The possibility of using near-infrared spectroscopy (NIR) coupled to chemometric exploratory data processing in order to obtain a fast, cheap and nondestructive dating of human fossil bones is ...presented and discussed. The proposed approach has been applied to the differentiation of human fossil bones from two necropolises in the Middle Nile (Saggai and Geili). Principal component analysis of the spectral data after suitable pretreatment (standard normal variate + first derivative) allowed to evidence cluster of bones corresponding to the different antiquity of the samples, thus indicating that the proposed approach can lead to an accurate (although relative) dating of the fossil samples. Analysis of the PCA loading suggested that the spectral region that are most relevant for the observed differentiation is 4000–4500, 5150–5801 and 6898–7411 cm
−1
. A confirmation of the reliability of what found using NIR spectroscopy was obtained by comparing the results to those outcoming from the DTG analysis onto the same bone samples followed by PCA, according to a thermogravimetric–chemometric approach already successfully applied in previous researches. Lastly, in order to obtain a more holistic characterization of the samples, a further PCA processing was carried out after “fusion” of data from both analytical techniques.
Purpose
To compare TSH levels of hypothyroid patients treated with liquid LT4 at breakfast or 30 min before breakfast.
Patients and methods
Subjects, aged 18–75 years old, were eligible if they ...presented hypothyroidism, due to Hashimoto’s thyroiditis or after thyroidectomy for proven benign goiter. Seven hundred ninety-eight patients were recruited and enrolled in the study. Thirty-seven subjects withdrew from the trial. A total of 761 patients (mean age 46.2 ± 10.8 years) completed the study. The starting dose of LT4 was determined through clinical judgment, taking into account TSH levels, estimated residual thyroid function, age, body weight and comorbidities. All patients underwent TSH, fT4, and fT3 evaluation to verify achievement of euthyroidism with their initial fasting state assumption of LT4 after 8 weeks of therapy. If euthyroidism was not achieved, an appropriately adjusted LT4 dose was administered for 8 weeks, after which thyroid function parameters were checked again. If euthyroidism was achieved, the patients were asked to take LT4 at breakfast and hormone levels were checked again after 6 months.
Results
At the end of the study period, no significant differences in serum TSH level were observed whether LT4 was ingested at breakfast or 30 min prior in a fasting state: 2.61 ± 1.79 vs. 2.54 ± 1.86 mIU/L, respectively (
p
= 0.455).
Conclusions
This study confirms in a large set of patients that a liquid LT4 formulation can be taken directly at breakfast and potentially improve therapeutic compliance.
Recent progress in the research of mesenchymal stromal cells/multipotent stromal cells (MSC) has revealed numerous beneficial innate characteristics, suggesting potential value in an array of ...cellular therapies. MSC are easily isolated from bone marrow (BM), fat and other tissues, and are readily propagated in vitro. Transplanted/injected MSC have been shown to migrate to a variety of organs and tissues; however, sites of inflammation and pathology elicit enhanced MSC homing for tissue remodeling and repair. Tumors utilize many of the same inflammatory mediators uncovered in wound healing and likewise provide a site for preferential MSC homing. Although incorporation into the tumor microenvironment is apparent, the role of recruited MSC in the tumor microenvironment remains unclear. Some published studies have shown enhancement of tumor growth and development, perhaps through immunomodulatory and pro-angiogenic properties, while others have shown no apparent effect or have demonstrated inhibition of tumor growth and extended survival. This controversy remains at the forefront as clinical applications of MSC commence in anti-tumor therapies as well as as adjuncts to stem cell transplantation and in ameliorating graft-versus-host disease. Careful analysis of past studies and thoughtful design of future experiments will help to resolve the discrepancies in the field and lead to clinical utility of MSC in disease treatment. This review highlights the current theories of the role of MSC in tumors and explores current controversies.
Umbilical cord matrix stem (UCMS) cells are unique stem cells derived from Wharton's jelly, which have been shown to express genes characteristic of primitive stem cells. To test the safety of these ...cells, human UCMS cells were injected both intravenously and subcutaneously in large numbers into severe combined immunodeficiency (SCID) mice and multiple tissues were examined for evidence of tumor formation. UCMS cells did not form gross or histological teratomas up to 50 days posttransplantation. Next, to evaluate whether UCMS cells could selectively engraft in xenotransplanted tumors, MDA 231 cells were intravenously transplanted into SCID mice, followed by intravenous transplantation of UCMS cells 1 and 2 weeks later. UCMS cells were found near or within lung tumors but not in other tissues. Finally, UCMS cells were engineered to express human interferon beta--designated 'UCMS-IFN-beta'. UCMS-IFN-beta cells were intravenously transplanted at multiple intervals into SCID mice bearing MDA 231 tumors and their effect on tumors was examined. UCMS-IFN-beta cells significantly reduced MDA 231 tumor burden in SCID mouse lungs indicated by wet weight. These results clearly indicate safety and usability of UCMS cells in cancer gene therapy. Thus, UCMS cells can potentially be used for targeted delivery of cancer therapeutics.
