Diabetic retinopathy is a ceramidopathy reversible by anti-ceramide immunotherapy.

Diabetic retinopathy is a microvascular disease that causes blindness. Using acid sphingomyelinase knockout mice, we reported that ceramide generation is critical for diabetic retinopathy development. Here, in patients with proliferative diabetic retinopathy, we identify vitreous ceramide imbalance with pathologic long-chain C16-ceramides increasing and protective very long-chain C26-ceramides decreasing. C16-ceramides generate pro-inflammatory/pro-apoptotic ceramide-rich platforms on endothelial surfaces. To geo-localize ceramide-rich platforms, we invented a three-dimensional confocal assay and showed that retinopathy-producing cytokines TNFα and IL-1ß induce ceramide-rich platform formation on retinal endothelial cells within seconds, with volumes increasing 2-logs, yielding apoptotic death. Anti-ceramide antibodies abolish these events. Furthermore, intravitreal and systemic anti-ceramide antibodies protect from diabetic retinopathy in standardized rodent ischemia reperfusion and streptozotocin models. These data support (1) retinal endothelial ceramide as a diabetic retinopathy treatment target, (2) early-stage therapy of non-proliferative diabetic retinopathy to prevent progression, and (3) systemic diabetic retinopathy treatment; and they characterize diabetic retinopathy as a "ceramidopathy" reversible by anti-ceramide immunotherapy.

A prospective health economic evaluation to determine the productivity loss due to premature mortality from oral cancer in India.

INTRODUCTION: India contributes two-thirds of the global mortality due to oral cancer and has a younger population at risk. The societal costs of this premature mortality are barely discussed. METHODS: Using the human capital approach, we aimed to estimate the productivity lost due to premature mortality, valued using individual socioeconomic data, related to oral cancer in India. A bottom-up approach was used to prospectively collect data of 100 consecutive patients with oral cancer treated between 2019 and 2020, with a follow-up of 36 months. RESULTS: The disease-specific survival for early and advanced stage was 85% and 70%, with a median age of 47 years. With 671 years lost prematurely, the loss of productivity was $41 900/early and $96 044/advanced stage. Based on population level rates, the total cost of premature mortality was $5.6 billion, representing 0.18% of GDP. CONCLUSION: India needs to implement tailored strategies to reduce the economic burden from premature mortality.

Areca nut and oral cancer.

INTRODUCTION: The association between areca nut consumption and oral cancer has been a subject of increasing concern in global public health. GLOBAL PERSPECTIVE: Areca nut, often chewed in various forms such as betel quid, is deeply rooted in cultural practices across Asia and other parts of the world. Epidemiological studies consistently reveal a significant correlation between areca nut use and the incidence of oral cancer, emphasizing the need for targeted preventive measures. The complex interplay of areca nut's bioactive compounds, particularly arecoline, with cellular processes, contributes to the initiation and progression of oral carcinogenesis. Mechanistic insights into the genotoxic and cytotoxic effects of its components underscore the urgency for comprehensive public health interventions. PUBLIC HEALTH: Efforts to address this public health challenge involve multidisciplinary approaches, encompassing education, policy implementation, and behavioral interventions. Understanding the socio-cultural factors influencing areca nut consumption is pivotal for designing effective awareness campaigns and cessation programs. CONCLUSION: As oral cancer remains a significant global health burden, unraveling the nuanced relationship between areca nut and its role in oral carcinogenesis is crucial for advancing preventive strategies and mitigating the impact of this modifiable risk factor.

Chemoprofiling and medicinal potential of underutilized leaves of Cyperus scariosus.

