Synthesis and Biological Evaluation of Amino Acid and Peptide Conjugates of 5-Bromovaleric Acid.

BACKGROUND: Among various carboxylic acid derivatives, valeric acid or pentanoic acid is found to be widely distributed in nature. It is a straight-chain alkyl carboxylic acid containing five carbon atoms. Due to the therapeutic value of valeric acid, it is used as a versatile nucleus in the pharmaceutical field. Valeric acid derivatives are associated with a broad spectrum of biological activities, like anticonvulsant, antiplatelet, antidiabetic, and plant growth activities. AIM: It has previously been revealed that peptide derivatives of carboxylic acids are accountable for enhanced antimicrobial activity. Therefore, it was hypothesized that coupling peptides with valeric acid would increase the antimicrobial properties of the target compounds. So, the objective of the present study was to synthesize peptide derivatives of 5-bromovaleric acid and evaluate their antibacterial and antifungal activities. METHODS: 5-bromovaleric acid was synthesized by the reaction of cyclopentanone and hydrogen peroxide in the presence of copper bromide and sodium bromide. Additionally, 5-bromovaleric acid was coupled with amino acid methyl esters, dipeptides, tripeptides, and tetrapeptides in the presence of dicyclohexylcarbodimide (DCC) and N-methylmorpholine (NMM) as a base under continuous stirring for 36 hours to produce its peptide derivatives. RESULTS: The results obtained showed that 5-bromovaleric acid possesses more potent antibacterial activity than N-terminal 5-bromovaleric acid conjugates of selected di-, tri, and tetra peptide Cterminal methyl esters against ciprofloxacin as a standard. The selected dipeptide and tripeptide Nterminal 5-bromovaleric acid-conjugated C-terminal methyl ester derivatives were more active than the selected tetrapeptide methyl ester analogue. Using fluconazole as a reference, the antifungal efficacy of 5-bromovaleric acid against C. albicans and A. niger declined as it was combined with C-terminal methyl esters of selected dipeptides, tripeptides, and tetrapeptides. CONCLUSION: The novel selected peptide derivatives had less antibacterial and antifungal action than the parent 5-bromovaleric acid. Antibacterial and antifungal investigations showed that 5- bromopentanoic acid peptide derivatives might impair antimicrobial efficacy. Further, attaching 5- bromopentanoic acid to di, tri, and tetra peptides did not boost their antibacterial potential.

Rapid Vision Loss Due to Multifocal Glioma: A Diagnostic Challenge.

INTRODUCTION: This is a unique case report in medical literature for its detailing of diagnostics of an uncommon presentation of a rapid unexplained bilateral vision loss of a 73-year-old male diabetic patient. This report highlights the crucial role of advanced molecular diagnostics in difficult neurological cases and also elucidates the difficulties involved in diagnosing optic nerve glioblastoma, an exceptionally rare and aggressive tumour. MAIN CONCERNS AND CLINICAL FINDINGS OF THE PATIENT: Slow and progressive loss of vision over 2 months, ultimately developing almost complete visual impairment in both eyes and a defect of right eye field of vision conclusively highlighted that the likely etiology was neuro-ophthalmic. Initially, the conditions were suspected to be an extended spectrum of diabetic eye disease complications but further deterioration was a hint towards something more substantive. PRIMARY DIAGNOSES, INTERVENTIONS AND OUTCOMES: This entailed in-depth diagnosis processes that included an MRI and the analysis of cerebrospinal fluid. The important discovery was through stereotactic biopsies of the optic nerve revealing a high-grade glial neoplasm. Next generation sequencing confirmed the pathology as IDH-wildtype glioblastoma. Despite management, his vision continued to deteriorate. Hence, an aggressive clinical course was followed. CONCLUSION: This case highlights the important learning need in considering glioblastoma of the optic chiasm as part of the differential diagnosis of rapid vision loss, which may present as multifocal brain lesions, especially in cases of rapid loss of vision where initial workup is negative. Quite a useful lesson that can be drawn from this case relates to the diagnostic process with advanced molecular profiling, more attention given to clinical suspicion and cutting-edge diagnostic tools applied in atypical presentation of neurological conditions.

