The Cracking Behavior of Two Dental Composite Materials Validated through Multifractal Analyzes.

The aim of this in vitro study was to analyze, both experimentally and theoretically, the mechanical behavior of two types of composite materials used in restoring dental integrity. The samples of each composite resin, namely Filtek Supreme XT (3M ESPE, St. Paul, MN, USA) and Filtek Z250 (3M ESPE, St. Paul, MN, USA), were experimentally analyzed by determining their compressive strength and fracture behavior. The fractured fragments of the samples were subjected to surface evaluation by scanning electron microscopy. The compressive stress-compressive strain dependencies revealed stronger cracking of the Filtek Supreme XT composite than Filtek Z250 prior to fracture. Theoretically, the evaluation was made by means of holographic implementations of such types of composite materials. A Hooke-type equation in a differential form is presented, which links the proposed theoretical model with the experimentally obtained data.

Clostridium difficile Infections in an Emergency Surgical Unit from North-East Romania.

Background and Objectives: Colitis with Clostridium difficile is an important health problem that occurs with an intensity that varies between mild and severe. Surgical interventions are required only in fulminant forms. There is little evidence regarding the best surgical intervention in these cases. Materials and Methods: Patients with C. difficile infection were identified from the two surgery clinics from the 'Saint Spiridon' Emergency Hospital Iași, Romania. Data regarding the presentation, indication for surgery, antibiotic therapy, type of toxins, and post-operative outcomes were collected over a 3-year period. Results: From a total of 12,432 patients admitted for emergency or elective surgery, 140 (1.12%) were diagnosed with C. difficile infection. The mortality rate was 14% (20 cases). Non-survivors had higher rates of lower-limb amputations, bowel resections, hepatectomy, and splenectomy. Additional surgery was necessary in 2.8% of cases because of the complications of C. difficile colitis. In three cases, terminal colostomy was performed and as well as one case with subtotal colectomy with ileostomy. All patients who required the second surgery died within the 30-day mortality period. Conclusions: In our prospective study, the incidence was increased both in cases of patients with interventions on the colon and in those requiring limb amputations. Surgical interventions are rarely required in patients with C. difficile colitis.

PARTIAL ADRENALECTOMY - HOW FAR CAN WE GO?

Organ preservation and functional resections are the mainstays of most surgical sub-specialties at the present time. This is even more evident in endocrine surgery, where the product of secretion of these petit organs is of paramount importance. Partial adrenalectomy and cortical sparing techniques have evolved to actually compete with total adrenalectomy, the historical gold standard treatment. Much refined imaging techniques can readily identify smaller adrenal lesions that can be addressed surgically or percutaneously given the indication. The trend towards partial adrenalectomy is straightforward in bilateral disease where steroid replacement can be avoided while for unilateral disease, normal hormonal levels can be obtained. The reviewed publications offer deep insight into the advancement of partial or cortical sparing adrenal procedures from pioneering work to large cohort studies.

DNA bipedal motor walking dynamics: an experimental and theoretical study of the dependency on step size.

We present a detailed coarse-grained computer simulation and single molecule fluorescence study of the walking dynamics and mechanism of a DNA bipedal motor striding on a DNA origami. In particular, we study the dependency of the walking efficiency and stepping kinetics on step size. The simulations accurately capture and explain three different experimental observations. These include a description of the maximum possible step size, a decrease in the walking efficiency over short distances and a dependency of the efficiency on the walking direction with respect to the origami track. The former two observations were not expected and are non-trivial. Based on this study, we suggest three design modifications to improve future DNA walkers. Our study demonstrates the ability of the oxDNA model to resolve the dynamics of complex DNA machines, and its usefulness as an engineering tool for the design of DNA machines that operate in the three spatial dimensions.

Toward Interactions through Information in a Multifractal Paradigm.

In a multifractal paradigm of motion, Shannon's information functionality of a minimization principle induces multifractal-type Newtonian behaviors. The analysis of these behaviors through motion geodesics shows the fact that the center of the Newtonian-type multifractal force is different from the center of the multifractal trajectory. The measure of this difference is given by the eccentricity, which depends on the initial conditions. In such a context, the eccentricities' geometry becomes, through the Cayley-Klein metric principle, the Lobachevsky plane geometry. Then, harmonic mappings between the usual space and the Lobachevsky plane in a Poincaré metric can become operational, a situation in which the Ernst potential of general relativity acquires a classical nature. Moreover, the Newtonian-type multifractal dynamics, perceived and described in a multifractal paradigm of motion, becomes a local manifestation of the gravitational field of general relativity.