Agro-waste is the outcome of the under-utilization of bioresources and a lack of knowledge to re-use this waste in proper ways or a circular economy approach. In the Indian medicinal system, the root of Cyperus scariosus (CS) is used at a large scale due to their vital medicinal properties. Unfortunately, the aerial part of CS is treated as agro-waste and is an under-utilized bioresource. Due to a lack of knowledge, CS is treated as a weed. This present study is the first ever attempt to explore CS leaves as medicinally and a nutrient rich source. To determine the food and nutritional values of the neglected part of Cyperus scariosus R.Br. (CS), i.e. CS leaves, phytochemicals and metal ions of CS were quantified by newly developed HPLC and ICPOES-based methods. The content of the phytochemicals observed in HPLC analysis for caffeic acid, catechin, epicatechin, trans-p-coumaric acid, and trans-ferulic acid was 10.51, 276.15, 279.09, 70.53, and 36.83 µg/g, respectively. In GC-MS/MS analysis, fatty acids including linolenic acid, phytol, palmitic acid, etc. were identified. In ICPOES analysis, the significant content of Na, K, Ca, Cu, Fe, Mg, Mn, and Zn was observed. The TPC and TFC of the CS leaves was 17.933 mg GAE eq./g and 130.767 mg QCE eq./g along with an IC50 value of 2.78 mg/mL in the DPPH assay and better antacid activity was measured than the standard (CaCO3). The methanolic extract of CS leaves showed anti-microbial activity against Staphylococcus aureus (15 ± 2 mm), Pseudomonas aeruginosa (12 ± 2 mm) and Escherichia coli (10 ± 2 mm). In silico studies confirmed the in vitro results obtained from the antioxidant, antiacid, and anti-microbial studies. In addition, in silico studies revealed the anti-cancerous and anti-inflammatory potential of the CS leaves. This study, thus, demonstrated the medicinal significance of the under-utilized part of CS and the conversion of agro-waste into mankind activity as a pharmaceutical potent material. Consequently, the present study highlighted that CS leaves have medicinal importance with good nutritional utility and have a large potential in the pharmaceutical industry along with improving bio-valorization and the environment.

Unpacking the influencing factors of telehealth usage among older consumers.

This research unpacks the challenges and motivations of telehealth usage among older consumers-an understudied population in the extant telehealth literature. Through surveying a sample of older consumers who regularly migrate to winter in the southern areas of the United States, our qualitative analysis uncovers motivations (i.e., convenience, ease of use, efficiency, and a forced option) and challenges (i.e., telehealth limitations, privacy concerns, and lack of trust, access, and skills) of older consumers' telehealth usage. Furthermore, logistic regression identifies attitude toward telehealth, gender, and health status as significant predictors of telehealth usage behavior. Contributions to theory and practice are also discussed.

Molecular characterization of Red banana and its somaclonal variant: a comprehensive study.

The prized Red banana, selected for superior qualities, demands strong genetic uniformity for successful clonal propagation and preservation. Ensuring this uniformity early in the growth of in vitro Red banana plants is essential, as gene mutations and chromosome rearrangements during tissue culture can jeopardize both cloning and germplasm conservation. In this situation, molecular markers play a pivotal role in confirming genetic stability. Thus the study aims to discover a marker that identifies tissue-cultured Red bananas from their virescent variants during initial sub-culturing. A marker linked to anthocyanin has been identified which effectively differentiated Red bananas from virescent variants and it was further validated in various banana cultivars, ornamental Musa species and their interspecific hybrids. The PCR-based marker showed remarkable specificity, discerning Red bananas from virescent variants during tissue culture. It also distinguished green and red offspring, cutting time and resource costs, and shortening the banana breeding cycle. Supplementary Information: The online version contains supplementary material available at 10.1007/s13205-023-03868-6.

Establishment of the mechanism of purification and levigation of green chemistry-assisted biocomposites of red ochre (Gairika): synthesis, characterization, and antibacterial, prebiotic, antioxidant, and antacid activities of the traditional Ayurvedic medicine Laghu Sutashekhara Rasa.