Cone Beam Computed Tomography-Based Evaluation of the Accuracy of Implant Surgery with Conventional (Free Hand) Implant Placement vs Computer Fabricated 3D Guide Implant Placement.

Introduction: Dental implants have been used in a variety of conventional technique-based forms for many years which had its own drawbacks. With the advent of cone beam CT, proper surgical and prosthetic planning is possible now a days. To achieve ideal implant placement, good prosthetic fabrication and overall successful prognosis computer fabricated guide aided surgery have been developed. Aim and Objective: The aim of this study was to compare and evaluate the accuracy of implant placement in partially edentulous patients with conventional free hand technique and computer fabricated guide of implant placement by comparing pre- and post-CBCT data. Methods: The present split mouth study design was conducted with forty sample size on twenty randomly selected patients who were treated with bilateral partially edentulous sites requiring dental implants. Patients were treated with both conventional (free hand) technique and computer fabricated 3D guide aided technique of implant placement. Comparison of accuracy of implant placement was done by comparing the pre- and postoperative CBCT data in terms of mean coronal deviation, mean apical deviation and mean angular deviation. Results and Conclusion: The results showed that there is no statistically significant difference between mean coronal deviation, mean apical deviation and mean angular deviation of planned and placed implants in both conventional technique (free hand technique) and computer fabricated 3D guide aided implant placement technique. Hence, this study concluded that conventional technique of implant placement is equally efficient in comparison with computer fabricated guide aided surgery in terms of accuracy of implant placement.

Older Adults' Trust and Distrust in COVID-19 Public Health Information: Qualitative Critical Incident Study.

BACKGROUND: The COVID-19 infodemic has imposed a disproportionate burden on older adults who face increased challenges in accessing and assessing public health information, but little is known about factors influencing older adults' trust in public health information during COVID-19. OBJECTIVE: This study aims to identify sources that older adults turn to for trusted COVID-19 public health information and factors that influence their trust. In addition, we explore the relationship between public health information sources and trust factors. METHODS: Adults aged 65 years or older (N=30; mean age 71.6, SD 5.57; range 65-84 years) were recruited using Prime Panels. Semistructured phone interviews, guided by critical incident technique, were conducted in October and November 2020. Participants were asked about their sources of COVID-19 public health information, the trustworthiness of that information, and factors influencing their trust. Interview data were examined with thematic analysis. RESULTS: Mass media, known individuals, and the internet were the older adults' main sources for COVID-19 public health information. Although they used social media for entertainment and personal communication, the older adults actively avoided accessing or sharing COVID-19 information on social media. Factors influencing their trust in COVID-19 public health information included confirmation bias, personal research, resigned acceptance, and personal relevance. CONCLUSIONS: These findings shed light on older adults' use of information sources and their criteria for evaluating the trustworthiness of public health information during a pandemic. They have implications for the future development of effective public health communication, policies, and interventions for older adults during health crises.

Protective efficacy and correlates of immunity of immunodominant recombinant Babesia microti antigens.

Babesia microti, an intraerythrocytic apicomplexan parasite, is the primary causative agent of human babesiosis and an emerging threat to public health in the United States and elsewhere. An effective vaccine against B. microti would reduce disease severity in acute babesiosis patients and shorten the parasitemic period in asymptomatic individuals, thereby minimizing the risk of transfusion-transmitted babesiosis. Here we report on immunogenicity, protective efficacy, and correlates of immunity following immunization with four immunodominant recombinantly produced B. microti antigens-Serine Reactive Antigen 1 (SERA1), Maltese Cross Form Related Protein 1 (MCFRP1), Piroplasm ß-Strand Domain 1 (PißS1), and Babesia microti Alpha Helical Cell Surface Protein 1 (BAHCS1)-delivered subcutaneously in Montanide ISA 51/CpG adjuvant in three doses to BALB/c mice. Following B. microti parasite challenge, BAHCS1 led to the highest reduction in peak parasitemia (67.8%), followed by SERA1 (44.8%) and MCFRP1 (41.9%); PißS1 (27.6%) had minimal protective effect. All four B. microti antigens induced high ELISA total IgG and each isotype; however, antibody levels did not directly correlate with anti-parasitic activity in mice. Increased prechallenge levels of some cell populations including follicular helper T cells (TFH) and memory B cells, along with a set of six cytokines [IL-1α, IL-2, IL-3, IL-6, IL-12(p40), and G-CSF] that belong to both innate and adaptive immune responses, were generally associated with protective immunity. Our results indicate that mechanisms driving recombinant B. microti antigen-induced immunity are complex and multifactorial. We think that BAHCS1 warrants further evaluation in preclinical studies.

