Assistive Robotics for Upper Limb Physical Rehabilitation:A Systematic Review and Future Prospects

Physical assistive robotics are oriented to support and improve functional capacities of people.In physical rehabilitation,robots are indeed useful for functional recovery of affected limb.However,there are still open questions related to technological aspects.This work presents a systematic review of upper limb rehabilitation robotics in order to analyze and establish technological challenges and future directions in this area.A bibliometric analysis was performed for the systematic literature review.Literature from the last six years,conducted between August 2020 and May 2021,was reviewed.The methodology for the literature search and a bibliometric analysis of the metadata are presented.After a preliminary search resulted in 820 articles,a total of 66 articles were included.A concurrency network and bibliographic analysis were provided.And an analysis of occurrences,taxonomy,and rehabilitation robotics reported in the literature is presented.This review aims to provide to the scientific community an overview of the state of the art in assistive robotics for upper limb physical rehabilitation.The literature analysis allows access to a gap of unexplored options to define the technological prospects applied to upper limb physical rehabilitation robotics.

水下蝶泳打腿技术的理论与实践——运动学特征,涡流的产生以及在出发、转身、划水过程中的应用

从理论上介绍了鱼类摆尾技术的流体力学研究成果,并在实践中与运动员蝶泳腿技术分析相结合,指出水下蝶泳打腿(UUS,亦称水下波动游泳)的运动学、动力学特征以及在游泳出发、转身和划水过程中的应用。

Use of subcutaneous tocilizumab to prepare intravenous solutions for COVID-19 emergency shortage:Comparative analytical study of physicochemical quality attributes

COVID-19,a disease caused by the novel coronavirus SARS-Co V-2,has produced a serious emergency for global public health,placing enormous stress on national health systems in many countries.Several studies suggest that cytokine storms(interleukins)may play an important role in severe cases of COVID-19.Neutralizing key inflammatory factors in cytokine release syndrome(CRS)could therefore be of great value in reducing the mortality rate.Tocilizumab(TCZ)in its intravenous(IV)form of administration-Ro Actemra?20 mg/m L(Roche)-is indicated for treatment of severe CRS patients.Preliminary investigations have concluded that inhibition of IL-6 with TCZ appears to be efficacious and safe,with several ongoing clinical trials.This has led to a huge increase in demand for IV TCZ for treating severe COVID-19 patients in hospitals,which has resulted in drug shortages.Here,we present a comparability study assessing the main critical physicochemical attributes of TCZ solutions used for infusion,at 6 mg/m L and 4 mg/m L,prepared from Ro Actemra?20 mg/m L(IV form)and from Ro Actemra?162 mg(0.9 m L solution pre-filled syringe,subcutaneous(SC)form),to evaluate the use of the latter for preparing clinical solutions required for IV administration,so that in a situation of shortage of the IV medicine,the SC form could be used to prepare the solutions for IV delivery of TCZ.It is important to remember that during the current pandemic all the medicines are used off-label,since none of them has yet been approved for the treatment of COVID-19.

Electromagnetic Field Released in Collision-Impact Events Generate in the Matrix Interface Fractal Scalable Invariant Geometric Triangular Chiral Hexagonal Structures

In biology, cancer is the most beautiful natural model of a chaotic system, which under uncontrolled proliferations, generates extreme disorder that finally causes intercellular collisions. The authors have described and documented fractal self-assembly of geometric triangular chiral hexagonal crystal-like complex organizations (GTCHC) and interface comet tail effect patterns in cancer processes. According to this novel observation cancer incorporates a real visualization world with a great surprising finding in biology, physics, and geology. This visualization platform literally allows us to see what would otherwise remain completely invisible. From theory to practice this irreducible geometric matrix allowed us to identify in geology, real measurable green infrared-electromagnetic stripe line in interface with hexagonal geomorphic pattern, triangular chiral pyramidal rock structures, geology well defined mirror images, template platform to bio signature characterization of ancestral primitive polar head-tail organization, embryoid and human-like shape pattern embedded as giant fossils in rocks that have never been seen before. Electromagnetic field released in collision-impact events generate in the matrix interphase fractal scalable invariant order of geometric triangular chiral hexagonal structures. The laws of biology and geology can finally be redirected to the laws of physics;specifically magnetic fields create a new kind of classification based on these fractal structural similarities of the relationship. Further interdisciplinary collaboration must be carried out to study these geometric self-assembly geological structures, ancient sediments and rocks that could provide insights into antecedents of life.