Gairika (red ochre) has a long history of influencing human civilization. Gairika is a rich source of nutrients used for reproductive and brain health. Gairika is mentioned as an antacid drug in Indian Ayurvedic medicine under Laghu Sutashekhara Rasa (LSR). However, a detailed study on LSR has not been reported to date. In the present study, LSR was prepared, and a pharmaceutical SOP (standardization procedure) was reported to obtain batch-to-batch reproducibility. LSR was characterized using FTIR, XRD, SEM-EDX, and TGA analyses. LSR was tested in vitro for its antacid activity. Advanced instrumentation revealed that LSR formation produced symmetrical particles (5-8 µm) with kaolin, kaolinite, quartz, goethite, and hematite, along with the phytoconstituents of Goghrita (clarified cow's butter), Shunthi, and Nagawalli, as confirmed by GC-MS/MS analysis. The FTIR study revealed the formation of a chelating complex of goethite and hematite along with their phytoconstituents. XRD analysis confirmed the presence of kaolin, kaolinite, quartz, goethite, and hematite. Using in vitro antacid experiments, LSR and Shunthi demonstrated significant antacid activity as compared to antacid drugs and standards in the market, such as CaCO3. The DPPH assay revealed IC50 values of 12.16 ± 1.23 mg/mL, which is 0.0029 of Trolox-equivalent antioxidant activity. The inhibition (18 ± 4 mm) against pathogens (S. aureus, E. coli, P. aeruginosa, and B. subtilis) and the prominent growth of gut microbiota-supported strains (S. boulardii, L. paracasei, and L. plantarum) observed on LSR formulation were indicative of LSR application as a prebiotic. Here, the mechanism of purification and levigation mentioned in the classical literature of LSR was established. Overall, purification of Gairika with cow ghee and levigation with Nagawalli may enhance the solubility, bioavailability, and shelf-life of LSR through hydration and co-crystallization mechanisms. This is the first comprehensive report on the pharmaceutical validation of LSR and its characterization. The results of the present study could contribute to the development and reliable reproduction of LSR and the utility of environmental red ochre as a medicine in combination with Shunthi (Zingiber officinale Roxb.), as prescribed under Indian Ayurvedic medicine.

Harnessing Rhizospheric Microbes for Eco-friendly and Sustainable Crop Production in Saline Environments.

Soil salinization is a global issue that negatively impacts crop yield and has become a prime concern for researchers worldwide. Many important crop plants are susceptible to salinity-induced stresses, including ionic and osmotic stress. Approximately, 20% of the world's cultivated and 33% of irrigated land is affected by salt. While various agricultural practices have been successful in alleviating salinity stress, they can be costly and not environment-friendly. Therefore, there is a need for cost-effective and eco-friendly practices to improve soil health. One promising approach involves utilizing microbes found in the vicinity of plant roots to mitigate the effects of salinity stress and enhance plant growth as well as crop yield. By exploiting the salinity tolerance of plants and their associated rhizospheric microorganisms, which have plant growth-promoting properties, it is possible to reduce the adverse effects of salt stress on crop plants. The soil salinization is a common problem in the world, due to which we are unable to use the saline land. To make proper use of this land for different crops, microorganisms can play an important role. Looking at the increasing population of the world, this will be an appreciated effort to make the best use of the wasted land for food security. The updated information on this issue is needed. In this context, this article provides a concise review of the latest research on the use of salt-tolerant rhizospheric microorganisms to mitigate salinity stress in crop plants.

Current Perspective and Mechanistic Insights on Bioactive Plant Secondary Metabolites for the Prevention and Treatment of Cardiovascular Diseases.