In-silico identification of lysine residue for lysozyme immobilization on dialdehyde cellulose.

In the realm of enzymes, the Enzyme Immobilization technique can be extremely beneficial. More research into computational approaches could lead to a better understanding as well as lead us in the direction of a more environmentally friendly and greener path. In this study, molecular modelling techniques were used to collect information regarding the immobilization of Lysozyme (EC 3.2.1.17) on Dialdehyde Cellulose (CDA). Lysine, being the most nucleophilic, is most likely to interact with dialdehyde cellulose. Enzyme substrate interactions have been studied with and without the refinement of modified lysozyme molecules. A total of six CDA-modified lysine residues were selected for the study. The docking process for all modified lysozymes was carried out using four distinct docking programs: Autodock Vina, GOLD, Swissdock, and iGemdock. The binding affinity (-7.8 & -8.0 kcal mol-1 in case of non-refinement and -4.7 & -5.0 kcal mol-1 in case of refinement), calculated from Autodock vina, as well as the interaction similarity of Lys116 immobilized lysozyme with its substrate, were found to be 75 % (W/o simulation) & 66.7 % (With simulation) identical with the reference case (unmodified lysozyme) if Lys116 is bound to Dialdehyde Cellulose. The approach described here is utilized to identify amino acid residues that are used in the immobilization of lysozyme.

Predictive factors for treatment outcomes with intravitreal anti-vascular endothelial growth factor injections in diabetic macular edema in clinical practice.

BACKGROUND: Intravitreal anti-vascular endothelial growth factor (anti-VEGF) injections are the standard of care for diabetic macular edema (DME), a common complication of diabetes. This study aimed to identify factors influencing DME intravitreal anti-VEGF treatment outcomes in real-world practice. METHODS: This was a multi-center retrospective observational study using medical chart review of participants receiving anti-VEGF injections for DME (N = 248). Demographic and clinical variables were assessed for association with best corrected visual acuity (BCVA) and central macular thickness (CMT) outcomes using regression models. RESULTS: There was a significant improvement in BCVA (p < 0.001) and CMT (p < 0.001) after 12 months of treatment, although 21% of participants had decreased BCVA, and 41% had a < 10% CMT reduction at 12 months. Higher baseline BCVA (p = 0.022, OR=-0.024, 95% CI=-0.046,-0.004) and longer duration of diabetic retinopathy (p = 0.048, OR=-0.064, 95% CI=-0.129,-0.001) were negative predictors for BCVA response, whereas Aflibercept treatment (p = 0.017, OR = 1.107, 95% CI = 0.220,2.051) compared with other drugs and a positive "early functional response" (p < 0.001, OR=-1.393, 95% CI=-1.946,-0.857) were positive predictors. A higher baseline CMT (p < 0.001, OR = 0.019, 95% CI = 0.012,0.0261) and an "early anatomical response", (p < 0.001, OR=-1.677, 95% CI=-2.456, -0.943) were predictors for greater reduction in CMT. Overall, the variables could predict only 23% of BCVA and 52% of CMT response. CONCLUSIONS: The study shows a significant proportion of DME patients do not respond to anti-VEGF therapy and identifies several clinical predictors for treatment outcomes. TRIAL REGISTRATION: The study was approved through the Human Research Ethics Committee, University of Tasmania (approval number H0012902), and the Southern Adelaide Clinical Human Research Ethics Committee (approval number 86 - 067).

Chemical Constituents Based Approach for the Management of Diabetes.