The fiber-modified adenoviral vector Delta-24-RGD (D24RGD) offers vast therapeutic potential. Direct injection of D24RGD has been used to successfully target ovarian tumors in mice. However, systemic ...toxicity, especially in the liver, profoundly limits the efficacy of direct viral vector delivery. Mesenchymal stem cells (MSC) have the ability to function as a vector for targeted gene therapy because of their preferential engraftment into solid tumors and participation in tumor stroma formation. We show that MSC-guided delivery of D24RGD is specific and efficient and reduces the overall systemic toxicity in mice to negligible levels compared with D24RGD alone. In our model, we found efficient targeted delivery of MSC-D24RGD to both breast and ovarian cell lines. Furthermore, immunohistochemical staining for adenoviral hexon protein confirmed negligible levels of systemic toxicity in mice that were administered MSC-D24RGD compared with those that were administered D24RGD. These data suggest that delivery of D24RGD through MSC not only increases the targeted delivery efficiency, but also reduces the systemic exposure of the virus, thereby reducing overall systemic toxicity to the host and ultimately enhancing its value as an anti-tumor therapeutic candidate.
Background: Insulin resistance is a significant risk factor for hepatic fibrosis in patients with both non-alcoholic fatty liver disease (NAFLD) and chronic hepatitis C (CHC), either directly or by ...favouring hepatic steatosis. Several methods are available to assess insulin resistance, but their impact on this issue has never been evaluated. Aims: To determine the relative contribution of steatosis, metabolic abnormalities and insulin resistance, measured by different basal and post-load parameters, to hepatic fibrosis in CHC and in NAFLD patients. Methods: In 90 patients with CHC and 90 pair-matched patients with NAFLD, the degree of basal insulin resistance (by the homeostasis model assessment, (HOMA)) and post-load insulin sensitivity (by the oral glucose insulin sensitivity (OGIS) index) was assessed, together with the features of the metabolic syndrome according to Adult Treatment Panel III definition. Data were correlated with hepatic histopathology. Results: The prevalence of basal insulin resistance (HOMA values >75th percentile of normal) was 23.3% in CHC patients and 57.8% in NAFLD, but it increased to 28.8 and 67.8% when measured by post-load insulin resistance (OGIS <25th percentile). In a multivariate model, after adjustment for age, gender and body mass index, OGIS was a predictor of severe fibrosis in CHC and in NAFLD patients, independently of steatosis. An OGIS value below the cut-off of the 25th percentile increased the likelihood ratio of severe fibrosis by a factor of 1.5–2 and proved to be a more sensitive and generally more specific test than HOMA-R for the identification of subjects with severe fibrosis both in NAFLD and in CHC. Conclusions: Post-load insulin resistance (OGIS <9.8 mg/kg/min) is associated with severe hepatic fibrosis in both NAFLD and CHC patients, and may help identify subjects at risk of progressive disease.
This article describes a design of an field-programmable gate array (FPGA) implementation of a clock and data recovery (CDR) system. The core will be integrated in the FPGA configuration for the ...front-end electronics (FEE) board of the Jiangmen underground neutrino observatory (JUNO) experiment. The front-end will be placed on the main detector, underground and underwater, making the electronics not accessible after installation. The timing and trigger system relies on a synchronous link connection over CAT5e cable (up to 100 m long) between the front-end and the back-end electronics (BEE), where a twisted-pair is dedicated to clock-forwarding. The robustness of the recovery clock system is essential for the stability of the FPGA firmware. The proposed project is intended to improve the clock recovery operation by increasing the immunity of the link to sudden electromagnetic interference (EMI). On top of this, the core allows to free a twisted-pair in the link, since the clock can be recovered from the data and there is no more need for a clock-dedicated transmission. This will optimize the link granting the possibility to implement other features. The design is based on two components: a numerically-controlled oscillator (NCO), in order to create a controlled frequency clock signal, and a digital phase detector (PD) to match the clock frequency with the data rate. NCOs are often coupled with a digital-to-analog converter (DAC) to create direct digital synthesizers (DDSs), which are able to produce analog waveforms of any desired frequency. In the presented case instead, the NCO generates a digital clock signal of an arbitrary frequency, while the PD manages this frequency by intercepting any shifting on the relative phase between the clock and the data. A phase aligner (PA) module guarantees that data are sampled in the middle of the eye pattern, which represents the optimal sampling point. The article presents an overview of the NCO-based CDR design and implementation, together with some tests and results in order to verify the CDR reliability. Moreover, in the last section, some other possible applications of the core are illustrated.