Cardiovascular diseases (CVDs) are one of the most prevalent medical conditions of modern era and are one of the primary causes of adult mortality in both developing and developed countries. Conventional medications such as use of aspirin, beta-blockers, statins and angiotensin- converting enzyme inhibitors involve use of drugs with many antagonistic effects. Hence, alternative therapies which are safe, effective, and relatively cheap are increasingly being investigated for the treatment and prevention of CVDs. The secondary metabolites of medicinal plants contain several bioactive compounds which have emerged as alternatives to toxic modern medicines. The detrimental effects of CVDs can be mitigated via the use of various bioactive phytochemicals such as catechin, isoflavones, quercetin etc. present in medicinal plants. Current review intends to accumulate previously published data over the years using online databases concerning herbal plant based secondary metabolites that can help in inhibition and treatment of CVDs. An in-depth review of various phytochemical constituents with therapeutic actions such as antioxidant, anti-inflammatory, vasorelaxant, anti-hypertensive and cardioprotective properties has been delineated. An attempt has been made to provide a probable mechanistic overview for the pertinent phytoconstituent which will help in achieving a better prognosis and effective treatment for CVDs.

Characterizing the regulatory Fas (CD95) epitope critical for agonist antibody targeting and CAR-T bystander function in ovarian cancer.

Receptor clustering is the most critical step to activate extrinsic apoptosis by death receptors belonging to the TNF superfamily. Although clinically unsuccessful, using agonist antibodies, the death receptors-5 remains extensively studied from a cancer therapeutics perspective. However, despite its regulatory role and elevated function in ovarian and other solid tumors, another tumor-enriched death receptor called Fas (CD95) remained undervalued in cancer immunotherapy until recently, when its role in off-target tumor killing by CAR-T therapies was imperative. By comprehensively analyzing structure studies in the context of the binding epitope of FasL and various preclinical Fas agonist antibodies, we characterize a highly significant patch of positively charged residue epitope (PPCR) in its cysteine-rich domain 2 of Fas. PPCR engagement is indispensable for superior Fas agonist signaling and CAR-T bystander function in ovarian tumor models. A single-point mutation in FasL or Fas that interferes with the PPCR engagement inhibited apoptotic signaling in tumor cells and T cells. Furthermore, considering that clinical and immunological features of the autoimmune lymphoproliferative syndrome (ALPS) are directly attributed to homozygous mutations in FasL, we reveal differential mechanistic details of FasL/Fas clustering at the PPCR interface compared to described ALPS mutations. As Fas-mediated bystander killing remains vital to the success of CAR-T therapies in tumors, our findings highlight the therapeutic analytical design for potentially effective Fas-targeting strategies using death agonism to improve cancer immunotherapy in ovarian and other solid tumors.

A Comparative Analysis of Phytochemicals, Metal Ions, Volatile Metabolites in Heart Wood, Stem Bark and Leaves of Salix alba L. along with in Vitro Antioxidant, Antacid, Antimicrobial Activities for Sake of Environment Conservation by Substitution of Stem Bark With Leaf.

The genus of Salix is used in food, medicine and nutraceuticals, and standardized by using the single marker compound Salicin only. Stem bark is the official part used for the preparation of various drugs, nutraceuticals and food products, which may lead to overexploitation and damage of tree. There is need to search substitution of the stem bark with leaf of Salix alba L. (SA), which is yet not reported. Comparative phytochemicals viz. Salicin, Procyanidin B1 and Catechin were quantified in the various parts of SA viz. heart wood (SA-HW), stem bark (SA-SB) and leaves (SA-L) of Salix alba L.by using newly developed HPLC method. It was observed that SA-HW and SA-L contained far better amount of Salicin, Procyanidin B and Catechin as compared to SA-SB (SA-HW~SA-L≫SA-SB). Essential and toxic metal ions of all three parts were analysed using newly developed ICP-OES method, where SA-L were founded as a rich source of micronutrients and essential metal ions as compared to SA-SB and SA-HW. GC-MS analysis has shown the presence of fatty acids and volatile compounds. The observed TPC and TFC values for all three parts were ranged from 2.69 to 32.30 mg GAE/g of wt. and 37.57 to 220.76 mg QCE/g of wt. respectively. In DPPH assay the IC50 values of SA-SB, SA-HW, and SA-L were 1.09 (±0.02), 5.42 (±0.08), and 8.82 (±0.10) mg/mL, respectively. The order of antibacterial activities against E. coli, S. aureus, P. aeruginosa, and B. subtilis strains was SA-L>SA-HW>SA-SB with strong antibacterial activities against S. aureus, and B. subtilis strains. The antacid activities order was SA-L>SA-SB>SA-HW. The leaves of SA have shown significant source of nutrients, phytochemicals and medicinal properties than SA-HW and SA-SB. The leaves of SA may be considered as substitute of stem bark to save the environment or to avoid over exploitation, but after the complete pharmacological and toxicological studies.