Histological Aspects and Quantitative Assessment of Ki67 as Prognostic Factors in Breast Cancer Patients: Result from a Single-Center, Cross Sectional Study.

Background and objectives: Our aim is to explore the relationship between the levels of protein encoded by Ki67 and the histopathological aspects regarding the overall survival and progression-free survival in a single university center. A secondary objective was to examine other factors that can influence these endpoints. New approaches to the prognostic assessment of breast cancer have come from molecular profiling studies. Ki67 is a nuclear protein associated with cell proliferation. Together with the histological type and tumor grade, it is used to appreciate the aggressiveness of the breast tumors. Materials and Methods: We conducted a retrospective single-institution study, at Elias University Emergency Hospital, Bucharest, Romania, in which we enrolled women with stage I to III breast cancer. The protocol was amended to include the immunohistochemistry determination of Ki67 and the histological aspects. The methodology consisted in using a Kaplan-Meier analysis for the entire sample and restricted mean survival time up to 36 months. Results: Both lower Ki67 and low tumor grade are associated with better prognosis in terms of overall survival (OS) and progression-free survival (PFS) for our patients' cohort. In our group, the histological type did not impact the time to progression or survival. Conclusions: Both overall survival and progression-free survival may be influenced by the higher value of Ki67 and less differentiated tumors. Further studies are needed in order to establish if the histologic type may impact breast cancer prognostic, probably together with other histologic and molecular markers.

A Close Encounter - Left Pneumonia and Pancreatic Tail Fistula after Laparoscopic Left Adrenalectomy.

Laparoscopic adrenalectomy is currently considered the gold standard for adrenal tumors up to 6 cm, and although with far less morbidity than the open alternative, when it comes to its complications we should not look away. The case concerns a 51-year old obese male that underwent left laparoscopic adrenalectomy for incidentaloma and developed pancreatic tail fistula. Without an evident pancreatic lesion during surgery and an uneventful early postoperative course the patient was discharged only to return 4 days later with respiratory symptoms and mild abdominal discomfort in the left upper quadrant. The CT scan diagnosed a left subphrenic fluid collection and left basal pneumonia, thus the patient underwent laparoscopic reintervention for drainage of the pancreatic fluid collection and received conventional antibiotherapy for pneumonia. The patient was discharged in good condition with the drainage tube in situ. The drainage tube was extracted 14 days later.

TOTAL THYROIDECTOMY FOR MALIGNANCY - IS CENTRAL NECK DISSECTION A RISK FACTOR FOR RECURRENT NERVE INJURY AND POSTOPERATIVE HYPOCALCEMIA? A TERTIARY CENTER EXPERIENCE IN ROMANIA.

INTRODUCTION: Surgery for thyroid cancer carries a higher risk of morbidity given the region's complicated anatomy, the setting of malignancy and extent of the surgery. AIM: To investigate the rate of complications related to the recurrent nerve and parathyroid glands lesions in patients with thyroid carcinoma that undergo thyroid surgery and lymph node dissection. PATIENTS AND METHODS: The data of 71 patients who underwent total thyroidectomy and 19 patients who underwent total thyroidectomy and central neck dissection with various associated neck dissection techniques were investigated using appropriate statistical tests. RESULTS: As expected, the rate of recurrent nerve injury observed in the neck dissection group was higher than in the total thyroidectomy group (15.7% vs. 2.8%, p=0.05). As for postoperative hypocalcemia, the rate observed in the neck dissection group, both for postoperative day 1 (p<0.0001) and day 30 (p=0.0003) was higher than in the total thyroidectomy group (68.4% vs. 19.7% postoperative day 1, 31.5% vs. 4.2% postoperative day 30). CONCLUSIONS: The risk of morbidity concerning the recurrent nerve injury and postoperative hypoparathyroidism increases with the extent of surgery. Extensive surgery may achieve proper oncologic outcomes but increases the risk of postoperative morbidity and decreases quality of life. In deciding for extensive surgery, both patient and medical team need to understand these risks.

