Green route to fabrication of Semal-ZnO nanoparticles for efficient solar-driven catalysis of noxious dyes in diverse aquatic environments.

This work successfully demonstrates a sustainable and environmentally friendly approach for synthesizing Semal-ZnO nanoparticles (NPs) using the aqueous leaf extract of Bombax ceiba L. These NPs exhibit an absorption peak at approximately 390 nm in the UV-visible spectrum and an energy gap (Eg) of 3.11 eV. Detailed analyses of the morphology and particle size using various spectroscopic and microscopic techniques, XRD, FE-SEM with EDS, and HR-TEM reveal crystallographic peaks attributable to the hexagonal phase, with an average crystal size of 17 nm. The Semal-ZnO NPs also exhibit a notable photocatalytic efficiency for degrading methylene blue (MB) and methyl orange (MO) under sunlight in different water samples collected from diverse natural sources, indicating that they are promising photocatalysts for environmental remediation. The photocatalytic efficiency of the biofabricated Semal-ZnO NPs is impressive, exhibiting a photodegradation rate of up to 99% for MB and 79% for MO in different water samples under exposure to sunlight. The novel phytofabricated Semal-ZnO NPs are thus a beacon of hope for the environment, with their desirable photocatalytic efficiency, pseudo-first-order kinetics, and ability to break down noxious dye pollutants in various aquatic environments.

Transcriptional control of embryonic and adult neural progenitor activity.

Neural precursors generate neurons in the embryonic brain and in restricted niches of the adult brain in a process called neurogenesis. The precise control of cell proliferation and differentiation in time and space required for neurogenesis depends on sophisticated orchestration of gene transcription in neural precursor cells. Much progress has been made in understanding the transcriptional regulation of neurogenesis, which relies on dose- and context-dependent expression of specific transcription factors that regulate the maintenance and proliferation of neural progenitors, followed by their differentiation into lineage-specified cells. Here, we review some of the most widely studied neurogenic transcription factors in the embryonic cortex and neurogenic niches in the adult brain. We compare functions of these transcription factors in embryonic and adult neurogenesis, highlighting biochemical, developmental, and cell biological properties. Our goal is to present an overview of transcriptional regulation underlying neurogenesis in the developing cerebral cortex and in the adult brain.

Immune checkpoint inhibitors efficacy across solid cancers and the utility of PD-L1 as a biomarker of response: a systematic review and meta-analysis.