Quantification of Phytochemicals and Metal Ions as well as the Determination of Volatile Compounds, Antioxidant, Antimicrobial and Antacid Activities of the Mimosa pudica L. Leaf: Exploration of Neglected and Under-Utilized Part.

Mimosa pudica L. (MP) is well-known plant in traditional medicinal system, especially in India. Unfortunately, leaves of MP are less explored. To determine the food and nutritional value of the neglected part of Mimosa pudica L. (MP), that is MP leaves, phytochemicals and metal ions of MP were quantified by newly developed HPLC and ICPOES-based methods. The content of phytochemicals observed using HPLC analysis for chlorogenic acid, catechin, and epicatechin was 141.823 (±8.171), 666.621 (±11.432), and 293.175 (±12.743) µg/g, respectively. Using GC/MS/MS analysis, fatty acid like oleic acid were identified. In ICP-OES analysis, a significant content of Na, K, Ca, Cu, Fe, Mg, Mn, and Zn was observed. The observed TPC and TFC for MP leaf extracts was 44.327 (±1.041) mg GAE/ g of wt. and 214.217 (±4.372) mg QCE/ g of wt., respectively. The DPPH assay depicted a strong antioxidant activity of MP leaf extracts with IC50 values of 0.796 (±0.081) mg/mL and a TEAC value of 0.0356 (±0.0003). A significant antacid activity (666 mg MP+400 mg CaCO3 >400 mg CaCO3 ≫666 mg Gelusil) of MP leaves was noticed. The methanolic extract of MP leaves demonstrated anti-microbial activity against Staphylococcus aureus (15±2mm), Pseudomonas aeruginosa (12±2mm) and Escherichia coli (10±2mm). In silico studies confirmed the in vitro results obtained for antioxidant, antiacid, and anti-microbial activities. In addition, in silico studies revealed the anti-cancerous and anti-inflammatory potential of the MP leaves. In summary, this study demonstrated the medicinal significance of MP leaves and the conversion of agro-waste or the under-utilized part of MP into pharmaceutical potent materials. Consequently, the present study highlighted that MP leaves alone have medicinal importance with good nutritional utility and possess large promise in the pharma industry along with improving bio-valorization and the environment.

Occurrence and distribution of microplastics in long-term biosolid-applied rehabilitation land: An overlooked pathway for microplastic entry into terrestrial ecosystems in Australia.

Wastewater treatment plants (WWTPs) efficiently eliminate over 98% of microplastics (MPs) from wastewater discharge, subsequently accumulating them in sludge. This sludge is frequently employed as fertilizer in agricultural practices or land rehabilitation. While there is significant research on biosolid application in agriculture, the discussion regarding its application in rehabilitating industrial zones and MPs contamination is limited. The current study investigates the abundance, distribution, and composition of MPs in rehabilitation land with long-term biosolid-application in Australia. Three minesite fields (designated 1-3), each with distinct biosolid application histories since 2011, 2012, and 2017, and a control field without any biosolid application history, were chosen for this study. The abundances of MPs in biosolid-applied fields 1-3 (6.04 ± 1.92 x 102 MP kg-1; 4.94 ± 0.73 x 102 MP kg-1; 2.48 ± 0.70 x 102 MP kg-1) were considerably higher compared to non-biosolid-applied field (0.70 ± 0.63 x 102 MP kg -1). This indicates that the application of biosolids significantly contributes to the presence of MPs in the soil. Moreover, the results suggest that with each successive application, the abundance of MPs increases. The abundance and size of MPs in both biosolid and non-biosolid soils decreased as the soil depth increased. Microbeads were dominant in soils where biosolids were applied (up to 61.9%), while fibres were dominant in non-biosolid soils (accounting for 85.7%). The distribution of plastic polymer types varied among fields and soil depths. Most MPs were microbeads of polyamide (PA), fragments of polyethylene (PE), foam of polystyrene (PS), and fibres of rayon. This research presents evidence that the extended utilization of biosolids results in elevated MP pollution in minesite rehabilitation land, highlighting a frequently overlooked origin of MP contamination in terrestrial settings. Additional evaluations needed to understand ecological risks of MPs in soil ecosystems affected by biosolid application.

