Development and characterization of nanobody against envenomation by Naja naja oxiana.

Snakebites are considered a significant health issue. Current antivenoms contain polyclonal antibodies, which vary in their specificity against different venom components. Development and characterization of next generation antivenoms including nanobodies against Naja naja oxiana was the main aim of this study. Crude venom was injected into the Sephadex G50 filtration gel chromatography column and then toxic fractions were obtained. Then the corresponding fraction was injected into the HPLC column and the toxic peaks were identified. N. naja oxiana venom was injected into a camel and specific nanobodies screening was performed against the toxic peak using phage display technique. The obtained results showed that among the 12 clones obtained, N24 nanobody was capable of neutralizing P1, the most toxic peak obtained from HPLC chromatography. The molecular weight of P1 was measured with a mass spectrometer and was found to be about seven kDa. The results of the neutralization test of crude N. naja oxiana venom with N24 nanobody showed that 250 µg of recombinant nanobody could neutralize the toxic effects of 20 µg equivalent to LD50 × 10 of crude venom in mice. The findings indicate the potential of the developed nanobody to serve as a novel antivenom therapy.

Protective Effects of the Aqueous Extract of Malva sylvestris Plant against the Lethality and Histopathological Damage in Experimental Envenoming of Hemiscorpius lepturus Venom in Balb/c Mice.

INTRODUCTION: Hemiscorpius lepturus envenomation is a serious health problem in the southern provinces of Iran. The antiserum produced in Iran to counteract this scorpion venom is not entirely effective due to the risk of anaphylactic shock and other adverse effects. METHODS: Therefore, more efficient alternatives to treat patients deserve attention, and plants are extensively good candidates to be studied. This study aimed to assess the potential of the aqueous fraction of Malva sylvestris in inhibiting the toxic effects of H. lepturus venom. Injection of sub-lethal dose of H. lepturus venom leads to severe tissue damage in vital organs including the kidney, liver, heart and intestine, after 24 hours. RESULTS: By injecting 80 mg of the aqueous extract of M. sylvestris into the peritoneum helped treat the damaged tissues caused by H. lepturus venom in mice. CONCLUSION: Thus, Malva sylvestris could serve as an alternative treatment for scorpion sting envenomation and may be used as a drug to neutralize relevant toxic effects in patients stung by H. lepturus.

CTXP, The Major Cobra Toxin Peptide from Naja Naja Oxiana Venom; A Promising Target for Antivenom Agent Development.

BACKGROUND AND OBJECTIVE: Snakebite envenoming is a serious public health issue causing more than 135,000 annual deaths worldwide. Naja Naja Oxiana is one of the most clinically important venomous snakes in Iran and Central Asia. Conventional animal-derived polyclonal antibodies are the major treatment of snakebite envenoming. Characterization of venom components helps to pinpoint the toxic protein responsible for clinical manifestations in victims, which aids us in developing efficient antivenoms with minimal side effects. Therefore, the present study aimed to identify the major lethal protein of Naja Naja Oxiana by top-down proteomics. METHODS: Venom proteomic profiling was performed using gel filtration (GF), reversed-phase (RP) chromatography, and intact mass spectrometry. The toxicity of GF-, and RP-eluted fractions was analyzed in BALB/c mice. The rabbit polyclonal antisera were produced against crude venom, GF fraction V (FV), and RP peak 1 (CTXP) and applied in neutralization assays. RESULTS: Toxicity studies in BALB/c identified FV as the major toxic fraction of venom. Subsequently, RP separation of FV resulted in eight peaks, of which peak 1, referred to as "CTXP" (cobra toxin peptide), was identified as the major lethal protein. In vivo neutralization assays using rabbit antisera showed that polyclonal antibodies raised against FV and CTXP are capable of neutralizing at least 2-LD50s of crude venom, FV, and CTXP in all tested mice. CONCLUSION: Surprisingly, the Anti-CTXP antibody could neutralize 8-LD50 of the CTXP peptide. These results identified CTXP (a 7 kDa peptide) as a potential target for the development of novel efficient antivenom agents.

Evaluation of health-related quality of life before and after total hip arthroplasty in the elderly in Iran: a prospective cohort study.