BACKGROUND: A number of complexities in compliance with long-term diabetes have been elicited. It has become a global concern without any convincing medicinal, therapeutical methodology. Both hyperglycaemia and oxidative pressure are major notable parts that play a significant role in the initialization of diabetic inconvenience. Natural medications have gained a lot of attention in recent years as expected restorative specialists in the prevention and treatment of diabetic complications due to their many objectives and less poisonous outcomes. This survey means to evaluate the accessible information on therapeutic spices for constriction and the executives of diabetic complications. MATERIALS AND METHODS: Bibliographic investigation was accomplished by checking old-style course books and papers, directing overall bases of logical information (SCOPUS, PUBMED, SCIELO, Google Scholar, NISCAIR,) to recapture accessible distributed writing. For the assessment of plants with the potential in calming diabetic complications, several inclusion models rely on the numerous medicinal spices as well as their crucial mixes. Furthermore, several models, including plants, have been considered, each of which has a suitable impact on increasing oxidative pressure in diabetes. RESULTS: Different therapeutic plants/plant withdrawals containing alkaloids, terpenoids, phenolic compounds, flavonoids, saponins, and phytosterol-type synthetic constituents were uncovered that are profitable in the administration of diabetic complexities. Results may be attributed to the improvement of oxidative pressure, constant hyperglycemia, and twitch of different metabolic pathways related to the pathogenesis of diabetic confusions. CONCLUSION: An optimistic approach for new medication terminology to treat diabetic confusion is screening compound competitors from homegrown medication. Investigation of the activity of different plant extracts as well as their potency profile and to determine their job in the treatment of diabetic inconveniences must be there. In addition, an ideal rat model which imitates human diabetic complications ought to be created.

Misinformation and COVID-19 vaccine hesitancy.

BACKGROUND: COVID-19 vaccine hesitancy has emerged as a major public health challenge. Although medical and scientific misinformation has been known to fuel vaccine hesitancy in the past, misinformation surrounding COVID-19 seems to be rampant, and increasing evidence suggests that it is contributing to COVID-19 vaccine hesitancy today. The relationship between misinformation and COVID-19 vaccine hesitancy is complex, however, and it is relatively understudied. METHODS: In this article, we report qualitative data from two related but distinct studies from a larger project. Study 1 included semi-structured, open-ended interviews conducted in October-November 2020 via phone with 30 participants to investigate the relationship between misinformation and COVID-19 vaccine hesitancy. Study 1's results then informed the design of open-ended questions for Study 2, an online survey conducted in May-June 2021 to consider the relationship between misinformation and vaccine hesitancy further. The data were examined with thematic analysis. RESULTS: Study 1 led to the identification of positive and negative themes related to attitudes toward COVID-19 vaccines. In Study 2, responses from vaccine-hesitant participants included six categories of misinformation: medical, scientific, political, media, religious, and technological. Across both Study 1 and Study 2, six vaccine hesitancy themes were identified from the data: concerns about the vaccines' future effects, doubts about the vaccines' effectiveness, commercial profiteering, preference for natural immunity, personal freedom, and COVID-19 denial. CONCLUSIONS: The relationship between misinformation and vaccine hesitancy is complicated. Various types of misinformation exist, with each related to a specific type of vaccine hesitancy-related attitude. Personal freedom and COVID-19 denial are vaccine attitudes of particular interest, representing important yet understudied phenomena. Medical and scientific approaches may not be sufficient to combat misinformation based in religion, media, or politics; and public health officials may benefit from partnering with experts from those fields to address harmful misinformation that is driving COVID-19 vaccine hesitancy.

Range of the perfluorooctanoate (PFOA) safe dose for human health: An international collaboration.

Many government agencies and expert groups have estimated a dose-rate of perfluorooctanoate (PFOA) that would protect human health. Most of these evaluations are based on the same studies (whether of humans, laboratory animals, or both), and all note various uncertainties in our existing knowledge. Nonetheless, the values of these various, estimated, safe-doses vary widely, with some being more than 100,000 fold different. This sort of discrepancy invites scrutiny and explanation. Otherwise what is the lay public to make of this disparity? The Steering Committee of the Alliance for Risk Assessment (2022) called for scientists interested in attempting to understand and narrow these disparities. An advisory committee of nine scientists from four countries was selected from nominations received, and a subsequent invitation to scientists internationally led to the formation of three technical teams (for a total of 24 scientists from 8 countries). The teams reviewed relevant information and independently developed ranges for estimated PFOA safe doses. All three teams determined that the available epidemiologic information could not form a reliable basis for a PFOA safe dose-assessment in the absence of mechanistic data that are relevant for humans at serum concentrations seen in the general population. Based instead on dose-response data from five studies of PFOA-exposed laboratory animals, we estimated that PFOA dose-rates 10-70 ng/kg-day are protective of human health.