Background: Immune checkpoint inhibitors (ICPI) are a tumor agnostic treatment. However, trials of their use have been site specific. Here we summarize the trial data and explore the utility of programmed death-ligand 1 (PD-L1) expression as a biomarker to direct their pan-cancer use. Method: A systematic review of literature, following PRISMA guidelines, was performed. Medline, Embase, Cochrane CENTRAL, NHS Health and Technology, and Web of Science were searched from their conception to June 2022 limited to the English language. The search terms and method were devised by a specialist medical librarian. Studies were limited to adults with solid cancers (excluding melanomas) treated with ICPIs. Only phase III randomized control trials (RCT) were included. The primary outcome was overall survival and secondary outcomes were progression free survival, PD-L1 expression, quality of life outcomes and adverse event data. Where present in eligible clinical trials, hazard ratios (HR), risk ratios (RR), standard error (SE) and 95% confidence intervals (CI) were extracted or calculated. Heterogeneity across studies was described with the use of an I2 score (Low: 25, 50%: moderate, 75% low heterogeneity). HR pools inverse variance methods were adopted by Random Effects (RE). Means were standardized across any heterogenous scale limits. Results: In total 46,510 participants were included in the meta-analysis. Overall, meta-analysis favored the use of ICPIs with an overall survival (OS) HR of 0.74 (95% CI 0.71 to 0.78). Lung cancers showed the most benefit in OS [HR 0.72 (95% 0.66-0.78)] followed by head and neck cancers [HR 0.75 (95% CI 0.66-0.84)] and gastroesophageal junction cancers [HR 0.75 (95% CI 0.61-0.92)]. ICPIs seem to be efficacious at both primary presentation and recurrence [OS HR 0.73 (95% CI 0.68-0.77)] vs. [OS HR 0.79 (95% CI 0.72 to 0.87)] respectively. Interestingly, subgroup analysis comparing studies in which most cancers demonstrated PD-L1 expression vs. those studies in which a minority of cancer demonstrated PD-L1 expression reported similar effect of ICPI use on OS; oddly the data favored ICPI use in studies with a minority of PD-L1 expression. Specifically, studies with minority PD-L1 expression had an HR 0.73 (95% CI 0.68-0.78) vs. studies with majority PD-L1 expression HR 0.76 (95% CI 0.70-0.84). This was maintained even when studies exploring the same cancer site were directly compared. Subgroup analysis was performed comparing the impact on OS subdivided by the specific ICPI used. Where meta-analysis was performed, Nivolumab led to the greatest impact [HR 0.70 (95% CI 0.64-0.77)] with Avelumab failing to reach significance [HR 0.93 (95% CI 0.80-1.06)]. However, overall heterogenicity was high (I2 = 95%). Finally, the use of ICPIs led to an improved side effect profile when compared with standard chemotherapy [RR 0.85 (95% CI 0.73-0.98)]. Conclusion: ICPIs improve survival outcomes in all cancer types. These effects are seen in the primary, recurrent, chemotherapy sensitive, chemotherapy resistant disease. These data support their use as a tumor agnostic therapy. Furthermore, they are well tolerated. However, PD-L1 as a biomarker for the targeting of ICPI use seems problematic. Other biomarkers such as mismatch repair or tumor mutational burden should be explored in randomized trials. In addition, there are still limited trials looking at ICPI use outside of lung cancer.

International rates of receipt of psychological therapy for psychosis and schizophrenia: systematic review and meta-analysis.

BACKGROUND: International clinical practice guidelines commonly recommend the provision of psychological therapies for psychosis and schizophrenia as an adjunct to medication. However, access to recommended therapies in routine clinical practice is limited. The aim of this review was to synthesise the available data on the provision of recommended psychological therapies for psychosis and schizophrenia across international mental health systems. METHODS: Electronic databases (PsychINFO, Pubmed and EMBASE) were searched for audits, service evaluation projects, or surveys, which reported data on rates of offer or receipt of any recommended psychological therapy or therapeutic intervention as part of routine clinical care. RESULTS: Twenty-two eligible studies from 9 countries were identified (N participants = 79,407). The most commonly recommended therapies in national guidelines were Cognitive-Behavioural Therapy for Psychosis (CBTp) and Family Interventions (FI). The overall pooled prevalence of rate of receipt of CBTp was 24% [95% CI 0.15-0.32] based on 15 studies (N = 42,494), with a higher rate of receipt of therapy found when pooling data from Early Intervention services only (41% [95% CI 0.21-0.60], 6 studies, N = 11,068). The overall pooled prevalence of rate of receipt of FI was 30% [95% CI 0.22-0.37] based on 14 studies (N = 13,863). CONCLUSIONS: Overall rates of receipt of recommended psychological therapies for psychosis were low across the 9 countries data were available for in this review. However, there were high rates of heterogeneity across studies, meaning that pooled estimates should be interpreted with caution. Sources of heterogeneity included different service settings (e.g. early intervention vs. non-early intervention services), and varying methods used to collect the data (e.g. audit of electronic health records vs. self-report etc.). There were no available data from the continents of South America, Asia, or Africa, meaning that a truly global picture of provision of psychological therapies for psychosis and schizophrenia is currently lacking.

Targeting Artemisinin-Resistant Malaria by Repurposing the Anti-Hepatitis C Virus Drug Alisporivir.

