Effects of isotretinoin on tooth movement, orthodontically induced and non-orthodontic root resorption: A micro-CT and study.

OBJECTIVES: This study aims to investigate whether cumulative dose-dependent isotretinoin (Roaccutane®) could affect orthodontic tooth movement (OTM) and root resorption. MATERIALS AND METHODS: Ninety male Wistar Albino rats were divided into 4 groups. While, the control (SALINE), solvent (SOYBEAN) and orthodontic drug (ISOTM) groups underwent orthodontic force, the non-orthodontic drug group (ISO) did not. The rats were administrated saline, soybean oil (SBO) and isotretinoin diluted in SBO (ISOTM, ISO) for 30 days, respectively. Six rats were euthanized in each orthodontic group. Fifty grams of orthodontic force was applied to the remaining rats' first molars using the incisors as anchorage. Six more rats in each group were euthanized on the 7th, 14th and 21st days of the force application. In the ISO group, six rats were euthanized on the 37th, 44th and 51st days of administration. Six rats that were euthanized for ISOTM on the 30th day were also used for ISO to reduce the number of rats used. Micro-computed tomography (micro-CT) and histological analysis were performed. RESULTS: Independent of orthodontic force, isotretinoin caused root resorption in the apical region. However, there was no statistically significant influence of isotretinoin on OTM and orthodontically induced root resorption (OIRR). CONCLUSIONS: Despite the lack of strong evidence supporting the orthodontically induced resorptive effect of isotretinoin, this study provided findings regarding the resorptive effects of isotretinoin on non-orthodontic root resorption. Therefore, the present results underscore the importance of close monitoring during orthodontic treatment to mitigate potential root resorption in patients who use isotretinoin because of acne complaints.

Predicting the secondary dynamic mode interference phenomenon in thermoacoustic instability control.

This paper brings a novel mathematical perspective in assessing the rise of the secondary dynamic modes to prominence during the suppression of thermoacoustic instability. This phenomenon is observed by many earlier investigators; however, without a complete analytical reasoning. We consider a Rijke tube with both a passive Helmholtz resonator and an active feedback control to suppress instabilities. The core dynamics is represented as a linear time-invariant multiple time-delay system of neutral type. Parametric stability of the resulting infinite-dimensional dynamics is investigated using a recent analytical tool: cluster treatment of characteristic roots paradigm. This tool reveals the stability outlook of such systems exhaustively and non-conservatively in the parameter space of the system. First, we examine the stability with and without the Helmholtz resonator. We then select an unstable operation for the resonator-mounted Rijke tube, impose a time-delayed integral feedback control over it and reveal the stabilizing controller parameters using the cluster treatment of characteristic roots methodology. When high control gains are inappropriately selected, the new analytical procedure declares how the secondary dynamic modes of the system exhibit instability although the initially unstable mode is now stabilized. All of these stability assessments are cross-validated using experimental results from a laboratory-scale Rijke tube set-up.

A study of Helmholtz resonators to stabilize thermoacoustically driven pressure oscillations.

This paper studies passive control of thermoacoustic instabilities from an unconventional mathematical perspective. These instabilities are notoriously known to result from the complex dynamic exchange between the unsteady heat release and the acoustic waves within a finite volume such as a combustor. One possible passive control strategy is to utilize Helmholtz resonators. Under certain simplifications, the ensemble combustion dynamics including the resonators reduces to a linear-time invariant-multiple time-delayed system (LTI-MTDS). As the main contribution of the paper, an exact analytical procedure is proposed to determine the placement of the resonators to avoid instabilities. A unique mathematical paradigm, called the cluster treatment of characteristic roots, is used to accomplish this task. It declares exactly the necessary and sufficient stability conditions for an LTI-MTDS in the space of the system parameters. This concept paper is written with the mindset that this analytical tool can invite yet unexplored design capabilities for similar noise control applications where acoustic dampers are used.

An Adaptive Control Method for Ros-Drill Cellular Microinjector with Low-Resolution Encoder.