Trust in COVID-19 public health information.

Understanding the factors that influence trust in public health information is critical for designing successful public health campaigns during pandemics such as COVID-19. We present findings from a cross-sectional survey of 454 US adults-243 older (65+) and 211 younger (18-64) adults-who responded to questionnaires on human values, trust in COVID-19 information sources, attention to information quality, self-efficacy, and factual knowledge about COVID-19. Path analysis showed that trust in direct personal contacts (B = 0.071, p = .04) and attention to information quality (B = 0.251, p < .001) were positively related to self-efficacy for coping with COVID-19. The human value of self-transcendence, which emphasizes valuing others as equals and being concerned with their welfare, had significant positive indirect effects on self-efficacy in coping with COVID-19 (mediated by attention to information quality; effect = 0.049, 95% CI 0.001-0.104) and factual knowledge about COVID-19 (also mediated by attention to information quality; effect = 0.037, 95% CI 0.003-0.089). Our path model offers guidance for fine-tuning strategies for effective public health messaging and serves as a basis for further research to better understand the societal impact of COVID-19 and other public health crises.

Cellulose tosylate as support for α-amylase immobilization.

Tremendous potential exists to use cellulose as a support for the immobilization of enzymes. In the current study, cellulose was transformed into cellulose tosylate, and α-Amylase was immobilized using the derivatized polymer. Techniques like Fourier transform infrared, scanning electron microscopy, thermogravimetric analysis, and X-ray diffraction methods were used to characterize the support. The support is a perfect illustration of how both covalent and hydrophobic/ionic types of immobilizations can be experimentally used on support. The support was found to show max degradation at 320.2 °C with 3.2 % residual substance and crystallinity of about 56.6 %. The support presented maximum enzyme loading at the support: enzyme ratio of 1:4. The immobilized enzyme displayed two ideal pH values (about 4.6 and 7) and two ideal temperatures (approximately 60 °C & 40 °C). It was discovered that the immobilized α-amylase could be used easily eight times with 9.9 % residual activity. The findings of this study show that the immobilized cellulose tosylate enzyme has the potential for application in both acidic and neutral pH environments with the best activity for commercial use.

Unravelling the Therapeutic Potential of Nano-Delivered Functional Foods in Chronic Respiratory Diseases.

Chronic inflammation of the respiratory tract is one of the most concerning public health issues, as it can lead to chronic respiratory diseases (CRDs), some of which are more detrimental than others. Chronic respiratory diseases include chronic obstructive pulmonary disease (COPD), asthma, lung cancer, and pulmonary fibrosis. The conventional drug therapies for the management and treatment of CRDs only address the symptoms and fail to reverse or recover the chronic-inflammation-mediated structural and functional damage of the respiratory tract. In addition, the low efficacy and adverse effects of these drugs have directed the attention of researchers towards nutraceuticals in search of potential treatment strategies that can not only ameliorate CRD symptoms but also can repair and reverse inflammatory damage. Hence, there is a growing interest toward investigating the medicinal benefits of nutraceuticals, such as rutin, curcumin, zerumbone, and others. Nutraceuticals carry many nutritional and therapeutic properties, including anti-inflammatory, antioxidant, anticancer, antidiabetic, and anti-obesity properties, and usually do not have as many adverse effects, as they are naturally sourced. Recently, the use of nanoparticles has also been increasingly studied for the nano drug delivery of these nutraceuticals. The discrete size of nanoparticles holds great potential for the level of permeability that can be achieved when transporting these nutraceutical compounds. This review is aimed to provide an understanding of the use of nutraceuticals in combination with nanoparticles against CRDs and their mechanisms involved in slowing down or reversing the progression of CRDs by inhibiting pro-inflammatory signaling pathways.

Transcriptomic and proteomic retinal pigment epithelium signatures of age-related macular degeneration.