Study of DNA Origami Dimerization and Dimer Dissociation Dynamics and of the Factors that Limit Dimerization.

Organizing DNA origami building blocks into higher order structures is essential for fabrication of large structurally and functionally diverse devices and molecular machines. Unfortunately, the yields of origami building block attachment reactions are typically not sufficient to allow programed assembly of DNA devices made from more than a few origami building blocks. To investigate possible reasons for these low yields, a detailed single-molecule fluorescence study of the dynamics of rectangular origami dimerization and origami dimer dissociation reactions is conducted. Reactions kinetics and yields are investigated at different origami and ion concentrations, for different ion types, for different lengths of bridging strands, and for the "sticky end" and "weaving welding" attachment techniques. Dimerization yields are never higher than 86%, which is typical for such systems. Analysis of the dynamic data shows that the low yield cannot be explained by thermodynamic instability or structural imperfections of the origami constructs. Atomic force microscopy and gel electrophoresis evidence reveal self-dimerization of the origami monomers, likely via blunt-end interactions made possible by the presence of bridging strands. It is suggested that this mechanism is the major factor that inhibits correct dimerization and means to overcome it are discussed.

Nucleosome Core Particle Disassembly and Assembly Kinetics Studied Using Single-Molecule Fluorescence.

The stability of the nucleosome core particle (NCP) is believed to play a major role in regulation of gene expression. To understand the mechanisms that influence NCP stability, we studied stability and dissociation and association kinetics under different histone protein (NCP) and NaCl concentrations using single-pair Förster resonance energy transfer and alternating laser excitation techniques. The method enables distinction between folded, unfolded, and intermediate NCP states and enables measurements at picomolar to nanomolar NCP concentrations where dissociation and association reactions can be directly observed. We reproduced the previously observed nonmonotonic dependence of NCP stability on NaCl concentration, and we suggest that this rather unexpected behavior is a result of interplay between repulsive and attractive forces within positively charged histones and between the histones and the negatively charged DNA. Higher NaCl concentrations decrease the attractive force between the histone proteins and the DNA but also stabilize H2A/H2B histone dimers, and possibly (H3/H4)2 tetramers. An intermediate state in which one DNA arm is unwrapped, previously observed at high NaCl concentrations, is also explained by this salt-induced stabilization. The strong dependence of NCP stability on ion and histone concentrations, and possibly on other charged macromolecules, may play a role in chromosomal morphology.

A bipedal DNA motor that travels back and forth between two DNA origami tiles.

In this work, the successful operation of a dynamic DNA device constructed from two DNA origami building blocks is reported. The device includes a bipedal walker that strides back and forth between the two origami tiles. Two different DNA origami tiles are first prepared separately; they are then joined together in a controlled manner by a set of DNA strands to form a stable track in high yield as confirmed by single-molecule fluorescence (SMF). Second, a bipedal DNA motor, initially attached to one of the two origami units and operated by sequential interaction with "fuel" and "antifuel" DNA strands, moves from one origami tile to another and then back again. The operational yield, measured by SMF, was similar to that of a motor operating on a similar track embedded in a single origami tile, confirming that the transfer across the junction from one tile to the other does not result in dissociation that is any more than that of steps on a single tile. These results demonstrate that moving parts can reliably travel from one origami unit to another, and it demonstrates the feasibility of dynamic DNA molecular machines that are made of more than a single origami building block. This study is a step toward the development of motors that can stride over micrometer distances.

Developing DNA nanotechnology using single-molecule fluorescence.