Study and ICH validation of a reverse-phase liquid chromatographic method for the quantification of the intact monoclonal antibody cetuximab

Cetuximab （CTX） is a potent chimeric mouse/human monoclonal antibody （mAb） approved worldwide for treatment of metastatic colorectal cancer. Among the various biological and physical analyses per- formed for full study on this biopharmaceutic, the determination of the concentration preparations throughout manufacturing and subsequent handling in hospital is particularly relevant. In the present work, the study and validation of a method for quantifying intact CTX by reverse-phase high-perfor- mance liquid chromatography with diode array detection （（RP）HPLC/DAD） is presented. With that end, we checked the performance of a chromatographic method for quantifying CTX and conducted a study to validate the method as stability-indicating in accordance with the International Conference on Harmo- nization guidelines （ICH） for biotechnological drugs; therefore, we evaluated linearity, accuracy, preci- sion, detection and quantification limits, robustness and system suitability. The specificity of the method and the robustness of the mAb formulation against external stress factors were estimated by compre- hensive chromatographic analysis by subjecting CTX to several informative stress conditions. As de- monstrated, the method is rapid, accurate, and reproducible for CTX quantification. It was also suc- cessfully used to quantify CTX in a long-term stability study performed under hospital conditions.

Comparing different domains of analysis for the characterisation of N-glycans on monoclonal antibodies

With the size of the biopharmaceutical market exponentially increasing,there is an aligned growth in the importance of data-rich analyses,not only to assess drug product safety but also to assist drug development driven by the deeper understanding of structure/function relationships.In monoclonal antibodies,many functions are regulated by N-glycans present in the constant region of the heavy chains and their mechanisms of action are not completely known.The importance of their function focuses analytical research efforts on the development of robust,accurate and fast methods to support drug development and quality control.Released N-glycan analysis is considered as the gold standard for glycosylation characterisation;however,it is not the only method for quantitative analysis of glycoform heterogeneity.In this study,ten different analytical workflows for N-glycan analysis were compared using four monoclonal antibodies.While observing good comparability between the quantitative results generated,it was possible to appreciate the advantages and disadvantages of each technique and to summarise all the observations to guide the choice of the most appropriate analytical workflow according to application and the desired depth of data generated.

Geometric triangular chiral hexagon complexes and clonal embryogenic body organization on the Turin Shroud crucified man image: A predictable tissue response to injury

The shroud continues to remain one of the most studied and controversial artifacts in human history. Many tests, X-ray fluorescence, reflectance, spectrometry and low energy/high-resolution X ray transmission have shown that the crucified body is not compatible with a painted image. Researchers confirm that the alleged blood is real blood. We documented the self-assembly of geometric triangular chiral hexagon complex (GTCHC) with structural organization of embryoid bodies in cancer tissues. The identification of these structures is not only limited to malignant tumors but also appears in extreme injured tissues. Our interest is to determine if we can predict and identify these patterns in the Shroud of Turin. Based on pattern recognition image was analyzed over 100 shroud images. We identified a central spectral emission line that exhibits a characteristic signature on a plot of residual electromagnetic radiation, head area narrowing and low extremities broadening, indication of decay energy changes in the velocity of the molecules in the traversal trajectory. This Electromagnetic collision event generates in the cloth stagnant blood areas with patterns identical to those identified for us in cancer damage tissues. Inflammatory cytokines activate stem cells and Notch signaling proteins in cascade of interactions to generate real clonal human embryoid template. Can we predict function from structure? These structures evoke life, regeneration, but not death. Our findings suggest the image of a crucified man on the Shroud of Turin is a real physical electromagnetic collision event in response to extreme tissue injury, with the fact that supports our previous findings in cancer tissues as real and predictable. Proteins derived from these emergent damage tissue derivate stem cells could be used to design biologic templates in regenerative medicine and develop novel strategies in cancer therapy.