A novel control methodology which uses a low-resolution encoder is presented for a cellular microinjection technology called the Ros-Drill (rotationally oscillating drill). It is developed primarily for ICSI (intracytoplasmic sperm injection) operations, with the objective of generating a desired oscillatory motion at the tip of a micro glass pipette. It is an inexpensive setup, which creates high-frequency (higher than 500 Hz) and small-amplitude (around 0.2 deg) rotational oscillations at the tip of an injection pipette. These rotational oscillations enable the pipette to drill into cell membranes with minimum biological damage. Such a motion control procedure presents no particular difficulty when it uses sufficiently precise motion sensors. However, size, costs, and accessibility of technology to the hardware components severely constrain the sensory capabilities. Consequently, the control mission and the trajectory tracking are adversely affected. This paper presents two contributions: (a) a dedicated novel adaptive feedback control method to achieve a satisfactory trajectory tracking capability. We demonstrate via experiments that the tracking of the harmonic rotational motion is achieved with desirable fidelity; (b) some important analytical features and related observations associated with the controlled harmonic motion which is created by the low-resolution feedback control structure.

Dynamic response of micropipettes during piezo-assisted intracytoplasmic sperm injection.

In the intracytoplasmic sperm injection (ICSI) process, a piezoelectric actuator is commonly used to assist the piercing of cell membrane. The longitudinal pulses that are performed by the piezo actuator, however, cause undesired lateral vibrations at the drawn tip of the injection micropipette. This mechanism is not well understood, despite its critical role in piezo-assisted cellular microinjection. We provide an analytical model to characterize the micropipette tip vibrations under assumed base excitation arising from the piezoelectric pulses. The resulting dynamic response is determined by using the Duhamel integral method. This study quantifies the effect of fluid damping, embedded mercury, and the apparent cell membrane elasticity. We found that, in practice, a small mercury droplet filled in pipette essentially creates higher shear forces at the membrane-pipette interface. The increased shear due to underdamped eigenmodes is conceived to assist the piercing of the cell membrane.

Geometric characterization of cell membrane of mouse oocytes for ICSI.

Intracytoplasmic sperm injection (ICSI) is a broadly utilized assisted reproductive technology. A number of technologies for this procedure have evolved lately, such as the most commonly utilized piezo-assisted ICSI technique (P-ICSI). An important problem with this technique, however, is that it requires a small amount of mercury to stabilize the tip of the penetration micropipette. A completely different and mercury-free injection technology, called the rotationally oscillating drill (Ros-Drill) (RD-ICSI), was recently developed. It uses microprocessor-controlled rotational oscillations of a spiked micropipette after the pipette deforms the membrane to a certain tension level. Inappropriate selection of this initiation instant typically results in cell damage, which ultimately leads to unsuccessful ICSI. During earlier manual clinical tests of Ros-Drill, the technicians' expertise determined this instant in an ad hoc fashion. In this paper, we introduce a computer-vision-based tool to mechanize this process with the objective of maintaining the repeatability and introducing potential automation. Computer images are used for monitoring the membrane deformations and curvature variations as the basis for decision making. The main contribution of this paper is in the specifics of the computer logic to perform the monitoring. These new tools are expected to provide a practicable means for automating the Ros-Drill-assisted ICSI operation.

Rotationally oscillating drill (Ros-Drill) for mouse ICSI without using mercury.

Intracytoplasmic sperm injection (ICSI) is an important assisted reproductive technology (ART). Due to deployment difficulties and low efficiency of the earlier (conventional) version of ICSI, especially in the mouse, a piezo-assisted ICSI technique had evolved as a popular ART methodology in recent years. An important and remaining problem with this technique, however, is that it requires small amounts of mercury to stabilize the pipette tip when piezoelectric force pulses are applied. To eliminate this problem we developed and tested a completely different and mercury-free technology, called the "Ros-Drill" (rotationally oscillating drill). The technique uses microprocessor-controlled rotational oscillations on a spiked micropipette without mercury or piezo. Preliminary experimental results show that this new microinjection technology gives high survival rate (>70% of the injected oocytes) and fertilization rate (>80% of the survived oocytes), and blastocyst formation rates in early trials (approximately 50% of the survived oocytes). Blastocysts created by Ros-Drill ICSI were transferred into the uteruses of pseudopregnant surrogate mothers and healthy pups were born and weaned. The Ros-Drill ICSI technique is automated and therefore; it requires a very short preliminary training for the specialists, as evidenced in many successful biological trials. These advantages of Ros-Drill ICSI over conventional and piezo-assisted ICSI are clearly demonstrated and it appears to have resolved an important problem in reproductive biology.