CONSPECTUS: An important effort in the DNA nanotechnology field is focused on the rational design and manufacture of molecular structures and dynamic devices made of DNA. As is the case for other technologies that deal with manipulation of matter, rational development requires high quality and informative feedback on the building blocks and final products. For DNA nanotechnology such feedback is typically provided by gel electrophoresis, atomic force microscopy (AFM), and transmission electron microscopy (TEM). These analytical tools provide excellent structural information; however, usually they do not provide high-resolution dynamic information. For the development of DNA-made dynamic devices such as machines, motors, robots, and computers this constitutes a major problem. Bulk-fluorescence techniques are capable of providing dynamic information, but because only ensemble averaged information is obtained, the technique may not adequately describe the dynamics in the context of complex DNA devices. The single-molecule fluorescence (SMF) technique offers a unique combination of capabilities that make it an excellent tool for guiding the development of DNA-made devices. The technique has been increasingly used in DNA nanotechnology, especially for the analysis of structure, dynamics, integrity, and operation of DNA-made devices; however, its capabilities are not yet sufficiently familiar to the community. The purpose of this Account is to demonstrate how different SMF tools can be utilized for the development of DNA devices and for structural dynamic investigation of biomolecules in general and DNA molecules in particular. Single-molecule diffusion-based Förster resonance energy transfer and alternating laser excitation (sm-FRET/ALEX) and immobilization-based total internal reflection fluorescence (TIRF) techniques are briefly described and demonstrated. To illustrate the many applications of SMF to DNA nanotechnology, examples of SMF studies of DNA hairpins and Holliday junctions and of the interactions of DNA strands with DNA origami and origami-related devices such as a DNA bipedal motor are provided. These examples demonstrate how SMF can be utilized for measurement of distances and conformational distributions and equilibrium and nonequilibrium kinetics, to monitor structural integrity and operation of DNA devices, and for isolation and investigation of minor subpopulations including malfunctioning and nonreactive devices. Utilization of a flow-cell to achieve measurements of dynamics with increased time resolution and for convenient and efficient operation of DNA devices is discussed briefly. We conclude by summarizing the various benefits provided by SMF for the development of DNA nanotechnology and suggest that the method can significantly assist in the design and manufacture and evaluation of operation of DNA devices.

White mulberry supplementation as adjuvant treatment of obesity.

Body weight is controlled by our genes and managed by a neuro-hormonal system, in particular by insulin and glucagon. The meristematic extract of Japanese white mulberry blocks the alpha-glucosidase and then the intestinal hydrolysis of polysaccharides, thereby reducing the glycaemic index of carbohydrates. The target of our research was to evaluate the adjuvant slimming effect of the extract of white Japanese mulberry in the dietetic treatment of some patients who are obese or overweight. 46 overweight people were enrolled and divided into two subgroups: the subjects of both subgroups were given an identical balanced diet of 1300 kcal: subjects of the subgroup alpha received 2400 mg of white Japanese mulberry extract, the subgroup b subjects receive placebo. Each subgroup was followed-up every 30 days at 30, 60 and 90 days of treatment. Both in the periodic inspections and in the final inspection measurements of body weight and waist circumference in all the subjects and thigh circumference in women only were repeated. All subjects repeated blood tests. In the subgroup alpha, weight loss was about 9 kg in 3 months, equal to approximately 10 percent of the initial weight, significantly higher than subgroup beta (P<0.0001); moreover, the plasma insulin and glucose curves of the volunteers in this subgroup at the end of the trial were lower than those performed at the time of enrolment. In the 20 women of the beta subgroup treated with only low-calorie diet and with placebo, weight reduction was globally of 3.2 kg, approximately equal to 3 percent of the initial weight; moreover, the blood glucose curves and the insulin curves showed a slight decline compared to baseline, but not so significantly as was the case for group alpha. Waist circumference and thigh circumference (in women) decreased in all participants, obviously more evidently in subjects who lost more kg. The extract of white Japanese mulberry may represent a reliable adjuvant therapy in the dietetic treatment of some patients who are obese or overweight.

Rational design of DNA motors: fuel optimization through single-molecule fluorescence.

While numerous DNA-based molecular machines have been developed in recent years, high operational yield and speed remain a major challenge. To understand the reasons for the limited performance, and to find rational solutions, we applied single-molecule fluorescence techniques and conducted a detailed study of the reactions involved in the operation of a model system comprised of a bipedal DNA walker that strides on a DNA origami track powered by interactions with fuel and antifuel strands. Analysis of the kinetic profiles of the leg-lifting reactions indicates a pseudo-first-order antifuel binding mechanism leading to a rapid and complete leg-lifting, indicating that the fuel-removal reaction is not responsible for the 1% operational yield observed after six steps. Analysis of the leg-placing reactions showed that although increased concentrations of fuel increase the reaction rate, they decrease the yield by consecutively binding the motor and leading to an undesirable trapped state. Recognizing this, we designed asymmetrical hairpin-fuels that by regulating the reaction hierarchy avoid consecutive binding. Motors operating with the improved fuels show 74% yield after 12 consecutive reactions, a dramatic increase over the 1% observed for motors operating with nonhairpin fuels. This work demonstrates that studying the mechanisms of the reactions involved in the operation of DNA-based molecular machines using single-molecule fluorescence can facilitate rationally designed improvements that increase yield and speed and promote the applicability of DNA-based machines.

