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The study reported in this paper deals with a computer-based methodology for the synthesis of an optimal tool path for robot manipulators in the presence of obstacles and singularities of the workspace. The methodology plans optimal path to achieve the best robot kinematic and dynamic performance criteria formulated through proper objective functions. The algorithm uses robot design parameters, the size and the location of the obstacles, and the initial and the goal states to generate a collision-free optimal tool path. Using these inputs the robot workspace is generated and discretized, and the obstacles are modeled as forbidden regions of the workspace. The search for the optimal path begins with the definition of a searchspace that includes the starting and the end points. All possible paths in the searchspace connecting these points are enumerated through the formation of a network graph structure. An intelligent heuristic search scheme has been developed to enumerate the network of allowable paths. The optimal path is then obtained as a sequence of via points connecting the initial and the final states by applying Dijkstra's minimum cost algorithm. Contrary to most existing methodologies, the computational complexity of this algorithm decreases with an increase in the number and/or the size of the obstacles in the workspace. An interactive computer program has been developed to implement this methodology for a general planar two-link manipulator. This path planning methodology can be applied to any manipulator for which the workspace and the obstacles can be geometrically represented. The algorithm has been applied to some industrial SCARA robots and the results are discussed.

Oxidative stress and mitochondrial dysfunction are associated with the pathogenesis of several human diseases. The excessive generation of reactive oxygen species (ROS) and/or lack of adequate antioxidant defenses causes DNA mutations in mitochondria, damages the mitochondrial respiratory chain, and alters membrane permeability and mitochondrial defense mechanisms. All these alterations are linked to the development of numerous diseases. Curcumin, an active ingredient of turmeric plant rhizomes, exhibits numerous biological activities (i.e., antioxidant, anti-inflammatory, anticancer, and antimicrobial). In recent years, many researchers have shown evidence that curcumin has the ability to reduce the oxidative stress- and mitochondrial dysfunction-associated diseases. In this review, we discuss curcumin’s antioxidant mechanism and significance in oxidative stress reduction and suppression of mitochondrial dysfunction in mammals. We also discuss the research gaps and give our opinion on how curcumin research in mammals should proceed moving forward.

Background and Introduction: Expansion of GAA triplet repeats in the first intron of the frataxin gene causes Friedreich's ataxia. Genetic testing in such condition is important to initiate the appropriate genetic counseling for the family members. The conventional genetic tests used in the diagnosis of Friedreich's ataxia are southern blot, short and long PCR. Recently, triplet repeat primed polymerase chain reaction (TP-PCR) methodology was described in the diagnosis of Friedreich's ataxia, especially for detection of long repeats. Accurate genetic diagnosis of Friedreich's ataxia helps in differentiating it from other ataxias and helps provide appropriate genetic counseling for such families. Extended family screening and genetic counseling can prevent birth of children with Friedreich's ataxia in these families. Materials and Methods: TP-PCR was carried out in 37 samples obtained from Neurology clinic, Sanjay Gandhi Post Graduate Institute of Medical Sciences. The amplified products were subjected to genotyping on a ABI 310 genetic analyser. For heterozygosity, the samples were processed for short and long range PCR. Results: A total of 37 samples of suspected cases of Friedreich ataxia were analysed. Of these, 81% samples were confirmed as Friedreich ataxia and 19% of samples were found to be negative for Friedreich's ataxia by TP-PCR. Extended family screening was done in 2 of the families. Among the 7 individuals screened, 4 were identified as carriers and genetic counseling was provided to them. Conclusions: This is first report from India which describes the molecular diagnosis of Friedreich's ataxia by TP-PCR, its utility in extended family screening and genetic counseling. It qualifies as a highly reliable, sensitive and robust technique that can easily be set up in any laboratory. [ABSTRACT FROM AUTHOR]