New technology for cellular piercing: rotationally oscillating mu-injector, description and validation tests.

ICSI (intracytoplasmic sperm injection) procedure is one of the most commonly used cellular-injection processes. In ICSI a drawn glass pipette is pushed against the biological cell and a series of force impulses are exerted on it axially to achieve the piercing through the zona and the membrane in sequence for the ensuing injection. In most advanced applications a piezo actuator creates this impulsive forcing. This procedure presently requires a very small mercury column inside the glass pipette which is found to be helpful especially for minimizing the transverse oscillations. Despite the toxic mercury, the procedure is commonly utilized in many laboratories. Earlier investigations point out that considerable lateral tip oscillations of the injection pipette remain as the piezo-electric pulses are introduced. Such oscillations damage the cell membrane and impart adverse effects on the success rate of the injection. In this study, we introduce a novel microinjection procedure, which will remedy the shortfalls of the present technology. The highlight of this procedure is the introduction of rotational oscillations to the pipette during the drilling. These oscillations of small amplitudes (few degrees) and high enough frequencies (100 Hz and higher) are shown to create very effective piercing. The so-called Ros-Drill is a mercury-free and minimally invasive device of which the prototypes are designed and built including the relevant peripheral control hardware and software. Preliminary experimental results are presented on mouse oocytes and they are very encouraging. In the early trials on mouse oocytes, several blastocyst stage developments are reported using new drilling device. We also explain in this text the implementation protocols developed for the new technology.

New optical sensor for monitoring the micropipette motion.

A novel noncontact sensor is developed to monitor the displacements of a drawn glass pipette tip. These pipettes are commonly used in various cellular-injection applications, from in vitro fertilization to cloning. The physics of the underlying cellular-piercing process, however, is quite complex and presently not fully understood primarily due to the absence of appropriate motion sensors. A high-sensitivity noncontact sensor is needed to study this delicate microdynamics. We report here on an optical microdevice, which is developed for this objective. In the core of the sensing, properly positioned four photodiodes receive the light, which emanates from the target micropipette. Appropriate electronics and sensitivity-enhancement techniques are also utilized. The experimental results are presented from a preliminary test study on a prototype setup. These results are very encouraging in that we can already report submicrometer-level motion-detection capability.

Effect of mercury column on the microdynamics of the piezo-driven pipettes.

This study is on an interesting phenomenon concerning cellular microinjection procedures which are used for various biomedical applications, and in particular intracytoplasmic sperm injection. Recent years have brought considerable practical improvements in these operations. One of them suggests aspirating a very small quantity of mercury in the injection pipettes prior to piercing into cells. This process is proven to enhance the rate of success considerably. We present a unique study in determining the influence of mercury on the microdynamics of the pipette. The effort contains both numerical simulations and corresponding experimental verification. Ultimately we offer two critical results: (1) The mercury column increases the mass loading and expectedly decreases the natural frequencies of the pipette and (2) The lateral oscillations, which play a destructive role in piercing, are subdued in amplitude due to the mass loading of mercury. Simulation results are presented, which are also verified experimentally using high-speed digital imaging. As a consequence of these findings we also propose some alternative design directions for future microinjection devices.

Microdynamics of the piezo-driven pipettes in ICSI.

Undesirably low success rates have been reported in the intracytoplasmic sperm injection procedure. Recently a method using piezo-driven pipettes with a very small mercury column contributed substantial improvements in this process. Despite the toxicity of mercury, this new procedure is commonly utilized in many laboratories. However, there is no study available to date on the micromechanics of this procedure. The underlying principles of piercing are not clear for both cases, with and without the mercury. Presently, the pressure burst, which is caused by the abrupt axial motion of the mercury column, is attributed to this effect. Here, we take the mercury-filled pipettes and try to understand the governing physics. The findings point out the occurrence of considerable lateral tip oscillations of the injection pipette as the piezoelectric pulse train is introduced. We claim that the lateral dynamics play an important role in the piercing and should be considered to enlighten the process and the effects of the mercury. These claims are analytically studied and experimentally verified.