Enhanced osteogenic differentiation in zoledronate-treated osteoporotic patients

Bisphosphonates are well known inhibitors of osteoclast activity and thus may be employed to influence osteoblast activity. The present study was designed to evaluate the in vivo effects of zoledronic acid (ZA) on the proliferation and osteoblastic commitment of mesenchymal stem cells (MSC) in osteoporotic patients. We studied 22 postmenopausal osteoporotic patients. Densitometric, biochemical, cellular and molecular data were collected before as well as after 6 and 12 months of ZA treatment. Peripheral blood MSC-like cells were quantified by colony-forming unit fibroblastic assay; their osteogenic differentiation potential was evaluated after 3 and 7 days of induction, respectively. Circulating MSCs showed significantly increased expression levels of osteoblastic marker genes such as Runt-related transcription factor 2 (RUNX2), and Osteonectin (SPARC) during the 12 months of monitoring time. Lumbar bone mineral density (BMD) variation and SPARC gene expression correlated positively. Bone turnover marker levels were significantly lowered after ZA treatment; the effect was more pronounced for C terminal telopeptide (CTX) than for Procollagen Type 1 N-Terminal Propeptide (P1NP) and bone alkaline phosphatase (bALP). Our findings suggest a discrete anabolic activity supported by osteogenic commitment of MSCs, consequent to ZA treatment. We confirm its anabolic effects in vivo on osteogenic precursors

Learning strategies and metacognitive awareness in medical technology students of a national university in Metropolitan Lima, 2022

El proceso de aprendizaje es uno de los factores de mayor importancia que se evalúan dentro de los modelos de calidad educativa, en los cuales influyen diversos procesos internos y externos, por ello se busca medir el grado de relación entre algunos estos procesos, tomando ello como referencia el presente estudio buscó establecer la correlación entre las estrategias de aprendizaje y la conciencia metacognitiva, siendo considerados como procesos externos e internos, respectivamente. Para ello se utilizó el cuestionario ACRA abreviado de De la Fuente y Justicia (2003), y el cuestionario de conciencia metacognitiva de Gutiérrez y Montoya (2021). La muestra estuvo conformada por 90 estudiantes de la carrera de tecnología médica de una universidad nacional de Lima metropolitana, los cuales fueron seleccionados mediante muestreo probabilístico por estratos. Al realizar la prueba de hipótesis se encontró una relación alta, directa y significante entre las variables estudiadas, lo cual indica que aquellos estudiantes que conocen una mayor cantidad de estrategias cognitivas y de control del aprendizaje y las aplican de manera adecuada logran un mayor nivel de conciencia metacognitiva favoreciendo su proceso de aprendizaje

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GATK hard filtering: tunable parameters to improve variant calling for next generation sequencing targeted gene panel data

BACKGROUND: NGS technology represents a powerful alternative to the standard Sanger sequencing in the context of clinical setting. The proprietary software that are generally used for variant calling often depend on preset parameters that may not fit in a satisfactory manner for different genes. GATK, which is widely used in the academic world, is rich in parameters for variant calling. However the self-adjusting parameter calibration of GATK requires data from a large number of exomes. When these are not available, which is the standard condition of a diagnostic laboratory, the parameters must be set by the operator (hard filtering). The aim of the present paper was to set up a procedure to assess the best parameters to be used in the hard filtering of GATK. This was pursued by using classification trees on true and false variants from simulated sequences of a real dataset data. RESULTS: We simulated two datasets, with different coverages, including all the sequence alterations identified in a real dataset according to their observed frequencies. Simulated sequences were aligned with standard protocols and then regression trees were built up to identify the most reliable parameters and cutoff values to discriminate true and false variant calls. Moreover, we analyzed flanking sequences of region presenting a high rate of false positive calls observing that such sequences present a low complexity make up. CONCLUSIONS: Our results showed that GATK hard filtering parameter values can be tailored through a simulation study based-on the DNA region of interest to ameliorate the accuracy of the variant calling

Orientus ishidae (Hemiptera: Cicadellidae): biology, direct damage and preliminary studies on apple proliferation infection in apple orchard

The mosaic leafhopper, Orientus ishidae (Matsumura), is an Asian species widespread in Europe that can cause leaf damage in wild trees and transmit disease phytoplasmas to grapevines. Following an O. ishidae outbreak reported in 2019 in an apple orchard in northern Italy, the biology and damage caused by this species to apples were investigated during 2020 and 2021. Our studies included observations on the O. ishidae life cycle, leaf symptoms associated to its trophic activity, and its capability to acquire "Candidatus Phytoplasma mali," a causal agent of Apple Proliferation (AP). The results indicate that O. ishidae can complete the life cycle on apple trees. Nymphs emerged between May and June, and adults were present from early July to late October, with the peak of flight between July and early August. Semi-field observations allowed for an accurate description of leaf symptoms that appeared as a distinct yellowing after a one-day exposure. In field experiments, 23% of the leaves were found damaged. In addition, 16-18% of the collected leafhoppers were found carrying AP phytoplasma. We conclude that O. ishidae has the potential to be a new apple tree pest. However, further studies are required to better understand the economic impact of the infestations