BACKGROUND: Owing to the direct impact of total hip arthroplasty (THA) on health-related quality of life (HRQOL) and the higher prevalence of THA in the elderly, this study aimed to compare HRQOL before, and after THA in the Iranian elderly. METHODS: The present prospective cohort study was performed on 161 THA candidates. Demographic data were extracted from records of patients. Before, 6, and 12 months after THA, a Short Form 36 health survey (SF-36) was used to assess HRQOL. Before THA, 6 and 12 months after THA, Physical (PCS), and mental component scores (MCS) were obtained from a hundred separately for each subscale of the questionnaire. The Paired t-test was used to compare HRQOL before and after THA. RESULTS: Both 6 and 12 months after THA, HRQOL was significantly increased compared to previous THA (P = 0.001). In the first half-year after THA, vitality and emotional state were not different from pre-surgery. However, 12 months after THA, these two subscales also were significantly improved. Although, 6 months after THA, the PCS has dramatically gone up compared to the previous THA (P = 0.012), despite MCS was remained steady. Nonetheless, by comparison with the before surgery, 12 months after THA, MSC notably improved (P = 0.048). CONCLUSION: HRQOL was appreciably improved by the THA in the elderly after 12 months. The improvement in HRQoL in the first 6 months after THA is related to the promotion in the physical aspect (PCS score), and in the second 6 months after THA is related to the promotion in the psychological aspect (MCS score).

Static Modeling of Soft Reinforced Bending Actuator Considering External Force Constraints.

Soft robots are utilized in various operations such as rehabilitation, manipulation, and locomotion. These robots are sometimes excited by means of rubber based bending actuators, which are highly nonlinear and hyperelastic. In addition, in contrast to robots with rigid links and common actuators, continuous deformation of soft bending actuators in the presence of external forces makes the modeling more complicated. Thus, introducing a proper mathematical framework that accurately describes mechanical behavior of these actuators is still a challenge. In this research study, an analytical static model based on the Neo-Hookean material model is proposed. By resorting to the proposed model, a nonlinear relation between the actuator shape and inlet actuation pressure is extracted. Next, by means of the Euler-Bernoulli beam theory, the effect of external forces on the actuator configuration is investigated. Finally, experimental results are presented to validate the proposed theoretical model. In this regard, first, the actuator nonlinear behavior in a free motion is appropriately verified. Then, the actuator configuration, in the presence of two conventional external forces, called following and fixed direction, is analyzed.

A compact valveless pressure control source for soft rehabilitation glove.

BACKGROUND: Soft pneumatic robots have shown great promises in hand rehabilitation systems as alternatives to conventional rigid systems. However, their application is limited to clinical rehabilitation programs due to their dependency on large-sized compressors as air suppliers. This disadvantage triggered the search for compact portable pneumatic sources. METHOD: A compact valveless pneumatic source to control the bending angle of a soft actuator is proposed in this paper. The source incorporates two series of serially connected commercially available microcompressors to provide additional pressure and flowrate in two directions. In the proposed design, an inner-loop controller, controls the output characteristics of the source while an outer-loop controller handles the trajectory tracking of the angular position. RESULTS: Experimental results show that the source is capable of providing up to 160 kPa of output. The controller is able to track up to 2 rad/sec sinusoidal trajectory with a maximum 0.066 rad root-mean-square error. CONCLUSION: Experimental measurements showed satisfactory results in the maximum ratings and tracking errors whilst relatively low average power was consumed by eliminating control valves.

Position and Force Control of a Soft Pneumatic Actuator.

Recent advances in robotic systems have increased the need for various kinds of robots in many fields, such as aerospace and medical. Utilizing hard robots in such fields can cause irrecoverable damages; therefore, scientists have taken inspiration from nature to build robots with soft bodies. In this article, a soft pneumatic actuator that reshapes in the x-y plane is controlled. This continuous soft robot uses air pressure as actuation to control the end point position of the robot through curvature motion, and the force applied to a load cell. System identification approaches are used to model the behavior of the soft actuator, simulate time response, and design a suitable controller. After modeling the behavior of the actuator, a cascaded control strategy is used to control the robot. To increase precision in tracking control, using the Prandtl-Ishlinskii (P-I) method, existing hysteresis in the response of the system is measured, simulated, and then compensated using the inverse P-I method. The performance of the system, in the presence of the designed control architecture, is simulated and implemented on an experimental setup in the laboratory. Finally, tracking results are presented and compared for this soft actuator.