The emergence of Plasmodium falciparum resistance raises an urgent need to find new antimalarial drugs. Here, we report the rational repurposing of the anti-hepatitis C virus drug, alisporivir, a nonimmunosuppressive analog of cyclosporin A, against artemisinin-resistant strains of P. falciparum. In silico docking studies and molecular dynamic simulation predicted strong interaction of alisporivir with PfCyclophilin 19B, confirmed through biophysical assays with a Kd value of 354.3 nM. Alisporivir showed potent antimalarial activity against chloroquine-resistant (PfRKL-9 with resistance index [Ri] 2.14 ± 0.23) and artemisinin-resistant (PfKelch13R539T with Ri 1.15 ± 0.04) parasites. The Ri is defined as the ratio between the IC50 values of the resistant line to that of the sensitive line. To further investigate the mechanism involved, we analyzed the expression level of PfCyclophilin 19B in artemisinin-resistant P. falciparum (PfKelch13R539T). Semiquantitative real-time transcript, Western blot, and immunofluorescence analyses confirmed the overexpression of PfCyclophilin 19B in PfKelch13R539T. A 50% inhibitory concentration in the nanomolar range, together with the targeting of PfCyclophilin 19B, suggests that alisporivir can be used in combination with artemisinin. Since artemisinin resistance slows the clearance of ring-stage parasites, we performed a ring survival assay on artemisinin-resistant strain PfKelch13R539T and found significant decrease in parasite survival with alisporivir. Alisporivir was found to act synergistically with dihydroartemisinin and increase its efficacy. Furthermore, alisporivir exhibited antimalarial activity in vivo. Altogether, with the rational target-based Repurposing of alisporivir against malaria, our results support the hypothesis that targeting resistance mechanisms is a viable approach toward dealing with drug-resistant parasite.

Complementary crosstalk between palmitoylation and phosphorylation events in MTIP regulates its role during Plasmodium falciparum invasion.

Post-translational modifications (PTMs) including phosphorylation and palmitoylation have emerged as crucial biomolecular events that govern many cellular processes including functioning of motility- and invasion-associated proteins during Plasmodium falciparum invasion. However, no study has ever focused on understanding the possibility of a crosstalk between these two molecular events and its direct impact on preinvasion- and invasion-associated protein-protein interaction (PPI) network-based molecular machinery. Here, we used an integrated in silico analysis to enrich two different catalogues of proteins: (i) the first group defines the cumulative pool of phosphorylated and palmitoylated proteins, and (ii) the second group represents a common set of proteins predicted to have both phosphorylation and palmitoylation. Subsequent PPI analysis identified an important protein cluster comprising myosin A tail interacting protein (MTIP) as one of the hub proteins of the glideosome motor complex in P. falciparum, predicted to have dual modification with the possibility of a crosstalk between the same. Our findings suggested that blocking palmitoylation led to reduced phosphorylation and blocking phosphorylation led to abrogated palmitoylation of MTIP. As a result of the crosstalk between these biomolecular events, MTIP's interaction with myosin A was found to be abrogated. Next, the crosstalk between phosphorylation and palmitoylation was confirmed at a global proteome level by click chemistry and the phenotypic effect of this crosstalk was observed via synergistic inhibition in P. falciparum invasion using checkerboard assay and isobologram method. Overall, our findings revealed, for the first time, an interdependence between two PTM types, their possible crosstalk, and its direct impact on MTIP-mediated invasion via glideosome assembly protein myosin A in P. falciparum. These insights can be exploited for futuristic drug discovery platforms targeting parasite molecular machinery for developing novel antimalarial therapeutics.

Effectiveness of tea tree oil versus chlorhexidine in the treatment of periodontal diseases: a systematic review.

