A Fixed Point Theorem In 2-Banach Space For Banach Contraction Principle

In This Paper we prove An Extension of Banach contraction principle through rational expression in 2-Banach space satisfying Three continuous mappings . Some result with S. banach (1922). And discuss about fixed point theory in 2-Banach space also established a fixed point theorem in 2-Banach space which generalized the result of many mathematician. Mathematics Subject classification: 47H10,54H25 Keywords: Banach Space, Common Fixed point, Triangle inequality , Normed space,                2- Normed space, 2-Banach space

Comparison of Baska Mask Versus I-Gel in Short Gynaecological Laparoscopic Surgeries Under General Anaesthesia in Adult Female: A Randomized Interventional Study

Background: Various newer generations of Supraglottic Airway Devices (SAD) with improved designs and performance are available for use by anaesthesiologist. We conducted the present study to compare 3rd generation SAD Baska Mask with 2nd generation SAD I-gel with the aim of comparing their clinical performance in terms of insertion parameters and oropharyngeal leak pressure in short laparoscopic gynaecological surgeries in adult females. Methods: 80 adult female patients were randomly allocated to either Baska Mask (n=40) or I-gel (n=40) groups. Insertion characteristics that included number of attempts, mean insertion time and manipulation frequency were recorded and compared. Oropharyngeal leak pressure was measured just after insertion of device and after 5 min of creating pneumoperitoneum in both devices and were compared. Results: Baska Mask insertion was successfully achieved in first attempt in 38/40 patients in Baska group vs 35/40 patients in I-gel group. Mean oropharyngeal leak pressure (OLP) in Baska Mask versus I-gel just after insertion was (29.24±4.20cm H20 vs 26.33±2.51cm H2O, P=0.003) whereas it was (29.42±2.70 vs 26.18±2.54 cm H2O) after 5 min of creating pneumoperitoneum. Both groups were comparable in terms of removal characteristics and postoperative laryngopharyngeal airway morbidities. Conclusion: Baska Mask provided more effective ventilation in terms of greater oropharyngeal leak pressure as compared to I-gel. However Baska Mask was more difficult to insert and the incidence of postoperative laryngopharyngeal morbidity was higher in case of Baska Mask

Enhancement of c-Myc degradation by BLM helicase leads to delayed tumor initiation

The spectrum of tumors that arise owing to the overexpression of c-Myc and loss of BLM is very similar. Hence, it was hypothesized that the presence of BLM negatively regulates c-Myc functions. By using multiple isogenic cell lines, we observed that the decrease of endogenous c-Myc levels that occurs in the presence of BLM is reversed when the cells are treated with proteasome inhibitors, indicating that BLM enhances c-Myc turnover. Whereas the N-terminal region of BLM interacts with c-Myc, the rest of the helicase interacts with the c-Myc E3 ligase Fbw7. The two BLM domains act as ‘clamp and/or adaptor’, enhancing the binding of c-Myc to Fbw7. BLM promotes Fbw7-dependent K48-linked c-Myc ubiquitylation and its subsequent degradation in a helicase-independent manner. A subset of BLM-regulated genes that are also targets of c-Myc were determined and validated at both RNA and protein levels. To obtain an in vivo validation of the effect of BLM on c-Myc-mediated tumor initiation, isogenic cells from colon cancer cells that either do or do not express BLM had been manipulated to block c-Myc expression in a controlled manner. By using these cell lines, the metastatic potential and rate of initiation of tumors in nude mice were determined. The presence of BLM decreases c-Myc-mediated invasiveness and delays tumor initiation in a mouse xenograft model. Consequently, in tumors that express BLM but not c-Myc, we observed a decreased ratio of proliferation to apoptosis together with a suppressed expression of the angiogenesis marker CD31. Hence, partly owing to its regulation of c-Myc stability, BLM acts as a ‘caretaker tumor suppressor’

Structural Inequalities and Intersectionality are the Root Causes of Gender Discrimination & Sexual Harassment