Development of a human scFv antibody targeting the lethal Iranian cobra (Naja oxiana) snake venom.

Snakebite is one of the health concerns worldwide. Naja oxiana is one of the venomous snakes with a high mortality rate. Anti-serum therapy is the only treatment of the victims. However, in some cases, antiserum injection leads to some side effects in host like serum sickness and anaphylactic shock. It is crucial to develop a neutralizing agent with low side effects. The human antibody library (non-immunized library) was used to isolate specific antibodies against N.oxiana venom components. Four rounds of biopanning were performed to enrich scFv-displaying phages against the venom of N. oxiana. Enrichment of scFv-displaying phages against N. oxiana venom was analyzed by polyclonal Enzyme-Linked Immunosorbent Assay (ELISA). Specific antibody fragments against N. oxiana venom were selected through monoclonal ELISA, and were expressed in E. coli bacterial cells. Purification of the selected clones was performed by using nickel affinity chromatography. Neutralization and protective capacity of specific antibody fragments were analyzed in C57BL/6 mice (i.v. injection). Results of biopanning and polyclonal ELISA demonstrate a successful enrichment process. Five specific antibody fragments with the highest signal in monoclonal ELISA were selected, expressed, and purified. The purity of expressed antibody fragments was monitored by SDS-PAGE and Western blot. The selected antibody fragments were able to neutralize two LD50 of N. oxiana venom and protected all mice when injected 15 min post-envenomation. The data indicate that such selected antibodies are promising tools for further studies and in the development of novel protective agents against N. oxiana venom.

Modeling a Telemedicine Screening Program for Diabetic Retinopathy in Iran and Implementing a Pilot Project in Tehran Suburb.

PURPOSE: To model a community-based telescreening program for diabetic retinopathy (DR) in Iran and to implement a pilot project at the Iranian Diabetes Society (IDS) branch in a Tehran suburb. METHODS: In this mixed model study, a web application called the "Iranian Retinopathy Teleophthalmology Screening (IRTOS)" was launched. The educational course for DR screening was established for general practitioners (GPs). Registered patients in IDS branch were recalled for fundus photography; images were transferred to the reading center via IRTOS to be graded by GPs, and patients were informed about the results via mobile messaging. All images were independently reviewed by a retina specialist as the gold standard. Patients who required further assessment were referred to an eye hospital. RESULTS: Overall, 604 subjects with diabetes were screened; of these, 50% required referral. The sensitivity and specificity for diagnosis of any stage of DR by trained GPs were 82.8% and 86.2%, respectively, in comparison to the gold standard. The corresponding values for detecting any stage of diabetic macular edema (DME) were 63.5% and 96.6%, respectively. CONCLUSIONS: Telescreening was an effective method for detecting DR in a Tehran suburb. This screening model demonstrated its capacity for promoting diabetic eye care services at the national level. However, the sensitivity for detecting DME needs to be improved by modifying the referral pathway and promoting the skill of GPs.

Adaptive super-twisting observer for fault reconstruction in electro-hydraulic systems.

An adaptive-gain super-twisting sliding mode observer is proposed for fault reconstruction in electro-hydraulic servo systems (EHSS) receiving bounded perturbations with unknown bounds. The objective is to address challenging problems in classic sliding mode observers: chattering effect, conservatism of observer gains, strong condition on the distribution of faults and uncertainties. In this paper, the proposed super-twisting sliding mode observer relaxes the condition on the distribution of uncertainties and faults, and the gain adaptation law leads to eliminate observer gain overestimation and attenuate chattering effects. After using the equivalent output-error-injection feature of sliding mode techniques, a fault reconstruction strategy is proposed. The experimental results are presented, confirming the effectiveness of the proposed adaptive super-twisting observer for precise fault reconstruction in electro-hydraulic servo systems.

Leakage fault detection in Electro-Hydraulic Servo Systems using a nonlinear representation learning approach.

Electro-Hydraulic Servo Systems (EHSS) are employed as actuators to track the desired trajectory and exert force in heavy-duty industrial applications. The EHSS is often prone to problems such as leakage and actuator seal damage during the course of its utilization. These faults which cannot be directly detected from current sensor values, can eventually result in complications and degrade control performance. The goal of this research is to use representation learning concepts to detect these faults with decreased complexity. The objective is to find a nonlinear mapping to transform raw data into another space in which classification becomes easier. The data are driven from the hydraulic supply pressure signal. To find the mapping, a custom-built optimization algorithm is proposed along with a suitable cost function to carry out the search for the new representation. The performance of the resulting transformation is tested in an experimental setting to show the merits of the proposed method.