Background Plaque biofilm that adheres to tooth surfaces and gingiva is the main aetiology of periodontitis. Chlorhexidine (CHX) is considered as a gold standard anti-plaque and anti-gingivitis agent but it has side effects such as permanent staining of teeth and dysgeusia. Tea tree oil (TTO) is an essential oil extracted from the leaves of Melaleuca alternifolia. Many studies have reported that TTO exerts strong antibacterial, antifungal, antiviral and anti-inflammatory activities.Primary study objective The review aims to answer the question of whether TTO (intervention) is a viable alternative to CHX (comparator) for the management of gingival and periodontal disease (outcomes) in adolescents and adults (population).Methods/design The following search terms were used in PubMed, Scopus, Proquest, Web of Science, EBSCO (dentistry and open access), Cochrane database, Clinical.gov.org and ctri.nic.in to search for relevant articles: patients with periodontal disease; OR periodontitis; OR gingivitis; OR gingival inflammation; AND essential oil; OR tea tree oil; OR Melaleuca alternifolia; AND chlorhexidine; AND reduction in gingival index; OR reduction in plaque index; OR reduction in bleeding from gums. The initial check for the title and abstract screening followed by removal of duplicates in Mendeley Reference Manager (version 1.19.4) based on the inclusion and exclusion criteria were performed.Primary outcome measures Parameters such as plaque index (PI), plaque surface score, gingival index (GI), bleeding index or bleeding as measured by % of sites with bleeding on probing (BOP) or bleeding scores, papillary bleeding index (PBI), were the primary outcomes considered.Results TTO is found to be superior to CHX in reducing signs of gingival inflammation; however, CHX is superior to TTO in inhibiting plaque formation, probably due to its increased substantivity.Conclusion TTO may be used as an alternative to CHX for reduction of gingival inflammation in conjunction with efficient plaque control measures.

Analytical methods to determine and sense heavy metal pollutants using MXene and MXene-based composites: Mechanistic prophecy into sensing properties.

The presence of heavy metal ions in the biosphere is of grave concern, as these are toxic and impact living organisms. Lack of pure drinking water can spread waterborne diseases like cholera, dysentery, typhoid, etc. The presence of heavy metals like arsenic and radioactive materials can cause cancer. The detection and removal of these heavy metals are important for sustaining life. Herein, MXene comes to the rescue as a crucial and potential material, which can sense and adsorb heavy metal ions. Developed in 2011, MXenes are an emerging class of 2D nanomaterials that are appropriate substitutes for existing heavy metal ions sensing materials and have shown excellent efficiency due to their better hydrophilicity, capacity of transportation of electrons, functionalization, and a great variety in compositions as compared to the other nanomaterials properties. This work gives an insight into the chemistry and synthesis of MXenes for further utilization as a sensor in heavy metal ions toxicity and underlines the key future challenges to knowing the full prospective of MXenes in environmental systems.

Implementing a health labour market analysis to address health workforce gaps in a rural region of India.

BACKGROUND: Human Resources for Health (HRH) are essential for making meaningful progress towards universal health coverage (UHC), but health systems in most of the developing countries continue to suffer from serious gaps in health workforce. The Global Strategy on Human Resources for Health-Workforce 2030, adopted in 2016, includes Health Labor Market Analysis (HLMA) as a tool for evidence based health workforce improvements. HLMA offers certain advantages over the traditional approach of workforce planning. In 2018, WHO supported a HLMA exercise in Chhattisgarh, one of the predominantly rural states of India. METHODS: The HLMA included a stakeholder consultation for identifying policy questions relevant to the context. The HLMA focused on state HRH at district-level and below. Mixed methods were used for data collection and analysis. Detailed district-wise data on HRH availability were collected from state's health department. Data were also collected on policies implemented on HRH during the 3 year period after the start of HLMA and changes in health workforce. RESULTS: The state had increased the production of doctors but vacancies persisted until 2018. The availability of doctors and other qualified health workers was uneven with severe shortages of private as well as public HRH in rural areas. In case of nurses, there was a substantial production of nurses, particularly from private schools, however there was a lack of trusted accreditation mechanism and vacancies in public sector persisted alongside unemployment among nurses. Based on the HLMA, pragmatic recommendations were decided and followed up. Over the past 3 years since the HLMA began an additional 4547 health workers including 1141 doctors have been absorbed by the public sector. The vacancies in most of the clinical cadres were brought below 20%. CONCLUSION: The HLMA played an important role in identifying the key HRH gaps and clarifying the underlying issues. The HLMA and the pursuant recommendations were instrumental in development and implementation of appropriate policies to improve rural HRH in Chhattisgarh. This demonstrates important progress on key 2030 Global Strategy milestones of reducing inequalities in access to health workers and improving financing, retention and training of HRH.