Osteogenic effects of covalently tethered rhBMP-2 and rhBMP-9 in an MMP-sensitive PEG hydrogel nanocomposite.

While bone morphogenic protein-2 (BMP-2) is one of the most widely studied BMPs in bone tissue engineering, BMP-9 has been purported to be a highly osteogenic BMP. This work investigates the individual osteogenic effects of recombinant human (rh) BMP-2 and rhBMP-9, when tethered into a hydrogel, on encapsulated human mesenchymal stem cells (MSCs). A matrix-metalloproteinase (MMP)-sensitive hydrogel nanocomposite, comprised of poly(ethylene glycol) crosslinked with MMP-sensitive peptides, tethered RGD, and entrapped hydroxyapatite nanoparticles was used. The rhBMPs were functionalized with free thiols and then covalently tethered into the hydrogel by a thiol-norbornene photoclick reaction. rhBMP-2 retained its full bioactivity post-thiolation, while the bioactivity of rhBMP-9 was partially reduced. Nonetheless, both rhBMPs were highly effective at enhancing osteogenesis over 12-weeks in a chemically-defined medium. Expression of ID1 and osterix, early markers of osteogenesis; collagen type I, a main component of the bone extracellular matrix (ECM); and osteopontin, bone sialoprotein II and dentin matrix protein I, mature osteoblast markers, increased with increasing concentrations of tethered rhBMP-2 or rhBMP-9. When comparing the two BMPs, rhBMP-9 led to more rapid collagen deposition and greater mineralization long-term. In summary, rhBMP-2 retained its bioactivity post-thiolation while rhBMP-9 is more susceptible to thiolation. Despite this shortcoming with rhBMP-9, both rhBMPs when tethered into this hydrogel, enhanced osteogenesis of MSCs, leading to a mature osteoblast phenotype surrounded by a mineralized ECM. STATEMENT OF SIGNIFICANCE: Osteoinductive hydrogels are a promising vehicle to deliver mesenchymal stem cells (MSCs) for bone regeneration. This study examines the in vitro osteoinductive capabilities when tethered bone morphogenic proteins (BMPs) are incorporated into a degradable biomimetic hydrogel with cell adhesive ligands, matrix metalloproteinase sensitive crosslinks for cell-mediated degradation, and hydroxyapatite nanoparticles. This study demonstrates that BMP-2 is readily thiolated and tethered without loss of bioactivity while bioactivity of BMP-9 is more susceptible to immobilization. Nonetheless, when either BMP2 or BMP9 are tethered into this hydrogel, osteogenesis of human MSCs is enhanced, bone extracellular matrix is deposited, and a mature osteoblast phenotype is achieved. This bone-biomimetic hydrogel is a promising design for stem cell-mediated bone regeneration.

Prognostic Impact of Poor Differentiation of Squamous Cell Carcinoma in Treatment Naïve Node-Negative Early Oral Cancers.

