosteric changes in P-Rex1, but functional assays indicate that membrane localization is also required for full activation. Thus, a multidomain assembly is key to the regulation of P-Rex1 by Gβγ and the formation of a membrane-localized scaffold optimized for recruitment of other signaling proteins such as PKA and PTEN.

Legionella species are widespread in natural water sources and man-made aqueous environments, as well as fresh-water. The present study was conducted owing to the lack of research regarding the prevalence of Legionella spp in the water sources of Ahvaz city in southwest Iran. In this study the macrophage infectivity potentiator (mip) gene sequencing was used for identification of various Legionella species isolated from different water sources. In this study, 144 water samples were collected and inoculated on the buffered charcoal-yeast extract (BCYE) agar and modified Wadowsky-Yee (MWY) medium. The DNA was extracted from positive cultures. The Legionella species were confirmed by amplifying a 654 bp fragment of the 16S rRNA gene. The mip gene of all isolates were amplified by PCR and purified for sequencing. The mip gene sequences were analyzed by jPHYDIT software version 1. The results showed a 13.9% (20/144) prevalence of Legionella spp. in water sources of Ahvaz city, southwest Iran. Analyzing of the mip gene sequences showed, out of 20 Legionella isolates, 13 isolates (54.1%) were positive for L. pneumophila, 5 isolates (20.8%) were positive for L. worsleinsis, one isolates for each one of L. dumoffi and L. fairfieldensis, (4.1%). According to our research, the occurrence of Legionella spp in water sources could be a hazard for the health systems especially in the hospitals. The regular monitoring of these water sources by health planners may therefore be useful for decreasing the risk for Legionella spp. infections.

Purpose: Pancreatic cancer remains a major health concern; in the next 2 years, it will become the second leading cause of cancer deaths in the United States. Health disparities in the treatment of pancreatic cancer exist across many disciplines, including race and ethnicity, socioeconomic status (SES), and insurance. This narrative review discusses what is known about these disparities, with the goal of highlighting targets for equity promoting interventions. Methods: We performed a narrative review of health disparities in pancreatic cancer spanning greater than ten areas, including epidemiology, treatment, and outcome, using the PubMed NIH database from 2000 to 2019 in the Unites States. Results: African Americans (AAs) tend to present at diagnosis with later stage disease. AAs and Hispanics have lower rates of surgical resection, are more likely to be treated at low volume hospitals, and often experience higher rates of morbidity and mortality compared to white patients, although control for confounders is often limited. Insurance and SES also factor into the delivery of treatment for pancreatic cancer. Conclusion: Disparities by race and SES exist in the diagnosis and treatment of pancreatic cancer that are largely driven by race and SES. Improved understanding of underlying causes could inform interventions.

To assess the cross-sectional and prospective associations between depressive symptoms, neuroticism, and participation in breast and cervical screening in the UK.

Demand is labelled 'clinically unnecessary' when patients do not need the levels of clinical care or urgency provided by the service they contact.

The spatial and temporal dynamics of cell contractility plays a key role in tissue morphogenesis, wound healing, and cancer invasion. Here, we report a simple optochemical method to induce cell contractions in vivo during Drosophila morphogenesis at single-cell resolution. We employed the photolabile Ca2+ chelator o-nitrophenyl EGTA to induce bursts of intracellular free Ca2+ by laser photolysis in the epithelial tissue. Ca2+ bursts appear within seconds and are restricted to individual target cells. Cell contraction reliably followed within a minute, causing an approximately 50% drop in the cross-sectional area. Increased Ca2+ levels are reversible, and the target cells further participated in tissue morphogenesis. Depending on Rho kinase (ROCK) activity but not RhoGEF2, cell contractions are paralleled with non-muscle myosin II accumulation in the apico-medial cortex, indicating that Ca2+ bursts trigger non-muscle myosin II activation. Our approach can be, in principle, adapted to many experimental systems and species, as no specific genetic elements are required.

To evaluate the efficacy and safety of hip replacement and intramedullary nails for treating unstable intertrochanteric fractures in elderly patients.

To report the radiological and clinical outcomes of the modified scarf osteotomy for the treatment of hallux valgus deformity in adolescents.

We investigated a panel of 14 compounds belonging to the monothiocarbamate (MTC) and dithiocarbamate (DTC) series against the β-carbonic anhydrase 3 (β-CA3) of Mycobacterium tuberculosis (Mtb). We also evaluated all compounds for toxicity using 1-5-day post fertilisation zebrafish embryos. 11 out of the 14 investigated derivatives showed effective nanomolar or submicromolar in vitro inhibition against the β-CA3 (KIs 2.4-812.0 nM), and among them four DTCs of the series (8-10 and 12) showed very significant inhibition potencies with KIs between 2.4 and 43 nM. Out of 14 compounds screened for toxicity and safety 9 compounds showed no adverse phenotypic effects on the developing zebrafish larvae at five days of exposure. The results of in vitro inhibition and the toxicological evaluation of our study suggest that 5 compounds are suitable for further in vivo preclinical characterisation in zebrafish model.