Hepatitis C virus NS5A region mutation in chronic hepatitis C genotype 1 patients who are non-responders to two or more treatments and its relationship with response to a new treatment

To determine the number of mutations in the NS5A region of the hepatitis C virus (HCV) and its relationship to the response to antiviral therapy in patients with chronic hepatitis C genotype 1 who are non-responders to two or more treatments. METHODSSequences within HCV NS5A [PKR binding domain (PKRBD) and the interferon-sensitivity-determining region (ISDR)] were analysed via direct sequencing in a selected cohort of 72 patients, with a total of 201 treatments [interferon-alpha (IFN-α), n = 49; IFN-α + ribavirin (RBV), n = 75; pegylated (peg) IFN-α + RBV, n = 47; first-generation direct-acting antivirals (DAAs), n = 13; and second-generation DAAs, n = 17]. Of these, 48/201 achieved a sustained virological response (SVR) and 153/201 achieved no virological response (NVR). RESULTSFor both regions, treatments resulting in SVR were associated with more baseline mutations than were treatments resulting in NVR (SVR vs NVR; PKRBD: 5.82 ± 3 vs 4.86 ± 2 mutations, P = 0.045; ISDR: 2.65 ± 2 vs 1.51 ± 1.7 mutations, P = 0.005). A decrease or no change in the number of mutations over time between treatments in the PKRBD or ISDR, as shown by sequencing, was associated with patients who usually failed to respond to treatment (PKRBD, P = 0.02; ISDR, P = 0.001). Moreover, patients showing a post-treatment baseline viral load > 600000 IU/mL and increased ISDR mutations with respect to the previous treatment were 9.21 times more likely to achieve SVR (P = 0.001). CONCLUSIONThe obtained results show that among patients who have shown no response to two or more antiviral treatments, the likelihood of achieving SVR increases with the genetic variability in the ISDR region (≥ 2 mutations or number of substitutions from the HCV-J and HCV-1 prototype), especially when the viral load is greater than 600000 IU/mL.

Cadmium Distribution in Tobacco Growing Soil Fractions: Its Influence on Dried Leaf Contents

Many authors have studied cadmium concentrations in tobacco leaves. However, crops such as tobacco store Cd mainly in their leaves and these are for human consumption. The objective of this study is to establish the cadmium levels present in each of the soils fractions throughout the growing period of tobacco plants, and to examine the influence of these fractions on the total content cadmium in dried leaves. The field select is situated near ofGranadacity (soils from Vega de Granada) loamy calcareous thermic typic Xerorthent. The plant (Nicotiana tabacum, cvs. RJ36 variety), and the soil dedicated to the tobacco crop were contaminated with a fixed amount of Cd (100 mg/kg of CdCl2) in the proximity of the root influence area. The contents of Cd are analysed in channel waters, in different soil fractions and dried tobacco leaves (mg/kg) with the different treatments. In conclusion, the water for irrigation is not a contamination risk for the soil even when user over lengthy periods of time. The fraction presenting higher average values is the one of Cd bound to CaCO3 with 0.161 ppm, and the Cd bioavailable fractions is second in importance, and propose a Cd content sequence in fractions, higher to lower: Cd-Carbonates > Cd-Bioavailable > Cd-Organically bound > Cd-Exchangeable > Cd-Soluble.