Hand Rehabilitation Treatment for Charcot-Marie-Tooth Disease: An Open Label Pilot Study

Charcot-Marie-Tooth neuropathy affects mainly and early the lower limbs, but hands deformities are a relevant problem, which involves the quality of life of the patients. Unfortunately, there are few studies about the evaluation of the upper limbs and very rare works about the rehabilitation. A treatment study at the moment is missing and it is important to search rehabilitation exercises to improve the dexterity and the quality of life of the patients. METHODS: We recruited 9 patients with clinical and genetic diagnosis of CMT and we proposed a rehabilitation protocol which includes muscle recruitment, stretching and proprioceptive exercises for the hand with the duration of 4 weeks (two sessions for week). We evaluated the patients before and one week after the treatment with Thumb Opposition Test, Sollerman Hand Function Scale, dynamometry (tripod pinch and hand grip). RESULTS: The rehabilitation protocol has been well tolerated and there were not dropouts. We did not observe any worsening in every scale we used. Every parameter tested showed an improvement especially in the right/dominant hand. CONCLUSION: This study demonstrates that this three phases treatment is well tolerated by patients, it is not detrimental for the hands status and perfectly reproducible by professionals. Moreover, this could be the basis for future randomized single blind projects

2,6-Diphenyl-imidazopyridine derivatives as novel prototypes of anticancer agents targeting aldehyde dehydrogenase

Aldehyde dehydrogenase (ALDH) superfamily comprises 19 different enzyme types located in specific subcellular districts, including cytosol and mitocondria. Their main function is to oxidize endogenous and exogenous aldehydes produced in human cells. In particular, isoforms 1A1, 1A2 and 1A3 catalyze the transformation of retinal into retinoic acid, which is a potent differentiation tissue factor for cellular development. Overexpression of these three isoforms in cancer stem cells (CSC), underlined in recent studies, is to date extremely important in cancer field, as it offers the chance to use these proteins both as prognostic marker and as novel targets in the fight against cancer. Here we present a novel series of 2,6-diphenyl-imidazol[1,2-a]pyridines, designed as aldehyde dehydrogenase inhibitors by means of a structured-based optimizations of a previously developed lead, GA11. The novel compounds were evaluated in vitro for their activity and selectivity against the three isoforms of the ALDH1A family, and investigated through crystallization and modeling studies for their ability to interact with the catalytic site of the 1A3 isoform. Tested in vitro on different populations of CSCs, obtained from glioma, colorectal and prostate tissue specimens, they exhibited a relevant anti-proliferative efficacy, thus paving the way for treating cancer by means of the still untapped aldehyde dehydrogenases

New Insights into the Runt Domain of RUNX2 in Melanoma Cell Proliferation and Migration

The mortality rate for malignant melanoma (MM) is very high, since it is highly invasive and resistant to chemotherapeutic treatments. The modulation of some transcription factors affects cellular processes in MM. In particular, a higher expression of the osteogenic master gene RUNX2 has been reported in melanoma cells, compared to normal melanocytes. By analyzing public databases for recurrent RUNX2 genetic and epigenetic modifications in melanoma, we found that the most common RUNX2 genetic alteration that exists in transcription upregulation is, followed by genomic amplification, nucleotide substitution and multiple changes. Additionally, altered RUNX2 is involved in unchecked pathways promoting tumor progression, Epithelial Mesenchymal Transition (EMT), and metastasis. In order to investigate further the role of RUNX2 in melanoma development and to identify a therapeutic target, we applied the CRISPR/Cas9 technique to explore the role of the RUNT domain of RUNX2 in a melanoma cell line. RUNT-deleted cells showed reduced proliferation, increased apoptosis, and reduced EMT features, suggesting the involvement of the RUNT domain in different pathways. In addition, del-RUNT cells showed a downregulation of genes involved in migration ability. In an in vivo zebrafish model, we observed that wild-type melanoma cells migrated in 81% of transplanted fishes, while del-RUNT cells migrated in 58%. All these findings strongly suggest the involvement of the RUNT domain in melanoma metastasis and cell migration and indicate RUNX2 as a prospective target in MM therapy