We have conducted this study to understand the impact of poor differentiation (PD), as a sole poor prognostic factor, in early oral cancers. This was a retrospective analysis of a prospectively maintained database of clinically node-negative early T stage OSCC patients operated between 2012 and 2014. Impact of PD on the survival and role of adjuvant therapy in these patients was noted. Out of 1172 patients screened, 280 patients were found to be eligible for the study. 11.4% patients had PDSCC. It was found to be associated with tongue cancers and peri-neural invasion. It had a significant impact on OS and DFS (48.7 months vs 81.4 months, p < 0.00 and 44.6 months vs 73.5 months, p < 0.00 respectively. Hazard ratio for DFS: 4.08. Although patients with PDSCC had better survival with radiotherapy, but this was not statistically significant. Poor differentiation as a stand-alone factor impacts survival in patients with early oral cancer. It may be seen more often in patients with tongue cancer and may have associated PNI. The role of adjuvant therapy in such patients is not clear.

Can Patients Accurately Recall their Preoperative Pain and Functional Scores Following Rotator Cuff Repair and Total Shoulder Arthroplasty?

Objectives: Accurate analysis of preoperative shoulder pain and function is important for understanding treatment efficacy and producing high-quality research. Oftentimes, preoperative patient-reported outcomes (PROs) are missing. Therefore the accuracy of recalled preoperative PROs may be important. We investigate the ability of patients who underwent rotator cuff repair (RCR) or shoulder arthroplasty (TSA) to recall their preoperative PROs. Methods: We identified 145 patients who underwent either RCR or TSA and had preoperative PROs. All patients completed the ASES, SANE, SST, and VAS surveys within 3 months prior to surgery. Patients were contacted between one and four years after surgery and asked to recall their baseline pain and shoulder function prior to surgery. The mean difference was calculated by determining the difference between the mean recalled score and the mean actual score. Intraobserver reliability analysis was performed, comparing recall and actual score for each using the 2-way mixed-effects intraclass correlation coefficient (ICC) model. The ICC values > 0.75 were considered excellent, values between 0.4 and 0.75 were considered moderate, and values of < 0.4 demonstrated a weak agreement. Results: For patients who underwent RCR, the mean differences between actual and recalled ASES, SANE, SST and VAS pain were 6.3 (P=0.004), 2.0 (P=0.155), -0.04 (P=0.625) and - 1.0 (P<0.001), respectively. In patients who underwent TSA, the mean differences between actual and recalled ASES, SANE, SST and VAS pain were 4.5 (P =0.038), -3.9 (P=0.262), -1.2 (P=0.001) and -1.5 (P<0.001), respectively. ASES, SST, and VAS show moderate reliability, and SANE reliability was weak in both RCR and TSA populations. Patients had a tendency to recall higher pain scores than actual preoperative pain scores. Conclusion: In patients who underwent RCR or TSA, there was too much variability between individual patient's ability to accurately recall preoperative pain and function to reliably use recall data for research purposes.

Core microbiota of wheat rhizosphere under Upper Indo-Gangetic plains and their response to soil physicochemical properties.

Wheat is widely cultivated in the Indo-Gangetic plains of India and forms the major staple food in the region. Understanding microbial community structure in wheat rhizosphere along the Indo-Gangetic plain and their association with soil properties can be an important base for developing strategies for microbial formulations. In the present study, an attempt was made to identify the core microbiota of wheat rhizosphere through a culture-independent approach. Rhizospheric soil samples were collected from 20 different sites along the upper Indo-Gangetic plains and their bacterial community composition was analyzed based on sequencing of the V3-V4 region of the 16S rRNA gene. Diversity analysis has shown significant variation in bacterial diversity among the sites. The taxonomic profile identified Proteobacteria, Chloroflexi, Actinobacteria, Bacteroidetes, Acidobacteria, Gemmatimonadetes, Planctomycetes, Verrucomicrobia, Firmicutes, and Cyanobacteria as the most dominant phyla in the wheat rhizosphere in the region. Core microbiota analysis revealed 188 taxa as core microbiota of wheat rhizosphere with eight genera recording more than 0.5% relative abundance. The order of most abundant genera in the core microbiota is Roseiflexus> Flavobacterium> Gemmatimonas> Haliangium> Iamia> Flavisolibacter> Ohtaekwangia> Herpetosiphon. Flavobacterium, Thermomonas, Massilia, Unclassified Rhizobiaceae, and Unclassified Crenarchaeota were identified as keystone taxa of the wheat rhizosphere. Correlation studies revealed, pH, organic carbon content, and contents of available nitrogen, phosphorus, and iron as the major factors driving bacterial diversity in the wheat rhizosphere. Redundancy analysis has shown the impact of different soil properties on the relative abundance of different genera of the core microbiota. The results of the present study can be used as a prelude to be developing microbial formulations based on core microbiota.