Objective: Autoimmune polyendocrine syndrome type 1 (APS1) is a rare autosomal recessive disorder characterized by progressive organ-specific autoimmunity. There is scant information on APS1 in ethnic groups other than European Caucasians. We studied clinical aspects and autoimmune regulator (AIRE) gene mutations in a cohort of Indian APS1 patients. Design: Twenty-three patients (19 families) from six referral centres in India, diagnosed between 1996 and 2016, were followed for [median (range)] 4 (0.2–19) years. Methods: Clinical features, mortality, organ-specific autoantibodies and AIRE gene mutations were studied. Results: Patients varied widely in their age of presentation [3.5 (0.1–17) years] and number of clinical manifestations [5 (2–11)]. Despite genetic heterogeneity, the frequencies of the major APS1 components (mucocutaneous candidiasis: 96%; hypoparathyroidism: 91%; primary adrenal insufficiency: 55%) were similar to reports in European series. In contrast, primary hypothyroidism (23%) occurred more frequently and at an early age, while kerato-conjunctivitis, urticarial rash and autoimmune hepatitis were uncommon (9% each). Six (26%) patients died at a young age [5.8 (3–23) years] due to septicaemia, hepatic failure and adrenal/hypocalcaemic crisis from non-compliance/unexplained cause. Interferon-α and/or interleukin-22 antibodies were elevated in all 19 patients tested, including an asymptomatic infant. Eleven AIRE mutations were detected, the most common being p.C322fsX372 (haplotype frequency 37%). Four mutations were novel, while six others were previously described in European Caucasians. Conclusions: Indian APS1 patients exhibited considerable genetic heterogeneity and had highly variable clinical features. While the frequency of major manifestations was similar to that of European Caucasians, other features showed significant differences. A high mortality at a young age was observed.

Confocal reflectance imaging typically suffers from high background and poor sensitivity. We demonstrate sensitive and low-background reflectance imaging of cells encapsulated in transparent 3D hydrogels. Nanoscale cell morphology is visualized with sensitivity similar to confocal fluorescence, with low laser power, minimal specimen preparation, and reduced toxicity.

The requirement for accurate treatments for skin diseases and wounds, generated a rising interest towards multifunctional polymer composites, that are capable of mimicking the natural compositions in human body. Also, electroactive composite films disseminate endogenous electrical stimulations that encourage cell migration and its proliferation at wound site, proposing greater opportunities in upgrading the conventional wound patches. In this work, the composite film made of graphene oxide, Ag 2 O, PVA and chitosan were developed for wound healing applications, by the solution casting method. The even dispersibility of nanofiller in polymeric matrix was validated from the physicochemical analyses. The increment in roughness of the composite film surface was noted from AFM images. The thermal stability and porous nature of the polymer composite were also verified. A conductivity value of 0.16 × 10 -4 Scm -1 was obtained for the film. From MTT assay, it was noted that the films were non-cytotoxic and supported cell adhesion along with cell proliferation of macrophage (RAW 264.7) cells. Moreover, the composite film also demonstrated non-hemolytic activity of <2 %, as well as excellent antibacterial activity towards E. coli and S. aureus. Thus, the obtained results validated that the prepared composite film could be chosen as an innovative candidate for developing state-of-the-art wound dressings., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Introduction: Glioma is a brain tumour occurring in all age groups but common in adults. Despite advances in the understanding of tumours, we cannot improve the survival of the patients and do not have an appropriate biomarker for progression and prognosis prediction. The base excision repair mechanism maintains the integrity of the genome, preventing tumour formation. However, continuous chemical damage to the cells results in mutations that escape the repair mechanism and support tumour growth. The tumour microenvironment in cancer is crucial in determining the tumour growth, development, and response to treatments. The present study explored the significance of Base Excision Repair genes (BER) in modulating the tumour microenvironment., Methods: We used the publically available data sets from the Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) to explore the role of the base excision repair gene in the modulating tumour microenvironment. The data was analysed for the expression of base excision repair genes, their correlation with the immune markers, their prognostic potential, and enrichment analysis to understand the pathways they modulate in low-grade glioma (LGG) progression., Results: The analysis showed BER genes contribute an integral role in the overall and disease-free survival of LGG. Genes like MUTYH, PNKP, UNG and XRCC1 showed a correlation with the immune infiltration levels and a significant correlation with various immune markers associated with different immune cells, including tumour-associated macrophages. MUTYH, UNG and XRCC1 correlated with IDH1 mutation status, and functional enrichment analysis showed that these genes are enriched in several pathways like Wnt, PD-1 and Integrin signalling., Conclusion: Our findings suggest that the BER genes MUTYH, PNKP, UNG and XRCC1 can potentially be prognostic biomarkers and highly correlate with the immune cells of the tumour microenvironment., Competing Interests: Declaration of Competing Interest The authors have no relevant financial or nonfinancial interests to disclose., (Copyright © 2024 Elsevier GmbH. All rights reserved.)