Host SUMOylation Pathway Negatively Regulates Protective Immune Responses and Promotes Leishmania donovani Survival.

SUMOylation is one of the post-translational modifications that have recently been described as a key regulator of various cellular, nuclear, metabolic, and immunological processes. The process of SUMOylation involves the modification of one or more lysine residues of target proteins by conjugation of a ubiquitin-like, small polypeptide known as SUMO for their degradation, stability, transcriptional regulation, cellular localization, and transport. Herein, for the first time, we report the involvement of the host SUMOylation pathway in the process of infection of Leishmania donovani, a causative agent of visceral leishmaniasis. Our data revealed that infection of L. donovani to the host macrophages leads to upregulation of SUMOylation pathway genes and downregulation of a deSUMOylating gene, SENP1. Further, to confirm the effect of the host SUMOylation on the growth of Leishmania, the genes associated with the SUMOylation pathway were silenced and parasite load was analyzed. The knockdown of the SUMOylation pathway led to a reduction in parasitic load, suggesting the role of the host SUMOylation pathway in the disease progression and parasite survival. Owing to the effect of the SUMOylation pathway in autophagy, we further investigated the status of host autophagy to gain mechanistic insights into how SUMOylation mediates the regulation of growth of L. donovani. Knockdown of genes of host SUMOylation pathway led to the reduction of the expression levels of host autophagy markers while promoting autophagosome-lysosome fusion, suggesting SUMOylation-mediated autophagy in terms of autophagy initiation and autophagy maturation during parasite survival. The levels of reactive oxygen species (ROS) generation, nitric oxide (NO) production, and pro-inflammatory cytokines were also elevated upon the knockdown of genes of the host SUMOylation pathway during L. donovani infection. This indicates the involvement of the SUMOylation pathway in the modulation of protective immune responses and thus favoring parasite survival. Taken together, the results of this study indicate the hijacking of the host SUMOylation pathway by L. donovani toward the suppression of host immune responses and facilitation of host autophagy to potentially facilitate its survival. Targeting of SUMOylation pathway can provide a starting point for the design and development of novel therapeutic interventions to combat leishmaniasis.

CD47 Binding on Vascular Endothelial Cells Inhibits IL-17-Mediated Leukocyte Adhesion.

To address the conflicting role of thrombospondin (TSP)-1 reported in acute and chronic pathologies, this study investigated the role of TSP-1 in regulating leukocyte recruitment and regulation of VCAM-1 expression using mouse models of uveitis. The spontaneously increased VCAM-1 expression and leukocyte adhesion in retinas of TSP-1-deficient mice suggested a TSP-1-mediated regulation of VCAM-1 expression. In a chronic uveitis model, induced by immunizing wild-type mice with specific interphotoreceptor retinoid-binding protein (IRBP) peptide, topically applied TSP-1-derived CD47-binding peptide significantly reduced the clinical disease course and retinal leukocyte adhesion as compared to the control peptide-treated group. In contrast, in LPS-mediated acute uveitis, TSP-1 deficiency significantly reduced the retinal leukocyte adhesion. The results of our in vitro study, using vascular endothelial cell (EC) cultures, demonstrate that unlike TNF-α, VCAM-1 expression induced by IL-17 is associated with a reduced expression of endogenous TSP-1. Such reduced endogenous TSP-1 expression in IL-17-stimulated ECs helps limit the CD36-mediated increased VCAM-1 expression, while favoring CD47-mediated inhibition of VCAM-1 expression and leukocyte adhesion. Thus, our study identifies TSP-1:CD47 interaction as a molecular pathway that modulates IL-17-mediated VCAM-1 expression, contributing to its anti-inflammatory effect in chronic inflammatory conditions.