Antiadhesive and cytotoxic effect of Iranian Vipera lebetina snake venom on lung epithelial cancer cells.

BACKGROUND: Cancer is one of the major health problems worldwide. Hence, finding potent therapeutics from natural sources seems necessary. Snake venom of Vipera lebetina contains potential component with anticancer activities such as antiproliferation, migration, invasion, adhesion, and angiogenesis effect. Evaluation of cytotoxic and antiadhesive effect of V. lebetina venom on lung epithelial cancer tumor cell (TC-1) was the main aim of this study. MATERIALS AND METHODS: Here, we purified snake venom of V. lebetina by fast protein liquid chromatography (FPLC) using Sephacryl S-200 hr column. The fractions collected and evaluated by SDS-PAGE analysis. The cytotoxicity and antiadhesive effect of crude venom and fractions on TC-1 cells were demonstrated using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and adhesion assay, respectively. RESULTS: Our results showed six fractions in FPLC diagram. V. lebetina crude venom and fractions showed dose-dependent cytotoxic effect on TC-1 cells. Fractions 2 and 5 showed high cytotoxic effect with high IC50 value (IC50 = 6 µg/ml for fraction 2 and IC50 = 7.3 µg/ml for fraction 5). Fractions 2 and 5 selected for analysis antiadhesive effect on TC-1 cells. Furthermore, our results showed that both fractions 2 and 5 had antiadhesive effect on TC-1 cells. CONCLUSION: Because of potent cytotoxic and antiadhesive effect of V. lebetina fractions on lung epithelial cancer cell line, it could be promising tools for further analysis as anticancer therapeutic development.

A three-dimensional large deformation model for soft tissue using meshless method.

BACKGROUND: Recently, a great number of studies have been carried out to model soft tissue deformation in contact with surgical instruments to aid the development of surgical simulators. Precise methods to model the soft tissue such as the Finite Element Method (FEM) lack accuracy in large deformations. METHODS: An innovative meshless method is used, which has high precision and is applicable to large deformations. The meshless simulation method is implemented for a 2D beam and a 3D cube. Experiments are conducted for two silicone-gel samples to verify the correctness of the method. RESULTS: The meshless results in 2D and 3D show better accuracy for large deformations in comparison with the FEM. This method is used to model human organs such as liver and gallbladder. CONCLUSION: It is concluded that the proposed model exhibits good accuracy as well as speed. Thus, it seems promising to be employed in surgical simulators. Copyright © 2015 John Wiley & Sons, Ltd.

An energy-saving nonlinear position control strategy for electro-hydraulic servo systems.

The electro-hydraulic servo system (EHSS) demonstrates numerous advantages in size and performance compared to other actuation methods. Oftentimes, its utilization in industrial and machinery settings is limited by its inferior efficiency. In this paper, a nonlinear backstepping control algorithm with an energy-saving approach is proposed for position control in the EHSS. To achieve improved efficiency, two control valves including a proportional directional valve (PDV) and a proportional relief valve (PRV) are used to achieve the control objectives. To design the control algorithm, the state space model equations of the system are transformed to their normal form and the control law through the PDV is designed using a backstepping approach for position tracking. Then, another nonlinear set of laws is derived to achieve energy-saving through the PRV input. This control design method, based on the normal form representation, imposes internal dynamics on the closed-loop system. The stability of the internal dynamics is analyzed in special cases of operation. Experimental results verify that both tracking and energy-saving objectives are satisfied for the closed-loop system.

A switched energy saving position controller for variable-pressure electro-hydraulic servo systems.

The electro-hydraulic servo system (EHSS) demonstrates a relatively low level of efficiency compared to other available actuation methods. The objective of this paper is to increase this efficiency by introducing a variable supply pressure into the system and controlling this pressure during the task of position tracking. For this purpose, an EHSS structure with controllable supply pressure is proposed and its dynamic model is derived from the basic laws of physics. A switching control structure is then proposed to control both the supply pressure and the cylinder position at the same time, in a way that reduces the overall energy consumption of the system. The stability of the proposed switching control system is guaranteed by proof, and its performance is verified by experimental testing.