Sexual harassment and gender discrimination overlap affecting people (including children) of all genders, however data shows an overwhelmingly high prevalence of violence or harassment experienced by women in areas of conflict, professional life and in their homes as well as in the healthcare workplace. It is pervasive, persistent and all too common. Workplace sexual harassment an discrimination although illegal, is particularly is more common in women who are young, early in their careers, in temporary employment, from under-represented or marginalised groups based on ethnicity, immigrant status, gender non-conformity or disability. Majority of perpetrators are men, who are older and enjoy the privilege of disproportionate power and in certain toxic male-dominated healthcare environments. Two recent stories of sexual harassment in healthcare prompted many women to follow suit and share similar stories referring to flashbacks, post-traumatic stress, damage to careers, pressure to leave their job, self-harm and suicidal thoughts, brought about by their experiences. Yet there are examples of women as role models breaking down historical barriers such as Hilary and Chandi in their polar adventures. Tackling such structural inequality requires remedies that go beyond incremental approaches focussed on individuals and include transformation of the organisational and societal climate by interventions, affirmative policies and courageous, compassionate leadership. Workplace sexual harassment and discrimination is unacceptable, not inevitable and needs to be eradicated

Understanding Pathophysiology of Sporadic Parkinson\u27s Disease in Drosophila Model: Potential Opportunities and Notable Limitations

Parkinson’s disease (PD) is the second most common neurodegenerative disorder affecting approximately 1% of the population over age 50. PD is widely accepted as a multifactorial disease with both genetic and environmental contributions. Despite extensive research conducted in the area the precise etiological factors responsible remain elusive. In about 95% Parkinsonism is considered to have a sporadic component. There are currently no established curative, preventative, or disease-modifying interventions, stemming from a poor understanding of the molecular mechanisms of pathogenesis. Here lies the importance of animal models. Pharmacological insults cause Parkinsonian like phenotypes in Drosophila, thereby modelling sporadic PD. The pesticides paraquat and rotenone induced oxidative damage causing cluster specific DA neuron loss together with motor deficits. Studies in fly PD model have deciphered that signaling pathways such as phosphatidylinositol 3-kinase (PI3K/Akt and target of rapamycin (TOR), c-Jun N-terminal kinase (JNK) have been defective. Further, these studies have demonstrated that fruit fly can be a potential model to screen chemical compounds for their neuroprotective efficacy

RECQL4 is essential for the transport of p53 to mitochondria in normal human cells in the absence of exogenous stress

Mutations in RECQL4 helicase are associated with Rothmund–Thomson syndrome (RTS). A subset of RTS patients is predisposed to cancer and is sensitive to DNA damaging agents. The enhanced sensitivity of cells from RTS patients correlates with the accumulation of transcriptionally active nuclear p53. We found that in untreated normal human cells these two nuclear proteins, p53 and RECQL4, instead colocalize in the mitochondrial nucleoids. RECQL4 accumulates in mitochondria in all phases of the cell cycle except S phase and physically interacts with p53 only in the absence of DNA damage. p53–RECQL4 binding leads to the masking of the nuclear localization signal of p53. The N-terminal 84 amino acids of RECQL4 contain a mitochondrial localization signal, which causes the localization of RECQL4–p53 complex to the mitochondria. RECQL4–p53 interaction is disrupted after stress, allowing p53 translocation to the nucleus. In untreated normal cells RECQL4 optimizes de novo replication of mtDNA, which is consequently decreased in fibroblasts from RTS patients. Wild-type RECQL4-complemented RTS cells show relocalization of both RECQL4 and p53 to the mitochondria, loss of p53 activation, restoration of de novo mtDNA replication and resistance to different types of DNA damage. In cells expressing Δ84 RECQL4, which cannot translocate to mitochondria, all the above functions are compromised. The recruitment of p53 to the sites of de novo mtDNA replication is also regulated by RECQL4. Thus these findings elucidate the mechanism by which p53 is regulated by RECQL4 in unstressed normal cells and also delineates the mitochondrial functions of the helicase