There are currently no treatments for geographic atrophy, the advanced form of age-related macular degeneration. Hence, innovative studies are needed to model this condition and prevent or delay its progression. Induced pluripotent stem cells generated from patients with geographic atrophy and healthy individuals were differentiated to retinal pigment epithelium. Integrating transcriptional profiles of 127,659 retinal pigment epithelium cells generated from 43 individuals with geographic atrophy and 36 controls with genotype data, we identify 445 expression quantitative trait loci in cis that are asssociated with disease status and specific to retinal pigment epithelium subpopulations. Transcriptomics and proteomics approaches identify molecular pathways significantly upregulated in geographic atrophy, including in mitochondrial functions, metabolic pathways and extracellular cellular matrix reorganization. Five significant protein quantitative trait loci that regulate protein expression in the retinal pigment epithelium and in geographic atrophy are identified - two of which share variants with cis- expression quantitative trait loci, including proteins involved in mitochondrial biology and neurodegeneration. Investigation of mitochondrial metabolism confirms mitochondrial dysfunction as a core constitutive difference of the retinal pigment epithelium from patients with geographic atrophy. This study uncovers important differences in retinal pigment epithelium homeostasis associated with geographic atrophy.

The Conundrum of the PFOA human half-life, an international collaboration.

The Steering Committee of the Alliance for Risk Assessment (ARA) opened a call for scientists interested in resolving what appeared to be a conundrum in estimating of the half-life of perfluorooctanoate (PFOA) in humans. An Advisory Committee was formed from nominations received and a subsequent invitation led to the development of three small independent working groups to review appropriate information and attempt a resolution. Initial findings were shared among these groups and a conclusion developed from the ensuing discussions. Many human observational studies have estimated the PFOA half-life. Most of these studies note the likely occurrence of unmonitored PFOA exposures, which could inflate values of the estimated PFOA half-life. Also, few of these studies estimated the half-life of PFOA isomers, the branched chains of which likely have shorter half-lives. This could deflate values of the estimated linear PFOA half-life. Fortunately, several studies informed both of these potential problems. The majority opinion of this international collaboration is that the studies striking the best balance in addressing some of these uncertainties indicate the likely central tendency of the human PFOA half-life is less than 2 years. The single best value appears to be the geometric mean (GM) of 1.3 years (Zhang et al., 2013, Table 3), based on a GM = 1.7 years in young females (n = 20) and GM = 1.2 years in males of all ages and older females (n = 66). However, a combined median value from Zhang et al. (2013) of 1.8 years also adds value to this range of central tendency. While the Collaboration found this study to be the least encumbered with unmonitored PFOA exposures and branched isomers, more studies of similar design would be valuable. Also valuable would be clarification around background exposures in other existing studies in case adjustments to half-life estimates are attempted.

Identifying Genetic Biomarkers Predicting Response to Anti-Vascular Endothelial Growth Factor Injections in Diabetic Macular Edema.

Intraocular anti-vascular endothelial growth factor (VEGF) therapies are the front-line treatment for diabetic macular edema (DME); however, treatment response varies widely. This study aimed to identify genetic determinants associated with anti-VEGF treatment response in DME. We performed a genome-wide association study on 220 Australian patients with DME treated with anti-VEGF therapy, genotyped on the Illumina Global Screening Array, and imputed to the Haplotype Reference Consortium panel. The primary outcome measures were changes in central macular thickness (CMT in microns) and best-corrected visual acuity (BCVA in ETDRS letters) after 12 months. Association between single nucleotide polymorphism (SNP) genotypes and DME outcomes were evaluated by linear regression, adjusting for the first three principal components, age, baseline CMT/BCVA, duration of diabetic retinopathy, and HbA1c. Two loci reached genome-wide significance (p < 5 × 10−8) for association with increased CMT: a single SNP on chromosome 6 near CASC15 (rs78466540, p = 1.16 × 10−9) and a locus on chromosome 12 near RP11-116D17.1 (top SNP rs11614480, p = 2.69 × 10−8). Four loci were significantly associated with reduction in BCVA: two loci on chromosome 11, downstream of NTM (top SNP rs148980760, p = 5.30 × 10−9) and intronic in RP11-744N12.3 (top SNP rs57801753, p = 1.71 × 10−8); one near PGAM1P1 on chromosome 5 (rs187876551, p = 1.52 × 10−8); and one near TBC1D32 on chromosome 6 (rs118074968, p = 4.94 × 10−8). In silico investigations of each locus identified multiple expression quantitative trait loci and potentially relevant candidate genes warranting further analysis. Thus, we identified multiple genetic loci predicting treatment outcomes for anti-VEGF therapies in DME. This work may potentially lead to managing DME using personalized treatment approaches.