What Can We Still Learn from Brain Autopsies in COVID-19?

Neuropathological findings have been published from ∼900 patients who died with or from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections, representing less than 0.01% of the close to 6.4 million deaths reported to the World Health Organization 2 years into the coronavirus disease 2019 (COVID-19) pandemic. In this review, we extend our prior work summarizing COVID-19 neuropathology by including information on published autopsies up to June 2022, and neuropathological studies in children, COVID-19 variants, secondary brain infections, ex vivo brain imaging, and autopsies performed in countries outside of the United States or Europe. We also summarize research studies that investigate mechanisms of neuropathogenesis in nonhuman primates and other models. While a pattern of cerebrovascular pathology and microglial-predominant inflammation remains the primary COVID-19-associated neuropathological finding, there is no singular understanding of the mechanisms that underlie neurological symptoms in acute COVID-19 or the post-acute COVID-19 condition. Thus, it is paramount that we incorporate microscopic and molecular findings from brain tissue into what we know about the clinical disease so that we attain best practice guidance and direct research priorities for the study of the neurological morbidity of COVID-19.

Determining the impact of COVID-19 pandemic on adjuvant therapy for oral cancer - A matched-pair analysis.

Background: The ongoing coronavirus disease 2019 (COVID-19) pandemic has hard-pressed the health care systems beyond their capabilities, causing a lack of appropriate cancer treatment delivery. The aim of this study was to assess the impact of pandemic-related restrictions on adjuvant therapy delivery for oral cancer patients during these demanding times. Materials and Methods: Oral cancer patients who were operated on between February and July 2020 and scheduled to receive prescribed adjuvant therapy during the COVID-19-related restrictions (Group I) were included in the study. The data were matched for the length of hospital stay and type of prescribed adjuvant therapy, with a set of patients who were similarly managed 6 months preceding the restrictions (Group II). Demographic and treatment-specific details, including inconveniences faced in procuring prescribed treatment, were obtained. Factors associated with delay in receiving adjuvant therapy were compared using regression models. Results: A total of 116 oral cancer patients were considered for analysis, comprising 69% (n = 80) adjuvant radiotherapy alone and 31% (n = 36) concurrent chemoradiotherapy. The mean hospital stay was 13 days. In Group I, 29.3% (n = 17) of patients were not able to receive any form of their prescribed adjuvant therapy at all, which was 2.43 times higher than Group II (P = 0.038). None of the disease-related factors significantly predicted delay in receiving adjuvant therapy. Of the delay, 76.47% (n = 13) was present during the initial part of the restrictions, with the most common reason being unavailability of appointments (47.1%, n = 8), followed by inability to reach treatment centers (23.5%, n = 4) and redeem reimbursements (23.5%, n = 4). The number of patients who were delayed the start of radiotherapy beyond 8 weeks after surgery was double in Group I (n = 29) than in Group II (n = 15; P = 0.012). Conclusions: This study highlights a small part of the rippling effect the COVID-19 restrictions have on oral cancer management and pragmatic actions may be needed by policymakers to deal with such challenges.