The Role of Tissue Geometry in Spinal Cord Regeneration.

Unlike peripheral nerves, axonal regeneration is limited following injury to the spinal cord. While there may be reduced regenerative potential of injured neurons, the central nervous system (CNS) white matter environment appears to be more significant in limiting regrowth. Several factors may inhibit regeneration, and their neutralization can modestly enhance regrowth. However, most investigations have not considered the cytoarchitecture of spinal cord white matter. Several lines of investigation demonstrate that axonal regeneration is enhanced by maintaining, repairing, or reconstituting the parallel geometry of the spinal cord white matter. In this review, we focus on environmental factors that have been implicated as putative inhibitors of axonal regeneration and the evidence that their organization may be an important determinant in whether they inhibit or promote regeneration. Consideration of tissue geometry may be important for developing successful strategies to promote spinal cord regeneration.

Outcomes of macular buckling with a T-shaped buckle for myopic tractional maculopathies associated with posterior staphyloma: An Indian experience.

PURPOSE: : To report the anatomic and visual outcomes following macular buckling in patients affected by pathological myopia-associated foveoschisis (FS) and macular detachment with or without macular hole (MH). METHODS: A retrospective interventional consecutive case series wherein 25 highly myopic eyes (mean axial length 28.46 mm; range, 25-33.8 mm) of 24 patients (16 females and 8 males; mean age 54.1 years; range, 35-74 years) presenting with macular detachment associated with a posterior staphyloma (PS), who underwent macular buckling, were evaluated. Patients with absence or reduction in subretinal fluid by more than 90% during the final follow-up along with inversion of contour of staphyloma were considered to have a successful anatomical outcome and those with improvement or maintenance in visual acuity were considered to have a successful functional outcome. The mean duration of follow-up was 11.2 months. RESULTS: At the time of initial presentation, the mean age of the 24 patients was 54.1 ± 10.28 years. Macular detachment along with FS was present in all cases, whereas full-thickness macular hole-related retinal detachment was present in nine cases. Swept-source optical coherence tomography parameters showed reduction of FS with foveal reattachment in all eyes except one at last visit. Mean axial length decreased from 28.5 mm preoperatively (range 26-33.8 mm) to 26.2 mm (range 24-29.3 mm). The mean best-corrected visual acuity changed from 1.16 log MAR to 1.096 Log MAR (P = 0.165). Visual acuity improved in 10 eyes (40%), remained stable in 11 eyes (44%) and decreased in 4 eyes (16%). CONCLUSION: Macular buckling is a good surgical technique with encouraging anatomic and visual outcomes in patients with myopic macular detachment associated with PS. Highly selective cases of myopic traction maculopathy can have a viable option of macular buckle surgery in stabilizing the retinal tractional changes, and thereby, vision loss.

Artificial Intelligence Efficiently Identifies Regional Differences in the Progression of Tomographic Parameters of Keratoconic Corneas.

PURPOSE: To develop an artificial intelligence (AI) model to effectively assess local versus global progression of keratoconus using multiple tomographic parameters. METHODS: This was a retrospective review of medical records of patients diagnosed as having keratoconus. A total of 1,884 Pentacam (Oculus Optikgeräte GmbH) scans of 366 eyes (296 patients) were analyzed. Based on an increase in maximum anterior curvature (Kmax), the eyes were classified as actual "progression" and "no progression." The corresponding changes in other Pentacam parameters were incorporated to train and cross-validate (five-fold) the AI models. Three AI models were trained (an increase in Kmax by A = 0.75 diopters [D], B = 1.00 D, and C = 1.25 D). The area under the curve (AUC), sensitivity, specificity, and classification accuracy, along with other metrics, were evaluated. RESULTS: The AUC, sensitivity, specificity, and classification accuracy were 0.90, 85%, 82%, and 83%, respectively, for Model A; 0.91, 86%, 82%, and 88%, respectively, for Model B; and 0.93, 89%, 81%, and 91%, respectively, for Model C. All models also predicted that 60% to 62% of the actual progression eyes had concomitant progression-associated changes in the other Pentacam parameters (global progression). However, there was discordance between increase in Kmax and concomitant associated changes in the other parameters in 38.8% to 40% of the eyes (local progression). CONCLUSIONS: The AI models identified the eyes where the increase in Kmax and corresponding progression-associated changes in the other parameters were in agreement. These eyes may require corneal cross-linking earlier than the rest. [J Refract Surg. 2021;37(4):240-248.].