Disentangling subpopulations in single-molecule FRET and ALEX experiments with photon distribution analysis.

Among the advantages of the single-molecule approach when used to study biomolecular structural dynamics and interaction is its ability to distinguish between and independently observe minor subpopulations. In a single-molecule Förster resonance energy transfer (FRET) and alternating laser excitation diffusion experiment, the various populations are apparent in the resultant histograms. However, because histograms are calculated based on the per-burst mean FRET and stoichiometry ratio and not on the internal photon distribution, much of the acquired information is lost, thereby reducing the capabilities of the method. Here we suggest what to our knowledge is a novel statistical analysis tool that significantly enhances these capabilities, and we use it to identify and isolate static and dynamic subpopulations. Based on a kernel density estimator and a proper photon distribution analysis, for each individual burst, we calculate scores that reflect properties of interest. Specifically, we determine the FRET efficiency and brightness ratio distributions and use them to reveal 1), the underlying structure of a two-state DNA-hairpin and a DNA hairpin that is bound to DNA origami; 2), a minor doubly labeled dsDNA subpopulation concealed in a larger singly labeled dsDNA; and 3), functioning DNA origami motors concealed within a larger subpopulation of defective motors. Altogether, these findings demonstrate the usefulness of the proposed approach. The method was developed and tested using simulations, its rationality is described, and a computer algorithm is provided.

Correlation between Androgen Receptor Expression and Immunohistochemistry Type as Prognostic Factors in a Cohort of Breast Cancer Patients: Result from a Single-Center, Cross Sectional Study.

BACKGROUND: We investigated the correlation between the androgen receptor (AR) and immunohistochemistry (IHC) as a prognostic factor in breast cancer (BC). AR is expressed in 60-80% of BC. METHODS: We evaluated the prognostic values of AR expression among 143 patients with BC for 36 months. The protocol was amended to measure androgen, estrogen and progesterone receptor expression by IHC and the percentage of hormone positive nuclei was quantified. We determined and quantified the Her2/neu status using IHC and in situ hybridization. The methodology consisted in using a Kaplan-Meier analysis and restricted mean survival time up to 36 months. The principal endpoints of the study were overall survival (OS) and progression free survival (PFS). RESULTS: 57% of patients (n = 82) from our group had AR+ (≥ 1%). Patients with AR+ had better OS, 35.50 vs. 33.40 months, with p = 0.027. Moreover, PFS was prolonged for patients AR+, 32.60 vs. 30.50 months, with p = 0.38. Triple negative breast cancer (TNBC) patients had lower OS and no difference was observed for PFS. CONCLUSIONS: Both OS and PFS were favorably influenced by the presence of AR. TNBC had worse outcomes compared with patients with hormonal or/and Her 2/neu positive disease in terms of OS.

Single-molecule mechanical fingerprinting with DNA nanoswitch calipers.

Decoding the identity of biomolecules from trace samples is a longstanding goal in the field of biotechnology. Advances in DNA analysis have substantially affected clinical practice and basic research, but corresponding developments for proteins face challenges due to their relative complexity and our inability to amplify them. Despite progress in methods such as mass spectrometry and mass cytometry, single-molecule protein identification remains a highly challenging objective. Towards this end, we combine DNA nanotechnology with single-molecule force spectroscopy to create a mechanically reconfigurable DNA nanoswitch caliper capable of measuring multiple coordinates on single biomolecules with atomic resolution. Using optical tweezers, we demonstrate absolute distance measurements with ångström-level precision for both DNA and peptides, and using multiplexed magnetic tweezers, we demonstrate quantification of relative abundance in mixed samples. Measuring distances between DNA-labelled residues, we perform single-molecule fingerprinting of synthetic and natural peptides, and show discrimination, within a heterogeneous population, between different posttranslational modifications. DNA nanoswitch calipers are a powerful and accessible tool for characterizing distances within nanoscale complexes that will enable new applications in fields such as single-molecule proteomics.