Accurate estimation of population size is key to understanding the ecology of disease vectors, as well as the epidemiology of the pathogens they carry and to plan effective control activities. ...Population size can be estimated through mark—release—recapture (MRR) experiments that are based on the assumption that the ratio of recaptured individuals to the total captures approximates the ratio of marked individuals released to the total population. However, methods to obtain population size estimates usually consider pooled data and are often based on the total number of marked and unmarked captures. We here present a logistic regression model, based on the principle of the well-known Fisher—Ford method, specific for MRR experiments where the information available is the number of marked mosquitoes released, the number of marked and unmarked mosquitoes caught in each trap and on each day, and the geographic coordinates of the traps. The model estimates population size, taking into consideration the distance between release points and traps, the time between release and recapture, and the loss of marked mosquitoes to death or dispersal. The performance and accuracy of the logistic regression model has been assessed using simulated data from known population sizes. We then applied the model to data from MRR experiments with Aedes albopictus Skuse performed on the campus of “Sapienza” University in Rome (Italy).
Medusahead (Taeniatherum caput-medusae, Poales: Poaceae) is an annual grass native to central Asia and the Mediterranean region. It is a noxious, invasive weed in much of western North America. As ...such, it is the target of a classical biological control programme established by USDA-ARS. During explorations carried out in 2014 a new species of eriophyid mite, Aculodes altamurgiensis de Lillo & Vidovic, 2018 (Acari: Eriophyidae), was discovered on medusahead in southern Italy; it was also collected from medusahead in Bulgaria, Serbia, Turkey, and Iran in subsequent years. In the field A. altamurgensis has consistently been associated with the target weed while never having been detected from sympatric grass (Poales: Poaceae) species (e.g. Stipa austroitalica, Avena sativa, Triticum durum, T. aestivum), suggesting that A. altamurgensis is highly specific to medusahead. An open-field host-specificity test was carried out in Rome, Italy in 2016 in which an Italian population of A. altamurgensis was infested onto 11 different grass genotypes, including five crop species and five different populations of medusahead (two from Italy and three populations that are invasive in the USA). The results supported the previous observations that A. altamurgiensis is highly specific to medusahead and merits further evaluation as a candidate for biological control of this invasive grass. However, the Italian population of A. altamurgiensis showed variable colonisation rates on different medusahead populations, indicating that populations of A. altamurgiensis from other regions should also be tested to determine if they can colonise medusahead at more uniformly high rates, particularly on the targeted invasive populations in the USA.
ABSTRACTThis study was designed to evaluate the effects of hypokinesia and hypodynamia on cytoskeletal and related protein contents in human skeletal muscles. Twelve proteins: dystrophin and its ...associated proteins (DGC), dysferlin, talin, vinculin and meta‐vinculin, α‐actinin, desmin, actin, and myosin, were quantitatively analyzed during an 84‐day long‐term bedrest (LTBR). The preventive or compensatory effects of maximal resistance exercise (MRE) as a countermeasure were evaluated. Most of these proteins are involved in several myopathies, and they play an important role in muscle structure, fiber cohesion, cell integrity maintenance, and force transmission. This is the first comparison of the cytoskeletal protein contents between slow postural soleus (SOL) and mixed poly‐functional vastus lateralis (VL) human muscles. Protein contents were higher in VL than in SOL (from 12 to 94%). These differences could be mainly explained by the differential mechanical constraints imposed on the muscles, i.e., cytoskeletal protein contents increase with mechanical constraints. After LTBR, proteins belonging to the DGC, dysferlin, and proteins of the costamere exhibited large increases, higher in SOL (from 67 to 216%) than in VL (from 32 to 142%). Plasma membrane remodeling during muscle atrophy is probably one of the key points for interpreting these modifications, and mechanisms other than those involved in the resistance of the cytoskeleton to mechanical constraints may be implicated (membrane repair). MRE compensates the cytoskeletal changes induced by LTBR in SOL, except for γ‐sarcoglycan (+70%) and dysferlin (+108%). The exercise only partly compensated the DGC changes induced in VL, and, as for SOL, dysferlin remained largely increased (+132%). Moreover, vinculin and metavinculin, which exhibited no significant change in VL after LTBR, were increased with MRE during LTBR, reinforcing the pre‐LTBR differences between SOL and VL. This knowledge will contribute to the development of efficient space flight countermeasures and rehabilitation methods in clinical situations where musculoskeletal unloading is a component.
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