The effect of insulin on response to intravitreal anti-VEGF injection in diabetic macular edema in type 2 diabetes mellitus.

OBJECTIVES: To assess whether insulin therapy impacts the effectiveness of anti-vascular endothelial growth factor (anti-VEGF) injection for the treatment of diabetic macular edema (DME) in type 2 diabetes mellitus. METHODS: This was a retrospective multi-center analysis. The best-corrected visual acuity (BCVA) at 12 months, BCVA change, central macular thickness (CMT), CMT change, and cumulative injection number were compared between the insulin and the oral hypoglycemic agent (OHA) groups. RESULTS: The mean final BCVA and CMT improved in both the insulin (N = 137; p < 0.001; p < 0.001, respectively) and the OHA group (N = 61; p = 0.199; p < 0.001, respectively). The two treatment groups were comparable for final BCVA (p = 0.263), BCVA change (p = 0.184), final CMT (p = 0.741), CMT change (p = 0.458), and the cumulative injections received (p = 0.594). The results were comparable between the two groups when stratified by baseline vision (p > 0.05) and baseline HbA1c (p > 0.05). CONCLUSION: Insulin therapy does not alter treatment outcomes for anti-VEGF therapy in DME.

Unravelling the molecular mechanisms underlying chronic respiratory diseases for the development of novel therapeutics via in vitro experimental models.

Chronic respiratory diseases have collectively become a major public health concern and have now taken form as one of the leading causes of mortality worldwide. Most chronic respiratory diseases primarily occur due to prolonged airway inflammation. In addition, critical environmental factors such as cigarette smoke, industrial pollutants, farm dust, and pollens may also exacerbate such diseases. Moreover, alterations in the genetic sequence of an individual, abnormalities in the chromosomes or immunosuppression resulting from bacterial, fungal, and viral infections may also play a key role in the pathogenesis of respiratory diseases. Over the years, multiple in vitro models have been employed as the basis of existing as well as emerging advancements in chronic respiratory disease research. These include cell lines, gene expression techniques, single cell RNA sequencing, cytometry, culture techniques, as well as serum/sputum biomarkers that can be used to elucidate the molecular mechanisms underlying these diseases, and to identify novel diagnostic and management options for these diseases. This review summarizes the current understanding of the pathogenesis of various chronic respiratory diseases derived through in vitro experimental models, where the knowledge obtained from these studies can greatly benefit researchers in the discovery and development of novel screening techniques and advanced therapeutic strategies that could be translated into clinical use in the future.

In-silico identification of lysine residue for α-Amylase immobilization on dialdehyde cellulose.

Enzymes are the precious gift of nature to humans. The wise utilization of enzymes may reduce energy needs of humans and the Immobilization technique can help a lot in this regard. This aspect overcomes limitations of the enzymes, therefore providing an opportunity to explore enzymatic chemistry further. In the present context, it is quite cumbersome & costly to identify the amino acid of enzymes involved in the covalent mode of Immobilization. In the present study, molecular modeling techniques were used to do this difficult task. The present work used molecular modeling methods to extract information about the immobilization of α-Amylase (E.C.3.2.1.1) on Dialdehyde Cellulose. The Lysine residue is the most probable residue to interact with Dialdehyde Cellulose. In the present work, a total of 23 lysine residues were used to study covalent binding behavior with α-Amylase. It was found that if Lys142 is involved in binding with Dialdehyde Cellulose then binding affinity (-6.1 & -5.9 kcal mol-1), as well as the involvement of amino acids of both free α-Amylase and Lys142 immobilized α-Amylase with the starch substrate, were found to be similar. The technique reported here is used for the identification of amino acid residue for the Immobilization of enzymes.