Reproduction ecology of the recently invasive snake Hemorrhois hippocrepis on the island of Ilbiza Elba

Knowing the causes of biological invasion success can be relevant to combat future invasive processes.The recent invasion of the horseshoe whip snake Hemorrhois hippocrepis on the island of Ibiza provides the opportunity to compare natural history traits between invasive and source populations,and to unravel what makes this snake a successful invader that is threatening the only endemic vertebrate of the island,Podarcis pityusensis.This study compares the basic reproductive traits of mainland native and invasive populations of the snake.Our results revealed that invasive populations were characterized by female maturity at a smaller size,extended reproductive period,and much lower reproduction frequency compared to the native population.In contrast,some major reproductive traits--the abdominal fat body cycle,clutch size,hatchling body size,and hatchling body condition,did not differ between the two populations.Some of these results must reflect the environmental differences in the recently invaded island with respect to the source area,and overall plasticity of reproductive traits.Plasticity is evolutionarily interesting,and may aid the succesful growth of this species in their invasiveness of Mediterranean islands like Ibiza.The most significant finding is that this expression of phenotypic plasticity occurred rapidly in this invasive population,within a period of 14 years maximum.Our results on the reproduction ecology of the invasive population were not conclusive regarding the factors determining the invasiveness of the snake and pointed to alternative causes.

Collapse of the endemic lizard Podarcis pityusensis on the island of Ibiza mediated by an invasive snake

The invasive snake Hemorrhois hippocrepis colonized the island of Ibiza(Balearic Islands)in 2003 as stowaways inside trunks of olive trees imported for gardening.It has quickly spread since 2010,posing a threat to the island’s only remaining endemic vertebrate,the Ibiza wall lizard Podarcis pityusensis.We map the yearly expansion rate of the snake and estimate via transect surveys how severely it affects the distribution and abundance of the endemic lizard.As well,we surveyed 9 of 30 small lizard populations on islets surrounding Ibiza that have been isolated since the Last Glacial Maximum.Snakes had invaded 49%of Ibiza’s land area by 2018,and censuses show a critical contrast in lizard abundance between areas with and without snakes;almost all censuses in areas without snakes show lizard presence whereas nearly all censuses in areas with H.hippocrepis lack lizard sightings.Moreover,at least one subspecies previously thriving on one of the offshore islets has become extinct,and there have been several snakes recorded swimming between Ibiza and the surrounding islets.Therefore,lizard populations have been dramatically reduced or have vanished within the range of the snake,and our results quantitatively support upgrading this species’threat level for extinction.This study can inform to programs to manage invasive snake populations and to conservation actions to recover the endemic lizard.

Advances in spray products for skin regeneration

To date,skin wounds are still an issue for healthcare professionals.Although numerous approaches have been developed over the years for skin regeneration,recent advances in regenerative medicine offer very promising strategies for the fabrication of artificial skin substitutes,including 3D bioprinting,electrospinning or spraying,among others.In particular,skin sprays are an innovative technique still under clinical evaluation that show great potential for the delivery of cells and hydrogels to treat acute and chronic wounds.Skin sprays present significant advantages compared to conventional treatments for wound healing,such as the facility of application,the possibility to treat large wound areas,or the homogeneous distribution of the sprayed material.In this article,we review the latest advances in this technology,giving a detailed description of investigational and currently commercially available acellular and cellular skin spray products,used for a variety of diseases and applying different experimental materials.Moreover,as skin sprays products are subjected to different classifications,we also explain the regulatory pathways for their commercialization and include the main clinical trials for different skin diseases and their treatment conditions.Finally,we argue and suggest possible future trends for the biotechnology of skin sprays for a better use in clinical dermatology.

Is cancer-related death associated with circadian rhythm?

Dear editor,Biological periodicities occur based on a periodicity in a spectrum of frequencies ranging from milliseconds to years.A circadian rhythm is any biological process that displays an endogenous oscillation of about 24 h[1].Cir-cadian rhythm is the adaption of our bodies’biological processes to the day and night cycle.The biological clock is reset daily to synchronize with the exposure to sunlight because our internal clock repeats at around 24 h[1].Because of the use of artificial light,our internal clock is influenced by multiple factors,including social interac-tions[1].