Observation of a train of attosecond pulses from high harmonic generation.

In principle, the temporal beating of superposed high harmonics obtained by focusing a femtosecond laser pulse in a gas jet can produce a train of very short intensity spikes, depending on the relative phases of the harmonics. We present a method to measure such phases through two-photon, two-color photoionization. We found that the harmonics are locked in phase and form a train of 250-attosecond pulses in the time domain. Harmonic generation may be a promising source for attosecond time-resolved measurements.

The evaluation of skin lesions, according to the Toven Method - an interprofessional communication tool.

BACKGROUND: In the wound care field, effective communication within the interdisciplinary staff is essential and the use of tools that foster it is important. The use of a common language among professionals in the assessment and monitoring process, along with documentation of the outcome, avoids the useless repetition of performances by professionals, with a considerable save of time. OBJECTIVE: One year after its publication, we wanted to evaluate the effectiveness of the Toven Evaluation Form as an interdisciplinary communication tool, for the assessment of cutaneous lesions, according to the Toven Method. MATERIAL: The instrument got under observation also allows the graphic recording of the characteristics of the skin lesions (size, wound conditions, undermining and perilesional skin) according to specific pre-established rules, in an easy and intuitive way for the evaluator and the rest of the multidisciplinary team. It is an integral part of the Toven File. An anonymous, specially created questionnaire containing 20 questions was used for its evaluation. METHODS: A fact-finding inquiry was initiated by recruiting a multidisciplinary sample of 101 professionals who managed skin lesions in their activity. Before completing the form, all the participants attended a two-hour training course, which took place through a lecture and a practical session. RESULTS: Sample composition: 76.2% females, 23.8% males; 63.4% nurses, 10.9% Wound Care Specialist nurses; 16,8% doctors; 8.9% physiotherapists. Of these, 69.3% had work experience >5 years. The technical quality of the instrument was considered excellent by 83.2% of professionals and good by 16.8% of them. The data recorded with the aid of the instrument were considered complete by 100% of the sample. Furthermore, 99% of the sample interviewed declared that the tool is easy to use and would be interested in including it in daily practice; 100% declares that the use of the form can facilitate its work, which can be easily understood and used by the entire multidisciplinary team and which can be an effective tool for the improvement of interdisciplinary communication.

Treatment of Peristomal granulomatosis with a Neem and Red Hypericum Oil application: Case studies.

BACKGROUND: Peristomal granulomatosis is a chronic inflammatory disease of uncertain aetiology, and a high recurrence rate. It frequently occurs in patients with enterostomy and urostomy. The most frequent type affects the mucocutaneous junction, causing bleeding and painful nodular lesions, which complicate management of the ostomy pouching system. Currently, only invasive treatments are available, consisting in cauterisation or surgical removal of the granuloma. Our objective was to evaluate efficacy of a topic mixture oil, composed by a 1:1 of extracts of Neem and Red Hypericum; amongst its many therapeutical properties, it is proven to inhibit the over-granulation process. METHOD: Two clinical cases presenting typical peristomal granulomatosis were selected. On first access after recruitment, the patients underwent an accurate nursing anamnesis, a global assessment was carried out according to the Toven Method and an assessment of peristomal sore skin according to SACS 2.0. Granulomatosis wounds were treated with the oil mixture, applied on a hydrofiber pad, secured over the wound site by means of a transparent film. This allowed the release of active ingredients while ensuring the pouching system secure adhesion. The chosen protocol consisted in 2 dressing changes per week, while monitoring the granulomatosis wound evolution by means of a TOR Form validated data form and documenting progress by taking photographs. RESULTS: Initially a regression of the inflammatory process was observed, with significant decrease of bleeding and pain. Gradually, the proliferating lesions reduced in size (both width and extent), and eventually healed completely. The product was very well tolerated, even when in contact with the stoma mucous membrane. No recurrence signs were observed either at the follow up visit 15 days from end of treatment, and in clinical case N.2 equally none were present two months after treatment. CONCLUSIONS: Compared to conventional methods which are invasive, not resolving, and not tolerated by patients, the product was demonstrated to be an innovative therapeutical solution, easy to apply, with no side effects and well-liked by patients. The excellent results obtained require further confirmation and validation through new studies on a statistically significant number of cases.