Influence of segmental supply of Cilioretinal artery on morphology of diabetic macular edema.

BACKGROUND: The supply of Cilioretinal artery (CRA) to different layers of the retina influences retinal pathologies such as diabetic retinopathy (DR). Since the supply of CRA is segmental, our aim was to analyze the location of CRA with respect to non - center involving diabetic macular edema (DME) differentiated by various segments and center involving DME based on Early Treatment of Diabetic Retinopathy Study (ETDRS) scale using optical coherence tomography (OCT). METHODS: A retrospective study was conducted in which forty-three patients with various stages of DR and the presence of CRA were identified. Presence and location of CRA was recognized using fundus fluorescein angiography. Classification of DME was based on ETDRS subfields on OCT. RESULTS: Evaluation of 26 men and 17 women with varying degrees of severity involving DR revealed the presence of unilateral CRA in 40 subjects and bilateral CRA in 3 subjects. When CRA supplied the central area, maximum retinal thickness was noted at the temporal quadrant (271.67 ± 164.02 µm) along with non - center involving DME (194.87 ± 121.06 µm); when CRA supplied the lower area, maximum retinal thickness was noted at the superior quadrant (293.64 ± 159.36 µm) along with center involving DME (395 ± 285.75 µm) and when it supplied the upper area, maximum retinal thickness was noted at the nasal quadrant (293.49 ± 176.18 µm) along with center involving DME (292 ± 192.79 µm). CONCLUSION: The presence of CRA seems to influence the morphology of the retina amongst patients diagnosed with DR by altering the segments involved in DME based on its supply location. However, further studies with a larger sample size are warranted to strenghten this association.

Pathogen induced subversion of NAD+ metabolism mediating host cell death: a target for development of chemotherapeutics.

Hijacking of host metabolic status by a pathogen for its regulated dissemination from the host is prerequisite for the propagation of infection. M. tuberculosis secretes an NAD+-glycohydrolase, TNT, to induce host necroptosis by hydrolyzing Nicotinamide adenine dinucleotide (NAD+). Herein, we expressed TNT in macrophages and erythrocytes; the host cells for M. tuberculosis and the malaria parasite respectively, and found that it reduced the NAD+ levels and thereby induced necroptosis and eryptosis resulting in premature dissemination of pathogen. Targeting TNT in M. tuberculosis or induced eryptosis in malaria parasite interferes with pathogen dissemination and reduction in the propagation of infection. Building upon our discovery that inhibition of pathogen-mediated host NAD+ modulation is a way forward for regulation of infection, we synthesized and screened some novel compounds that showed inhibition of NAD+-glycohydrolase activity and pathogen infection in the nanomolar range. Overall this study highlights the fundamental importance of pathogen-mediated modulation of host NAD+ homeostasis for its infection propagation and novel inhibitors as leads for host-targeted therapeutics.

Trending biocontrol strategies against Cronobacter sakazakii: A recent updated review.