Parkinson’s Disease: Insights from Drosophila Model

Parkinson’s disease (PD) is a medical condition that has been known since ancient times. It is the second most common neurodegenerative disorder affecting approximately 1% of the population over 50 years. It is characterized by both motor and non-motor symptoms. Most of PD cases are sporadic while 5–10% cases are familial. Environment factors such as exposure to pesticides, herbicides and other heavy metals are expected to be the main cause of sporadic form of the disease. Mutation of the susceptible genes such as SNCA, PINK1, PARKIN, DJ1, and others are considered to be the main cause of the familial form of disease. Drosophila offers many advantages for studying human neurodegenerative diseases and their underlying molecular and cellular pathology. Shorter life span; large number of progeny; conserved molecular mechanism(s) among fly, mice and human; availability of many techniques, and tools to manipulate gene expression makes drosophila a potential model system to understand the pathology associated with PD and to unravel underlying molecular mechanism(s) responsible for dopaminergic neurodegeneration in PD—understanding of which will be of potential assistance to develop therapeutic strategies to PD. In the present review, we made an effort to discuss the contribution of fly model to understand pathophysiology of PD, in understanding the biological functions of genes implicated in PD; to understand the gene-environment interaction in PD; and validation of clues that are generated through genome-wide association studies (GWAS) in human through fly; further to screen and develop potential therapeutic molecules for PD. In nutshell, fly has been a great model system which has immensely contributed to the biomedical research relating to understand and addressing the pathology of human neurological diseases in general and PD in particular

Fluorescence microscopy-based sensitive method to quantify dopaminergic neurodegeneration in a Drosophila model of Parkinson’s disease

Death of dopaminergic (DAergic) neurons in the substantia nigra pars compacta of the human brain is the characteristic pathological feature of Parkinson’s disease (PD). On exposure to neurotoxicants, Drosophila too exhibits mobility defects and diminished levels of brain dopamine. In the fly model of sporadic PD, our laboratory has demonstrated that there is no loss of DAergic neuronal number, however, a significant reduction in fluorescence intensity (FI) of secondary antibodies that target the primary antibody-anti-tyrosine hydroxylase (TH). Here, we present a sensitive, economical, and repeatable assay to characterize neurodegeneration based on the quantification of FI of the secondary antibody. As the intensity of fluorescence correlates with the amount of TH synthesis, its reduction under PD conditions denotes the depletion in the TH synthesis, suggesting DAergic neuronal dysfunction. Reduction in TH protein synthesis is further confirmed through Bio-Rad Stain-Free Western Blotting. Quantification of brain DA and its metabolites (DOPAC and HVA) using HPLC-ECD further demonstrated the depleted DA level and altered DA metabolism as evident from enhanced DA turnover rate. Together all these PD marker studies suggest that FI quantification is a refined and sensitive method to understand the early stages of DAergic neurodegeneration. FI quantification is performed using ZEN 2012 SP2, a licensed software from Carl Zeiss, Germany. This method will be of good use to biologists, as it with few modifications, can also be implemented to characterize the extent of degeneration of different cell types. Unlike the expensive and cumbersome confocal microscopy, the present method using fluorescence microscopy will be a feasible option for fund-constrained neurobiology laboratories in developing countries

Strategies to combat Gram-negative bacterial resistance to conventional antibacterial drugs: a review

The emergence of antimicrobial resistance raises the fear of untreatable diseases. Antimicrobial resistance is a multifaceted and dynamic phenomenon that is the cumulative result of different factors. While Gram-positive pathogens, such as methicillin-resistant Staphylococcus aureus and Clostridium difficile, were previously the most concerning issues in the field of public health, Gram-negative pathogens are now of prime importance. The World Health Organization’s priority list of pathogens mostly includes multidrug-resistant Gram-negative organisms particularly carbapenem-resistant Enterobacterales, carbapenem-resistant Pseudomonas aeruginosa, and extensively drug-resistant Acinetobacter baumannii. The spread of Gram-negative bacterial resistance is a global issue, involving a variety of mechanisms. Several strategies have been proposed to control resistant Gram-negative bacteria, such as the development of antimicrobial auxiliary agents and research into chemical compounds with new modes of action. Another emerging trend is the development of naturally derived antibacterial compounds that aim for targets novel areas, including engineered bacteriophages, probiotics, metal-based antibacterial agents, odilorhabdins, quorum sensing inhibitors, and microbiome-modifying agents. This review focuses on the current status of alternative treatment regimens against multidrug-resistant Gram-negative bacteria, aiming to provide a snapshot of the situation and some information on the broader context