Cronobacter sakazakii is an emerging foodborne pathogen, causing life-threatening infections in newborns and premature infants. Cronobacter spp. can survive under difficult processing conditions thereby contaminate the Powdered Infant Formula (PIF) during the manufacturing process. Infantile infections are associated with the consumption of contaminated PIF that was either contaminated intrinsically or extrinsically. This necessitates the development of sustainable strategies to manage the risk of Cronobacter infections. Natural methods of preservation holds promise as a viable alternative strategy to address the critical problem of emerging antimicrobial resistance and also to limit the negative effects of commonly used physico-chemical methods in food processing. The present study reviews the efficacies, potentials and developmental trends of biological antagonists and a combinatorial therapy to eliminate C. sakazakii using in vitro and in vivo methods. The mode of action of each biocontrol method has been discussed comprehensively. Most of these biocontrol agents interfere with the cell membrane integrity and its functions. However, none of the individual methods are able to eliminate the pathogen completely from the model food system i.e. reconstituted PIF. Each of the biological control strategies (agent) has its limitations in terms of their dose and method of application. A synergistic effect has been observed between the biological agent and physico-chemical treatments that may have the potential to ensure pathogen-free foods. Future research studies should evaluate the synergistic activities of these methods for their implication in infant foods as well as to understand the mechanisms of inactivation.

Lactobacillus gastricus BTM 7 prevents intestinal colonization by biofilm forming Cronobacter sakazakii in Caenorhabditis elegans model host.

The study reports protective role of potential probiotic cultures against infection by biofilm forming Cronobacter sakazakii in Caenorhabditis elegans model system. Among the fifteen indigenous potential probiotics, the cell free supernatant of Lactobacillus gastricus BTM7 possessed highest antimicrobial action and biofilm inhibition against C. sakazakii. The competitive exclusion assays revealed that preconditioning with probiotics resulted in increased mean life span of the nematode to 12-13 days as compared to 5-6 days when the pathogen was administered alone. Enhanced expression of the marker genes (pmk-1, daf-16 and skn-1) was observed during the administration of probiotic cultures. The highest expression of pmk-1 (2.5 folds) was observed with administration of L. gastricus BTM7. The principal component analysis on selected variables revealed that L. gastricus BTM7 has the potential to limit the infection of C. sakazakii in C. elegans and enhance the expression of key genes involved in extending life span of the worm.

Routing Based Multi-Agent System for Network Reliability in the Smart Microgrid.

Microgrids help to achieve power balance and energy allocation optimality for the defined load networks. One of the major challenges associated with microgrids is the design and implementation of a suitable communication-control architecture that can coordinate actions with system operating conditions. In this paper, the focus is to enhance the intelligence of microgrid networks using a multi-agent system while validation is carried out using network performance metrics i.e., delay, throughput, jitter, and queuing. Network performance is analyzed for the small, medium and large scale microgrid using Institute of Electrical and Electronics Engineers (IEEE) test systems. In this paper, multi-agent-based Bellman routing (MABR) is proposed where the Bellman-Ford algorithm serves the system operating conditions to command the actions of multiple agents installed over the overlay microgrid network. The proposed agent-based routing focuses on calculating the shortest path to a given destination to improve network quality and communication reliability. The algorithm is defined for the distributed nature of the microgrid for an ideal communication network and for two cases of fault injected to the network. From this model, up to 35%-43.3% improvement was achieved in the network delay performance based on the Constant Bit Rate (CBR) traffic model for microgrids.

Probiotic mediated NF-κB regulation for prospective management of type 2 diabetes.

Diabetes and other lifestyle disorders have been recognized as the leading cause of morbidity and mortality globally. Nuclear factor kappa B (NF-κB) is a major factor involved in the early pathobiology of diabetes and studies reveal that hyperglycemic conditions in body leads to NF-κB mediated activation of several cytokines, chemokines and inflammatory molecules. NF-κB family comprises of certain DNA-binding protein factors that elicit the transcription of pro-inflammatory molecules. Various studies have identified NF-κB as a promising target for diabetic management. Probiotics have been proposed as bio-therapeutic agents for treatment of inflammatory disorders and many other chronic clinical stages. The precise mechanisms by which probiotics acts is yet to be fully understood, however research findings have indicated their role in NF-κB modulation. The current review highlights NF-κB as a bio-therapeutic target for probable management of type 2 diabetes through probiotic intervention.